Faculty Bibliography
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department:Ophthalmology
recent-years:2
school:SOM
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455
Novel Methods of Identifying Individual and Neighborhood Risk Factors for Loss to Follow-Up After Ophthalmic Screening
PRCIS/CONCLUSIONS:Residence in a middle-class neighborhood correlated with lower follow-up compared to residence in more affluent neighborhoods. The most common explanations for not following up were the process of making an appointment and lack of symptoms. PURPOSE/OBJECTIVE:To explore which individual and neighborhood-level factors influence follow-up as recommended after positive ophthalmic and primary care screening in a vulnerable population using novel methodologies. PARTICIPANTS/METHODS:and Methods: From 2017 to 2018, 957 participants were screened for ophthalmic disease and cardiovascular risk factors as part of the Real-Time Mobile Teleophthalmology study. Individuals who screened positive for either ophthalmic or cardiovascular risk factors were contacted to determine whether or not they followed up with a healthcare provider. Data from the Social Vulnerability Index, a novel virtual auditing system, and personal demographics were collected for each participant. A multivariate logistic regression was performed to determine which factors significantly differed between participants who followed up and those who did not. RESULTS:As a whole, the study population was more socioeconomically vulnerable than the national average (mean summary Social Vulnerability Index score=0.81). Participants whose neighborhoods fell in the middle of the national per capita income distribution had lower likelihood of follow-up compared to those who resided in the most affluent neighborhoods (relative risk ratio=0.21, P-value<0.01). Participants cited the complicated process of making an eye care appointment and lack of symptoms as the most common reasons for not following up as instructed within four months. CONCLUSIONS:Residence in a middle-class neighborhood, difficulty accessing eye care appointments, and low health literacy may influence follow up among vulnerable populations.
PMID: 37974319
ISSN: 1536-481x
CID: 5610472
Vasa Previa in Singleton Pregnancies: Diagnosis and Clinical Management Based on an International Expert Consensus
BACKGROUND:There are limited data to guide the diagnosis and management of vasa previa. Currently, what is known is largely based on case reports or series and cohort studies. OBJECTIVE:(s): To systematically collect and classify expert opinions and achieve consensus on the diagnosis and clinical management of vasa previa using focus group discussions (FGD) and a Delphi technique. STUDY DESIGN/METHODS:A four-round FGD and a three-round Delphi survey of an international panel of experts on vasa previa were conducted. Experts were selected based on their publication record on vasa previa. First, we convened an FGD panel of 20 experts and agreed on which issues were unresolved in the diagnosis and management of vasa previa. A three-round anonymous electronic survey was then sent to the full expert panel. Survey questions were presented on the diagnosis and management of vasa previa that the experts were asked to rate on a 5-point Likert scale (from strongly disagree = 1 to strongly agree = 5). Consensus was defined as a median score of 5. Following responses to each round, any statements that had median scores of 3 or less were deemed to have had no consensus and excluded. Statements with a median score of 4 were revised and re-presented to the experts in the next round. Consensus and non-consensus statements were then aggregated. RESULTS:Sixty-eight international experts were invited to participate in the study, of which 57 participated. Experts were from 13 countries on five continents and have contributed to over 80% of published cohort studies on vasa previa, as well as national and international society guidelines. Completion rates were 84%, 93%, 91% for the first, second, and third rounds, respectively, and 71% completed all three rounds. The panel reached a consensus on 26 statements regarding the diagnosis and key points of management of vasa previa, including: 1) While there is no agreement on a distance between the fetal vessels and the cervical internal os to define vasa previa, the definition should not be limited to a 2 cm distance; 2) All pregnancies should be screened for vasa previa with routine examination for placental cord insertion and a color Doppler sweep of the region over the cervix at the second-trimester anatomy scan; 3) When a low-lying placenta or placenta previa is found in the second trimester, a transvaginal ultrasound with Doppler should be performed at around 32 weeks to rule out vasa previa; 4) Outpatient management of asymptomatic patients without risk factors for preterm birth is reasonable; 5)Asymptomatic patients with vasa previa should be delivered by scheduled cesarean between 35- and 37-weeks of gestation; and 6) There was no agreement on routine hospitalization, avoidance of intercourse, or use of 3-dimensional ultrasound for diagnosis of vasa previa. CONCLUSIONS:Through FGD and a Delphi process, an international expert panel reached consensus on the definition, screening, clinical management, and timing of delivery in vasa previa, which could inform the development of new clinical guidelines.
PMID: 38494071
ISSN: 1097-6868
CID: 5639942
Anomaly-guided weakly supervised lesion segmentation on retinal OCT images
The availability of big data can transform the studies in biomedical research to generate greater scientific insights if expert labeling is available to facilitate supervised learning. However, data annotation can be labor-intensive and cost-prohibitive if pixel-level precision is required. Weakly supervised semantic segmentation (WSSS) with image-level labeling has emerged as a promising solution in medical imaging. However, most existing WSSS methods in the medical domain are designed for single-class segmentation per image, overlooking the complexities arising from the co-existence of multiple classes in a single image. Additionally, the multi-class WSSS methods from the natural image domain cannot produce comparable accuracy for medical images, given the challenge of substantial variation in lesion scales and occurrences. To address this issue, we propose a novel anomaly-guided mechanism (AGM) for multi-class segmentation in a single image on retinal optical coherence tomography (OCT) using only image-level labels. AGM leverages the anomaly detection and self-attention approach to integrate weak abnormal signals with global contextual information into the training process. Furthermore, we include an iterative refinement stage to guide the model to focus more on the potential lesions while suppressing less relevant regions. We validate the performance of our model with two public datasets and one challenging private dataset. Experimental results show that our approach achieves a new state-of-the-art performance in WSSS for lesion segmentation on OCT images.
PMID: 38493532
ISSN: 1361-8423
CID: 5639892
The Evolution of Full Thickness Macular Hole After Short Exposure to High Powered Hand-held Laser Pointer
PURPOSE/OBJECTIVE:To report a case of a full thickness macular hole (FTMH) after exposure to an extremely powerful handheld laser pointer. METHODS:We evaluated a 14-year-old male with a laser induced FTMH one month after a momentary exposure to a 5000 mW blue laser pointer. Imaging modalities including fundus color, autofluorescence, and spectral domain optical coherence tomography (SD-OCT), acquired both at our clinic and by the referring physician soon after the injury, are used to describe the clinical evolution of the case. RESULTS:Soon after the injury an intensely white, circular opacification of the retina approximately 400 µm in diameter was seen in the fovea. Early SD-OCT images showed full thickness hyperreflectivity, likely representing tissue necrosis. One month later, a FTMH and eradication of the retinal pigment epithelium at its base were evident in the fundus color, autofluorescence and SD-OCT images. CONCLUSION/CONCLUSIONS:High power laser pointers have become easily available online. The presenting findings after exposure to such high-power devices are distinct from those reported after exposure to weaker laser pointers. While long exposure to weaker lasers typically produces extensive, calligraphic figures and yellow placoid lesions involving only the outer retina, in our case a very brief exposure led to focal, full-thickness injury of the fovea.
PMID: 36730459
ISSN: 1937-1578
CID: 5420372
Out of sight, but not out of mind: Zoster sine herpete case study and survey of Zoster Eye Disease Study (ZEDS) Group
SCOPUS:85181254856
ISSN: 2451-9936
CID: 5629032
Evolution of the 'omega sign' on optical coherence tomography
PURPOSE/OBJECTIVE:To present the early post-operative evolution of retained subretinal perfluoro-n-octane (PFO) as captured on OCT. METHODS:Case report of a patient. RESULTS:A 58-year-old woman was noted to have subretinal PFO after undergoing autologous retinal graft for macular hole closure under PFO tamponade. Serial OCT identified the subretinal PFO as early as the first postoperative day and demonstrates progressive consolidation and encapsulation of the PFO bubble by the surrounding outer retina. CONCLUSION/CONCLUSIONS:Subretinal PFO is usually seen several weeks in the postoperative course once the gas endotamponade has resorbed sufficiently for OCT imaging. In this case, PFO tamponade enabled its imaging early. Its subsequent evolution into the classic "omega sign" may suggest a granulomatous encapsulation of the PFO bubble.
PMID: 36026714
ISSN: 1937-1578
CID: 5338502
Subacute Vision Loss in a Patient With HIV
PMID: 37995149
ISSN: 1536-5166
CID: 5608722
Anti-inflammatory medication use after cataract surgery: online survey of practice patterns
PURPOSE/OBJECTIVE:To determine current prescribing patterns for topical or intraocular/periocular anti-inflammatory medications (AIMs) after routine cataract surgery. SETTING/METHODS:kera-net online members. DESIGN/METHODS:Cross-sectional survey. METHODS:An online survey was distributed to subscribers of kera-net, a global online platform sponsored by the Cornea Society. Questions were asked regarding the use of topical or intraocular/periocular AIM after cataract surgery and types of medications prescribed. RESULTS:Of 217 surgeon respondents (23% response rate), 171 (79%) practiced in the United States and 171 (79%) were cornea subspecialists. Most of the respondents (n = 196, 97%) prescribed topical corticosteroids after routine cataract surgery. The most frequently prescribed were prednisolone acetate (n = 162, 83%), followed by dexamethasone (n = 26, 13%), difluprednate (n = 24, 12%), and loteprednol etabonate (n = 13, 7%). Corticosteroids comprised (n = 40, 32%) of total intraocular/periocular injections, with triamcinolone acetonide 10 or 40 mg (n = 19, 47.5%) most commonly used. 23 surgeons (58%) who utilized intraocular/periocular corticosteroids also prescribed topical corticosteroids. Topical nonsteroidal anti-inflammatory drugs were prescribed postoperatively by 148 surgeons (73%). CONCLUSIONS:Most surgeons prescribed topical AIM after routine cataract surgery. Many surgeons injected intraocular or periocular AIM while prescribing topical AIM. The diversity of practice patterns may reflect the lack of clear evidence-based guidelines.
PMCID:10878440
PMID: 38381616
ISSN: 1873-4502
CID: 5634322
Out of sight, but not out of mind: Zoster sine herpete case study and survey of Zoster Eye Disease Study (ZEDS) Group [Case Report]
PMCID:10797137
PMID: 38261902
ISSN: 2451-9936
CID: 5624862
Improved reconstruction of crossing fibers in the mouse optic pathways with orientation distribution function fingerprinting
PURPOSE/OBJECTIVE:The accuracy of diffusion MRI tractography reconstruction decreases in the white matter regions with crossing fibers. The optic pathways in rodents provide a challenging structure to test new diffusion tractography approaches because of the small crossing volume within the optic chiasm and the unbalanced 9:1 proportion between the contra- and ipsilateral neural projections from the retina to the lateral geniculate nucleus, respectively. METHODS: RESULTS:ODF-FP outperformed by over 100% all the tested methods in terms of the ratios between the contra- and ipsilateral segments of the reconstructed optic pathways as well as the spatial overlap between tractography and MEMRI. CONCLUSION/CONCLUSIONS:In this challenging model system, ODF-Fingerprinting reduced uncertainty of diffusion tractography for complex structural formations of fiber bundles.
PMID: 37927121
ISSN: 1522-2594
CID: 5612792
Differentiating stages of functional vision loss from glaucoma using the Disc Damage Likelihood Scale and cup:disc ratio
BACKGROUND:Glaucoma staging is critical for treatment planning but has rarely been tested in severe/end-stage disease. We compared the performance of the Disc Damage Likelihood Scale (DDLS) and cup:disc ratio (CDR) using a functional glaucoma staging system (GSS) as the reference standard. METHODS:Post hoc analysis of a randomised controlled trial at the Eye Department of Kilimanjaro Christian Medical Centre, Tanzania. Eligible participants (aged ≥18 years) with open-angle glaucoma, intraocular pressure (IOP) of >21 mm Hg, were randomised to timolol 0.5% eye drops or selective laser trabeculoplasty. Fundoscopy established vertical and horizontal CDRs and DDLS. Visual acuity and static visual fields were graded (GSS). The study used area under the receiver operating characteristic (AROC) curves and Spearman's rank correlation coefficients to compare staging systems. Logistic regression with generalised estimating equations determined risk factors of functional severe/end-stage glaucoma. RESULTS:382 eyes (201 participants) were evaluated; 195 (51%) had severe or end-stage glaucoma; mean IOP was 26.7 (SD 6.9) mm Hg. DDLS yielded an AROC of 0.90 (95% CI 0.87 to 0.93), vertical cup:disc ratio (vCDR) of 0.88 (95% CI 0.85 to 0.91, p=0.048) for identifying severe/end-stage disease. Correlation coefficients comparing GSS to DDLS and vCDRs were 0.73 and 0.71, respectively. Advanced structural stages, vision impairment, higher IOP and less financial resources were risk factors of functional severe/end-stage glaucoma. CONCLUSION/CONCLUSIONS:This study indicates that both structural staging systems can differentiate severe/end-stage glaucoma from less severe disease, with a moderate advantage of DDLS over CDR. Clinical examination of the optic disc plays an important role in addition to functional assessment when managing severe/end-stage glaucoma.
PMID: 36653163
ISSN: 1468-2079
CID: 5498142
Canadian journal of ophthalmology = Journal canadien d'ophtalmologie. 2024.DOI: 10.1016/j.jcjo.2024.01.007
Widefield multimodal imaging of presumed bilateral diffuse uveal melanocytic proliferation
PMID: 38387860
ISSN: 1715-3360
CID: 5634502
Accuracy of intraocular lens formulas in combined phacovitrectomy
PURPOSE/OBJECTIVE:To assess the refractive accuracy of eight intraocular lens (IOL) formulas in eyes that underwent combined phacovitrectomy. METHODS:A retrospective chart review of 59 eyes that underwent uncomplicated phacovitrectomy between 2017 and 2020 at the Johns Hopkins Wilmer Eye Institute. Inclusion criteria were postoperative best corrected visual acuity of 20/40 or better within 6 months of surgery and IOL implantation in the capsular bag. The Barrett Universal II (BUII), Emmetropia Verifying Optical (EVOv2.0), Hill-Radial Basis Function (Hill-RBFv3.0), Hoffer Q, Holladay I, Kane, Ladas Super Formula (LSF), and SRK/T formulas were compared for accuracy in predicting postoperative spherical equivalents (SE) using Wilcoxon rank sum tests. Pearson's correlation coefficients were used to assess correlations between biometric parameters and errors for all formulas. RESULTS:Prediction errors of SE ranged from - 1.69 to 1.43 diopters (D), mean absolute errors (MAE) ranged from 0.39 to 0.47 D, and median absolute errors (MedAE) ranged from 0.23 to 0.37 D among all formulas. The BUII had the lowest mean error (- 0.043), MAE (0.39) and MedAE (0.23). The BUII also had the highest percentage of eyes with predicted error within ± 0.25 D (51%) and ± 0.50 D (83%). Based on MedAE however, no pairwise comparisons resulted in statistically significant differences. Axial length (AL) was positively correlated with the error from the Hoffer Q and Holladay I formulas (correlation coefficients = 0.34, 0.30, p values < 0.01, 0.02 respectively). CONCLUSION/CONCLUSIONS:While all eight IOL formulas had comparable accuracy in predicting refractive outcomes in eyes undergoing combined phacovitrectomy, the BUII and Kane formulas had a tendency to greater accuracy.
PMID: 38372824
ISSN: 1573-2630
CID: 5634022
Editorial for "Rich Club Reorganization in Nurses Before and After the Onset of Occupational Burnout: A Longitudinal MRI Study" [Editorial]
PMID: 38363174
ISSN: 1522-2586
CID: 5635982
The relevance of arterial blood pressure in the management of glaucoma progression: a systematic review
BACKGROUND:Glaucoma is one of the leading causes of global blindness and is expected to co-occur more frequently with vascular morbidities in the upcoming years, as both are aging-related diseases. Yet, the pathogenesis of glaucoma is not entirely elucidated and the interplay between intraocular pressure, arterial blood pressure and ocular perfusion pressure is poorly understood. OBJECTIVE:This systematic review aims to provide clinicians with the latest literature regarding the management of arterial blood pressure in glaucoma patients. METHODS:A systematic search was performed in Medline, Embase, Web of Science and Cochrane Library. Articles written in English assessing the influence of arterial blood pressure and systemic antihypertensive treatment of glaucoma and its management were eligible for inclusion. Additional studies were identified by revising references included in selected articles. RESULTS:80 articles were included in this systemic review. A bimodal relation between blood pressure and glaucoma progression was found. Both high and low blood pressure increase the risk of glaucoma. Glaucoma progression was, possibly via ocular perfusion pressure variation, strongly associated with nocturnal dipping and high variability in the blood pressure over 24-hours. CONCLUSIONS:We concluded that systemic blood pressure level associates with glaucomatous damage and provided recommendations for the management and study of arterial blood pressure in glaucoma. Prospective clinical trials are needed to further support these recommendations.
PMID: 37995334
ISSN: 1941-7225
CID: 5608762
Chamber shallowing technique for challenging DMEK cases: Tucking cellulose spears under the speculum to augment posterior pressure
Some anterior chambers do not readily shallow because of insufficient posterior pressure and/or very deep anterior chamber anatomy, which can make unscrolling descemet membrane endothelial keratoplasty (DMEK) tissue more challenging with an unmodified tap technique. We present a hands-free method for augmenting posterior pressure by temporarily tucking cellulose sponges under the blades of the eyelid speculum. The sponges transfer some of the eyelid speculum's weight onto the bulbar surface posterior to the iris, thereby indenting the sclera and causing the iris diaphragm to bulge further forward. This hands-free technique can transform a potentially challenging DMEK case into a more straightforward one by facilitating both a shallow anterior chamber and a bimanual unscrolling technique. However, it only works in bicameral eyes with a vitreous body (e.g., an eye with penetrating keratoplasty, vitreous syneresis, and axial myopia) and will not work in unicameral eyes after vitrectomy (e.g., an eye with an Anterior Chamber Intraocular Lens (ACIOL)).
PMID: 38317304
ISSN: 1998-3689
CID: 5632872
Association of Psychosocial Factors with Activation Among Patients with Glaucoma
OBJECTIVE:To investigate the association of psychosocial factors with health self-management behaviors and beliefs among patients with POAG. DESIGN/METHODS:Prospective cross-sectional cohort study. PARTICIPANTS/METHODS:Patients (n=202) with mild, moderate, or advanced bilateral POAG. METHODS:Patients (n=1,164) were identified from electronic medical records at a single academic medical center. Letters soliciting participation were mailed to 591 randomly selected potential participants. Psychometric measures and a determinants of health questionnaire were administered by phone to 202 study participants. MAIN OUTCOME MEASURES/METHODS:The NEI VFQ-8 (NEI-VFQ), the Multidimensional Health Locus of Control (MHLC), the Perceived Medical Condition Self-Management Scale-4 (PMCSMS), the Patient Health Questionnaire-9 (PHQ), the Patient Activation Measure-13 (PAM), health literacy and a determinants of health questionnaire. RESULTS:=2.6%, 95% CI= [-0.664,-0.051], p=0.023). On multivariate analysis adjusting for age, sex and race, for each unit increase in PHQ, mean PAM score decreased (95% CI = [0.061,1.35], p=0.032); for each unit increase in MHLC 'Doctors', mean PAM score increased (95% CI=[-1.448,3.453], p<0.001); for each unit increase in MHLC 'Internal', mean PAM score increased (95% CI=[0.639,1.137 ], p<0.001); for each unit increase in MHLC 'Chance' , mean PAM score decreased (95% CI=[-0.685,-0.098], p=0.009). CONCLUSION/CONCLUSIONS:We identified modifiable behavioral factors that could increase patients' self-perceived ability and confidence to manage their own eye care. Locus of control (MHLC), level of depression (PHQ), and self-rated functional vision (NEI-VFQ) were each associated with patient behaviors, attitudes and beliefs needed for health self-management (activation, assessed by the PAM) and may be important determinants of adherence behaviors. Targeting change in patients' care beliefs and behaviors may improve activation and treatment outcomes.
PMID: 38320666
ISSN: 2589-4196
CID: 5632572
Silicone Oil From Syringes-A Potentially Overlooked Issue for Intravitreal Injections-Reply
PMID: 38175624
ISSN: 2168-6173
CID: 5628372
FROM DRUSEN TO TYPE 3 MACULAR NEOVASCULARIZATION
PURPOSE/OBJECTIVE:To investigate the imaging features preceding the occurrence of type 3 (T3) macular neovascularization (MNV) using tracked spectral-domain optical coherence tomography. METHOD/METHODS:From a cohort of eyes with T3 MNV and ≥ 12 months of previously tracked spectral-domain optical coherence tomography, T3 lesions that developed above soft drusen were selected for optical coherence tomography analysis. Retinal imaging findings at the location where type T3 MNV occurred were analyzed at each follow-up until the onset of T3 MNV. The following optical coherence tomography parameters were assessed: drusen size (height and width), outer nuclear layer/Henle fiber layer thickness at the drusen apex, and the presence of intraretinal hyperreflective foci, retinal pigment epithelium disruption, incomplete retinal pigment epithelium and outer retina atrophy, and complete retinal pigment epithelium and outer retina atrophy. RESULTS:From a cohort of 31 eyes with T3 MNV, T3 lesions developed above soft drusen in 20 eyes (64.5%). Drusen showed progressive growth ( P < 0.001) associated with outer nuclear layer/Henle fiber ( P < 0.001) thinning before T3 MNV. The following optical coherence tomography features were identified preceding the occurrence of T3 MNV, typically at the apex of the drusenoid lesion: disruption of the external limiting membrane/ellipsoid zone and/or the retinal pigment epithelium, hyperreflective foci, and incomplete retinal pigment epithelium and outer retina atrophy/complete retinal pigment epithelium and outer retina atrophy. CONCLUSION/CONCLUSIONS:The results demonstrate specific anatomic alterations preceding the occurrence of T3 MNV that most commonly originates above soft drusen. Drusen growth, reduced outer nuclear layer/Henle fiber thickness, and retinal pigment epithelium atrophy at the drusen apex precede the development of T3 MNV. Identifying these optical coherence tomography features should warrant close monitoring for identification of T3 MNV, which can benefit from prompt intravitreal anti-vascular endothelial growth factor therapy.
PMID: 37756671
ISSN: 1539-2864
CID: 5624252
Early inner plexiform layer thinning and retinal nerve fiber layer thickening in excitotoxic retinal injury using deep learning-assisted optical coherence tomography
Excitotoxicity from the impairment of glutamate uptake constitutes an important mechanism in neurodegenerative diseases such as Alzheimer's, multiple sclerosis, and Parkinson's disease. Within the eye, excitotoxicity is thought to play a critical role in retinal ganglion cell death in glaucoma, diabetic retinopathy, retinal ischemia, and optic nerve injury, yet how excitotoxic injury impacts different retinal layers is not well understood. Here, we investigated the longitudinal effects of N-methyl-D-aspartate (NMDA)-induced excitotoxic retinal injury in a rat model using deep learning-assisted retinal layer thickness estimation. Before and after unilateral intravitreal NMDA injection in nine adult Long Evans rats, spectral-domain optical coherence tomography (OCT) was used to acquire volumetric retinal images in both eyes over 4 weeks. Ten retinal layers were automatically segmented from the OCT data using our deep learning-based algorithm. Retinal degeneration was evaluated using layer-specific retinal thickness changes at each time point (before, and at 3, 7, and 28 days after NMDA injection). Within the inner retina, our OCT results showed that retinal thinning occurred first in the inner plexiform layer at 3 days after NMDA injection, followed by the inner nuclear layer at 7 days post-injury. In contrast, the retinal nerve fiber layer exhibited an initial thickening 3 days after NMDA injection, followed by normalization and thinning up to 4 weeks post-injury. Our results demonstrated the pathological cascades of NMDA-induced neurotoxicity across different layers of the retina. The early inner plexiform layer thinning suggests early dendritic shrinkage, whereas the initial retinal nerve fiber layer thickening before subsequent normalization and thinning indicates early inflammation before axonal loss and cell death. These findings implicate the inner plexiform layer as an early imaging biomarker of excitotoxic retinal degeneration, whereas caution is warranted when interpreting the ganglion cell complex combining retinal nerve fiber layer, ganglion cell layer, and inner plexiform layer thicknesses in conventional OCT measures. Deep learning-assisted retinal layer segmentation and longitudinal OCT monitoring can help evaluate the different phases of retinal layer damage upon excitotoxicity.
PMCID:10835918
PMID: 38303097
ISSN: 2051-5960
CID: 5626852
Non-invasive markers of inflammation in alcohol-associated liver disease: A scoping review
Clinical manifestations of liver inflammation in alcohol-associated liver disease (ALD) can range from asymptomatic to severe alcoholic hepatitis. While biopsy is the gold standard for identifying liver inflammation, it is an invasive procedure with risks of bleeding, visceral damage, and infection. We aim to establish the state of the current literature on non-invasive markers of inflammation in ALD. We searched Ovid MEDLINE, Embase, and the Cochrane Library for original studies on the association between one or more non-invasive biomarker(s) and histological inflammation or hepatitis in ALD patients. Exclusion criteria were lack of histological data, abstract only, non-English-language articles, and animal studies. Two independent reviewers screened abstracts, reviewed full texts, and extracted data from included papers. Our search identified 8051 unique studies. Title and abstract screening resulted in 563 studies, and full-text screening resulted in 31 studies for final inclusion. The majority were single-center observational cohorts with an average sample size of 124. Review of these studies identified 44 unique biomarkers and 8 calculated scores associated with histological inflammation and/or hepatitis, in addition to a metabolomic panel of 468 metabolites. Six studies examined diagnostic accuracy for histological inflammation and/or hepatitis. The highest area under the receiver operating characteristic curve was 0.932 using a model based on four metabolites. This review highlights the available literature on non-invasive markers of inflammation in ALD. There is a dearth of studies that evaluate the diagnostic accuracy of these biomarkers, and larger studies are needed to confirm findings identified in small cohorts.
PMID: 38054575
ISSN: 1440-1746
CID: 5595672
Canadian journal of ophthalmology = Journal canadien d'ophtalmologie. 2024:59(1):e84-e85.DOI: 10.1016/j.jcjo.2023.09.002
Papillorenal syndrome with extensive retinoschisis
PMID: 37770011
ISSN: 1715-3360
CID: 5627862
Shedding light on ultrasound in action: Optical and optoacoustic monitoring of ultrasound brain interventions
Monitoring brain responses to ultrasonic interventions is becoming an important pillar of a growing number of applications employing acoustic waves to actuate and cure the brain. Optical interrogation of living tissues provides a unique means for retrieving functional and molecular information related to brain activity and disease-specific biomarkers. The hybrid optoacoustic imaging methods have further enabled deep-tissue imaging with optical contrast at high spatial and temporal resolution. The marriage between light and sound thus brings together the highly complementary advantages of both modalities toward high precision interrogation, stimulation, and therapy of the brain with strong impact in the fields of ultrasound neuromodulation, gene and drug delivery, or noninvasive treatments of neurological and neurodegenerative disorders. In this review, we elaborate on current advances in optical and optoacoustic monitoring of ultrasound interventions. We describe the main principles and mechanisms underlying each method before diving into the corresponding biomedical applications. We identify areas of improvement as well as promising approaches with clinical translation potential.
PMID: 38184194
ISSN: 1872-8294
CID: 5627622
Ophthalmology Workforce Projections in the United States, 2020 to 2035
PURPOSE/OBJECTIVE:To analyze ophthalmology workforce supply and demand projections from 2020 to 2035. DESIGN/METHODS:Observational cohort study using data from the National Center for Health Workforce Analysis (NCHWA). METHODS:Data accessed from the Department of Health and Human Services, Health Resources and Services Administration (HRSA) website were compiled to analyze the workforce supply and demand projections for ophthalmologists from 2020 to 2035. MAIN OUTCOME MEASURES/METHODS:Projected workforce adequacy over time. RESULTS:From 2020 to 2035, the total ophthalmology supply is projected to decrease by 2650 full-time equivalent (FTE) ophthalmologists (12% decline) and total demand is projected to increase by 5150 FTE ophthalmologists (24% increase), representing a supply and demand mismatch of 30% workforce inadequacy. The level of projected adequacy was markedly different based on rurality by year 2035 with 77% workforce adequacy versus 29% workforce adequacy in metro and nonmetro geographies, respectively. By year 2035, ophthalmology is projected to have the second worst rate of workforce adequacy (70%) of 38 medical and surgical specialties studied. CONCLUSIONS:The HRSA's Health Workforce Simulation Model forecasts a sizeable shortage of ophthalmology supply relative to demand by the year 2035, with substantial geographic disparities. Ophthalmology is one of the medical specialties with the lowest rate of projected workforce adequacy by 2035. Further dedicated workforce supply and demand research for ophthalmology and allied professionals is needed to validate these projections, which may have significant future implications for patients and providers. FINANCIAL DISCLOSURE(S)/BACKGROUND:Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
PMID: 37739231
ISSN: 1549-4713
CID: 5614082
Finding Ophthalmic Risk and Evaluating the Value of Eye exams and their predictive Reliability (FOREVER)-A cohort study in a Danish high street optician setting: Design and methodology
PURPOSE/OBJECTIVE:The purpose of the study was to describe the rationale and design of Project FOREVER (Finding Ophthalmic Risk and Evaluating the Value of Eye exams and their predictive Reliability). DESIGN/METHODS:Project FOREVER will build a comprehensive database of clinical eye and vision data collected from ~280 000 adults at 100 optician stores across Denmark. The FOREVER database (FOREVERdb) includes detailed data from refraction, visual acuity, intraocular pressure, corneal thickness, visual field assessments and retinal fundus images. Linkage to the comprehensive Danish national registries with, that is diagnostic and prescribing data permits investigation of rare associations and risk factors. 30 000 individuals over 50 also provide a saliva sample for later genetic studies and blood pressure measurements. Of these 30 000, 10 000 will also get optical coherence tomography (OCT) nerve and retinal scans. This subpopulation data is reviewed by ophthalmologists for disease detection. All participants will be asked to complete a questionnaire assessing lifestyle, self-perceived eye health and general health. Enrolment of participants began in April 2022. PERSPECTIVE/CONCLUSIONS:The FOREVERdb is a powerful tool to answer a wide range of research questions that can pave the way for better eye health. This database will provide valuable insights for future studies investigating the correlations between eye and general health in a Danish population cohort, enabling research to identify potential risk factors for a range of diseases.
PMID: 37140185
ISSN: 1755-3768
CID: 5498182
Central serous chorioretinopathy: An evidence-based treatment guideline
Central serous chorioretinopathy (CSC) is a relatively common disease that causes vision loss due to macular subretinal fluid leakage and is often associated with reduced vision-related quality of life. In CSC, the leakage of subretinal fluid through defects in the retinal pigment epithelial layer's outer blood-retina barrier appears to occur secondary to choroidal abnormalities and dysfunction. The treatment of CSC is currently the subject of controversy, although recent data obtained from several large randomized controlled trials provide a wealth of new information that can be used to establish a treatment algorithm. Here, we provide a comprehensive overview of our current understanding regarding the pathogenesis of CSC, current therapeutic strategies, and an evidence-based treatment guideline for CSC. In acute CSC, treatment can often be deferred for up to 3-4 months after diagnosis; however, early treatment with either half-dose or half-fluence photodynamic therapy (PDT) combined with the photosensitive dye verteporfin may be beneficial in selected cases. In chronic CSC, half-dose or half-fluence PDT, which targets the abnormal choroid, should be considered the preferred treatment. If PDT is unavailable, chronic CSC with focal, non-central leakage on angiography may be treated using conventional laser photocoagulation. CSC with concurrent macular neovascularization should be treated with half-dose/half-fluence PDT and/or intravitreal injections of an anti-vascular endothelial growth factor compound. Given the current shortage of verteporfin and the paucity of evidence supporting the efficacy of other treatment options, future studies-ideally, well-designed randomized controlled trials-are needed in order to evaluate new treatment options for CSC.
PMID: 38301969
ISSN: 1873-1635
CID: 5626772
Hyporeflective Subretinal Lucency in Central Serous Chorioretinopathy
PMID: 38284952
ISSN: 1549-4713
CID: 5627822
Performance Assessment of an Artificial Intelligence Chatbot in Clinical Vitreoretinal Scenarios
PURPOSE/OBJECTIVE:To determine how often ChatGPT is able to provide accurate and comprehensive information regarding clinical vitreoretinal scenarios. To assess the types of sources ChatGPT primarily utilizes and to determine if they are hallucinated. METHODS:A retrospective cross-sectional study. We designed 40 open-ended clinical scenarios across 4 main topics in vitreoretinal disease. Responses were graded on correctness and comprehensiveness by two blinded retina specialists. The primary outcome was the number of clinical scenarios that ChatGPT answered correctly and comprehensively. Secondary outcomes included: theoretical harm to patients, the distribution of the type of references utilized by the chatbot, and the frequency of hallucinated references. RESULTS:In June 2023, ChatGPT answered 83% (33/40) of clinical scenarios correctly but provided a comprehensive answer in only 52.5% (21/40) of cases. Subgroup analysis demonstrated an average correct score of 86.7% in nAMD, 100% in DR, 76.7% in retinal vascular disease and 70% in the surgical domain. There were 6 incorrect responses with 1 (16.7%) case of no harm, 3 (50%) cases of possible harm and 2 (33.3%) cases of definitive harm. CONCLUSION/CONCLUSIONS:ChatGPT correctly answered more than 80% of complex open-ended vitreoretinal clinical scenarios, with a reduced capability to provide a comprehensive response.
PMID: 38271674
ISSN: 1539-2864
CID: 5625242
Motion Contrast, Phase Gradient, and Simultaneous OCT Images Assist in the Interpretation of Dark-Field Images in Eyes with Retinal Pathology
The cellular-level visualization of retinal microstructures such as blood vessel wall components, not available with other imaging modalities, is provided with unprecedented details by dark-field imaging configurations; however, the interpretation of such images alone is sometimes difficult since multiple structural disturbances may be present in the same time. Particularly in eyes with retinal pathology, microstructures may appear in high-resolution retinal images with a wide range of sizes, sharpnesses, and brightnesses. In this paper we show that motion contrast and phase gradient imaging modalities, as well as the simultaneous acquisition of depth-resolved optical coherence tomography (OCT) images, provide additional insight to help understand the retinal neural and vascular structures seen in dark-field images and may enable improved diagnostic and treatment plans.
PMCID:10814023
PMID: 38248061
ISSN: 2075-4418
CID: 5624552
LIMBARE: An Advanced Linear Mixed-Effects Breakpoint Analysis With Robust Estimation Method With Applications to Longitudinal Ophthalmic Studies
PURPOSE/UNASSIGNED:Broken stick analysis is a widely used approach for detecting unknown breakpoints where the association between measurements is nonlinear. We propose LIMBARE, an advanced linear mixed-effects breakpoint analysis with robust estimation, especially designed for longitudinal ophthalmic studies. LIMBARE accommodates repeated measurements from both eyes and over time, and it effectively addresses the presence of outliers. METHODS/UNASSIGNED:The model setup of LIMBARE and the computing algorithm for point and confidence interval estimates of the breakpoint were introduced. The performance of LIMBARE and other competing methods was assessed via comprehensive simulation studies and application to a longitudinal ophthalmic study with 216 eyes (145 subjects) followed for an average of 3.7 ± 1.3 years to examine the longitudinal association between structural and functional measurements. RESULTS/UNASSIGNED:In simulation studies, LIMBARE showed the smallest bias and mean squared error for estimating the breakpoint, with an empirical coverage probability of corresponding confidence interval estimates closest to the nominal level for scenarios with and without outlier data points. In the application to the longitudinal ophthalmic study, LIMBARE detected two breakpoints between visual field mean deviation (MD) and retinal nerve fiber layer thickness and one breakpoint between MD and cup-to-disc ratio, whereas the cross-sectional analysis approach detected only one and none, respectively. CONCLUSIONS/UNASSIGNED:LIMBARE enhances breakpoint estimation accuracy in longitudinal ophthalmic studies, and the cross-sectional analysis approach is not recommended for future studies. TRANSLATIONAL RELEVANCE/UNASSIGNED:Our proposed method and companion R package provide a valuable computational tool for advancing longitudinal ophthalmology research and exploring the association relationships among ophthalmic variables.
PMCID:10807490
PMID: 38241038
ISSN: 2164-2591
CID: 5624452
Combining Riboflavin/UV-A Light and Rose Bengal/Green Light Corneal Cross-Linking Increases the Resistance of Corneal Enzymatic Digestion
PURPOSE/UNASSIGNED:The purpose of this study was to determine if concurrent riboflavin/UV-A light (RF/UV-A) and rose Bengal/green light (RB/green) epi-off PACK-CXL enhances corneal resistance to enzymatic digestion compared to separate chromophore/light treatments. METHODS/UNASSIGNED:Ex vivo porcine corneas were allocated as follows. Group A corneas were soaked with riboflavin (RF) and were either not irradiated (A1, controls) or were irradiated with 10 (A2) or 15 J/cm² (A3) UV-A light at 365 nm, respectively. Group B corneas were soaked with RB and either not irradiated (B1, controls) or were illuminated with 10 (B2) or 15 J/cm² (B3) green light at 525 nm, respectively. Corneas in group C were soaked with both RF and RB and were either not irradiated (C1, controls) or were subjected to the same session consecutive 10 J/cm2 (C2) or 15 J/cm2 (C3) UV-A and green light exposure. Following treatment, all corneas were exposed to 0.3% collagenase A to assess digestion time until corneal button dissolution. RESULTS/UNASSIGNED:A1 to A3 digestion times were 21.38, 30.5, and 32.25 hours, respectively, with A2 and A3 showing increased resistance to A1. B1-3 had digestion times of 31.2, 33.81, and 34.38 hours, with B3 resisting more than B1. C1 to C3 times were 33.47, 39.81, and 51.94 hours; C3 exhibited superior resistance to C1 and C2 (both P < 0.05). CONCLUSIONS/UNASSIGNED:Same-session combined RF/UV-A and RB/green PACK-cross-linking significantly increases corneal enzymatic digestion resistance over standalone treatments. TRANSLATIONAL RELEVANCE/UNASSIGNED:Combining RF-based and RB-based PACK-CXL considerably increases corneal collagenase digestion resistance, potentially minimizing ulcer size in clinical contexts.
PMCID:10833050
PMID: 38289609
ISSN: 2164-2591
CID: 5627502
Spontaneous Reattachment of a Detached Sutured Descemet-Stripping Automated Endothelial Keratoplasty Graft
Introduction: This is a case report of a spontaneous reattachment of Descemet-stripping automated endothelial keratoplasty (DSAEK). This graft was primarily sutured, and 20% sulfur hexafluoride (SF6) was injected into the anterior chamber, followed by graft detachment and spontaneous reattachment, 3 months later. Case Presentation: A 78-year-old male presented with DSAEK graft detachment, which was the patient's second DSAEK (the first also did not adhere). During the second surgery, the DSAEK graft was sutured and 20% SF6 was injected intraoperatively. Graft reattachment occurred without any intervention or repositioning 3 months after the 2nd DSAEK surgery. Conclusion: Spontaneous DSEAK late graft reattachment is possible, particularly in the setting of an anchoring suture. In some patients, waiting can be an option that can spare the patient the possible risks of graft repositioning, rebubbling, or repeating the DSAEK. Suturing the DSAEK graft primarily may have served as an anchor to keep the graft approximate and aid in attachment. A graft suture can be considered in the setting of a previously failed DSAEK due to DSAEK graft detachment.
SCOPUS:85182893300
ISSN: 1663-2699
CID: 5629412
Motion Contrast, Phase Gradient, and Simultaneous OCT Images Assist in the Interpretation of Dark-Field Images in Eyes with Retinal Pathology
The cellular-level visualization of retinal microstructures such as blood vessel wall components, not available with other imaging modalities, is provided with unprecedented details by dark-field imaging configurations; however, the interpretation of such images alone is sometimes difficult since multiple structural disturbances may be present in the same time. Particularly in eyes with retinal pathology, microstructures may appear in high-resolution retinal images with a wide range of sizes, sharpnesses, and brightnesses. In this paper we show that motion contrast and phase gradient imaging modalities, as well as the simultaneous acquisition of depth-resolved optical coherence tomography (OCT) images, provide additional insight to help understand the retinal neural and vascular structures seen in dark-field images and may enable improved diagnostic and treatment plans.
SCOPUS:85183192427
ISSN: 2075-4418
CID: 5629192
Model-based correction of rapid thermal confounds in fluorescence neuroimaging of targeted perturbation
SIGNIFICANCE/UNASSIGNED:An array of techniques for targeted neuromodulation is emerging, with high potential in brain research and therapy. Calcium imaging or other forms of functional fluorescence imaging are central solutions for monitoring cortical neural responses to targeted neuromodulation, but often are confounded by thermal effects that are inter-mixed with neural responses. AIM/UNASSIGNED:Here, we develop and demonstrate a method for effectively suppressing fluorescent thermal transients from calcium responses. APPROACH/UNASSIGNED: RESULTS/UNASSIGNED: CONCLUSIONS/UNASSIGNED:The developed method for canceling transient thermal fluorescence quenching could also find applications with optical stimulation techniques to monitor thermal effects and disentangle them from neural responses. This approach may help deepen our understanding of the mechanisms and macroscopic effects of ultrasound neuromodulation, further paving the way for tailoring the stimulation regimes toward specific applications.
PMCID:10871046
PMID: 38371339
ISSN: 2329-423x
CID: 5634002
Risk of Stroke, Myocardial Infarction, Deep Vein Thrombosis, Pulmonary Embolism, and Death After Retinal Vein Occlusion
PURPOSE/OBJECTIVE:To examine rates of stroke, myocardial infarction (MI), deep vein thrombosis (DVT), pulmonary embolism (PE), and death in patients after retinal vein occlusion (RVO) compared to controls. DESIGN/METHODS:Retrospective cohort study. METHODS:An aggregated electronic health records research network, TriNetX, was used to identify patients with diagnosis of RVO and a control group of patients with cataract. Patients were excluded if they had history of stroke, MI, DVT, or PE within 2 years of diagnosis of RVO or cataract. Propensity score matching was performed to control for baseline demographics and medical comorbidities. Main outcomes included relative risk (RR) of death, stroke, MI, DVT, and PE after RVO compared to those in matched controls. RESULTS:A total of 45,304 patients were included in each cohort. There was elevated risk of death in the RVO cohort compared to the control cohort at 1 year (RR = 1.30, P < .01), 5 years (RR = 1.22, P < .01), and 10 years (RR = 1.08, P < .01). There was elevated risk of stroke at 1 year (RR = 1.61, P < .01), 5 years (RR = 1.31, P < .01), and 10 years (RR = 1.18, P < .01). There was elevated risk of MI at 1 year (RR = 1.26, P < .01) and 5 years (RR = 1.13, P < .01), but not at 10 years (RR = 1.06, P = .12). There was mildly elevated risk of DVT at 1 year (RR = 1.65, P < .01) but not at 5 years (RR = 0.94, P = .94) or 10 years (RR = 1.05, P = .37). There was no elevated risk of PE at 1 year (RR = 0.98, P = 0.80), 5 years (RR = 0.95, P = .42), or 10 years (RR = 0.85, P =.40). CONCLUSIONS:There is an increased rate of death, stroke, and MI after RVO compared to those in matched controls. We emphasize the need for long-term systemic evaluation after RVO.
PMID: 37660963
ISSN: 1879-1891
CID: 5613472
Assessment of Remote Training, At-Home Testing, and Test-Retest Variability of a Novel Test for Clustered Virtual Reality Perimetry
OBJECTIVE:To assess the feasibility of remotely training glaucoma patients to take a 10-session clustered virtual reality (VR) visual field (VF) test (Vivid Vision Perimetry [VVP-10]) at home, analyze results for test-retest variability, and assess correspondence with conventional perimetry. DESIGN/METHODS:Cross-sectional study. SUBJECTS/METHODS:Twenty-one subjects with glaucoma were enrolled and included in the feasibility assessment of remote training. Thirty-six eyes were used for test-retest analysis and determination of concordance with the Humphrey Field Analyzer (HFA). METHODS:Subjects were provided with a mobile VR headset containing the VVP-10 test software and trained remotely via video conferencing. Subjects were instructed to complete 10 sessions over a 14-day period. MAIN OUTCOME MEASURES/METHODS:Feasibility was determined by the number of subjects who were able to independently complete VVP-10 over the 14-day period after 1 remote training session. The intraclass correlation coefficient (ICC) for average fraction seen across 10 sessions and the standard error (SE) of the mean were primary outcome measures for assessing test-retest variability. Correlation with HFA mean sensitivity (MS) across eyes, was a secondary outcome measure. RESULTS:Twenty subjects (95%) successfully completed the VVP-10 test series after 1 training session. The ICC for VVP-10 was 0.95 (95% confidence interval [CI], 0.92-0.97). The mean SE in units of fraction seen was 0.012. The Spearman correlations between VVP-10 average fraction seen and HFA MS were 0.87 (95% CI, 0.66-0.98) for moderate-to-advanced glaucoma eyes, and decreased to 0.67 (95% CI, 0.28-0.94) when all eyes were included. CONCLUSIONS:Remote training of patients at home is feasible, and subsequent remote clustered VF testing using VVP-10 by patients on their own, without any further interactions with caregivers or study staff, was possible. At-home VVP-10 results demonstrated low test-retest variability. Future studies must be conducted to determine if VVP-10, taken at home as convenient for the patient, may be a viable supplement to provide equivalent or complementary results to that of standard in-clinic assessment of visual function in glaucoma. FINANCIAL DISCLOSURE(S)/BACKGROUND:Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
PMID: 37619815
ISSN: 2589-4196
CID: 5598802
Interim Analysis of Clinical Outcomes with Open versus Closed Conjunctival Implantation of the XEN45 Gel Stent
OBJECTIVE:To examine the longitudinal postoperative outcomes of open versus closed conjunctiva implantation of the XEN45 gel stent. DESIGN/METHODS:Retrospective multicenter study. SUBJECTS/METHODS:One hundred ninety-three patients with glaucoma underwent XEN45 implantation via an open or closed conjunctiva approach. METHODS:Data on patient demographics; diagnoses; preoperative and postoperative clinical data; outcome measures, including intraocular pressure (IOP); use of glaucoma medications; visual acuity; and complications were collected. Statistical analyses were performed with P < 0.05 as significant. MAIN OUTCOME MEASURES/METHODS:Failure was defined as < 20% reduction in IOP from the medicated baseline or a IOP of > 21 mmHg at 2 consecutive visits at postoperative month 1 and beyond, the need for subsequent operative intervention or additional glaucoma surgery, or a catastrophic event, such as loss of light perception. Eyes that had not failed by these criteria and were not on glaucoma medications were considered complete successes. Overall success was defined as those who achieved success either with or without topical medications. RESULTS:Patients were followed for an average of 17 months. Complete success was achieved in 42.5% and 24.7% of the open and closed groups, respectively (P = 0.01). Overall success was achieved in 64.2% and 37.0% of the open and closed groups, respectively (P < 0.001) at the last follow-up. Bleb needling was performed in 12.4% of eyes in the open group compared with 40% of eyes in the closed group. An IOP spike of ≥ 10 mmHg was twice as likely to occur in the closed group compared with the open group during the postoperative period (40% vs. 18%; P = 0.001). CONCLUSIONS:Implantation of XEN45 with opening of the conjunctiva resulted in a lower IOP with greater success and lower needling rate compared with those achieved with the closed conjunctiva technique. Similar rates of postoperative complications and vision loss were noted in each group. Although both procedures provide substantial IOP reduction, the open technique appears to result in higher success rates and fewer postoperative interventions. FINANCIAL DISCLOSURE(S)/BACKGROUND:Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
PMID: 37709048
ISSN: 2589-4196
CID: 5593442
Letter to the Editor regarding "Cutis marmorata telangiectatica congenita: Incidence of extracutaneous manifestations and a proposed clinical definition" [Letter]
PMID: 38494785
ISSN: 1525-1470
CID: 5639992
Bilateral subperiosteal orbital hematomas following cerebral aneurysm embolization: An atypical presentation of acute vision loss
PMID: 38154176
ISSN: 1532-2653
CID: 5623322
Analysis of ChatGPT responses to patient-oriented questions on common ophthalmic procedures [Letter]
PMID: 38140836
ISSN: 1442-9071
CID: 5612022
Distinctive Optical Coherence Tomography Angiography and Indocyanine Green Angiography Imaging Patterns in Topiramate-Induced Choroidal Effusion
PURPOSE/OBJECTIVE:To describe novel findings seen on optical coherence tomography angiography (OCTA) and indocyanine green angiography (ICGA) in a young male patient presenting with bilateral topiramate-induced choroidal effusion. METHODS:Retrospective case report. A comprehensive ophthalmic examination was conducted and multimodal imaging techniques, including B-scan ultrasound, OCT, OCTA, and ICGA were analyzed. RESULTS:A male in his 30s presented with a myopic shift due to bilateral choroidal effusion induced by a medication containing topiramate prescribed for weight loss. ICGA showed multiple hypofluorescent spots within the choroid corresponding to areas of reduced OCTA flow signal in both the inner and deeper en face choroidal slabs. Symptoms and abnormal imaging findings resolved within five days of discontinuing the medication. CONCLUSION/CONCLUSIONS:Findings observed with OCTA and ICGA together suggest multifocal reversible areas of reduced choroidal vascular flow occurring in a topiramate-induced choroidal effusion. We propose that this transient hypoperfusion is due to compression from deeper choroidal vessels with a congested choroid.
PMID: 38109671
ISSN: 1937-1578
CID: 5612492
Central Bouquet Hemorrhage. Clinical and multimodal imaging features
PURPOSE/OBJECTIVE:To describe the clinical characteristics, multimodal imaging features, and anatomic basis of a distinctive pattern of deep retinal hemorrhages located in the central fovea, a presentation referred to as "central bouquet hemorrhage" (CBH). METHODS:Retrospective, observational, multicenter case series of eyes with CBH. Multimodal imaging features were reviewed and analyzed. RESULTS:Ten eyes from 10 patients (4 women and 6 men), with a mean age of 55.6±21.7 years (range 25-84 years) were included. Underlying etiologies were neovascular age-related macular degeneration (40%), lacquer cracks in pathological myopia (30%), macular telangiectasia type 2 (10%), proliferative diabetic retinopathy (10%), and ocular trauma associated with angioid streaks (10%). On ophthalmoscopy, all eyes with CBH displayed a deep retinal hemorrhage with round margins in the central fovea and associated with petaloid hemorrhages radiating in the surrounding Henle fiber layer (HFL). Cross-sectional optical coherence tomography (OCT) showed a well-delineated round hyperreflective lesion involving the central foveal HFL/outer nuclear layer (ONL) in all cases. Accompanying hyperreflective hemorrhages tracking along the obliquely oriented HFL were present in all eyes. Resolution occurred in all patients, either spontaneously (30%) or after treatment with intravitreal anti-vascular endothelial growth factor injections (70%), and was associated with partial visual acuity improvement (from 20/113 to 20/36). CONCLUSION/CONCLUSIONS:"Central bouquet hemorrhage" is a novel descriptive term describing a characteristic round pattern of intraretinal blood in the fovea associated with HFL hemorrhage and encountered in a spectrum of macular disease.
PMID: 38109663
ISSN: 1539-2864
CID: 5612482
A Rare Case of Uremic Optic Neuropathy Without Optic Disc Edema and With a Unique Imaging Correlate: Bilateral Diffusion Restriction of the Optic Nerves
PMID: 38085604
ISSN: 1536-5166
CID: 5589192
Reassessment of hyperautofluorescent rings in retinitis pigmentosa using novel retinal imaging techniques
SCOPUS:85168321794
ISSN: 2451-9936
CID: 5567622
Progressive myelinated retinal nerve fibers in a 10-year-old boy with Crouzon syndrome after craniofacial surgery
Purpose: We present a case of a 10-year-old boy with Crouzon syndrome that demonstrates progressive myelinated retinal nerve fibers (MRNF). Observations: A 10-year-old boy was referred for ophthalmic examination due to clusters of opaque white fibers around his optic nerve. Past surgical history includes craniofacial surgery at 3 years of age secondary to the deteriorating vision from increased intracranial pressure and papilledema. Upon examination (now 6.5 years post-craniofacial surgery), the patient denied any ocular complaints. The fundus examination showed progressively enlarged myelination of the retinal nerve fiber layer (right eye > left eye). Although previous cases of MRNF with Crouzon syndrome have been reported, our case is unique given its post-operative status with early onset of MRNF. Conclusion and importance: This case report documents the photographic progression of bilateral myelinated retinal nerve fibers (MRNF) in a pediatric case of Crouzon syndrome post-craniofacial surgery secondary to increased intracranial pressure and papilledema. Based on our patient, craniofacial decompression surgery may not prevent the development of MRNF. The exact mechanisms of MRNF are still being studied. Further investigations correlating craniofacial surgeries, increased intracranial pressure, and progression of myelinated retinal nerve fibers are needed to understand this process.
SCOPUS:85165282427
ISSN: 2451-9936
CID: 5548102
Reducing Ophthalmic Health Disparities Through Transfer Learning: A Novel Application to Overcome Data Inequality
PURPOSE/UNASSIGNED:Race disparities in the healthcare system and the resulting inequality in clinical data among different races hinder the ability to generate equitable prediction results. This study aims to reduce healthcare disparities arising from data imbalance by leveraging advanced transfer learning (TL) methods. METHOD/UNASSIGNED:We examined the ophthalmic healthcare disparities at a population level using electronic medical records data from a study cohort (N = 785) receiving care at an academic institute. Regression-based TL models were usesd, transferring valuable information from the dominant racial group (White) to improve visual field mean deviation (MD) rate of change prediction particularly for data-disadvantaged African American (AA) and Asian racial groups. Prediction results of TL models were compared with two conventional approaches. RESULTS/UNASSIGNED:Disparities in socioeconomic status and baseline disease severity were observed among the AA and Asian racial groups. The TL approach achieved marked to comparable improvement in prediction accuracy compared to the two conventional approaches as evident by smaller mean absolute errors or mean square errors. TL identified distinct key features of visual field MD rate of change for each racial group. CONCLUSIONS/UNASSIGNED:The study introduces a novel application of TL that improved reliability of the analysis in comparison with conventional methods, especially in small sample size groups. This can improve assessment of healthcare disparity and subsequent remedy approach. TRANSLATIONAL RELEVANCE/UNASSIGNED:TL offers an equitable and efficient approach to mitigate healthcare disparities analysis by enhancing prediction performance for data-disadvantaged group.
PMCID:10697175
PMID: 38038606
ISSN: 2164-2591
CID: 5589882
Bilateral exudative retinal detachments after subretinal gene therapy with voretigene neparvovec-rzyl for RPE65 Leber Congenital Amaurosis
Purpose: To report panuveitis with exudative retinal detachments in a healthy 27-year-old woman with biallelic mutations in the RPE65 gene, who underwent bilateral sequential gene therapy with subretinal administration of voretigene neparvovec-rzyl. Observations: Visual acuity improved for 30 days after surgery as oral corticosteroids were tapered. At postoperative week 6, vision declined due to sudden onset uveitis and exudative retinal detachments in both eyes. HLA Class II typing revealed the haplotype associated with sympathetic ophthalmia and Vogt-Koyanagi-Harada (VKH). The inflammation improved after corticosteroid, mycophenolate mofetil, and adalimumab therapy while vision remained poor. Conclusions and Importance: Surgically-induced sympathetic ophthalmia is a plausible explanation for the clinical findings; surgery of both eyes within one week would conceal the inciting eye. VKH or inflammation related to the gene therapy are other possible etiologies but severe bilateral panuveitis has not been reported with voretigene neparvovec-rzyl. Informed consent for gene therapy surgery should include a discussion of the rare complication of sympathetic ophthalmia following vitrectomy surgery.
SCOPUS:85165081546
ISSN: 2451-9936
CID: 5548142
Omidenepag Isopropyl in Latanoprost Low/Nonresponders With Primary Open Angle Glaucoma or Ocular Hypertension: A Phase 3, Nonrandomized, Two-Phase, Open-Label Study
PRCIS/CONCLUSIONS:This study demonstrates the efficacy and safety of once-daily 0.002% omidenepag isopropyl (OMDI) in patients with primary open angle glaucoma (POAG) or ocular hypertension (OHT) who do not respond or respond poorly to latanoprost. PURPOSE/OBJECTIVE:The purpose of this study was to evaluate the intraocular pressure (IOP)-lowering efficacy and safety of OMDI in latanoprost low/nonresponders with POAG or OHT. MATERIALS AND METHODS/METHODS:Phase 3, nonrandomized, 2-phase, open-label, multicenter study (NCT03697811) in the United States. Key inclusion criteria included individuals aged 18 years or above, POAG or OHT diagnosis in both eyes, IOP ≥22 mm Hg in ≥1 eye, and ≤34 mm Hg in both eyes at all time points. Overall, 107 patients were enrolled; 104 completed treatment. Included a screening period (≤35-day washout period and 8-week latanoprost run-in period) and a 3-month treatment period comprising one drop of OMDI 0.002% once daily in both eyes. The primary study endpoint was changed from baseline in the mean diurnal (MD) IOP at month 3. Safety endpoints included incidence of adverse events, serious adverse events, and adverse drug reactions. RESULTS:At baseline (visit 4), 75 (70.1%) patients had POAG, 32 (29.9%) had OHT, and 68 (63.6%) had prior use of prostaglandin/prostaglandin analogs (37.4% of whom used latanoprost). The mean (SD) baseline MD IOP was 23.34 mm Hg (2.12). The mean (SD) 3-month (visit 7) MD IOP change from baseline (following latanoprost run-in period and OMDI treatment period) was an additional decrease of 2.96 mm Hg (2.83) ( P <0.0001). No significant safety issues were reported during OMDI treatment. CONCLUSIONS:These data demonstrate OMDI efficacy and safety in latanoprost low/nonresponders with POAG or OHT, suggesting OMDI is a treatment option in the patient population in this study.
PMCID:10681282
PMID: 37853676
ISSN: 1536-481x
CID: 5628112
Risk of Stroke, Myocardial Infarction, and Death After Retinal Artery Occlusion
IMPORTANCE/UNASSIGNED:Patients with retinal artery occlusions (RAOs) are recommended to have emergent stroke workup, although the true risk of death and subsequent vascular events post-RAO is not clear. OBJECTIVE/UNASSIGNED:To determine short-term and long-term rates of stroke, myocardial infarction (MI), and death in patients after RAO compared with a control cohort. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This retrospective cohort study used aggregated electronic health records from January 1, 2003, through April 14, 2023, from TriNetX, a network with data from more than 111 million patients. Patients with RAO and a cataract control group were identified and matched for age, sex, race, and comorbidities, including hypertension, diabetes, hyperlipidemia, and smoking status. Patients were excluded if they had a stroke or MI within 2 years before the diagnosis of RAO or cataract. EXPOSURE/UNASSIGNED:International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, diagnosis code for RAO or age-related cataract. MAIN OUTCOMES AND MEASURES/UNASSIGNED:Rate of death, stroke, and MI at 2 weeks, 30 days, 1 year, 5 years, and 10 years after RAO compared with matched controls. RESULTS/UNASSIGNED:There were a total of 34 874 patients with at least 1 year of follow-up in the RAO cohort. The mean (SD) age at the RAO event was 66 (15.2) years. The rate of death after RAO diagnosis was higher than after cataract diagnosis at 2 weeks (0.14% vs 0.06%; relative risk [RR], 2.45; 95% CI, 1.46-4.12; risk difference [RD], 0.08%; 95% CI, 0.04%-0.13%; P < .001), 30 days (0.29% vs 0.14%; RR, 2.10; 95% CI, 1.49-2.97; RD, 0.15%; 95% CI, 0.08%-0.22%; P < .001), 1 year (3.51% vs 1.99%; RR, 1.78; 95% CI, 1.61-1.94; RD, 1.41%; 95% CI, 1.17%-1.66%; P < .001), 5 years (22.74% vs 17.82%; RR, 1.28; 95% CI, 1.23-1.33; RD, 4.93%; 95% CI, 4.17%-5.68%; P < .001), and 10 years (57.86% vs 55.38%; RR, 1.05; 95% CI, 1.02-1.07; RD, 2.47%; 95% CI, 1.25%-3.69%; P < .001). Risk of stroke after RAO was higher at 2 weeks (1.72% vs 0.08%; RR, 21.43; 95% CI, 14.67-31.29; RD, 1.64%; 95% CI, 1.50%-1.78%; P < .001), 30 days (2.48% vs 0.18%; RR, 14.18; 95% CI, 10.94-18.48; RD, 2.31%; 95% CI, 2.14%-2.47%; P < .001), 1 year (5.89% vs 1.13%; RR, 5.20; 95% CI, 4.67-5.79; RD, 4.64%; 95% CI, 4.37%-4.91%; P < .001), 5 years (10.85% vs 4.86%; RR, 2.24; 95% CI, 2.09-2.40; RD, 6.00%; 95% CI, 5.50%-6.50%; P < .001), and 10 years (14.59% vs 9.18%; RR, 1.59; 95% CI, 1.48-1.70; RD, 5.41%; 95% CI, 4.62%-6.21%; P < .001). Risk of MI after RAO was higher at 2 weeks (0.16% vs 0.06%; RR, 3.00; 95% CI, 1.79-5.04; RD, 0.11%; 95% CI, 0.06%-0.16%; P < .001), 30 days (0.27% vs 0.10%; RR, 2.61; 95% CI, 1.78-3.83; RD, 0.17%; 95% CI, 0.10%-0.23%; P < .001), 1 year (1.66% vs 0.97%; RR, 1.72; 95% CI, 1.51-1.97; RD, 0.59%; 95% CI, 0.42%-0.76%; P < .001), 5 years (6.06% vs 5.00%; RR, 1.21; 95% CI, 1.12-1.31; RD, 1.07%; 95% CI, 0.64%-1.50%; P < .001), and 10 years (10.55% vs 9.43%; RR, 1.12; 95% CI, 1.04-1.21; RD, 1.13%; 95% CI, 0.39%-1.87%; P = .003). CONCLUSIONS AND RELEVANCE/UNASSIGNED:This study showed an increased risk of death, stroke, and MI in patients with RAO at both short-term and long-term intervals after RAO compared with a matched control population diagnosed with cataract. These findings suggest a potential need for multidisciplinary evaluation and long-term systemic follow-up of patients post-RAO.
PMCID:10603578
PMID: 37883068
ISSN: 2168-6173
CID: 5613002
Myopia Management: Outdoor Time to Reverse the Trend
PMID: 37990440
ISSN: 1542-233x
CID: 5608432
Tamoxifen Retinopathy on High-Resolution OCT
PMID: 37498267
ISSN: 2468-6530
CID: 5589992
Impact of high-risk prenatal screening results for 22q11.2 deletion syndrome on obstetric and neonatal management: Secondary analysis from the SMART study
OBJECTIVE:One goal of prenatal genetic screening is to optimize perinatal care and improve infant outcomes. We sought to determine whether high-risk cfDNA screening for 22q11.2 deletion syndrome (22q11.2DS) affected prenatal or neonatal management. METHODS:This was a secondary analysis from the SMART study. Patients with high-risk cfDNA results for 22q11.2DS were compared with the low-risk cohort for pregnancy characteristics and obstetrical management. To assess differences in neonatal care, we compared high-risk neonates without prenatal genetic confirmation with a 1:1 matched low-risk cohort. RESULTS:Of 18,020 eligible participants enrolled between 2015 and 2019, 38 (0.21%) were high-risk and 17,982 (99.79%) were low-risk for 22q11.2DS by cfDNA screening. High-risk participants had more prenatal diagnostic testing (55.3%; 21/38 vs. 2.0%; 352/17,982, p < 0.001) and fetal echocardiography (76.9%; 10/13 vs. 19.6%; 10/51, p < 0.001). High-risk newborns without prenatal diagnostic testing had higher rates of neonatal genetic testing (46.2%; 6/13 vs. 0%; 0/51, P < 0.001), echocardiography (30.8%; 4/13 vs. 4.0%; 2/50, p = 0.013), evaluation of calcium levels (46.2%; 6/13 vs. 4.1%; 2/49, P < 0.001) and lymphocyte count (53.8%; 7/13 vs. 15.7%; 8/51, p = 0.008). CONCLUSIONS:High-risk screening results for 22q11.2DS were associated with higher rates of prenatal and neonatal diagnostic genetic testing and other 22q11.2DS-specific evaluations. However, these interventions were not universally performed, and >50% of high-risk infants were discharged without genetic testing, representing possible missed opportunities to improve outcomes for affected individuals.
PMID: 38066724
ISSN: 1097-0223
CID: 5591652
From Soma to Synapse: Imaging Age-Related Rod Photoreceptor Changes in the Mouse with Visible Light OCT
PURPOSE/UNASSIGNED:Although the outer nuclear layer (ONL) and outer plexiform layer (OPL) each exhibit a complex internal organization, near-infrared OCT depicts both as monolithic bands. Here, using visible light OCT in the C57BL/6J mouse retina, sublaminar age-related changes in photoreceptor features were imaged and interpreted. These features were (1) oscillations in reflectivity, or striations, in the ONL and (2) a moderately reflective subband in the OPL. DESIGN/UNASSIGNED:Cross-sectional study. PARTICIPANTS/UNASSIGNED:Pigmented mice (C57BL/6J, n = 14). METHODS/UNASSIGNED:A 1.0-μm axial resolution visible light spectral/Fourier domain OCT system was used for in vivo retinal imaging. Light and electron microscopy were performed ex vivo. Linear mixed effects models or regression were employed for statistical analysis. MAIN OUTCOME MEASURES/UNASSIGNED:Comparison of OCT subbands with corresponding histological features, as well as quantification of subband thickness and reflectivity. RESULTS/UNASSIGNED:Corresponding histological comparisons confirm that striations in the ONL arise from the rowlike arrangement of photoreceptor nuclei and reveal that the moderately reflective OPL subband arises from rod spherules. Compression of outer ONL striations with age suggests changes in soma organization. Thinning of the moderately reflective OPL subband with age supports a reduction of synapses in the OPL. Critically, the ONL somas are tightly correlated with the purported spherule layer but not with the rest of the OPL. CONCLUSIONS/UNASSIGNED:Visible light OCT imaging of the mouse OPL resolves postsynaptic and synaptic differences. Visible light OCT can study rod photoreceptor changes from the soma to the synapse in the living mouse retina. FINANCIAL DISCLOSURES/UNASSIGNED:Proprietary or commercial disclosure may be found after the references.
PMCID:10302163
PMID: 37388138
ISSN: 2666-9145
CID: 5540552
Prevalence of Body Dysmorphic Disorder in Orbital Plastic Surgery and Its Relationship with the Use of Social Media
BACKGROUND:The prevalence of body dysmorphic disorder (BDD) in the general population ranges from 0.7 to 2.4%; however, higher rates are seen among aesthetic patients. Given the recent rise in popularity of cosmetic surgery, particularly in the post-COVID pandemic setting, the authors hypothesize the prevalence has increased. The purpose of the study is to examine the prevalence of BDD in patients presenting to an oculoplastic surgery clinic at an academic center and determine correlation with social media use. METHODS:This is a survey of patients presenting to the oculoplastic surgery clinic. Participants completed the Dysmorphic Concern Questionnaire (DCQ), in addition to survey questions about social media use. Main outcomes included a positive screen and social media use. RESULTS:A total of 175 patients that presented to the oculoplastic and reconstructive surgery clinic were surveyed. All patients, including cosmetic, functional, and non-surgical, were offered participation in the survey. 9.13% of all patients screened positive for BDD. Patients that screened positive were more commonly female (71.43%). The distribution of patients with BDD was even between Hispanics (52.38%) and non-Hispanics, and 85.71% of patients with BDD were Caucasian. Of patients that screened positive, 71.43% use social media. CONCLUSIONS:The prevalence of BDD may have increased in the past seven years and is seen most in females and Caucasians. There is a positive correlation with social media, which has increased in popularity since the COVID-19 pandemic. It is important to maintain a high clinical suspicion for BDD and consider screening if there is concern. LEVEL OF EVIDENCE IV/METHODS:This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
PMID: 37464215
ISSN: 1432-5241
CID: 5534022
Biologically derived epicardial patch induces macrophage mediated pathophysiologic repair in chronically infarcted swine hearts
There are nearly 65 million people with chronic heart failure (CHF) globally, with no treatment directed at the pathologic cause of the disease, the loss of functioning cardiomyocytes. We have an allogeneic cardiac patch comprised of cardiomyocytes and human fibroblasts on a bioresorbable matrix. This patch increases blood flow to the damaged heart and improves left ventricular (LV) function in an immune competent rat model of ischemic CHF. After 6 months of treatment in an immune competent Yucatan mini swine ischemic CHF model, this patch restores LV contractility without constrictive physiology, partially reversing maladaptive LV and right ventricular remodeling, increases exercise tolerance, without inducing any cardiac arrhythmias or a change in myocardial oxygen consumption. Digital spatial profiling in mice with patch placement 3 weeks after a myocardial infarction shows that the patch induces a CD45pos immune cell response that results in an infiltration of dendritic cells and macrophages with high expression of macrophages polarization to the anti-inflammatory reparative M2 phenotype. Leveraging the host native immune system allows for the potential use of immunomodulatory therapies for treatment of chronic inflammatory diseases not limited to ischemic CHF.
PMCID:10676365
PMID: 38007534
ISSN: 2399-3642
CID: 5617542
Combined Face and Whole Eye Transplantation: Cadaveric Rehearsals and Feasibility Assessment
Background: In properly selected patients, combined face and whole eye transplantation (FWET) may offer a more optimal aesthetic and potentially functional outcome while avoiding the complications and stigma of enucleation and prosthetics. This study presents the most comprehensive cadaveric assessment for FWET to date, including rehearsal allograft procurement on a brain-dead donor. Methods: Over a 2-year period, 15 rehearsal dissections were performed on 21 cadavers and one brain-dead donor. After identification of a potential recipient, rehearsals assessed clinical feasibility and enabled operative planning, technical practice, refinement of personalized equipment, and improved communication among team members. Operative techniques are described. Results: Facial allograft procurement closely followed previously described face transplant techniques. Ophthalmic to superficial temporal (O-ST) vessel anastomosis for globe survival was assessed. Craniectomy allowed for maximal optic nerve and ophthalmic vessel pedicle length. Appropriate pedicle length and vessel caliber for O-ST anastomosis was seen. Research procurement demonstrated collateral blood flow to the orbit and surrounding structures from the external carotid system as well as confirmed the feasibility of timely O-ST anastomosis. Personalized cutting guides enabled highly accurate bony inset. Conclusions: This study formalizes an approach to FWET, which is feasible for clinical translation in judiciously selected patients. O-ST anastomosis seems to minimize retinal ischemia time and allow perfusion of the combined allograft on a single external carotid pedicle. Although restoration of vision likely remains out of reach, globe survival is possible.
SCOPUS:85178043696
ISSN: 2169-7574
CID: 5621122
Transdifferentiation and Intrachoroidal Migration of Melanotic Retinal Pigment Epithelium in Punctate Inner Choroiditis
PURPOSE/OBJECTIVE:To report the multimodal imaging features of hyperpigmented chorioretinal lesions originating from the retinal pigment epithelium (RPE) within punched-out lesions of punctate inner choroidopathy (PIC). METHODS:Retrospective case report. Multimodal imaging findings including fundus photography, optical coherence tomography (OCT), and OCT-angiography (OCTA) were analyzed. RESULTS:A 49-year-old female with myopic degeneration developed progressive lesions of PIC requiring immunosuppressive therapy with adalimumab. Within areas of punched-out chorioretinal atrophic lesions, the occurrence of hyperpigmented lesions were observed which enlarged and extended into the choroid over a multiyear follow-up. CONCLUSION/CONCLUSIONS:This case illustrates the development of pigmented choroidal lesions appearing to originate from the RPE through transdifferentiation following previous chorioretinal inflammatory lesions. The introduction of adalimumab treatment may have activated the cellular migration of the RPE. To the best of our knowledge, this is the first report of intrachoroidal RPE migration in PIC.
PMID: 37973041
ISSN: 1937-1578
CID: 5610412
Ocular trauma
[S.l.] : CRC Press, 2023
pp. 108-117
ISBN: 9781032328034
CID: 5614792
MULTIZONAL OUTER RETINOPATHY AND RETINAL PIGMENT EPITHELIOPATHY (MORR): A Newly Recognized Entity or an Unusual Variant of AZOOR?
PURPOSE:To describe specific clinical, multimodal imaging, and natural history features of an unusual variant of acute zonal occult outer retinopathy. METHODS:Retrospective, observational, longitudinal, multicenter case series. Patients exhibiting this unusual clinical condition among cases previously diagnosed with acute zonal occult outer retinopathy were included. Multimodal imaging, laboratory evaluations, and genetic testing for inherited retinal diseases were reviewed. RESULTS:Twenty eyes from 10 patients (8 females and 2 males) with a mean age of 54.1 ± 13.3 years (range, 38-71 years) were included. The mean follow-up duration was 13.1 ± 5.3 years (range, 8-23 years). Presenting symptoms were bilateral in 7 patients (85% of eyes) and included scotomata and photopsia. All patients had bilateral lesions at presentation involving the peripapillary and far peripheral retina. Baseline optical coherence tomography showed alteration of the retinal pigment epithelium and photoreceptor layers corresponding to zonal areas of fundus autofluorescence abnormalities. Centrifugal and centripetal progression of the peripapillary and far-peripheral lesions, respectively, occurred over the follow-up, resulting in areas of complete outer retinal and retinal pigment epithelium atrophy. CONCLUSION:Initial alteration of photoreceptors and retinal pigment epithelium and a stereotypical natural course that includes involvement of the far retinal periphery, characterize this unusual condition. It may represent a variant of acute zonal occult outer retinopathy or may be a new entity. We suggest to call it multizonal outer retinopathy and retinal pigment epitheliopathy .
PMCID:10589432
PMID: 37748093
ISSN: 1539-2864
CID: 5614102
PUNCTATE INNER PACHYCHOROIDOPATHY: Demographic and Clinical Features of Inner Choroidal Inflammation in Eyes with Pachychoroid Disease
PURPOSE:To perform an unsupervised machine learning clustering of patients with punctate inner choroidopathy (PIC) and provide new insights into the significance of pachychoroid disease features in PIC eyes. METHODS:Retrospective multicenter study, including 102 eyes from 82 patients diagnosed with PIC. Demographics, clinical data, and multimodal imaging, including fundus photography, optical coherence tomography, and indocyanine green angiography, were collected. Clusters of eyes were identified, and multilevel logistic regression analysis was performed to compare between-group differences. RESULTS:Using 17 clinical features, two distinct clusters of patients with PIC were identified. Cluster 1 patients were characterized by older age, high myopia, myopic maculopathy features, thin choroids, multiple lesions, and a higher likelihood of developing patchy chorioretinal atrophy. Cluster 2 consisted of younger age, emmetropia or low myopia, thick choroids, choroidal vascular hyperpermeability on late-phase indocyanine green angiography, and high prevalence of focal choroidal excavation. These features exhibited significant differences ( P < 0.05) between the two clusters. CONCLUSION:While PIC typically affects young myopic female patients with thin choroids, a subset of patients with PIC exhibits features associated with pachychoroid disease. Considering the potential influence of choroidal venous insufficiency on PIC manifestations and secondary complications, we propose the term "punctate inner pachychoroidopathy" to characterize this distinct subtype of PIC.
PMID: 37657077
ISSN: 1539-2864
CID: 5614042
INFLAMMATORY CELL ACTIVITY IN TREATED NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: A Histologic Case Study [Case Report]
BACKGROUND:Imaging indicators of macular neovascularization risk can help determine patient eligibility for new treatments for geographic atrophy secondary to age-related macular degeneration. Because type 1 macular neovascularization includes inflammation, we assessed by histology the distribution of cells with inflammatory potential in two fellow eyes with age-related macular degeneration. METHODS:Two eyes of a White woman in her 90's with type 3 macular neovascularization treated with antivascular endothelial growth factor were prepared for high-resolution histology. Eye-tracked spectral domain optical coherence tomography applied to the preserved donor eyes linked in vivo imaging to histology. Cells were enumerated in the intraretinal, subretinal, and subretinal retinal pigment epithelium (RPE)-basal lamina compartments on 199 glass slides. Cells with numerous organelles were considered to RPE-derived; cells with sparse RPE organelles were considered non-RPE phagocytes. RESULTS:Both eyes had soft drusen and abundant subretinal drusenoid deposit. In the retina and subretinal space, RPE-derived cells, including hyperreflective foci, were common (n = 125 and 73, respectively). Non-RPE phagocytes were infrequent (n = 5 in both). Over drusen, RPE morphology transitioned smoothly from the age-normal layer toward the top, suggesting transdifferentiation. The sub-RPE-basal lamina space had RPE-derived cells (n = 87) and non-RPE phagocytes (n = 49), including macrophages and giant cells. CONCLUSION:Numerous sub-RPE-basal lamina cells of several types are consistent with the documented presence of proinflammatory lipids in drusen and aged Bruch's membrane. The relatively compartmentalized abundance of infiltrating cells suggests that drusen contents are more inflammatory than subretinal drusenoid deposit, perhaps reflecting their environments. Ectopic RPE occurs frequently. Some manifest as hyperreflective foci. More cells may be visible as optical coherence tomography technologies evolve.
PMID: 37871271
ISSN: 1539-2864
CID: 5611612
Imaging Histology Correlations of Intraretinal Fluid in Neovascular Age-Related Macular Degeneration
PURPOSE/UNASSIGNED:Fluid presence and dynamism is central to the diagnosis and management of neovascular age-related macular degeneration. On optical coherence tomography (OCT), some hyporeflective spaces arise through vascular permeability (exudation) and others arise through degeneration (transudation). Herein we determined whether the histological appearance of fluid manifested this heterogeneity. METHODS/UNASSIGNED:Two eyes of a White woman in her 90s with anti-vascular endothelial growth factor treated bilateral type 3 neovascularization secondary to age-related macular degeneration were osmicated, prepared for submicrometer epoxy resin sections, and correlated to eye-tracked spectral domain OCT. Examples of intraretinal tissue fluid were sought among similarly prepared donor eyes with fibrovascular scars, in a web-based age-related macular degeneration histopathology resource. Fluid stain intensity was quantified in reference to Bruch's membrane and the empty glass slide. RESULTS/UNASSIGNED:Exudative fluid by OCT was slightly reflective and dynamically responded to anti-vascular endothelial growth factor. On histology, this fluid stained moderately, possessed a smooth and homogenous texture, and contained blood cells and fibrin. Nonexudative fluid in degenerative cysts and in outer retinal tubulation was minimally reflective on OCT and did not respond to anti-vascular endothelial growth factor. By histology, this fluid stained lightly, possessed a finely granular texture, and contained mainly tissue debris. Quantification supported the qualitative impressions of fluid stain density. Cells containing retinal pigment epithelium organelles localized to both fluid types. CONCLUSIONS/UNASSIGNED:High-resolution histology of osmicated tissue can distinguish between exudative and nonexudative fluid, some of which is transudative. TRANSLATIONAL RELEVANCE/UNASSIGNED:OCT and histological features of different fluid types can inform clinical decision-making and assist in the interpretation of newly available automated fluid detection algorithms.
PMCID:10637202
PMID: 37943552
ISSN: 2164-2591
CID: 5609862
Keratoplasty in the United States: Trends and Indications From 2015 to 2020
PURPOSE/OBJECTIVE:The aim of this study was to report trends in keratoplasty techniques and indications in the United States from 2015 to 2020. METHODS:This retrospective review of annual reports from the Eye Bank Association of America assessed domestic corneal graft distribution and surgical indication data for various types of keratoplasty. Trends in procedure volume and indications from 2015 to 2020 were analyzed using the Cochran-Armitage test. RESULTS:The total number of corneal transplants increased from 47,903 in 2015 to 49,143 in 2019, with a decline to 42,257 in 2020, most likely due to COVID-19. Penetrating keratoplasty (PK) volume decreased from 2015 to 2020 (19,160-15,402, 40% to 36.4%, P < 0.001), continuing a trend from the previous decade. Descemet membrane endothelial keratoplasty as a percentage of all keratoplasty procedures increased (9.8%-27.8%, P < 0.001), whereas Descemet stripping automated endothelial keratoplasty (47%-33.9%, P < 0.001) and anterior lamellar keratoplasty (ALK) decreased (2.3%-1.2%, P < 0.001).From 2017 to 2020, repeat corneal transplant was the most common specific indication for PK while ectasias/thinnings decreased in prevalence (15.6%-11.5%, P < 0.001). Ectasias/thinnings and endothelial dystrophy remained the leading indications for ALK and endothelial keratoplasty, respectively. CONCLUSIONS:From 2015 to 2020, keratoplasty trends in the United States showed a continuation of the decrease in PK and increase in Descemet membrane endothelial keratoplasty observed in the previous decade. The most common domestic indications from 2017 to 2020 have been repeat corneal graft, endothelial dystrophy, and ectasias/thinnings for PK, EK, and ALK, respectively.
PMID: 36730420
ISSN: 1536-4798
CID: 5420362
Miniature Palpebral Plexiform Neurofibroma in Neurofibromatosis Type 2
A 27-year-old woman with well-documented neurofibromatosis 2 developed a soft, painless, nodular lesion on the skin surface of the left upper eyelid over 2 years. Following excision, histopathology revealed a plexiform neurofibroma with intradermal nodules comprised of benign round and spindle cells that reacted diffusely with immunohistochemical stains SOX-10 and S100. A subset showed focal reactivity for neurofilament and CD34. A perineurium surrounded each nodule with cells staining positively for markers EMA (epithelial membrane antigen) and GLUT1 (glucose transporter 1). Plexiform neurofibromas are rare tumors that occur in 5%-15% of patients with neurofibromatosis 1. Cutaneous abnormalities in neurofibromatosis 2 have not been widely studied although reports have described schwannomas, plexiform schwannomas, and occasional neurofibromas. Plexiform neurofibromas in neurofibromatosis 2 have rarely been illustrated and the current case represents a unique bona fide eyelid example to date.
PMID: 37338324
ISSN: 1537-2677
CID: 5542602
Anti-vascular endothelial growth factor dosing frequency and visual outcomes in macular oedema following branch retinal vein occlusion
OBJECTIVES/OBJECTIVE:To determine the relationship between treatment frequency with intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents and visual acuity (VA) outcomes in eyes with macular oedema (MO) secondary to branch retinal vein occlusion (BRVO) in US clinical practice. METHODS:Study eyes that initiated anti-VEGF injections between January 2012 and May 2016 were followed for ≥1 year in a retrospective analysis of medical records (Vestrum Health database). Eyes were analysed in 2 cohorts by treatment duration (years 1 and 2) and then in 2 subcohorts by injection frequency (≤6 or ≥7 injections/year). RESULTS:Among 3099 eyes with MO secondary to BRVO, 1197 (38.6%) received ≤6 injections (mean injections, 4.6; baseline mean VA, 53 letters) and 1902 (61.4%) received ≥7 injections through 1 year (mean injections, 8.8; baseline mean VA, 52 letters). At year 1, mean VA gain from baseline was 10.4 versus 13.9 letters in eyes receiving ≤6 versus ≥7 injections (p < 0.001). At year 2, mean VA in eyes receiving ≤6 (n = 42) versus ≥7 injections (n = 227) was 64 versus 68 letters, respectively (p = 0.19). Mean VA change between the start and end of year 2 in eyes receiving ≥7 injections in year 1 and ≤6 in year 2 differed significantly from that of eyes receiving ≥7 injections in both years (-3.0 vs 0.7 letters, respectively; p < 0.001). CONCLUSIONS:In routine clinical practice, more frequent dosing with anti-VEGF agents was associated with greater visual benefits in eyes with MO secondary to BRVO.
PMID: 37156863
ISSN: 1476-5454
CID: 5509262
Combined Face and Whole Eye Transplantation: Cadaveric Rehearsals and Feasibility Assessment
BACKGROUND/UNASSIGNED:In properly selected patients, combined face and whole eye transplantation (FWET) may offer a more optimal aesthetic and potentially functional outcome while avoiding the complications and stigma of enucleation and prosthetics. This study presents the most comprehensive cadaveric assessment for FWET to date, including rehearsal allograft procurement on a brain-dead donor. METHODS/UNASSIGNED:Over a 2-year period, 15 rehearsal dissections were performed on 21 cadavers and one brain-dead donor. After identification of a potential recipient, rehearsals assessed clinical feasibility and enabled operative planning, technical practice, refinement of personalized equipment, and improved communication among team members. Operative techniques are described. RESULTS/UNASSIGNED:Facial allograft procurement closely followed previously described face transplant techniques. Ophthalmic to superficial temporal (O-ST) vessel anastomosis for globe survival was assessed. Craniectomy allowed for maximal optic nerve and ophthalmic vessel pedicle length. Appropriate pedicle length and vessel caliber for O-ST anastomosis was seen. Research procurement demonstrated collateral blood flow to the orbit and surrounding structures from the external carotid system as well as confirmed the feasibility of timely O-ST anastomosis. Personalized cutting guides enabled highly accurate bony inset. CONCLUSIONS/UNASSIGNED:This study formalizes an approach to FWET, which is feasible for clinical translation in judiciously selected patients. O-ST anastomosis seems to minimize retinal ischemia time and allow perfusion of the combined allograft on a single external carotid pedicle. Although restoration of vision likely remains out of reach, globe survival is possible.
PMCID:10653600
PMID: 38025647
ISSN: 2169-7574
CID: 5617242
Molecular cues for immune cells from small leucine-rich repeat proteoglycans in their extracellular matrix-associated and free forms
In this review we highlight emerging immune regulatory functions of lumican, keratocan, fibromodulin, biglycan and decorin, which are members of the small leucine-rich proteoglycans (SLRP) of the extracellular matrix (ECM). These SLRPs have been studied extensively as collagen-fibril regulatory structural components of the skin, cornea, bone and cartilage in homeostasis. However, SLRPs released from a remodeling ECM, or synthesized by activated fibroblasts and immune cells contribute to an ECM-free pool in tissues and circulation, that may have a significant, but poorly understood foot print in inflammation and disease. Their molecular interactions and the signaling networks they influence also require investigations. Here we present studies on the leucine-rich repeat (LRR) motifs of SLRP core proteins, their evolutionary and functional relationships with other LRR pathogen recognition receptors, such as the toll-like receptors (TLRs) to bring some molecular clarity in the immune regulatory functions of SLRPs. We discuss molecular interactions of fragments and intact SLRPs, and how some of these interactions are likely modulated by glycosaminoglycan side chains. We integrate findings on molecular interactions of these SLRPs together with what is known about their presence in circulation and lymph nodes (LN), which are important sites of immune cell regulation. Recent bulk and single cell RNA sequencing studies have identified subsets of stromal reticular cells that express these SLRPs within LNs. An understanding of the cellular source, molecular interactions and signaling consequences will lead to a fundamental understanding of how SLRPs modulate immune responses, and to therapeutic tools based on these SLRPs in the future.
PMID: 37793508
ISSN: 1569-1802
CID: 5609552
Reply [Letter]
PMID: 37642620
ISSN: 1549-4713
CID: 5618412
Retinal Findings and Cardiovascular Risk: Prognostic Conditions, Novel Biomarkers, and Emerging Image Analysis Techniques
Many retinal diseases and imaging findings have pathophysiologic underpinnings in the function of the cardiovascular system. Myriad retinal conditions, new imaging biomarkers, and novel image analysis techniques have been investigated for their association with future cardiovascular risk or utility in cardiovascular risk prognostication. An intensive literature search was performed to identify relevant articles indexed in PubMed, Scopus, and Google Scholar for a targeted narrative review. This review investigates the literature on specific retinal disease states, such as retinal arterial and venous occlusions and cotton wool spots, that portend significantly increased risk of future cardiovascular events, such as stroke or myocardial infarction, and the implications for personalized patient counseling. Furthermore, conditions diagnosed primarily through retinal bioimaging, such as paracentral acute middle maculopathy and the newly discovered entity known as a retinal ischemic perivascular lesion, may be associated with future incident cardiovascular morbidity and are also discussed. As ever-more-sophisticated imaging biomarkers and analysis techniques are developed, the review concludes with a focused analysis of optical coherence tomography and optical coherence tomography angiography biomarkers under investigation for potential value in prognostication and personalized therapy in cardiovascular disease.
PMCID:10672409
PMID: 38003879
ISSN: 2075-4426
CID: 5609062
Three-Dimensional Modeling of CpG DNA Binding with Matrix Lumican Shows Leucine-Rich Repeat Motif Involvement as in TLR9-CpG DNA Interactions
Lumican is an extracellular matrix proteoglycan known to regulate toll-like receptor (TLR) signaling in innate immune cells. In experimental settings, lumican suppresses TLR9 signaling by binding to and sequestering its synthetic ligand, CpG-DNA, in non-signal permissive endosomes. However, the molecular details of lumican interactions with CpG-DNA are obscure. Here, the 3-D structure of the 22 base-long CpG-DNA (CpG ODN_2395) bound to lumican or TLR9 were modeled using homology modeling and docking methods. Some of the TLR9-CpG ODN_2395 features predicted by our model are consistent with the previously reported TLR9-CpG DNA crystal structure, substantiating our current analysis. Our modeling indicated a smaller buried surface area for lumican-CpG ODN_2395 (1803 Å2) compared to that of TLR9-CpG ODN_2395 (2094 Å2), implying a potentially lower binding strength for lumican and CpG-DNA than TLR9 and CpG-DNA. The docking analysis identified 32 amino acids in lumican LRR1-11 interacting with CpG ODN_2395, primarily through hydrogen bonding, salt-bridges, and hydrophobic interactions. Our study provides molecular insights into lumican and CpG-DNA interactions that may lead to molecular targets for modulating TLR9-mediated inflammation and autoimmunity.
PMID: 37834438
ISSN: 1422-0067
CID: 5604482
Variability in Capillary Perfusion Is Increased in Regions of Retinal Ischemia Due to Branch Retinal Vein Occlusion
PURPOSE:To investigate alterations in macular perfusion variability due to branch retinal vein occlusion (BRVO) using a novel approach based on optical coherence tomography angiography (OCTA) coefficient of variation (CoV) analysis. METHODS:Thirteen eyes of 13 patients with macular ischemia due to BRVO were studied. Multiple consecutive en face OCTA images were acquired. Bias field correction, spatial alignment, and normalization of intensities across the images were performed followed by pixelwise computation of standard deviation divided by the mean to generate a CoV map. Region of interest-based CoV values, derived from this map, for arterioles, venules, and the microvasculature were compared between regions with macular ischemia and control areas of the same eye. Control areas were regions of the same macula that were not affected by the BRVO and had normal retinal vascular structure as seen on multimodal imaging and normal retinal vascular density measurements as quantified using OCTA. RESULTS:CoV increased by a mean value of 17.6% within the microvasculature of ischemic regions compared to the control microvasculature (P < 0.0001). CoV measurements of microvasculature were consistently greater in the ischemic area of all 13 eyes compared to control. There were no differences in CoV measurements between ischemic and control areas for arterioles (P = 0.13) and venules (P = 1.0). CONCLUSIONS:Greater variability in microvasculature perfusion occurs at sites of macular ischemia due to BRVO. We report a novel way for quantifying macular perfusion variability using OCTA. This technique may have applicability for studying the pathophysiology of other retinal vascular diseases.
PMCID:10615145
PMID: 37856113
ISSN: 1552-5783
CID: 5614242
Histology, dimensions, and fluorescein staining characteristics of nodular and cuticular drusen in age-related macular degeneration
PURPOSE/OBJECTIVE:To enable in vivo analysis of drusen composition and lifecycle, we assessed macular nodular and cuticular drusen using histology. METHODS:Median and interquartile range (IQR) of base widths of single (non-confluent) nodular drusen in 3 sources were determined histologically: 43 eyes of 43 clinically undocumented donors, in an online resource; one eye with punctate hyperfluorescence in fluorescein angiography (FA); and two eyes of one patient with bilateral "starry sky" cuticular drusen. All tissues were processed for high-resolution epoxy-resin histology and for cuticular drusen, transmission electron microscopy. RESULTS:All drusen localized between the retinal pigment epithelium basal lamina and inner collagenous layer of Bruch's membrane. They were solid, globular, homogeneously stained with toluidine blue, and uncovered by basal laminar deposit and basal mounds. Median base widths were 13.0 µm (Source 1, N=128 drusen, IQR 7.7, 20.0 µm), 15.3 µm (Source 2, N=87, IQR 10.6, 20.5 µm), and 7.3 µm (Source 3, N=78, IQR 3.9, 14.1 µm). CONCLUSIONS:In three samples, >90% of solitary nodular drusen were <30 µm, the visibility threshold in color fundus photography; these drusen are hyperfluorescent in FA. Whether these progress to soft drusen, known as high-risk from epidemiology studies and hypofluorescent, may be determinable from multimodal imaging datasets that include FA.
PMID: 37399252
ISSN: 1539-2864
CID: 5539052
38250733">Shape in medical imaging : International Workshop, ShapeMI 2023, held in conjunction with MICCAI 2023, Vancouver, BC, Canada, October 8, 2023, Proceedings. ShapeMI (Workshop) (2023 : Vancouver, B.C.). 2023:14350:236-247.DOI: 10.1007/978-3-031-46914-5_19
Modeling Longitudinal Optical Coherence Tomography Images for Monitoring and Analysis of Glaucoma Progression
Glaucoma causes progressive visual field deterioration and is the leading cause of blindness worldwide. Glaucomatous damage is irreversible and greatly impacts quality of life. Therefore, it is critically important to detect glaucoma early and closely monitor progression to preserve functional vision. Glaucoma is routinely monitored in the clinical setting using optical coherence tomography (OCT) for derived measures such as the thickness of important visual structures. There is not a consensus of what measures represent the most relevant biomarkers of glaucoma progression. Further, despite the increasing availability of longitudinal OCT data, a quantitative model of 3D structural change over time associated with glaucoma does not exist. In this paper we present an algorithm that will perform hierarchical geodesic modeling at the imaging level, considering 3D OCT images as observations of structural change over time. Hierarchical modeling includes subject-wise trajectories as geodesics in the space of diffeomorphisms and population level (glaucoma vs control) trajectories are also geodesics which explain subject-wise trajectories as deviations from the mean. Our preliminary experiments demonstrate a greater magnitude of structural change associated with glaucoma compared to normal aging. Our algorithm has the potential application in patient-specific monitoring and analysis of glaucoma progression as well as a statistical model of population trends and population variability.
PMCID:10798144
PMID: 38250733
CID: 5624612
Histology of Type 3 Macular Neovascularization and Microvascular Anomalies in Treated Age-Related Macular Degeneration: A Case Study
Purpose: To investigate intraretinal neovascularization and microvascular anomalies by correlating in vivo multimodal imaging with corresponding ex vivo histology in a single patient. Design: A case study comprising clinical imaging from a community-based practice, and histologic analysis at a university-based research laboratory (clinicopathologic correlation). Participants: A White woman in her 90s treated with numerous intravitreal anti-VEGF injections for bilateral type 3 macular neovascularization (MNV) secondary to age-related macular degeneration (AMD). Methods: Clinical imaging comprised serial infrared reflectance, eye-tracked spectral-domain OCT, OCT angiography, and fluorescein angiography. Eye tracking, applied to the 2 preserved donor eyes, enabled the correlation of clinical imaging signatures with high-resolution histology and transmission electron microscopy. Main Outcome Measures: Histologic/ultrastructural descriptions and diameters of vessels seen in clinical imaging. Results: Six vascular lesions were histologically confirmed (type 3 MNV, n = 3; deep retinal age-related microvascular anomalies [DRAMAs], n = 3). Pyramidal (n = 2) or tangled (n = 1) morphologies of type 3 MNV originated at the deep capillary plexus (DCP) and extended posteriorly to approach without penetrating persistent basal laminar deposit. They did not enter the subretinal pigment epithelium (RPE)"“basal laminar space or cross the Bruch membrane. Choroidal contributions were not found. The neovascular complexes included pericytes and nonfenestrated endothelial cells, within a collagenous sheath covered by dysmorphic RPE cells. Deep retinal age-related microvascular anomaly lesions extended posteriorly from the DCP into the Henle fiber and the outer nuclear layers without evidence of atrophy, exudation, or anti-VEGF responsiveness. Two DRAMAs lacked collagenous sheaths. External and internal diameters of type 3 MNV and DRAMA vessels were larger than comparison vessels in the index eyes and in aged normal and intermediate AMD eyes. Conclusions: Type 3 MNV vessels reflect specializations of source capillaries and persist during anti-VEGF therapy. The collagenous sheath of type 3 MNV lesions may provide structural stabilization. If so, vascular characteristics may be useful in disease monitoring in addition to fluid and flow signal detection. Further investigation with longitudinal imaging before exudation onset will help determine if DRAMAs are part of the type 3 MNV progression sequence. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.
SCOPUS:85150961252
ISSN: 2666-9145
CID: 5460022
Stellate Multiform Amelanotic Choroidopathy (SMACH). Clinical and Multimodal Imaging Features
PURPOSE/OBJECTIVE:To describe the clinical and multimodal imaging features of stellate multiform amelanotic choroidopathy (SMACH; also known as serous maculopathy due to aspecific choroidopathy). METHODS:Retrospective observational case series of eyes presenting with SMACH. Multimodal imaging including fundus photography, optical coherence tomography (OCT), OCT-angiography (OCTA), and indocyanine green angiography (ICGA) was analyzed. RESULTS:Eighteen eyes from 18 patients (mean age: 28±19 years) were included. The mean follow-up duration was 9 years. Ophthalmoscopy showed a yellowish-orange, dendriform choroidal lesion. At presentation, subretinal fluid (SRF) was seen in 10/18 cases (56%). Eight patients (44%) showed no evidence of SRF during a mean follow-up of 6 years. Cross-sectional OCT showed hyperreflective fibrous-like changes within the inner choroid with choriocapillaris flow preservation on OCTA. En face OCT showed a hyperreflective choroidal lesion with finger-like projections oriented in a stellate configuration. On ICGA, SMACH showed early and late hypofluorescence. None of the cases showed lesion growth. CONCLUSIONS:SMACH appears to be a unilateral choroidopathy characterized by distinctive multimodal imaging features. As SRF was absent in some cases, while a dendriform pattern was a consistent finding in all eyes, we propose renaming this entity "stellate multiform amelanotic choroidopathy", a name which retains its prior abbreviation "SMACH".
PMID: 37127025
ISSN: 1539-2864
CID: 5544792
Characterisation of the vascular anterior surface of type 1 macular neovascularisation after anti-VEGF therapy
BACKGROUND:To evaluate whether the status of vasculature at the top of type 1 macular neovascularisation (MNV) could function as mediator of the observed protective effect against the development of complete retinal pigment epithelial and outer retinal atrophy (cRORA). METHODS:In consecutive treatment-naïve patients, the vasculature at the anterior surface of the MNV was isolated using a slab designed to extract the most superficial vascular portion of the MNV lesion showing a choriocapillaris (CC)-like structure which we termed the 'neo-CC'. The ratio between the neo-CC area (isolated using this custom slab) and the MNV area (isolated using the standard outer retina-CC slab) at baseline and at last follow-up was evaluated. RESULTS:Forty-four eyes from 44 patients were included. 20 showed cRORA by the final follow-up (median 23 months), whereas 24 did not progress to atrophy (median 23.5 months). The proportion of MNV with neo-CC at the anterior surface was significantly lower in eyes which progressed to cRORA compared with those which did not. The multivariate regression showed that a lower proportion of neo-CC coverage over the MNV was associated with an increased odds for cRORA development. CONCLUSIONS:More extensive coverage of neo-CC is associated with a lower likelihood of development of macular atrophy in eyes receiving antivascular endothelial growth factor therapy, suggesting the protective effect of a type 1 MNV may be mediated by the development of a neo-CC and may provide insights into the biological significance of MNV as a response mechanism in eyes with age-related macular degeneration.
PMID: 35537801
ISSN: 1468-2079
CID: 5214342
American journal of obstetrics & gynecology. 2023:229(3):300.e1-300.e9.DOI: 10.1016/j.ajog.2023.03.026
Obstetrical, perinatal, and genetic outcomes associated with nonreportable prenatal cell-free DNA screening results
BACKGROUND:The clinical implications of nonreportable cell-free DNA screening results are uncertain, but such results may indicate poor placental implantation in some cases and be associated with adverse obstetrical and perinatal outcomes. OBJECTIVE:This study aimed to assess the outcomes of pregnancies with nonreportable cell-free DNA screening in a cohort of patients with complete genetic and obstetrical outcomes. STUDY DESIGN/METHODS:This was a prespecified secondary analysis of a multicenter prospective observational study of prenatal cell-free DNA screening for fetal aneuploidy and 22q11.2 deletion syndrome. Participants who underwent cell-free DNA screening from April 2015 through January 2019 were offered participation. Obstetrical outcomes and neonatal genetic testing results were collected from 21 primary-care and referral centers in the United States, Europe, and Australia. The primary outcome was risk for adverse obstetrical and perinatal outcomes (aneuploidy, preterm birth at <28, <34, and <37 weeks' gestation, preeclampsia, small for gestational age or birthweight <10th percentile for gestational week, and a composite outcome that included preterm birth at <37 weeks, preeclampsia, small for gestational age, and stillbirth at >20 weeks) after nonreportable cell-free DNA screening because of low fetal fraction or other causes. Multivariable analyses were performed, adjusting for variables known to be associated with obstetrical and perinatal outcomes, nonreportable results, or fetal fraction. RESULTS:In total, 25,199 pregnant individuals were screened, and 20,194 were enrolled. Genetic confirmation was missing in 1165 (5.8%), 1085 (5.4%) were lost to follow-up, and 93 (0.5%) withdrew; the final study cohort included 17,851 (88.4%) participants who had cell-free DNA, fetal or newborn genetic confirmatory testing, and obstetrical and perinatal outcomes collected. Results were nonreportable in 602 (3.4%) participants. A sample was redrawn and testing attempted again in 427; in 112 (26.2%) participants, results were again nonreportable. Nonreportable results were associated with higher body mass index, chronic hypertension, later gestational age, lower fetal fraction, and Black race. Trisomy 13, 18, or 21 was confirmed in 1.6% with nonreportable tests vs 0.7% with reported results (P=.013). Rates of preterm birth at <28, 34, and 37 weeks, preeclampsia, and the composite outcome were higher among participants with nonreportable results, and further increased among those with a second nonreportable test, whereas the rate of small for gestational age infants was not increased. After adjustment for confounders, the adjusted odds ratios were 2.2 (95% confidence interval, 1.1-4.4) and 2.6 (95% confidence interval, 0.6-10.8) for aneuploidy, and 1.5 (95% confidence interval, 1.2-1.8) and 2.1 (95% confidence interval, 1.4-3.2) for the composite outcome after a first and second nonreportable test, respectively. Of the patients with nonreportable tests, 94.9% had a live birth, as opposed to 98.8% of those with reported test results (adjusted odds ratio for livebirth, 0.20 [95% confidence interval, 0.13-0.30]). CONCLUSION/CONCLUSIONS:Patients with nonreportable cell-free DNA results are at increased risk for a number of adverse outcomes, including aneuploidy, preeclampsia, and preterm birth. They should be offered diagnostic genetic testing, and clinicians should be aware of the increased risk of pregnancy complications.
PMID: 36965866
ISSN: 1097-6868
CID: 5502542
The Biosimilar Paradox: How Anti-VEGF Biosimilars will Increase Patient and Overall Healthcare Costs
PURPOSE/OBJECTIVE:Anti-vascular endothelial growth factor (anti-VEGF) medications for intraocular use are a major and increasing cost, and biosimilars may be a means of reducing the high cost of many biologic medications. However, a bevacizumab biosimilar, which is currently pending FDA approval (bevacizumab-vikg), may paradoxically increase the cost burden of intravitreal anti-VEGF, as "off-label" repackaged drug may no longer be allowed per the Drug Quality and Security Act (DQSA). We aim to investigate the potential impact of biosimilars on the health system and patient costs in the US. DESIGN/METHODS:Cost analysis of anti-VEGF medications. PARTICIPANTS/METHODS:Medicare data from October 2022, previously published market share data from 2019. METHODS:Average sales price (ASP) of ranibizumab, aflibercept, and bevacizumab are calculated from Medicare allowable payments. ASPs of biosimilars are calculated from wholesale acquisition costs from a representative distributor. The cost of an intraocular bevacizumab formulation is modeled at $500 and $900/1.25mg dose. MAIN OUTCOME MEASURES/METHODS:Overall costs of anti-VEGF drugs to Medicare Part B and patients. RESULTS:If an intraocular bevacizumab biosimilar were to be priced at $500, costs to Medicare would increase by $457 million from $3.01 billion to $3.47 billion (15.2% increase). Patient responsibility would increase by $117 million from $768 million to $884 million. Similarly, if intraocular bevacizumab were priced at $900, Medicare costs would increase by $897 million to $3.91 billion (29.8% increase), and patient responsibility would increase by $229 million to $997 million. If bevacizumab were $500/dose, switching all patients currently on ranibizumab or aflibercept to respective biosimilars would only compensate for 28.8% of the increased cost. Current prices of ranibizumab and aflibercept biosimilars would have to decrease by an aggregate of 15.7% to $616.80, $1027.97, and $1436.88/injection for ranibizumab 0.3 mg, 0.5 mg, and aflibercept, respectively. CONCLUSIONS:An FDA-approved bevacizumab biosimilar for ophthalmic use could significantly increase costs to the healthcare system and patients, raising concerns for access. This increase in cost would not be offset by ranibizumab and aflibercept biosimilar use at current prices. These data support the need for an exemption of section 503B of the DQSA and continued use of repackaged off-label bevacizumab.
PMID: 37116720
ISSN: 1549-4713
CID: 5465612
Ophthalmologist Turnover in the United States: Analysis of Workforce Changes from 2014 through 2021
PURPOSE/OBJECTIVE:Physician turnover is costly to health care systems and can affect patient experience due to discontinuity of care. This study aimed to assess the frequency of turnover by ophthalmologists and characteristics associated with turnover. DESIGN/METHODS:A retrospective cross-sectional study. PARTICIPANTS/METHODS:Actively practicing US ophthalmologists included in the Centers for Medicare & Medicaid Services (CMS) Physician Compare and Physician and Other Supplier Public Use File between 2014 and 2021. METHODS:Using two separate publicly available Medicare data sets, we collated data for ophthalmologists associated with practices in each year between 2014 and 2021. We calculated the rate of turnover as (1) annually in each year window and (2) cumulatively as the total proportion of 2014 practices separated by 2021. Multivariate logistic regression analysis was used to identify physician and practice characteristics associated with cumulative turnover. Additionally, we evaluated changes in annual turnover surrounding the Coronavirus disease 2019 pandemic. MAIN OUTCOME MEASURES/METHODS:Ophthalmologist turnover, defined as a change of an ophthalmologist's National Provider Identifier practice affiliation from one year to the next. RESULTS:Of 13,264 ophthalmologists affiliated with 3,306 unique practices, 34.1% separated from at least one practice between 2014 and 2021. Annual turnover ranged from 3.7% (2017) to 19.4% (2018), with an average rate of 9.4%. Factors associated with increased turnover included solo practice (adjusted odds ratio [aOR], 9.59, p<0.01), university-affiliation (aOR, 1.55, p<0.01), practice location in the Northeast (aOR 1.39, p<0.01), and practice size of 2-4 members (aOR, 1.21, p<0.01). Factors associated with decreased turnover included male gender (aOR, 0.87, p<0.01), and greater than 5 years of practice: 6-10 years (aOR, 0.63), 11-19 years (aOR, 0.54), 20-29 years (aOR, 0.36), and ≥30 years (aOR, 0.18) (p < 0.01 for all). In the initial year of the COVID-19 pandemic (2020), annual turnover grew from 7.8% to 11.0%, then fell to 8.7% in the pandemic post-vaccine period (2021). CONCLUSIONS:One-third of US ophthalmologists separated from at least one practice from 2014-2021. Turnover patterns differ by various physician and practice characteristics, the knowledge of which may prove useful when developing strategies to optimize future workforce stability. Because reasons for turnover cannot be solely determined using administrative data, further investigation is warranted given the potential clinical and financial implications.
PMID: 37164243
ISSN: 1549-4713
CID: 5509382
Validation of the RCOphth and UKEGS glaucoma risk stratification tool 'GLAUC-STRAT-fast'
BACKGROUND/AIMS/OBJECTIVE:The aim of this study was to validate the Glaucoma Risk Stratification Tool (GLAUC-STRAT-fast) currently recommended by the Royal College of Ophthalmologists for the risk stratification of patients with glaucoma in the UK National Health Service Hospital Eye Service. METHODS:test for proportions. RESULTS:There was an association between the baseline stratification and the number of treatment escalations needed to maintain the eye-specific target intraocular pressure (p=0.001), the number of visits needed throughout the 3-year follow-up period (p=0.001), the need for trabeculectomy (p<0.001) and absolute loss of MD over the course of the monitoring period (p<0.001). The rate of VF progression was not associated with baseline risk stratification for TD or PD progression (p≥0.007, with Bonferroni correction). CONCLUSION/CONCLUSIONS:The GLAUC-STRAT fast tool is a useful tool for risk stratifying eyes with ocular hypertension or open angle glaucoma. Further research is needed to confirm and validate its applicability to more advanced glaucomas and generalisability to clinical use. TRIAL REGISTRATION NUMBER/BACKGROUND:The LiGHT trial is registered at controlled-trials.com (ISRCTN32038223).
PMID: 35534178
ISSN: 1468-2079
CID: 5498042
Response to "Comment on: Five Year visual field outcomes of the Horizon Trial" [Letter]
PMID: 37196841
ISSN: 1879-1891
CID: 5498192
The Chrysanthemum Phenotype of Idiopathic Multifocal Choroiditis
PURPOSE/OBJECTIVE:To describe the clinical characteristics and multimodal imaging (MMI) features of a distinctive subtype of active idiopathic multifocal choroiditis (iMFC) lesions with grey-yellow chorioretinal lesions surrounded by smaller satellite dots, a presentation referred to as "chrysanthemum lesions". METHODS:Retrospective, observational, multi-center case series of eyes with active iMFC and chrysanthemum lesions. Multimodal imaging features were reviewed and presented. RESULTS:Twenty-five eyes from 20 patients (12 women and 8 men), with a mean age of 35.8±17.0 years (range, 7 - 78 years) were included. Chrysanthemum lesions were equally located in the macula (48.0%) or the mid/far-periphery (52.0%). The number of lesions per eye varied from 1 (16.0%) to more than 20 (56.0%). On optical coherence tomography (OCT), chrysanthemum lesions showed typical features of iMFC, including subretinal hyperreflective material splitting the retinal pigment epithelium/Bruch's membrane (RPE/BrM). Chrysanthemum lesions were hypoautofluorescent on fundus autofluorescence imaging, hyperfluorescent on fluorescein angiography, hypofluorescent on indocyanine green angiography, and associated with choriocapillaris flow signal deficit on OCT-angiography. CONCLUSION/CONCLUSIONS:Active iMFC may present with findings resembling chrysanthemum lesions. The distinctive lesion morphology on ophthalmoscopic examination, the high number of lesions, and the high prevalence of exclusive mid- and far-peripheral involvement may represent a distinctive phenotype of iMFC.
PMID: 37071923
ISSN: 1539-2864
CID: 5466132
Can Glaucoma Suspect Data Help to Improve the Performance of Glaucoma Diagnosis?
PURPOSE:The presence of imbalanced datasets in medical applications can negatively affect deep learning methods. This study aims to investigate how the performance of convolutional neural networks (CNNs) for glaucoma diagnosis can be improved by addressing imbalanced learning issues through utilizing glaucoma suspect samples, which are often excluded from studies because they are a mixture of healthy and preperimetric glaucomatous eyes, in a semi-supervised learning approach. METHODS:A baseline 3D CNN was developed and trained on a real-world glaucoma dataset, which is naturally imbalanced (like many other real-world medical datasets). Then, three methods, including reweighting samples, data resampling to form balanced batches, and semi-supervised learning on glaucoma suspect data were applied to practically assess their impacts on the performances of the trained methods. RESULTS:The proposed method achieved a mean accuracy of 95.24%, an F1 score of 97.42%, and an area under the curve of receiver operating characteristic (AUC ROC) of 95.64%, whereas the corresponding results for the traditional supervised training using weighted cross-entropy loss were 92.88%, 96.12%, and 92.72%, respectively. The obtained results show statistically significant improvements in all metrics. CONCLUSIONS:Exploiting glaucoma suspect eyes in a semi-supervised learning method coupled with resampling can improve glaucoma diagnosis performance by mitigating imbalanced learning issues. TRANSLATIONAL RELEVANCE:Clinical imbalanced datasets may negatively affect medical applications of deep learning. Utilizing data with uncertain diagnosis, such as glaucoma suspects, through a combination of semi-supervised learning and class-imbalanced learning strategies can partially address the problems of having limited data and learning on imbalanced datasets.
PMCID:10424152
PMID: 37555737
ISSN: 2164-2591
CID: 5594912
A Review of Cost-Effectiveness Analyses for Open Angle Glaucoma Management
PURPOSE:Cost-effectiveness analyses (CEAs) quantify and compare both costs and measures of efficacy for different interventions. As the costs of glaucoma management to patients, payers, and physicians are increasing, we seek to investigate the role of CEAs in the field of glaucoma and how such studies impact clinical management. METHODS:We adhered to the "Preferred Reporting Items for Systematic Reviews and Meta-analyses" guidelines for our systematic review structure. Eligible studies included any full-text articles that investigated cost-effectiveness or cost-utility as it relates to the field of open angle glaucoma management in the United States. Risk of bias assessment was conducted using the validated Joanna Briggs Institute Critical Appraisal Checklist for Economic Evaluations. RESULTS:Eighteen studies were included in the review. Dates of publication ranged from 1983 to 2021. Most of the studies were published in the 2000s and performed CEAs in the domains of treatment/therapy, screening, and adherence for patients with primary angle open glaucoma. Of the 18 articles included, 14 focused on treatment, 2 on screening, and 2 on adherence. Most of these studies focused on the cost-effectiveness of different topical medical therapies, whereas only a few studies explored laser procedures, surgical interventions, or minimally invasive procedures. Economic models using decision analysis incorporating state-transition Markov cycles or Montecarlo simulations were widely used, however, the methodology among studies was variable, with a wide spectrum of inputs, measures of outcomes, and time horizons used. CONCLUSION:Overall, we found that cost-effectiveness research in glaucoma in the United States remains relatively unstructured, resulting in unclear and conflicting implications for clinical management.
PMID: 37311022
ISSN: 1536-481x
CID: 5595092
Twelve-Month Clinical and Histopathological Performance of a Novel Synthetic Cornea Device in Rabbit Model
PURPOSE:To report the biological stability and postoperative outcomes of a second-generation, single-piece, flexible synthetic cornea in a rabbit model. METHODS:Device materials and design were amended to enhance biointegration. Optic skirt design devices were made from compact perfluoroalkoxy alkane with porous expanded polytetrafluoroethylene ingrowth surface overlying the skirt and optic wall. Sixteen devices were implanted into intrastromal pocket in rabbit eyes. Rabbits were randomly assigned to 6- and 12-month follow-up cohorts (n = 8 in each) postoperatively. Monthly examinations and optical coherence tomography assessed cornea-device integration, iridocorneal angle, optic nerve, and retina. RESULTS:There were no intraoperative complications. All devices were in situ at exit, with clear optics. No retroprosthetic membrane, glaucoma, cataract formation, or retinal detachment was observed. Two rabbits in the 6-month group had mild, focal anterior lamella thinning without retraction adjacent to the optic near tight sutures. Three postoperative complications occurred in the 12-month group. One rabbit diagnosed with endophthalmitis was euthanized on day 228. Mild sterile focal retraction of anterior lamella occurred in two rabbits, which were terminated on days 225 and 315. Light microscopic examination of enucleated globes demonstrated fibroplasia with new collagen deposition into the porous scaffold without significant inflammation, encapsulation, or granuloma formation. CONCLUSIONS:Clinical evaluations, imaging, and histopathological findings indicate favorable outcomes of this synthetic corneal device in a rabbit model. Early feasibility studies in humans are being planned. TRANSLATIONAL RELEVANCE:Favorable 12-month results of the device in rabbits demonstrate vision-restoring potential in corneally blind individuals at high risk of failure with donor keratoplasty.
PMCID:10431210
PMID: 37561510
ISSN: 2164-2591
CID: 5595182
Apocrine Cystadenoma of the Eyelid, a Rare Neoplasm: Expanded Immunohistologic Profile [Case Report]
An 83-year-old woman experienced the slow enlargement of a right lower eyelid mass. Histopathologic examination of the excised tissue showed a mucin-filled cystic tumor emanating from an apocrine bilayer that displayed bleb-like apocrine decapitation secretion. The outer flattened myoepithelial layer of the bilayer reacted with immunohistochemical stains for smooth muscle actin and calponin. In foci, the tumor exhibited a cribriform architecture with small pockets of mucin. Tumor cells were reactive for cytokeratin 7, Gross Cystic Disease Fluid Protein 15 (BRST-2), estrogen and progesterone receptors, androgen receptors, mammaglobin, epithelial membrane antigen, and GATA3. Ki67 showed a very low proliferation fraction. The lesion exemplifies the fourth instance of an eyelid apocrine cystadenoma in the literature.
PMID: 37010052
ISSN: 1537-2677
CID: 5634832
Environmental influences on ophthalmic conditions: A scoping review
BACKGROUND:Environmental factors have been implicated in various eye pathologies. The purpose of this review is to synthesise the published research on environmental effects on eye disease. METHODS:Four databases were searched for terms relating to environmental exposures and ophthalmic disease. Titles and abstracts were screened followed by full-text review. Data was extracted from 118 included studies. Quality assessment was conducted for each study. RESULTS:Air pollutants, including nitrogen dioxide, nitrites, sulphur dioxide, particulate matter, carbon monoxide, ozone and hydrocarbons are associated with ocular conditions ranging from corneal damage to various retinopathies, including central retinal artery occlusion. Certain chemicals and metals, such as cadmium, are associated with increased risk of age-related macular degeneration. Climate factors, such as sun exposure, have been associated with the development of cataracts. Living in rural areas was associated with various age-related eye diseases whereas people living in urban settings had higher risk for dry eye disease and uveitis. CONCLUSION/CONCLUSIONS:Environmental exposures in every domain are associated with various ophthalmic conditions. These findings underscore the importance of continued research on the interplay between the environment and eye health.
PMID: 37309709
ISSN: 1442-9071
CID: 5505112
Surgical innovation in ophthalmology: challenges and opportunities
PMID: 36477730
ISSN: 1476-5454
CID: 5498112
Coded aperture snapshot spectral imaging fundus camera
Spectral imaging holds great promise for the non-invasive diagnosis of retinal diseases. However, to acquire a spectral datacube, conventional spectral cameras require extensive scanning, leading to a prolonged acquisition. Therefore, they are inapplicable to retinal imaging because of the rapid eye movement. To address this problem, we built a coded aperture snapshot spectral imaging fundus camera, which captures a large-sized spectral datacube in a single exposure. Moreover, to reconstruct a high-resolution image, we developed a robust deep unfolding algorithm using a state-of-the-art spectral transformer in the denoising network. We demonstrated the performance of the system through various experiments, including imaging standard targets, utilizing an eye phantom, and conducting in vivo imaging of the human retina.
PMID: 37491567
ISSN: 2045-2322
CID: 5592162
Neuro-Ophthalmologic Variability in Presentation of Genetically Confirmed Wolfram Syndrome: A Case Series and Review [Case Report]
Wolfram syndrome is a neurodegenerative disorder caused by pathogenic variants in the genes WFS1 or CISD2. Clinically, the classic phenotype is composed of optic atrophy, diabetes mellitus type 1, diabetes insipidus, and deafness. Wolfram syndrome, however, is phenotypically heterogenous with variable clinical manifestations and age of onset. We describe four cases of genetically confirmed Wolfram syndrome with variable presentations, including acute-on-chronic vision loss, dyschromatopsia, and tonic pupils. All patients had optic atrophy, only three had diabetes, and none exhibited the classic Wolfram phenotype. MRI revealed a varying degree of the classical features associated with the syndrome, including optic nerve, cerebellar, and brainstem atrophy. The cohort's genotype and presentation supported the reported phenotype-genotype correlations for Wolfram, where missense variants lead to milder, later-onset presentation of the Wolfram syndrome spectrum. When early onset optic atrophy and/or diabetes mellitus are present in a patient, a diagnosis of Wolfram syndrome should be considered, as early diagnosis is crucial for the appropriate referrals and management of the associated conditions. Nevertheless, the condition should also be considered in otherwise unexplained, later-onset optic atrophy, given the phenotypic spectrum.
PMCID:10376978
PMID: 37508961
ISSN: 2076-3425
CID: 5593192
Improving Information Extraction from Pathology Reports using Named Entity Recognition
Pathology reports are considered the gold standard in medical research due to their comprehensive and accurate diagnostic information. Natural language processing (NLP) techniques have been developed to automate information extraction from pathology reports. However, existing studies suffer from two significant limitations. First, they typically frame their tasks as report classification, which restricts the granularity of extracted information. Second, they often fail to generalize to unseen reports due to variations in language, negation, and human error. To overcome these challenges, we propose a BERT (bidirectional encoder representations from transformers) named entity recognition (NER) system to extract key diagnostic elements from pathology reports. We also introduce four data augmentation methods to improve the robustness of our model. Trained and evaluated on 1438 annotated breast pathology reports, acquired from a large medical center in the United States, our BERT model trained with data augmentation achieves an entity F1-score of 0.916 on an internal test set, surpassing the BERT baseline (0.843). We further assessed the model's generalizability using an external validation dataset from the United Arab Emirates, where our model maintained satisfactory performance (F1-score 0.860). Our findings demonstrate that our NER systems can effectively extract fine-grained information from widely diverse medical reports, offering the potential for large-scale information extraction in a wide range of medical and AI research. We publish our code at https://github.com/nyukat/pathology_extraction.
PMCID:10350195
PMID: 37461545
CID: 5588752
SCLERAL EXCAVATION AT OBLIQUE MUSCLE INSERTIONS: IMAGING CHARACTERISTICS AND CORRELATION WITH SCLERAL PLAQUES AND SCLEROCHOROIDAL CALCIFICATION [Case Report]
PURPOSE/OBJECTIVE:To compare the imaging features of lesions showing hyporeflective posterior scleral excavation found near the insertions of the oblique extraocular muscles to the features and the natural course of Cogan scleral plaques. METHODS:Multimodal imaging with color fundus photography, spectral-domain optical coherence tomography (OCT), swept-source optical coherence tomography, and B-scan ultrasonography. RESULTS:A 71-year-old man and an 89-year-old man presented with ring-shaped hypopigmented lesions measuring between 200 μm and 300 μm transversally, and located along the superior vascular arcade and temporal to the fovea. All lesions were identified near the insertion of oblique muscles, with one observed in the temporal macula, and two found along the superotemporal arcades. Enhanced depth imaging-optical coherence tomography showed hyporeflective boat-shaped areas of scleral excavation with reduced choroidal thickness along their margins. B-scan ultrasonography showed the lesions to be intensely reflective with varying degrees of posterior shadowing. CONCLUSION/CONCLUSIONS:To our knowledge, this is the first report of excavated hyporeflective scleral lesions found near the oblique muscle insertions. Imaging and clinical data support the diagnosis of a posterior form of Cogan scleral plaque and are consistent with the natural course of this entity.
PMID: 37364195
ISSN: 1937-1578
CID: 5539962
Patient Utilization of Premium Intraocular Lenses Before and During the COVID-19 Pandemic
PURPOSE/OBJECTIVE:To compare the choice of intraocular lens (IOL) and sociodemographic characteristics between patients who underwent elective cataract surgery before the COVID-19 pandemic and during the pandemic at the Wilmer Eye Institute. METHODS:A retrospective chart review of patients who underwent cataract surgery before the COVID-19 pandemic (June 1 to November 30, 2019) and during the pandemic (June 1 to November 30, 2020) was conducted. Sociodemographic information, including age, sex, race, and insurance, and choice of IOL (premium or standard) were analyzed. The association between timing of surgery and choice of IOL was analyzed using multivariable logistic regression. RESULTS:The study included 2,877 patients (3,946 eyes) before COVID-19 and 2,564 patients (3,605 eyes) during COVID-19. However, 9.0% (357/3,946) of surgeries before COVID-19 used premium IOLs compared with 11.1% (399/3,605) during COVID-19 (P=0.004). There was no difference in the racial characteristics of patients between before and during COVID-19. After adjusting for time of surgery and demographics, the odds of choosing premium IOLs for black patients was 0.32 times the odds for white patients (P<0.001). There was an increase in private-insured patients but a decrease in Medicare-insured patients during COVID-19. After adjusting for time of surgery and demographics, private-insured patients had higher odds of choosing premium IOLs (P<0.001), whereas Medicaid-insured patients had lower odds (P=0.007) when compared with Medicare-insured patients. CONCLUSION/CONCLUSIONS:More patients chose premium IOLs during COVID-19 than before COVID-19, concurrent with change in insurance status. White patients were more likely to choose premium IOLs than black patients, as were private-insured patients compared with Medicare-insured patients.
PMID: 37167587
ISSN: 1542-233x
CID: 5509412
Expanding indications for corneal cross-linking
PURPOSE OF REVIEW/OBJECTIVE:The aim of this study was to summarize the recent developments in corneal cross-linking (CXL) and its indications, including corneal ectasias, refractive surgery and infectious keratitis. RECENT FINDINGS/RESULTS:Advances in CXL technology, such as the use of higher-intensity LED ultraviolet (UV) light sources and a better understanding of the UV-riboflavin photochemical reaction, have enabled safer and more effective methods of cross-linking thin and ultra-thin corneas, and more effective accelerated transepithelial/'epi-on' CXL procedures that are beginning to supplant the Dresden protocol as the 'gold standard' CXL method. CXL is also being used in combination with laser surgery, not only to expand the patient base who can receive refractive surgery, but also to help rehabilitate vision in patients with ectasia. CXL, and CXL combined with photorefractive keratectomy (PRK), can result in corneal flattening of 1-2 D, and corneal regularization of 4-5 D, respectively. Finally, photoactivated chromophore for keratitis-corneal cross-linking (PACK-CXL) has been shown to be an effective therapy for infectious keratitis, both alone, and in combination with antimicrobial drugs. SUMMARY/CONCLUSIONS:CXL has evolved from a single technique to treat a single corneal ectasia, keratoconus, to several techniques with several indications, spanning a spectrum of corneal ectasias, as well as visual rehabilitation, refractive procedures and infectious keratitis treatment.
PMID: 37097193
ISSN: 1531-7021
CID: 5484972
Nascent Geographic Atrophy as a Predictor of Type 3 Macular Neovascularization Development
PURPOSE/OBJECTIVE:To investigate the association of nascent geographic atrophy (GA) preceding the development of exudative type 3 macular neovascularization (MNV) in patients with age-related macular degeneration (AMD). DESIGN/METHODS:Retrospective longitudinal study. PARTICIPANTS/METHODS:Patients with AMD diagnosed with treatment-naive exudative type 3 MNV in 1 or both eyes were evaluated. Inclusion criteria included serial tracked structural OCT examinations for ≥ 2 years before the detection of exudative type 3 MNV. METHODS:Clinical characteristics and retinal imaging, including structural OCT at baseline and at each follow-up examination, were analyzed. Eyes showing the presence of nascent GA during the follow-up were selected for analysis of prevalence, and clinical characteristics at the site of subsequent type 3 MNV development. MAIN OUTCOME MEASURES/METHODS:Description of the prevalence and clinical characteristics of nascent GA at the site of subsequent type 3 MNV development. RESULTS:Overall, 97 eyes affected by type 3 MNV meeting inclusion criteria were analyzed. Of 97 eyes (71 patients), 22 eyes of 21 patients (mean age 82 ± 9 years) showed nascent GA preceding exudative type 3 MNV. The observed prevalence of nascent GA preceding exudative type 3 MNV was 22.7% (95% confidence interval, 14.4%-31.0%). Exudative type 3 MNV developed a mean of 9 ± 6 months after detection of nascent GA. The presence of reticular pseudodrusen in the study eye did not significantly influence the timing of exudative type 3 MNV development after the observation of nascent GA (P > 0.1 in all analyses). Reduced best-corrected visual acuity was recorded at the exudative type 3 stage in comparison with the nascent GA stage (P = 0.003). CONCLUSIONS:As nascent GA may precede the development of exudative type 3 MNV, the detection of nascent GA in eyes with AMD may warrant closer surveillance to identify early exudative type 3 MNV warranting treatment. FINANCIAL DISCLOSURE(S)/BACKGROUND:Proprietary or commercial disclosure may be found after the references.
PMID: 36736896
ISSN: 2468-6530
CID: 5462172
How Ophthalmologists Can Decarbonize Eye Care: A Review of Existing Sustainability Strategies and Steps Ophthalmologists Can Take
TOPIC/OBJECTIVE:Understanding approaches to sustainability in cataract surgery and their risks and benefits CLINICAL RELEVANCE: In the United States, healthcare is responsible for approximately 8.5% of greenhouse gas (GHG), and cataract surgery is one of the most commonly performed surgical procedures. Ophthalmologists can contribute to reducing GHG emissions, which lead to a steadily increasing list of health concerns ranging from trauma to food instability. METHODS:We conducted a literature review to identify the benefits and risks of sustainability interventions. We then organized these interventions into a decision tree for use by individual surgeons. RESULTS:Identified sustainability interventions fall into the domains of advocacy and education, pharmaceuticals, process, and supplies and waste. Existing literature shows certain interventions may be safe, cost-effective, and environmentally friendly. These include dispensing medications home to patients after surgery, multi-dosing appropriate medications, training staff to properly sort medical waste, reducing the number of supplies used during surgery, and implementing immediate sequential bilateral cataract surgery where clinically appropriate. The literature was lacking on the benefits or risks for some interventions, such as switching specific single use supplies to reusables or implementing a hub-and-spoke style theatre setup. Many of the advocacy and education interventions have inadequate literature specific to ophthalmology but are likely to have minimal risks. CONCLUSIONS:Ophthalmologists can engage in a variety of safe and effective approaches to reduce or eliminate dangerous GHG emissions associated with cataract surgery.
PMID: 36889466
ISSN: 1549-4713
CID: 5432802
Five-Year Visual Field Outcomes of the HORIZON Trial
PURPOSE/OBJECTIVE:To compare visual field (VF) progression between glaucoma patients receiving cataract surgery alone (CS) or with a Hydrus microstent (CS-HMS). DESIGN/METHODS:Post hoc analysis of VF data from the HORIZON multicenter randomized controlled trial. METHODS:A total of 556 patients with glaucoma and cataract were randomized 2:1 to either CS-HMS (369) or CS (187) and followed up for 5 years. VF was performed at 6 months and then every year after surgery. We analyzed data for all participants with at least 3 reliable VFs (false positives < 15%). Average between-group difference in rate of progression (RoP) was tested using a Bayesian mixed model and a 2-sided Bayesian P value <.05 (main outcome). A multivariable model measured the effect of intraocular pressure (IOP). A survival analysis compared the probability of global VF sensitivity dropping by predefined cutoffs (2.5, 3.5, 4.5, and 5.5 dB) from baseline. RESULTS:Data from 352 eyes in the CS-HMS arm and 165 in the CS arm were analyzed (2966 VFs). The mean RoP was -0.26 dB/y (95% credible interval -0.36, -0.16) for CS-HMS and -0.49 dB/y (95% credible interval -0.63, -0.34) for CS. This difference was significant (P = .0138). The difference in IOP only explained 17% of the effect (P < .0001). Five-year survival analysis showed an increased probability of VF worsening by 5.5 dB (P = .0170), indicating a greater proportion of fast progressors in the CS arm. CONCLUSIONS:CS-HMS has a significant effect on VF preservation in glaucoma patients compared with CS alone, reducing the proportion of fast progressors.
PMID: 36813144
ISSN: 1879-1891
CID: 5498152
GABA decrease is associated with degraded neural specificity in the visual cortex of glaucoma patients
Glaucoma is an age-related neurodegenerative disease of the visual system, affecting both the eye and the brain. Yet its underlying metabolic mechanisms and neurobehavioral relevance remain largely unclear. Here, using proton magnetic resonance spectroscopy and functional magnetic resonance imaging, we investigated the GABAergic and glutamatergic systems in the visual cortex of glaucoma patients, as well as neural specificity, which is shaped by GABA and glutamate signals and underlies efficient sensory and cognitive functions. Our study shows that among the older adults, both GABA and glutamate levels decrease with increasing glaucoma severity regardless of age. Further, our study shows that the reduction of GABA but not glutamate predicts the neural specificity. This association is independent of the impairments on the retina structure, age, and the gray matter volume of the visual cortex. Our results suggest that glaucoma-specific decline of GABA undermines neural specificity in the visual cortex and that targeting GABA could improve the neural specificity in glaucoma.
PMCID:10310759
PMID: 37386293
ISSN: 2399-3642
CID: 5538742
A clinically viable approach to restoring visual function using optogenetic gene therapy
Optogenetic gene therapies offer a promising strategy for restoring vision to patients with retinal degenerative diseases, such as retinitis pigmentosa (RP). Several clinical trials have begun in this area using different vectors and optogenetic proteins (Clinical Identifiers: NCT02556736, NCT03326336, NCT04945772, and NCT04278131). Here we present preclinical efficacy and safety data for the NCT04278131 trial, which uses an AAV2 vector and Chronos as the optogenetic protein. Efficacy was assessed in mice in a dose-dependent manner using electroretinograms (ERGs). Safety was assessed in rats, nonhuman primates, and mice, using several tests, including immunohistochemical analyses and cell counts (rats), electroretinograms (nonhuman primates), and ocular toxicology assays (mice). The results showed that Chronos-expressing vectors were efficacious over a broad range of vector doses and stimulating light intensities, and were well tolerated: no test article-related findings were observed in the anatomical and electrophysiological assays performed.
PMCID:10213293
PMID: 37251979
ISSN: 2329-0501
CID: 5543192
OPTICAL COHERENCE TOMOGRAPHY FEATURES RELEVANT TO NEOVASCULAR AGE-RELATED MACULAR DEGENERATION MANAGEMENT AND NONNEOVASCULAR AGE-RELATED MACULAR DEGENERATION PROGRESSION: CLINICOPATHOLOGIC CORRELATION [Case Report]
PURPOSE/OBJECTIVE:Clinicopathologic correlation of two optical coherence tomography (OCT) features in neovascular age-related macular degeneration. METHODS:Case report, clinicopathologic correlation. RESULTS:A patient in her 90s was diagnosed with Type 3 macular neovascularization secondary to age-related macular degeneration in the index right eye and underwent intravitreal antivascular endothelial growth factor treatment for 5 years. A double-layer sign on in vivo OCT was correlated to calcified drusen on histology. Furthermore, hyperfluorescence on fluorescein angiography corresponded on histology to choroidal hypertransmission on OCT and retinal pigment epithelium atrophy above calcified drusen. CONCLUSION/CONCLUSIONS:A double-layer sign on OCT can represent nonneovascular subretinal pigment epithelium material including wide and flat calcific nodules. Furthermore, hyperfluorescence on FA, among different origins, can be due to a window defect corresponding to retinal pigment epithelium atrophy, which can be confirmed with OCT. Clinicopathological correlation using high-resolution histology can demonstrate the fine details available to clinical decision making through currently available in vivo OCT imaging.
PMID: 36944176
ISSN: 1937-1578
CID: 5539762
SUBRETINAL LIPID GLOBULES AN EARLY BIOMARKER OF MACULAR NEOVASCULARIZATION IN EYES WITH INTERMEDIATE AGE-RELATED MACULAR DEGENERATION
PURPOSE/OBJECTIVE:To explore the association between subretinal lipid globules (SLGs) detected in eyes with intermediate age-related macular degeneration with the presence of nonexudative macular neovascularization. METHODS:This was a retrospective analysis of 113 consecutive patients with bilateral intermediate age-related macular degeneration (226 eyes) followed for a least 6 months. All eyes underwent multimodal imaging with fundus autofluorescence, spectral-domain optical coherence tomography, and optical coherence tomography angiography. Subretinal lipid globules were identified on spectral-domain optical coherence tomography as round hyporeflective lesions measuring 31 to 157 µ m located between the ellipsoid zone and the retinal pigment epithelium/Bruch membrane complex. Nonexudative macular neovascularization was detected with optical coherence tomography angiography. The features of NE-MNV lesions detected in eyes with SLGs were compared with those in eyes without SLGs. RESULTS:Subretinal lipid globules were identified in 15 eyes of which 14 eyes (93.3%) demonstrated NE-MNV on optical coherence tomography angiography. In the remaining 98 eyes without SLGs, 18 (18.4%) displayed NE-AMD on optical coherence tomography angiography. The macular neovascularization area was larger in the SLG subgroup (+0.38 vs. +0.21 mm 2 , P = 0.008) and showed faster horizontal growth (+727 µ m, CI 95% 250.4, 1,205.4) than MNV in eyes without SLGs (+64.9 µ m, CI 95%, 24.3, 154) on optical coherence tomography B-scans. After a mean of 11.6 months, the conversion rate to exudative MNV was similar between eyes with SLGs and those without SLGs [8/26 (38.5%) versus 3/13 (27.3%), P = 0.56)]. CONCLUSION/CONCLUSIONS:The detection of SLGs in eyes with intermediate age-related macular degeneration was strongly correlated with the presence of NE-MNV. Although these MNV lesions were larger and grew faster than NE-MNV detected in eyes lacking SLGs, the rates of conversion to exudative MNV appeared similar.
PMID: 36763979
ISSN: 1539-2864
CID: 5626282
An Unusual Optical Coherence Tomography Appearance in Coats Disease
PMID: 36940416
ISSN: 1539-2864
CID: 5626292
Segmentation-Free OCT-Volume-Based Deep Learning Model Improves Pointwise Visual Field Sensitivity Estimation
PURPOSE/UNASSIGNED:The structural changes measured by optical coherence tomography (OCT) are related to functional changes in visual fields (VFs). This study aims to accurately assess the structure-function relationship and overcome the challenges brought by the minimal measurable level (floor effect) of segmentation-dependent OCT measurements commonly used in prior studies. METHODS/UNASSIGNED:We developed a deep learning model to estimate the functional performance directly from three-dimensional (3D) OCT volumes and compared it to the model trained with segmentation-dependent two-dimensional (2D) OCT thickness maps. Moreover, we proposed a gradient loss to utilize the spatial information of VFs. RESULTS/UNASSIGNED:Our 3D model was significantly better than the 2D model both globally and pointwise regarding both mean absolute error (MAE = 3.11 + 3.54 vs. 3.47 ± 3.75 dB, P < 0.001) and Pearson's correlation coefficient (0.80 vs. 0.75, P < 0.001). On a subset of test data with floor effects, the 3D model showed less influence from floor effects than the 2D model (MAE = 5.24 ± 3.99 vs. 6.34 ± 4.58 dB, P < 0.001, and correlation 0.83 vs. 0.74, P < 0.001). The gradient loss improved the estimation error for low-sensitivity values. Furthermore, our 3D model outperformed all prior studies. CONCLUSIONS/UNASSIGNED:By providing a better quantitative model to encapsulate the structure-function relationship more accurately, our method may help deriving VF test surrogates. TRANSLATIONAL RELEVANCE/UNASSIGNED:DL-based VF surrogates not only benefit patients by reducing the testing time of VFs but also allow clinicians to make clinical judgments without the inherent limitations of VFs.
PMCID:10318595
PMID: 37382575
ISSN: 2164-2591
CID: 5538692
Age-Related Differences in Ocular Features of a Naturalistic Free-Ranging Population of Rhesus Macaques
PURPOSE:Rhesus macaques (Macaca mulatta) are the premier nonhuman primate model for studying human health and disease. We investigated if age was associated with clinically relevant ocular features in a large cohort of free-ranging rhesus macaques from Cayo Santiago, Puerto Rico. METHODS:We evaluated 120 rhesus macaques (73 males, 47 females) from 0 to 29 years old (mean ± SD: 12.6 ± 6.4) from September to December 2021. The ophthalmic evaluation included intraocular pressure (IOP) assessment, corneal pachymetry, biomicroscopy, A-scan biometry, automated refraction, and fundus photography after pupil dilation. The associations of age with the outcomes were investigated through multilevel mixed-effects models adjusted for sex and weight. RESULTS:On average, IOP, pachymetry, axial length, and automated refraction spherical equivalent were 18.37 ± 4.68 mmHg, 474.43 ± 32.21 µm, 19.49 ± 1.24 mm, and 0.30 ± 1.70 diopters (D), respectively. Age was significantly associated with pachymetry (β coefficient = -1.20; 95% confidence interval [CI], -2.27 to -0.14; P = 0.026), axial length (β coefficient = 0.03; 95% CI, 0.01 to 0.05; P = 0.002), and spherical equivalent (β coefficient = -0.12; 95% CI, -0.22 to -0.02; P = 0.015). No association was detected between age and IOP. The prevalence of cataracts in either eye was 10.83% (95% CI, 6.34-17.89) and was significantly associated with age (odds ratio [OR] = 1.20; 95% CI, 1.06-1.36; P = 0.004). Retinal drusen in either eye was observed in 15.00% (95% CI, 9.60-22.68) of animals, which was also significantly associated with age (OR = 1.14; 95% CI, 1.02-1.27; P = 0.020). CONCLUSIONS:Rhesus macaques exhibit age-related ocular associations similar to those observed in human aging, including decreased corneal thickness, increased axial length, myopic shift, and higher prevalence of cataract and retinal drusen.
PMCID:10241312
PMID: 37261386
ISSN: 1552-5783
CID: 5541582
High Variation in Inner Retinal Reflectivity Predicts Poor Visual Outcome in Patients With Central Retinal Vein Occlusion: SCORE2 Report 21
PURPOSE:To assess the association of a novel spectral domain optical coherence tomography biomarker with 6-month visual acuity in in the Study of COmparative Treatments for REtinal Vein Occlusion 2. METHODS:Spectral domain optical coherence tomography volume scans were evaluated for inner retinal hyperreflectivity, quantified by optical intensity ratio (OIR) and OIR variation. Baseline visual acuity letter score (VALS), baseline OCT biomarkers, and month 1 OIR were correlated with VALS at month 6. Regression trees, a machine learning technique yielding readily interpretable models, were used to assess for variable interaction. RESULTS:Only baseline VALS correlated positively with month 6 VALS in multivariate regression. Regression trees detected a novel functional and anatomical interaction in a subgroup. Among patients with a baseline VALS worse than 43, those with an OIR variation at month 1 of more than 0.09 had a mean of 13 fewer letters of vision at 6 months compared with patients with an OIR variation of 0.09 or less. CONCLUSIONS:Baseline VALS was the strongest predictor of month 6 VALS. Regression tree analysis detected an interaction effect, in which higher OIR variation at month 1 predicted worse 6-month VALS in patients with low VALS at baseline. OIR variation may serve as a predictor for poor visual outcome despite treatment of macular edema secondary to retinal vein occlusion in patients with poor vision at baseline. TRANSLATIONAL RELEVANCE:Pixel heterogeneity in three-dimensional OCT data may serve as measure of disruption of the retinal laminations, and this factor may carry visually prognostic value.
PMCID:10309158
PMID: 37367722
ISSN: 2164-2591
CID: 5538562
Hyperpigmented epiretinal membrane in macular telangiectasia type 2: imaging characteristics and correlation with transretinal pigment migration
OBJECTIVES/OBJECTIVE:To explore the features of black hyperpigmentation in macular telangiectasia (MacTel) type 2 and correlate these findings with the characteristics of hyperpigmented epiretinal membranes (ERMs) using multimodal imaging. METHODS:A case series of three patients with MacTel type 2 and hyperpigmented ERMs imaged with colour fundus photography, fluorescein angiography (FA), spectral-domain optical coherence tomography (OCT) and swept-source OCT angiography. Registration of different types of imaging was done using ImageJ v1.53f51 (National Institutes of Health, USA). RESULTS:Three female patients with late-stage MacTel type 2 presented with unilateral hyperpigmented ERMs in the absence of peripheral retinal breaks. In one patient, an extensive ERM occurred along with a full-thickness macular hole (FTMH); in 2 patients, smaller ERMs were seen adjacent to superficial retinal veins. Serial imaging demonstrated that transretinal pigment migration preceded epiretinal proliferation of the hyperpigmented ERM towards superficial retinal veins. CONCLUSION/CONCLUSIONS:Hyperpigmented ERMs may occur in the late phases of MacTel type 2 following a FTMH or transretinal migration of pigmented cells to the retinal surface. Once on the retinal surface, black pigment cells seem to proliferate centripetally toward superficial retinal veins.
PMID: 36138103
ISSN: 1476-5454
CID: 5335622
Virtual reality as a means to explore assistive technologies for the visually impaired
Visual impairment represents a significant health and economic burden affecting 596 million globally. The incidence of visual impairment is expected to double by 2050 as our population ages. Independent navigation is challenging for persons with visual impairment, as they often rely on non-visual sensory signals to find the optimal route. In this context, electronic travel aids are promising solutions that can be used for obstacle detection and/or route guidance. However, electronic travel aids have limitations such as low uptake and limited training that restrict their widespread use. Here, we present a virtual reality platform for testing, refining, and training with electronic travel aids. We demonstrate the viability on an electronic travel aid developed in-house, consist of a wearable haptic feedback device. We designed an experiment in which participants donned the electronic travel aid and performed a virtual task while experiencing a simulation of three different visual impairments: age-related macular degeneration, diabetic retinopathy, and glaucoma. Our experiments indicate that our electronic travel aid significantly improves the completion time for all the three visual impairments and reduces the number of collisions for diabetic retinopathy and glaucoma. Overall, the combination of virtual reality and electronic travel aid may have a beneficial role on mobility rehabilitation of persons with visual impairment, by allowing early-phase testing of electronic travel aid prototypes in safe, realistic, and controllable settings.
PMCID:10281573
PMID: 37339135
ISSN: 2767-3170
CID: 5542612
Intraocular pressure and diurnal fluctuation of open-angle glaucoma and ocular hypertension: a baseline report from the LiGHT China trial cohort
AIMS:To report the baseline intraocular pressure (IOP) characteristics and its diurnal fluctuation in the Laser in Glaucoma and Ocular Hypertension China cohort. METHODS:622 primary open-angle glaucoma (POAG) patients and 149 ocular hypertension (OHT) patients were recruited at Zhongshan Ophthalmic Center from 2015 to 2019. Standardised ocular examinations were performed including IOP measurement using the Goldmann applanation tonometer. Daytime phasing IOP was recorded at 8:00, 10:00, 11:30, 14:30, 17:00 hour. RESULTS:The mean baseline IOP was 20.2 mm Hg for POAG patients and 24.4 mm Hg for OHT. Multiple regression analysis revealed that thicker central corneal thickness (CCT) was correlated with higher IOP in both POAG and OHT. Male gender and younger age were correlated with higher IOP only for POAG. As for diurnal IOP fluctuation, mean IOP fluctuation was 3.4 mm Hg in POAG eyes and 4.4 mm Hg in OHT. The peak and trough IOP occurred at 8:00 and 14:30 hour in both POAG and OHT eyes. CONCLUSIONS:Younger age, male gender and thicker CCT are correlated to higher IOP in POAG patients while only thicker CCT is related to higher IOP in OHT patients. Peak IOP appears mostly at early morning or late afternoon and trough value occurs mostly at early afternoon.
PMID: 35086806
ISSN: 1468-2079
CID: 5498012
Geographic and socioeconomic access disparities to Phase 3 clinical trials in ophthalmology in the United States
BACKGROUND/OBJECTIVE/OBJECTIVE:To identify geographic and socioeconomic variables associated with residential proximity to Phase 3 ophthalmology clinical trial sites. METHODS:The geographic location of clinical trial sites for Phase 3 clinical trials in ophthalmology was identified using ClinicalTrials.gov. Driving time from each United States (US) census tract centroid to nearest clinical trial site was calculated using real traffic patterns. Travel data were crosslinked to census-tract level public datasets from United States Census Bureau American Community Survey (ACS). Cross-sectional multivariable regression was used to identify associations between census-tract sociodemographic factors and driving time (>60 min) from each census tract centroid to the nearest clinical trial site. RESULTS:There were 2330 unique clinical trial sites and 71,897 census tracts. Shortest median time was to retina sites [33.7 min (18.7, 70.1 min)]. Longest median time was to neuro-ophthalmology sites [119.8 min (48.7, 240.4 min)]. Driving >60 min was associated with rural tracts [adjusted odds ratio (aOR) 7.60; 95% CI (5.66-10.20), p < 0.0001]; Midwest [aOR 1.84(1.15-2.96), p = 0.01], South [aOR 2.57 (1.38-4.79), p < 0.01], and West [aOR 2.52 (1.52-4.17), p < 0.001] v. Northeast; and tracts with higher visual impairment [aOR 1.07 (1.03-1.10), p < 0.001)]; higher poverty levels [4th v.1st Quartile of population below poverty, aOR 2.26 (1.72-2.98), p < 0.0001]; and lower education levels [high school v. Bachelor's degree or higher aOR 1.02 (1.00-1.03), p = 0.0072]. CONCLUSIONS:There are significant geographic and socioeconomic disparities in access to ophthalmology clinical trial sites for rural, non-Northeastern, poorer, and lower education level census tracts, and for census tracts with higher levels of self-reported visual impairment.
PMCID:10275860
PMID: 36123561
ISSN: 1476-5454
CID: 5524262
A rare case of mucoepidermoid carcinoma ex pleomorphic adenoma of the lacrimal gland [Case Report]
Carcinoma ex pleomorphic adenoma (CEPA) of the lacrimal gland is a rare malignant tumor that arises from a pre-existing pleomorphic adenoma. Lacrimal gland CEPA with mucoepidermoid histological subtype is exceedingly rare. Diagnosis can be aided by radiographic findings, though the gold standard is histopathological analysis following excisional biopsy. Management options include complete surgical excision with or without adjuvant radiation therapy based on tumor grade and invasiveness. We present a 76-year-old woman with 6 months of diplopia and unilateral proptosis. Her initial exam was remarkable for hypoglobus, proptosis, and limited elevation of the right eye. Computed tomography (CT) scan demonstrated a superior, well-circumscribed, extraconal orbital mass. An excisional biopsy was performed, and histopathological findings were consistent with mucoepidermoid carcinoma ex pleomorphic adenoma with positive margins in the tumor capsule. The patient received radiation therapy and remains markedly improved with no disease recurrence at 5 months post-operatively.
PMID: 34939520
ISSN: 1744-5108
CID: 5533942
Wearables for Persons with Blindness and Low Vision: Form Factor Matters
Based on statistics from the WHO and the International Agency for the Prevention of Blindness, an estimated 43.3 million people have blindness and 295 million have moderate and severe vision impairment globally as of 2020, statistics expected to increase to 61 million and 474 million respectively by 2050, staggering numbers. Blindness and low vision (BLV) stultify many activities of daily living, as sight is beneficial to most functional tasks. Assistive technologies for persons with blindness and low vision (pBLV) consist of a wide range of aids that work in some way to enhance one's functioning and support independence. Although handheld and head-mounted approaches have been primary foci when building new platforms or devices to support function and mobility, this perspective reviews potential shortcomings of these form factors or embodiments and posits that a body-centered approach may overcome many of these limitations.
PMID: 37115821
ISSN: 1949-3614
CID: 5465582
Ex Vivo OCT-Based Multimodal Imaging of Human Donor Eyes for Research into Age-Related Macular Degeneration
A progression sequence for age-related macular degeneration (AMD) learned from optical coherence tomography (OCT)-based multimodal (MMI) clinical imaging could add prognostic value to laboratory findings. In this work, ex vivo OCT and MMI were applied to human donor eyes prior to retinal tissue sectioning. The eyes were recovered from non-diabetic white donors aged ≥80 years old, with a death-to-preservation time (DtoP) of ≤6 h. The globes were recovered on-site, scored with an 18 mm trephine to facilitate cornea removal, and immersed in buffered 4% paraformaldehyde. Color fundus images were acquired after anterior segment removal with a dissecting scope and an SLR camera using trans-, epi-, and flash illumination at three magnifications. The globes were placed in a buffer within a custom-designed chamber with a 60 diopter lens. They were imaged with spectral domain OCT (30° macula cube, 30 µm spacing, averaging = 25), near-infrared reflectance, 488 nm autofluorescence, and 787 nm autofluorescence. The AMD eyes showed a change in the retinal pigment epithelium (RPE), with drusen or subretinal drusenoid deposits (SDDs), with or without neovascularization, and without evidence of other causes. Between June 2016 and September 2017, 94 right eyes and 90 left eyes were recovered (DtoP: 3.9 ± 1.0 h). Of the 184 eyes, 40.2% had AMD, including early intermediate (22.8%), atrophic (7.6%), and neovascular (9.8%) AMD, and 39.7% had unremarkable maculas. Drusen, SDDs, hyper-reflective foci, atrophy, and fibrovascular scars were identified using OCT. Artifacts included tissue opacification, detachments (bacillary, retinal, RPE, choroidal), foveal cystic change, an undulating RPE, and mechanical damage. To guide the cryo-sectioning, OCT volumes were used to find the fovea and optic nerve head landmarks and specific pathologies. The ex vivo volumes were registered with the in vivo volumes by selecting the reference function for eye tracking. The ex vivo visibility of the pathology seen in vivo depends on the preservation quality. Within 16 months, 75 rapid DtoP donor eyes at all stages of AMD were recovered and staged using clinical MMI methods.
PMID: 37306417
ISSN: 1940-087x
CID: 5541382
Quantitative assessment of choriocapillaris flow deficits and type 1 macular neovascularization growth in age-related macular degeneration
During the past 15 years, new treatment paradigms for neovascular age-related macular degeneration (nvAMD) have evolved due to the advent of intravitreal anti-vascular endothelial growth factor (VEGF) therapy and rapid advances in retinal imaging. Recent publications describe eyes with type 1 macular neovascularization (MNV) as showing more resistance to macular atrophy than eyes with other lesion types. We sought to explore whether the perfusion status of the native choriocapillaris (CC) surrounding type 1 MNV influences its pattern of growth. To evaluate this effect, we analyzed a case series of 22 eyes from 19 nvAMD patients with type 1 MNV exhibiting growth on swept-source optical coherence tomography angiography (SS-OCTA) over a minimum follow-up of 12 months. We observed an overall weak correlation between type 1 MNV growth and CC flow deficits (FDs) average size (τ = 0.17, 95% CI [- 0.20, 0.62]) and a moderate correlation with CC FD % (τ = 0.21, 95% CI [- 0.16, 0.68]). Type 1 MNV was located beneath the fovea in most of the eyes (86%) and median visual acuity was 20/35 Snellen equivalent. Our results support that type 1 MNV recapitulates areas of CC blood flow impairment while serving to preserve foveal function.
PMCID:10220043
PMID: 37236984
ISSN: 2045-2322
CID: 5541552
Impact on neonatal morbidities after a change in policy to administer antenatal corticosteroids to mothers at risk for late preterm delivery
OBJECTIVES/OBJECTIVE:Antenatal corticosteroids (ACS) administered to mothers at risk for preterm delivery before 34 weeks has been standard care to improve neonatal outcomes. After introducing a new obstetric policy based on updated recommendations advising the administration of ACS to pregnant women at risk for late preterm (LPT) delivery (34-36 6/7 weeks), we set out to determine the short-term clinical impact on those LPT neonates. METHODS:Retrospective chart review of LPT neonates delivered at NYU Langone Medical Center both one year before and after the policy went into place. We excluded subjects born to mothers with pre-gestational diabetes, multiple gestations, and those with congenital/genetic abnormalities. We also excluded subjects whose mothers already received ACS previously in pregnancy. Subjects were divided into pre-policy and post-policy groups. Neonatal and maternal data were compared for both groups. RESULTS:388 subjects; 180 in the pre-policy and 208 in the post-policy group. This policy change resulted in a significant increase in ACS administration to mothers who delivered LPT neonates (67.3 vs. 20.6%, p<0.001). In turn, there was a significant reduction in LPT neonatal intensive care unit (NICU) admissions (44.2 vs. 54.4%, p=0.04) and need for respiratory support (27.9 vs. 42.8%, p<0.01). However, we also found an increased incidence of hypoglycemia (49.5 vs. 28.3%, p<0.001). CONCLUSIONS:This LPT ACS policy appears effective in reducing the need for LPT NICU level care overall. However, clinicians must be attentive to monitor for adverse effects like hypoglycemia, and there remains a need for better understanding of potential long-term impacts.
PMID: 36318716
ISSN: 1619-3997
CID: 5358552
Recurrent Anterior Uveitis Associated with Major Fluctuations in Choroidal Thickness in Patient with Pachychoroid Disorder
PURPOSE/OBJECTIVE:To describe remarkable choroidal thickness fluctuations corresponding to episodes of recurrent anterior uveitis with subretinal fluid development when exceeding a choroidal thickness threshold. METHODS:A patient with pachychoroid pigment epitheliopathy and unilateral acute anterior uveitis of the left eye was evaluated over a period of 3 years with multimodal retinal imaging including optical coherence tomography (OCT). Longitudinal changes in subfoveal choroidal thickness (CT) were measured and correlated with episodes of recurrent inflammation. RESULTS:Over the course of 5 recurrent episodes of inflammation in the left eye treated with oral antiviral and topical steroid therapy, subfoveal CT increased as much as 200 um or more. Subfoveal CT in the fellow quiescent right eye by contrast, was within normal limits and minimally changed throughout the follow up. Increased CT occurred with each episode of anterior uveitis and decreased by 200 µm or more during periods of quiescence in the affected left eye. Subretinal fluid and macular edema developed with a maximum CT of 468 um and spontaneously resolved when CT decreased after treatment. CONCLUSION/CONCLUSIONS:In eyes with pachychoroid disease, anterior segment inflammation may lead to marked increases in subfoveal CT and the development of subretinal fluid at a threshold thickness value.
PMID: 37229756
ISSN: 1937-1578
CID: 5543862
Angiographic biomarkers are significant predictors of treatment response to intravitreal aflibercept in diabetic macular edema
This prospective single-center study aims to identify biomarkers that predict improvement in best-corrected visual acuity (BCVA) and central retinal thickness (CRT) at 6 months, in 76 eyes with diabetic macular edema (DME) treated monthly with intravitreal aflibercept. At baseline, all patients underwent standardized imaging with color photography, optical coherence tomography (OCT), fluorescein angiography (FA) and OCT angiography (OCTA). Glycosylated hemoglobin, renal function, dyslipidemia, hypertension, cardiovascular disease and smoking were recorded. Retinal images were graded in a masked fashion. Baseline imaging, systemic and demographic variables were investigated to detect associations to BCVA and CRT change post aflibercept. Predictors of BCVA improvement included greater macular vessel density quantified using OCTA (p = 0.001) and low-density lipoprotein (LDL) ≥ 2.6 mmol/L (p = 0.017). Lower macular vessel density eyes showed a significant reduction in CRT but no BCVA improvement. Predictors of CRT reduction included peripheral non-perfusion seen on ultrawide-field FA (p = 0.005) and LDL ≥ 2.6 mmol/L (p < 0.001). Retinal angiographic biomarkers derived from OCTA and ultrawide-field FA may help predict functional and anatomic response to anti-vascular endothelial growth factor (VEGF) therapy in patients with DME. Elevated LDL is associated with treatment response in DME. These results may be used to better-select patients who will benefit from intravitreal aflibercept for treatment of DME.
PMCID:10199070
PMID: 37208427
ISSN: 2045-2322
CID: 5503672
Dual-pharmacophore artezomibs hijack the Plasmodium ubiquitin-proteasome system to kill malaria parasites while overcoming drug resistance
Artemisinins (ART) are critical anti-malarials and despite their use in combination therapy, ART-resistant Plasmodium falciparum is spreading globally. To counter ART resistance, we designed artezomibs (ATZs), molecules that link an ART with a proteasome inhibitor (PI) via a non-labile amide bond and hijack parasite's own ubiquitin-proteasome system to create novel anti-malarials in situ. Upon activation of the ART moiety, ATZs covalently attach to and damage multiple parasite proteins, marking them for proteasomal degradation. When damaged proteins enter the proteasome, their attached PIs inhibit protease function, potentiating the parasiticidal action of ART and overcoming ART resistance. Binding of the PI moiety to the proteasome active site is enhanced by distal interactions of the extended attached peptides, providing a mechanism to overcome PI resistance. ATZs have an extra mode of action beyond that of each component, thereby overcoming resistance to both components, while avoiding transient monotherapy seen when individual agents have disparate pharmacokinetic profiles.
PMID: 37148884
ISSN: 2451-9448
CID: 5503222
Journal of AAPOS: American association for pediatric ophthalmology & strabismus. 2023:27(3):137.e1-6.DOI: 10.1016/j.jaapos.2023.03.004
The impact of the COVID-19 lockdown on retinopathy of prematurity screening and management in the United States: a multicenter study
PURPOSE/OBJECTIVE:To study the effect of the pandemic-related lockdown (physical distance measures and movement restrictions) on the characteristics and management of retinopathy of prematurity (ROP). METHODS:In this controlled, multicenter cohort study, the medical records of patients born prematurely and screened for ROP in the neonatal intensive care unit during four time periods were reviewed retrospectively: (1) November 1, 2018, to March 15, 2019; (2) March 16, 2019, to August 2, 2019 (lockdown control period); (3) November 1, 2019, to March 15, 2020; and (4) March 16, 2020-August 2, 2020. RESULTS:A total of 1,645 patients met inclusion criteria. Among the 1,633 patients with complete data, mean gestational age (GA) at birth was 28.2, 28.4, 28.0, and 28.3 weeks across time periods 1 to 4, respectively (P = 0.16). The mean birth weight of all patients was 1079.1 ± 378.60 g, with no significant variation across time periods (P = 0.08). There were fewer patients screened during the lockdown period (n = 411) compared with the period immediately before (n = 491) and the same period in the prior year (n = 533). Significantly more patients were screened using indirect ophthalmoscopy, compared to digital imaging (telemedicine), during the lockdown (P < 0.01). There were 11.7%, 7.7%, 9.0%, and 8.8% of patients requiring treatment in each time period, respectively (P = 0.42), with a median postmenstrual age at initial treatment of 37.2, 36.45, 37.1, and 36.3 weeks, respectively (P = 0.32). CONCLUSIONS:We recorded a decrease in the number of infants meeting criteria for ROP screening during the lockdown. The GA at birth and birth weight did not differ. Significantly more infants were screened with indirect ophthalmoscopy, compared to digital imaging, during the lockdown.
PMCID:10166609
PMID: 37164223
ISSN: 1528-3933
CID: 5507982
Opportunities to address gaps in early detection and improve outcomes of liver cancer
Death rates from primary liver cancer (hepatocellular carcinoma [HCC]) have continued to rise in the United States over the recent decades despite the availability of an increasing range of treatment modalities, including new systemic therapies. Prognosis is strongly associated with tumor stage at diagnosis; however, most cases of HCC are diagnosed beyond an early stage. This lack of early detection has contributed to low survival rates. Professional society guidelines recommend semiannual ultrasound-based HCC screening for at-risk populations, yet HCC surveillance continues to be underused in clinical practice. On April 28, 2022, the Hepatitis B Foundation convened a workshop to discuss the most pressing challenges and barriers to early HCC detection and the need to better leverage existing and emerging tools and technologies that could improve HCC screening and early detection. In this commentary, we summarize technical, patient-level, provider-level, and system-level challenges and opportunities to improve processes and outcomes across the HCC screening continuum. We highlight promising approaches to HCC risk stratification and screening, including new biomarkers, advanced imaging incorporating artificial intelligence, and algorithms for risk stratification. Workshop participants emphasized that action to improve early detection and reduce HCC mortality is urgently needed, noting concern that many of the challenges we face today are the same or similar to those faced a decade ago and that HCC mortality rates have not meaningfully improved. Increasing the uptake of HCC screening was identified as a short-term priority while developing and validating better screening tests and risk-appropriate surveillance strategies.
PMCID:10212536
PMID: 37144952
ISSN: 2515-5091
CID: 5533332
Foveal Development and Posterior Precortical Vitreous Pocket Formation
PMCID:10125119
PMID: 37068222
ISSN: 1539-2864
CID: 5464842
Retinal racemose hemangioma (retinal arteriovenous communication) diagnosed and managed with multimodal imaging
PURPOSE/OBJECTIVE:Retinal racemose hemangioma (RRH) is a rare congenital abnormality of the retinal vasculature with a variety of secondary manifestations that can cause vision loss, including macular edema. This report aims to demonstrate the utility of swept-source optical coherence tomography angiography (SS-OCTA) in further characterizing this abnormality. METHODS:Case report with multimodal imaging including SS-OCTA. RESULTS:A 56-year-old woman with blurred vision was diagnosed macular edema secondary to RRH. Localization of the arterial-venous connection was identified with SS-OCTA at the deep capillary plexus (DCP). Conservative management of the associated foveal exudation ultimately led to a favorable outcome. DISCUSSION/CONCLUSIONS:Observation or topical therapy may be useful and warranted in select cases of RRH. The anomalous vascular connection in RRH appears to originate at the level of the DCP in this case, however larger studies are necessary for corroboration. Evolving angiographic modalities like SS-OCTA may continue to provide insights for this rare disease.
PMID: 34033599
ISSN: 1937-1578
CID: 4887762
The relationship between dietary patterns and ophthalmic disease
PURPOSE OF REVIEW/OBJECTIVE:There is a rising interest in the impact of diet on the pathogenesis of common ophthalmic conditions. The purpose of this review is to summarize the potential preventive and therapeutic power of dietary interventions described in recent basic science and epidemiological literature. RECENT FINDINGS/RESULTS:Basic science investigations have elucidated a variety of mechanisms by which diet may impact ophthalmic disease, particularly through its action on chronic oxidative stress, inflammation and macular pigmentation. Epidemiologic investigations have shown the real-world influence of diet on the incidence and progression of a number of ophthalmic diseases, particularly cataract, age-related macular degeneration (AMD) and diabetic retinopathy. A large observational cohort study found a 20% reduction in the incidence of cataract among vegetarians compared with nonvegetarians. Two recent systematic reviews found that higher adherence to Mediterranean dietary patterns was associated with a decreased risk of progression of AMD to later stages. Finally, large meta-analyses found that patients following plant-based and Mediterranean diets had significant reductions of mean haemoglobin A1c scores and incidence of diabetic retinopathy as compared with controls. SUMMARY/CONCLUSIONS:There is a significant and growing body of evidence that Mediterranean diet and plant-based diets - those that maximize fruits, vegetables, legumes, whole grains and nuts; and that minimize animal products and processed foods - help prevent vision loss from cataract, AMD and diabetic retinopathy. These diets may hold benefits for other ophthalmic conditions, as well. Nevertheless, there is a need for further randomized, controlled and longitudinal studies in this area.
PMID: 36866844
ISSN: 1531-7021
CID: 5462352
Potential Rare Danger of Presumably Benign Artificial Tears [Comment]
PMID: 36947074
ISSN: 2168-6173
CID: 5502512
Chorioretinitis sclopetaria and orbital emphysema caused by a high-velocity liquid missile
PURPOSE/OBJECTIVE:To highlight a case of chorioretinitis sclopetaria, with concomitant macular hole formation and orbital emphysema, caused by a commercial-grade pressure washer. PATIENT/METHODS:A 19-year-old male presented to the emergency department with a left eye injury, incurred after being sprayed with a commercial-grade pressure washer. He endorsed ipsilateral blurred vision, pain, and linear floaters. Left eye visual acuity was 20/40. Dilated fundus exam showed inferior vitreous hemorrhage, retinal whitening, and pre-, intra-, and sub-retinal hemorrhages, consistent with chorioretinitis sclopetaria. Optical coherence tomography revealed a full-thickness macular hole. Computed tomography scan of the orbits showed subcutaneous and post-septal orbital emphysema. Two months following injury, vitreous and retinal hemorrhages and macular hole resolved. Five months following injury, visual acuity improved to 20/20. DISCUSSION/CONCLUSIONS:Chorioretinitis sclopetaria is defined as a full-thickness chorioretinal disruption resulting from a high-velocity projectile passing adjacent to or into the orbit without penetrating the globe. Chorioretinal deformation and ocular comorbidities are influenced by the velocity of the missile and its spatial relationship to the orbit. While this pattern of injury is typically associated with indirect trauma to the globe by a BB or a bullet, this is the first report of chorioretinitis sclopetaria precipitated by a high-velocity liquid missile.
PMID: 34001762
ISSN: 1937-1578
CID: 5264712
Eccrine Cyst (Hidrocystoma) of the Inner Canthus: A Rare Entity With Immunohistologic Confirmation
A small ruptured cyst was excised from the left inner canthus of a 68-year-old woman. Histopathology displayed a cyst lined by a double layer of cuboidal epithelium and filled with amorphous material. The lining cells were strongly positive for cytokeratins 5/6 and 14, with weak reactivity with cytokeratin 7. These findings were identical to those in a single previous report of an eccrine cyst of the eyelid, making this the second example of a bona fide eccrine hidrocystoma of the eyelid.
PMID: 36806128
ISSN: 1537-2677
CID: 5433812
Pigmented Inflamed Seborrheic Keratosis of the Bulbar Conjunctiva
A 57-year-old Black man presented with the recent onset of a pigmented temporal epibulbar lesion. As pigmentation of conjunctival epithelial lesions is correlated with complexion pigmentation, the lesion was presumed to represent a pigmented ocular surface squamous neoplasia (OSSN). Excisional biopsy, however, revealed a pigmented conjunctival seborrheic keratosis, a rare occurrence. The lesion lacked cytologic atypia. Intralesional processes of dendritic melanocytes were demonstrated by hematoxylin-eosin and Melan-A stains. Melanophages also contributed to clinical pigmentation. Subepithelial lymphocytic infiltration, elevated Ki67 proliferative rate, prominent mitotic activity, and subtle spongiosis afforded evidence of inflammation rather than malignancy in a lesion devoid of cytologic atypia.
PMID: 36806147
ISSN: 1537-2677
CID: 5433822
Prospective Assessment of Otologic Adverse Events due to Teprotumumab: Preliminary Results
OBJECTIVE:To assess a series of patients receiving teprotumumab therapy and objectively quantify the rates of otologic adverse events. STUDY DESIGN:A prospective cohort study of adult patients receiving teprotumumab between May 2020 and January 2022. SETTING:Tertiary referral center. METHODS:Prior to treatment initiation, an ototoxicity-specific audiometric battery was completed, which included conventional audiometry (frequencies 250-8000 Hz), ultrahigh-frequency audiometry (9000-20,000 Hz), tympanometry, speech discrimination scores, and distortion product otoacoustic emissions (DPOAEs). Testing was then repeated after treatment completion. RESULTS:In total, 35 patients were recruited, with a median (range) age of 48.5 years (21-74), and 8 (22.8%) were male. The most common subjective symptom reported was a hearing decline (25.7%), followed by aural fullness (17.1%) and tinnitus (14.3%). Fourteen patients had both pre- and posttreatment audiometric data. Among them, 3 patients (21.4%) were found to have changes in standard frequency audiometry, and 10 (71.4%) had changes in high-frequency audiometry, with 2 patients having changes in both. Less than half (n = 5) of the 11 patients with changes in standard or high-frequency pure tone hearing noted subjective hearing decline. Changes in DPOAE were noted in 4 patients out of 13 (30.7%). Two patients discontinued treatment due to hearing decline. Finally, 3 patients (8.6%) were diagnosed with patulous eustachian tube (PET) by an otolaryngologist, and another 3 patients are suspected to have PET based on symptom description during ophthalmologic follow-up. CONCLUSION:In our cohort, a high incidence of otologic symptoms was found to be associated with teprotumumab usage. Subjective hearing decline, changes in ultrahigh-frequency hearing as well as eustachian tube dysfunction may be encountered and suggest the potential ototoxicity of teprotumumab.
PMID: 36939482
ISSN: 1097-6817
CID: 5462732
Ocular manifestations of central insulin resistance
Central insulin resistance, the diminished cellular sensitivity to insulin in the brain, has been implicated in diabetes mellitus, Alzheimer's disease and other neurological disorders. However, whether and how central insulin resistance plays a role in the eye remains unclear. Here, we performed intracerebroventricular injection of S961, a potent and specific blocker of insulin receptor in adult Wistar rats to test if central insulin resistance leads to pathological changes in ocular structures. 80 mg of S961 was stereotaxically injected into the lateral ventricle of the experimental group twice at 7 days apart, whereas buffer solution was injected to the sham control group. Blood samples, intraocular pressure, trabecular meshwork morphology, ciliary body markers, retinal and optic nerve integrity, and whole genome expression patterns were then evaluated. While neither blood glucose nor serum insulin level was significantly altered in the experimental or control group, we found that injection of S961 but not buffer solution significantly increased intraocular pressure at 14 and 24 days after first injection, along with reduced porosity and aquaporin 4 expression in the trabecular meshwork, and increased tumor necrosis factor α and aquaporin 4 expression in the ciliary body. In the retina, cell density and insulin receptor expression decreased in the retinal ganglion cell layer upon S961 injection. Fundus photography revealed peripapillary atrophy with vascular dysregulation in the experimental group. These retinal changes were accompanied by upregulation of pro-inflammatory and pro-apoptotic genes, downregulation of anti-inflammatory, anti-apoptotic, and neurotrophic genes, as well as dysregulation of genes involved in insulin signaling. Optic nerve histology indicated microglial activation and changes in the expression of glial fibrillary acidic protein, tumor necrosis factor α, and aquaporin 4. Molecular pathway architecture of the retina revealed the three most significant pathways involved being inflammation/cell stress, insulin signaling, and extracellular matrix regulation relevant to neurodegeneration. There was also a multimodal crosstalk between insulin signaling derangement and inflammation-related genes. Taken together, our results indicate that blocking insulin receptor signaling in the central nervous system can lead to trabecular meshwork and ciliary body dysfunction, intraocular pressure elevation, as well as inflammation, glial activation, and apoptosis in the retina and optic nerve. Given that central insulin resistance may lead to neurodegenerative phenotype in the visual system, targeting insulin signaling may hold promise for vision disorders involving the retina and optic nerve.
PMID: 36255004
ISSN: 1673-5374
CID: 5360332
Vitamin A deficiency and the retinal "double carrot" sign with optical coherence tomography
BACKGROUND:Spectral-domain optical coherence tomography (SD-OCT) and full-field electroretinography (ERG) allow retinal assessment with vitamin A deficiency (VAD). Using SD-OCT, this study aimed to characterize and follow a novel retinal abnormality in patients with VAD and intramuscular supplementation. METHODS:Patients with VAD were retrospectively reviewed, including SD-OCT and electroretinography. RESULTS:Three patients had VAD following bariatric or colon surgery and varying supplementation. All had nyctalopia, extinguished scotopic rod-specific function with ERG, and decreased serum vitamin A. None demonstrated surface abnormalities. All received intramuscular vitamin A with subjective resolution of symptoms. On SD-OCT, four of six eyes exhibited homogenous foveal hyperreflectivity anterior to retinal pigment epithelium-Bruch complex, reminiscent of a "double carrot", which improved following supplementation. ERG findings demonstrated improved scotopic rod-specific function in all cases; however, photopic function remained diminished in two cases. CONCLUSIONS:Structural improvement of the proposed "double carrot" sign occurs soon after vitamin A supplementation. While scotopic function improves rapidly following supplementation, cone function recovers more slowly. Therefore, foveal changes such as the "double carrot" sign suggest that structural recovery of cones precedes functional recovery.
PMID: 35840717
ISSN: 1476-5454
CID: 5269592
Asia-Pacific journal of ophthalmology (Philadelphia, Pa.). 2023:12(3):310-314.DOI: 10.1097/APO.0000000000000614
Federated AI, Current State, and Future Potential
Artificial intelligence and machine learning applications are becoming increasingly popular in health care and medical devices. The development of accurate machine learning algorithms requires large quantities of good and diverse data. This poses a challenge in health care because of the sensitive nature of sharing patient data. Decentralized algorithms through federated learning avoid data aggregation. In this paper we give an overview of federated learning, current examples in healthcare and ophthalmology, challenges, and next steps.
PMID: 37249902
ISSN: 2162-0989
CID: 5541882
Financial Health of Private Equity-Backed Groups: Perspectives From Eye Care
BACKGROUND:In private equity (PE) buyouts of medical practices, it is common for the PE firm to raise significant levels of debt in order to finance the purchase. This debt is subsequently shouldered by the acquired practice(s). There remains a scarcity of literature quantifying the effect of PE acquisition on the subsequent financial performance of eye care practices. We aim to identify and characterize debt valuations of ophthalmology and optometry private equity-backed group (OPEG) practices, which serve as an indicator of practice financial performance. METHODS:A cross-sectional study from March 2017 to March 2022 was conducted using business development company (BDC) quarterly/annual filings to the Securities and Exchange Commission (SEC). The 2021 BDC Report was used to identify all BDCs actively filing annual reports (Form 10-Ks) and quarterly reports (Form 10-Qs) in the United States in 2021. The public filings of BDCs lending to OPEGs were searched from the inception of the OPEG's debt instrument in a BDC's portfolio and the amortized cost and fair value of each debt instrument were tabulated. A panel linear regression was used to evaluate temporal changes in OPEG valuations. RESULTS: A total of 2,997 practice locations affiliated with 14 unique OPEGs and 17 BDCs were identified over the study period. Debt valuations of OPEGs decreased by 0.46% per quarter over the study period (95% CI: -0.88 to -0.03, P = 0.036). In the COVID-19 pre-vaccine period (March 2020 to December 2020), there was an excess (additional) 4.93% decrease in debt valuations (95% CI: -8.63 to -1.24, P = 0.010) when compared to pre-pandemic debt valuations (March 2017 to December 2019). Effects of COVID-19 on valuations stabilized during the pandemic post-vaccine period (February 2021 to March 2022), with no change in excess debt valuation compared to pre-pandemic baseline (0.60, 95% CI: -4.59 to 5.78, P = 0.822). There was an increase in practices that reported average discounted debt valuations from 20 practices (1.6%) associated with one OPEG to 1,213 practices (40.5%) associated with nine OPEGs (including 100% of newly acquired practices), despite the stabilization of COVID-19-related excess (additional) debt. CONCLUSIONS:Debt valuations of eye care practices have declined significantly post-PE investment from March 2017 to March 2022, suggesting that the financial health of these groups is volatile and vulnerable to economic contractions such as the COVID-19 pandemic. Eye care practice owners must consider long-term financial risks and impacts of subsequent patient care when selling their practice to a private equity group. Future research should assess the impact of secondary transactions of OPEGs on the financial health of practices, practitioner lifestyle, and patient outcomes.
PMCID:10293123
PMID: 37384090
ISSN: 2168-8184
CID: 5540452
Presence of Choroidal Caverns in Patients with Posterior and Panuveitis
Choroidal caverns (CCs) have been described in association with age-related macular degeneration and pachychoroid disease. However, it is unknown if caverns are found in patients with chronic non-infectious uveitis (NIU). Herein, we evaluated patients with NIU who had optical coherence tomography and indocyanine green angiography for CCs. Clinical and demographic characteristics were extracted from the chart review. Univariate and multivariate mixed-effects logistical models were used to assess the association between clinical and demographic factors and the presence of CCs. One hundred thirty-five patients (251 eyes) met the inclusion criteria: 1 eye had anterior uveitis, 5 had intermediate uveitis, 194 had posterior uveitis, and 51 had panuveitis. The prevalence of CCs was 10%. CCs were only observed in patients with posterior and panuveitis, with a prevalence of 10.8% and 7.8%, respectively. Multifocal choroiditis (MFC) was the type of uveitis where CCs were most frequently observed, with 40% of eyes with MFC having CCs. In addition, male sex (p = 0.024) was associated with CCs. There was no significant difference in the degree of intraocular inflammation or mean subfoveal choroidal thickness between CC+ and CC- eyes. This is the first study to describe CCs in uveitis. Overall, these findings suggest that caverns may be a sequela of structural and/or vascular perturbations in the choroid from uveitis.
PMCID:10215513
PMID: 37238939
ISSN: 2227-9059
CID: 5543982
Treatment expectations in glaucoma: what matters most to patients?
BACKGROUND/OBJECTIVES/OBJECTIVE:Recent clinical trials in glaucoma have used patient-reported outcome measures (PROMs) of health-related quality of life to evaluate interventions. However, existing PROMs may not be sufficiently sensitive to capture changes in health status. This study aims to determine what really matters to patients by directly exploring their treatment expectations and preferences. SUBJECTS/METHODS/METHODS:We conducted a qualitative study using one-to-one semi-structured interviews to elicit patients' preferences. Participants were recruited from two NHS clinics serving urban, suburban and rural populations in the UK. To be relevant across glaucoma patients under NHS care, participants were sampled to include a full range of demographic profiles, disease severities and treatment histories. Interview transcripts were evaluated using thematic analysis until no new themes emerged (saturation). Saturation was established when 25 participants with ocular hypertension, mild, moderate and advanced glaucoma had been interviewed. RESULTS:Themes identified were: Patients' experiences of living with glaucoma, patients' experiences of having glaucoma treatment, most important outcomes to patients, and COVID-related concerns. Participants specifically expressed their most important concerns, which were (i) disease-related outcomes (intraocular pressure control, maintaining vision, and being independent); and (ii) treatment-related outcomes (treatment that does not change, drop-freedom, and one-time treatment). Both disease-related and treatment-related experiences were covered prominently in interviews with patients across the spectrum of glaucoma severity. CONCLUSIONS:Outcomes related both to the disease and its treatment are important to patients with different severities of glaucoma. To accurately evaluate quality of life in glaucoma, PROMs may need to assess both disease-related and treatment-related outcomes.
PMCID:10124929
PMID: 37095276
ISSN: 1476-5454
CID: 5498172
TFOS Lifestyle: Impact of elective medications and procedures on the ocular surface
The word "elective" refers to medications and procedures undertaken by choice or with a lower grade of prioritization. Patients usually use elective medications or undergo elective procedures to treat pathologic conditions or for cosmetic enhancement, impacting their lifestyle positively and, thus, improving their quality of life. However, those interventions can affect the homeostasis of the tear film and ocular surface. Consequently, they generate signs and symptoms that could impair the patient's quality of life. This report describes the impact of elective topical and systemic medications and procedures on the ocular surface and the underlying mechanisms. Moreover, elective procedures performed for ocular diseases, cosmetic enhancement, and non-ophthalmic interventions, such as radiotherapy and bariatric surgery, are discussed. The report also evaluates significant anatomical and biological consequences of non-urgent interventions to the ocular surface, such as neuropathic and neurotrophic keratopathies. Besides that, it provides an overview of the prophylaxis and management of pathological conditions resulting from the studied interventions and suggests areas for future research. The report also contains a systematic review investigating the quality of life among people who have undergone small incision lenticule extraction (SMILE). Overall, SMILE seems to cause more vision disturbances than LASIK in the first month post-surgery, but less dry eye symptoms in long-term follow up.
PMID: 37087043
ISSN: 1937-5913
CID: 5484962
LONG-TERM PRESERVATION OF VISUAL ACUITY AFTER RESORPTION OF ACQUIRED VITELLIFORM LESIONS IN AGE-RELATED MACULAR DEGENERATION
PURPOSE/OBJECTIVE:To report the long-term (23 years) clinical and multimodal imaging features of acquired vitelliform lesions (AVLs) associated with non-neovascular age-related macular degeneration (AMD). METHODS:Retrospective case report. Color and red free fundus photographs, high-resolution optical coherence tomography (High-Res OCT), fluorescein (FA) and indocyanine green angiography (ICGA), and OCT-angiography (OCTA) were performed. RESULTS:A 58-year-old man presented with bilateral AVLs in the setting of non-neovascular AMD. At baseline, his best-corrected visual acuity (BCVA) was 20/30 in his right eye and 20/20 in his left eye. Red free fundus photographs showed AVLs with cuticular drusen in both eyes corresponding to a "stars-in-the-sky" pattern on FA. ICGA showed no evidence of macular neovascularization (MNV). Throughout the 23-year follow-up, the patient reported consuming 20mg/day of lutein supplement. At the end of follow-up, his BCVA was 20/20 in both eyes. Color fundus photographs showed resorption of the AVLs in both eyes and High-Res OCT showed relative preservation of the outer retinal bands in the fovea. OCTA confirmed the absence of MNV. CONCLUSION/CONCLUSIONS:In non-neovascular AMD, spontaneous resorption of AVLs may be associated with long-term maintenance of visual acuity and relative preservation of the outer retinal morphology.
PMID: 37071922
ISSN: 1937-1578
CID: 5466122
Combinations of Scheimpflug tomography, ocular coherence tomography and air-puff tonometry improve the detection of keratoconus
PURPOSE/OBJECTIVE:To determine whether combinations of devices with different measuring principles, supported by artificial intelligence (AI), can improve the diagnosis of keratoconus (KC). METHODS:Scheimpflug tomography, spectral-domain optical coherence tomography (SD-OCT), and air-puff tonometry were performed in all eyes. The most relevant machine-derived parameters to diagnose KC were determined using feature selection. The normal and forme fruste KC (FFKC) eyes were divided into training and validation datasets. The selected features from a single device or different combinations of devices were used to develop models based on random forest (RF) or neural networks (NN) trained to distinguish FFKC from normal eyes. The accuracy was determined using receiver operating characteristic (ROC) curves, area under the curve (AUC), sensitivity, and specificity. RESULTS:271 normal eyes, 84 FFKC eyes, 85 early KC eyes, and 159 advanced KC eyes were included. A total of 14 models were built. Air-puff tonometry had the highest AUC for detecting FFKC using a single device (AUC = 0.801). Among all two-device combinations, the highest AUC was accomplished using RF applied to selected features from SD-OCT and air-puff tonometry (AUC = 0.902), followed by the three-device combination with RF (AUC = 0.871) with the best accuracy. CONCLUSION/CONCLUSIONS:Existing parameters can precisely diagnose early and advanced KC, but their diagnostic ability for FFKC could be optimized. Applying an AI algorithm to a combination of air-puff tonometry with Scheimpflug tomography or SD-OCT could improve FFKC diagnostic ability. The improvement in diagnostic ability by combining three devices is modest.
PMID: 37055334
ISSN: 1476-5411
CID: 5484952
Under Pressure: Lamina Cribrosa Pore Path Tortuosity in Response to Acute Pressure Modulation
PURPOSE/UNASSIGNED:Lamina cribrosa (LC) deformation is hypothesized to play a major role in glaucoma pathogenesis. The purpose of this study was to determine in vivo how varying intraocular pressure (IOP) under fixed intracranial pressure (ICP), and vice versa, deforms the pore paths throughout the LC volume. METHODS/UNASSIGNED:Spectral-domain optical coherence tomography scans of the optic nerve head were acquired from healthy adult rhesus monkeys under different pressures. IOP and ICP were controlled with gravity-based perfusion systems into the anterior chamber and lateral ventricle, respectively. IOP and ICP were modulated from baseline to high (19-30 mmHg) and highest (35-50 mmHg) levels while maintaining a fixed ICP of 8 to 12 mmHg and IOP of 15 mmHg, respectively. After three-dimensional registration and segmentation, the paths of pores visible in all settings were tracked based on their geometric centroids. Pore path tortuosity was defined as the measured distance divided by the minimal distance between the most anterior and posterior centroids. RESULTS/UNASSIGNED:The median pore tortuosity at baseline varied among the eyes (range, 1.16-1.68). For the IOP effect under fixed ICP (six eyes, five animals), two eyes showed statistically significant increased tortuosity and one showed a decrease (P < 0.05, mixed-effects model). No significant change was detected in three eyes. When modulating ICP under fixed IOP (five eyes, four animals), a similar response pattern was detected. CONCLUSIONS/UNASSIGNED:Baseline pore tortuosity and the response to acute pressure increase vary substantially across eyes. TRANSLATIONAL RELEVANCE/UNASSIGNED:LC pore path tortuosity could be associated with glaucoma susceptibility.
PMCID:10082387
PMID: 37017959
ISSN: 2164-2591
CID: 5463732
Optical Coherence Tomography Angiography and Corresponding Histology-Reply
PMID: 36795381
ISSN: 2168-6173
CID: 5462212
Macular Optical Coherence Tomography-From Diagnosis to Prognostication
PMID: 36862402
ISSN: 2168-6173
CID: 5430922
Comparison of Incremental Costs and Medicare Reimbursement for Simple vs Complex Cataract Surgery Using Time-Driven Activity-Based Costing [Comment]
IMPORTANCE/UNASSIGNED:Cataract surgery is one of the most commonly performed surgeries across medicine and an integral part of ophthalmologic care. Complex cataract surgery requires more time and resources than simple cataract surgery, yet it remains unclear whether the incremental reimbursement for complex cataract surgery, compared with simple cataract surgery, offsets the increased costs. OBJECTIVE/UNASSIGNED:To measure the difference in day-of-surgery costs and net earnings between simple and complex cataract surgery. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This study is an economic analysis at a single academic institution using time-driven activity-based costing methodology to determine the operative-day costs of simple and complex cataract surgery. Process flow mapping was used to define the operative episode limited to the day of surgery. Simple and complex cataract surgery cases (Current Procedural Terminology codes 66984 and 66982, respectively) at the University of Michigan Kellogg Eye Center from 2017 to 2021 were included in the analysis. Time estimates were obtained using an internal anesthesia record system. Financial estimates were obtained using a mix of internal sources and prior literature. Supply costs were obtained from the electronic health record. MAIN OUTCOMES AND MEASURES/UNASSIGNED:Difference in day-of-surgery costs and net earnings. RESULTS/UNASSIGNED:A total of 16 092 cataract surgeries were included, 13 904 simple and 2188 complex. Time-based day-of-surgery costs for simple and complex cataract surgery were $1486.24 and $2205.83, respectively, with a mean difference of $719.59 (95% CI, $684.09-$755.09; P < .001). Complex cataract surgery required $158.26 more for costs of supplies and materials (95% CI, $117.00-$199.60; P < .001). The total difference in day-of-surgery costs between complex and simple cataract surgery was $877.85. Incremental reimbursement for complex cataract surgery was $231.01; therefore, complex cataract surgery had a negative earnings difference of $646.84 compared with simple cataract surgery. CONCLUSIONS AND RELEVANCE/UNASSIGNED:This economic analysis suggests that the incremental reimbursement for complex cataract surgery undervalues the resource costs required for the procedure, failing to cover increased costs and accounting for less than 2 minutes of increased operating time. These findings may affect ophthalmologist practice patterns and access to care for certain patients, which may ultimately justify increasing cataract surgery reimbursement.
PMID: 36892825
ISSN: 2168-6173
CID: 5459512
Case Report: Papilledema Secondary to Cerebral Venous Sinus Thrombosis after Severe COVID-19 Infection
SIGNIFICANCE/CONCLUSIONS:This case highlights ocular side effects of a rare, potentially life-threatening complication from coronavirus disease (COVID-19). Papilledema can occur due to increased intracranial pressure caused by cerebral venous sinus thrombosis, the incidence of which may be more likely in patients with a history of COVID-19 due to an induced hypercoagulable state. PURPOSE/OBJECTIVE:This case report presents a case of papilledema secondary to cerebral venous sinus thrombosis in a patient with a recent history of severe coronavirus disease (COVID-19). CASE REPORT/METHODS:A 29-year-old male hospitalized with a complicated course of coronavirus disease (COVID-19) was referred to the ophthalmology department for episodic blurry vision of both eyes and intermittent binocular diplopia. Clinical examination revealed diffuse bilateral optic disc edema. Magnetic resonance venography of the brain during his admission revealed subtotal occlusion of the right transverse sinus by thrombosis. At the time of diagnosis, the patient was already taking systemic anti-coagulation therapy for treatment of a recent pulmonary embolism also thought to be induced by COVID-19. After additional treatment with acetazolamide there was improvement in his optic nerve edema. CONCLUSIONS:Cerebral venous sinus thrombosis, a serious and potentially life-threatening condition, can occur as a rare complication of COVID-19. In such cases, patients may develop increased intracranial pressure, papilledema, and subsequent vison loss. Magnetic resonance venography should be ordered in patients with suspected papilledema to help rule out the presence of cerebral venous sinus thrombosis.
PMID: 36856578
ISSN: 1538-9235
CID: 5430842
Clinical and Optical Coherence Tomography Comparison Between Ocular Surface Squamous Neoplasia and Squamous Metaplasia
PURPOSE/OBJECTIVE:The purpose of this study was to compare the clinical characteristics and high-resolution optical coherence tomography (HR-OCT) findings between corneal squamous metaplasia and ocular surface squamous neoplasia (OSSN). METHODS:A retrospective case-control study of 8 patients, 4 with histologically confirmed squamous metaplasia and 4 with histologically confirmed OSSN, who presented to the Miami Veterans Administration Medical Center and Bascom Palmer Eye Institute between 2016 and 2020 was performed. Clinical characteristics, HR-OCT findings, and pathology were evaluated and compared. RESULTS:Four patients with squamous metaplasia and 4 with OSSN were evaluated. In the metaplasia group, 75% were male, 2 were White, and 2 were Black. In the OSSN group, all 4 were White males. All lesions were opalescent and occurred at the limbus; however, the borders were more smooth and rounded in the metaplastic lesions compared with OSSN. HR-OCT findings were indistinguishable between the 2 groups. CONCLUSIONS:There is overlap in clinical characteristics and HR-OCT findings between corneal squamous metaplasia and OSSN, highlighting one limitation of HR-OCT. As such, if a corneal opacity has some but not all HR-OCT findings of OSSN, squamous metaplasia should also be considered. A biopsy may be indicated to further evaluate and guide treatment.
PMCID:9547982
PMID: 35439777
ISSN: 1536-4798
CID: 5533992
Early anti-VEGF treatment for radiation maculopathy and optic neuropathy: lessons learned
Radiation therapy has saved both sight and life for eye cancer patients. The most common methods include ophthalmic plaque brachytherapy and external beam techniques. However, subsequent dose-dependent radiation vasculopathy invariably occurs within and around the targeted zone. In 2006, Finger discovered that periodic intravitreal anti-vascular endothelial growth factor (anti-VEGF) bevacizumab could reverse and suppress intraocular radiation vasculopathy. At first, it was administered at the onset of radiation-related vision loss. Though bevacizumab induced regression of macular oedema, retinal haemorrhages and cotton-wool infarcts, most patients were left with residual retinal damage, manifest as metamorphopsia and loss of vision. These results led to earlier and earlier anti-VEGF interventions: first after signs of progressive radiation retinopathy, and then for signs of radiation maculopathy, and finally for high-risk eyes with no clinical signs of retinopathy. Earlier initiation of intravitreal anti-VEGF therapy typically resulted in greater restoration and preservation of macular anatomy, reductions of retinal haemorrhages, resolution of cotton-wool spots and vision preservation. Recent research on optical coherence tomography angiography (OCT-A) has revealed that radiation vasculopathy occurs prior to clinical ophthalmic signs or symptoms. Therefore, it seemed reasonable to consider treating high-risk patients (considered certain to eventually develop radiation maculopathy) to prevent or delay vision loss. Herein, we describe the evolution of treatment for radiation maculopathy as well as recent research supporting anti-VEGF treatment of high-risk patients immediately following radiation to maximize vision outcomes.
PMCID:10050069
PMID: 35974178
ISSN: 1476-5454
CID: 5453162
Canadian journal of ophthalmology = Journal canadien d'ophtalmologie. 2023:58(2):125-130.DOI: 10.1016/j.jcjo.2021.09.003
Myopic macular pits: a case series with multimodal imaging
OBJECTIVE:To characterize the multimodal retinal findings of myopic macular pits, a feature of myopic degeneration. METHODS:A case series of patients with myopic macular pits were studied with multimodal imaging including color fundus photography, fundus autofluorescence (FAF), near infrared reflectance (NIR), spectral domain optical coherence tomography (OCT), optical coherence tomography angiography (OCTA), fluorescein angiography (FA) and indocyanine green angiography (ICG). RESULTS:Nine eyes of 6 patients with myopic macular pit were examined. Four patients presented with multiple pits and 3 with bilateral involvement. All pits were localized in a region of severe macular chorioretinal atrophy associated with myopic posterior staphyloma. In 3 eyes, the entrance of the posterior ciliary artery through the sclera was noted at the base of the pit. Schisis overlying the pit or adjacent to the pit was identified in 3 patients. CONCLUSION/CONCLUSIONS:Myopic macular pits are an additional rare sign of myopic degeneration, developing in regions of posterior staphyloma complicated by severe chorioretinal atrophy and thin sclera.
PMID: 34626545
ISSN: 1715-3360
CID: 5067892
En face ultra-widefield optical coherence tomography of the vortex vein system in central serous chorioretinopathy
PURPOSE/OBJECTIVE:To investigate whether non-invasive en face ultra-widefield (UWF) optical coherence tomography (OCT) can demonstrate salient features of the choroidal vasculature in eyes with central serous chorioretinopathy (CSC). DESIGN/METHODS:Retrospective observational case series. PARTICIPANTS/METHODS:Patients diagnosed with CSC who underwent UWF indocyanine green angiography (ICGA) and widefield OCT imaging were included. METHODS:Widefield OCT imaging was performed with a horizontal 23 mm x vertical 20 mm field of view of 5 visual fixations (1 central and 4 peripheral fixations) to compose structural en face UWF OCT montage images and UWF choroidal thickness maps. Automated image alignment was performed prior to grading. MAIN OUTCOME MEASURES/METHODS:A comparison of choroidal vascular findings seen with UWF ICGA and en face UWF OCT images including size and distribution of choroidal venous drainage areas and identification of dilated choroidal veins ("pachyvessels") crossing the physiological choroidal watershed zones. Spatial correlation between choroidal vascular hyperpermeability (CVH) on UWF ICGA images and areas of choroidal thickening (ACT) on UWF choroidal thickness maps was determined. RESULTS:Forty-two eyes from 27 CSC patients with a mean age of 56 ±12 years (range, 31 to 77 years) were included. Quantitative measures of vortex vein drainage areas on en face UWF OCT images were significantly and positively correlated with those obtained with UWF ICGA (mean Pearson r=0.825, P < 0.01). Identification of pachyvessels crossing the choroidal watershed zones showed an excellent correlation between UWF ICGA and en face UWF OCT images (mean Spearman Ï= 0.873, P < 0,01). In all cases, CVH observed on UWF ICGA spatially co-localized with ACT on the UWF choroidal thickness map. Congestion within the entire drainage area of the dominant vortex systems was observed on UWF choroidal thickness maps. CONCLUSIONS:In eyes with CSC, non-invasive en face UWF OCT imaging can show distinctive features of choroidal venous insufficiency previously identified with UWF ICGA. UWF OCT choroidal thickness maps enable quantitative assessment of choroidal congestion.
PMID: 36228952
ISSN: 2468-6530
CID: 5361102
Children's and adolescents' rising animal-source food intakes in 1990-2018 were impacted by age, region, parental education and urbanicity
Animal-source foods (ASF) provide nutrition for children and adolescents' physical and cognitive development. Here, we use data from the Global Dietary Database and Bayesian hierarchical models to quantify global, regional and national ASF intakes between 1990 and 2018 by age group across 185 countries, representing 93% of the world's child population. Mean ASF intake was 1.9 servings per day, representing 16% of children consuming at least three daily servings. Intake was similar between boys and girls, but higher among urban children with educated parents. Consumption varied by age from 0.6 at <1 year to 2.5 servings per day at 15-19 years. Between 1990 and 2018, mean ASF intake increased by 0.5 servings per week, with increases in all regions except sub-Saharan Africa. In 2018, total ASF consumption was highest in Russia, Brazil, Mexico and Turkey, and lowest in Uganda, India, Kenya and Bangladesh. These findings can inform policy to address malnutrition through targeted ASF consumption programmes.
Copyright
Copyright
EMBASE:2022707858
ISSN: 2662-1355
CID: 5515632
Short- and long-term safety and efficacy of corneal collagen cross-linking in progressive keratoconus: A systematic review and meta-analysis of randomized controlled trials
ORIGINAL:0016951
ISSN: 2211-5056
CID: 5519252
Progressive keratoconus in patients older than 48 years [Case Report]
PURPOSE:To report cases of progressive keratoconus (KC) in patients aged ≥48 years and the successful arrest of progression using corneal cross-linking (CXL) with riboflavin and ultraviolet-A light. OBSERVATIONS:was used as an indicator of progression and KC progressed at a rate of 1.4 diopters in 6 months and 14.6 diopters in 14 months. All patients eventually received CXL, and all were aged ≥50 years at the time of the procedure. One eye required two CXL procedures to successfully stabilize the patient's cornea. CONCLUSION:Despite the probability of KC progression strongly declining after the age of 40 years, it never becomes zero. It is therefore advisable to continue regular follow-up corneal tomography examinations in patients with KC, even in their fifth and sixth decades of life.
PMID: 36481131
ISSN: 1476-5411
CID: 5484902
Design and Conduct of Randomized Clinical Trials Evaluating Surgical Innovations in Ophthalmology: A Systematic Review
PURPOSE:Surgical innovations are necessary to improve patient care. After an initial exploratory phase, novel surgical technique should be compared with alternative options or standard care in randomized controlled trials (RCTs). However, surgical RCTs have unique methodological challenges. Our study sought to investigate key aspects of the design, conduct, and reporting of RCTs of novel surgeries. DESIGN:Systematic review. METHODS:The protocol was prospectively registered in PROSPERO (CRD42021253297). RCTs evaluating novel surgeries for cataract, vitreoretinal, glaucoma, and corneal diseases were included. Medline, EMBASE, Cochrane Library, and Clinicaltrials.gov were searched. The search period was January 1, 2016, to June 16, 2021. RESULTS:A total of 52 ophthalmic surgery RCTs were identified in the fields of glaucoma (n = 12), vitreoretinal surgery (n = 5), cataract (n = 19), and cornea (n = 16). A description defining the surgeon's experience or level of expertise was reported in 30 RCTs (57%) and was presented in both control and intervention groups in 11 (21%). Specification of the number of cases performed in the particular surgical innovation being assessed prior to the trial was reported in 10 RCTs (19%) and an evaluation of quality of the surgical intervention in 7 (13%). Prospective trial registration was recorded in 12 RCTs (23%) and retrospective registration in 13 (25%); and there was no registration record in the remaining 28 (53%) studies. CONCLUSIONS:Important aspects of the study design such as the surgical learning curve, surgeon's previous experience, quality assurance, and trial registration details were often missing in novel ophthalmic surgical procedures. The Idea, Development, Exploration, Assessment, Long-term follow-up (IDEAL) framework aims to improve the quality of study design.
PMID: 36565904
ISSN: 1879-1891
CID: 5498122
International journal of environmental research & public health. 2023:20(7).DOI: 10.3390/ijerph20075349
In a Large Healthcare System in the Bronx, Teleretinal Triaging Was Found to Increase Screening and Healthcare Access for an Underserved Population with a High Incidence of T2DM and Retinopathy
The early treatment of diabetic retinopathy (DR) prevents vision-threatening proliferative retinopathy (PDR) and macular edema (DME). Our study evaluates telemedicine (teleretinal) screening for DR in an inner-city healthcare network with a high ethnic diversity and disease burden. Fundus photographs were obtained and graded in a centralized reading center between 2014 and 2016. Patients with positive screenings were referred to a retina specialist. An analysis of sensitivity and specificity and a subgroup analysis of prevalence, disease severity, and follow-up adherence were conducted. In 2251 patients, the '1-year' and 'Overall' follow-ups were 35.1% and 54.8%, respectively. Severe grading, male gender, and age were associated with better follow-up compliance. The DR, PDR, and DME prevalence was 24.9%, 4.1%, and 5.9%, respectively, and was significantly associated with HbA1c. The sensitivity and specificity for DR, PDR, and DME were 70% and 87%, 87% and 75%, and 37% and 95%, respectively. No prevalence differences were noted between ethnicities. Annual diabetic eye exam adherence increased from 55% to 85% during the study period. Teleretinal triaging is sensitive and specific for DR and improved diabetic eye exam compliance for underserved populations when integrated into large healthcare networks. The adherence to follow-up recommendations was better among older patients and among those with more severe retinopathy.
PMCID:10094588
PMID: 37047964
ISSN: 1660-4601
CID: 5464192
The BLV App Arcade: a new curated repository and evaluation rubric for mobile applications supporting blindness and low vision
PURPOSE/UNASSIGNED:Visual impairment-related disabilities have become increasingly pervasive. Current reports estimate a total of 36 million persons with blindness and 217 million persons with moderate to severe visual impairment worldwide. Assistive technologies (AT), including text-to-speech software, navigational/spatial guides, and object recognition tools have the capacity to improve the lives of people with blindness and low vision. However, access to such AT is constrained by high costs and implementation barriers. More recently, expansive growth in mobile computing has enabled many technologies to be translated into mobile applications. As a result, a marketplace of accessibility apps has become available, yet no framework exists to facilitate navigation of this voluminous space. MATERIALS AND METHODS/UNASSIGNED:We developed the BLV (Blind and Low Vision) App Arcade: a fun, engaging, and searchable curated repository of app AT broken down into 11 categories spanning a wide variety of themes from entertainment to navigation. Additionally, a standardized evaluation metric was formalized to assess each app in five key dimensions: reputability, privacy, data sharing, effectiveness, and ease of use/accessibility. In this paper, we describe the methodological approaches, considerations, and metrics used to find, store and score mobile applications. CONCLUSION/UNASSIGNED:The development of a comprehensive and standardized database of apps with a scoring rubric has the potential to increase access to reputable tools for the visually impaired community, especially for those in low- and middle-income demographics, who may have access to mobile devices but otherwise have limited access to more expensive technologies or services.
PMID: 36927193
ISSN: 1748-3115
CID: 5495902
Clinical risk stratification in glaucoma
Glaucoma is the leading cause of preventable sight loss in the United Kingdom and the provision of timely glaucoma care has been highlighted as a significant challenge in recent years. Following a recent high-profile investigation, The Healthcare Safety Investigation Branch recommended the validation of risk stratification models to safeguard the vision-related quality of life of glaucoma patients. There continues to be no nationally agreed evidence-based risk stratification model for glaucoma care across the United Kingdom. Some models have used simple measures of disease staging such as visual field mean deviation as surrogates for risk, but more refined, individualised risk stratification models should include factors related to both visual impairment and visual disability. Candidate tools should also incorporate both ocular and systemic co-morbidities, rate of disease progression, visual needs and driving status and undergo clinical refinement and validation to justify implementation. The disruption to routine glaucoma care caused by the COVID-19 pandemic has only highlighted the importance of such risk stratification models and has accelerated their development, application and evaluation. This review aims to critically appraise the available evidence underpinning current approaches for glaucoma risk stratification and to discuss how these may be applied to contemporary glaucoma care within the United Kingdom. Further research will be essential to justify and validate the utility of glaucoma risk stratification models in everyday clinical practice.
PMCID:10013986
PMID: 36918628
ISSN: 1476-5454
CID: 5498162
Premature Emulsification of Silicone Oil After Retinal Detachment Repair in the Setting of High-Intensity Exercise
PURPOSE/OBJECTIVE:To describe a rare case of silicone oil emulsification which occurred only three months postoperatively. We discuss the implications for postoperative counseling. METHODS:Retrospective chart review of a single patient. RESULTS:39-year-old female who presented with a right eye macula-on retinal detachment which was repaired with scleral buckle, vitrectomy, and silicone oil tamponade. Her course was complicated by extensive silicone oil emulsification within 3 months postoperatively, most likely due to shear forces induced by her daily CrossFit exercise regimen. CONCLUSION/CONCLUSIONS:Typical postoperative precautions after a retinal detachment repair include no heavy lifting or strenuous activity for one week. These restrictions may need to be more stringent and long-term for patients with silicone oil to prevent early emulsification.
PMID: 36913668
ISSN: 1937-1578
CID: 5524272
A Smart Service System for Spatial Intelligence and Onboard Navigation for Individuals with Visual Impairment (VIS4ION Thailand): study protocol of a randomized controlled trial of visually impaired students at the Ratchasuda College, Thailand
BACKGROUND:ION (Visually Impaired Smart Service System for Spatial Intelligence and Onboard Navigation), an advanced wearable technology, to enable real-time access to microservices, providing a potential solution to close this gap and deliver consistent and reliable access to critical spatial information needed for mobility and orientation during navigation. METHODS:ION. In addition, we will test another cohort of students for navigational, health, and well-being improvements, comparing weeks 1 to 4. We will also conduct a process evaluation according to the Saunders Framework. Finally, we will extend our computer vision and digital twinning technique to a 12-block spatial grid in Bangkok, providing aid in a more complex environment. DISCUSSION/CONCLUSIONS:Although electronic navigation aids seem like an attractive solution, there are several barriers to their use; chief among them is their dependence on either environmental (sensor-based) infrastructure or WiFi/cell "connectivity" infrastructure or both. These barriers limit their widespread adoption, particularly in low-and-middle-income countries. Here we propose a navigation solution that operates independently of both environmental and Wi-Fi/cell infrastructure. We predict the proposed platform supports spatial cognition in BLV populations, augmenting personal freedom and agency, and promoting health and well-being. TRIAL REGISTRATION/BACKGROUND:ClinicalTrials.gov under the identifier: NCT03174314, Registered 2017.06.02.
PMCID:9990238
PMID: 36879333
ISSN: 1745-6215
CID: 5432642
Urinary Metabolomics of Central Serous Chorioretinopathy
PURPOSE/OBJECTIVE:To analyze the urinary metabolomic profile of central serous chorioretinopathy (CSC) cases. METHODS:In a cross-sectional study, 80 participants with CSC were compared with 80 age- and sex-matched controls. Urinary metabolites were measured using Metabolon's Discovery HD4TM platform. RESULTS:Of 1031 metabolites total that were measured in urine samples, 53 were up-regulated and 27 down-regulated in CSC participants compared with controls. After exclusion of potentially confounding xenobiotics and bile compounds that could represent digestive processes, 14 metabolites were significantly higher and 12 metabolites were significantly lower in cases compared with controls. One upregulated metabolite (tetrahydrocortisol sulfate) is involved in the corticosteroid sub-pathway. The down-regulated metabolites are unrelated to the identified corticosteroid sub-pathway. CONCLUSION/CONCLUSIONS:The upregulation of urinary tetrahydrocortisol sulfate in CSC cases provides a precise molecular basis to further study the role of corticosteroids in producing choroidal venous congestion.
PMID: 36512801
ISSN: 1539-2864
CID: 5382062
Correspondence
PMID: 36729944
ISSN: 1539-2864
CID: 5447912
Risk factors and management of choroidal effusions
PURPOSE OF REVIEW/OBJECTIVE:Choroidal effusions are recognized as a common early postoperative complication of glaucoma surgery, and although often benign, they may cause significant ocular morbidity. This article aims to summarize current research on the risk factors and management of choroidal effusions. RECENT FINDINGS/RESULTS:Glaucoma drainage device (GDD) implantation and trabeculectomy are the most commonly performed surgeries for the management of moderate to severe glaucoma. Common postoperative complications of these procedures include hypotony and the development of choroidal effusions. Choroidal effusions have recently been associated with the oral administration of certain drugs, including select monoclonal antibody, antiseizure and bisphosphonate medications. Risk factors for effusion development include specific patient characteristics such as pseudoexfoliative glaucoma, older age and hypertension. Although choroidal effusions typically resolve with medical therapy alone, surgical intervention may be required. Various methods of surgical intervention, such as surgical drainage or GDD tube ligation, can be utilized to treat choroidal effusions when conservative management with medical treatment fails, but themselves carry alternative risks that must be considered. SUMMARY/CONCLUSIONS:Minimizing the incidence and duration of hypotony following ophthalmic surgery and careful monitoring of patients starting certain oral medications are important in limiting the occurrence of choroidal effusions. Risk factors for choroidal effusions have been recently identified in the literature. A better understanding of these risk factors, as well as the outcomes of choroidal effusion management, can help to reduce the occurrence of effusions overall and minimize ocular morbidity.
PMID: 36730733
ISSN: 1531-7021
CID: 5420422
Congenital Corneal Opacity in 22q11.2 Deletion Syndrome: A Case Series
PURPOSE/OBJECTIVE:The purpose of this study was to describe the deep phenotype of congenital corneal opacities (CCO) in patients with 22q11.2 deletion syndrome (22q11.2 DS) and to identify putative regions or genes that could explain the CCO. METHODS:A retrospective chart review was conducted to identify patients with 22q11.2 DS seen in the ophthalmology clinic of a tertiary referral children's hospital. Thirty patients were identified, with molecular confirmation. Twenty-six did not show structural anterior segment anomalies aside from posterior embryotoxon (n = 4), whereas 4 had bilateral CCO, of which 3 had preoperative images. We reviewed medical, operative, and pathology reports; anterior segment optical coherence tomography; high-frequency ultrasound; histopathologic slides; and genetic testing. To identify putative genes responsible for CCO, chromosomal breakpoints in patients with and without CCO were compared. RESULTS:In the 3 patients with preoperative imaging and CCO, a pattern of paracentral corneal opacification with central clearing accompanied by iridocorneal or keratolenticular adhesions was observed. Anterior segment optical coherence tomography and histopathologic images showed central stromal thinning with a residual structure consistent with Descemet membrane. One patient presented at birth with unilateral corneal perforation, suggestive of likely stromal thinning. A comparison of the breakpoints across all cases failed to reveal unique regions or genes in patients with CCO. CONCLUSIONS:22q11.2 DS can rarely be associated with CCO. We describe a consistent pattern of central clearing related to posterior stromal thinning, with or without ICA/KLA. Possible candidate genes for corneal opacification in 22q11.2 DS remain elusive.
PMID: 36455075
ISSN: 1536-4798
CID: 5374112
Double-Scroll Formation by Fluid Column Manipulation in Preloaded DMEK Grafts Prepared From Younger and Older Donor Tissue
PURPOSE/OBJECTIVE:The purpose of this study was to determine whether manipulation of preloaded single-scroll Descemet membrane endothelial keratoplasty (DMEK) grafts within the fluid column of an injector can safely and reliably result in formation of double-scroll DMEK grafts and whether there are differential effects on younger versus older donor tissue. METHODS:Pairs of DMEK grafts prepared from older (65-80 years) and younger (48-64 years) donors were preloaded into a Straiko modified Jones tube. One member of the pair was manipulated within the fluid column to form a double-scroll graft, and the other remained unmanipulated. Outcomes measured include success rate for double-scroll formation, endothelial cell loss (ECL), and relative scroll width. RESULTS:Older donor grafts formed double scrolls with a 100% success rate. ECL of older donor manipulated grafts was statistically higher than that of unmanipulated mate grafts (17.4% ± 3.5% vs. 13.0% ± 4.2%, P = 0.03), but was still within the acceptable range for transplant. Younger donor grafts were successfully manipulated into double scrolls with a 67% success rate, and there was no difference in the ECL of manipulated and unmanipulated grafts (15.5% ± 4.4% vs. 13.0% ± 4.5%, P = 0.24). For all grafts and conformations, there was a significant relationship between relative scroll width and ECL (P < 0.01). CONCLUSIONS:Fluid column manipulation can be used reliably to form double-scroll DMEK grafts. For younger donor grafts, manipulation yields a double scroll without increasing ECL. For older donor grafts, manipulation results in a minimal, acceptable increase in ECL. Surgeons should weigh the advantage of an easily opened graft against the risk of increased ECL when considering this technique.
PMID: 36255778
ISSN: 1536-4798
CID: 5360402
Solitary Intratarsal Blue Nevus
A 42-year-old woman presented with a small pigmented lesion of the palpebral conjunctiva that had been present for a few months. Because of the possibility of melanoma, the lesion was resected. Microscopic examination displayed an intratarsal blue nevus at the level of the meibomian glands comprised of bland nonpigmented and pigmented cells that enveloped a sebaceous gland and its ducts. The cells were of admixed spindle and epithelioid configuration and were immunoreactive for Melan-A. The Ki67 proliferative marker was negative in these cells, contrasting with the epithelium of the overlying conjunctiva and the sebaceous ducts, and thereby militating against the diagnosis of melanoma. Clusters of melanophages were also present. Although an intratarsal blue nevus has been described as a component of a combined nevus, the current lesion demonstrates the occurrence of a sole tarsal blue nevus. Palpebral pigmented lesions should be customarily excised because many are melanomas.
PMID: 36136733
ISSN: 1537-2677
CID: 5335602
Globe Compression by Bone Fragments in Orbital Blow-in Fractures: A Case Series and Systematic Review
PURPOSE/OBJECTIVE:The purpose of this study was to describe the clinical characteristics, management, and outcomes of orbital blow-in fractures involving compression of the globe by bone fragments. METHODS:A retrospective case series and systematic literature review were performed. RESULTS:Three male patients (mean age 29 years) with orbital blow-in fractures causing globe indentation presented with extraocular movement restriction, choroidal folds, and B-scan ultrasonography demonstrating deformation of the globe contour by a hyperechoic bone fragment. All underwent surgical repair within 1 day of presentation resulting in improved visual outcomes. An additional 10 cases were identified in the literature review. The majority of patients were male (80%) with a mean age of 29 years. Fractures originated primarily from the lateral orbital wall (50%) or the orbital roof (40%). Globe compression was evident on CT of the orbit (100%) and ultrasonography (30%). Common presenting signs included decreased visual acuity (70%), restriction of supraduction (40%) or abduction (40%), choroidal folds (30%), brow laceration (40%), periorbital edema (40%), and hypoglobus (40%). Most patients underwent surgical intervention (80%) involving fracture reduction (50%) or fragment removal (38%). Reported postsurgical outcomes were excellent with resolution of diplopia, motility, and visual acuity. CONCLUSION/CONCLUSIONS:Globe indentation from blow-in fractures are rare. Clinicians should be suspicious in cases of high-velocity trauma to the superolateral orbit with hypoglobus, motility limitation, and indentation of the globe upon dilated exam. Prompt diagnosis and early surgical removal of the compressive orbital bone fragments in a multidisciplinary fashion can lead to good visual, functional, and cosmetic outcomes.
PMID: 36190787
ISSN: 1537-2677
CID: 5361582
Effect of fluence levels on prophylactic corneal cross-linking for laser in situ keratomileusis and transepithelial photorefractive keratectomy
PURPOSE/OBJECTIVE:The purpose of this study is to assess the effect of various fluence levels on prophylactic corneal cross-linking (CXL) combined with femtosecond laser in situ keratomileusis (FS-LASIK-Xtra) or transepithelial photorefractive keratectomy (TransPRK-Xtra) on biomechanics, demarcation line (DL), and stromal haze. METHODS:) were performed as part of either an FS-LASIK-Xtra or TransPRK-Xtra procedure. Data were collected preoperatively and at 1 week and 1, 3, and 6 months postoperatively. Main outcome measures were (1) dynamic corneal response parameters and the stress-strain index (SSI) from Corvis, (2) actual DL depth (ADL), and (3) stromal haze on OCT images analysed by a machine learning algorithm. RESULTS:Eighty-six eyes from 86 patients underwent FS-LASIK-Xtra-HF (21 eyes), FS-LASIK-Xtra-LF (21 eyes), TransPRK-Xtra-HF (23 eyes), and TransPRK-Xtra-LF (21 eyes). SSI increased similarly by around 15% in all groups 6 months postoperatively (p = 0.155). All other corneal biomechanical parameters were statistically significant worsening postoperatively, but the change was similar in all groups. At 1 month postoperatively, there was no statistical difference in mean ADL among four groups (p = 0.613), mean stromal haze was similar between the two FS-LASIK-Xtra groups, but higher in the TransPRK-Xtra-HF group compared with the TransPRK-Xtra-LF group. CONCLUSIONS:FS-LASIK-Xtra and TransPRK-Xtra lead to a similar ADL and improve SSI equally. Lower fluence prophylactic CXL might be recommended as it achieves similar mean ADL with potentially less induced stromal haze, especially in TransPRK. The clinical relevance and applicability of such protocols remains to be assessed.
PMID: 36794626
ISSN: 1755-3768
CID: 5484942
Rhegmatogenous retinal detachment after retinopathy of prematurity laser treatment [Case Report]
PURPOSE/UNASSIGNED:Rhegmatogenous retinal detachment (RRD) after retinopathy of prematurity (ROP) laser is rare but has been reported to occur at the border of heavy laser or in combination with tractional retinal detachment (TRD). We describe a rare case of a RRD that developed during treatment for ROP with both laser and intravitreal injections. OBSERVATIONS/UNASSIGNED:The retinal detachment resolved with scleral buckling surgery with residual macular atrophy. CONCLUSIONS AND IMPORTANCE/UNASSIGNED:This case highlights the importance of retinal imaging, careful funduscopic examination, and consideration of the risk of RRDs after intravitreal injections and laser in neonates with ROP.
PMCID:9807741
PMID: 36605183
ISSN: 2451-9936
CID: 5533822
Biosimilars for retinal diseases: United States-Europe awareness survey (Bio-USER - survey)
PURPOSE/UNASSIGNED:To assess the awareness of biosimilar intravitreal anti-VEGF agents among retina specialists practicing in the United States (US) and Europe. METHODS/UNASSIGNED:A 16-question online survey was created in English and distributed between Dec 01, 2021 and Jan 31, 2022. A total of 112 respondents (retinal physicians) from the US and Europe participated. RESULTS/UNASSIGNED:The majority of the physicians (56.3%) were familiar with anti-VEGF biosimilars. A significant number of physicians needed more information (18.75%) and real world data (25%) before switching to a biosimilar. About one half of the physicians were concerned about biosimilar safety (50%), efficacy (58.9 %), immunogenicity (50%), and their efficacy with extrapolated indications (67.8 %). Retinal physicians from the US were less inclined to shift from off-label bevacizumab to biosimilar ranibizumab or on-label bevacizumab (if approved) compared to physicians from Europe (p=0.0001). Furthermore, physicians from the US were more concerned about biosimilar safety (p=0.0371) and efficacy compared to Europe (p= 0.0078). CONCLUSIONS/UNASSIGNED:The Bio-USER survey revealed that while the majority of retinal physicians need additional information regarding the safety, efficacy and immunogenicity when making clinical decisions regarding their use. Retinal physicians from US are more comfortable in continuing to use off-label bevacizumab compared to physicians from Europe.
PMID: 36726203
ISSN: 1744-7682
CID: 5447902
Signal Processing in Medicine and Biology: Innovations in Big Data Processing
[S.l.] : Springer International Publishing, 2023
Extent: 1 v.
ISBN: 9783031212352
CID: 5501492
Multimodal Imaging and Microperimetry of Retinal Pigment Epithelium Tear-Associated Resurfacing Tissue
PMID: 36695804
ISSN: 1539-2864
CID: 5426572
Combined Hamartoma of the Retina and Retinal Pigment Epithelium at Pediatric Age: Surgical versus Conservative Approach
PURPOSE/OBJECTIVE:To report outcomes of pediatric patients with combined hamartoma of the retina and the retina pigment epithelium (CHRRPE) followed up conservatively or after pars plana vitrectomy (PPV). METHODS:This retrospective multicenter study included sixty-two eyes of 59 pediatric patients with CHRRPE from 13 different international centers with an average age of 7.7±4.7 (0.3-17) years at the time of the diagnosis, and having undergone PPV or followed conservatively. At baseline and each visit, visual acuity values, optical coherence tomography (OCT) for features and central foveal thickness (CFT), and tumor location were noted. Lesions were called as zone 1, if it involves the macular and peripapillary area, and the others were called as zone 2 lesions. RESULTS:Twenty-one eyes of 20 patients in the intervention group and 41 eyes of 39 patients in the conservative group were followed for a mean of 36.2±40.4 (6-182) months. BCVA improved in 11 (68.8%) of 16 eyes in the intervention group and 4 (12.9%) of 31 eyes in the conservative group (p<0.001). The mean CFT decreased from 602.0±164.9 μm to 451.2±184.3 μm in the intervention group, while it increased from 709.5±344.2 μm to 791.0±452.1 μm in zone 1 eyes of the conservative group. Posterior location of tumor, irregular configuration of the foveal contour and ellipsoid zone defect in OCT, subretinal exudate and prominent vascular tortuosity were associated with poor visual acuity. CONCLUSIONS:Vitreoretinal surgery is safe and effective in improving vision and reducing retinal distortion in zone 1 CHRRPE in children.
PMID: 36228191
ISSN: 1539-2864
CID: 5361072
Methods and Impact for Using Federated Learning to Collaborate on Clinical Research
BACKGROUND:The development of accurate machine learning algorithms requires sufficient quantities of diverse data. This poses a challenge in health care because of the sensitive and siloed nature of biomedical information. Decentralized algorithms through federated learning (FL) avoid data aggregation by instead distributing algorithms to the data before centrally updating one global model. OBJECTIVE:To establish a multicenter collaboration and assess the feasibility of using FL to train machine learning models for intracranial hemorrhage (ICH) detection without sharing data between sites. METHODS:Five neurosurgery departments across the United States collaborated to establish a federated network and train a convolutional neural network to detect ICH on computed tomography scans. The global FL model was benchmarked against a standard, centrally trained model using a held-out data set and was compared against locally trained models using site data. RESULTS:A federated network of practicing neurosurgeon scientists was successfully initiated to train a model for predicting ICH. The FL model achieved an area under the ROC curve of 0.9487 (95% CI 0.9471-0.9503) when predicting all subtypes of ICH compared with a benchmark (non-FL) area under the ROC curve of 0.9753 (95% CI 0.9742-0.9764), although performance varied by subtype. The FL model consistently achieved top three performance when validated on any site's data, suggesting improved generalizability. A qualitative survey described the experience of participants in the federated network. CONCLUSION/CONCLUSIONS:This study demonstrates the feasibility of implementing a federated network for multi-institutional collaboration among clinicians and using FL to conduct machine learning research, thereby opening a new paradigm for neurosurgical collaboration.
PMID: 36399428
ISSN: 1524-4040
CID: 5385002
EPIRETINAL MEMBRANE WITH FOVEAL HERNIATION: Visual and Surgical Outcomes
PURPOSE:Foveal herniation occurs when neuroretinal tissue protrudes through and above the level of an epiretinal membrane. This study describes the visual symptoms and spectral domain optical coherence tomography findings associated with foveal herniation and evaluates the postoperative visual, anatomical, and surgical outcomes. METHODS:A multicenter retrospective review of patients diagnosed with epiretinal membrane identified 59 patients with preoperative foveal herniation on spectral domain optical coherence tomography. Data regarding visual symptoms, preoperative and postoperative best-corrected visual acuity (BCVA), central retinal thickness, macular volume, and size of foveal herniation were collected, and statistical analysis was performed. RESULTS:A total of 58 of the 59 patients with foveal herniation underwent surgical epiretinal membrane peeling, with foveal contour restored in 53.5% of patients after surgery. Average BCVA improved from 20/80 to 20/40 Snellen equivalent at most-recent postoperative visit (P < 0.0001). The average central retinal thickness decreased from 632 µm to 432 µm (P < 0.0001) and the average macular volume decreased from 11.3 mm3 to 9.5 mm3 (P < 0.0001) at 3 months postoperatively. Preoperatively, greater herniation height was associated with worse BCVA (P = 0.008), greater central retinal thickness (P = 0.01), retinoschisis, cystoid macular edema, foveolar detachment, ellipsoid zone abnormality, and external limiting membrane abnormalities (P < 0.05). Postoperatively, there was a decrease in retinoschisis, cystoid macular edema, foveolar detachment, ellipsoid zone, and external limiting membrane abnormality (P < 0.05) on spectral domain optical coherence tomography. CONCLUSION:Patients with larger foveal herniation height had greater preoperative central retinal thickness, worse preoperative and postoperative BCVA, and more intraretinal abnormalities on spectral domain optical coherence tomography. Surgical epiretinal membrane peeling in patients with foveal herniation resulted in a significant improvement in patients' BCVA and microstructural abnormalities.
PMID: 36695789
ISSN: 1539-2864
CID: 5419592
The Antibacterial Efficacy of High-Fluence PACK Cross-Linking Can Be Accelerated
PURPOSE:To determine whether high-fluence photoactivated chromophore for keratitis cross-linking (PACK-CXL) can be accelerated. METHODS:Solutions of Staphylococcus aureus and Pseudomonas aeruginosa with 0.1% riboflavin were prepared and exposed to 365 nm ultraviolet (UV)-A irradiation of intensities and fluences from 9 to 30 mW/cm2 and from 5.4 to 15.0 J/cm2, respectively, representing nine different accelerated PACK-CXL protocols. Irradiated solutions and unirradiated controls were diluted, plated, and inoculated on agar plates so that the bacterial killing ratios (BKR) could be calculated. Additionally, strains of Achromobacter xylosoxidans, Staphylococcus epidermidis, and Stenotrophomonas maltophilia were exposed to a single accelerated PACK-CXL protocol (intensity: 30 mW/cm2, total fluence: 15.0 J/cm2). RESULTS:With total fluences of 5.4, 10.0, and 15.0 J/cm2, the range of mean BKR for S. aureus was 45.78% to 50.91%, 84.13% to 88.16%, and 97.50% to 99.90%, respectively; the mean BKR for P. aeruginosa was 69.09% to 70.86%, 75.37% to 77.93%, and 82.27% to 91.44%, respectively. The mean BKR was 41.97% for A. xylosoxidans, 65.38% for S. epidermidis, and 78.04% for S. maltophilia for the accelerated PACK-CXL protocol (30 mW/cm2, 15 J/cm2). CONCLUSIONS:The BKR of high-fluence PACK-CXL protocols can be accelerated while maintaining a high, but species-dependent, BKR. The Bunsen to Roscoe law is respected in fluences up to 10 J/cm2 in S. aureus and P. aeruginosa, whereas fluences above 10 J/cm2 show strain dependence. TRANSLATIONAL RELEVANCE:The high-fluence PACK-CXL protocols can be accelerated in clinical practice while maintaining high levels of BKR.
PMCID:9924428
PMID: 36757342
ISSN: 2164-2591
CID: 5484932
Reply [Letter]
PMID: 36424280
ISSN: 2468-6530
CID: 5384402
Author Correction: Global dietary quality in 185 countries from 1990 to 2018 show wide differences by nation, age, education, and urbanicity (Nature Food, (2022), 3, 9, (694-702), 10.1038/s43016-022-00594-9)
EMBASE:2021228968
ISSN: 2662-1355
CID: 5513812
Long-term outcomes of patients with limited-stage ocular adnexal DLBCL treated with combined modality therapy in the rituximab era [Letter]
PMCID:10407681
PMID: 36484627
ISSN: 1365-2141
CID: 5647002
Scleral contact lenses fitted to extremely steep corneas [Letter]
PMID: 36670016
ISSN: 1773-0597
CID: 5516692
Laser in Glaucoma and Ocular Hypertension (LiGHT) Trial: Six-Year Results of Primary Selective Laser Trabeculoplasty versus Eye Drops for the Treatment of Glaucoma and Ocular Hypertension
PURPOSE/OBJECTIVE:The Laser in Glaucoma and Ocular Hypertension (LiGHT) Trial has shown selective laser trabeculoplasty (SLT) to be clinically and cost-effective as a primary treatment of open-angle glaucoma (OAG) and ocular hypertension (OHT) at 3 years. This article reports health-related quality of life (HRQoL) and clinical effectiveness of initial treatment with SLT compared with intraocular pressure (IOP)-lowering eye drops after 6 years of treatment. DESIGN/METHODS:Prospective, multicenter randomized controlled trial. PARTICIPANTS/METHODS:Treatment-naive eyes with OAG or OHT initially treated with SLT or IOP-lowering drops. METHODS:Patients were allocated randomly to initial SLT or eye drops. After the initial 3 years of the trial, patients in the SLT arm were permitted a third SLT if necessary; patients in the drops arm were allowed SLT as a treatment switch or escalation. This study is registered at controlled-trials.com (identifier, ISRCTN32038223). MAIN OUTCOME MEASURES/METHODS:The primary outcome was HRQoL at 6 years; secondary outcomes were clinical effectiveness and adverse events. RESULTS:Of the 692 patients completing 3 years in the LiGHT Trial, 633 patients (91.5%) entered the extension, and 524 patients completed 6 years in the trial (82.8% of those entering the extension phase). At 6 years, no significant differences were found for the EuroQol EQ-5D 5 Levels, Glaucoma Utility Index, and Glaucoma Quality of Life-15 (P > 0.05 for all). The SLT arm showed better Glaucoma Symptom Scale scores than the drops arm (83.6 ± 18.1 vs. 81.3 ± 17.3, respectively). Of eyes in the SLT arm, 69.8% remained at or less than the target IOP without the need for medical or surgical treatment. More eyes in the drops arm exhibited disease progression (26.8% vs. 19.6%, respectively; P = 0.006). Trabeculectomy was required in 32 eyes in the drops arm compared with 13 eyes in the SLT arm (P < 0.001); more cataract surgeries occurred in the drops arm (95 compared with 57 eyes; P = 0.03). No serious laser-related adverse events occurred. CONCLUSIONS:Selective laser trabeculoplasty is a safe treatment for OAG and OHT, providing better long-term disease control than initial drop therapy, with reduced need for incisional glaucoma and cataract surgery over 6 years.
PMID: 36122660
ISSN: 1549-4713
CID: 5498102
Novel severe oculocutaneous manifestations of human monkeypox virus infection and their historical analogues
WHO has declared human mpox (formerly known as monkeypox) a global public health emergency since July, 2022. When case numbers were increasing, so did clinicians' exposures to new elements of the disease. Additionally, the burden of mpox is particularly apparent in immunocompromised patients, who can have more variable and severe manifestations of disease across organ systems. In this Grand Round, we report novel and severe oculocutaneous manifestations of mpox in this population, which are both sight and life threatening. Specifically, we highlight two patients with mpox and AIDS who had refractory skin necrosis that progressed to either ocular compromise or panfacial gangrene, or both. Both patients ultimately died due to systemic complications of their infections. Through clinical analogies, we show how past experiences with related orthopoxviruses, such as variola virus (smallpox) and vaccinia virus, can add useful context for understanding and treating these new disease states. We suspect that in patients who are immunocompromised, monkeypox virus can clinically evolve not only via viraemia but also through direct intradermal spread. We propose that intradermal spread occurs by a process clinically and immunologically analogous to progressive vaccinia, a complication previously seen after conventional smallpox vaccination. We share evidence in support of this theory and implications regarding early management and post-exposure prophylaxis for at-risk populations. Content note: this Grand Round contains graphic images of mpox lesions of the eyes and face.
PMCID:9870321
PMID: 36702137
ISSN: 1474-4457
CID: 5419692
Iridotomy to slow progression of visual field loss in angle-closure glaucoma
BACKGROUND:Primary angle-closure glaucoma is a type of glaucoma associated with a physically obstructed anterior chamber angle. For example, contact between the iris and lens at the pupillary margin creates a pupillary block that increases resistance to aqueous outflow. Obstruction of the anterior chamber angle blocks drainage of fluids (aqueous humor) within the eye and may raise intraocular pressure (IOP). Elevated IOP is associated with glaucomatous optic nerve damage and visual field loss. Laser peripheral iridotomy ('iridotomy') is a procedure to eliminate pupillary block by allowing aqueous humor to pass directly from the posterior to anterior chamber, which is achieved by creating a hole in the iris using laser. Iridotomy is used to treat patients with primary angle-closure glaucoma, patients with primary angle-closure (narrow angles and no signs of glaucomatous optic neuropathy), and patients who are primary angle-closure suspects (patients with reversible obstruction). However, the effectiveness of iridotomy on slowing progression of visual field loss is uncertain. OBJECTIVES:To assess the effects of iridotomy compared with no iridotomy for primary angle-closure glaucoma, primary angle-closure, and primary angle-closure suspect. SEARCH METHODS:We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2021, Issue 10), which contains the Cochrane Eyes and Vision Trials Register; MEDLINE Ovid; Embase Ovid; PubMed; LILACS; ClinicalTrials.gov; and the WHO ICTRP. The date of the most recent search was 10 October 2021. SELECTION CRITERIA:Randomized or quasi-randomized controlled trials that compared iridotomy with no iridotomy in primary angle-closure suspects, people with primary angle-closure, or people with primary angle-closure glaucoma in one or both eyes were eligible. DATA COLLECTION AND ANALYSIS:We used standard Cochrane methodology and assessed the certainty of the body of evidence for prespecified outcomes using the GRADE approach. MAIN RESULTS:= 0%; 3 studies, 3006 eyes of 1503 participants). Other ocular adverse events (e.g. eye pain, dry eye, redness of eyes, and ocular discomfort), although rare, were more common in eyes treated with iridotomy than in eyes in the control group. AUTHORS' CONCLUSIONS: We did not find sufficient evidence to draw any meaningful conclusions on the use of iridotomy for the purpose of slowing progression of visual field loss. No study reported on progressive visual field loss, the primary outcome of this review. Although there is moderate certainty evidence that iridotomy results in improved gonioscopic findings, in is unclear if these findings translate to clinically meaningful benefits.
PMID: 36621864
ISSN: 1469-493x
CID: 5498132
Vogt-Koyanagi-Harada-like Uveitis Followed by Melanoma-Associated Retinopathy with Focal Chorioretinal Atrophy and Choroidal Neovascularization in a Patient with Metastatic Cutaneous Melanoma
PURPOSE/OBJECTIVE:To report a case of Vogt-Koyanagi-Harada (VKH)-like uveitis followed by melanoma-associated retinopathy (MAR) with focal chorioretinal atrophy and subsequent choroidal neovascularization (CNV) in a patient with metastatic cutaneous melanoma. OBSERVATION/METHODS:A 68-year-old man with a history cutaneous melanoma presented with VKH-like uveitis. Work up revealed a pelvic mass, which was excised and found to be metastatic melanoma. Two years later, the patient developed MAR with focal chorioretinal atrophy and adjacent CNV. CONCLUSION/CONCLUSIONS:and Importance: Patients with metastatic cutaneous melanoma can develop distinct and sequential paraneoplastic ocular complications. Onset of a VKH-like uveitis may be a good prognostic factor for survival in patients with metastatic cutaneous melanoma.
PMID: 33394953
ISSN: 1937-1578
CID: 4738552
In vivo characterization of the near-infrared genetically encoded calcium indicator NIR-GECO2G
[S.l.] : SPIE, 2023
pp. ?-?
ISBN: 9781510658356
CID: 5502002
The Definition of Glaucomatous Optic Neuropathy in Artificial Intelligence Research and Clinical Applications
Objective: Although artificial intelligence (AI) models may offer innovative and powerful ways to use the wealth of data generated by diagnostic tools, there are important challenges related to their development and validation. Most notable is the lack of a perfect reference standard for glaucomatous optic neuropathy (GON). Because AI models are trained to predict presence of glaucoma or its progression, they generally rely on a reference standard that is used to train the model and assess its validity. If an improper reference standard is used, the model may be trained to detect or predict something that has little or no clinical value. This article summarizes the issues and discussions related to the definition of GON in AI applications as presented by the Glaucoma Workgroup from the Collaborative Community for Ophthalmic Imaging (CCOI) US Food and Drug Administration Virtual Workshop, on September 3 and 4, 2020, and on January 28, 2022. Design: Review and conference proceedings. Subjects: No human or animal subjects or data therefrom were used in the production of this article. Methods: A summary of the Workshop was produced with input and approval from all participants. Main Outcome Measures: Consensus position of the CCOI Workgroup on the challenges in defining GON and possible solutions. Results: The Workshop reviewed existing challenges that arise from the use of subjective definitions of GON and highlighted the need for a more objective approach to characterize GON that could facilitate replication and comparability of AI studies and allow for better clinical validation of proposed AI tools. Different tests and combination of parameters for defining a reference standard for GON have been proposed. Different reference standards may need to be considered depending on the scenario in which the AI models are going to be applied, such as community-based or opportunistic screening versus detection or monitoring of glaucoma in tertiary care. Conclusions: The development and validation of new AI-based diagnostic tests should be based on rigorous methodology with clear determination of how the reference standards for glaucomatous damage are constructed and the settings where the tests are going to be applied.
SCOPUS:85150788401
ISSN: 2589-4234
CID: 5447732
Phenomenology Based Decomposition of Sea Clutter with a Secondary Target Classifier
[S.l.] : Institute of Electrical and Electronics Engineers Inc., 2023
pp. ?-?
ISBN: 9781665436694
CID: 5549882
Paracentral Acute Middle Maculopathy Associated with Hypercoagulability in Pregnancy
PURPOSE/OBJECTIVE:To report a case of paracentral acute middle maculopathy (PAMM) in an otherwise healthy young, multiparous woman in her second trimester of pregnancy. METHODS:Case report RESULTS:: A 38-year-old woman in her twentieth week of pregnancy presented with a four-day history of an acute paracentral scotoma in her left eye. Fundoscopic examination of the left eye was significant for a white-gray lesion inferonasal to the fovea which corresponded with spectral domain-optical coherence tomography (SD-OCT) hyperreflectivity at the outer plexiform layer-inner nuclear layer junction and optical coherence tomography angiography (OCTA) non-perfusion. A diagnosis of paracentral acute middle maculopathy was made. The patient was sent for a hypercoagulability work-up that revealed elevated factor VIII activity, which has been associated with increased risk of complications during pregnancy. CONCLUSION/CONCLUSIONS:PAMM in pregnancy may be secondary to an underlying hypercoaguable condition. We recommend systemic evaluation and referral to a high-risk pregnancy specialist if PAMM is diagnosed during pregnancy. Additionally, OCTA in PAMM may demonstrate reperfusion of the affected vessels.
PMID: 33229916
ISSN: 1937-1578
CID: 4680432
Extreme intraocular pressure and steroid-dependent iritis
A 50-year-old ophthalmic technician was referred by her retina specialist for urgent consultation due to markedly elevated intraocular pressure (IOP) unresponsive to medical therapy. Her history included chronic polyarticular juvenile rheumatoid arthritis and chronic uveitis requiring ongoing topical steroid therapy. She had a sub-Tenon injection of Kenalog (triamcinolone) 18 months prior to referral. Chronic topical anti-inflammatory therapy included nepafenac (Ilevro) and prednisolone acetate 2 times a day. Attempts to discontinue topical steroid resulted in worsening inflammation. The patient was referred when the IOP measured 44 mm Hg in the left eye despite aggressive medical therapy, including acetazolamide. The IOP improved slightly when loteprednol was substituted for prednisolone acetate. Current medications in the left eye include brimonidine 3 times a day, loteprednol 2 times a day, nepafenac 2 times a day, and fixed combination latanoprost + netarsudil at bedtime. Her only medication in the right eye was travoprost. She is intolerant to dorzolamide. She was also taking acetazolamide 500 mg 2 times a day. She was not taking any anticoagulants. Past surgical history included cataract surgery in each eye. She has not had laser trabeculoplasty in either eye. Examination revealed uncorrected visual acuity of J1+ in the right eye (near) and 20/30 in the left eye (mini-monovision). There was no afferent pupillary defect. There was mild band keratopathy in each eye while the central cornea was clear in both eyes without keratic precipitates. Here angles were open to gonioscopy without peripheral anterior synechia. There was mild to moderate flare in each eye with trace cells. The IOP was 17 mm Hg in the right eye and 31 mm Hg in the left. Central corneal thickness measured 560 μm and 559 μm in the right and left eye respectively. There was a well-positioned intraocular lens within each capsule with a patent posterior capsulotomy. There was mild vitreous syneresis but no vitreous cell. The cup to disc ratio was 0.5 in each eye with a symmetrical neural rim. The retina was flat without macular edema. Visual field was normal in both eyes (Figures 1 and 2). Optical coherence tomography of retinal nerve fiber layer (RNFL) is shown in Figure 3 and retinal ganglion cell layer is shown in Supplemental Figure 1 (http://links.lww.com/JRS/A756).JOURNAL/jcrs/04.03/02158034-202301000-00020/figure1/v/2022-12-26T045736Z/r/image-tiffJOURNAL/jcrs/04.03/02158034-202301000-00020/figure2/v/2022-12-26T045736Z/r/image-tiffJOURNAL/jcrs/04.03/02158034-202301000-00020/figure3/v/2022-12-26T045736Z/r/image-tiff Please comment on your management of this patient's left eye.
PMID: 36573765
ISSN: 1873-4502
CID: 5471002
Interferometric diffusing wave spectroscopy imaging with an electronically variable time-of-flight filter
Diffuse optics (DO) is a light-based technique used to study the human brain, but it suffers from low brain specificity. Interferometric diffuse optics (iDO) promises to improve the quantitative accuracy and depth specificity of DO, and particularly, coherent light fluctuations (CLFs) arising from blood flow. iDO techniques have alternatively achieved either time-of-flight (TOF) discrimination or highly parallel detection, but not both at once. Here, we break this barrier with a single iDO instrument. Specifically, we show that rapid tuning of a temporally coherent laser during the sensor integration time increases the effective linewidth seen by a highly parallel interferometer. Using this concept to create a continuously variable and user-specified TOF filter, we demonstrate a solution to the canonical problem of DO, measuring optical properties. Then, with a deep TOF filter, we reduce scalp sensitivity of CLFs by 2.7 times at 1 cm source-collector separation. With this unique combination of desirable features, i.e., TOF-discrimination, spatial localization, and highly parallel CLF detection, we perform multiparametric imaging of light intensities and CLFs via the human forehead.
SCOPUS:85152433292
ISSN: 2334-2536
CID: 5461112
Visible light optical coherence tomography reveals age-related photoreceptor changes in the mouse
[S.l.] : SPIE, 2023
pp. ?-?
ISBN: 9781510658257
CID: 5501982
Decoding diffuse light scattering dynamics in layered tissues: path length versus fluctuation time scale
Dynamic multiple light scattering (DMLS) has found numerous applications, including soft matter physics and biomedical optics. Yet biological tissues may have complex internal geometries, presenting a challenge for noninvasive measurements. Deciphering laminar dynamics is crucial to accurately interpret tissue or organ physiology. Seminal DMLS work noted that one can probe deeper layers indirectly by analyzing light fluctuations on shorter time scales. Recent technologies have enabled probing deeper layers directly by analyzing fluctuations at longer path lengths. The following question arises: are the indirect and direct approaches synergistic or redundant? Here, by adding an optical switch to path-length-filtered interferometric diffusing wave spectroscopy, we experimentally address this question in the context of a forearm occlusion study. We find that both approaches afford better distinction of light scattering dynamics in layered tissues than either approach alone. This motivates further development of methods that integrate both decorrelation time scale and light path length to probe layered tissues.
SCOPUS:85178166023
ISSN: 0146-9592
CID: 5622922
Asia-Pacific journal of ophthalmology (Philadelphia, Pa.). 2023:12(1):80-93.DOI: 10.1097/APO.0000000000000596
Applications of Artificial Intelligence and Deep Learning in Glaucoma
Diagnosis and detection of progression of glaucoma remains challenging. Artificial intelligence-based tools have the potential to improve and standardize the assessment of glaucoma but development of these algorithms is difficult given the multimodal and variable nature of the diagnosis. Currently, most algorithms are focused on a single imaging modality, specifically screening and diagnosis based on fundus photos or optical coherence tomography images. Use of anterior segment optical coherence tomography and goniophotographs is limited. The majority of algorithms designed for disease progression prediction are based on visual fields. No studies in our literature search assessed the use of artificial intelligence for treatment response prediction and no studies conducted prospective testing of their algorithms. Additional challenges to the development of artificial intelligence-based tools include scarcity of data and a lack of consensus in diagnostic criteria. Although research in the use of artificial intelligence for glaucoma is promising, additional work is needed to develop clinically usable tools.
PMID: 36706335
ISSN: 2162-0989
CID: 5419802
Asia-Pacific journal of ophthalmology (Philadelphia, Pa.). 2023:12(1):1-3.DOI: 10.1097/APO.0000000000000585
Transformation of Eye Care Through Innovations
PMID: 36541333
ISSN: 2162-0989
CID: 5426202
Interferometric diffuse optics: recent advances and future outlook
The field of diffuse optics has provided a rich set of neurophotonic tools to measure the human brain noninvasively. Interferometric detection is a recent, exciting methodological development in this field. The approach is especially promising for the measurement of diffuse fluctuation signals related to blood flow. Benefitting from inexpensive sensor arrays, the interferometric approach has already dramatically improved throughput, enabling the measurement of brain blood flow faster and deeper. The interferometric approach can also achieve time-of-flight resolution, improving the accuracy of acquired signals. We provide a historical perspective and summary of recent work in the nascent area of interferometric diffuse optics. We predict that the convergence of interferometric technology with existing economies of scale will propel many advances in the years to come.
PMCID:9587754
PMID: 36284601
ISSN: 2329-423x
CID: 5359422
Predictors of Receiving Keratoplasty for Fuchs' Endothelial Corneal Dystrophy among Medicare Beneficiaries
OBJECTIVE:To identify factors associated with receipt of endothelial keratoplasty (EK) and penetrating keratoplasty (PK) in patients with Fuchs' endothelial corneal dystrophy (FECD). DESIGN/METHODS:Retrospective cohort study. PARTICIPANTS/METHODS:Medicare beneficiaries ≥65 years with a diagnosis of FECD between 2011-2019. METHODS:The 100% Medicare fee-for-service administrative claims database was queried for treatment-naive patients with a diagnosis of FECD. A multivariable logistic model including age, race and ethnicity, sex, geography, ocular comorbidities and surgeries, Charlson comorbidity index (CCI), and socioeconomic status was used to identify factors associated with receipt of EK and PK. Kaplan Meier survival analyses were performed to determine the rate of EK after cataract surgery and complex/other anterior segment surgery. MAIN OUTCOME MEASURES/METHODS:The factors associated with receipt of a first-time EK or PK, plus the rate of EK following cataract or complex/other anterior segment surgery. RESULTS:Of 719066 beneficiaries identified, 31372 (4.4%) received a first-time EK, and 2426 (0.3%) received a first-time PK. In a multivariable analysis, female sex decreased likelihood of both PK and EK (for EK, aOR 0.83 [95% CI 0.81-0.85]; for PK, aOR 0.84 [95% CI 0.78-0.92]), while Western residence (1.33 [1.29-1.38]; 1.25 [1.11-1.42]) compared to Southern and history of complex/other anterior segment surgery (1.62 [1.54-1.70]; 5.52 [4.97-6.12]) increased likelihood of both procedures. Compared to White (non-Hispanic), likelihood of EK was decreased for Black (0.76 [0.72-0.80]), Asian/Pacific Islander (0.54 [0.48-0.61]), and Hispanic/Latino (0.62 [0.55-0.70]) race and ethnicity, while for the same groups likelihood of PK was increased (for Black 1.32 [1.14-1.53]; Asian/Pacific Islander 1.46 [1.13-1.89]; Hispanic/Latino 1.62 [1.25-2.11]). Additional factors decreasing likelihood of EK were increasing age (for >85, 0.60 [0.58-0.62]), Northeastern residence (0.81 [0.78-0.84]) compared to Southern, and Charlson comorbidity index score of 7+ (0.50 [0.44-0.57]) compared to 0. Following cataract or complex/other anterior segment surgery, rates of EK were 1.3% and 3.3% at one year, and 2.3% and 5.6% at eight years, respectively. CONCLUSIONS:In a multivariable analysis, female beneficiaries are less likely to receive EK or PK for FECD compared to males, whereas non-White beneficiaries are less likely to receive EK and more likely to receive PK compared to White beneficiaries.
PMID: 35932840
ISSN: 1549-4713
CID: 5288492
Reply: Mechanisms of Corneal Strengthening by Ring Implants [Comment]
PMID: 36630435
ISSN: 1081-597x
CID: 5484922
Expansion of patient eligibility for virtual glaucoma clinics: a long-term strategy to increase the capacity of high-quality glaucoma care
AIMS:The virtual glaucoma clinic (VGC) is a well-established diagnostic pathway for delivery of glaucoma care. Current UK national guidance recommends VGCs for patients with ocular hypertension, glaucoma suspects or early glaucoma. This study evaluates whether expanded eligibility criteria, including other glaucoma phenotypes and disease stages, can deliver safe and effective care with a positive patient experience. METHODS:Records of over 8000 patients were reviewed in order to determine suitability for VGC attendance using expanded eligibility criteria. Patients with three prior consecutive visits within the glaucoma service were included. Follow-up interval, clinic type, visual acuity (VA), intraocular pressure (IOP) and visual field performance were recorded. Patient satisfaction was recorded for a sample of 118 patients. RESULTS:2017 patients over 31 months were included. Two-thirds of eyes had ocular comorbidities, a fifth of eyes had undergone prior cataract surgery and 10% of eyes had undergone a prior laser treatment for glaucoma. After three visits, 32% of patients remained in the VGC, 42% were seen in face-to-face clinics and 25% were discharged. There were no clinically significant changes in VA, IOP and visual field performance during follow-up. 72% of patients expressed a preference to continue their care within VGCs. CONCLUSIONS:This study demonstrates that VGCs with expanded patient eligibility criteria can deliver high-quality glaucoma care that is safe, effective and with high levels of patient satisfaction. This approach provides a long-term solution to adapt delivery of glaucoma care to our expanding and ageing population.
PMID: 34321213
ISSN: 1468-2079
CID: 5497952
Direct selective laser trabeculoplasty in open angle glaucoma study design: a multicentre, randomised, controlled, investigator-masked trial (GLAUrious)
INTRODUCTION:Laser trabeculoplasty is an effective and widely used treatment for glaucoma. A new laser technology, the Eagle direct selective laser trabeculoplasty (DSLT) device, may provide automated, fast, simple, safe and effective laser treatment for glaucoma in a broader range of clinical settings. This trial aims to test the hypothesis that translimbal DSLT is effective and not inferior to selective laser trabeculoplasty (SLT) in reducing intraocular pressure (IOP) in open angle glaucoma (OAG). METHODS AND ANALYSIS:This is a multicentre, randomised, controlled, investigator-masked study. The primary efficacy outcome is intergroup difference in mean change from baseline IOP measured at 6 months. Secondary outcomes include mean percentage reduction in IOP at 3, 6 and 12 months; proportion of participants with at least 20% reduction in IOP from baseline at 6 months; change in ocular hypotensive medications at 12 months and evaluation of safety. Participants were aged >= 40 years with OAG, including exfoliative or pigmentary glaucoma, or ocular hypertension with untreated or washed out IOP 22-35 mm Hg. TREATMENTS:DSLT: 120 shots, 3 ns, 400 µm spot size, energy 1.4-1.8 mJ delivered at the limbus over 2 s. SLT: approximately 100 shots, 3 ns, 400 µm spot size administered 360 degrees at the limbus using any gonioscopy lens, energy 0.3-2.6 mJ. A sample size of 164 is sufficient to detect a non-inferiority margin of 1.95 mm Hg for change from baseline IOP. CLINICAL TRIAL REGISTRATION NUMBER:NCT03750201, ISRCTN14033075.
PMCID:9763163
PMID: 34433548
ISSN: 1468-2079
CID: 5497982
Distribution and Clinical Characteristics of Periorbital Infantile Hemangiomas
PMID: 36473202
ISSN: 2689-3622
CID: 5383032
Vitelliform maculopathy: Diverse etiologies originating from one common pathway
Vitelliform lesions (VLs) are associated with a wide array of macular disorders but are the result of one common pathway: retinal pigment epithelium (RPE) impairment and phagocytic dysfunction. VLs are defined by the accumulation of yellowish subretinal material. In the era of multimodal advanced retinal imaging, VLs can be further characterized by subretinal hyperreflectivity with optical coherence tomography and hyperautofluorescence with fundus autofluorescence. VLs can be the result of genetic or acquired retinal diseases. In younger patients, VLs usually occur in the setting of Best disease. Additional genetic causes of VL include pattern dystrophy or adult-onset vitelliform macular dystrophy. In older patients, acquired VLs can be associated with a broad spectrum of etiologies, including tractional, paraneoplastic, toxic, and degenerative disorders. The main cause of visual morbidity in eyes with VLs is the onset of macular atrophy and macular neovascularization. Histopathological studies have provided new insights into the location, nature, and lifecycle of the vitelliform material comprised of melanosomes, lipofuscin, melanolipofuscin, and outer segment debris located between the RPE and photoreceptor layer. Impaired phagocytosis by the RPE cells is the unifying pathway leading to VL development. We discuss and summarize the nature, pathogenesis, multimodal imaging characteristics, etiologies, and natural course of vitelliform maculopathies.
PMID: 36720370
ISSN: 1879-3304
CID: 5434792
Illuminating Neural Computation Using Precision Optogenetics-Controlled Synthetic Perception
Connecting neuronal activity to perception requires tools that can probe neural codes at cellular and circuit levels, paired with sensitive behavioral measures. In this chapter, we present an overview of current methods for connecting neural codes to perception using precision optogenetics and psychophysical measurements of synthetically induced percepts. We also highlight new methodologies for validating precise control of optical and behavioral manipulations. Finally, we provide a perspective on upcoming developments that are poised to advance the field.
Copyright
Copyright
EMBASE:640500153
ISSN: 1940-6045
CID: 5512082
Automated 360-degree goniophotography with the NIDEK Gonioscope GS-1 for glaucoma
This study was registered with ClinicalTrials.gov (ID: NCT03715231). A total of 20 participants (37 eyes) who were 18 or older and had glaucoma or were glaucoma suspects were enrolled from the NYU Langone Eye Center and Bellevue Hospital. During their usual ophthalmology visit, they were consented for the study and underwent 360-degree goniophotography using the NIDEK Gonioscope GS-1. Afterwards, the three ophthalmologists separately examined the images obtained and determined the status of the iridocorneal angle in four quadrants using the Shaffer grading system. Physicians were masked to patient names and diagnoses. Inter-observer reproducibility was determined using Fleiss' kappa statistics. The interobserver reliability using Fleiss' statistics was shown to be significant between three glaucoma specialists with fair overall agreement (Fleiss' kappa: 0.266, p < .0001) in the interpretation of 360-degree goniophotos. Automated 360-degree goniophotography using the NIDEK Gonioscope GS-1 have quality such that they are interpreted similarly by independent expert observers. This indicates that angle investigation may be performed using this automated device and that interpretation by expert observers is likely to be similar. Images produced from automated 360-degree goniophotography using the NIDEK Gonioscope GS-1 are similarly interpreted amongst glaucoma specialists, thus supporting use of this technique to document and assess the anterior chamber angle in patients with, or suspected of, glaucoma and iridocorneal angle abnormalities.
PMCID:9990915
PMID: 36881575
ISSN: 1932-6203
CID: 5432702
Diverging patterns of plasticity in the nucleus basalis of Meynert in early- and late-onset blindness
Plasticity in the brain is impacted by an individual's age at the onset of the blindness. However, what drives the varying degrees of plasticity remains largely unclear. One possible explanation attributes the mechanisms for the differing levels of plasticity to the cholinergic signals originating in the nucleus basalis of Meynert. This explanation is based on the fact that the nucleus basalis of Meynert can modulate cortical processes such as plasticity and sensory encoding through its widespread cholinergic projections. Nevertheless, there is no direct evidence indicating that the nucleus basalis of Meynert undergoes plastic changes following blindness. Therefore, using multiparametric magnetic resonance imaging, we examined if the structural and functional properties of the nucleus basalis of Meynert differ between early blind, late blind and sighted individuals. We observed that early and late blind individuals had a preserved volumetric size and cerebrovascular reactivity in the nucleus basalis of Meynert. However, we observed a reduction in the directionality of water diffusion in both early and late blind individuals compared to sighted individuals. Notably, the nucleus basalis of Meynert presented diverging patterns of functional connectivity between early and late blind individuals. This functional connectivity was enhanced at both global and local (visual, language and default-mode networks) levels in the early blind individuals, but there were little-to-no changes in the late blind individuals when compared to sighted controls. Furthermore, the age at onset of blindness predicted both global and local functional connectivity. These results suggest that upon reduced directionality of water diffusion in the nucleus basalis of Meynert, cholinergic influence may be stronger for the early blind compared to the late blind individuals. Our findings are important to unravelling why early blind individuals present stronger and more widespread cross-modal plasticity compared to late blind individuals.
PMCID:10123399
PMID: 37101831
ISSN: 2632-1297
CID: 5465242
Follow-up Rates After Teleretinal Screening for Diabetic Retinopathy: Assessing Patient Barriers to Care
PMCID:10037748
PMID: 37006661
ISSN: 2474-1272
CID: 5495952
Culture of Human Retinal Explants for Ex Vivo Assessment of AAV Gene Delivery
Due to the clinically established safety and efficacy profile of recombinant adeno-associated viral (rAAV) vectors, they are considered the "go to" vector for retinal gene therapy. Design of a rAAV-mediated gene therapy focuses on cell tropism, high transduction efficiency, and high transgene expression levels to achieve the lowest therapeutic treatment dosage and avoid toxicity. Human retinal explants are a clinically relevant model system for exploring these aspects of rAAV-mediated gene delivery. In this chapter, we describe an ex vivo human retinal explant culture protocol to evaluate transgene expression in order to determine the selectivity and efficacy of rAAV vectors for human retinal gene therapy.
PMID: 36481906
ISSN: 1940-6029
CID: 5378792
Surgical Approach with Pars Plana Vitrectomy for Subretinal Gene Therapy
Gene therapy is emerging as a treatment for inherited diseases including retinitis pigmentosa. Through surgery, specifically with pars plana vitrectomy, the subretinal space can be accessed to directly administer this treatment. The goal herein is to provide an overview of this approach.
PMID: 36481913
ISSN: 1940-6029
CID: 5378802
Choroidal Effusions after Glaucoma Drainage Implant Surgery: Risk Factors and Surgical Management
OBJECTIVE:To report the incidence of patients who developed choroidal effusions after glaucoma drainage implant (GDI) surgery and determine risk factors for and outcomes of surgical intervention. DESIGN/METHODS:Retrospective case series. SUBJECTS/METHODS:Medical records of 605 patients who underwent GDI surgery from January 1, 2017 to June 7, 2021 at New York University Langone Health and New York Eye and Ear Infirmary of Mount Sinai were reviewed. METHODS:Preoperative, intraoperative, and postoperative clinical data were obtained. Multivariate logistic regression evaluated the factors associated with the need for surgical intervention. Patient records were analyzed for effusion resolution, intraocular pressure (IOP), visual acuity (VA), and complications across treatment modalities. MAIN OUTCOME MEASURES/METHODS:Incidence of choroidal effusion development and need for surgical intervention. RESULTS:Baerveldt glaucoma implant placement (P = 0.05; OR, 4.8), and anterior chamber shallowing (AC; P < 0.001; OR, 25.1) in the presence of effusions. The subgroup that required multiple surgeries for effusion resolution had a significantly lower mean IOP at the most recent follow-up compared with those who received medical management only (P < 0.001). A higher percentage of patients who required surgical intervention lost VA at the most recent follow-up compared with patients whose effusions resolved with conservative management (i.e., medical management, AC viscoelastic injection). CONCLUSIONS:Choroidal effusions after GDI surgery resolved with conservative management in most patients. A history of SLT or GDI placement, implantation of a BGI-350, and the presence of a shallow chamber were risk factors for surgical intervention. Although interventions, such as surgical drainage are at times necessary, a better understanding of their impacts can help guide postoperative decisions. The risks and benefits of these procedures must be carefully considered in these high-risk eyes. FINANCIAL DISCLOSURE(S)/BACKGROUND:Proprietary or commercial disclosure may be found after the references.
PMID: 36925067
ISSN: 2589-4196
CID: 5462592
Home Monitoring of Glaucoma Using a Home Tonometer and a Novel Virtual Reality Visual Field Device: Acceptability and Feasibility
OBJECTIVE:Our aim was to assess the acceptability and feasibility of iCare HOME tonometer (HT) and Virtual Field (VF) devices in the home monitoring of glaucoma. DESIGN/METHODS:Prospective feasibility and acceptability study. SUBJECTS/METHODS:Twenty patients (39 eyes) with primary open-angle glaucoma, open-angle glaucoma, ocular hypertension, or suspected glaucoma. METHODS:Patients were trained and instructed to bring 2 devices home for 1 week and use the HT 4 times/day for 4 days and the VF 3 times total. MAIN OUTCOME MEASURES/METHODS:For acceptability, we conducted satisfaction surveys and semistructured, qualitative interviews with a thematic analysis. Feasibility was assessed by device usage and quality of tests. RESULTS:Most patients (73.7%) felt that the HT was easy to use, and 100% of them found the HT useful. All patients (100%) felt that VF was easy to use, and 94.4% of them found the VF useful. All patients (100%) obtained acceptable intraocular pressure and completed a VF test at home. We identified 4 key themes, with 33 subthemes. The key themes include the following: (1) advantages of home monitoring; (2) difficulties with home monitoring; (3) future considerations in home monitoring; and (4) the experience of patients with glaucoma. CONCLUSIONS:The HT and VF were acceptable and feasible in a small cohort of motivated subjects. Patients were able to perform these tests proficiently at home, and they were generally enthused to obtain more data about their intraocular health, as it allowed them a heightened sense of security and insight about their chronic disease, as well as a reduction in foreseeable barriers to care. Home monitoring may also improve upon glaucoma care by enhancing patient empowerment and fostering community bonds. The VF should be further evaluated to ensure validity.
PMID: 35577312
ISSN: 2589-4196
CID: 5249182
Health Literacy and Ophthalmology: A scoping review
As of 2020, it is estimated that 43.3 million people are blind, and an additional 553 million have mild to severe vision impairment.50 At least 1 billion worldwide have a vision impairment that could have been prevented or has yet to be addressed.54 Poor health literacy may be a significant contributor to the prevalence of eye disease. With implications on disease burden, progression, and health outcomes, a greater understanding of the role health literacy plays in ophthalmology is needed. This is the first scoping review to assess the impact of health literacy on eye health outcomes and blindness, including ocular screening rates/follow-up rates, treatment adherence, and self-care practices. PubMed, Embase, and CINAHL databases were searched systematically through November 12, 2021, and we evaluated the association between health literacy and ophthalmic outcomes in 4 domains: clinical outcomes, treatment adherence rates, screening/follow-up rates, and self-care practices. There is evidence to suggest that health literacy is associated with ophthalmic outcomes in all these domains. To better understand how health literacy impacts eye health, further longitudinal studies examining the effect of health literacy (using standardized health literacy measures) on ophthalmic outcomes are needed. We believe a specific ophthalmic health literacy survey could help achieve this goal and help target interventions to ultimately improve outcomes among ophthalmology patients.
PMID: 35995252
ISSN: 1879-3304
CID: 5338152
Cost-effectiveness of Prophylactic Laser Peripheral Iridotomy in Primary Angle-Closure Suspects
PURPOSE/OBJECTIVE:To investigate the cost-effectiveness (CE) of prophylactic laser peripheral iridotomy (LPI) in primary angle-closure (PAC) suspects (PACSs). DESIGN/METHODS:Cost-effectiveness analysis utilizing Markov models. SUBJECTS/METHODS:Patients with narrow angles (PACSs). METHODS:Progression from PACSs through 4 states (PAC, PAC glaucoma, blindness, and death) was simulated using Markov cycles. The cohort entered at 50 years and received either LPI or no treatment. Transition probabilities were calculated from published models, and risk reduction of LPI was calculated from the Zhongshan Angle Closure Prevention trial. We estimated costs of Medicare rates, and previously published utility values were used to calculate quality-adjusted life year (QALY). Incremental CE ratios (ICER) were evaluated at $50 000. Probabilistic sensitivity analyses (PSAs) addressed uncertainty. MAIN OUTCOME MEASURES/METHODS:Total cost, QALY, and ICER. RESULTS:Over 2 years, the ICER for the LPI cohort was > $50 000. At 6 years, the LPI cohort was less expensive with more accrued QALY. In PSA, the LPI arm was cost-effective in 24.65% of iterations over 2 years and 92.69% over 6 years. The most sensitive parameters were probability of progressing to PAC and cost and number of annual office visits. CONCLUSIONS:By 6 years, prophylactic LPI was cost-effective. The rate of progressing to PAC and differing practice patterns most impacted CE. With uncertainty of management of narrow angles, cost may be a decision management tool for providers. FINANCIAL DISCLOSURE(S)/BACKGROUND:The authors have no proprietary or commercial interest in any materials discussed in this article.
PMID: 37212626
ISSN: 2589-4196
CID: 5543582
Fraud Claims Filed Involving Practicing Ophthalmologists from 1985 Through 2020
INTRODUCTION/UNASSIGNED:Like all United States physicians, ophthalmologists may be implicated in lawsuits claiming fraudulent medical practice. In order to educate, raise awareness, and mitigate fraudulent practice, we reviewed a legal database and analyzed fraud claims in ophthalmology lawsuits. METHODS/UNASSIGNED:A retrospective legal literature review was performed on jury verdicts and settlements from the online legal database LexisNexis Academic from 1985 through 2020 that were filed by or against an ophthalmologist, involved a fraud claim, and included a final decision or settlement. Cases were evaluated for factors including demographics of plaintiffs and defendants, type of fraud claim, ophthalmologist party status (plaintiff or defendant), decision outcome, and amount awarded (when applicable). RESULTS/UNASSIGNED:Of the 27 cases analyzed, all ophthalmologist defendants involved were male and the most common sub-specialty for an ophthalmologist defendant was refractive surgery. The most common fraud type was a fraud claim involving a malpractice lawsuit (12 of 27), followed by contract fraud and billing fraud. While the ophthalmologists in malpractice-related fraud cases experienced more rulings in favor of the defendant on the fraud claims (8 of 12), ophthalmologists in billing fraud cases experienced fewer rulings in their favor (0 of 5). DISCUSSION/UNASSIGNED:Ophthalmology lawsuits involving fraud claims occurred in various settings, including malpractice lawsuits, contract cases, and Medicare and Medicaid billing. Defendants were all male and most commonly refractive surgeons.
PMCID:9883985
PMID: 36718348
ISSN: 1177-5467
CID: 5416142
Private equity in ophthalmology and optometry: a time series analysis from 2012 to 2021
PURPOSE/UNASSIGNED:To identify temporal and geographic trends in private equity (PE)-backed acquisitions of ophthalmology and optometry practices in the United States from 2012 to 2021. METHODS/UNASSIGNED:In this cross-sectional time series, acquisition data from 10/21/2019 to 9/1/2021 and previously published data from 1/1/2012 to 10/20/2019 were analyzed. Acquisition data were compiled from 6 financial databases, 5 industry news outlets, and publicly available press releases. Linear regression models were used to compare rates of acquisition. Outcomes included number of total acquisitions, practice type, locations, provider details, and geographic footprint. RESULTS/UNASSIGNED:= 0.20]). CONCLUSIONS/UNASSIGNED:PE acquisitions increased during the period 2012-2021 as companies continue to utilize regionally focused strategies for acquisitions.
PMCID:10125728
PMID: 37101563
ISSN: 1542-8958
CID: 5459522
Sudden-onset unilateral painless vision loss
A 75-year-old Caucasian woman presented with sudden-onset multifocal scotomas in her right eye's central vision for 1 day. There were subtle white intraretinal foveal lesions that correlated with patchy inner retinal hyperreflectivity on optical coherence tomography, suggestive of paracentral acute middle maculopathy. Initial cerebrovascular work-up was negative. Review of systems was positive for lethargy and jaw claudication. The sedimentation rate and c-reactive protein were elevated, but platelet count was normal. The patient was started on 60 mg oral prednisone daily and underwent bilateral temporal artery that confirmed the diagnosis of giant cell arteritis.
PMID: 34634290
ISSN: 1879-3304
CID: 5264722
Corneal cross-linking: results and complications
Philadelphia, PA : Elsevier, 2023
pp. 403-412
ISBN: 9780323759793
CID: 5518392
Optimized Artificial Intelligence for Enhanced Ectasia Detection Using Scheimpflug-Based Corneal Tomography and Biomechanical Data
PURPOSE/OBJECTIVE:To optimize artificial intelligence (AI) algorithms to integrate Scheimpflug-based corneal tomography and biomechanics to enhance ectasia detection. DESIGN/METHODS:Multicenter cross-sectional case-control retrospective study. METHODS:A total of 3886 unoperated eyes from 3412 patients had Pentacam and Corvis ST (Oculus Optikgeräte GmbH) examinations. The database included 1 eye randomly selected from 1680 normal patients (N) and from 1181 "bilateral" keratoconus (KC) patients, along with 551 normal topography eyes from patients with very asymmetric ectasia (VAE-NT), and their 474 unoperated ectatic (VAE-E) eyes. The current TBIv1 (tomographic-biomechanical index) was tested, and an optimized AI algorithm was developed for augmenting accuracy. RESULTS:The area under the receiver operating characteristic curve (AUC) of the TBIv1 for discriminating clinical ectasia (KC and VAE-E) was 0.999 (98.5% sensitivity; 98.6% specificity [cutoff: 0.5]), and for VAE-NT, 0.899 (76% sensitivity; 89.1% specificity [cutoff: 0.29]). A novel random forest algorithm (TBIv2), developed with 18 features in 156 trees using 10-fold cross-validation, had a significantly higher AUC (0.945; DeLong, P < .0001) for detecting VAE-NT (84.4% sensitivity and 90.1% specificity; cutoff: 0.43; DeLong, P < .0001) and a similar AUC for clinical ectasia (0.999; DeLong, P = .818; 98.7% sensitivity; 99.2% specificity [cutoff: 0.8]). Considering all cases, the TBIv2 had a higher AUC (0.985) than TBIv1 (0.974; DeLong, P < .0001). CONCLUSIONS:AI optimization to integrate Scheimpflug-based corneal tomography and biomechanical assessments augments accuracy for ectasia detection, characterizing ectasia susceptibility in the diverse VAE-NT group. Some patients with VAE may have true unilateral ectasia. Machine learning considering additional data, including epithelial thickness or other parameters from multimodal refractive imaging, will continuously enhance accuracy. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.
PMID: 36549584
ISSN: 1879-1891
CID: 5484912
Current Concepts of the Uveitis-Glaucoma-Hyphema (UGH) Syndrome
PURPOSE/UNASSIGNED:To discuss the pathophysiology, etiology, and current management strategies of uveitis-glaucoma-hyphema (UGH) syndrome. METHODS/UNASSIGNED:Literature review. RESULTS/UNASSIGNED:The classic UGH syndrome associated with anterior chamber intraocular lenses (ACIOL) have decreased in incidence with the modernization of IOL design and surgical techniques. The current UGH syndrome is increasing in prevalence largely related to a parallel increase in late onset dislocations of intraocular lenses (IOLs) and the developing techniques to remedy that condition. The modern features of UGH can present as cystoid macular edema, intraocular pressure elevation typically not attributed to UGH, and recurrent vitreous hemorrhage, unlike the original description as described by Ellingson in 1978. Medical management to control inflammation, reduce intraocular pressure, and reduced the bleeding diathesis are mainstays of therapy. However, surgery with IOL repositioning or exchange should be reserved for cases that are refractory to or progressing despite medical treatment. CONCLUSIONS/UNASSIGNED:UGH syndrome is an increasingly common, poorly understood, and often subtle, manifestation of an anatomic disturbance post intraocular surgery that persists with continued evolution of intraocular surgical techniques and new imaging modalities to aid in its diagnosis.
PMID: 36476057
ISSN: 1460-2202
CID: 5378702
Deep Capillary Plexus Features in Acute Macular Neuroretinopathy: Novel Insights Based on the Anatomy of Henle Fiber Layer
PURPOSE:The purpose of this study was to identify a precise location of deep capillary plexus (DCP) injury in acute macular neuroretinopathy (AMN) lesions using multimodal imaging. METHODS:En face structural optical coherence tomography (OCT) images were manually segmented to delineate outer retinal AMN lesions involving the ellipsoid zone and interdigitation zone. AMN lesion centroid was calculated, and image distortion was applied to correct for Henle fiber layer (HFL) length and orientation. The resulting image was registered with the corresponding en face OCT angiography (OCTA) image segmented at the DCP and structural OCT volume before grading for vascular and structural features, respectively. RESULTS:Thirty-nine AMN lesions from 16 eyes (11 female patients, mean age 34 ± 4 years) were analyzed. After correcting for HFL anatomy, in 62% of AMN lesions, the centroid co-localized with a capillary vortex (pattern 1); flow defects were detected in 33% of lesions (pattern 2); and in 5% of lesions no specific pattern could be identified (pattern 3). The detection of a specific pattern increased after correcting the projection of AMN lesion for HFL anatomy (28% vs. 5%, P = 0.04). Outer nuclear layer thickness was lower in the centroid area in 10 (29%) AMN lesions from 6 patients, all corresponding to lesions fitting pattern 2 (r = 0.78, P < 0.001). CONCLUSIONS:AMN lesions might be a result of DCP impairment at the level of the capillary vortex or draining venule. In eyes with AMN, the location of outer retinal changes associated with DCP ischemia appears to be influenced by the length and orientation of HFL.
PMCID:9730735
PMID: 36469026
ISSN: 1552-5783
CID: 5382832
Presbyopic Corneal Inlay Extrusion Consequent to Sterile Keratolysis: Surgical Revision and Long-Term Management
PURPOSE/OBJECTIVE:The purpose of this study was to report a serious complication of early sterile keratolysis associated with a presbyopia inlay implantation combined with hyperopic laser in situ keratomileusis (LASIK). METHODS:A 55-year-old hyperopic man underwent uneventful topography-guided bilateral femtosecond laser-assisted hyperopic LASIK, combined with same-day polymer refractive inlay implantation in the nondominant eye for additional presbyopia correction. Within 2 months, anterior sterile keratolysis and partial extrusion required surgical explantation of the inlay, and long-term medical management over 9 years achieved effective visual rehabilitation documented also with corneal imaging. RESULTS:Immediate postoperative results were binocular 20/20 uncorrected distance visual acuity and J1 uncorrected near visual acuity. The early progressive anterior sterile keratolysis and partial extrusion necessitated surgical explantation at 2 months, severe anterior scarring of the perforated flap area and severe focal flattening of the cornea of over 10 diopters, developed despite aggressive topical corticosteroid use. The uncorrected distance visual acuity in the OS dropped from 20/25 to 20/400. The LASIK flap portion that underwent keratolysis and perforated, remodeled long-term from a scarred, epithelial plug with early significant surface concavity to evidently a mild subepithelial localized hazy area with regularized curvature over a period of 9 years. CONCLUSIONS:Some refractive synthetic corneal inlays have been recalled because they may result in significant corneal haze. We present herein a case of severe keratolysis that necessitated surgical explantation and further document long-term care for eventual visual rehabilitation.
PMID: 35942531
ISSN: 1536-4798
CID: 5286782
Normative Data and Conversion Equation for Spectral-Domain Optical Coherence Tomography in an International Healthy Control Cohort
BACKGROUND:Spectral-domain (SD-) optical coherence tomography (OCT) can reliably measure axonal (peripapillary retinal nerve fiber layer [pRNFL]) and neuronal (macular ganglion cell + inner plexiform layer [GCIPL]) thinning in the retina. Measurements from 2 commonly used SD-OCT devices are often pooled together in multiple sclerosis (MS) studies and clinical trials despite software and segmentation algorithm differences; however, individual pRNFL and GCIPL thickness measurements are not interchangeable between devices. In some circumstances, such as in the absence of a consistent OCT segmentation algorithm across platforms, a conversion equation to transform measurements between devices may be useful to facilitate pooling of data. The availability of normative data for SD-OCT measurements is limited by the lack of a large representative world-wide sample across various ages and ethnicities. Larger international studies that evaluate the effects of age, sex, and race/ethnicity on SD-OCT measurements in healthy control participants are needed to provide normative values that reflect these demographic subgroups to provide comparisons to MS retinal degeneration. METHODS:Participants were part of an 11-site collaboration within the International Multiple Sclerosis Visual System (IMSVISUAL) consortium. SD-OCT was performed by a trained technician for healthy control subjects using Spectralis or Cirrus SD-OCT devices. Peripapillary pRNFL and GCIPL thicknesses were measured on one or both devices. Automated segmentation protocols, in conjunction with manual inspection and correction of lines delineating retinal layers, were used. A conversion equation was developed using structural equation modeling, accounting for clustering, with healthy control data from one site where participants were scanned on both devices on the same day. Normative values were evaluated, with the entire cohort, for pRNFL and GCIPL thicknesses for each decade of age, by sex, and across racial groups using generalized estimating equation (GEE) models, accounting for clustering and adjusting for within-patient, intereye correlations. Change-point analyses were performed to determine at what age pRNFL and GCIPL thicknesses exhibit accelerated rates of decline. RESULTS:The healthy control cohort (n = 546) was 54% male and had a wide distribution of ages, ranging from 18 to 87 years, with a mean (SD) age of 39.3 (14.6) years. Based on 346 control participants at a single site, the conversion equation for pRNFL was Cirrus = -5.0 + (1.0 × Spectralis global value). Based on 228 controls, the equation for GCIPL was Cirrus = -4.5 + (0.9 × Spectralis global value). Standard error was 0.02 for both equations. After the age of 40 years, there was a decline of -2.4 μm per decade in pRNFL thickness ( P < 0.001, GEE models adjusting for sex, race, and country) and -1.4 μm per decade in GCIPL thickness ( P < 0.001). There was a small difference in pRNFL thickness based on sex, with female participants having slightly higher thickness (2.6 μm, P = 0.003). There was no association between GCIPL thickness and sex. Likewise, there was no association between race/ethnicity and pRNFL or GCIPL thicknesses. CONCLUSIONS:A conversion factor may be required when using data that are derived between different SD-OCT platforms in clinical trials and observational studies; this is particularly true for smaller cross-sectional studies or when a consistent segmentation algorithm is not available. The above conversion equations can be used when pooling data from Spectralis and Cirrus SD-OCT devices for pRNFL and GCIPL thicknesses. A faster decline in retinal thickness may occur after the age of 40 years, even in the absence of significant differences across racial groups.
PMID: 36049213
ISSN: 1536-5166
CID: 5337812
Comparing Acute IOP-Induced Lamina Cribrosa Deformations Premortem and Postmortem
PURPOSE/UNASSIGNED:Lamina cribrosa (LC) deformations caused by elevated intraocular pressure (IOP) are believed to contribute to glaucomatous neuropathy and have therefore been extensively studied, in many conditions, from in vivo to ex vivo. We compare acute IOP-induced global and local LC deformations immediately before (premortem) and after (postmortem) sacrifice by exsanguination. METHODS/UNASSIGNED:The optic nerve heads of three healthy monkeys 12 to 15 years old were imaged with spectral-domain optical coherence tomography under controlled IOP premortem and postmortem. Volume scans were acquired at baseline IOP (8-10 mm Hg) and at 15, 30, and 40 mm Hg IOP. A digital volume correlation technique was used to determine the IOP-induced three-dimensional LC deformations (strains) in regions visible premortem and postmortem. RESULTS/UNASSIGNED:Both conditions exhibited similar nonlinear relationships between IOP increases and LC deformations. Median effective and shear strains were, on average, over all eyes and pressures, smaller postmortem than premortem, by 14% and 11%, respectively (P's < 0.001). Locally, however, the differences in LC deformation between conditions were variable. Some regions were subjected premortem to triple the strains observed postmortem, and others suffered smaller deformations premortem than postmortem. CONCLUSIONS/UNASSIGNED:Increasing IOP acutely caused nonlinear LC deformations with an overall smaller effect postmortem than premortem. Locally, deformations premortem and postmortem were sometimes substantially different. We suggest that the differences may be due to weakened mechanical support from the unpressurized central retinal vessels postmortem. TRANSLATIONAL RELEVANCE/UNASSIGNED:Additional to the important premortem information, comparison with postmortem provides a unique context essential to understand the translational relevance of all postmortem biomechanics literature.
PMCID:9728494
PMID: 36454578
ISSN: 2164-2591
CID: 5374102
Soft drusen accumulation within a full-thickness macular hole: new insights into the mechanisms of lipid cycling pathways in age-related macular degeneration
PMID: 35296802
ISSN: 1476-5454
CID: 5190922
Volume Rendering of Deep Retinal Age-Related Microvascular Anomalies
PURPOSE/OBJECTIVE:To characterize and distinguish non-neovascular deep retinal age-related microvascular anomalies (DRAMA) from type 3 macular neovascularization (MNV) using volume rendering of optical coherence tomography (OCT) and OCT angiography (OCTA). DESIGN/METHODS:Retrospective, consecutive case series. SUBJECTS/METHODS:Consecutive patients with age-related macular degeneration (AMD) exhibiting de novo non-neovascular abnormalities within the deep vascular plexus (DCP) on high-resolution (High-Res) spectral domain and swept-source OCT/OCTA. Patients with retinal vascular alterations attributable to other disease entities were excluded. METHODS:Complete ophthalmologic examination and multimodal imaging including confocal fundus photography (CFP), spectral domain OCT (SD-OCT), High-Res SD-OCT and OCTA, and volume-averaged swept-source OCTA (SS-OCTA). Volume rendering of High-Res OCTA and averaged SS-OCTA were used to analyze capillary abnormalities and inflow/outflow connectivity pathways. MAIN OUTCOME MEASURES/METHODS:The primary outcomes were the characteristics of capillary abnormalities (number, size, shape, reflectivity, and location) and inflow/outflow connectivity pathways. Secondary outcomes were nearby changes in CFP and structural OCT (hyperreflective foci, outer retinal atrophy, and retinal pigment epithelium (RPE) atrophy). RESULTS:From 8 eyes of 8 patients, 2 DRAMA subtypes were identified: small diameter perifoveal capillary dilations with hyperreflective walls within the inner nuclear layer (type 1, n=4) and vascular outpouchings, typically multiple, extending posteriorly into Henle's fiber layer with reflectivity similar to adjacent normal retinal capillaries (type 2, n=10). Four eyes had both DRAMA subtypes. Three-dimensional visualization of OCTA data demonstrated DRAMA corresponding to dilations of DCP capillaries without direct inflow or outflow connections to the superficial plexus. Fundus photographs showed circular red dots in 3 eyes, all corresponding to type 1 DRAMA. DRAMA co-localized with hyperreflective foci in all cases. No lesions were found anterior to areas of retinal pigment epithelium or outer retina atrophy. Asymptomatic intraretinal exudation varied through a follow-up of up to 6 years, with no lesions progressing to type 3 MNV. CONCLUSIONS:In eyes with non-neovascular AMD, DRAMA includes two types of capillary dilations occurring without remodeling of the surrounding vascular network. DRAMA can resemble microvascular changes due to other causes and can masquerade as type 3 MNV. Mild intraretinal exudation can vary during follow up without progression to type 3 MNV.
PMID: 35772694
ISSN: 2468-6530
CID: 5281332
Two cases of unilateral cone-rod dysfunction presenting in adult females
PURPOSE/OBJECTIVE:To describe cases of unilateral cone-rod dysfunction presenting in two middle-aged females. METHODS:This case series highlights two middle-aged female patients with progressive visual decline in one eye. Fundus photography, fundus autofluorescence (FAF), spectral-domain optical coherence tomography (SD-OCT), multi-focal electroretinogram (mfERG), full-field electroretinogram(ffERG), and genetic testing were obtained. RESULTS:In the first patient, mfERG showed an extinguished response and ffERG demonstrated markedly reduced a-wave and b-wave amplitudes (more pronounced under photopic conditions) in the right eye. SD-OCT showed attenuation of the ellipsoid zone of the right eye. Similar findings were appreciated in the second patient. Genetic testing in the first patient identified three heterozygous variants in PRPH2, RCBTB1, and USH2A. The second patient was found to have heterozygous variants in BBS1 and ABCA4. CONCLUSION/CONCLUSIONS:These two cases add to the literature of case reports of unilateral cone-rod and rod-cone dystrophies. However, the underlying etiology of the unilateral pattern of cone-rod dysfunction and the significance of the heterozygous mutations found in both cases remains uncertain.
PMID: 36070159
ISSN: 1573-2622
CID: 5332462
The utility of home tonometry for peri-interventional decision-making in glaucoma surgery: Case series [Case Report]
PURPOSE/UNASSIGNED:To describe twelve cases in which home intraocular pressure (IOP) monitoring complimented clinical decision-making in glaucoma management. OBSERVATIONS/UNASSIGNED:Home IOP monitoring elucidated peaks and amplitudes of variation that were not captured by in-clinic IOP measurements during the pre- or post-interventional period. CONCLUSIONS & IMPORTANCE/UNASSIGNED:Home monitoring can establish pre-treatment IOP patterns that are not evident during in-clinic measurements. Home monitoring can also demonstrate response to treatment more quickly than in-clinic monitoring, and provide more information about nyctohemoral fluctuations than is ascertained by in-clinic tonometry.
PMCID:9562449
PMID: 36247209
ISSN: 2451-9936
CID: 5470992
Prevention of angle-closure glaucoma: balancing risk and benefit [Editorial]
PMCID:9674842
PMID: 35725765
ISSN: 1476-5454
CID: 5498092
Reply: The spectrum of complement pathway activation is integral to the pathogenesis of severe COVID-19
PMID: 36327115
ISSN: 1460-2156
CID: 5358732
Subretinal drusenoid deposits are strongly associated with coexistent high-risk vascular diseases
Background/aims Demonstrate that subretinal drusenoid deposits (SDDs) in age-related macular degeneration (AMD) are linked to coexistent high-risk vascular diseases (HRVDs). Methods Cross-sectional study. Two hundred AMD subjects (aged 51-100 years; 121 women, 79 men) were recruited. Spectral domain optical coherence tomography, autofluorescence and near-infrared reflectance imaging, and lipid profiles were obtained. Subjects were assigned by health history questionnaires into those with or without HRVDs, defined as: cardiac valve defect (eg, aortic stenosis), myocardial defect (eg, myocardial infarction) and stroke/transient ischaemic attack. Masked readers assigned subjects into two groups: SDD (with or without drusen) and drusen (only). Univariate testing was performed by χ 2 test. We built multivariate regression models to test relationships of coexistent HRVD to SDD status, lipid levels and other covariates. Results The prevalence of HRVD was 41.2% (40/97) and 6.8% (7/103) in the SDD and non-SDD groups, respectively (correlation of SDD with HRVD, p=9×10 -9, OR 9.62, 95% CI 4.04 to 22.91). Multivariate regressions: only SDDs and high-density lipoprotein (HDL) in the first two HDL quartiles remained significant for HRVD (p=9.8×10 -5, 0.021, respectively). Multivariate regression model: SDDs and an HDL in Q1 or Q2 identified the presence of HRVD with the accuracy of 78.5%, 95% CI 72.2% to 84.0%. Conclusions High-risk cardiovascular and neurovascular diseases were accurately identified in an AMD cohort from SDDs and HDL levels. The SDDs may be related to inadequate ocular perfusion resulting from the systemic vasculopathies. Further research with this paradigm is warranted and might reduce mortality and morbidity from vascular disease.
SCOPUS:85143502124
ISSN: 2397-3269
CID: 5393012
Accuracy of clinical versus oculographic detection of pathological saccadic slowing
Saccadic slowing as a component of supranuclear saccadic gaze palsy is an important diagnostic sign in multiple neurologic conditions, including degenerative, inflammatory, genetic, or ischemic lesions affecting brainstem structures responsible for saccadic generation. Little attention has been given to the accuracy with which clinicians correctly identify saccadic slowing. We compared clinician (n = 19) judgements of horizontal and vertical saccade speed on video recordings of saccades (from 9 patients with slow saccades, 3 healthy controls) to objective saccade peak velocity measurements from infrared oculographic recordings. Clinician groups included neurology residents, general neurologists, and fellowship-trained neuro-ophthalmologists. Saccades with normal peak velocities on infrared recordings were correctly identified as normal in 57% (91/171; 171 = 9 videos × 19 clinicians) of clinician decisions; saccades determined to be slow on infrared recordings were correctly identified as slow in 84% (224/266; 266 = 14 videos × 19 clinicians) of clinician decisions. Vertical saccades were correctly identified as slow more often than horizontal saccades (94% versus 74% of decisions). No significant differences were identified between clinician training levels. Reliable differentiation between normal and slow saccades is clinically challenging; clinical performance is most accurate for detection of vertical saccade slowing. Quantitative analysis of saccade peak velocities enhances accurate detection and is likely to be especially useful for detection of mild saccadic slowing.
PMID: 36183516
ISSN: 1878-5883
CID: 5359142
Acute Exudative Polymorphous Vitelliform Maculopathy Associated with Primary Epstein-Barr Virus Infection
PURPOSE/OBJECTIVE:To report a case of acute exudative polymorphous vitelliform maculopathy (AEPVM) associated with primary Epstein-Barr virus (EBV) infection. METHODS:Multimodal imaging including color fundus photography, spectral domain optical coherence tomography (SD-OCT), blue light fundus autofluorescence (FAF), fluorescein angiography (FA) and indocyanine green angiography (ICGA). RESULTS:A 24-year-old otherwise healthy woman presented with an acute bilateral visual disturbance associated with cervical lymphadenopathy. SD-OCT showed bilateral foveal serous retinal detachment (SRD) with thickening of the ellipsoid zone (EZ) throughout the posterior pole corresponding to hyperautofluorescence on FAF, faint diffuse hyperfluorescence on FA without leakage, and mild late hyperfluorescence on ICGA. Systemic workup revealed an acute EBV infection. Within several weeks, multifocal SRDs developed in the macula and paramacula. The SRDs then became increasingly hyperautofluorescent with SD-OCT showing subretinal hyperreflective material. This vitelliform material then slowly resolved while the thickness of the surrounding EZ normalized. The FA and ICGA appeared normal at month 8. Visual acuity was 20/20 in both eyes at all times. No treatment was initiated. CONCLUSION/CONCLUSIONS:AEPVM may be associated with an acute EBV-infection. Acutely, multimodal imaging revealed findings consistent with RPE dysfunction and reduced photopigment density. Subsequent accumulation of vitelliform material gradually resolved over an 8 month follow up.
PMID: 33031214
ISSN: 1937-1578
CID: 4627132
Multimodal imaging of a choroidal nevus with caverns in the setting of pachychoroid disease
PURPOSE/OBJECTIVE:To describe the multimodal imaging findings of extensive choroidal caverns within a choroidal nevus in an eye with pachychoroid spectrum disease. METHODS:A 69 year-old woman was referred with a known history of branch retinal vein occlusion (BRVO) in the right eye and choroidal nevus in the left eye. Fundus examination of both eyes (OU) revealed subretinal yellow deposits, suggestive of pachydrusen. Retinal venous collaterals were noted in the temporal macular of the right eye. A lightly pigmented choroidal lesion with nearly confluent overlying drusen and retinal pigment epithelial (RPE) alterations, consistent with chronic choroidal nevus, was noted in the macula of the left eye. RESULTS:Optical coherence tomography B-scans revealed thickened choroid (pachychoroid) with subfoveal choroidal thickness of 504 and 580 µm with large hyporeflective spaces suggestive of pachyvessels OU. In the region of the choroidal nevus, the choroidal vascular spaces appeared comparatively large and were classified as "caverns", measuring up to 480 µm in diameter. OCT angiography (OCTA) and indocyanine green angiography (ICGA) demonstrated absence of flow within the caverns. ICGA further illustrated choroidal vascular hyperpermeability with patchy hyperfluorescent areas OU. Widefield swept source OCT showed mild posterior scleral bowing, a feature occasionally documented with choroidal nevus, and highlighted greater hyporeflectivity and hypertransmission on OCT within the caverns compared to the non-cavernous choroidal vessels. CONCLUSION/CONCLUSIONS:Choroidal caverns can occur within choroidal nevus in the setting of pachychoroid disease.
PMID: 33653986
ISSN: 1937-1578
CID: 4801432
The OCT angular sign of Henle fiber layer (HFL) hyperreflectivity (ASHH) and the pathoanatomy of the HFL in macular disease
The Henle fiber layer (HFL) is comprised of bundles of unmyelinated photoreceptor axons intermingled with outer Müller cell processes. The photoreceptor axons extend from the cell bodies located in the outer nuclear layer and radially project toward the outer plexiform layer, the inner third of which includes the synaptic junctional complexes and the outer two-thirds of which includes the HFL. The oblique path of the HFL provides unique structural and reflectance properties and this radial anatomy is highlighted in many macular disorders including those with macular star exudation and HFL hemorrhage. Recent investigations using multimodal imaging techniques, especially cross sectional and en face optical coherence tomography (OCT), have provided new perspectives regarding HFL disruption in retinal diseases. The aim of this review is to highlight the pathoanatomy and multimodal imaging, especially OCT, associated with HFL disruption that is present in various macular diseases. After describing the current knowledge of the embryology, anatomy, and physiology of the HFL, we review the existing imaging modalities that allow in vivo visualization of the HFL in the healthy and diseased retina. Finally, we report the clinical and imaging findings of acute HFL alteration in various macular disorders, including degenerative, inflammatory, and vascular conditions. Also, we propose a novel and signature OCT biomarker indicative of acute photoreceptor disruption involving the HFL, termed the "angular sign of HFL hyperreflectivity" (ASHH) of macular disease, to unify the pathoanatomy common to these various macular disorders and to provide clarity regarding the underlying pathogenesis.
PMID: 36333227
ISSN: 1873-1635
CID: 5358882
Recurrent Acute Retinal Necrosis
PURPOSE/OBJECTIVE:To describe a patient with recurrent acute retinal necrosis (ARN), her treatment, and propose a possible pathophysiologic mechanism. METHOD/METHODS:Case report. RESULTS:A four-year-old girl presented elsewhere with bilateral ARN, was treated, but developed a retinal detachment in the left eye that failed vitrectomy surgery. She was referred 10 years later with recurrent ARN. The infection was difficult to get under control, but eventually responded to intravenous acyclovir and foscarnet. She was given laser photocoagulation. She was placed on oral valacyclovir prophylaxis and was disease free for 10 years at which point she decided to go to South America on vacation and stop her valacyclovir. Within a few days she developed a recurrence of ARN and flew back for treatment. She had discrete areas of retinal necrosis, vasculitis, and the laser photocoagulation lesions appeared to be ringed by a retinal change suggestive of retinitis. She responded to antiviral treatment, but developed a retinal detachment that was successfully treated. Her visual acuity was 20/20 six years later, and she was using antiviral prophylaxis. CONCLUSIONS:Recurrent ARN can respond to aggressive treatment. Chorioretinal scars, such as from photocoagulation, may be potential sites of viral invasion during recurrences. Anti-viral prophylaxis may be indicated for at risk patients.
PMID: 33346624
ISSN: 1937-1578
CID: 4726242
Contact Lens Safety for the Correction of Refractive Error in Healthy Eyes
ABSTRACT/UNASSIGNED:Contact lenses are a safe and effective method for correction of refractive error and worn by an estimated 45 million Americans. Because of the widespread availability and commercial popularity of contact lenses, it is not well appreciated by the public that contact lenses are U.S. Food and Drug Administration (FDA)-regulated medical devices. Contact lenses are marketed in numerous hard and soft materials that have been improved over decades, worn in daily or extended wear, and replaced in range of schedules from daily to yearly or longer. Lens materials and wear and care regimens have impact on the risks of contact lens-related corneal inflammatory events and microbial keratitis. This article reviews contact lens safety, with specific focus on the correction of refractive error in healthy eyes.
PMCID:9584055
PMID: 36282872
ISSN: 1542-233x
CID: 5357952
Optic nerve tortuosity and displacements during horizontal eye movements in healthy and highly myopic subjects
AIMS/OBJECTIVE:(1) To assess the morphology and 3-dimensional (3D) displacements of the eye globe and optic nerve (ON) in adduction/abduction using MRI. (2) To assess differences between healthy emmetropic and highly myopic (HM) subjects. METHODS:MRI volumes of both eyes from 18 controls and 20 HM subjects in primary gaze, abduction and adduction (15°) were postprocessed. All ONs were manually segmented and fitted to a 3D curve to assess ON tortuosity. ON displacements were evaluated in four quasicoronal planes which were perpendicular to the ON in primary gaze and were 3 mm apart. RESULTS:Axial length was higher in the HM group (28.62±2.60 vs 22.84±0.89 mm; p<0.0001). Adjusted ON tortuosities (ie, ON tortuosities estimated before myopia onset) were lower in HM eyes (0.9063±0.0591) versus controls (1.0152±0.02981) in primary gaze, adduction (0.9023±0.05538 vs 1.0137±0.0299) and abduction (0.9100±0.0594 vs 1.0182±0.0316); p<0.0001 for all cases. In all eyes, ON displacements in adduction were significantly different from those in abduction in the naso-temporal direction (p<0.0001 in all planes) but not in the supero-inferior direction. ON displacements in the posterior segments of the ON were smaller in the HM group in both gaze directions and were larger in the anterior-most ON segment in adduction only. CONCLUSION/CONCLUSIONS:The adjusted tortuosity of the ON was significantly lower in HM eyes, suggesting that eyes destined towards HM exhibited higher ON traction forces during eye movements before the onset of myopia. Our ON metrics may be valuable to explore a potential link between eye movements and axial elongation.
PMID: 34039559
ISSN: 1468-2079
CID: 4888022
Clinical impact of the worldwide shortage of verteporfin (Visudyne®) on ophthalmic care
INTRODUCTION/BACKGROUND:Since July 2021, a worldwide shortage of verteporfin (Visudyne®) occurred: an essential medicine required for photodynamic therapy (PDT). PDT with verteporfin has a broad range of indications in ophthalmology, including chronic central serous chorioretinopathy, polypoidal choroidal vasculopathy and choroidal haemangioma. For these disorders, PDT is either the first-choice treatment or regarded as a major treatment option. MATERIALS AND METHODS/METHODS:A questionnaire was sent to key opinion leaders in the field of medical retina throughout the world, to assess the role of PDT in their country and the effects of the shortage of verteporfin. In addition, information on the application of alternative treatments during shortage of verteporfin was obtained, to further assess the impact of the shortage. RESULTS:Our questionnaire indicated that the shortage of verteporfin had a major impact on ophthalmic care worldwide and was regarded to be a serious problem by most of our respondents. However, even though there is ample evidence to support the use of PDT in several chorioretinal diseases, we found notable differences in its use in normal patient care throughout the world. Various alternative management strategies were noted during the verteporfin shortage, including lowering the dose of verteporfin per patient, the use of alternative treatment strategies and the use of a centralized system for allocating the remaining ampoules of verteporfin in some countries. CONCLUSION/CONCLUSIONS:The shortage of verteporfin has had a large effect on the care of ophthalmic patients across the world and may have resulted in significant and irreversible vision loss. Mitigation strategies should be developed in consultation with all stakeholders to avoid future medication shortages of verteporfin and other unique ophthalmic medications. These strategies may include mandatory stock keeping, compulsory licensing to an alternative manufacturer or incentivizing the development of competition, for example through novel public-private partnerships.
PMID: 35388619
ISSN: 1755-3768
CID: 5206982
Clinical and Morphologic Characteristics of Perivenular Fern-like Leakage on Ultra-Widefield Fluorescein Angiography
PURPOSE/OBJECTIVE:To analyze the spectrum of the perivenular fern-like leakage on ultra-widefield fluorescein angiography (UWFA) and to discuss its potential implications in the current understanding of the retinal venous outflow. DESIGN/METHODS:Retrospective observational case series. PARTICIPANTS/METHODS:Eyes presenting with a fern-like pattern of dye leakage on UWFA were included in this study. METHODS:Analysis of the clinical characteristics and multimodal imaging findings using UWFA and wide-angle swept-source optical coherence tomography angiography (SS-OCTA). MAIN OUTCOME MEASURES/METHODS:To elucidate the disease spectrum, anatomic origin and clinical implications of this fern-like leakage. RESULTS:Multimodal retinal imaging from 40 eyes of 29 patients with fern-like leakage on UWFA was studied. Underlying etiologies included a wide range of inflammatory disorders including pars planitis (18 eyes), and central retinal vein occlusion (2 eyes). On UWFA, the fern-like leakage originated from the retinal capillaries and venules directly adjacent to the veins and spared the peri-arterial zone. This perivenular fern-like leakage involved the far periphery in all cases and progressed more diffusely and centripetally in cases with more severe intra-ocular inflammation. On wide-angle SS-OCTA, deep capillary plexus (DCP) flow signal impairment precisely co-localized with the perivenular fern-like leakage identified on UWFA. CONCLUSIONS:The fern-like leakage on UWFA refers to the distinctive perivenular dye leakage originating from the retinal capillaries and venules. Multimodal imaging correlation suggests predominant impairment at the level of the DCP. Axial symmetry of the fern-like leakage with the veins and sparing of the peri-arterial zone may support the dominant venous role of the DCP.
PMID: 35545196
ISSN: 2468-6530
CID: 5214492
CLINICAL EFFICACY AND PREDICTIVE BIOMARKERS OF ONC201 IN H3K27M-MUTANT DIFFUSE MIDLINE GLIOMA [Meeting Abstract]
Patients with H3K27M-mutated diffuse midline glioma (DMG) have no proven effective therapies beyond radiation. ONC201, a DRD2 antagonist and mitochondrial ClpP agonist, has shown promise in this population. Clinical and genetic variables associated with ONC201 response in H3K27M-mutant DMG continue to be investigated. A combined clinical and genetic study evaluated patients with H3K27M-DMG treated with single-agent ONC201 at the established phase 2 dose. Clinical outcomes of patients treated on two recently completed multi-site clinical studies (NCT03416530 and NCT03134131, n = 75) were compared with historical control data from patients with confirmed H3K27M-DMG (n = 391 total, n = 119 recurrent). Patients treated with ONC201 monotherapy following initial radiation, but prior to recurrence, demonstrated a median overall survival (OS) of 25.6 months from diagnosis and recurrent patients demonstrated a median OS of 16.2 months from recurrence, both of these more than doubling historical outcomes. Using a Cox model to correct for age, gender and tumor location, OS of ONC201-treated patients with H3K27M-mutant tumors remained significantly better than non-ONC201-treated historical controls (p = 0.0001). A survival and radiographic analysis based on tumor location, revealed stronger responses in thalamic patients. In patients with thalamic tumors treated after initial radiation (n = 16), median OS was not reached with median follow up of 22.1 months (historical control median OS of 12.5 months, n = 83, p = 0.0001). Significant correlations were found between baseline cerebral blood flow (CBF) on perfusion imaging and OS (Pearson's r = 0.75, p = 0.003) and between nrCBF and PFS (r = 0.77, p = 0.002). Baseline tumor sequencing from treated patients (n = 20) demonstrates EGFR mutation (n = 3) and high EGFR expression as a marker of resistance and improved response in tumors with MAPK-pathway alterations (n = 5). In conclusion, ONC201 demonstrates unprecedented clinical and radiographic efficacy in H3K27M-mutant DMG with outcomes enriched in patients with thalamic tumors, treatment prior to recurrence, MAPKpathway alterations, and patients with relatively high CBF
EMBASE:639939966
ISSN: 1523-5866
CID: 5513292
Single cell RNA-seq of human cornea organoids identifies cell fates of a developing immature cornea
The cornea is a protective and refractive barrier in the eye crucial for vision. Understanding the human cornea in health, disease, and cell-based treatments can be greatly advanced with cornea organoids developed in culture from induced pluripotent stem cells. While a limited number of studies have investigated the single-cell transcriptomic composition of the human cornea, its organoids have not been examined similarly. Here, we elucidated the transcriptomic cell fate map of 4-month-old human cornea organoids and human donor corneas. The organoids harbor cell clusters that resemble cells of the corneal epithelium, stroma, and endothelium, with subpopulations that capture signatures of early developmental states. Unlike the adult cornea where the largest cell population is stromal, the organoids contain large proportions of epithelial and endothelial-like cells. These corneal organoids offer a 3D model to study corneal diseases and integrated responses of different cell types.
PMCID:9802453
PMID: 36712326
ISSN: 2752-6542
CID: 5430182
Repeated application of riboflavin during corneal cross-linking does not improve the biomechanical stiffening effect ex vivo
PURPOSE:To evaluate whether repeated application of riboflavin during corneal cross-linking (CXL) has an impact on the corneal biomechanical strength in ex-vivo porcine corneas. DESIGN:Laboratory investigation. METHODS:for 30 min); while the corneas in Group 3 were not irradiated and served as control. During irradiation, Group 1 (CXL-PBS-Ribo) received repeated riboflavin solution application while corneas in Group 2 (CXL-PBS) received only repeated iso-osmolar PBS solution. Immediately after the procedure, 5-mm wide corneal strips were prepared, and elastic modulus was calculated to characterize biomechanical properties. RESULTS:Significant differences in stress-strain extensiometry were found between two cross-linked groups with control group (P = 0.005 and 0.002, respectively). No significant difference was observed in the normalized stiffening effect between Groups 1 and 2 (P = 0.715). CONCLUSIONS:The repeated application of riboflavin solution during UV-A irradiation does not affect the corneal biomechanical properties achieved with standard epi-off CXL. Riboflavin application during CXL may be omitted without altering the biomechanical stiffening induced by the procedure.
PMID: 36167218
ISSN: 1096-0007
CID: 5484862
Reply: Ex Vivo Eye Rubbing Evidence [Comment]
PMID: 36367268
ISSN: 1081-597x
CID: 5484892
Chronic anophthalmic socket pain in the setting of deep orbital pseudocysts
An 89-year-old woman presented with chronic pain and foreign body sensation in a healthy-appearing anophthalmic socket. Computed tomography of the orbits showed hyperdense, cystic lesions superior and posterior to the orbital implant. Orbital exploration was performed; the orbital implant and lesions were removed. Histopathology revealed cystic structures composed of fibrocellular tissue lined with histiocytes and multinucleated giant cells, consistent with pseudocysts. Postoperatively, the patient noted the resolution of her symptoms. While the etiology of the pseudocysts remains unclear, we hypothesize that the answer can be traced back to the original surgery. The cysts may have formed after extravasation of fluid or proteinaceous material from the eye, from glycerin on the donor sclera, or after introduction of foreign material during retrobulbar injection of local anesthesia. This is the first report of pseudocysts occurring in the orbit posterior to an implant.
PMID: 36278956
ISSN: 1744-5108
CID: 5534012
Medical Management versus PACK-CXL in Dogs with Infectious Keratitis: A Randomized Controlled Trial Protocol
Infectious keratitis is a common and painful disease, usually caused by bacteria in dogs. Brachycephalic breeds are at increased risk. Despite medical therapy, enzymatic corneal melting can lead to ulcer perforation and globe loss. Treatment alternatives are needed due to an increase in antibiotic resistance and growing popularity of brachycephalic dogs. Photoactivated Chromophore for Keratitis-Corneal Cross-linking (PACK-CXL) reduces enzymatic collagenolysis and damages multiple targets within microorganisms, resulting in corneal tissue stabilization and elimination of bacteria, irrespective of their antibiotic resistance status. A randomized controlled trial providing evidence of PACK-CXL effectiveness in dogs is lacking. We aim to determine whether PACK-CXL is a viable alternative to conventional medical therapy for canine infectious keratitis. Two hundred-and-seventy client-owned dogs with presumed infectious keratitis will be allocated to two equally sized treatment groups (PACK-CXL or medical therapy) in a masked, randomized, controlled, multicenter trial in eleven clinics. The primary outcome measure is treatment success defined as complete epithelial closure within 28 days. The sample size is based on a group sequential design with two interim analyses, which will be overseen by a Data Safety and Monitoring Board. Ethical approvals have been obtained. The study protocol is preregistered at preclinicaltrials.eu. Publishing trial protocols improves study reproducibility and reduces publication bias.
PMCID:9597735
PMID: 36290247
ISSN: 2076-2615
CID: 5484882
A randomized phase 2 clinical trial of phentolamine mesylate eye drops in patients with severe night vision disturbances
PURPOSE/OBJECTIVE:Dim light vision disturbances (DLD) comprise a wide range of symptoms affecting the quality of vision at low illumination including glare, halos, and starbursts. This exploratory study investigated 1.0% phentolamine mesylate ophthalmic solution (PMOS) as a treatment to improve vision and image quality for patients with DLD. METHODS:In this placebo-controlled, randomized, double-masked clinical trial, 24 adult patients with severe DLD were randomized in a 2:1 ratio to receive either one dose of PMOS or placebo. Subjects were eligible if they reported experiencing severe night vision difficulty that was not eliminated by distance spectacle correction and scored ≥0.3 log units below the normal range of contrast sensitivity assessed under mesopic conditions with glare at ≥2 spatial frequencies. Key efficacy outcomes were change from baseline in pupil diameter, contrast sensitivity, and visual acuity. Safety measures including intraocular pressure, conjunctival hyperemia, and systemic effects were also assessed. RESULTS:Eight subjects were randomized to placebo (63% female; mean age 47 years) and 16 were randomized to PMOS (75% female; mean age 42 years). Mean (SD) pupil diameter of PMOS-treated subjects decreased significantly - 1.3 mm (0 to - 2.8 mm) with p < 0.0001. Mean contrast sensitivity with glare in PMOS-treated subjects improved significantly post-treatment at spatial frequencies 3, 6, 12, and 18 cycles per degree (p ≤ 0.03). PMOS also demonstrated improvements in the numbers of letters read for mesopic and photopic, high- and low-contrast visual acuity (LCVA). Importantly, a statistically greater proportion of PMOS-treated eyes registered mesopic LCVA 5 letter (69% vs. 31%, p = 0.029) and 10 letter (34% vs. 6%, p = 0.04) improvement, with a trend at 15 letters (19% vs. 0%, p = 0.16). PMOS was well tolerated with the only reported side effect being a mild increase in conjunctival hyperemia. CONCLUSION/CONCLUSIONS:PMOS was well tolerated and effectively reduced pupil size with improvements in contrast sensitivity and visual acuity in adults with severe DLD. Future Phase 3 studies should be conducted to further evaluate its potential to treat DLD. TRIAL REGISTRATION/BACKGROUND:The trial registration number is NCT04004507 (02/07/2019). Retrospectively registered.
PMCID:9548101
PMID: 36209072
ISSN: 1471-2415
CID: 5351832
Demarcation Line Depth in Epithelium-Off Corneal Cross-Linking Performed at the Slit Lamp
We aimed to evaluate the depth of the demarcation line following accelerated epithelium-off corneal cross-linking (A-CXL) performed at the slit lamp with the patient sitting in an upright position. Twenty-three eyes from twenty patients, undergoing epi-off A-CXL (9 mW/cm2 for 10 min) using a CXL device at the slit lamp in the upright position. Demarcation line depth was assessed at 1 month after the procedure using anterior segment optical coherence tomography (AS-OCT) and specialized software. Surgery was uneventful in all cases. The average postoperative demarcation line depth achieved was 189.4 µm (standard deviation: 58.67 µm). The demarcation line depth achieved with patients sitting upright, receiving CXL at the slit lamp, is similar to published data on CXL performed in the supine position, suggesting that demarcation line depth is not dependent on patient orientation during CXL.
PMCID:9570784
PMID: 36233740
ISSN: 2077-0383
CID: 5484872
COVID-19 vaccination may enhance hippocampal neurogenesis in adults
Emerging evidence suggests a detrimental impact of COVID-19 illness on the continued hippocampal neurogenesis in adults. In contrast, the existing literature supports an enhancing effect of COVID-19 vaccination on adult hippocampal neurogenesis. Vaccines against respiratory infections, including influenza, have been shown to enhance hippocampal neurogenesis in adult-age animals. We propose that a similar benefit may happen in COVID-19 vaccinated adults. The vaccine-induced enhancement of the hippocampal neurogenesis in adults thus may protect against age-related cognitive decline and mental disorders. It alsohints at an added mental health benefit of the COVID-19 vaccination programs in adults.
PMCID:9527215
PMID: 36202167
ISSN: 1090-2139
CID: 5351662
Corneal Cross-Linking: Epi-On
When treating corneal ectasias, successful corneal cross-linking (CXL) requires three factors: riboflavin saturation of the corneal stroma, ultraviolet (UV) light, and oxygen. Riboflavin is too large to pass through epithelial tight junctions, so traditionally epithelial debridement is performed before riboflavin is applied making this approach an epithelium-off (epi-off) technique. However, this can result in pain as the epithelium regrows, corneal haze, and an increased infection risk postoperatively, which needs careful management with pharmacotherapy. Epithelium-on (epi-on) CXL should reduce the extent of these issues. Riboflavin can be passed through the epithelium into the stroma either by iontophoresis or with penetration enhancers, however this alone results in suboptimal cross-linking effects, as the epithelium not only absorbs around 20% of incoming UV energy, it also acts as a barrier to oxygen diffusion into the stroma. While it is simple to adjust the UV fluence delivered to the stroma to compensate for the energy lost in the epithelium, compensating for the lack of stromal oxygen is less simple. Several approaches (including oxygen goggles) have been taken to achieve this. However, adding iontophoresis and supplemental oxygen through goggles in the operating theater adds complexities that could be engineered out. Accordingly, the technique has advanced in the laboratory to a point where penetration enhancers, optimized UV irradiation profiles, and atmospheric oxygen can now provide epi-on CXL with the same corneal strengthening efficacy as epi-off CXL, suggesting simple, effective epi-on CXL could soon be in clinical use.
PMID: 36107842
ISSN: 1536-4798
CID: 5484842
Indolent Non-Progressive Multifocal Choroidal Lymphoid Lesions: A Clinical-Histopathological Correlation
PURPOSE/OBJECTIVE:To present a clinicopathologic correlation of indolent, non-progressive multifocal choroidal lesions, clinically presumed to be lymphoid in nature, using multimodal imaging and histopathological analysis of a donor eye. DESIGN/METHODS:Case study and clinicopathologic correlation. PARTICIPANT/METHODS:A 77-year-old man of Caucasian ancestry was followed for nineteen years with indolent non-progressive multifocal choroidal infiltration of his right eye, presumed to be lymphocytic in nature based on the appearance of the lesions. METHODS:Multimodal imaging including fundus photography, B-scan ultrasonography, optical coherence tomography, fluorescein angiography, and indocyanine green angiography were performed throughout 19 years of follow up prior to the patient's death. The involved eye was preserved 21 hours postmortem and analyzed using standard histopathological and immunohistochemical techniques. MAIN OUTCOME MEASURES/METHODS:Correlation of findings on multimodal imaging with histopathological and immunohistochemical findings in the involved eye. RESULTS:Clinical examination over the course of 19 years showed no deterioration in visual acuity of the involved eye. Multimodal imaging revealed yellow-orange choroidal lesions that showed no appreciable progression during the 19 year follow up. These areas stained minimally on fluorescein angiography. Indocyanine green angiography revealed tortuous choroidal vessels and fluorescence blockage. Enhanced-depth imaging optical coherence tomography revealed hyporeflective homogenous choroidal thickening. Light microscopy, histopathology, and immunohistochemistry showed that the lesions were composed of small, mature-appearing B-cells that spared the choriocapillaris. The findings were most consistent with an extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma). CONCLUSIONS:Indolent non-progressive multifocal choroidal lymphoid lesions in this patient remained confined to the choroid on clinical examination and imaging for almost two decades, with no clinical evidence of extension into the retina. Light microscopy, histopathology, and immunohistochemistry postmortem showed that the lesions were composed of small, mature-appearing B-cells that spared the choriocapillaris. The findings were consistent with an extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma). This entity is distinct from more aggressive uveal and choroidal lymphoma and is expected to remain relatively stationary on long-term clinical follow-up, with a good visual prognosis.
PMID: 35338027
ISSN: 2468-6530
CID: 5220502
Canadian journal of ophthalmology = Journal canadien d'ophtalmologie. 2022:57(5):e177-e179.DOI: 10.1016/j.jcjo.2022.02.001
Preserved retinal sensitivity following spontaneous regression of soft drusen [Letter]
PMID: 35283106
ISSN: 1715-3360
CID: 5220672
Documentation of recovery from vitamin A deficiency-related retinopathy via multimodal imaging and electroretinogram testing
PURPOSE/OBJECTIVE:To describe vitamin A deficiency using multimodal functional visual assessments and imaging. METHODS/CASE/UNASSIGNED:A 50-year-old female with past medical history significant for Roux-en-Y gastric bypass surgery complained of nyctalopia and "yellowing" of vision. RESULTS:Vitamin A levels were noted to be < 0.06 mg/L (normal 0.3-0.12 mg/L). Fundus examination was notable for peripheral yellow punctate lesions, superior arcuate defects on HVF 30-2 testing, an indistinct ellipsoid zone on SD-OCT, and absent rod responses and severely reduced amplitudes for the cone photoreceptors on full-field ERG. These findings resolved with initiation of parenteral vitamin A supplementation. CONCLUSION/CONCLUSIONS:This report documents an example of vitamin A deficiency in the developed world. We aim to provide a comprehensive description of clinical examination and multimodal imaging findings before and after vitamin supplementation for vitamin A deficiency.
PMID: 35896849
ISSN: 1573-2622
CID: 5276712
Selective laser trabeculoplasty (SLT) performed by optometrists-enablers and barriers to a shift in service delivery
BACKGROUND/OBJECTIVES:To explore the acceptability, training requirements, enablers and barriers of optometrist-delivered SLT. SUBJECTS/METHODS:Optometrists, fellowship and consultant grade ophthalmologists, hospital managers and patients were interviewed using pre-defined topic guides. Interviews were audio-recorded, transcribed, and subjected to thematic analysis. Overarching themes were defined by the study aims and the topic guides; subthemes were derived from the interview data. RESULTS:Sixty-six participants (three managers, eight glaucoma specialist consultant ophthalmologists, seven clinical glaucoma fellows, 12 optometrists (two of them performing SLT), two ophthalmic nurses and 34 patients) participated in the study. Overarching themes (and subthemes) were: necessity of non-medical SLT delivery, clinical practice and training, advantages, disadvantages, concerns, challenges, community delivery of SLT, patient values and other healthcare professionals that could also deliver SLT. CONCLUSIONS:Certain clinical pre-requisites, such as gonioscopy and independent prescribing rights, were perceived as necessary for undertaking SLT training. An optometrist-delivered SLT service was expected to benefit the NHS, but there was an identified need of a standardised training scheme and robust governance. Patients were accepting of an optometrist-delivered SLT service in the hospital eye service.
PMID: 34389819
ISSN: 1476-5454
CID: 5497972
Correction to: Selective laser trabeculoplasty (SLT) performed by optometrists -enablers and barriers to a shift in service delivery
PMID: 34931052
ISSN: 1476-5454
CID: 5498002
Correlation between Macular Neovascularization (MNV) Type and Druse Type in Neovascular Age-Related Macular Degeneration (AMD) Based on the CONAN Classification
To investigate associations and predictive factors between macular neovascularization (MNV) lesion variants and drusen types in patients with treatment-naïve neovascular age-related macular degeneration (AMD).
PMCID:9598373
PMID: 36289632
ISSN: 2227-9059
CID: 5359502
The Role of OCT Criteria and Machine Learning in Multiple Sclerosis and Optic Neuritis Diagnosis
BACKGROUND AND OBJECTIVES/OBJECTIVE:Recent studies have suggested that inter-eye differences (IEDs) in peripapillary retinal nerve fiber layer (pRNFL) or ganglion cell+inner plexiform (GCIPL) thickness by spectral-domain optical coherence tomography (SD-OCT) may identify people with a history of unilateral optic neuritis (ON). However, this requires further validation. Machine learning classification may be useful for validating thresholds for OCT IEDs and for examining added utility for visual function tests, such as low-contrast letter acuity (LCLA), in the diagnosis of people with multiple sclerosis (PwMS) and for unilateral ON history. METHODS:Participants were from 11 sites within the International Multiple Sclerosis Visual System (IMSVISUAL) consortium. pRNFL and GCIPL thicknesses were measured using SD-OCT. A composite score combining OCT and visual measures was compared individual measurements to determine the best model to distinguish PwMS from controls. These methods were also used to distinguish those with history of ON among PwMS. ROC curve analysis was performed on a training dataset (2/3 of cohort), then applied to a testing dataset (1/3 of cohort). Support vector machine (SVM) analysis was used to assess whether machine learning models improved diagnostic capability of OCT. RESULTS:Among 1,568 PwMS and 552 controls, variable selection models identified GCIPL IED, average GCIPL thickness (both eyes), and binocular 2.5% LCLA as most important for classifying PwMS vs. controls. This composite score performed best, with AUC=0.89 (95% CI 0.85, 0.93), sensitivity=81% and specificity=80%. The composite score ROC curve performed better than any of the individual measures from the model (p<0.0001). GCIPL IED remained the best single discriminator of unilateral ON history among PwMS (AUC=0.77, 95% CI 0.71,0.83, sensitivity=68%, specificity=77%). SVM analysis performed comparably to standard logistic regression models. CONCLUSIONS:A composite score combining visual structure and function improved the capacity of SD-OCT to distinguish PwMS from controls. GCIPL IED best distinguished those with history of unilateral ON. SVM performed as well as standard statistical models for these classifications. CLASSIFICATION OF EVIDENCE/METHODS:The study provides Class III evidence that SD-OCT accurately distinguishes multiple sclerosis from normal controls as compared to clinical criteria.
PMID: 35764402
ISSN: 1526-632x
CID: 5281122
Transitioning from a standalone practice to a private equity-partnered practice and impact on clinical operations
PURPOSE OF REVIEW/OBJECTIVE:Private equity has made significant inroads into the specialty of ophthalmology. The purpose of this review is to evaluate the effect of private equity on clinical operations in an ophthalmic practice. RECENT FINDINGS/RESULTS:Private equity had become an important source of capital and management expertise that has resulted in the consolidation of many ophthalmic practices as an alternative to working for a hospital system, insurance carrier, or independent private practice. SUMMARY/CONCLUSIONS:The recent growth of private equity presence in ophthalmology has resulted in significant changes in clinical operations. These changes in clinical operations include the increased importance of data management and data analytics, economies of scale, synergies, and introduction of patient-shared billing opportunities. Although physician input into clinical operations is decreased, provisional care decision-making can be maintained.
PMID: 35916566
ISSN: 1531-7021
CID: 5287662
High-Resolution Spectral Domain Optical Coherence Tomography of Congenital Grouped Albinotic Spots
PMID: 35994587
ISSN: 1539-2864
CID: 5312452
Driving forces and current trends in private equity acquisitions within ophthalmology
PURPOSE OF REVIEW/OBJECTIVE:Private equity investment in ophthalmology has dramatically increased over the past 20 years. Despite a massive influx in private equity investment in ophthalmology, little is known regarding if and how private equity investment might affect practice behavior. This review seeks to discuss why private equity investment may be expanding in ophthalmology and explore recent data on demographic and billing trends before and after private equity acquisition. RECENT FINDINGS/RESULTS:Recent publications have identified ophthalmology and optometry practices acquired by private equity from 2012 to 2021. Practice demographics and provider billing habits before and after private equity acquisition were analyzed from 2012 to 2019 and 2012 to 2017, respectively, using Internal Revenue Service, United States Census, and Medicare fee-for-service data. SUMMARY/CONCLUSIONS:Private equity investment in ophthalmology is increasing and may be because of a growing demand from an aging population, fragmented network of healthcare practices, and potential for ancillary billable services. Private equity practices acquired between 2012 and 2019 were mostly in metropolitan areas with higher proportions of private insurance coverage. Ophthalmologists and optometrists in practices acquired between 2012 and 2016 showed increased utilization of diagnostic testing and cataract surgery in the year following private equity acquisition compared with the year prior to private equity acquisition.
PMID: 35838270
ISSN: 1531-7021
CID: 5269432
Visible Light Optical Coherence Tomography Reveals the Relationship of the Myoid and Ellipsoid to Band 2 in Humans
Purpose/UNASSIGNED:We employ visible light optical coherence tomography (OCT) to investigate the relationship between the myoid, ellipsoid, and band 2 in the living human retina. Rather than refute existing theories, we aim to reveal new bands and better delineate the structures at hand. Methods/UNASSIGNED:An upgraded spectral/Fourier domain visible light OCT prototype, with 1.0-µm axial resolution, imaged 13 eyes of 13 young adult human subjects (23-40 years old) without a history of ocular pathology. The external limiting membrane (band 1) and band 2 edges were segmented. Reflectivity was examined along the inner segment (IS), defined as extending from band 1 to the band 2 center, and within band 2 itself. Results/UNASSIGNED:Images highlight a nearly continuously resolved extrafoveal internal limiting membrane, the peripheral single-cell thick ganglion cell layer, and the peripheral photoreceptor axonal fiber layer, a peripheral division of band 2 into bands 2a and 2b, and a reflectivity-based division of the IS into "m" and "e" zones. Discussion/UNASSIGNED:Topography and transverse intensity variations of the outermost band 2b suggest an association with rods. The "m" and "e" zone border is consistent with the myoid-ellipsoid boundary, even recapitulating the well-documented distribution of mitochondria throughout the IS at the foveal center. Theories of outer retinal reflectivity in OCT must adequately explain these observations. Translational Relevance/UNASSIGNED:Findings support that band 2 does partially overlap with the ellipsoid in transversally averaged OCT images due to photoreceptor IS length dispersion but argue that the inner ellipsoid must be inner to band 2, as suggested by prior quantitative measurements.
PMCID:9440607
PMID: 36053140
ISSN: 2164-2591
CID: 5332202
PACK Cross-Linking as Adjuvant Therapy Improves Clinical Outcomes in Culture-Confirmed Bacterial Keratitis
PURPOSE/OBJECTIVE:We recently showed the positive clinical effects of combining accelerated corneal cross-linking (PACK-CXL) with antibiotic treatment in patients with presumed bacterial keratitis. In this study, we compare the impacts of a combined PACK-CXL/standard antibiotic treatment (PACK-ABX group) with standard antibiotic treatment alone (ABX group) in patients with culture-confirmed bacterial keratitis. METHODS:We reviewed patients with moderate and severe bacterial keratitis and confirmed bacterial cultures. Clinical outcomes were compared for standard antibiotic treatment alone, before the initiation of PACK-CXL, and after adjuvant use of PACK-CXL. RESULTS:A total of 47 eyes of 47 patients were included: 26 eyes in the PACK-ABX group and 21 eyes in the ABX group. Pathogens, baseline demographics (besides age), and clinical parameters were similar between the 2 groups. The PACK-ABX patients had better final uncorrected visual acuity [mean difference 0.57 Logarithm of the Minimum Angle of Resolution, 95% Confidence Interval (CI): 0.16-0.99, P = 0.07] and best-corrected visual acuity (mean difference 0.70 Logarithm of the Minimum Angle of Resolution, 95% CI: 0.23-1.16, P = 0.04), shorter reepithelialization time (mean difference 9.63 days, 95% CI: 3.14-16.12, P = 0.004), and reduced number of clinic visits (mean difference 4.8 meetings, 95% CI: 1.4-8.2, P = 0.007) and need for tectonic grafts (0 vs. 33.3%, P = 0.002). A multivariate analysis controlling for age, sex, ulcer size, and Gram stain showed that PACK-ABX treatment remained significantly associated with reepithelialization time (β = 14.5, P = 0.001). CONCLUSIONS:In our study, PACK-CXLs addition to the standard of care in cases of culture-proven bacterial keratitis had a positive effect on the final visual acuity and time to resolution, compared with the standard-of-care treatment.
PMID: 34743099
ISSN: 1536-4798
CID: 5484662
Repeatability of a Scheimpflug tonometer to measure biomechanical parameters before and after myopic refractive surgery
PURPOSE:To assess the repeatability of several corneal biomechanical parameters with a Scheimpflug tonometer (Corvis ST) in myopic eyes and eyes that underwent transepithelial photorefractive keratectomy (transPRK), small-incision lenticule extraction (SMILE), or femtosecond laser-assisted in situ keratomileusis (FS-LASIK) surgery. SETTING:Eye Hospital of Wenzhou Medical University, Wenzhou, China. DESIGN:Prospective randomized controlled study. METHODS:315 eyes from 315 patients (135 myopes, 58 post-transPRK, 52 post-SMILE, and 70 post-FS-LASIK) were included. 3 consecutive scans were performed to evaluate the repeatability of the 40 parameters examined. RESULTS:315 eyes were included. In all eyes, the coefficient of variation (CoV) for intraocular pressure (IOP) and biomechanical-corrected IOP (bIOP) ranged from 7.29% to 9.47% and 6.11% to 7.75%, respectively; the CoV of pachymetry was <0.8%. The intraclass correlation coefficient of Corvis Biomechanical Index-Laser Vision Correction (LVC) was 0.680 for post-transPRK, 0.978 for post-SMILE, and 0.911 for post-FS-LASIK. The CoV of Stress-Strain Index (SSI) was 204.93% for post-transPRK, 91.92% for post-SMILE, and 171.72% for post-FS-LASIK. The CoV of the 6 clinically important dynamic corneal response parameters ranged from 2.0% to 7.8% for myopia, 1.8% to 11.1% for post-transPRK, 2.1% to 8.7% for post-SMILE, and 1.8% to 8.8% for post-FS-LASIK. CONCLUSIONS:Excellent intrameasurement repeatability of IOP, bIOP, and pachymetry was observed in all groups; SSI measurement in post-LVC corneas displayed more variation. Caution is warranted when assessing SSI in post-LVC corneas for the purpose of diagnosing iatrogenic ectasia or evaluating biomechanical remodeling of postoperative refractive corneas.
PMID: 35171143
ISSN: 1873-4502
CID: 5484742
Recommendations for OCTA reporting in retinal vascular disease: A Delphi approach by International Experts
PURPOSE/OBJECTIVE:To develop a consensus nomenclature for reporting optical coherence tomography angiography (OCTA) findings in retinal vascular disease (e.g., diabetic retinopathy, retinal vein occlusion) by international experts. DESIGN/METHODS:Delphi-based survey SUBJECTS, PARTICIPANTS AND/OR CONTROLS: Twenty-five retinal vascular disease and OCTA imaging experts METHODS, INTERVENTION, OR TESTING: A Delphi method of consensus development was used, comprising two rounds of online questionnaires, followed by a face-to-face meeting conducted virtually. Twenty-five experts in retinal vascular disease and retinal OCTA imaging were selected to constitute the OCTA Nomenclature in Delphi Study Group for retinal vascular disease. The four main areas of consensus were: definition of parameters of "widefield (WF)" OCTA, measurement of decreased vascular flow on conventional and WF-OCTA, nomenclature of OCTA findings, and OCTA in retinal vascular disease management and staging. The study endpoint was defined by the degree of consensus for each question: "strong consensus" was defined as ≥ 85% agreement, "consensus" as 80-84% and "near consensus" as 70-79%. MAIN OUTCOME MEASURES/METHODS:Consensus and near-consensus on OCTA nomenclature in retinal vascular disease RESULTS: A consensus was reached that a meaningful change in percentage of flow on WF-OCTA imaging should be an increase or decrease ≥30% of the absolute imaged area of flow signal and that a "large area" of WF-OCTA reduced flow signal should also be defined as ≥ 30% of absolute imaged area. The presence of new vessels (NV) and intra-retinal microvascular abnormalities (IRMAs), the foveal avascular zone (FAZ) parameters, the presence and amount of "no flow" area and the assessment of vessel density in various retinal layers should be added for the staging and classification of DR. Decreased flow ≥ 30% of the absolute imaged area should define an ischemic central retinal vein occlusion (CRVO). Several other items did not meet consensus requirements or were rejected in the final discussion round. CONCLUSIONS:This study provides international consensus recommendations for reporting OCTA findings in retinal vascular disease, which may help to improve the interpretability and description in clinic and clinical trials. Further validation in these settings is warranted and ongoing. Efforts are continuing to address unresolved questions.
PMID: 35202889
ISSN: 2468-6530
CID: 5172352
Functional NOTCH4 Variants Increase Notch Signaling and Susceptibility for Systemic Sclerosis [Meeting Abstract]
Background/Purpose: Genome wide association studies (GWAS) in systemic sclerosis (SSc) have identified several genetic loci, but the search for the causal variant and gene continues. In this study, using the Genome Research in African American Scleroderma Patients (GRASP) cohort, we evaluated previously reported genes from GWAS in SSc, primarily conducted in European ancestral populations. We further characterized the functional role of two variants in the Neurogenic Locus Notch Homolog Protein 4 (NOTCH4) gene.
Method(s): We identified 32 genes associated with SSc susceptibility at p-value < 10-6 in the GWAS catalog. The genebased sequence kernel association test (SKAT) test was used for association analysis and Bonferroni's correction for multiple testing. Expression quantitative trait loci (eQTL) analysis was performed using the Genotype-Tissue Expression (GTEx) data. Lymphoblastoid cell lines (LCLs) from the 1000 Genomes Project that were wildtype (WT) and heterozygous (HET) for the rs8192564 (a 5' UTR variant with CADD score >15) and rs17604492 (missense) were used to confirm the expression of NOTCH4 genes using RT-PCR and ELISA. Human lung microvascular endothelial cells (HULEC) were stimulated with NOTCH4 ligand-DLL4 to replicate increased signaling via this pathway.
Result(s): On comparing 379 AA SSc patients and 411 controls, only the NOTCH4 gene remained significant after multiple testing correction (Table 1A). This NOTCH4 association remained significant and was independent of the HLA variants, after conditional analysis. To validate these results, we examined an independent cohort of 590 patients and 360 controls and the NOTCH4 association remained significant. After multiple testing correction, diffuse cutaneous SSc, interstitial lung disease, and anti-fibrillarin antibody subsets remained statistically significant (Table 1B). eQTL analysis using GTEx data showed that both variants were associated with increased NOTCH4 expression in the HET LCLs and the rs17604492 variant also increased HEY2, (a downstream, nuclear signaling molecule for the Notch pathway) (Fig. 1B-D). Increased expression of NOTCH4 was confirmed in rs8192564 HET LCLs by RT-PCR (Fig. 1E). ELISA and western blot analysis using the lysates Fig. 1. A. NOTCH4 rs17604492 variant alters glycine to arginine at position 942; B. rs8192564 eQTL analysis for wild type (WT) and heterozygous (Het) LCLs; C, D. rs17604492 eQTL analysis for WT and het LCLs; E. RT-PCR for NOTCH4 expression in LCLs WT and het for risk variants; F. ELISA for NOTCH4 protein in LCLs WT and het for risk variants; G. Western blot for NOTCH4 protein in LCLs and endothelial cells; H. RNAseq for HEY2; I. RNA-seq for ACTA2. *normalized expression from LCLs confirmed the increased expression of NOTCH4 in LCLs carrying the risk alleles (Fig. 1F, G). Increased expression of the HEY2 and ACTA2 genes was observed on stimulating HULECs with DLL4 (Fig. 1 H, I). A previously published study has shown increased NOTCH4 expression in the skin of SSc patients (Fig. 2 A-D).
Conclusion(s): Functional variants in the NOTCH4 gene are associated with AA SSc patients and are independent of the HLA genes. Increased Notch signaling in endothelial cells can induce endothelial-to-mesenchymal transition and increased ACTA2 expression along with neoangiogenic circulation with sparse branching and dilated capillaries. SSc associated variants are associated with increased NOTCH4 expression and constitutively increase Notch4 signaling. Inhibitors of the gamma-secretase complex that cause cleavage of Notch intracellular domain have been shown to have a potent anti-fibrotic effect in different murine models of SSc and could be a potential therapeutic agent in SSc
Method(s): We identified 32 genes associated with SSc susceptibility at p-value < 10-6 in the GWAS catalog. The genebased sequence kernel association test (SKAT) test was used for association analysis and Bonferroni's correction for multiple testing. Expression quantitative trait loci (eQTL) analysis was performed using the Genotype-Tissue Expression (GTEx) data. Lymphoblastoid cell lines (LCLs) from the 1000 Genomes Project that were wildtype (WT) and heterozygous (HET) for the rs8192564 (a 5' UTR variant with CADD score >15) and rs17604492 (missense) were used to confirm the expression of NOTCH4 genes using RT-PCR and ELISA. Human lung microvascular endothelial cells (HULEC) were stimulated with NOTCH4 ligand-DLL4 to replicate increased signaling via this pathway.
Result(s): On comparing 379 AA SSc patients and 411 controls, only the NOTCH4 gene remained significant after multiple testing correction (Table 1A). This NOTCH4 association remained significant and was independent of the HLA variants, after conditional analysis. To validate these results, we examined an independent cohort of 590 patients and 360 controls and the NOTCH4 association remained significant. After multiple testing correction, diffuse cutaneous SSc, interstitial lung disease, and anti-fibrillarin antibody subsets remained statistically significant (Table 1B). eQTL analysis using GTEx data showed that both variants were associated with increased NOTCH4 expression in the HET LCLs and the rs17604492 variant also increased HEY2, (a downstream, nuclear signaling molecule for the Notch pathway) (Fig. 1B-D). Increased expression of NOTCH4 was confirmed in rs8192564 HET LCLs by RT-PCR (Fig. 1E). ELISA and western blot analysis using the lysates Fig. 1. A. NOTCH4 rs17604492 variant alters glycine to arginine at position 942; B. rs8192564 eQTL analysis for wild type (WT) and heterozygous (Het) LCLs; C, D. rs17604492 eQTL analysis for WT and het LCLs; E. RT-PCR for NOTCH4 expression in LCLs WT and het for risk variants; F. ELISA for NOTCH4 protein in LCLs WT and het for risk variants; G. Western blot for NOTCH4 protein in LCLs and endothelial cells; H. RNAseq for HEY2; I. RNA-seq for ACTA2. *normalized expression from LCLs confirmed the increased expression of NOTCH4 in LCLs carrying the risk alleles (Fig. 1F, G). Increased expression of the HEY2 and ACTA2 genes was observed on stimulating HULECs with DLL4 (Fig. 1 H, I). A previously published study has shown increased NOTCH4 expression in the skin of SSc patients (Fig. 2 A-D).
Conclusion(s): Functional variants in the NOTCH4 gene are associated with AA SSc patients and are independent of the HLA genes. Increased Notch signaling in endothelial cells can induce endothelial-to-mesenchymal transition and increased ACTA2 expression along with neoangiogenic circulation with sparse branching and dilated capillaries. SSc associated variants are associated with increased NOTCH4 expression and constitutively increase Notch4 signaling. Inhibitors of the gamma-secretase complex that cause cleavage of Notch intracellular domain have been shown to have a potent anti-fibrotic effect in different murine models of SSc and could be a potential therapeutic agent in SSc
EMBASE:639966405
ISSN: 2326-5205
CID: 5513022
Systemic Sclerosis-Associated Class II HLA Alleles Restrict the Diversity of the CDR3 and the T Cell Receptor Repertoire in African American Patients [Meeting Abstract]
Background/Purpose: Systemic sclerosis (SSc) is an autoimmune, fibrotic disorder that disproportionately affects African Americans (AA). Previous work from our lab and others has suggested a pivotal role of HLA-II genes in SSc pathogenesis. HLA-II alleles encode for variations in antigen binding grooves of HLA proteins that present antigens to T-cell receptors (TCRs) and can contribute to antigen-specific immune responses. The TCR repertoire is HLA-restricted, antigen-specific, and recognizes antigens presented by HLA proteins. In this study, we explored the diversity of the hypervariable complementarity determining region 3 (CDR3) and TCR repertoire in SSc patients. We also examined the role of HLA-II alleles, especially HLA-DPB1*13:01, in the selection of the specific sequence and amino acid composition of the TCR in SSc patients.
Method(s): Genomic DNA from 132 AA SSc patients from the GRASP consortium along with 50 AA healthy control samples were extracted and the TCRbeta chain was deep sequenced using the immunoSEQ assay (Adaptive Biotechnologies, USA). Data was analyzed using Immunarch to identify differences in unique clones, CDR3 length, V gene usage, J gene usage, and amino acid usage in the FG-Loop of the TCRbeta chain between the two SSc groups. Benjamini Hochberg FDR was used to correct for multiple testing.
Result(s): The CDR3 length was similar between SSc patients and controls (Figure 1A, B). The TCRbeta repertoire was clonally expanded in HLA-DPB1*13:01+ SSc patients as compared to patients who did not carry this allele (Figure 1C). The proportion of small and hyperexpanded TCRbeta clonotypes was increased in HLA-DPB1*13:01+ SSc patients (Figure 1D). Analysis of V gene and J gene usage identified statistically significantly increased usage of TRBV5-1, TRBV7-3, TRBJ2-1, and TRBJ2-2 genes and a decreased usage of TRBV6-1, TRBV6-4, TRBV6-5, TRBV25-1, and TRBJ1-5 genes in SSc patients compared to controls and the differences were statistically significant (Figure 2A, B). Overall amino acid usage of the FG loop of the TCRbeta chain (antigen binding region) identified increased usage of hydrophobic amino acids, leucine and valine, and reduced usage of negatively charged glutamine in the FG loop of SSc patients compared to controls. Positional amino acid usage analysis of the FG loop of the TCRbeta chain revealed increased usage of leucine at position 108 with decreased usage of tyrosine, glutamine, and aspartate. Figure 1. A. CDR3 length distribution in SSc patients (SSc) and controls; B. CDR3 length distribution in control, HLA-DPB1*1301-, HLADPB1* 1301+ group; C. Number of unique clones in control, HLA-DPB1*1301-, HLA-DPB1*1301+ group; D. Proportion of TCR clonotype groups within frequency ranges: rare (0 to 10-5); small-(10-5 to 10-4); medium (10-4 to 10-3); large (10-3 to 10-2); and hyperexpanded (10-2 to 1).
Conclusion(s): This is the first study to report an association between HLA-II alleles and specific CDR3 composition in SSc patients. We examined the TCRbeta repertoire of a large number of AA SSc patients and identified differential V and J gene and FG-loop amino acid usage that correlated with the presence of a specific HLA-II allele. Hydrophobic amino acid usage in the FG loop of the TCRbeta chain has been reported to increase the avidity of TCR-MHC interaction and increased autoreactivity. Based on our findings, we can hypothesize that the TCRbeta sequences favored by the SSc-associated HLA-II alleles are involved in autoantigen recognition and autoimmunity. These results highlight the important role of HLA-II alleles and T cells in SSc pathogenesis
Method(s): Genomic DNA from 132 AA SSc patients from the GRASP consortium along with 50 AA healthy control samples were extracted and the TCRbeta chain was deep sequenced using the immunoSEQ assay (Adaptive Biotechnologies, USA). Data was analyzed using Immunarch to identify differences in unique clones, CDR3 length, V gene usage, J gene usage, and amino acid usage in the FG-Loop of the TCRbeta chain between the two SSc groups. Benjamini Hochberg FDR was used to correct for multiple testing.
Result(s): The CDR3 length was similar between SSc patients and controls (Figure 1A, B). The TCRbeta repertoire was clonally expanded in HLA-DPB1*13:01+ SSc patients as compared to patients who did not carry this allele (Figure 1C). The proportion of small and hyperexpanded TCRbeta clonotypes was increased in HLA-DPB1*13:01+ SSc patients (Figure 1D). Analysis of V gene and J gene usage identified statistically significantly increased usage of TRBV5-1, TRBV7-3, TRBJ2-1, and TRBJ2-2 genes and a decreased usage of TRBV6-1, TRBV6-4, TRBV6-5, TRBV25-1, and TRBJ1-5 genes in SSc patients compared to controls and the differences were statistically significant (Figure 2A, B). Overall amino acid usage of the FG loop of the TCRbeta chain (antigen binding region) identified increased usage of hydrophobic amino acids, leucine and valine, and reduced usage of negatively charged glutamine in the FG loop of SSc patients compared to controls. Positional amino acid usage analysis of the FG loop of the TCRbeta chain revealed increased usage of leucine at position 108 with decreased usage of tyrosine, glutamine, and aspartate. Figure 1. A. CDR3 length distribution in SSc patients (SSc) and controls; B. CDR3 length distribution in control, HLA-DPB1*1301-, HLADPB1* 1301+ group; C. Number of unique clones in control, HLA-DPB1*1301-, HLA-DPB1*1301+ group; D. Proportion of TCR clonotype groups within frequency ranges: rare (0 to 10-5); small-(10-5 to 10-4); medium (10-4 to 10-3); large (10-3 to 10-2); and hyperexpanded (10-2 to 1).
Conclusion(s): This is the first study to report an association between HLA-II alleles and specific CDR3 composition in SSc patients. We examined the TCRbeta repertoire of a large number of AA SSc patients and identified differential V and J gene and FG-loop amino acid usage that correlated with the presence of a specific HLA-II allele. Hydrophobic amino acid usage in the FG loop of the TCRbeta chain has been reported to increase the avidity of TCR-MHC interaction and increased autoreactivity. Based on our findings, we can hypothesize that the TCRbeta sequences favored by the SSc-associated HLA-II alleles are involved in autoantigen recognition and autoimmunity. These results highlight the important role of HLA-II alleles and T cells in SSc pathogenesis
EMBASE:639964779
ISSN: 2326-5205
CID: 5513162
The Clinical Signal-to-Noise Ratio of OCT Angiography: Key Applications for Routine Clinical Use [Comment]
PMID: 36084992
ISSN: 2468-6530
CID: 5332672
Validation of the New York University Langone Eye Test Application, a Smartphone-Based Visual Acuity Test
Purpose/UNASSIGNED:To validate and assess user satisfaction and usability of the New York University (NYU) Langone Eye Test application, a smartphone-based visual acuity (VA) test. Design/UNASSIGNED:Mixed-methods cross-sectional cohort study. Participants/UNASSIGNED:Two hundred forty-four eyes of 125 participants were included. All participants were adults 18 years of age or older. Participants' eyes with a VA of 20/400 (1.3 logarithm of the minimum angle of resolution [logMAR]) or worse were excluded. Methods/UNASSIGNED:Patients were tested using the clinical standard Rosenbaum near card and the NYU Langone Eye Test application on an iPhone and Android device. Each test was performed twice to measure reliability. Ten patients were selected randomly for subsequent semistructured qualitative interviews with thematic analysis. Main Outcome Measures/UNASSIGNED:Visual acuity was the parameter measured. Bland-Altman analysis was used to measure agreement between the results of the NYU Langone Eye Test application and Rosenbaum card, as well as test-retest reliability of each VA. The correlation between results was calculated using the intraclass correlation coefficient. Satisfaction survey and semistructured interview questions were developed to measure usability and acceptability. Results/UNASSIGNED:Bland-Altman analysis revealed an agreement between the application and the Rosenbaum near card of 0.017 ± 0.28 logMAR (iPhone) and 0.009 ± 0.29 logMAR (Android). The correlation between the application and the Rosenbaum near card was 0.74 for both the iPhone and Android. Test-retest reliability was 0.003 ± 0.22 logMAR (iPhone), 0.01 ± 0.25 logMAR (Android), and 0.01 ± 0.23 logMAR (Rosenbaum card). Of the 125 participants, 97.6% found the application easy to use, and 94.3% were overall satisfied with the application. Thematic analysis yielded 6 key themes: (1) weaknesses of application, (2) benefits of the application, (3) tips for application improvement, (4) difficulties faced while using the application, (5) ideal patient for application, and (6) comparing application with traditional VA testing. Conclusions/UNASSIGNED:The NYU Langone Eye Test application is a user-friendly, accurate, and reliable measure of near VA. The application's integration with the electronic health record, accessibility, and easy interpretation of results, among other features, make it ideal for telemedicine use.
PMCID:9560635
PMID: 36245756
ISSN: 2666-9145
CID: 5360102
The Impact of Repetitive and Prolonged Eye Rubbing on Corneal Biomechanics
PURPOSE/OBJECTIVE:To evaluate the effect of simulated repetitive eye rubbing on the corneal biomechanics of porcine eyes using an ex vivo model system. METHODS:The average rubbing force that patients with keratoconus apply to their eyelids was previously determined. Fresh porcine eyes with eyelids were either exposed to 10,500 rub cycles from a custom-built eye rubbing machine that rubbed with a similar force to knuckle human eye rubbing (n = 33) or no rubbing at all (control; n = 37). A total of 10,500 rubs are equivalent to 1 year of rubbing six times daily, five movements per rub. The corneal biomechanical properties of these eyes were then tested by measuring the elastic modulus of 5-mm strips. RESULTS:= .984). CONCLUSIONS:.
PMID: 36098386
ISSN: 1081-597x
CID: 5484832
Managing risk in the face of adversity: design and outcomes of rapid glaucoma assessment clinics during a pandemic recovery
BACKGROUND:The provision of timely care to the high volume of glaucoma patients stratified as "low risk" following pandemic-related appointment deferrals continues to prove challenging for glaucoma specialists. It is unknown whether stratification as "low risk" remains valid over time, raising the potential risk of harm during this period if left unmonitored. This study aimed to evaluate whether Rapid Glaucoma Assessment Clinics (RGACs) are an effective method of assessing "low-risk" patients in order to identify those who may need an escalation of care, therefore reducing the risk of the future incidents of preventable vision loss. METHODS:RGACs were developed which comprised a brief advance telephone history by a clinician and then ophthalmic technician-measured visual acuity and intraocular pressure in clinic. We report outcomes from the first month of operation describing attendance patterns, the proportion of patients from this "low risk" cohort requiring escalation and underlying reasons for treatment escalations. RESULTS:639 patients were invited to attend RGACs. 75% attended their booked appointment. Pre-attendance telephone consultations were associated with lower non-attendance rates (13.9% vs 29.3%, p < 0.00001). 15% of patients were no longer deemed to remain at "low risk" with further expedited clinical review scheduled. 10.4% of patients required an escalation in treatment following review. CONCLUSIONS:RGACs are an effective approach to deliver high throughput clinical assessments for large numbers of "low-risk" glaucoma patients with deferred appointments. They enable the rapid identification and treatment of patients who would otherwise face significantly delayed review reducing the risk of future preventable vision loss.
PMCID:8354099
PMID: 34376818
ISSN: 1476-5454
CID: 5497962
Is selective laser trabeculoplasty shifting the glaucoma treatment paradigm in developing countries? [Editorial]
PMID: 35568384
ISSN: 1468-2079
CID: 5498062
Adverse Effects and Safety in Glaucoma Patients: Agreement on Clinical Trial Outcomes for Reports on Eye Drops (ASGARD)-A Delphi Consensus Statement
PURPOSE:The purpose of this study is to establish consensus among experts on outcomes and methods to be used in clinical trials to assess adverse effects of anti-glaucomatous eye drops. DESIGN:Modified Delphi method. METHODS:Clinical experts from Europe, North America, South America, the Middle East, and Asia were invited to participate in 2 sequential web-based surveys administered from June 27 to August 29, 2021. A total of 91 clinical experts were invited to participate. Of these, 71 (78%) experts from 23 different countries accepted the invitation and answered the first questionnaire. The importance of items was ranked using a 10-point scale (1 as not important, 10 as very important). RESULTS:A total of 84 items were rated in round one by 71 participants. Of these, 68 (81%) reached consensus. In round 2, 19 items, including 3 additional items, were rated by 53 (75%) participants. Consensus was reached in 98% of investigated items. Eight outcomes were agreed as important to assess when conducting future trials: ocular surface, dryness, epithelial damage, local adverse effects related to eye drops as reported by patients, periocular surroundings and eyelids, quality of life questionnaires, hyperemia, visual acuity, tear film, and anterior chamber inflammation. CONCLUSION:We propose a consensus-based series of outcomes and assessment methods to be used in clinical trials assessing adverse effects of antiglaucomatous eye drops. This, we hope, will improve the comparability of results from future trials and thus facilitate meta-analyses and progress in this field.
PMID: 35594917
ISSN: 1879-1891
CID: 5498072
"Persistence of Memory" - Multimodal imaging of delayed sympathetic ophthalmia [Case Report]
PURPOSE/UNASSIGNED:To describe a case of late post-surgical sympathetic ophthalmia documented with multimodal imaging. OBSERVATIONS/UNASSIGNED:A 74-year-old male presented to the urgent care of the New York Eye and Ear Infirmary with blurry vision and discomfort in his left eye for three weeks. His vision was 20/50, with intraocular pressure of 13 mmHg, and slit lamp examination was significant for conjunctival congestion, 1+ anterior segment cell and flare, and diffuse keratic precipitates. His right eye was no light perception with a condensed hyphema, intraocular lens and inferonasal tube. His medical history included coronary artery bypass, prostate cancer, hyperlipidemia, and hypertension. His ocular history included blunt trauma to the right eye at age 11 with development of a traumatic macular hole and later rhegmatogenous retinal detachment at age 53, repaired with multiple vitreoretinal procedures. He developed glaucoma in the right eye and was treated with a tube shunt and ultimately transscleral cyclophotocoagulation (TSCPC) 7 years later, 13 years prior to his presentation of the left eye. Dilated fundus examination of his left eye revealed diffuse chorioretinal folds in the macula without any discrete chorioretinal lesions. Ultrasound of the right showed serous macular detachments with scleral thickening. Presumptive diagnosis of sympathetic ophthalmia was made and oral corticosteroid therapy was initiated. Subsequent SD-OCT and en-face OCT-A demonstrated Dalen-Fuchs nodules within the macula underlying areas of resolved serous detachment, after 6 weeks of oral steroids and initiation of immunomodulatory therapy (IMT). CONCLUSIONS/UNASSIGNED:Sympathetic ophthalmia may rarely present with very delayed onset, and TSCPC is an uncommon inciting event. These patients may develop serous detachment, choroidal folds and inflammatory nodules identifiable on exam and multimodal imaging, which can resolve when treated appropriately. OCT-A may provide utility in monitoring response to immunosuppressive treatment in these patients.
PMCID:9284322
PMID: 35845745
ISSN: 2451-9936
CID: 5532672
Annual review of genomics & human genetics. 2022:23:193-222.DOI: 10.1146/annurev-genom-083117-021702
Genetic Disorders of the Extracellular Matrix: From Cell and Gene Therapy to Future Applications in Regenerative Medicine
Metazoans have evolved to produce various types of extracellular matrix (ECM) that provide structural support, cell adhesion, cell-cell communication, and regulated exposure to external cues. Epithelial cells produce and adhere to a specialized sheet-like ECM, the basement membrane, that is critical for cellular homeostasis and tissue integrity. Mesenchymal cells, such as chondrocytes in cartilaginous tissues and keratocytes in the corneal stroma, produce a pericellular matrix that presents optimal levels of growth factors, cytokines, chemokines, and nutrients to the cell and regulates mechanosensory signals through specific cytoskeletal and cell surface receptor interactions. Here, we discuss laminins, collagen types IV and VII, and perlecan, which are major components of these two types of ECM. We examine genetic defects in these components that cause basement membrane pathologies such as epidermolysis bullosa, Alport syndrome, rare pericellular matrix-related chondrodysplasias, and corneal keratoconus and discuss recent advances in cell and gene therapies being developed for some of these disorders. Expected final online publication date for the Annual Review of Genomics and Human Genetics, Volume 23 is October 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
PMID: 35537467
ISSN: 1545-293x
CID: 5214312
Transepithelial Enhanced Fluence Pulsed Light M Accelerated Crosslinking for Early Progressive Keratoconus with Chemically Enhanced Riboflavin Solutions and Air Room Oxygen
PURPOSE/OBJECTIVE:transepithelial enhanced fluence pulsed light M accelerated crosslinking in the treatment of progressive keratoconus (KC) with chemically enhanced hyper-concentrated riboflavin solutions without iontophoresis and with air-room oxygenation. SETTING/METHODS:Siena Crosslinking Center, Siena, Italy. METHODS:ACXL (EFPL M TECXL). The 12 min and 58 s pulsed light (1 s on/1 s off) UV-A exposure treatments were performed with a biphasic corneal soaking using Paracel I 0.25% for 4 min and Paracel II 0.22% for 6 min riboflavin solutions and New KXL I UV-A emitter (Glaukos-Avedro, Waltham, USA) at an air room of 21% oxygenation. All patients completed the 3-year follow-up. RESULTS:CDVA showed a statistically significant improvement in the third postoperative month (Δ + 0.17 d. e.) with a final gain of +0.22 d. eq. AK showed a statistically significant decrease in the sixth postoperative month (Δ - 1.15 diopters). K itmax showed a statistically significant decrease at 1-year follow-up (Δ - 1.3 diopters). The coma value improved significantly by the sixth month (Δ - 0.54 µm). MCT remained stable during the entire follow-up. No adverse events were recorded. Corneal OCT revealed a mean demarcation line depth at 282.6 ± 23.6 μm. CONCLUSIONS:Transepithelial enhanced fluence pulsed light M accelerated crosslinking with chemically enhanced riboflavin solution halted KC progression in young adult patients without iontophoresis and no intraoperative oxygen supplementation addressing the importance of increased fluence.
PMCID:9457355
PMID: 36078972
ISSN: 2077-0383
CID: 5484822
Malpractice Cases Arising From Telephone Based Telemedicine Triage in Ophthalmology
PURPOSE/UNASSIGNED:To determine the allegation, precipitating medical issue, and outcome of telephone triage focused malpractice litigation among ophthalmologists. METHODS/UNASSIGNED:The WestLaw Edge database was reviewed using terms pertaining to ophthalmology and telemedicine. The search ranged from 4/7/30 to 1/25/22. RESULTS/UNASSIGNED:Of the 510 lawsuits, 3.5% (18/510) met inclusion criteria. 94.5% (17/18) alleged delays in evaluation and/or treatment. 61.1% (11/18) alleged incorrect diagnoses, 38.9% (7/18) claimed improper discussion of risks or informed consent, and 5.6% (1/18) alleged delayed referrals. The precipitating medical issues included retinal detachment in 33.3% (6/18) of cases, post-procedure and post-trauma endophthalmitis in 33.3% (6/18) of cases, ocular trauma without endophthalmitis in 22.2% (4/18) of cases, and bilateral acute retinal necrosis and allergic reactions each accounting for 5.6% (1/18) of cases. CONCLUSION/UNASSIGNED:Telephone triage creates potential malpractice litigation. Delay in in-person clinical evaluation and alleged failure to inform patients of possible irreversible vision loss may lead to potential malpractice litigation. We suggest offering the option of same day in person evaluation and informing the patient how delay may lead to irreversible vision loss.
PMID: 35980308
ISSN: 1744-5205
CID: 5300092
Towards a better understanding of non-exudative choroidal and macular neovascularization
Non-exudative macular and choroidal neovascularization (MNV and CNV) usually refers to the entity of treatment-naïve type 1 neovascularization in the absence of associated signs of exudation. Histopathological studies, dating back in the early 70s, identified the presence of non-exudative MNV, but the first clinical report of this finding was in the late 90s using indocyanine green angiography in eyes with age-related macular degeneration (AMD). With more advanced retinal imaging, there has been an ever increasing appreciation of non-exudative MNV associated with AMD and CNV with other macular disorders. However, consensus regarding the exact definition and the clinical management of this entity is lacking. Furthermore, there may be variation in the imaging features and clinical course suggesting that a spectrum of disease may exist. Herein, we review the large body of published work that has provided a better understanding of non-exudative MNV and CNV in the last decade. The prevalence, multimodal imaging features, clinical course, and response to treatment are discussed to elucidate further key insights about this entity. Based on these observations, this review also proposes a new theory about the origin and course of different sub-types of non-exudative MNV/CNV which can have different etiologies and pathways according to the clinical context of disease.
PMID: 35970724
ISSN: 1873-1635
CID: 5299832
The Effect of Sample Medication Use on Subsequent Anti-VEGF Agent Selection for Neovascular Age-Related Macular Degeneration
PURPOSE/UNASSIGNED:Medication samples of anti-VEGF agents can represent a good option for retina specialists to provide timely treatment for newly converted neovascular age-related macular degeneration (nvAMD) while prior-authorizations (PA) are pending. Our study examines the effect of medication sample use (ranibizumab or aflibercept) on future anti-vascular endothelial growth factor (VEGF) agent selection in nvAMD. DESIGN/UNASSIGNED:Retrospective cohort study. PARTICIPANTS/UNASSIGNED:nvAMD patients who underwent an initial anti-VEGF injection with a sample medication were compared to nvAMD control patients who never received a medication sample. METHODS/UNASSIGNED:Charts from 2017 through 2020 were reviewed for data regarding demographics, anti-VEGF agent selection, and visual acuity outcomes for both groups. The utilization of different anti-VEGF agents in each group was compared at various time points using chi-square tests for independence of proportions. MAIN OUTCOME MEASURES/UNASSIGNED:Anti-VEGF agent selection for the first four injections and at one year were examined. RESULTS/UNASSIGNED:injection, and 1 year) in sample (96.2%, 95.9%, 91.9%, 93.4%, respectively), and control groups (98.1%, 94.2%, 94.9%, 87.8%, respectively). Bevacizumab usage was significantly lower among eyes receiving samples relative to controls at the second (1.9% vs. 38.7%, p <Â .001), third (3.1% vs. 41.3%, p <Â .001), fourth injections (4.7% vs. 40.4%, p <Â .001), and at 1 year (0% vs. 33.8%, p <Â .001). Aflibercept usage was significantly higher in sample eyes relative to controls at the second (78.3% vs. 43.4%, p <Â .001), third (76.3% vs. 41.5%, p <Â .001), and fourth injections (76.7% vs. 43.4%, p <Â .001), and at 1 year (77.0% vs. 52.7%, p <Â .001). CONCLUSIONS/UNASSIGNED:Sample medications in nvAMD may be initiated for many reasons, including awaiting PA approval. Our study found that eyes receiving a sample anti-VEGF agent (ranibizumab or aflibercept) for their initial injection were less likely to receive bevacizumab at future visits relative to eyes that did not receive an anti-VEGF sample, even after one year of treatment. Given the persistent use of more expensive medications at subsequent injections for patients who were initiated on samples, insurance payors may consider waiving PA requirements for bevacizumab to avoid a paradoxical increase in health-care costs.
PMID: 35923110
ISSN: 1744-5205
CID: 5288152
Topical Glaucoma Therapy Is Associated With Alterations of the Ocular Surface Microbiome
Purpose:To investigate the ocular surface microbiome of patients with unilateral or asymmetric glaucoma being treated with topical ophthalmic medications in one eye and to determine whether microbial community changes were related to measures of ocular surface disease. Methods:V3-V4 16S rRNA sequencing was conducted on ocular surface swabs collected from both eyes of 17 subjects: 10 patients with asymmetric/unilateral glaucoma using topical glaucoma therapy on only one eye and seven age-matched, healthy controls with no history of ocular disease or eyedrop use. Samples were categorized into three groups: patients' glaucomatous eye treated with eyedrops, patients' contralateral eye without eyedrops, and healthy control eyes. Comparisons were made for microbial diversity and composition, with differences in composition tested for association with ocular surface disease measures including tear meniscus height, tear break-up time, and Dry Eye Questionnaire. Results:Samples obtained from the patients' treated and untreated eyes both had significantly greater alpha-diversity and relative abundance of gram-negative organisms compared to healthy controls. The microbial composition of patient eyes was associated with decreased tear meniscus height and tear break-up time, whereas metagenomic predictions, based on 16S rRNA data, suggested increased synthesis of lipopolysaccharide. Conclusions:The ocular surface microbiome of patients taking unilateral preserved glaucoma drops is characterized by a highly diverse array of gram-negative bacteria that is significantly different from the predominantly gram-positive microbes detected on healthy control eyes. These compositional differences were associated with decreased tear film measures and distinct inferred protein synthesis pathways, suggesting a potential link between microbial alterations and ocular surface inflammation.
PMCID:9434984
PMID: 36036910
ISSN: 1552-5783
CID: 5332022
Subcellular Comparison of Visible-Light Optical Coherence Tomography and Electron Microscopy in the Mouse Outer Retina
Purpose/UNASSIGNED:We employed in vivo, 1.0-µm axial resolution visible-light optical coherence tomography (OCT) and ex vivo electron microscopy (EM) to investigate three subcellular features in the mouse outer retina: reflectivity oscillations inner to band 1 (study 1); hyperreflective band 2, attributed to the ellipsoid zone or inner segment/outer segment (IS/OS) junction (study 2); and the hyperreflective retinal pigment epithelium (RPE) within band 4 (study 3). Methods/UNASSIGNED:Pigmented (C57BL/6J, n = 10) and albino (BALB/cJ, n = 3) mice were imaged in vivo. Enucleated eyes were processed for light and electron microscopy. Using well-accepted reference surfaces, we compared micrometer-scale axial reflectivity of visible-light OCT with subcellular organization, as revealed by 9449 annotated EM organelles and features across four pigmented eyes. Results/UNASSIGNED:In study 1, outer nuclear layer reflectivity peaks coincided with valleys in heterochromatin clump density (-0.34 ± 2.27 µm limits of agreement [LoA]). In study 2, band 2 depth on OCT and IS/OS junction depth on EM agreed (-0.57 ± 0.76 µm LoA), with both having similar distributions. In study 3, RPE electron dense organelle distribution did not agree with reflectivity in C57BL/6J mice, with OCT measures of RPE thickness exceeding those of EM (2.09 ± 0.89 µm LoA). Finally, RPE thickness increased with age in pigmented mice (slope = 0.056 µm/mo; P = 6.8 × 10-7). Conclusions/UNASSIGNED:Visible-light OCT bands arise from subcellular organization, enabling new measurements in mice. Quantitative OCT-EM comparisons may be confounded by hydration level, particularly in the OS and RPE. Caution is warranted in generalizing results to other species.
PMID: 35943734
ISSN: 1552-5783
CID: 5286842
Open-Angle Glaucomatous Optic Neuropathy is Related to Dips Rather than Increases in the Mean Arterial Pressure Over 24-H
BACKGROUND:Mean arterial pressure (MAP) drives ocular perfusion. Excessive 24-h MAP variability relates to glaucoma, however, whether this is due to dips or increases in the blood pressure (BP) is undocumented. We investigated the association of open-angle glaucoma (OAG) in relation to the five largest MAP dips/increases over 24-h, henceforth called dips/blips. METHODS:In the Maracaibo Aging Study (MAS), 93 participants aged ≥40y (women, 87.1%; mean age, 61.9y) underwent baseline ophthalmological and 24-h ambulatory BP monitoring assessments. OAG was the presence of optic nerve damage and visual field defects. Statistical methods included logistic regression and the generalized R2 statistic. For replication, 48 OAG cases at the Leuven Glaucoma Clinic were matched with 48 controls recruited from Flemish population. RESULTS:In MAS, 26 had OAG. OAG compared to non-OAG participants experienced longer and deeper dips (116.5 vs. 102.7 minutes; to 60.3 vs. 66.6 mmHg; 21.0 vs. 18.0 mmHg absolute or 0.79 vs. 0.81 relative dip compared to the preceding reading). The adjusted odds ratios associated with dip measures ranged from 2.25 (95% confidence interval [CI], 1.31-4.85; P=0.009) to 3.39 (95% CI, 1.368.46; P=0.008). On top of covariables and 24MAP level/variability, the dip measures increased the model performance (P≤0.025). Blips did not associate with OAG. The casecontrol study replicated the MAS observations. CONCLUSIONS:Dips rather than increases in the 24-h MAP level were associated with increased risk for OAG. An ophthalmological examination combined with 24h BP monitoring might be precautious steps required in normotensive and hypertensive patients at risk of OAG.
PMID: 35218651
ISSN: 1941-7225
CID: 5172652
Energy Dose-Response in Selective Laser Trabeculoplasty: A Review
PRCIS:A literature review of selective laser trabeculoplasty (SLT) energy dose-response found no definitive relationship between intraocular pressure (IOP) reduction with respect to total or pulse energy, race, pigmentation, or application pattern. PURPOSE:SLT is a safe and effective treatment for lowering IOP. Although evidence is mounting for the advantage of its use as a first-line treatment for IOP reduction, the SLT procedures in use vary widely. The purpose of this literature review was to investigate whether there were any relationships between SLT energy and efficacy for lowering IOP in the published literature. METHODS:A literature review was undertaken that included studies in which energy levels required for successful SLT treatment were investigated: in general, with respect to angle pigmentation, race or ethnicity, and treatment arc extent. RESULTS:There was no indication that higher (or lower) energy used in the treatment leads to greater (or less) IOP reduction. Similar results were obtained regarding the level of trabecular meshwork pigmentation. Race was not found to be associated with altered dose response in SLT. There were indications that treating the full 360 degrees, as opposed to smaller arcs, could be beneficial for more IOP reduction. IOP reduction from SLT was found to be similar to that provided by topical medications. CONCLUSIONS:The optimal energy level of SLT needed for IOP reduction has not yet been definitively established, with all reported pulse energies resulting in similar IOP reduction. Furthermore, similar lack of conclusive findings exists regarding optimal SLT energy dosage for use in different races and degrees of trabecular meshwork pigmentation. This parameter and each of the abovementioned factors requires further research.
PMCID:9362340
PMID: 35701875
ISSN: 1536-481x
CID: 5498082
Furthering the Adoption of Digital Imaging and Communications in Medicine Standards in Ophthalmology
PMID: 35737399
ISSN: 2168-6173
CID: 5282082
Repeated High-Fluence Accelerated Slitlamp-Based Photoactivated Chromophore for Keratitis Corneal Cross-Linking for Treatment-Resistant Fungal Keratitis [Case Report]
PURPOSE/OBJECTIVE:The purpose of this study was to report a case of fungal keratitis resistant to standard-of-care antimicrobial treatment and successful resolution, thanks to the repeated high-fluence accelerated photoactivated chromophore for keratitis-corneal cross-linking (PACK-CXL). METHODS:This was a case report. RESULTS:A 79-year-old male patient with previous Descemet membrane endothelial keratoplasty presented with a corneal ulcer that was resistant to topical antimicrobial therapy and amniotic membrane placement. Fungal keratitis was diagnosed, and the cornea was on the verge of perforation. After over a month of topical and systemic therapy without marked improvement, the patient underwent 2 repeated high-fluence accelerated CXL procedures (7.2 J/cm2 using a UV irradiation of 30 mW/cm2 for 4 minutes) over an interval of 8 days (accumulated fluence of 14.4 J/cm2), which resulted in significant clinical improvement, with consolidation into a quiescent scar. CONCLUSIONS:PACK-CXL protocols delivering a total UV fluence of 5.4 J/cm2 (as per the original Dresden protocol for corneal ectasia cross-linking) can be an effective primary therapy for initial or superficial corneal infections because approximately half of the energy is absorbed in the first 100 μm of a riboflavin-soaked cornea. However, fungal keratitis may require higher fluences than 5.4 J/cm2 because, unlike ectatic corneas, corneal ulcers are not transparent, and the infection may involve deep stroma. This case illustrates how repeated high-fluence accelerated PACK-CXL can be used to successfully treat fungal keratitis resistant to conventional topical and systemic medications.
PMID: 35830582
ISSN: 1536-4798
CID: 5484792
Graefe's archive for clinincal & experimental ophthalmology. 2022:260(8):2437-2447.DOI: 10.1007/s00417-022-05586-w
Macular neovascularization lesion type and vision outcomes in neovascular age-related macular degeneration: post hoc analysis of HARBOR
PURPOSE/OBJECTIVE:To characterize relationships between Consensus on Neovascular Age-Related Macular Degeneration Nomenclature (CONAN) Study Group classifications of macular neovascularization (MNV) and visual responses to ranibizumab in patients with neovascular age-related macular degeneration (nAMD). METHODS:This was a post hoc analysis of the phase 3 HARBOR trial of ranibizumab in nAMD. Analyses included ranibizumab-treated eyes with baseline multimodal imaging data; baseline MNV; subretinal and/or intraretinal fluid at screening, baseline, or week 1; and spectral-domain optical coherence tomography images through month 24 (n = 700). Mean best-corrected visual acuity (BCVA) over time and mean BCVA change at months 12 and 24 were compared between eyes with type 1, type 2/mixed type 1 and 2 (type 2/M), and any type 3 MNV at baseline. RESULTS:At baseline, 263 (37.6%), 287 (41.0%), and 150 (21.4%) eyes had type 1, type 2/M, and any type 3 lesions, respectively. Type 1 eyes had the best mean BCVA at baseline (59.0 [95% CI: 57.7-60.3] letters) and month 24 (67.7 [65.8-69.6] letters), whereas type 2/M eyes had the worst (50.0 [48.6-51.4] letters and 60.8 [58.7-62.9] letters, respectively). Mean BCVA gains at month 24 were most pronounced for type 2/M eyes (10.8 [8.9-12.7] letters) and similar for type 1 (8.7 [6.9-10.5] letters) and any type 3 eyes (8.3 [6.3-10.3] letters). CONCLUSION/CONCLUSIONS:Differences in BCVA outcomes between CONAN lesion type subgroups support the use of an anatomic classification system to characterize MNV and prognosticate visual responses to anti-vascular endothelial growth factor therapy for nAMD. TRIAL REGISTRATION/BACKGROUND:ClinicalTrials.gov identifier: NCT00891735. Date of registration: April 29, 2009.
PMCID:8891431
PMID: 35239009
ISSN: 1435-702x
CID: 5174592
Advanced retinal imaging and applications for clinical practice: A consensus review
Imaging is an integral part of the evaluation and management of retinal disorders. Each imaging modality has its own unique capabilities and can show a different aspect or perspective of disease. Multimodal retinal imaging provides a wealth of substantive and insightful information; however, the integration of all this complex data can be overwhelming. We discuss the applications and the strengths and limitations of the many different retinal imaging tools that are approved for clinical use. These modalities include color fundus photography, widefield imaging, fundus autofluorescence, near infrared reflectance, optical coherence tomography angiography, and en face optical coherence tomography. We also cover the advantages and disadvantages of a multimodal approach.
PMID: 35183611
ISSN: 1879-3304
CID: 5174972
American journal of obstetrics & gynecology. 2022:227(2):259.e1-259.e14.DOI: 10.1016/j.ajog.2022.01.019
Cell-free DNA screening for trisomies 21, 18 and 13 in pregnancies at low and high risk for aneuploidy with genetic confirmation
BACKGROUND:Cell-free DNA (cfDNA) non-invasive prenatal screening for trisomy (T) 21, 18, and 13 has been rapidly adopted into clinical practice. However, prior studies are limited by lack of follow up genetic testing to confirm outcomes and accurately assess test performance, particularly in women at low-risk for aneuploidy. OBJECTIVE:To compare the performance of cfDNA screening for T21, T18 and T13 between women at low and high-risk for aneuploidy in a large, prospective cohort with genetic confirmation of results. STUDY DESIGN/METHODS:A multicenter prospective observational study at 21 centers in 6 countries. Women who had SNP-based cfDNA screening for T21, T18 and T13 were enrolled. Genetic confirmation was obtained from prenatal or newborn DNA samples. Test performance and test failure (no-call) rates were assessed for the cohort and women with low and high prior risk for aneuploidy were compared. An updated cfDNA algorithm, blinded to pregnancy outcome, was also assessed. RESULTS:20,194 were enrolled at median gestational age of 12.6 weeks (IQR:11.6, 13.9). Genetic outcomes were confirmed in 17,851 (88.4%): 13,043 (73.1%) low-risk and 4,808 (26.9%) high-risk for aneuploidy. Overall, 133 trisomies were diagnosed (100 T21; 18 T18; 15 T13). cfDNA screen positive rate was lower in low- vs. high-risk (0.27% vs. 2.2%, p<0.0001). Sensitivity and specificity were similar between groups. The positive predictive value (PPV) for the low and high-risk groups was 85.7% vs. 97.5%, p=0.058 for T21; 50.0% vs. 81.3%, p=0.283 for T18; and 62.5% vs. 83.3, p=0.58 for T13, respectively. Overall, 602 (3.4%) patients had no-call result after the first draw and 287 (1.61%) after including cases with a second draw. Trisomy rate was higher in the 287 with no-call results than patients with a result on a first draw (2.8% vs. 0.7%, p=0.001). The updated algorithm showed similar sensitivity and specificity to the study algorhitm with a lower no-call rate. CONCLUSIONS:In women at low-risk for aneuploidy, SNP-based cfDNA has high sensitivity and specificity, PPV of 85.7% for T21 and 74.3% for the three common trisomies. Patients who receive a no-call result are at increased risk of aneuploidy and require additional investigation.
PMID: 35085538
ISSN: 1097-6868
CID: 5154712
Artificial Intelligence for Glaucoma: Creating and Implementing AI for Disease Detection and Progression
On September 3rd, 2020, the Collaborative Community on Ophthalmic Imaging (CCOI) conducted its first two-day virtual workshop on the role of artificial intelligence (AI) and related machine learning (ML) techniques for the diagnosis and treatment of various ophthalmic conditions. In a session entitled, "Artificial Intelligence For Glaucoma", a panel of glaucoma specialists, researchers, industry experts, and patients convened to share current research on the application of AI to commonly used diagnostic modalities including fundus photography, optical coherence tomography imaging, standard automated perimetry, and gonioscopy. The conference participants focused on the use of AI as a tool for disease prediction, highlighted its ability to address inequalities, and presented the limitations and challenges to its real-world clinical application. The panelists' discussion addressed AI and health equities from the clinical, societal and regulatory perspectives.
PMID: 35218987
ISSN: 2589-4196
CID: 5172692
Advanced Congenital Glaucoma with Corneal Staphyloma
PMID: 35788339
ISSN: 2589-4196
CID: 5280212
Reply [Letter]
PMID: 35798668
ISSN: 2589-4196
CID: 5280592
Medical Malpractice Lawsuits Involving Urology Trainees
OBJECTIVES/OBJECTIVE:To distinguish the various characteristics of medical malpractice lawsuits involving trainees to prevent future litigation. METHODS:LexisNexis, an online legal research database containing legal records from the United States, was retrospectively reviewed for malpractice cases involving urology interns, residents, or fellows from January 1, 1988, to December 31, 2020. RESULTS:A total of 16 cases were included, of which 7 (43.8%) involved urological allegations while 9 (56.2%) involved non-urological allegations. Five of the cases consisting of non-urological adverse outcomes led to mortality. Procedural error was claimed in 12 (75.0%) cases, negligence in 7 (43.8%), delayed evaluation in 6 (37.5%), lack of informed consent of procedure or complications in 5 (31.2.%), failure to pursue treatment in 4 (25.0%), inexperienced trainee in 2 (12.5%), failure to supervise trainee in 2, lack of informed consent of trainee involvement in 1, incorrect diagnosis in 1, and prolonged operative time in 1 case. CONCLUSIONS:Malpractice education, careful supervision, awareness during perioperative care, and detailed communication between patients and physicians should be highlighted in training programs to improve patient outcomes and mitigate risk of future malpractice.
PMID: 35093401
ISSN: 1527-9995
CID: 5153272
Optical imaging and spectroscopy for the study of the human brain: status report
This report is the second part of a comprehensive two-part series aimed at reviewing an extensive and diverse toolkit of novel methods to explore brain health and function. While the first report focused on neurophotonic tools mostly applicable to animal studies, here, we highlight optical spectroscopy and imaging methods relevant to noninvasive human brain studies. We outline current state-of-the-art technologies and software advances, explore the most recent impact of these technologies on neuroscience and clinical applications, identify the areas where innovation is needed, and provide an outlook for the future directions.
PMCID:9424749
PMID: 36052058
ISSN: 2329-423x
CID: 5337852
Single Administration of Intracameral Bimatoprost Implant 10 µg in Patients with Open-Angle Glaucoma or Ocular Hypertension
INTRODUCTION/BACKGROUND:This study evaluated the intraocular pressure (IOP)-lowering efficacy and safety of a single intracameral administration of bimatoprost implant 10 µg in adults with open-angle glaucoma or ocular hypertension. METHODS:Two identically designed, randomized, 20-month, parallel-group, phase 3 clinical trials (one study eye/patient) compared three administrations of 10- or 15-µg bimatoprost implant (day 1, weeks 16 and 32) with twice-daily topical timolol maleate 0.5%. An open-label, 24-month, phase 1/2 clinical trial compared one or two implants administered in the study eye with once-daily topical bimatoprost 0.03% in the fellow eye. Separate analyses of the pooled phase 3 and phase 1/2 study datasets evaluated outcomes in the 10-µg bimatoprost implant and comparator treatment arms after a single implant administration, up to the time of implant re-administration or rescue with IOP-lowering medication. RESULTS:In the phase 3 studies, 10-µg bimatoprost implant single administration demonstrated IOP reductions (hour 0) of 4.9-7.0 mmHg through week 15 from a mean (standard deviation, SD) baseline IOP of 24.5 (2.6) mmHg (n = 374); IOP in the topical timolol BID group was reduced by 6.0-6.3 mmHg from a mean (SD) baseline IOP of 24.5 (2.6) mmHg (n = 373). In the phase 1/2 study (n = 21), median time to use of additional IOP-lowering treatment (Kaplan-Meier analysis) was 273 days (approximately 9 months), and 5 of 21 enrolled patients (23.8%) required no additional IOP-lowering treatment up to 24 months after single administration. In each study, after a single implant administration there were no reports of corneal edema, corneal endothelial cell loss, or corneal touch, and no patients had 20% or greater loss in corneal endothelial cell density. CONCLUSIONS:Bimatoprost implant single administration lowers IOP and has a favorable safety profile. Additional studies are needed to further evaluate the duration of effect and factors predicting long-term IOP lowering after a single implant administration. TRIAL REGISTRATION NUMBERS/BACKGROUND:ClinicalTrials.gov NCT02247804, NCT02250651, and NCT01157364.
PMCID:9253216
PMID: 35643967
ISSN: 2193-8245
CID: 5333742
Association of Mood Disorders, Substance Abuse, and Anxiety Disorders in Children and Teens With Serious Structural Eye Diseases
PURPOSE:We sought to evaluate the association between 5 eye diseases (including glaucoma, cataract, congenital optic nerve disease, congenital retinal disease, and blindness/low vision) and mental illness in a pediatric population. DESIGN:Cross-sectional study. METHODS:A de-identified commercial insurance claims database, OptumLabs Data Warehouse, between January 1, 2007, and December 31, 2018, was used. Children and teens less than 19 years of age at the time of eye diagnosis were included. Demographics and mental illness claims were compared, looking at the association of mental illness and eye disease claims. RESULTS:A total of 11,832,850 children and teens were included in this study with mean age of 8.04 ± 5.94 years at the first claim. Of the patients with at least 1 of the 5 eye diseases (n = 180,297), 30.5% had glaucoma (n = 54,954), 9.5% had cataract (n = 17,214), 21.4% had congenital optic nerve disease (n = 38,555), 26.9% had congenital retinal disease (n = 48,562), and 25.9% had blindness or low vision (n = 46,778). There was a statistically significant association, after adjusting for confounding variables, between at least 1 of the 5 eye diseases and schizophrenia disorder (OR = 1.54, 95% CI = 1.48-1.61, P < .001), anxiety disorder (OR = 1.45, 95% CI = 1.43-1.48, P < .001), depressive disorder (OR = 1.27, 95% CI = 1.25-1.29, P < .001), and bipolar disorder (OR = 1.27, 95% CI = 1.21-1.31, P < .001), but a reversed association with substance use disorder (OR = 0.88, 95% CI = 0.86-0.90, P < .001). CONCLUSIONS:We found associations between eye disease in children and teens and mental illness. Understanding these relationships may improve mental illness screening and treatment in the pediatric population.
PMID: 35314189
ISSN: 1879-1891
CID: 5533812
Use of Porcine Urinary Bladder Matrix in Socket Reconstruction After Pediatric Orbital Exenteration
Reconstruction options after orbital exenteration can be challenging, time-consuming, and require intensive postoperative care. Engineered dermal acellular matrices offer a quick and easy option for wound healing that has proven to be successful in various settings. Specifically, the porcine urinary bladder matrix has demonstrated success in periocular and orbital wound healing. This report describes a pediatric patient who underwent repair with porcine urinary bladder matrix after orbital exenteration for recurrent alveolar rhabdomyosarcoma. The patient did not require any additional reconstructive procedures. To our knowledge, this is the youngest patient to receive a porcine urinary bladder matrix after exenteration.
PMID: 35420582
ISSN: 1537-2677
CID: 5533982
Response to Miles Kiernan Re: a rare case of mucoepidermoid carcinoma ex pleomorphic adenoma of the lacrimal gland [Case Report]
Our goal is to contribute to the medical literature with our case of CEPA and hope to better help fellow clinicians diagnose and treat these rare tumors.
PMID: 35635140
ISSN: 1744-5108
CID: 5534002
Neurovascular injury with complement activation and inflammation in COVID-19
The underlying mechanisms by which severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) leads to acute and long-term neurological manifestations remains obscure. We aimed to characterize the neuropathological changes in patients with coronavirus disease 2019 and determine the underlying pathophysiological mechanisms. In this autopsy study of the brain, we characterized the vascular pathology, the neuroinflammatory changes and cellular and humoral immune responses by immunohistochemistry. All patients died during the first wave of the pandemic from March to July 2020. All patients were adults who died after a short duration of the infection, some had died suddenly with minimal respiratory involvement. Infection with SARS-CoV-2 was confirmed on ante-mortem or post-mortem testing. Descriptive analysis of the pathological changes and quantitative analyses of the infiltrates and vascular changes were performed. All patients had multifocal vascular damage as determined by leakage of serum proteins into the brain parenchyma. This was accompanied by widespread endothelial cell activation. Platelet aggregates and microthrombi were found adherent to the endothelial cells along vascular lumina. Immune complexes with activation of the classical complement pathway were found on the endothelial cells and platelets. Perivascular infiltrates consisted of predominantly macrophages and some CD8+ T cells. Only rare CD4+ T cells and CD20+ B cells were present. Astrogliosis was also prominent in the perivascular regions. Microglial nodules were predominant in the hindbrain, which were associated with focal neuronal loss and neuronophagia. Antibody-mediated cytotoxicity directed against the endothelial cells is the most likely initiating event that leads to vascular leakage, platelet aggregation, neuroinflammation and neuronal injury. Therapeutic modalities directed against immune complexes should be considered.
PMID: 35788639
ISSN: 1460-2156
CID: 5280222
Leptin promotes striatal dopamine release via cholinergic interneurons and regionally distinct signaling pathways
Dopamine (DA) is a critical regulator of striatal network activity and is essential for motor activation and reward-associated behaviors. Previous work has shown that DA is influenced by the reward value of food, as well as by hormonal factors implicated in the regulation of food intake and energy expenditure. Changes in striatal DA signaling also have been linked to aberrant eating patterns. Here we test the effect of leptin, an adipocyte-derived hormone involved in feeding and energy homeostasis regulation, on striatal DA release and uptake. Immunohistochemical evaluation identified leptin receptor expression throughout mouse striatum, including on striatal cholinergic interneurons and their extensive processes. Using fast-scan cyclic voltammetry, we found that leptin causes a concentration-dependent increase in evoked extracellular DA concentration ([DA]o) in dorsal striatum and nucleus accumbens (NAc) core and shell in male mouse striatal slices, and also an increase in the rate of DA uptake. Further, we found that leptin increases cholinergic interneuron excitability, and that the enhancing effect of leptin on evoked [DA]o is lost when nicotinic acetylcholine (ACh) receptors are antagonized or when examined in striatal slices from mice lacking ACh synthesis. Evaluation of signaling pathways underlying leptin's action revealed a requirement for intracellular Ca2+, and the involvement of different downstream pathways in dorsal striatum and NAc core versus NAc shell. These results provide the first evidence for dynamic regulation of DA release and uptake by leptin within brain motor and reward pathways, and highlight the involvement of cholinergic interneurons in this process.SIGNIFICANCE STATEMENTGiven the importance of striatal dopamine in reward, motivation, motor behavior and food intake, identifying the actions of metabolic hormones on dopamine release in striatal subregions should provide new insight into factors that influence dopamine-dependent motivated behaviors. We find that one of these hormones, leptin, boosts striatal dopamine release through a process involving striatal cholinergic interneurons and nicotinic acetylcholine receptors. Moreover, we find that the intracellular cascades downstream from leptin receptor activation underlying enhanced dopamine release differ among striatal subregions. Thus, we not only show that leptin regulates dopamine release, but also identify characteristics of this process that could be harnessed to alter pathological eating behaviors.
PMID: 35906070
ISSN: 1529-2401
CID: 5277032
A New Postoperative Regimen after CXL and PRK Using Topical NSAID and Steroids on the Open Ocular Surface
Corneal epithelium removal during photorefractive keratotomy (PRK), TransPRK, or corneal cross-linking (CXL) means that patients experience pain and inflammation after the procedure, which need to be carefully managed with topical drug regimens. One highly effective class of topical analgesics is non-steroidal anti-inflammatory drugs (NSAIDs), but these must be used carefully, as their use has been associated with delayed re-epithelialization and, in rare cases, corneal melting. However, our clinical experience has been that the concomitant use of topical corticosteroids obviates this risk. Here, we present a mechanistic explanation for our observations, our TransPRK and epithelium-off CXL protocols, and the postoperative medication regimens where topical NSAIDs are used in combination with topical steroid therapy during the first two postoperative days (where pain and inflammation levels are the highest). We detail the results of a single-center retrospective case analysis that examined eyes that underwent TransPRK (n = 301) or epithelium-off CXL (n = 576). Topical NSAID use in the first two postoperative days to control pain and inflammation after PRK/TransPRK or epithelium-off CXL, when used in combination with topical steroid therapy, does not appear to be associated with corneal melting or delayed epithelial healing. This approach may represent an improvement over current methods of handling post-surgical pain in procedures that require corneal epithelial debridement.
PMCID:9315572
PMID: 35887874
ISSN: 2077-0383
CID: 5484812
Treatment and prevention of pathological mitochondrial dysfunction in retinal degeneration and in photoreceptor injury
Pathological deterioration of mitochondrial function is increasingly linked with multiple degenerative illnesses as a mediator of a wide range of neurologic and age-related chronic diseases, including those of genetic origin. Several of these diseases are rare, typically defined in the United States as an illness affecting fewer than 200,000 people in the U.S. population, or about one in 1600 individuals. Vision impairment due to mitochondrial dysfunction in the eye is a prominent feature evident in numerous primary mitochondrial diseases and is common to the pathophysiology of many of the familiar ophthalmic disorders, including age-related macular degeneration, diabetic retinopathy, glaucoma and retinopathy of prematurity - a collection of syndromes, diseases and disorders with significant unmet medical needs. Focusing on metabolic mitochondrial pathway mechanisms, including the possible roles of cuproptosis and ferroptosis in retinal mitochondrial dysfunction, we shed light on the potential of α-lipoyl-L-carnitine in treating eye diseases. α-Lipoyl-L-carnitine is a bioavailable mitochondria-targeting lipoic acid prodrug that has shown potential in protecting against retinal degeneration and photoreceptor cell loss in ophthalmic indications.
PMID: 35835206
ISSN: 1873-2968
CID: 5269372
A Pixel-Based Machine-Learning Model For Three-Dimensional Reconstruction of Vitreous Anatomy
Purpose/UNASSIGNED:To develop a machine-learning image processing model for three-dimensional (3D) reconstruction of vitreous anatomy visualized with swept-source optical coherence tomography (SS-OCT). Methods/UNASSIGNED:Healthy subjects were imaged with SS-OCT. Scans of sufficient quality were transferred into the Fiji is just ImageJ image processing toolkit, and proportions of the resulting stacks were adjusted to form cubic voxels. Image-averaging and Trainable Weka Segmentation using Sobel and variance edge detection and directional membrane projections filters were used to enhance and interpret the signals from vitreous gel, liquid spaces within the vitreous, and interfaces between the former. Two classes were defined: "Septa" and "Other." Pixels were selected and added to each class to train the classifier. Results were generated as a probability map. Thresholding was performed to remove pixels that were classified with low confidence. Volume rendering was performed with TomViz. Results/UNASSIGNED:Forty-seven eyes of 34 healthy subjects were imaged with SS-OCT. Thirty-four cube scans from 25 subjects were of sufficient quality for volume rendering. Clinically relevant vitreous features including the premacular bursa, area of Martegiani, and prevascular vitreous fissures and cisterns, as well as varying degrees of vitreous degeneration were visualized in 3D. Conclusions/UNASSIGNED:A machine-learning model for 3D vitreous reconstruction of SS-OCT cube scans was developed. The resultant high-resolution 3D movies illustrated vitreous anatomy in a manner like triamcinolone-assisted vitrectomy or postmortem dye injection. Translational Relevance/UNASSIGNED:This machine learning model now allows for comprehensive examination of the vitreous structure beyond the vitreoretinal interface in 3D with potential applications for common disease states such as the vitreomacular traction and Macular Hole spectrum of diseases or proliferative diabetic retinopathy.
PMCID:9279921
PMID: 35802368
ISSN: 2164-2591
CID: 5278392
Grouping of PFAS for human health risk assessment: Findings from an independent panel of experts
An expert panel was convened to provide insight and guidance on per- and polyfluoroalkyl substances (PFAS) grouping for the purposes of protecting human health from drinking water exposures, and how risks to PFAS mixtures should be assessed. These questions were addressed through multiple rounds of blind, independent responses to charge questions, and review and comments on co-panelists responses. The experts agreed that the lack of consistent interpretations of human health risk for well-studied PFAS and the lack of information for the vast majority of PFAS present significant challenges for any mixtures risk assessment approach. Most experts agreed that "all PFAS" should not be grouped together, persistence alone is not sufficient for grouping PFAS for the purposes of assessing human health risk, and that the definition of appropriate subgroups can only be defined on a case-by-case manner. Most panelists agreed that it is inappropriate to assume equal toxicity/potency across the diverse class of PFAS. A tiered approach combining multiple lines of evidence was presented as a possible viable means for addressing PFAS that lack analytical and/or toxicological studies. Most PFAS risk assessments will need to employ assumptions that are more likely to overestimate risk than to underestimate risk, given the choice of assumptions regarding dose-response model, uncertainty factors, and exposure information.
PMID: 35817206
ISSN: 1096-0295
CID: 5269042
Multimodal Noninvasive Functional Neurophotonic Imaging of Murine Brain-Wide Sensory Responses
Modern optical neuroimaging approaches are expanding the ability to elucidate complex brain function. Diverse imaging contrasts enable direct observation of neural activity with functional sensors along with the induced hemodynamic responses. To date, decoupling the complex interplay of neurovascular coupling and dynamical physiological states has remained challenging when employing single-modality functional neuroimaging readings. A hybrid fluorescence optoacoustic tomography platform combined with a custom data processing pipeline based on statistical parametric mapping is devised, attaining the first noninvasive observation of simultaneous calcium and hemodynamic activation patterns using optical contrasts. Correlated changes in the oxy- and deoxygenated hemoglobin, total hemoglobin, oxygen saturation, and rapid GCaMP6f fluorescence signals are observed in response to peripheral sensory stimulation. While the concurrent epifluorescence serves to corroborate and complement the functional optoacoustic observations, the latter further aids in decoupling the rapid calcium responses from the slowly varying background in the fluorescence recordings mediated by hemodynamic changes. The hybrid imaging platform expands the capabilities of conventional neuroimaging methods to provide more comprehensive functional readings for studying neurovascular and neurometabolic coupling mechanisms and related diseases.
PMID: 35798308
ISSN: 2198-3844
CID: 5284812
Sex diversity within U.S. residencies: a cross-sectional study of trends from 2011 to 2019
BACKGROUND:Despite females comprising 50.8% of the U.S. population, the percentage of females in the physician workforce is only 36.3%. Studies have examined sex trends within select specialties, however there is insufficient literature studying trends across all specialties. In this study, the authors examined trends in the proportion of female residents from 2011 to 2019 across all specialties, including both surgical and non-surgical. METHODS: Data on the proportion of female residents from 2011 to 2019 in all specialties was extracted from the Accreditation Council for Graduate Medical Education (ACGME) Data Resource Books and analyzed with the chi-square test for trend. RESULTS:From 2011 to 2019, there was a statistically significant increase in the percentage of female residents in surgical specialties (p < 0.001) and no significant change in the percentage of female residents in non-surgical specialties. In the same time period, the specialty with the highest percentage of females was Obstetrics & Gynecology (81.3%), and the specialty with the lowest percentage of females was Orthopedic Surgery (13.8%). CONCLUSIONS:Although there has been a positive overall trend in the percentage of females entering medical and surgical specialties, the percentage of females in medicine overall still lies below that of the entire population. Increased efforts are needed to increase female representation in medicine, especially in the U.S. in specialties where they are traditionally underrepresented.
PMCID:9254436
PMID: 35790934
ISSN: 1472-6920
CID: 5278362
Subretinal Drusenoid Deposits and Soft Drusen: Are They Markers for Distinct Retinal Diseases?
PURPOSE/OBJECTIVE:Soft drusen and subretinal drusenoid deposits (SDDs) characterize two pathways to advanced age-related macular degeneration (AMD), with distinct genetic risks, serum risks and associated systemic diseases. METHODS:126 Subjects with AMD were classified as SDD (with or without soft drusen), or non-SDD (drusen only) by retinal imaging, with serum risks, genetic testing, and histories of cardiovascular disease (CVD) and stroke. RESULTS:There were 62 SDD subjects and 64 non-SDD subjects, 51 total had CVD or stroke.SDD correlated significantly with: lower mean serum HDL (61±18 vs. 69±22 mg/dl, p= 0.038, t test); CVD and stroke (34/51 SDD, p= 0.001, chi square); ARMS2 risk allele (p= 0.019, chi square), but not with CFH risk allele (p = 0.66). Non-SDD (drusen only) correlated/trended with: APOE2 (p= 0.032) and CETP (p= 0.072) risk alleles (chi square). Multivariate independent risks for SDD were: CVD and stroke (p= 0.008), and ARMS2 homozygous risk (p= 0.038). CONCLUSION/CONCLUSIONS:SDD and non-SDD subjects have distinct systemic associations, serum and genetic risks. SDD are associated with CVD and stroke, ARMS2 risk, and lower HDL; non-SDD with higher HDL, CFH risk and two lipid risk genes. These and other distinct associations suggest these lesions are markers for distinct diseases.
PMID: 35213528
ISSN: 1539-2864
CID: 5175212
BRANCH RETINAL ARTERY OCCLUSION WITH PARACENTRAL ACUTE MIDDLE MACULOPATHY PRESUMABLY RELATED TO HEAVY CANNABIS USE [Case Report]
PURPOSE/OBJECTIVE:To report a case of branch retinal artery occlusion associated with paracentral acute middle maculopathy on spectral-domain optical coherence tomography presumably related to heavy cannabis consumption. METHODS:Retrospective case report. Spectral-domain optical coherence tomography, fluorescein angiography, and optical coherence tomography angiography were performed. RESULTS:A 21-year-old healthy man described the acute onset of superior visual field loss in his right eye. He admitted smoking approximately 15 g daily of cannabis for several weeks during COVID-19 confinement. Ophthalmoscopic examination of the right eye showed inferotemporal retinal whitening. Spectral-domain optical coherence tomography illustrated evidence of the ischemic cascade with diffuse hyperreflectivity of the inner and middle retinal layers within the central region of the retinal infarct and paracentral acute middle maculopathy at the border of the infarct. Optical coherence tomography angiography demonstrated predominant flow signal loss at the level of the deep retinal capillary plexus. Fluorescein angiography and complete systemic workup were unremarkable. CONCLUSION/CONCLUSIONS:Branch retinal artery occlusion and paracentral acute middle maculopathy may be related to heavy cannabis use as the result of transient arterial vasospasm.
PMID: 32947368
ISSN: 1937-1578
CID: 5280832
Autofluorescence and Yellowing Subhyaloid Blood with Proliferative Diabetic Retinopathy
PURPOSE/OBJECTIVE:To present a patient with a subhyaloid hemorrhage from proliferative diabetic retinopathy who showed a unique contrast between the fundus autofluorescent patterns of yellow with red blood. METHODS:Analysis of color and autofluorescence fundus photographs of a patient with an aging subhyaloid hemorrhage. RESULTS:The remnants of a resorbing subhyaloid hemorrhage had two layers, a superior yellow portion that was intensely hyperautofluorescent and an inferior relatively hypoautofluorescent red portion. We argue that the yellow appearance of the devitalized blood and fluorophores imaged are related to free base porphyrins. CONCLUSION/CONCLUSIONS:Fundus autofluorescence is a useful modality to image subhyaloid blood and may lend important insights into the fluorophores that hyperfluoresce. The blood breakdown products are potentially toxic and autofluorescence imaging may offer clues to their presence.
PMID: 32796227
ISSN: 1937-1578
CID: 4566212
Cost of Ranibizumab Port Delivery System vs Intravitreal Injections for Patients With Neovascular Age-Related Macular Degeneration
Importance/UNASSIGNED:The study team investigated costs associated with the ranibizumab port delivery system (PDS) for neovascular age-related macular (nAMD), an alternative to conventional intravitreal anti-vascular endothelial growth factor (VEGF) injections. Objective/UNASSIGNED:To investigate costs of intravitreal anti-VEGF injections vs ranibizumab PDS for patients with neovascular AMD (nAMD). Design, Setting, and Participants/UNASSIGNED:This cost analysis used trial data and Medicare reimbursement rates and included patients with nAMD who were receiving ranibizumab, aflibercept, bevacizumab injections, or ranibizumab PDS. Main Outcomes and Measures/UNASSIGNED:The number of intravitreal ranibizumab, aflibercept, and bevacizumab injections to break even with costs of ranibizumab PDS. Total direct medical costs over 1 year and 5 years for the ranibizumab PDS arm with refills at fixed 6-month intervals compared with monthly or bimonthly injections were calculated using Medicare rates. Scenario and sensitivity analyses accounted for uncertainty and variation. Results/UNASSIGNED:The mean (SD) number of ranibizumab, aflibercept, and bevacizumab injections to break even with the cost of ranibizumab PDS with 1 refill was 10.8 (1.3), 9.3 (1.1), and 34.5 (4.2), respectively. Ranibizumab PDS with fixed 6-month refills over 1 year cost $21 016 ($2102). Comparatively, monthly intravitreal ranibizumab cost $1943 (95% CI, -$3047 to $6932; P = .34) more, aflibercept cost $5702 (95% CI, $253-$11 151; P = .04) more, and bevacizumab cost $16 732 (95% CI, -$20 170 to -$13 294, P < .001) less. For bimonthly injections, aflibercept cost $7658 (95% CI, -$11 649.52 to -$3665.61; P = .006) less. Over 5 years, monthly intravitreal ranibizumab projected to cost $25 581 (95% CI, $2275-$48 887; P = .04) more, aflibercept cost $44 374 (95% CI, $18 623-$70 125; P = .008) more, and bevacizumab cost $67 793 (95% CI, -$82 501 to -$53 085; P < .001) less than PDS with fixed refills (mean [SD] cost, $89 218 [$8921]). For bimonthly injections, aflibercept cost $22 422 (95% CI, -$40 287 to -$45,56; P = .03) less. In scenario analyses, ranibizumab PDS with refills as needed offered cost savings compared with real-world intravitreal ranibizumab or aflibercept use at 5 years but not at 1 year. Conclusions and Relevance/UNASSIGNED:In this cost analysis, ranibizumab PDS with 1 refill cost more than intravitreal ranibizumab or aflibercept injections if less than or equal to approximately 11 or 10 injections, respectively, are required within the first year. Long term, if less than 4.4 and 3.8 injections are needed per refill, intravitreal ranibizumab and aflibercept is lower cost. Ranibizumab PDS costs more than intravitreal bevacizumab injections throughout scenarios.
PMID: 35708679
ISSN: 2168-6173
CID: 5250232
Contralateral Forced Eyelid Closure Increases Intraocular Pressure
OBJECTIVES/OBJECTIVE:The purpose of the study was to describe the influence of contralateral forced eyelid closure on intraocular pressure (IOP). METHODS:Twenty-one healthy volunteers with no ophthalmic history had their IOP measured in the supine position to simulate the intraoperative environment. Intraocular pressure was measured with a handheld tonometer over three scenarios: (1) both eyes in a relaxed state, (2) eyelid speculum in the right eye with both eyes open and relaxed, (3) eyelid speculum in the right eye with the fellow eye squeezing tightly. RESULTS:Intraocular pressure significantly increased with forced contralateral eyelid squeezing compared with the relaxed state by a mean of 7.71±5.08 mm Hg (95% Confidence Interval of 5.40-7.37), P<0.001. CONCLUSIONS:Contralateral eyelid squeezing can significantly increase intraoperative IOP measurements.
PMID: 35333794
ISSN: 1542-233x
CID: 5205892
Enrichment of IGF-1R and PPARγ signalling pathways in orbital inflammatory diseases: steps toward understanding pathogenesis
BACKGROUND:Orbital inflammatory disease (OID) encompasses a wide range of pathology including thyroid-associated orbitopathy (TAO), granulomatosis with polyangiitis (GPA), sarcoidosis and non-specific orbital inflammation (NSOI), accounting for up to 6% of orbital diseases. Understanding the underlying pathophysiology of OID can improve diagnosis and help target therapy. AIMS/OBJECTIVE:To test the hypothesis that shared signalling pathways are activated in different forms of OID. METHODS:In this secondary analysis, pathway analysis was performed on the previously reported differentially expressed genes from orbital adipose tissue using patients with OID and healthy controls who were characterised by microarray. For the original publications, tissue specimens were collected from oculoplastic surgeons at 10 international centres representing four countries (USA, Canada, Australia and Saudi Arabia). Diagnoses were independently confirmed by two masked ocular pathologists (DJW, HEG). Gene expression profiling analysis was performed at the Oregon Health & Science University. Eighty-three participants were included: 25 with TAO, 6 with orbital GPA, 7 with orbital sarcoidosis, 25 with NSOI and 20 healthy controls. RESULTS:Among the 83 subjects (mean (SD) age, 52.8 (18.3) years; 70% (n=58) female), those with OID demonstrated perturbation of the downstream gene expressions of the IGF-1R (MAPK/RAS/RAF/MEK/ERK and PI3K/Akt/mTOR pathways), peroxisome proliferator-activated receptor-γ (PPARγ), adipocytokine and AMPK signalling pathways compared with healthy controls. Specifically, GPA samples differed from controls in gene expression within the insulin-like growth factor-1 receptor (IGF-1R, PI3K-Akt (p=0.001), RAS (p=0.005)), PPARγ (p=0.002), adipocytokine (p=0.004) or AMPK (p=<0.001) pathways. TAO, sarcoidosis and NSOI samples were also found to have statistically significant differential gene expression in these pathways. CONCLUSIONS:Although OID includes a heterogenous group of pathologies, TAO, GPA, sarcoidosis and NSOI share enrichment of common gene signalling pathways, namely IGF-1R, PPARγ, adipocytokine and AMPK. Pathway analyses of gene expression suggest that other forms of orbital inflammation in addition to TAO may benefit from blockade of IGF-1R signalling pathways.
PMID: 33637620
ISSN: 1468-2079
CID: 4800892
American journal of obstetrics & gynecology. 2022:227(1):79.e1-79.e11.DOI: 10.1016/j.ajog.2022.01.002
Cell-free DNA screening for prenatal detection of 22q11.2 deletion syndrome
BACKGROUND:Prenatal screening has historically focused primarily on detection of fetal aneuploidies. Cell-free DNA (cfDNA) now enables noninvasive screening for subchromosomal copy number variants, including 22q11.2 deletion syndrome (22q11.2DS or DiGeorge syndrome), which is the most common microdeletion and a leading cause of congenital heart defects and neurodevelopmental delay. Although smaller studies have demonstrated the feasibility of screening for 22q11.2DS, large cohort studies with postnatal confirmatory testing to assess test performance have not been reported. OBJECTIVE:To assess the performance of SNP-based cfDNA prenatal screening for detection of 22q11.2DS. STUDY DESIGN/METHODS:Patients who had SNP-based cfDNA prenatal screening for 22q11.2DS were prospectively enrolled at 21 centers in 6 countries. Prenatal or newborn DNA samples were requested in all cases for genetic confirmation with chromosomal microarray. The primary outcome was sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of cfDNA for detection of all deletions, including the classical deletion and nested deletions that are ≥500kb, in the 22q11.2 low copy repeat A-D region. Secondary outcomes included the prevalence of 22q11.2DS and performance of an updated cfDNA algorithm that was evaluated blinded to pregnancy outcome. RESULTS:Of 20,887 women enrolled, genetic outcome was available in 18,289 (87.6%). Twelve 22q11.2DS cases were confirmed in the cohort, including five (41.7%) nested deletions, yielding a prevalence of 1:1524. In the total cohort, cfDNA reported 17,976 (98.3%) as low risk for 22q11.2DS and 38 (0.2%) as high-risk; 275 (1.5%) were non-reportable. Overall, 9 of 12 cases of 22q11.2 were detected, yielding a sensitivity of 75.0% (95% CI: 42.8, 94.5); specificity of 99.84% (95% CI: 99.77, 99.89); PPV of 23.7% (95% CI: 11.44, 40.24) and NPV of 99.98% (95% CI: 99.95, 100). None of the cases with a non-reportable result was diagnosed with 22q11.2DS. The updated algorithm detected 10/12 cases (83.3%; 95% CI: 51.6-97.9) with a lower false positive rate (0.05% vs. 0.16%, p<0.001) and a PPV of 52.6% (10/19; 95% CI 28.9-75.6). CONCLUSIONS:Noninvasive cfDNA prenatal screening for 22q11.2DS can detect most affected cases, including smaller nested deletions, with a low false positive rate.
PMID: 35033576
ISSN: 1097-6868
CID: 5131242
Indirect treatment comparison of idecabtagene vicleucel versus conventional care in triple-class exposed multiple myeloma
PMID: 35485211
ISSN: 2042-6313
CID: 5217672
Comparison between three different high fluence UVA levels in corneal collagen cross-linking for treatment of experimentally induced fungal keratitis in rabbits
INTRODUCTION/BACKGROUND:The aim of this study was to compare the efficacy of Photo-Activated Chromophore for Keratitis - Corneal Collagen Cross-linking (PACK-CXL) of three different total UVA fluence levels and topical voriconazole in treatment of fungal keratitis experimentally induced in rabbits. METHODS:This is an interventional experimental study including both eyes of 16 rabbits (32 eyes). Fungal keratitis was induced by intrastromal injection of Fusarium Solani into the cornea. The rabbits were then divided into four groups (8 eyes for each) from which group A received Voriconazole eye drops and considered as control group. Group B, C, D received single PACK-CXL session with total fluence levels of 7.2, 10.0 and 15.0 J/cm2 for each respectively. Daily clinical examination was recorded and all corneas were removed for microbiology and histopathology on day ten. RESULTS:The mean clinical signs score eyes treated with high fluence PACK-CXL showed evident clinical improvement from fourth to tenth day of treatment. This improvement was equivalent to that of Voriconazole treatment. The results showed better improvement with increasing the UVA total fluence levels but this difference was not statistically significant (P < 0.05). Similarly, the median CFU/ml declined on increasing UVA fluence but with no statistically significant values. Histopathological examination revealed better improvement of inflammatory signs on higher fluence levels compared to lower ones. CONCLUSIONS:) was as effective as Voriconazole in the treatment of fungal keratitis in rabbits. Increasing the fluence of UVA was associated with slightly better clinical outcomes with no added risks. More clinical studies are needed to confirm these results.
PMID: 35384782
ISSN: 1724-6016
CID: 5484752
Reply to the letter-to-the-editor: Morphological retinal changes in keratoconus [Comment]
PMID: 35568372
ISSN: 1937-5913
CID: 5484762
Intracorneal Ring Segment Implantation Results in Corneal Mechanical Strengthening Visualized With Optical Coherence Elastography
PURPOSE/OBJECTIVE:To quantify the mechanical impact of intracorneal ring segment (ICRS) implantation of different dimensions in an ex vivo eye model. METHODS:A total of 30 enucleated porcine eyes were assigned to ICRS implantation (thickness: 300 µm, angle: 120°, 210°, or 325°), tunnel creation only, or virgin control groups. For mechanical evaluation, each globe was mounted on a customized holder and intraocular pressure (IOP) was increased in steps of 0.5 mm Hg from 15 to 17 mm Hg, simulating physiologic diurnal IOP fluctuations. At each step, an optical coherence tomography volume scan was recorded. Deformations between subsequent scans and the locally induced axial strains were analyzed using a vector-based phase difference method. The effective E-modulus was derived from the overall induced strain as a measure of global mechanical impact. RESULTS:ICRS implantation increased the effective E-modulus from 146 and 163 kPa in virgin and tunnel-only eyes to 149, 192, and 330 kPa in eyes that received a 5-mm optical zone ICRS with 120°, 210°, and 325° arc length, respectively; and to 209 kPa in a 6-mm optical zone ICRS with 325° arc length. The most consistent effect was a shift toward positive strains in the posterior stroma by 0.1% to 0.46% (factor 1.15 to 2.15) after ICRS surgery. CONCLUSIONS:.
PMID: 35858197
ISSN: 1081-597x
CID: 5484802
Long-term Outcomes from the HORIZON Randomized Trial for a Schlemm's Canal Microstent in Combination Cataract and Glaucoma Surgery
PURPOSE:To present the 5-year results of the HORIZON trial comparing cataract surgery (CS) combined with an intracanalicular microstent with CS alone. DESIGN:Prospective, multicenter, controlled randomized clinical trial. PARTICIPANTS:Patients with cataract and primary open-angle glaucoma treated with 1 or more glaucoma medications, washed-out diurnal intraocular pressure (DIOP) of 22 to 34 mmHg, and no prior incisional glaucoma surgery. METHODS:Eyes were randomized 2:1 to receive a Hydrus Microstent (HMS; Ivantis, Inc) or no stent after successful CS. MAIN OUTCOME MEASURES:Intraocular pressure (IOP), glaucoma medication use, repeat glaucoma surgery, visual acuity, visual field, procedure-related adverse events, and corneal endothelial cell counts. RESULTS:Three hundred sixty-nine eyes were randomized to HMS treatment, and 187 eyes were randomized to CS only. Study groups were well matched for preoperative IOP, medication use, washed-out DIOP, and glaucoma severity. Five-year follow-up was completed in 80% of patients. At 5 years, the HMS group included a higher proportion of eyes with IOP of 18 mmHg or less without medications than the CS group (49.5% vs. 33.8%; P = 0.003), as well as a greater likelihood of IOP reduction of 20% or more without medications than the CS group (54.2% vs. 32.8%; P < 0.001). The number of glaucoma medications was 0.5 ± 0.9 in the HMS group and 0.9 ± 0.9 in the CS group (P < 0.001), and 66% of eyes in the HMS group were medication free compared with 46% in the CS group (P < 0.001). The cumulative risk of incisional glaucoma surgery was lower in the HMS group (2.4% vs. 6.2%; P = 0.027, log-rank test). No clinical or statistically significant differences were found in the rate of endothelial cell loss from 3 to 60 months between the HMS and CS alone groups (P = 0.261). CONCLUSIONS:The addition of a Schlemm's canal microstent in conjunction with CS was safe, resulted in lowered IOP and medication use, and reduced the need for postoperative incisional glaucoma filtration surgery compared with CS after 5 years. Long-term presence of the implant did not affect the corneal endothelium adversely.
PMID: 35218867
ISSN: 1549-4713
CID: 5498032
Distinct characteristics of central serous chorioretinopathy according to gender
To investigate the differences in clinical and genetic characteristics between males and females with central serous chorioretinopathy (CSC). Consecutive 302 patients (mean age; 56.3 ± 11.7, male/female: 249/53) with CSC were evaluated on the initial presentation. All CSC patients underwent fluorescein angiography and indocyanine green angiography (FA/ICGA), swept-source or spectral-domain optical coherence tomography (OCT), and fundus autofluorescence (FAF) to confirm a diagnosis. All patients were genotyped for rs800292 and rs1329428 variants of CFH using TaqMan technology. On the initial presentation, female patients were significantly older (p = 2.1 × 10-4, female 61.6 ± 12.4 vs male 55.1 ± 11.3) and had thinner subfoveal choroidal thickness (p = 3.8 × 10-5) and higher central retinal thickness (p = 3.0 × 10-3) compared to males. A descending tract was more frequently seen in males than in females (p = 8.0 × 10-4, 18.1% vs 0%). Other clinical characteristics were comparable between the sexes. The risk allele frequency of both variants including CFH rs800292 and CFH rs1329428 was comparable between males and females (CFH rs800292 A allele male 51.2% vs female 47.2%, CFH rs1329428 T allele male 56.2% vs 52.8%). On the initial presentation, age, subfoveal choroidal thickness and central retinal thickness differ between males and females in eyes with CSC. A descending tract may be a strong male finding in CSC.
PMID: 35732691
ISSN: 2045-2322
CID: 5266022
Correlation of Optical Coherence Tomography Angiography of Type 3 Macular Neovascularization With Corresponding Histology
Importance/UNASSIGNED:By validating optical coherence tomography angiography (OCTA) in the analysis of type 3 macular neovascularization secondary to age-related macular degeneration, the overall value of clinical OCTA for disease observation, diagnosis, and staging is increased. Objective/UNASSIGNED:To assess the association of in vivo OCTA of type 3 macular neovascularization secondary to age-related macular degeneration with corresponding ex vivo histology. Design, Setting, and Participants/UNASSIGNED:This study included clinical imaging, laboratory microscopy, and eye-tracked clinicopathologic correlation of a single case from a community-based practice evaluated at a university-based research laboratory from 2014 to 2019. Exposures/UNASSIGNED:Infrared reflectance and eye-tracked spectral-domain OCTA clinical imaging was correlated with ex vivo high-resolution histologic images of the preserved donor eye. Eye tracking, applied to the donor eye, enabled identification of histologic features corresponding with clinical OCTA signatures. Projection artifact removal based on 2-dimensional vessel-shape estimation and a Gaussian blur filter demonstrated a robust preservation of neovascular flow signal. Main Outcomes and Measures/UNASSIGNED:Histology findings associated with clinical OCTA signatures. Three-dimensional view of neovascularization via video. Results/UNASSIGNED:A White woman in her 90s with type 3 neovascularization secondary to age-related macular degeneration was treated with 37 intravitreal injections of ranibizumab and aflibercept in the right eye. The index lesion displayed a drusenoid pigment epithelium detachment, characteristic of type 3 neovascularization. OCTA decorrelation signal in the index lesion corresponded in histology to a collagen-ensheathed vascular complex contacting basal laminar deposit that outlasted the retinal pigment epithelium. The subretinal pigment epithelium-basal laminar space contained calcified material and glial processes. No connection between the choriocapillaris and this space was observed. Video showed a columnar tangle of flow signal in the outer nuclear layer, with inflow and outflow vessels connecting to the superficial artery and vein. Conclusions and Relevance/UNASSIGNED:While this study presents only 1 case in which a vascular connection between subretinal pigment epithelium-basal laminar space and choriocapillaris was undetected, these results support the potential value of OCTA for diagnosis. OCTA decorrelation signal of type 3 neovascularization corresponded with intraretinal neovessels on histology. Projection artifact removal based on 2-dimensional vessel-shape estimation and Gaussian blur filter demonstrated their potential value for further use in OCTA decorrelation signal processing.
PMID: 35446357
ISSN: 2168-6173
CID: 5218462
Macular Vascular Imaging and Connectivity Analysis Using High-Resolution Optical Coherence Tomography
Purpose:To characterize macular blood flow connectivity in vivo using high-resolution optical coherence tomography (HighRes OCT). Methods:Cross-sectional, observational study. Dense (6-µm interscan distance) perifoveal HighRes OCT raster scans were performed on healthy participants. To mitigate the limitations of projection-resolved OCT-angiography, flow and structural data were used to observe the vascular structures of the superficial vascular complex (SVC) and the deep vascular complex. Vascular segmentation and rendering were performed using Imaris 9.5 software. Inflow and outflow patterns were classified according to vascular diameter and branching order from superficial arteries and veins, respectively. Results:Eight eyes from eight participants were included in this analysis, from which 422 inflow and 459 outflow connections were characterized. Arteries had direct arteriolar connections to the SVC (78%) and to the intermediate capillary plexus (ICP, 22%). Deep capillary plexus (DCP) inflow derived from small-diameter vessels succeeding ICP arterioles. The most prevalent outflow pathways coursed through superficial draining venules (74%). DCP draining venules ordinarily merged with ICP draining venules and drained independently of superficial venules in 21% of cases. The morphology of DCP draining venules in structural HighRes OCT is distinct from other vessels crossing the inner nuclear layer and can be used to identify superficial veins. Conclusions:Vascular connectivity analysis supports a hybrid circuitry of blood flow within the human parafoveal macula. Translational Relevance:Characterization of parafoveal macular blood flow connectivity in vivo using a precise segmentation of HighRes OCT is consistent with ground-truth microscopy studies and shows a hybrid circuitry.
PMCID:9172017
PMID: 35648637
ISSN: 2164-2591
CID: 5277612
Potentially Missed Opportunities in Prevention of Acute Angle-Closure Crisis
Importance:If an anatomic narrow angle is not appropriately diagnosed and treated, it can result in acute angle-closure crisis (AACC) and lead to substantial vision loss. Objective:To identify patients who presented with AACC and assess for factors that may have been associated with risk of developing it. Design, Setting, and Participants:This population-based retrospective cohort study conducted from January 1, 2001, to December 31, 2015, included a 20% nationwide sample of 1179 Medicare beneficiaries. Patients aged 40 years or older with AACC were identified with billing codes. A 2-year lookback period from the date of initial presentation of AACC was used to identify patients who had at least 1 eye care visit, received a diagnosis of open-angle glaucoma (OAG) or suspected OAG, or received at least 1 medication associated with risk of AACC. Of the patients who had at least 1 eye care visit, those who underwent gonioscopy, received a diagnosis of an anatomic narrow angle before developing AACC, or both were identified. Main Outcomes and Measures:Proportions of patients who had at least 1 eye care visit, had OAG or suspected OAG, received at least 1 medication associated with risk of AACC, underwent gonioscopy, or received a diagnosis of an anatomic narrow angle before development of AACC. Results:A total of 1179 patients had a confirmed diagnosis of AACC. The mean (SD) age of patients with AACC was 66.7 (11.8) years (range, 40-96 years), 766 were women (65.0%), 57 were Asian (4.8%), 109 were Black (9.2%), 126 were Latino (10.7%), 791 were White (67.1%), and 96 were other race and ethnicity (8.1%). Of these patients, only 796 (67.5%) consulted an optometrist or ophthalmologist at least once during the 2-year lookback period. A total of 464 individuals (39.4%) had OAG or suspected OAG, and 414 (35.1%) had received at least 1 medication associated with increased risk of AACC before developing it. Of the 796 patients who consulted an optometrist or ophthalmologist in the lookback period, less than one-third underwent gonioscopy in the 2 years before developing AACC (n = 264 [33.2%]), and less than one-half of all patients undergoing gonioscopy received a diagnosis of an anatomic narrow angle (n = 113 [42.8%]). Most patients underwent gonioscopy in the 1 to 4 weeks preceding the AACC. Conclusions and Relevance:In this group of Medicare patients, there appear to have been multiple opportunities for interventions that may have averted AACC. Interventions aimed at addressing risk factors associated with AACC and improving performance of gonioscopy might be associated with reduced risk for ocular morbidity.
PMID: 35554487
ISSN: 2168-6173
CID: 5333732
Delayed Laser In Situ Keratomileusis Interface Haze 6 Months After Corneal Cross-linking for Ectasia
ORIGINAL:0016959
ISSN: 2768-1599
CID: 5519342
Missed Opportunities in Preventing Acute Angle Closure-Needlessly Blind? [Comment]
PMID: 35551583
ISSN: 2168-6173
CID: 5498052
Episcleral Apocrine Hidrocystoma Following Strabismus Surgery [Case Report]
Apocrine hidrocystomas are benign cystic tumors derived from apocrine sweat glands; they are most commonly located in the skin of the head and neck regions. Ophthalmic occurrences typically appear at the lash line and canthi of the eyelid, although rare instances have been described in the conjunctiva, caruncle, and orbit. The authors illustrate an exceptional instance of a mobile episcleral cyst in a 12-year-old girl that developed about 2 years following strabismus surgery. The cyst was located anterior to the insertion of the left medial rectus and was excised in response to the patient's complaints of irritation. Histopathology of the excised specimen displayed an empty cyst lined by a double layer of cuboidal epithelium with the inner layer exhibiting apical decapitation secretion. Confirmatory immunohistochemistry demonstrated reactivity of both layers with CK7 and the outer myoepithelial layer with D2-40. Postoperative and traumatic cysts formed after interruption of the bulbar conjunctiva are usually conjunctival cysts lined by stratified squamous nonkeratinizing epithelium.
PMID: 35797674
ISSN: 1537-2677
CID: 5268882
Apparent lack of association of COVID-19 vaccination with Herpes Zoster
Purpose/UNASSIGNED:Herpes zoster (HZ) has been identified as a potential association with the BNT162b2 COVID-19 vaccination. This study evaluated this possible association in a cohort of patients receiving the vaccination. Methods/UNASSIGNED:Epic electronic health records of adult patients who received at least one COVID-19 vaccination between January 12, 2020 and 9/30/2021 within the NYU Langone Health were reviewed to analyze a new diagnosis of herpes zoster within 3 months before compared to 3 months after vaccination. Results/UNASSIGNED:Of the 596,111 patients who received at least one COVID-19 vaccination, 716 patients were diagnosed with HZ within three months prior to vaccination, compared to 781 patients diagnosed within 3 months afterwards. Using the chi-square test for independence of proportions, there was not a statistically significant difference in frequency of HZ before (proportion: 0.0012, 95% CI: [0.0011, 0.0013]) vs. after vaccination (proportion: 0.0013, 95% CI: [0.0012, 0.0014]); (p = 0.093). Conclusions and importance/UNASSIGNED:This study did not find evidence of an association between COVID-19 vaccination and a new diagnosis of HZ. We encourage health care professionals to strongly recommend COVID-19 vaccinations per Centers for Disease Control (CDC) recommendations and vaccination against HZ according to Food and Drug Administration (FDA) approval for the recombinant zoster vaccine.
PMCID:9021123
PMID: 35474754
ISSN: 2451-9936
CID: 5217432
Canadian journal of ophthalmology = Journal canadien d'ophtalmologie. 2022:57(3):e89-e91.DOI: 10.1016/j.jcjo.2021.09.011
Rare case of extramacular choroidal macrovessel [Letter]
PMID: 34678174
ISSN: 1715-3360
CID: 5234592
Qualitative and quantitative comparison of ERGs with contact lens and adhesive skin electrodes
PURPOSE/OBJECTIVE:Traditional ERGs recorded using corneal electrodes can be difficult for some patients to tolerate. In the last several years, adhesive skin electrodes have gained in acceptance. In this report we present a qualitative comparison of waveforms as well as a quantitative analysis of correlation of amplitudes and implicit times of simultaneous ERG recordings using contact lens and skin electrodes. METHODS:89 subjects were included; all were referred for full-field ERG testing for multiple indications. ERGs (obtained according to ISCEV standards) were recorded simultaneously from both eyes with ERG-jet corneal contact lens electrodes and LKC Technologies Sensor Strip adhesive skin electrodes using multi-channel instrumentation (Diagnosys LLC, Espion3). Waveforms, a-wave and b-wave amplitudes and implicit times were compared. RESULTS:Waveform morphologies were similar between electrode types. Regression coefficients (conversion factors) for a-wave and b-wave amplitudes under both photopic and scotopic conditions were tightly clustered. Regression coefficients for implicit times were nearly equal to 1.0. The regression coefficient for the entire amplitude dataset was 0.349, with an overall correlation of 0. 869 between amplitude recorded with skin and contact lens electrodes. The regression coefficient for the entire implicit time dataset was 0.967, with an overall correlation of 0.964 between skin and contact lens electrodes. CONCLUSIONS:Our best estimate for the conversion factor between ERG amplitudes recorded with adhesive skin electrodes and contact lens electrodes is 0.349-amplitudes with skin electrodes are about 1/3 the amplitudes recorded simultaneously from the same eyes with contact lens electrodes, with a high correlation. Implicit times are nearly identical for the two electrode types.
PMID: 35304683
ISSN: 1573-2622
CID: 5183942
Dehazing of Visible-light OCT B-scans using deep neural model improves visualization and quantification of retinal sub-layers [Meeting Abstract]
Purpose : Multiple sublayers of retina can be visualized with visible light (vis-) OCT.However, image quality can be compromised due to patient movement, cataracts, small pupil size, and light scattering causing haziness and variability in signal to noise ratio in individual A-scans and in entire B-scans.The purpose of this study was to examine the effect of conventional and deep neural network dehazing techniques on the visibility and quantitative assessment of retinal sub-layers on vis-OCT images. Methods : 9 healthy and 5 glaucoma subjects were scanned 3 times during one session.Scanning was done on the superior nasal side of para-foveal region,1.5 mm from the fovea with a 3D speckle reduction raster scanning protocol(3x3x1.6 mm with 8192x16x1024 samplings) using a prototype vis-OCT system.16 A-scan lines were averaged to reduce speckle noise.Gray-scale image dehazing guided by depth information and pretrained Dehazenet deep model following deep convolutional neural network with residual learning(DnCNN) were applied on original B-scans.Quality improvement were evaluated using quality index(QI) and contrast to noise ratio(CNR) on dehazed B-scans.For each subject, the dehazed B-scan of Dehazenet and DnCNN from a fixed location adjacent to the fovea were selected.The distances between each of 3 bright inner plexiform layers(IPL) and retinal pigment epithelium(RPE) sublayers were segmented manually for thickness measurements using a 8 A-scan averaged profile(Fig.).Coefficient of variations (CVs) were calculated to assess the measurement repeatability of the sublayers on original and dehazed B-scans. Results : Healthy and glaucoma subjects were age 45.67+/-11.7and 59.60+/-13.4(p=0.07,t-test),visual field mean deviation(MD)-1.55 to1.20 dB,and from -26.42 to -7.70dB(p= 0.003,Wilcoxon),global mean circumpapillary retinal nerve fiber layer(RNFL)thickness 96.33+/-12.20 and 59.80+/-9.09mm(p<0.001,Wilcoxon),respectively.Dehazed B-scans obtained by deep models have statistically significant better QI and CNR(Table1).Overall intra-subject CVs showed significantly improved reproducibility on all measured sub-layers of dehazed B-scans compared to original scans for all subjects(Tables 2,3). Conclusions : Vis-OCT image quality can be improved using deep neural network dehazing model resulting in higher reproducible thickness measurements of retinal sublayers within subjects in dehazed B-scans
EMBASE:639126981
ISSN: 1552-5783
CID: 5379882
Relationships between the Optic Nerve Head in Optical Coherence Tomography and Optic Nerve Volume in Magnetic Resonance Imaging in Glaucoma [Meeting Abstract]
Purpose : Deep learning of optical coherence tomography (OCT) may help discriminate glaucomatous eyes from healthy controls. However, the underlying decision making processes remain unclear. Recently, through computing class activation maps, our feature agnostic artificial intelligence of OCT images using a 3D convolutional neural network identified the optic nerve head (ONH) and its surrounding regions as structures significantly associated with glaucoma classification (PMID: 31260494). To pursue their contributions further, here we analyzed the optic nerve morphology from OCT and magnetic resonance imaging (MRI) in a subset of glaucoma and healthy subjects. Methods : Nine early glaucoma, 12 advanced glaucoma, and 4 healthy control subjects underwent spectral-domain OCT at 30x30x2 mum3 and 3-Tesla anatomical MRI at 1x1x1mm3 . Maximum intensity projection was applied to en-face OCT scans at the ONH (Fig. 1). The areas of the ONH [inner regions of interest, (ROI)] and surrounding regions (outer ROIs) visible in OCT were measured using global thresholding in ImageJ. One-way ANOVAs with post-hoc Tukey's tests were performed on the inner and outer ROIs between the 3 groups. Also, a Pearson correlation analysis was performed between the ROI areas in OCT and optic nerve volume extracted from MRI between the eye and optic chiasm. Results : For OCT of the ONH, significant group effect was observed for the areas in the inner ROIs (ANOVA: F= 7.823, p=0.00133). Post-hoc analyses revealed a significant difference between healthy controls and advanced glaucoma (p=0.0082) and between early and advanced glaucoma (p=0.0057) but no significance between healthy controls and early glaucoma (p=0.80) (Fig. 2A). No significant group effect was observed in the outer ROIs (ANOVA: F=0.004, p=0.996) (Fig. 2B). There was a negative correlation between the inner ROI area in OCT and optic nerve volume in MRI (R=-0.47, p=0.0011) (Fig. 2C). Conclusions : The ONH tissues visible on OCT appeared to contribute more than their surrounding regions to distinguishing between glaucomatous eyes and healthy eyes. The negative correlation between ONH area in OCT and optic nerve volume in MRI suggested the need to further understand the interactions between ONH and deeper brain structures in glaucoma. (Figure Presented)
EMBASE:639126865
ISSN: 1552-5783
CID: 5379892
Lamina Cribrosa Microstructure in Non-Human Primates with Naturally Occurring Peripapillary Retinal Nerve Fiber Layer Thinning [Meeting Abstract]
Purpose : The lamina cribrosa (LC) is hypothesized to be the site of initial axonal damage in glaucoma with the peripapillary retinal nerve fiber layer (RNFL) thickness is widely used as a standard metric for quantifying this damage. The purpose of this study was to determine in vivo changes in the microstructure of the LC in eyes of non-human primates (NHP) with naturally occurring RNFL thinning. Methods : Spectral-domain OCT scans (Leica, Chicago, IL) of the optic nerve head (ONH) were acquired in vivo from a colony of 50 adult rhesus monkeys, suspected of having high prevalence of naturally occurring glaucoma. The circumpapillary global and quadrant RNFL thickness was analyzed using a custom automated segmentation software. From the set of 100 eyes, the 10 eyes with the thinnest global RNFL values were selected as the study group, while 10 eyes with RNFL values around the 50 percentile were used as the control group. A previously described automated segmentation algorithm was used for LC microstructure analysis. The LC microstructure was analyzed globally and in the th following volumetric sectors: quadrants, central and peripheral lamina, and 3 depth slabs (anterior, middle, posterior; Figure). Beam thickness/pore diameter ratio (BPR) and connective tissue volume fraction (CTVF: beam volume/total volume) were calculated globally and in sectors. Results : 20 eyes (15 animals) were analyzed (Table 1). While no significant difference was detected between groups for age, weight or disc size, the study group had significantly thinner RNFL than the control group (p<0.01). The study group had significantly larger BPR and CTVF compared with the control group (Table 2). Significant sectoral differences between study and control group RNFL thickness were noted for BPR and CTVF in the nasal and temporal quadrants, central LC, and in LC depth. Across eyes, the global RNFL thickness was moderately negatively correlated only with the global CTVF (lower RNFL thickness associated with higher CTVF; r2 =0.63, p=0.045). Conclusions : Eyes with thinner circumpapillary RNFL had thicker LC BPR and CTVF globally and in various sectors when compared to eyes with normal RNFL thickness. Whether these LC changes are the cause of RNFL damage or the result of remodeling of the LC requires further investigation. (Figure Presented)
EMBASE:639125500
ISSN: 1552-5783
CID: 5379902
A novel method of enhancing in vivo OCT lamina cribrosa visualization for automated segmentation [Meeting Abstract]
Purpose : Automated segmentation of in-vivo lamina cribrosa (LC) has been challenging, owing to the complex 3D structure and decreased visibility in the lamina depth. Frangi's vesselness filter, which was originally developed for angiogram segmentation, have been successfully demonstrated in segmenting the ex-vivo LC from micro-CT and second harmonic generation microscopy images. In this project we are proposing a new approach of segmenting the in vivo LC from OCT scans, incorporating the Frangi's vesselness principle to facilitate in vivo LC image analysis in much greater detail compared to our previously described 3D analysis method. Methods : In-vivo spectral-domain OCT scans (Leica, Chicago, IL) were acquired from healthy non-human primates. Scans of varying degree of image quality were selected for the analysis and underwent automated brightness and local contrast enhancement. 3D Frangi's vesselness filter was applied using a fixed setting for scans of all qualities. Our previously described segmentation algorithm was then used to quantify the LC microstructure. The measurements generated from the Frangi analysis and from our own conventional method were compared with a standard reference (manually segmented LC by an expert). Paired t tests were performed to compare if the differences between standard reference and conventional method are greater than the differences between standard reference and Frangi analysis. The visibility of analyzable lamina and dice coefficient were also compared to the conventional method using the same test. Results : In vivo scans acquired from 5 rhesus macaques (3 males, 1 female, aged 4.3-10.7 yrs) were used for the analysis. No significant difference was detected for LC microstructure parameters between Frangi's approach and conventional method with respect to the standard reference, except for significantly higher pore count in Frangi's method (p=0.003; Table). Furthermore, visibility (Figure) was significantly higher for the Frangi method compared to the conventional approach (p<0.001) with no difference detected for the semantic segmentation, as reflected by the dice coefficient. Conclusions : The use of Frangi analysis substantially increase the analyzable lamina while providing similar quantification of the LC microstructure compared to our previous 3D analysis method. This improves the potential for automated and thorough volumetric analysis of in vivo OCT LC image
EMBASE:639124013
ISSN: 1552-5783
CID: 5379912
Chronic intraocular pressure elevation alters cerebrovascular reactivity in the visual cortex and basal forebrain [Meeting Abstract]
Purpose : Glaucoma is an eye disease with widespread involvement of the brain. Since visual cortex (VC) may possess lower choline levels in glaucoma, and basal forebrain (BF) has cholinergic projections to VC for modulating cerebral blood flow and visual processing, we postulate that the vascular functions of the VC and BF are involved in glaucoma (PMID: 31242454). Recently, we used a novel whole-brain relative cerebrovascular reactivity (rCVR) mapping technique via resting-state functional MRI (rsfMRI) without gas challenge, and observed rCVR decrease in VC and rCVR increase in BF in patients with increasing glaucoma severity (PMID: 34892116). However, the underlying mechanisms remain to be elucidated. Here, we applied a hydrogel-induced glaucoma mouse model to elevate intraocular pressure (IOP) (PMID: 31176841), mapped wholebrain rCVR using rsfMRI, and measured optomotor responses (OMR). We hypothesize that chronic IOP elevation can lead to rCVR changes in the glaucomatous brain along with visual impairments. Methods : For the glaucoma model, C57BL/6J mice (male, 15-weeks, n=15) received intracameral injection of cross-linking hydrogel to the right eye to obstruct aqueous outflow and induce chronic IOP elevation. Controls (male, 15-weeks, n=13) were untreated. IOP was measured in both eyes 2-3 times per week for 3 weeks, followed by OMR and rsfMRI experiments at 7 Tesla (Fig. 1A). Results : Sustained IOP elevation was confirmed in the right eyes of the glaucoma model (Fig. 1B). Over 90% of mouse optic nerve fibers are known to project to the contralateral visual brain; rCVR decreased in the left but not right VC, whereas rCVR increased in the right BF in the glaucoma model but not the controls (Fig. 2A). These rCVR changes were inversely coupled (Fig. 2B). In addition, IOP of the injected eye was inversely correlated with rCVR in the left VC, while positively correlated with rCVR in the right BF (Fig. 2C). OMR revealed a decrease in visual acuity and an increase in visual contrast threshold for the injected eye (Fig. 2D) indicating visual impairment. The decrease in visual acuity was inversely correlated with rCVR in the BF (Fig. 2E). Conclusions : Mouse rCVR mapping using rsfMRI detects widespread brain changes induced by chronic IOP elevation, and demonstrates vascular involvement in glaucoma both within and beyond the primary visual pathways
EMBASE:639121437
ISSN: 1552-5783
CID: 5379922
Can the Inner Nuclear Layer Thickness Help Detect Progression in Advanced Glaucoma? [Meeting Abstract]
Purpose : The ability to detect progression in eyes with advanced glaucoma is challenging because of known limitations of commonly used structural and functional parameters reaching their minimal measurable limit (floor effect) or increased measurement variability. We examined the ability of inner nuclear layer (INL) thickness measurements to demonstrate change longitudinally in eyes with early and advanced severity glaucoma. Methods : Subjects with glaucoma and >=4 visits were included in the study. Subjects in the ?Early/Moderate? group (EG) had average circumpapillary retinal nerve fiber layer (cRNFL) thicknesses >=60mum and subjects in the ?Advanced? group (AG) had average cRNFL thicknesses <=60mum. All subjects had comprehensive ophthalmic examination, Humphrey visual field (Zeiss, Dublin, CA) testing, and spectral-domain OCT (Cirrus HD-OCT; Zeiss) optic nerve head (ONH) and macula scans. Segmentation of the INL was performed using the Iowa Reference Algorithms (Retinal Image Analysis Lab, Iowa Institute for Biomedical Imaging, Iowa City, IA) and segmentation errors were manually corrected by a trained grader. Overall INL thickness along with the superior and inferior hemifields were used for analysis. Rates of progression were estimated from longitudinal OCT and visual field (VF) data using mixed effects models adjusting for baseline age, follow-up duration, and signal strength at each visit. Results : 23 eyes (23 subjects), 12 with EG and 11 with AG, were included in the study. At baseline, a statistically significant difference between groups was detected in MD, cRNFL, and GCIPL thicknesses (Table 1). In EG eyes, the rate of change was significantly different than a zero slope for cRNFL thickness, C:D ratio, and GCIPL thickness (Table 2). Inferior INL thickness was the only INL parameter showing significant rate of change. However, in the advanced group, all parameters (including both global and sectoral INL thicknesses) showed significant rate of change except for the cRNFL. Conclusions : Longitudinal measurements of INL thickness may be useful for following disease progression in subjects with advanced-stage glaucoma where cRNFL thickness is no longer useful
EMBASE:639121096
ISSN: 1552-5783
CID: 5379932
Cerebrospinal fluid dynamics and its coupling with global brain activity are altered in early glaucoma patients [Meeting Abstract]
Purpose : Glaucoma is a widespread neurodegenerative disease affecting the retinal ganglion cells, optic nerve, distal visual pathways and beyond. Recent studies suggest that cerebrospinal fluid (CSF) plays a role in clearing wastes from the brain and that CSF dynamics may be altered in neurodegenerative diseases. Since CSF dynamics can be facilitated by the global brain activity, in the present study, we investigated how the dynamics of CSF and its coupling with global brain activity may be altered in glaucoma using functional magnetic resonance imaging (fMRI). Methods : 19 early glaucoma patients (62.3+/-1.7 yrs) (mean+/-SEM), 19 advanced glaucoma patients (64.7+/-2.4 yrs), and 19 healthy subjects (59+/-2.4 yrs) underwent anatomical MRI and resting-state fMRI with eyes closed. Age did not differ across groups (P=0.188). We extracted the CSF signal time profiles from the fourth ventricle (Fig. 1A) and the global brain activity [blood-oxygenation-level-dependent signal time profiles] from the entire gray matter (Fig. 1B). Following previous literature (Han F, et al. PLOS Biol 2021;19), the coupling between the CSF signals and the global brain activity (CSF-BOLD coupling) was examined via cross correlation at the 4s time lag, where more negative values indicate stronger coupling. We also associated these correlations with the volumes of the anterior visual pathway in anatomical MRI. Results : A significant group difference was observed in the power (i.e., strength) of the low frequency (0.01-0.03Hz) in the CSF signals (P=0.013; Fig.1C). Specifically, early glaucoma patients showed significantly greater power than advanced glaucoma patients (Bonferroni P=0.010). The power of the global brain activity showed similar trends but did not reach significance (P=0.390; Fig.1D). The CSF-BOLD coupling at the 4s lag differed significantly across groups (P=0.007; Fig. 1E). Early glaucoma patients had significantly stronger coupling than advanced glaucoma patients (Bonferroni P=0.025) and healthy controls (Bonferroni P=0.013). Further, CSF-BOLD coupling was correlated with the volumes of optic nerve (right: R=-0.342, P=0.009; left: R=-0.344, P=0.009, Fig. 2D,E) and optic chiasm (R=0.264, P=0.047, Fig. 2F). Conclusions : Our observations of the altered CSF dynamics and CSF-BOLD coupling provide physiological evidence to support the recent hypothesis of widespread brain involvements in the early stage of glaucoma
EMBASE:639121005
ISSN: 1552-5783
CID: 5379942
Longitudinal changes in structural and functional measurements along the glaucoma severity spectrum [Meeting Abstract]
Purpose : Previously we described the longitudinal glaucoma relationship between structure and function using a broken stick analysis approach to identify the location where the rate of change accelerates or decelerates. In that analysis we used each measurement point as an independent point, aggregated all eyes from all visits, and treated longitudinal data as cross-sectional. Using improved statistical methodology, we accounted for repeated measurements and the use of data from both eyes in the longitudinal model. The purpose of this study is to identify the locations of tipping points and rates of change before and after them in structural and functional measurements. Methods : Subjects with comprehensive ophthalmic examination and 5 or more visits with qualified visual fields (VF; Humphrey Field Analyzer; Zeiss, Dublin, CA) and OCT (Cirrus HD-OCT; Zeiss) with ONH and macular scans were enrolled. Segmented mixed models that account for repeated measurements were utilized to estimate the tipping points and the difference-in-slope. The number of tipping points was determined by identifying the optimal model using Bayesian information criterion. Results : 216 eyes (164 open angle glaucoma, 45 glaucoma suspect, and 7 healthy eyes) of 145 subjects were analyzed (Table). Retinal nerve fiber layer (RNFL), and ganglion cell inner retinal layer (GCIPL) decreases and cup to disc ratio (CDR) increases since early stages of the disease were measured (Figure). Unlike previous cross-sectional reports, visual field mean deviation (MD) also decreases along with structural parameters since early stages of the disease. RNFL thinning stalls beyond MD<-15.63dB (Figure A) while GCIPL keeps decreasing (B), and CDR slowly increases (C) throughout the functional damage range. Direct comparison between the structural parameters shows that RNFL thinning decelerates in advanced disease compared to both GCIPL and CDR and GCIPL thinning decelerates compared to CDR. Conclusions : Structural and functional measurements (RNFL, GCIPL, CDR and MD) are useful to evaluate glaucoma change from early stages of the disease. As glaucoma progresses and RNFL reaches its minimal measurable level GCIPL, CDR and MD remain useful to evaluate the disease. The clinical routine for following subjects with glaucoma should account for the ability to measure relevant parameters at various stages of disease
EMBASE:639120931
ISSN: 1552-5783
CID: 5379952
Artificial Intelligence Algorithms in Diabetic Retinopathy Screening
PURPOSE OF REVIEW/OBJECTIVE:In this review, we focus on artificial intelligence (AI) algorithms for diabetic retinopathy (DR) screening and risk stratification and factors to consider when implementing AI algorithms in the clinic. RECENT FINDINGS/RESULTS:AI algorithms have been adopted, and have received regulatory approval, for automated detection of referable DR with clinically acceptable diagnostic performance. While these metrics are an important first step, performance metrics that go beyond measures of technical accuracy are needed to fully evaluate the impact of AI algorithm on patient outcomes. Recent advances in AI present an exciting opportunity to improve patient care. Using DR as an example, we have reviewed factors to consider in the implementation of AI algorithms in real-world clinical practice. These include real-world evaluation of safety, efficacy, and equity (bias); impact on patient outcomes; ethical, logistical, and regulatory factors.
PMID: 35438458
ISSN: 1539-0829
CID: 5218252
Hemi- and Central Retinal Vein Occlusion Associated with COVID-19 Infection in Young Patients without Known Risk Factors
PURPOSE/OBJECTIVE:Venous thromboembolic complications have been reported in association with coronavirus disease 2019 (COVID-19) infection. We raised awareness regarding a potential temporal association between COVID-19 infection and retinal vein occlusion (RVO). DESIGN/METHODS:Multicenter, retrospective, nonconsecutive case series. SUBJECTS/METHODS:Patients presenting with hemi-RVO (HRVO) or central RVO (CRVO) between March 2020 and March 2021, with confirmed COVID-19 infection, were included. The exclusion criteria were as follows: age >50 years, hypertension, diabetes, glaucoma, obesity, underlying hypercoagulable states, and those requiring intubation during hospitalization. METHODS:This was a multicenter, retrospective, nonconsecutive case series including patients presenting with hemi-RVO (HRVO) or central RVO (CRVO) between March 2020 and March 2021, with confirmed COVID-19 infection. The exclusion criteria were as follows: age >50 years, hypertension, diabetes, glaucoma, obesity, underlying hypercoagulable states, and those requiring intubation during hospitalization. MAIN OUTCOME MEASURES/METHODS:Ophthalmic findings, including presenting and final visual acuity (VA), imaging findings, and clinical course. RESULTS:Twelve eyes of 12 patients with CRVO (9 of 12) or HRVO (3 of 12) after COVID-19 infection were included. The median age was 32 years (range, 18-50 years). Three patients were hospitalized, but none were intubated. The median time from COVID-19 diagnosis to ophthalmic symptoms was 6.9 weeks. The presenting VA ranged from 20/20 to counting fingers, with over half (7 of 12) having a VA of ≥20/40. OCT revealed macular edema in 42% of the eyes; of these, 80% (4 of 5) were treated with anti-VEGF injections. Ninety-two percent (11 of 12) had partial or complete resolution of ocular findings at final follow-up. Four eyes (33%) had retinal thinning, as determined using OCT, by the end of the study interval. The final VA ranged from 20/20 to 20/60, with 11 of the 12 (92%) eyes achieving a VA of ≥20/40 at a median final follow-up period of 13 weeks (range, 4-52 weeks). CONCLUSIONS:Although we acknowledge the high seroprevalence of COVID-19 and that a causal relationship cannot be established, we reported this series to raise awareness regarding the potential risk of retinal vascular events due to a heightened thromboinflammatory state associated with COVID-19 infection.
PMCID:8907133
PMID: 35278727
ISSN: 2468-6530
CID: 5264742
Combining Spectral-Domain OCT and Air-Puff Tonometry Analysis to Diagnose Keratoconus
PURPOSE/OBJECTIVE:To investigate the diagnostic capacity of spectral-domain optical coherence tomography (SD-OCT) combined with air-puff tonometry using artificial intelligence (AI) in differentiating between normal and keratoconic eyes. METHODS:Patients who had either undergone uneventful laser vision correction with at least 3 years of stable follow-up or those who had forme fruste keratoconus (FFKC), early keratoconus (EKC), or advanced keratoconus (AKC) were included. SD-OCT and biomechanical information from air-puff tonometry was divided into training and validation sets. AI models based on random forest or neural networks were trained to distinguish eyes with FFKC from normal eyes. Model accuracy was independently tested in eyes with FFKC and normal eyes. Receiver operating characteristic (ROC) curves were generated to determine area under the curve (AUC), sensitivity, and specificity values. RESULTS:A total of 223 normal eyes from 223 patients, 69 FFKC eyes from 69 patients, 72 EKC eyes from 72 patients, and 258 AKC eyes from 258 patients were included. The top AUC ROC values (normal eyes compared with AKC and EKC) were Pentacam Random Forest Index (AUC = 0.985 and 0.958), Tomographic and Biomechanical Index (AUC = 0.983 and 0.925), and Belin-Ambrósio Enhanced Ectasia Total Deviation Index (AUC = 0.981 and 0.922). When SD-OCT and air-puff tonometry data were combined, the random forest AI model provided the highest accuracy with 99% AUC for FFKC (75% sensitivity; 94.74% specificity). CONCLUSIONS:.
PMID: 35686708
ISSN: 1081-597x
CID: 5484772
Comparative Contralateral Randomized Clinical Trial of Standard (3 mW/cm2) Versus Accelerated (9 mW/cm2) CXL in Patients With Down Syndrome: 3-Year Results
PURPOSE/OBJECTIVE:, 30 min) in patients with Down syndrome who had keratoconus. METHODS:In this contralateral randomized clinical trial, 27 patients with Down syndrome aged 15.78 ± 2.46 years (range: 10 to 19 years) were enrolled. CXL was performed using the KXL System (Avedro, Inc) under general anesthesia, and patients were followed up for 3 years. The main outcome measure was a change in average keratometry in the 3-mm zone around the steepest point (zonal Kmax-3mm). Secondary outcomes were changes in Corvis ST (Oculus Optikgeräte GmbH) biomechanical parameters and vision, refraction, and corneal tomography measurements. RESULTS:< .0167). Corneal stiffness in the accelerated group was stable for 2 years, and the decline mainly occurred during the third year. CONCLUSIONS:.
PMID: 35686709
ISSN: 1081-597x
CID: 5484782
Orbital Sarcoidosis Masquerading as Late Postoperative Blepharoplasty Complication: A Case Report [Case Report]
Orbital sarcoid is a rare entity and may be the first manifestation of systemic sarcoidosis. We report a case of orbital sarcoidosis where diagnosis was complicated by a history of lower eyelid blepharoplasty. The patient presented with progressive swelling of the left lower eyelid, which was assumed to be a late complication of her surgery. After failing multiple treatments, MRI orbits was obtained and revealed an enhancing lesion in the left orbit inseparable from the lacrimal gland and inferior oblique muscle. Biopsy showed noncaseating granulomatous inflammation, and the patient was eventually diagnosed with sarcoidosis.
PMID: 35323140
ISSN: 1537-2677
CID: 5533962
Insights from the IronTract challenge: Optimal methods for mapping brain pathways from multi-shell diffusion MRI
Limitations in the accuracy of brain pathways reconstructed by diffusion MRI (dMRI) tractography have received considerable attention. While the technical advances spearheaded by the Human Connectome Project (HCP) led to significant improvements in dMRI data quality, it remains unclear how these data should be analyzed to maximize tractography accuracy. Over a period of two years, we have engaged the dMRI community in the IronTract Challenge, which aims to answer this question by leveraging a unique dataset. Macaque brains that have received both tracer injections and ex vivo dMRI at high spatial and angular resolution allow a comprehensive, quantitative assessment of tractography accuracy on state-of-the-art dMRI acquisition schemes. We find that, when analysis methods are carefully optimized, the HCP scheme can achieve similar accuracy as a more time-consuming, Cartesian-grid scheme. Importantly, we show that simple pre- and post-processing strategies can improve the accuracy and robustness of many tractography methods. Finally, we find that fiber configurations that go beyond crossing (e.g., fanning, branching) are the most challenging for tractography. The IronTract Challenge remains open and we hope that it can serve as a valuable validation tool for both users and developers of dMRI analysis methods.
PMID: 35636227
ISSN: 1095-9572
CID: 5235852
Modified technique for sutureless amniotic membrane transplantation in acute Stevens-Johnson syndrome using fibrin sealant [Letter]
PMID: 35644447
ISSN: 1937-5913
CID: 5236012
COVID-19 vaccination hesitancy and its association with altered presentation of primary rhegmatogenous retinal detachment
PURPOSE/OBJECTIVE:Evaluate factors associated with coronavirus 2019 (COVID-19) vaccine hesitancy and clinical trends in primary rhegmatogenous retinal detachments (RRD) during first year of vaccine availability. DESIGN/METHODS:Single-center, clinical cohort study METHODS: : Consecutive patients from December 14, 2020 to December 12, 2021 presenting vaccinated (Prior-), subsequently vaccinated (Later-), or remaining unvaccinated (Never-Vax). Primary outcome was proportion with macula-off (mac-off) RRD. Secondary outcomes included logarithm of the minimum angle of resolution (logMAR) best-corrected visual acuity (BCVA), primary proliferative vitreoretinopathy (PVR), proportion lost to follow-up, and distance traveled. RESULTS:1,047 patients were divided into 391 Prior-, 252 Later-, and 404 Never-Vax cohorts. Significantly greater proportion of Later- and Never-Vax cohorts presented with mac-off RRDs (Prior-Vax = 44.5%; Later-Vax = 54%, P < 0.0001; Never-Vax = 57.9%, P < 0.0001) and primary PVR (Prior-Vax = 4.3%; Later-Vax = 13.6%, P < 0.0001; Never-Vax = 17.1%, P < 0.0001) compared to Prior-Vax cohort. Significantly greater proportion of Never-Vax cohort (7.7%, P < 0.0001) were lost to follow-up compared to Prior- (2.3%) and Later-Vax (2.2%) cohorts. Never-Vax cohort (median = 35 miles) traveled further compared to Prior- (median = 22.3 miles; P < 0.0001) and Later-Vax cohorts (25.45 miles; P = 0.0038). Prior-Vax cohort had significantly better (P < 0.05) initial (median = 0.30 logMAR) and final (0.18 logMAR) BCVA compared to Later- (Initial: 0.54 logMAR; Final: 0.30 logMAR) and Never-vax (Initial: 0.70 logMAR; Final: 0.40 logMAR) cohorts. CONCLUSIONS:COVID-19 vaccine hesitancy is associated with worse clinical presentation and outcomes for primary RRD.
PMID: 35609676
ISSN: 1879-1891
CID: 5264752
Synaptotagmins 1 and 7 Play Complementary Roles in Somatodendritic Dopamine Release
The molecular mechanisms underlying somatodendritic dopamine (DA) release remain unresolved, despite the passing of decades since its discovery. Our previous work showed robust release of somatodendritic DA in submillimolar extracellular Ca2+ concentration ([Ca2+]o). Here we tested the hypothesis that the high-affinity Ca2+ sensor synaptotagmin 7 (Syt7), is a key determinant of somatodendritic DA release and its Ca2+ dependence. Somatodendritic DA release from SNc DA neurons was assessed using whole-cell recording in midbrain slices from male and female mice to monitor evoked DA-dependent D2 receptor-mediated inhibitory currents (D2ICs). Single-cell application of an antibody to Syt7 (Syt7 Ab) decreased pulse train-evoked D2ICs, revealing a functional role for Syt7. The assessment of the Ca2+ dependence of pulse train-evoked D2ICs confirmed robust DA release in submillimolar [Ca2+]o in wild-type (WT) neurons, but loss of this sensitivity with intracellular Syt7 Ab or in Syt7 knock-out (KO) mice. In millimolar [Ca2+]o, pulse train-evoked D2ICs in Syt7 KOs showed a greater reduction in decreased [Ca2+]o than seen in WT mice; the effect on single pulse-evoked DA release, however, did not differ between genotypes. Single-cell application of a Syt1 Ab had no effect on train-evoked D2ICs in WT SNc DA neurons, but did cause a decrease in D2IC amplitude in Syt7 KOs, indicating a functional substitution of Syt1 for Syt7. In addition, Syt1 Ab decreased single pulse-evoked D2ICs in WT cells, indicating the involvement of Syt1 in tonic DA release. Thus, Syt7 and Syt1 play complementary roles in somatodendritic DA release from SNc DA neurons.SIGNIFICANCE STATEMENT The respective Ca2+ dependence of somatodendritic and axonal dopamine (DA) release differs, resulting in the persistence of somatodendritic DA release in submillimolar Ca2+ concentrations too low to support axonal release. We demonstrate that synaptotagmin7 (Syt7), a high-affinity Ca2+ sensor, underlies phasic somatodendritic DA release and its Ca2+ sensitivity in the substantia nigra pars compacta. In contrast, we found that synaptotagmin 1 (Syt1), the Ca2+ sensor underlying axonal DA release, plays a role in tonic, but not phasic, somatodendritic DA release in wild-type mice. However, Syt1 can facilitate phasic DA release after Syt7 deletion. Thus, we show that both Syt1 and Syt7 act as Ca2+ sensors subserving different aspects of somatodendritic DA release processes.
PMCID:9097777
PMID: 35361702
ISSN: 1529-2401
CID: 5220042
Microstructural Deformations Within the Depth of the Lamina Cribrosa in Response to Acute In Vivo Intraocular Pressure Modulation
Purpose:The lamina cribrosa (LC) is a leading target for initial glaucomatous damage. We investigated the in vivo microstructural deformation within the LC volume in response to acute IOP modulation while maintaining fixed intracranial pressure (ICP). Methods:In vivo optic nerve head (ONH) spectral-domain optical coherence tomography (OCT) scans (Leica, Chicago, IL, USA) were obtained from eight eyes of healthy adult rhesus macaques (7 animals; ages = 7.9-14.4 years) in different IOP settings and fixed ICP (8-12 mm Hg). IOP and ICP were controlled by cannulation of the anterior chamber and the lateral ventricle of the brain, respectively, connected to a gravity-controlled reservoir. ONH images were acquired at baseline IOP, 30 mm Hg (H1-IOP), and 40 to 50 mm Hg (H2-IOP). Scans were registered in 3D, and LC microstructure measurements were obtained from shared regions and depths. Results:Only half of the eyes exhibited LC beam-to-pore ratio (BPR) and microstructure deformations. The maximal BPR change location within the LC volume varied between eyes. BPR deformer eyes had a significantly higher baseline connective tissue volume fraction (CTVF) and lower pore aspect ratio (P = 0.03 and P = 0.04, respectively) compared to BPR non-deformer. In all eyes, the magnitude of BPR changes in the anterior surface was significantly different (either larger or smaller) from the maximal change within the LC (H1-IOP: P = 0.02 and H2-IOP: P = 0.004). Conclusions:The LC deforms unevenly throughout its depth in response to IOP modulation at fixed ICP. Therefore, analysis of merely the anterior LC surface microstructure will not fully capture the microstructure deformations within the LC. BPR deformer eyes have higher CTVF than BPR non-deformer eyes.
PMID: 35604666
ISSN: 1552-5783
CID: 5247842
Zoster Eye Disease Study: Rationale and Design
PURPOSE/OBJECTIVE:The purpose of this study was to describe the rationale and design of the Zoster Eye Disease Study (ZEDS). METHODS:ZEDS is a National Eye Institute-supported randomized clinical trial designed to determine whether 1 year of suppressive valacyclovir in patients with herpes zoster ophthalmicus (HZO) reduces complications because there is currently no high-quality evidence to support its use. Eligible patients are 18 years and older, immunocompetent, have a history of a typical rash at disease onset, and have had a record of active epithelial or stromal keratitis or iritis within 1 year before enrollment. Exclusion criteria include estimated glomerular filtration rate less than 45 or pregnancy. The primary endpoint is the time to first occurrence of new or worsening dendriform epithelial keratitis, stromal keratitis without or with ulceration, endothelial keratitis, or iritis due to HZO during 12 months of study treatment requiring prespecified treatment changes. The study has 80% power to detect a 30% difference between treatment groups, with a 30% rate of endpoints by 1 year assumed among controls. Secondary and exploratory questions include whether there is a persistent treatment benefit during the 6 months after treatment, whether development of postherpetic neuralgia varies by treatment group, and whether vaccinations against herpes zoster affect study outcomes and coronavirus disease 19 status. RESULTS:Over approximately 4 years, over 400 study participants have been enrolled. CONCLUSIONS:ZEDS aims to provide scientific evidence on whether suppressive valacyclovir treatment improves outcomes in HZO and should become the standard of care.
PMID: 35090154
ISSN: 1536-4798
CID: 5154932
Response to the Letter to the Editor: Patient Concerns Regarding Suspended Ophthalmic Care Due to COVID-19
PMID: 35320141
ISSN: 1536-481x
CID: 5235092
AUTOFLUORESCENT TIMELINE OF SPOTS AND DOTS IN MULTIPLE EVANESCENT WHITE DOT SYNDROME
PURPOSE/OBJECTIVE:To describe the recovery timeline of spots and dots in multiple evanescent white dot syndrome. METHODS:Sequential multimodal retinal imaging including fundus autofluorescence and cross-sectional and en face optical coherence tomography was performed to track the development and resolution of spots and dots in a case of multiple evanescent white dot syndrome. RESULTS:En face optical coherence tomography showed that the spots are the result of ellipsoid zone loss and are hyperautofluorescent due to unmasking of the underlying retinal pigment epithelium autofluorescence. Conversely, the dots are hyperreflective with cross-sectional and en face optical coherence tomography and hyperautofluorescent, which we propose may be due to accumulation of degenerated photoreceptor material including fluorophores with autofluorescent capability such as precursors of A2E. The earlier resolution of the hyperautofluorescent spots allowed for later detection of the hyperautofluorescent dots. CONCLUSION/CONCLUSIONS:This case report illustrates the different recovery timelines of spots and dots in multiple evanescent white dot syndrome. Although both lesion types are hyperautofluorescent, the mechanism of autofluorescence is distinctive and may be explained by their contrasting pathoanatomy.
PMID: 32032290
ISSN: 1937-1578
CID: 4300892
Asia-Pacific journal of ophthalmology (Philadelphia, Pa.). 2022:11(3):215-218.DOI: 10.1097/APO.0000000000000469
Promoting Transparency and Standardization in Ophthalmologic Artificial Intelligence: A Call for Artificial Intelligence Model Card
PMID: 35772083
ISSN: 2162-0989
CID: 5278692
Economic Evaluation of the Merit-Based Incentive Payment System for Ophthalmologists: Analysis of 2019 Quality Payment Program Data
Importance/UNASSIGNED:The Merit-Based Incentive Payment System (MIPS) is intended to promote high-value health care through quality-related Medicare payment adjustments. Objective/UNASSIGNED:To assess the economic evaluation of MIPS scoring and reporting on ophthalmologists. Design, Setting, and Participants/UNASSIGNED:In this retrospective, cross-sectional, multicenter economic evaluation conducted from October 10 to November 30, 2021, MIPS performance and related payment adjustments were evaluated using the US Centers for Medicare & Medicaid Service (CMS) public data files for ophthalmologists. Participants were stratified by reporting affiliation. Analysis of variance and summary statistics were used to characterize and compare total and subcategory MIPS scores and adjustments received by participants. Reported CMS methodology and performance year (PY) 2019 payment percentages were used to estimate payment adjustments for the following categories: positive MIPS adjustment plus potential additional adjustment for exceptional performance, positive MIPS adjustment, neutral payment adjustment, negative MIPS payment adjustment, and maximum negative MIPS payment adjustment. Study participants included ophthalmologists registered for Medicare Part B with participation in the Quality Payment Program (QPP) in PY 2019. Main Outcomes and Measures/UNASSIGNED:Proportion of ophthalmologists qualifying for payment adjustments and payment adjustments. Results/UNASSIGNED:For PY 2019, 76.5% of ophthalmologists (13 621) who registered for Medicare participated in the MIPS pathway of the QPP. Ophthalmologists practiced in a predominantly large metropolitan area (12 302; 90.3%). Roughly 99% of participants (11 182) received nonnegative reimbursement adjustments, and 92.6% (10 367) received positive adjustments. Ophthalmologists filing as individuals were less likely to achieve exceptional performance scores compared with those who had a filing category of advanced alternative payment model (APM; odds ratio [OR], 0.0003; 95% CI, 0.00002-0.00481) or group (OR, 0.21013; 95% CI, 0.19020-0.23215). When analyzing participating ophthalmologists with available Medicare payment data (11 193), a total of 8777 (78.4%) achieved exceptional MIPS scores corresponding to mean (SD) adjustments per physician of $244.60 ($217.36) to $4864.78 ($4323.08), or 0.07% ($2 146 835.21 of $3 212 011 252.88) to 1.33% ($42 698 166.89 of $3 212 011 252.88), of the total nondrug Medicare payment. Conclusions and Relevance/UNASSIGNED:Results of this economic evaluation showed that although 78.4% of ophthalmologists received exceptional positive payment adjustments, roughly 84% (798916 of 954615) of all health care professionals nationally achieved this benchmark. Exceptional MIPS was associated with filing as group or APM, resulting in, on average, a relatively small additional payment per participant; this suggests that ophthalmologists who file as individuals should consider an alternative filing approach. Changes in MIPS methodology may disproportionately affect certain ophthalmologists, which warrants further study.
PMCID:9011174
PMID: 35420641
ISSN: 2168-6173
CID: 5219092
Double-layer sign in neovascular age-related macular degeneration - do we treat?
PMID: 34132057
ISSN: 1755-3768
CID: 4932602
A Case for The Use of Artificial Intelligence in Glaucoma Assessment
We hypothesize that artificial intelligence applied to relevant clinical testing in glaucoma has the potential to enhance the ability to detect glaucoma. This premise was discussed at the recent Collaborative Community for Ophthalmic Imaging meeting, "The Future of Artificial Intelligence-Enabled Ophthalmic Image Interpretation: Accelerating Innovation and Implementation Pathways," held virtually September 3-4, 2020. The Collaborative Community in Ophthalmic Imaging (CCOI) is an independent self-governing consortium of stakeholders with broad international representation from academic institutions, government agencies, and the private sector whose mission is to act as a forum for the purpose of helping speed innovation in healthcare technology. It was one of the first two such organizations officially designated by the FDA in September 2019 in response to their announcement of the collaborative community program as a strategic priority for 2018-2020. Further information on the CCOI can be found online at their website (https://www.cc-oi.org/about). Artificial intelligence for glaucoma diagnosis would have high utility globally, as access to care is limited in many parts of the world and half of all people with glaucoma are unaware of their illness. The application of artificial intelligence technology to glaucoma diagnosis has the potential to broadly increase access to care worldwide, in essence flattening the Earth by providing expert level evaluation to individuals even in the most remote regions of the planet.
PMID: 34954220
ISSN: 2589-4196
CID: 5107932
Glymphatic imaging and modulation of the optic nerve
Optic nerve health is essential for proper function of the visual system. However, the pathophysiology of certain neurodegenerative disease processes affecting the optic nerve, such as glaucoma, is not fully understood. Recently, it was hypothesized that a lack of proper clearance of neurotoxins contributes to neurodegenerative diseases. The ability to clear metabolic waste is essential for tissue homeostasis in mammals, including humans. While the brain lacks the traditional lymphatic drainage system identified in other anatomical regions, there is growing evidence of a glymphatic system in the central nervous system, which structurally includes the optic nerve. Named to acknowledge the supportive role of astroglial cells, this perivascular fluid drainage system is essential to remove toxic metabolites from the central nervous system. Herein, we review existing literature describing the physiology and dysfunction of the glymphatic system specifically as it relates to the optic nerve. We summarize key imaging studies demonstrating the existence of a glymphatic system in the optic nerves of wild-type rodents, aquaporin 4-null rodents, and humans; glymphatic imaging studies in diseases where the optic nerve is impaired; and current evidence regarding pharmacological and lifestyle interventions that may help promote glymphatic function to improve optic nerve health. We conclude by highlighting future research directions that could be applied to improve imaging detection and guide therapeutic interventions for diseases affecting the optic nerve.
PMCID:8552868
PMID: 34558505
ISSN: 1673-5374
CID: 5110742
Cost-Effectiveness Analysis of Minimally Invasive Trabecular Meshwork Stents with Phacoemulsification
PURPOSE/OBJECTIVE:To investigate the costs and effects of implanting trabecular meshwork bypass stents during cataract surgery from a societal perspective in the United States. DESIGN/METHODS:Cost-utility analysis using Markov models and efficacy/safety data from published pivotal or randomized control trials (RCTs) of devices investigated. PARTICIPANTS/METHODS:Patients aged 65 years and older with mild to moderate primary open-angle glaucoma with or without visually significant cataract. METHODS:With the use of Markov models, glaucoma progression through 4 glaucoma states (mild, moderate, advanced, severe/blind) and death were simulated over 35 years. The cohort with cataract entered the model and received cataract surgery with or without device implantation. We included a medication management only reference group to calculate total costs and outcomes for those without cataract. Intraocular pressure (IOP) reductions from RCTs were converted to glaucoma state transition probabilities using visual field (VF) mean deviation (MD) decline rates from the Early Manifest Glaucoma Trial. Progressive thinning of the retinal nerve fiber layer (RNFL) on OCT imaging related to IOP control warranted further intervention, including adding medication, selective laser trabeculoplasty (SLT), or incisional glaucoma surgery. We estimated whole costs at Medicare rates and obtained utility values for glaucoma states from previous studies. Incremental costs per quality-adjusted life-year (QALY) gained were evaluated at a QALY threshold of $50 000. One-way deterministic sensitivity analysis, scenario analyses, and probabilistic sensitivity analyses addressed parameter uncertainty and demonstrated model robustness. MAIN OUTCOME MEASURES/METHODS:Total costs, QALY, and incremental cost-effectiveness ratio (ICER). RESULTS:Over 35 years in the base case, the Hydrus (Ivantis, Inc.) implanted with cataract surgery arm cost $48 026.13 and gained 12.26 QALYs. The iStent inject (Glaukos Corp.) implanted with cataract surgery arm cost $49 599.86 and gained 12.21 QALYs. Cataract surgery alone cost $54 409.25 and gained 12.04 QALYs. Initial nonsurgical management cost $57 931.22 and gained 11.74 QALY. The device arms dominated or were cost-effective compared with cataract surgery alone within 5 years and throughout sensitivity analyses. The iStent inject arm was cost-effective in 94.19% of iterations in probabilistic sensitivity analyses, whereas the Hydrus arm was cost-effective in 94.69% of iterations. CONCLUSIONS:Implanting the Hydrus Microstent or iStent inject during cataract surgery is cost-effective at a conservative QALY threshold.
PMID: 34563713
ISSN: 2589-4196
CID: 5061552
Trends, Factors, and Outcomes Associated with Immediate Sequential Bilateral Cataract Surgery (ISBCS) Among Medicare Beneficiaries
PURPOSE/OBJECTIVE:To report the incidence of immediate (ISBCS) and delayed sequential bilateral cataract surgery (DSBCS) and identify factors associated with undergoing ISBCS. DESIGN/METHODS:Retrospective cohort study. SUBJECTS/METHODS:Medicare beneficiaries aged ≥65 who underwent ISBCS and DSBCS from 2011 to 2019. METHODS:Population-based analysis of the 100% Medicare fee-for-service carrier claims data. Logistic regression models were performed to evaluate factors associated with ISBCS. MAIN OUTCOME MEASURES/METHODS:1) Incidence of ISBCS and DSBCS, 2) demographic, ocular and medical characteristics associated with receipt of ISBCS, and 3) rates of endophthalmitis and cystoid macular edema (CME) after ISBCS or DSBCS. RESULTS:A total of 4,014 (0.2%) ISBCS and 1,944,979 (99.8%) DSBCS patients were identified. Black (OR:2.31, 95%CI: 2.06-2.59), Asian (OR:1.82, 95%CI: 1.51-2.12), or Native American (OR:2.42, 95%CI: 1.81-3.23) patients were more likely to receive ISBCS compared to White patients. Patients residing in rural areas had higher likelihood of ISBCS (OR:1.26, 95%CI: 1.17-1.35) compared to metropolitan areas. Patients operated at a hospital compared to ambulatory setting (OR:2.71, 95%CI: 2.53-2.89) were more likely to receive ISBCS. Patients with bilateral complex vs. non-complex cataract (OR:3.23, 95%CI: 2.95-3.53) were more likely to receive ISBCS. Patients with a Charlson comorbidity index (CCI) of 1-2 (OR:1.45, 95%CI: 1.29-1.62), 3-4 (OR:1.70, 95%CI: 1.47-1.97), 5-6 (OR:1.97, 95%CI: 1.62-2.39), and CCI≥7 (OR:1.97, 95%CI: 1.55-2.50) were all more likely to receive ISBCS compared to those with CCI=0. In contrast, patients with glaucoma (OR:0.82, 95%CI: 0.76-0.89), macular degeneration (OR:0.75, 95%CI: 0.68-0.82), and macular hole/epiretinal membrane (OR:0.55, 95%CI: 0.48-0.65) were less likely to undergo ISBCS compared to those without. Cumulatively, there was no significant difference in endophthalmitis rate within 42 days between ISBCS (1.74 per 1,000 ISBCS) and DSBCS (1.01 per 1,000 DSBCS; p=0.15). Similarly, there was no significant cumulative difference between ISBCS (1.79 per 100 ISBCS) and DSBCS (1.96 per 100 DSBCS) CME rates (p=0.48). CONCLUSION/CONCLUSIONS:Overall utilization of ISBCS among Medicare beneficiaries remains low over the past decade, though rates of endophthalmitis and CME were comparable to DSBCS. Race, geography, systemic and ocular comorbidities were associated with receiving ISBCS. ISBCS represents a potential opportunity to improve access to cataract surgery.
PMID: 34971649
ISSN: 1549-4713
CID: 5108372
Trends in the Clinical Presentation of Primary Rhegmatogenous Retinal Detachments During the First Year of the COVID-19 Pandemic
PURPOSE:To evaluate the effect of 1 full year of the coronavirus disease 2019 (COVID-19) pandemic on clinical presentation of acute, primary rhegmatogenous retinal detachment (RRD). DESIGN:Single-center, retrospective observational cohort study. METHODS:Patients were divided into 2 cohorts: consecutive patients treated for primary RRD during the COVID-19 pandemic (March 9, 2020, to March 7, 2021; pandemic cohort) and patients treated during the corresponding time in previous year (March 11, 2019, to March 8, 2020; control cohort). MAIN OUTCOME MEASURES:Proportion of patients presenting with macula-involving (mac-off) or macula-sparring (mac-on) RRD. RESULTS:A total of 952 patients in the pandemic cohort and 872 patients in the control cohort were included. Demographic factors were similar. Compared with the control cohort, a significantly greater number of pandemic cohort patients presented with mac-off RRDs ([60.92%] pandemic, [48.17%] control, PÂ =Â .0001) and primary proliferative vitreoretinopathy ([15.53%] pandemic, [6.9%] control, PÂ =Â .0001). Pandemic cohort patients (10.81%) had significantly higher rates of lost to follow-up compared with the control cohort (4.43%; PÂ =Â .0001). Patients new to our clinic demonstrated a significant increase in mac-off RRDs in the pandemic cohort (65.35%) compared with the control cohort (50.40%; PÂ =Â .0001). Pandemic cohort patients showed worse median final best-corrected visual acuity (0.30 logarithm of the minimum angle of resolution) compared with the control cohort (0.18 logarithm of the minimum angle of resolution; PÂ =Â .0001). CONCLUSIONS:Patients with primary RRD during the first year of the COVID-19 pandemic were more likely to have mac-off disease, present with primary proliferative vitreoretinopathy, be lost to follow-up, and have worse final best-corrected visual acuity outcomes.
PMCID:8603252
PMID: 34801509
ISSN: 1879-1891
CID: 5264732
Titanium T-Plate as a Stabilizing Platform in the Management of Acquired Nystagmus and Oscillopsia Without a Null Zone
The primary goal of nystagmus treatment is to improve visual function and quality of life. Current surgical interventions are limited by regression of effect, serious complications, and reliance on a null zone. Tse and colleagues in 2017 reported the use of a T-plate/suture fixation platform for globe stabilization to treat acquired nystagmus and oscillopsia without a null zone in a patient with bilateral internuclear ophthalmoplegia. However, the improvement in nystagmus was not objectively quantified. This case series reports 2 patients who underwent bilateral T-plate placement which resulted in immediate and sustained improvement of nystagmus objectively measured by videonystagmography.
PMID: 35093990
ISSN: 1537-2677
CID: 5533952
Navigating the White Dot Syndromes with Optical Coherence Tomography (OCT) and OCT Angiography (OCT-A)
INTRODUCTION/UNASSIGNED:White dot syndromes are a heterogeneous group of diseases that affect different layers in the retina and choroid. Multimodal imaging is fundamental in the diagnosis, but also can be crucial in unveiling the pathogenesis of these entities. MATERIAL AND METHODS/UNASSIGNED:Literature review. RESULTS/UNASSIGNED:Optical coherence tomography (OCT) provides depth-resolved, histological grade images of the vitreous, retina, and choroid. This technology is very useful to localize the primary nature and level of pathology of the various white dot syndromes. En face OCT can provide additional information regarding the interrelationship of lesion types. Vascular involvement at the level of the retina, choriocapillaris or choroid can be assessed by en face OCT angiography (OCT-A) and is not limited by masking, leakage or staining as can occur with conventional angiography (fluorescein or indocyanine green angiography) which requires dye injection. CONCLUSION/UNASSIGNED:OCT and OCTA are fundamental in the diagnosis and follow-up of white dots syndromes.
PMID: 35412934
ISSN: 1744-5078
CID: 5218992
A novel glaucoma approach: Stem cell regeneration of the trabecular meshwork
Glaucoma is the leading cause of global irreversible blindness, necessitating research for new, more efficacious treatment options than currently exist. Trabecular meshwork (TM) cells play an important role in the maintenance and function of the aqueous outflow pathway, and studies have found that there is decreased cellularity of the TM in glaucoma. Regeneration of the TM with stem cells has been proposed as a novel therapeutic option by several reports over the last few decades. Stem cells have the capacity for self-renewal and the potential to differentiate into adult functional cells. Several types of stem cells have been investigated in ocular regenerative medicine: tissue specific stem cells, embryonic stem cells, induced pluripotent stem cells, and adult mesenchymal stem cells. These cells have been used in various glaucoma animal models and ex vivo models and have shown success in IOP homeostasis and TM cellularity restoration. They have also demonstrated stability without serious side effects for a significant period of time. Based on current knowledge of TM pathology in glaucoma and existing literature regarding stem cell regeneration of this tissue, we propose a human clinical study as the next step in understanding this potentially revolutionary treatment paradigm. The ability to protect and replace TM cells in glaucomatous eyes could change the field forever.
PMID: 35398015
ISSN: 1873-1635
CID: 5205042
Pathogenesis of keratoconus: NRF2-antioxidant, extracellular matrix and cellular dysfunctions
Keratoconus (KC) is a degenerative disease associated with cell and extracellular matrix (ECM) loss that causes gradual thinning and steepening of the cornea and loss of vision. Collagen cross linking with ultraviolet light treatment can strengthen the ECM and delay weakening of the cornea, but severe cases require corneal transplantation. KC is multifactorial and multigenic, but its pathophysiology is still an enigma. Multiple approaches are being pursued to elucidate the molecular changes that underlie the corneal phenotype to identify relevant genes for tailored candidate searches and to develop potential biomarkers and targets for therapeutic interventions. Recent proteomic and transcriptomic studies suggest dysregulations in oxidative stress, NRF2-regulated antioxidant programs, WNT-signaling, TGF-β, ECM and matrix metalloproteinases. This review aims to provide a broad update on the transcriptomic and proteomic studies of KC with a focus on findings that relate to oxidative stress, and dysregulations in cellular and extracellular matrix functions.
PMID: 35385756
ISSN: 1096-0007
CID: 5201652
Prevalence and characteristics of multifocal choroiditis /punctate inner choroidopathy in pathologic myopia eyes with patchy atrophy
PURPOSE/OBJECTIVE:To determine the prevalence and characteristics of multifocal choroiditis/punctate inner choroidopathy (MFC/PIC) in eyes with patchy atrophy due to pathologic myopia (PM). METHOD/METHODS:Five hundred eyes of 253 patients with patchy atrophy were examined between 2014 and 2020 at the Advanced Clinical Center for Myopia. The main outcome measures included the prevalence and characteristics of active MFC/PIC lesions diagnosed by optical coherence tomography (OCT). RESULTS:Fifty-five of the 500 eyes (11%) diagnosed with patchy atrophy had OCT features of active MFC/PIC lesions such as focal elevations of the RPE filled with medium hyperreflectivity material, curvilinear scars (Schlaegel lines), and/or areas of outer retinal atrophy. At the time when the MFC/PIC was diagnosed, the mean age was 57.3±12.0 years, and the mean axial length was 29.2±1.8 mm. Macular neovascularization (MNV) was found in 45 of eyes (81.8%) with MFC/PIC vs 151 eyes without such findings (33.9%; P <0.001). In 25 of the 55 eyes (45.5%), active MFC/PIC lesions were found before the development of the patchy atrophy. The Bruch's membrane defects were co-located with these lesions. CONCLUSIONS:Active MFC/PIC lesions were identified in a minority of eyes with PM, and a subset of these lesions were observed to progress to findings indistinguishable from myopic patchy atrophy. Evidence of MFC/PIC in eyes with PM appeared to be a risk factor for the development of MNV.
PMID: 34934033
ISSN: 1539-2864
CID: 5139012
3D Microstructure of the Healthy Non-Human Primate Lamina Cribrosa by Optical Coherence Tomography Imaging
Purpose/UNASSIGNED:The lamina cribrosa (LC) has an important role in the pathophysiology of ocular diseases. The purpose of this study is to characterize in vivo, noninvasively, and in 3D the structure of the LC in healthy non-human primates (NHPs). Methods/UNASSIGNED:Spectral-domain optical coherence tomography (OCT; Leica, Chicago, IL) scans of the optic nerve head (ONH) were obtained from healthy adult rhesus macaques monkeys. Using a previously reported semi-automated segmentation algorithm, microstructure measurements were assessed in central and peripheral regions of an equal area, in quadrants and depth-wise. Linear mixed-effects models were used to compare parameters among regions, adjusting for visibility, age, analyzable depth, graded scan quality, disc area, and the correlation between eyes. Spearmen's rank correlation coefficients were calculated for assessing the association between the lamina's parameters. Results/UNASSIGNED:Sixteen eyes of 10 animals (7 males and 3 females; 9 OD, 7 OS) were analyzed with a mean age of 10.5 ± 2.1 years. The mean analyzable depth was 175 ± 37 µm, with average LC visibility of 25.4 ± 13.0% and average disc area of 2.67 ± 0.45mm2. Within this volume, an average of 74.9 ± 39.0 pores per eye were analyzed. The central region showed statistically significantly thicker beams than the periphery. The quadrant-based analysis showed significant differences between the superior and inferior quadrants. The anterior LC had smaller beams and pores than both middle and posterior lamina. Conclusions/UNASSIGNED:Our study provides in vivo microstructure details of NHP's LC to be used as the foundation for future studies. We demonstrated mostly small but statistically significant regional variations in LC microstructure that should be considered when comparing LC measurements.
PMCID:9034718
PMID: 35435922
ISSN: 2164-2591
CID: 5206252
Association of Strabismus With Mood Disorders, Schizophrenia, and Anxiety Disorders Among Children
IMPORTANCE:Children with strabismus have poorer functional vision and decreased quality of life than those without strabismus. OBJECTIVE:To evaluate the association between strabismus and mental illness among children. DESIGN, SETTING, AND PARTICIPANTS:This cross-sectional study analyzed claims data from the OptumLabs Data Warehouse, a longitudinal deidentified commercial insurance claims database, from 12 005 189 patients enrolled in the health plan between January 1, 2007, and December 31, 2017. Eligibility criteria included age younger than 19 years at the time of strabismus diagnosis, enrollment in the health plan between 2007 and 2018, and having at least 1 strabismus claim based on International Classification of Diseases, Ninth Revision, Clinical Modification and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, Clinical Modification codes. Controls were children in the same database with no eye disease codes other than refractive error reported. Demographic characteristics and mental illness claims were compared. Statistical analysis was conducted from December 1, 2018, to July 31, 2021. MAIN OUTCOMES AND MEASURES:Presence of mental illness claims. RESULTS:Among the 12 005 189 patients (6 095 523 boys [50.8%]; mean [SD] age, 8.0 [5.9] years) in the study, adjusted odds ratios for the association of mental illnesses with strabismus were 2.01 (95% CI, 1.99-2.04) for anxiety disorder, 1.83 (95% CI, 1.76-1.90) for schizophrenia, 1.64 (95% CI, 1.59-1.70) for bipolar disorder, 1.61 (95% CI, 1.59-1.63) for depressive disorder, and 0.99 (95% CI, 0.97-1.02) for substance use disorder. There was a moderate association between each strabismus type (esotropia, exotropia, and hypertropia) and anxiety disorder, schizophrenia, bipolar disorder, and depressive disorder; odds ratios ranged from 1.23 (95% CI, 1.17-1.29) for the association between esotropia and bipolar disorder to 2.70 (95% CI, 2.66-2.74) for the association between exotropia and anxiety disorder. CONCLUSIONS AND RELEVANCE:This cross-sectional study suggests that there was a moderate association between strabismus and anxiety disorder, schizophrenia, bipolar disorder, and depressive disorder but not substance use disorder. Recognizing that these associations exist should encourage mental illness screening and treatment for patients with strabismus.
PMID: 35266979
ISSN: 2168-6173
CID: 5533802
Patients presenting with metastases: stage IV uveal melanoma, an international study
OBJECTIVE:To analyse ocular and systemic findings of patients presenting with systemic metastasis. METHODS AND ANALYSIS/UNASSIGNED:It is an international, multicentre, internet-enabled, registry-based retrospective data analysis. Patients were diagnosed between 2001 and 2011. Data included: primary tumour dimensions, extrascleral extension, ciliary body involvement, American Joint Committee on Cancer (AJCC)-tumour, node, metastasis staging, characteristics of metastases. RESULTS:Of 3610 patients with uveal melanoma, 69 (1.9%; 95% CI 1.5 to 2.4) presented with clinical metastasis (stage IV). These melanomas originated in the iris, ciliary body and choroid in 4%, 16% and 80% of eyes, respectively. Using eighth edition AJCC, 8 (11%), 20 (29%), 24 (35%), and 17 (25%) belonged to AJCC T-categories T1-T4. Risk of synchronous metastases increased from 0.7% (T1) to 1.5% (T2), 2.6% (T3) and 7.9% (T4). Regional lymph node metastases (N1a) were detected in 9 (13%) patients of whom 6 (67%) had extrascleral extension. Stage of systemic metastases (known for 40 (59%) stage IV patients) revealed 14 (35%), 25 (63%) and 1 (2%) had small (M1a), medium-sized (M1b) and large-sized (M1c) metastases, respectively. Location of metastases in stage IV patients were liver (91%), lung (16%), bone (9%), brain (6%), subcutaneous tissue (4%) and others (5%). Multiple sites of metastases were noted in 24%. Compared with the 98.1% of patients who did not present with metastases, those with synchronous metastases had larger intraocular tumours, more frequent extrascleral extension, ciliary body involvement and thus a higher AJCC T-category. CONCLUSIONS:Though higher AJCC T-stage was associated with risk for metastases at diagnosis, even small T1 tumours were stage IV at initial presentation. The liver was the most common site of metastases; however, frequent multiorgan involvement supports initial whole-body staging.
PMID: 33452185
ISSN: 1468-2079
CID: 4760072
Long-term visual and anatomic outcomes of patients with peripapillary pachychoroid syndrome
BACKGROUND/AIMS/OBJECTIVE:To analyse the long-term anatomic and visual outcomes of patients with peripapillary pachychoroid syndrome (PPS), a recently described entity in the pachychoroid disease spectrum. METHODS:This study retrospectively included patients from several retina centres worldwide. Visual acuity (VA), retinal thickness and choroidal thickness at baseline, 6 months and final follow-up were assessed. Temporal trends in VA and anatomic characteristics were evaluated. Visual and anatomic outcomes in eyes that were observed versus those that were treated were analysed. RESULTS:Fifty-six eyes of 35 patients were included with mean follow-up of 27±17 months. Median VA was 20/36 at baseline and remained stable through follow-up (p=0.77). Retinal thickness significantly decreased subfoveally (p=0.012), 1.5 mm nasal to the fovea (p=0.002) and 3.0 mm nasal to the fovea (p=0.0035) corresponding to areas of increased thickening at baseline. Choroidal thickness significantly decreased subfoveally (p=0.0030) and 1.5 mm nasal to the fovea (p=0.0030). Forty-three eyes were treated with modalities including antivascular endothelial growth factor injection, photodynamic therapy, and others. VA remained stable in treated eyes over follow-up (p=0.67). An isolated peripapillary fluid pocket in the outer nuclear layer was characteristic of PPS. CONCLUSION/CONCLUSIONS:Patients with PPS experienced decreased retinal oedema and decreased choroidal thickening throughout the course of disease. While some patients experienced visual decline, the overall visual outcome was relatively favourable and independent of trends in retinal or choroidal thickening.
PMID: 33355149
ISSN: 1468-2079
CID: 4731092
Graefe's archive for clinincal & experimental ophthalmology. 2022:260(4):1299-1306.DOI: 10.1007/s00417-021-05453-0
Assessment of the microvasculature in poppers maculopathy
PURPOSE/OBJECTIVE:To investigate a possible microvascular component of poppers maculopathy (PMP) using optical coherence tomography angiography (OCTA). METHODS:Twelve patients suffering from poppers maculopathy were included. Health records, optical coherence tomography (OCT), and OCTA data was gathered and compared to a healthy control group (HC). PMP lesion type was determined by manifestation in OCT. OCTA-based evaluation of retinal vascular plexus and choriocapillaris (CC) was executed. Vessel density (VD) and vessel length density (VLD) in superficial and deep capillary plexus (SCP, DCP), as well as flow deficits (FD), within the foveal avascular zone (FAZ) in CC were assessed. RESULTS:Median age of PMP patients was 40 (min 24; max 64) years, all male. Eleven patients presented with ellipsoid zone-type lesions; one patient showed a vitelliform-type lesion. No qualitative microvascular changes between PMP patients and HC were identified. Quantitative values for VD and VLD of SCP and DCP did not differ in between the two groups. The analysis of FDs in CC showed no deviation from PMP patients to HC. CONCLUSIONS:No vascular anomalies in qualitative and quantitative analysis in OCTA were detected in PMP patients. The constitution of the CC within FAZ of PMP patients does not differ from HC when assessed as FD.
PMID: 34800139
ISSN: 1435-702x
CID: 5049832
Predominance of hyperopia in autosomal dominant Best vitelliform macular dystrophy
BACKGROUND/AIMS/OBJECTIVE:-associated Stargardt disease. METHODS:This was a retrospective chart review of consecutive patients with molecularly confirmed AD-BVMD and Stargardt macular dystrophy seen at a single academic centre. Demographic information, including age, gender and genotype were extracted from the chart. The best corrected visual acuity (BCVA), as well as type and degree of refractive error on manifest refraction for each eye on each visit, were recorded and compared. RESULTS:A total of 178 eyes from 89 patients with AD-BVMD (35 women, 54 men; mean age 36.6 years) and 306 eyes from 153 patients (94 women, 59 men, mean age 30.2 years) with Stargardt disease were included in the study. Mean BCVA was excellent for both AD-BVMD and Stargardt eyes (logMAR 0.23 vs logMAR 0.31, respectively; p=0.55). At initial refraction, 73.0% of AD-BVMD eyes (130/178) were hyperopic, with mean spherical equivalent (SE) +1.38 dioptres (median +0.88) whereas 80.7% of Stargardt eyes (247/306) were myopic, with mean SE of -1.76 dioptres (median -1.19) (p<0.001). CONCLUSION/CONCLUSIONS:in ocular growth and development.
PMID: 33243830
ISSN: 1468-2079
CID: 4681022
Intimate partner violence and asthma in pediatric and adult populations
OBJECTIVE:To evaluate the relationship between intimate partner violence (IPV) and adult and childhood asthma outcomes. DATA SOURCES:We conducted a systematic literature review using 4 databases (PubMed, Ovid MEDLINE, Ovid Embase, and Ovid PsycINFO) with asthma and IPV-associated terms. STUDY SELECTIONS:We included published studies, available in English, to October 2021, which included IPV as an exposure and asthma as an outcome. Both adult and pediatric populations were included in the following settings: community, health care, and home. RESULTS:There were 37 articles identified. There was evidence among multiple studies to support increased prevalence of asthma in adults exposed to IPV and prevalence and incidence in children with parental IPV exposure. There were fewer studies evaluating IPV exposure and adult asthma morbidity, but they found statistically significant associations between IPV and increased rate of asthma exacerbations and worsened asthma control. There was sparse evidence evaluating a relationship between IPV and adult asthma mortality. There were no studies identified evaluating IPV and childhood asthma morbidity or mortality. CONCLUSION:The association between IPV and increased asthma prevalence, incidence, and worsened morbidity merits recognition and further investigation into potential mechanisms. Health care providers can implement practical strategies to help mitigate the negative effects of IPV on health and asthma. These include addressing potential impactful biopsychosocial factors and comorbidities, implementing routine screening and referrals, and partnering with community advocacy organizations. Given their positions of respect and power in society, health care providers can have lasting impacts on the lives of pediatric and adult patients affected by IPV.
PMID: 34995784
ISSN: 1534-4436
CID: 5285372
Emerging SARS-CoV-2 variants can potentially break set epidemiological barriers in COVID-19
Young age, female sex, absence of comorbidities, and prior infection or vaccination are known epidemiological barriers for contracting the new infection and/or increased disease severity. Demographic trends from the recent coronavirus disease 2019 waves, which are believed to be driven by newer severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, indicate that the aforementioned epidemiological barriers are being breached and a larger number of younger and healthy individuals are developing severe disease. The new SARS-CoV-2 variants have key mutations that can induce significant changes in the virus-host interactions. Recent studies report that, some of these mutations, singly or in a group, enhance key mechanisms, such as binding of the receptor-binding domain (RBD) of the viral spike protein with the angiotensin-converting enzyme 2 (ACE2) receptor in the host-cells, increase the glycosylation of spike protein at the antigenic sites, and enhance the proteolytic cleavage of the spike protein, thus leading to improved host-cell entry and the replication of the virus. The putative changes in the virus-host interactions imparted by the mutations in the RBD sequence can potentially be the reason behind the breach of the observed epidemiological barriers. Susceptibility for contracting SARS-CoV-2 infection and the disease outcomes are known to be influenced by host-cell expressions of ACE2 and other proteases. The new variants can act more efficiently, and even with the lesser availability of the viral entry-receptor and the associated proteases, can have more efficient host-cell entry and greater replication resulting in high viral loads and prolonged viral shedding, widespread tissue-injury, and severe inflammation leading to increased transmissibility and lethality. Furthermore, the accumulating evidence shows that multiple new variants have reduced neutralization by both, natural and vaccine-acquired antibodies, indicating that repeated and vaccine breakthrough infections may arise as serious health concerns in the ongoing pandemic.
PMID: 34811761
ISSN: 1096-9071
CID: 5063462
New insights into the genetic etiology of Alzheimer's disease and related dementias
Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele.
PMCID:9005347
PMID: 35379992
ISSN: 1546-1718
CID: 5213092
Utilization of Crowdfunding for Cataract and LASIK Procedures
PURPOSE/UNASSIGNED:To study the nature of crowdfunding campaigns for common ophthalmologic procedures. METHODS/UNASSIGNED:Cross sectional, retrospective study of campaigns on GoFundMe.com from January 1st, 2021 to July 31st, 2021. All domestic and international campaigns referring to cataract and intraocular lens placement or LASIK procedures, excluding those with non-ophthalmologic conditions or campaigns for multiple conditions. Descriptive analysis of campaigns including condition, country of origin of patient, total and median value raised, total and median value sought, age of the patient, funding goal met, insurance status when possible. Total and median funds raised and sought, international versus domestic campaigns, success rate for campaigns, percent of campaigns involving children, percent of campaigns mentioning insurance. RESULTS/UNASSIGNED:137 campaigns were identified, 67.9% (93/137) were for cataract and 32.1% (44/137) were for LASIK. 13.1% (18/137) of campaigns were international. 7.3% (10/137) campaigns were successful at reaching funding goals. Of successful campaigns, 70.0% (7/10) were for cataract and 30.0% (3/10) were for LASIK. Total value raised (in USD) was $131,763, where $106,593 was for cataract and $25,170 was for LASIK. The median value sought overall was $5,000, where the median sought for cataract procedures was $5,000 and the median for LASIK was $4,000. The median value raised was $395. 5.8% (8/137) of campaigns mentioned minors. 12.5% (1/8) of campaigns for children or minors successfully met funding goals compared to 7.0% (9/129) adult campaigns. The total funds raised for children or minors was $9,224 with a goal of $41,050. The total funds raised for adults was $122,539 out of a goal of $775,617. 14.6% (20/137) campaigns mentioned insurance coverage, of which 85% (17/20) were for cataract and 15.0% (3/20) were for LASIK. Premium lenses (toric, multifocal, etc.) were mentioned in 1.1% of cataract campaigns (1/93) as being cost prohibitive. CONCLUSIONS/UNASSIGNED:Crowdfunding is ineffective as a means for patients to raise funds for ophthalmic procedures. The broad range of financial requests within campaigns indicates a large patient knowledge gap in cost for procedures.
PMID: 35353643
ISSN: 1744-5205
CID: 5201152
Advanced Diffusion MRI of the Visual System in Glaucoma: From Experimental Animal Models to Humans
Glaucoma is a group of ophthalmologic conditions characterized by progressive retinal ganglion cell death, optic nerve degeneration, and irreversible vision loss. While intraocular pressure is the only clinically modifiable risk factor, glaucoma may continue to progress at controlled intraocular pressure, indicating other major factors in contributing to the disease mechanisms. Recent studies demonstrated the feasibility of advanced diffusion magnetic resonance imaging (dMRI) in visualizing the microstructural integrity of the visual system, opening new possibilities for non-invasive characterization of glaucomatous brain changes for guiding earlier and targeted intervention besides intraocular pressure lowering. In this review, we discuss dMRI methods currently used in visual system investigations, focusing on the eye, optic nerve, optic tract, subcortical visual brain nuclei, optic radiations, and visual cortex. We evaluate how conventional diffusion tensor imaging, higher-order diffusion kurtosis imaging, and other extended dMRI techniques can assess the neuronal and glial integrity of the visual system in both humans and experimental animal models of glaucoma, among other optic neuropathies or neurodegenerative diseases. We also compare the pros and cons of these methods against other imaging modalities. A growing body of dMRI research indicates that this modality holds promise in characterizing early glaucomatous changes in the visual system, determining the disease severity, and identifying potential neurotherapeutic targets, offering more options to slow glaucoma progression and to reduce the prevalence of this world's leading cause of irreversible but preventable blindness.
PMCID:8945790
PMID: 35336827
ISSN: 2079-7737
CID: 5220492
LATE RECURRENCE OF CHOROIDAL NEOVASCULARIZATION IN PATIENTS WITH MULTIFOCAL CHOROIDITIS: CLINICAL SURVEILLANCE IN PERPETUITY
PURPOSE/OBJECTIVE:To report a very late recurrence of choroidal neovascularization (CNV) in elderly patients with noninfectious multifocal choroiditis (MFC). METHODS:Retrospective case series of patients with MFC with confirmed recurrence of CNV. Choroidal neovascularization was diagnosed with multimodal imaging, including optical coherence tomography angiography. Multifocal choroiditis-associated CNV eyes were treated with intravitreal injections of anti-vascular endothelial growth factor medication. RESULTS:Four eyes of three patients were included in our study, with a mean (range) age of 73 years (67-78). The period between the original CNV and the recurrence was 53 years, with a range of 48-60 years. The mean number (range) of injections given after the late recurrence per eye was 7 (5-11). The mean duration (range) of follow-up post-treatment initiation was 93 (40-122) weeks. All eyes improved to 20/30 visual acuity or better at 6 months after initial treatment. CONCLUSION/CONCLUSIONS:Patients with MFC are never exempt from recurrent CNV, warranting follow-up in perpetuity. Age-related factors are important to consider which may increase the susceptibility for activating MFC-associated CNV in elderly people. Macular neovascularization could respond to a standard approach to management, in these patients with MFC, by a judicious use of intravitreal injections of anti-vascular endothelial growth factor therapy.
PMID: 31725597
ISSN: 1937-1578
CID: 4185702
MULTIMODAL IMAGING OF A PRESUMED EMBOLIC CILIORETINAL ARTERY OCCLUSION
PURPOSE/OBJECTIVE:To describe clinical features including multimodal imaging in a rare case of presumed embolic cilioretinal artery occlusion with long-term follow-up examination. METHODS:A 61-year-old man presented after noticing an acute-onset central scotoma in the left eye during coronary arteriography. Fundus color photography, red-free imaging, near-infrared reflectance, spectral domain optical coherence tomography (OCT), fluorescein angiography, and swept-source OCT angiography were performed. RESULTS:Color and red-free fundus imaging both showed retinal whitening in the territory corresponding to a cilioretinal artery in the left eye. Consistent with an ischemic event, the near-infrared reflectance showed a hyporeflective area in the same location. Spectral domain OCT showed hyperreflectivity and generalized thickening of the inner nuclear layer, ganglion cell layer, and retinal nerve fiber layer. Seven years later, color, red-free, and near-infrared reflectance imaging appeared normal, but the spectral domain OCT showed thinning of all retinal layers in the affected area. Furthermore, swept-source OCT angiography demonstrated markedly reduced capillary flow signal in the superficial and deep capillary plexuses, corresponding to a persistent scotoma described by the patient. CONCLUSION/CONCLUSIONS:This case report illustrates hallmark features of a rare presumed embolic cilioretinal artery occlusion and its long-term manifestations with thorough historical and multimodal imaging data. When standard fundus imaging with color, red-free, and near-infrared reflectance appears normal years after a retinal vascular insult, OCT and OCT angiography can corroborate a patient's persistent visual deficit and provide clarity to the diagnosis.
PMID: 31725598
ISSN: 1937-1578
CID: 4185712
SELF-INFLICTED LASER-INDUCED MACULOPATHY MASQUERADING AS POSTERIOR UVEITIS IN A PATIENT WITH SUSPECTED IgG4-RELATED DISEASE
PURPOSE/OBJECTIVE:To report the clinical presentation and imaging features in a case of bilateral self-inflicted handheld laser-induced maculopathy which masqueraded as progressive posterior uveitis in a patient with suspected IgG4-related disease. METHODS:Case report with clinical history, fundus photographs, fluorescein angiography, indocyanine green angiography, and swept-source optical coherence tomography. RESULTS:A young Asian Indian man presented with sudden progressive bilateral visual loss over the past 1 week. He was being treated with oral corticosteroids for multiple subcutaneous skin lesions believed to be due to IgG4-related disease. Findings included bilateral central areas of outer retinal disruption with eccentric linear and serpentine lesions showing hypoautofluorescence. Hyperreflective bands extending from the retinal pigment epithelium and interdigitation zone to the outer plexiform layer were present on swept-source optical coherence tomography. After careful history and evaluation of multimodal imaging, posterior uveitis was excluded, and a diagnosis of handheld laser-induced maculopathy was established. CONCLUSION/CONCLUSIONS:Pattern recognition is important in establishing a diagnosis of self-inflicted handheld laser-induced maculopathy which can masquerade as posterior uveitis. Increasing availability of powerful Class IIIb laser devices in both developed and developing countries will likely increase the incidence of this entity.
PMID: 31725490
ISSN: 1937-1578
CID: 4185692
Asymptomatic Retinal Vein Occlusion in a 13-Year-Old With Heterozygous Deletion of the PMP22 Gene and a Diagnosis of Hereditary Neuropathy With Liability to Pressure Palsies
PMID: 33870946
ISSN: 1536-5166
CID: 4846752
ACUTE FOVEALITIS
PURPOSE/OBJECTIVE:To describe the clinical, optical coherence tomography (OCT), and OCT angiography findings of a patient with a foveal disturbance from the acute phase to the resolution of the visual disturbances. METHOD/METHODS:The patient had a comprehensive ophthalmic examination to include OCT and OCT angiography. RESULTS:A 36-year-old man presented with decreased vision and distortion in the right eye. The right eye showed yellow-white punctate opacities in the central fovea. OCT showed numerous, well-defined, globular, aggregated, hyperreflective lesions that corresponded to the visible opacities along with a focal discontinuity of the outer retinal layers. Over 3 weeks, the patient's findings resolved, and the VA improved to 20/20. No abnormalities of the choriocapillaris flow were detected using OCT angiography. The lesion resolved without pigmentary change. CONCLUSION/CONCLUSIONS:The configuration of the hyperreflective deposits, the lack of pigmentary change, and the absence of OCT angiographic findings of flow problems in the choriocapillaris argue against a primary retinal pigment epithelial or choriocapillaris abnormality as the fundamental cause of the disease. The name acute fovealitis is suggested.
PMID: 32015272
ISSN: 1937-1578
CID: 4299952
Bilateral Optic Disc Edema in Multisystem Inflammatory Syndrome in Children Associated With COVID-19
PMID: 34417772
ISSN: 1536-5166
CID: 5189912
Acute Orbital Compartment Syndrome After Coil Embolization of a Contralateral Carotid Cavernous Fistula
PMID: 33449493
ISSN: 1536-5166
CID: 4747352
Letter to the Editor Re: Cost-analysis of Surgical Intraocular Pressure Management in Glaucoma
PMID: 34954750
ISSN: 1536-481x
CID: 5107952
Descemet Stripping Only for Fuchs Endothelial Corneal Dystrophy: Will It Become the Gold Standard?
ABSTRACT/UNASSIGNED:Descemet stripping only (DSO) has become a viable treatment option for certain cases of Fuchs Endothelial Corneal Dystrophy (FECD). This article describes the history of the development of DSO, its current status, and what successful DSO tells us about the pathophysiology of FECD. Remaining questions and future directions are also highlighted.
PMID: 34864799
ISSN: 1536-4798
CID: 5110042
Covid-19 vaccination and possible link to Herpes zoster [Case Report]
Purpose/UNASSIGNED:To report 3 otherwise healthy patients with Herpes zoster reactivation shortly after administration of a mRNA vaccine against the novel COVID-19 virus. Observations/UNASSIGNED:Patient 1 is a 54 year old who presented with Herpes zoster meningitis complicated by enhancing nodular leptomeningeal lesions of the spinal cord. The subsequent two patients had Herpes zoster ophthalmicus of the cornea (Case 2) and eyelid (Case 3). All three presented within 2 weeks of receiving the Pfizer/BioNTech COVID-19 vaccine. Conclusions/UNASSIGNED:Herpes zoster may be a side effect of m RNA vaccination against the Sars-CoV2 vaccine and requires further investigation.
PMCID:8789478
PMID: 35097240
ISSN: 2451-9936
CID: 5153322
Long-Term Outcomes of Bacillary Layer Detachment in Neovascular Age-Related Macular Degeneration
PURPOSE/OBJECTIVE:To evaluate the clinical characteristics, multimodal imaging features, and long-term treatment outcomes of eyes with neovascular age-related macular degeneration (nAMD) and bacillary layer detachment (BALAD) treated with intravitreal anti-VEGF therapy. DESIGN/METHODS:Retrospective, longitudinal, case series. PARTICIPANTS/METHODS:Treatment-naive patients with nAMD (n = 30) showing BALAD on OCT and undergoing anti-VEGF therapy. METHODS:Clinical records and multimodal imaging results of up to 4 years after diagnosis were reviewed. MAIN OUTCOME MEASURES/METHODS:Best-corrected visual acuity (BCVA) values were compared over time. The cumulative risk of and risk factors for subretinal fibrosis were assessed using Cox regression analyses, and adjusted hazard ratio (aHR) was computed. RESULTS:Thirty eyes of 30 patients were included. Macular neovascularization (MNV) subtypes were distributed as follows: type 1, 63%; type 2, 27%; mixed type 1 and 2, 3%; type 3, 3%; aneurysmal type 1, 3%. The BCVA significantly improved after anti-VEGF loading phase (Snellen equivalent, from 20 of 118 to 20 of 71, P = 0.03), but it returned to the baseline levels at 4 years (Snellen equivalent, 20 of 103, P = 0.6). The cumulative risk of subretinal fibrosis was 77% at 4 years. The risk factors associated with subretinal fibrosis included hemorrhagic BALAD (aHR, 2.02; 95% confidence interval [CI] 1.54-3.22; P < 0.01) and the presence of subretinal hyperreflective material (aHR, 1.83; 95% CI 1.35-3.14; P < 0.01). CONCLUSIONS:BALAD was found in association with all types of MNV in patients with nAMD. Long-term observation revealed poor functional outcomes related to the high risk of subretinal fibrosis.
PMID: 34587559
ISSN: 2468-6530
CID: 5147082
GNA11 Mutation in an Intracranial Melanocytoma with Orbital Involvement and Nevus of Ota
The prognostic value of mutations in G-protein genes GNAQ and GNA11 in patients with intracranial and orbital melanocytomas is unknown. The authors present a case of GNA11 mutation (GNA11Q209L) in a 32-year-old male suffering from a meningeal melanocytoma with orbital involvement and ipsilateral Nevus of Ota. The patient underwent gamma knife stereotactic radiosurgery without biopsy and later partial transcranial resection of the melanocytic tumor that was subject to immunohistochemical and molecular analysis. A 50-gene next-generation sequencing panel revealed a 626A>T mutation in the GNA11 gene. One year later, intracranial extension of the melanocytoma necessitated a ventriculoperitoneal shunt and immunotherapy. Future work is needed to determine how GNA11 mutations in melanocytomas influence prognosis and monitoring strategies.
PMID: 34750314
ISSN: 1537-2677
CID: 5050312
Virtual Reality Oculokinetic Perimetry Test Reproducibility and Relationship to Conventional Perimetry and OCT
Purpose/UNASSIGNED:Vivid Vision Perimetry (VVP; Vivid Vision, Inc) is a novel method for performing in-office and home-based visual field assessment using a virtual reality platform and oculokinetic perimetry. Here we examine the reproducibility of VVP Swift and compare results with conventional standard automated perimetry (SAP) and spectral-domain (SD) OCT. Design/UNASSIGNED:Cross-sectional study. Participants/UNASSIGNED:Fourteen eyes of 7 patients with open-angle glaucoma (OAG) (average age, 64.6 years; 29% women) and 10 eyes of 5 patients with suspected glaucoma (average age, 61.8 years; 40% women) were enrolled. Methods/UNASSIGNED:Patients with OAG and suspected glaucoma were enrolled prospectively and underwent 2 VVP Swift examinations. Results were compared with 1 conventional SAP examination (Humphrey Visual Field [HVF]; Zeiss) and 1 SD OCT examination. Main Outcome Measures/UNASSIGNED:Mean sensitivity (in decibels) obtained for each eye in 2 VVP Swift test sessions and a conventional SAP examination, thickness of the retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC) for the SD OCT examination, and mean test durations of the VVP Swift and SAP examinations. Results/UNASSIGNED:< 0.001), respectively. Conclusions/UNASSIGNED:Our results demonstrated that the VVP Swift test can generate reproducible results and is comparable with conventional SAP. This suggests that the device can be used by clinicians to assess visual function in glaucoma.
PMCID:9562375
PMID: 36276927
ISSN: 2666-9145
CID: 5359242
Descriptive Analysis of United States Glaucoma Fellowship Program Directors
PMID: 34655798
ISSN: 2589-4196
CID: 5062032
Ophthalmic imaging for the diagnosis and monitoring of glaucoma: A review
The last three decades have been a turning point for early glaucoma diagnosis and monitoring by newly developed imaging techniques. Improvements in imaging of the anterior segment (AS), retinal nerve fiber layer (RNFL), optic nerve head (ONH), and macular ganglion cell complex (GCC) came into existence and broke new ground for early diagnosis and progression survey. This review will summarize the different ophthalmic imaging techniques, their principles, pros and cons, ongoing development processes, and the future of imaging methods. The aim is to provide the clinician with an understanding of the role of imaging methods and provide insight for appropriate use and evaluation of their outputs in glaucoma diagnosis and treatment. This article is protected by copyright. All rights reserved.
PMID: 35050529
ISSN: 1442-9071
CID: 5131692
Selective laser trabeculoplasty for glaucoma in sub-Saharan Africa - Author's reply [Comment]
PMID: 35180415
ISSN: 2214-109x
CID: 5498022
Woman with COVID develops bilateral periorbital pain, edema
ORIGINAL:0015824
ISSN: 8750-3085
CID: 5298202
Intraocular Metastasis of Large T-cell Lymphoma Transformed from Mycosis Fungoides [Letter]
PURPOSE/UNASSIGNED:To describe a rare case of intraocular lymphoma that metastasized from cutaneous mycosis fungoides and transformed to large cell T cell lymphoma resulting in vitreoretinal pathology. METHODS/UNASSIGNED:Retrospective case report. RESULTS/UNASSIGNED:A 57-year-old male presented with 3Â months of blurred vision in the right eye. He reported only a medical history of psoriasis. Examination revealed keratic precipitates and dense vitritis in the right eye. He was taken for a diagnostic vitrectomy. Histopathology showed that atypical lymphoid cells and flow cytometry were consistent with transformed large cell T-cell lymphoma. During follow-up, pre- and inner retinal lesions were noted throughout the posterior pole. Histopathology of the psoriatic lesions was consistent with mycosis fungoides. He was initiated on systemic and intravitreal methotrexate with improvement in vision. CONCLUSIONS/UNASSIGNED:Ocular involvement in metastatic transformed T-cell lymphoma is extremely rare but can be present with vitritis and retinal deposits. Our patient responded well to intravitreal methotrexate therapy.
PMID: 35201959
ISSN: 1744-5078
CID: 5172312
In vivo MRI evaluation of anterograde manganese transport along the visual pathway following whole eye transplantation
BACKGROUND:administration into both native and transplanted eyes. RESULTS: No significant intraocular pressure difference was found between native and transplanted eyes, whereas comparable manganese enhancement was observed between native and transplanted intraorbital optic nerves, suggesting the presence of anterograde manganese transport after WET. No enhancement was detected across the coaptation site in the higher visual areas of the recipient brain. Comparison with Existing Methods: Existing imaging methods to assess WET focus on either the eye or local optic nerve segments without direct visualization and longitudinal quantification of physiological transport along the transplanted visual pathway, hence the development of in vivo MEMRI. CONCLUSION/CONCLUSIONS: Our established imaging platform indicated that essential physiological transport exists in the transplanted optic nerve after WET. As neuroregenerative approaches are being developed to connect the transplanted eye to the recipient's brain, in vivo MEMRI is well-suited to guide strategies for successful WET integration for vision restoration. Keywords (Max 6): Anterograde transport, magnetic resonance imaging, manganese, neuroregeneration, optic nerve, whole-eye transplantation.
PMID: 35202613
ISSN: 1872-678x
CID: 5167792
Histology and clinical lifecycle of acquired vitelliform lesion, a pathway to advanced age-related macular degeneration
PURPOSE/OBJECTIVE:To evaluate hypotheses about the role of acquired vitelliform lesion (AVL) in age-related macular degeneration (AMD) pathophysiology. DESIGN/METHODS:Laboratory histology study; retrospective, observational case series METHODS: : Two donor eyes in a research archive with AVL and AMD were analyzed with light and electron microscopy for AVL content at locations matched to ex vivo B-scans. A retrospective, observational clinical cohort study of 42 eyes of 30 patients at two referral clinics) determined the frequency of optical coherence tomography (OCT) features stratified by AVL fate. RESULTS:Histologic and clinical cases showed subretinal drusenoid deposit (SDD) and drusen. Ultrastructural AVL components in two donor eyes included retinal pigment epithelium (RPE) organelles (3-22% of volume), outer segments (2-10%), lipid droplets (0.2-12%), and a flocculent material (57-59%). Of 48 AVL (mean follow-up 46 ± 39 months), 50% collapsed to complete RPE and outer retinal atrophy (cRORA), 38% were stable, 10% resorbed, and 2% developed neovascularization. The ETDRS grid central subfield contained 77% of AVL. Hyperreflective foci, ellipsoid zone disruption, and hyperreflective thickening of the RPE-basal lamina-Bruch's membrane band were common at maximum AVL expansion. Collapsing and non-collapsing AVL had different growth rates (rapid vs slow, respectively). CONCLUSIONS:AVL deposits contain unexpectedly low levels of RPE organelles and outer segments. Subfoveal predilection, reflectivity on OCT, hyperautofluorescence, yellow color, and growth-regression phases suggest dysregulation of lipid transfer pathways specific to cone photoreceptors and supporting cells in formation of AVL deposit, analogous to drusen and SDD. Prediction of AVL outcomes via growth rates should be confirmed in larger clinical studies.
PMID: 35192790
ISSN: 1879-1891
CID: 5172122
Developing Affordable, Portable and Simplistic Diagnostic Sensors to Improve Access to Care
Ophthalmology is a highly technical specialty, especially in the area of diagnostic equipment. While the field is innovative, the access to cutting-edge technology is limited with reference to the global population. A significant way to improve overall healthcare is to understand the needs and possibilities of all possible consumers when developing sophisticated and accurate medical devices. The Smartphone-based Keratograph (SBK), is an example of a new project that uses real world feedback, addresses an unmet medical need, and implements commercially available components to create a device that is affordable, portable and simplistic to operate. The long-term goal of the SBK is to collect data from users for supervised machine-learning. This machine-learning aspect will ultimately aid in the development of an artificial intelligence device to enable even earlier detection of keratoconus, especially in children and adolescents. Again, the ultimate goal of any medical device should be to improve patient care, and to make a significant improvement on vision healthcare for the global population, providing access to this technology is essential.
PMCID:8840539
PMID: 35161926
ISSN: 1424-8220
CID: 5484732
ARE THERE TWO FORMS OF MULTIPLE EVANESCENT WHITE DOT SYNDROME?
PURPOSE:To analyze the nature of multiple evanescent white dot syndrome (MEWDS) and differentiate an idiopathic or primary form of MEWDS from a secondary form that is seen in association with other clinical conditions affecting the posterior segment of the eye. METHODS:Clinical and multimodal imaging findings including color fundus photography, fundus autofluorescence, fluorescein angiography, indocyanine green angiography, spectral-domain optical coherence tomography, and optical coherence tomography angiography of patients with secondary MEWDS are presented. RESULTS:Twenty consecutive patients with secondary MEWDS were evaluated. Fifteen patients were female. Most were young adults aged between 20 to 40 years with myopia (less than -6 diopters). Pathologic conditions associated with the secondary MEWDS reaction were high myopia (greater than -6 diopters) in two eyes, previous vitreoretinal surgery for rhegmatogenous retinal detachment in 2 eyes, and manifestations of multifocal choroiditis in 18 eyes. In all eyes, the MEWDS lesions followed a course of progression and resolution independent from the underlying condition. CONCLUSION:Secondary MEWDS seems to be an epiphenomenon ("EpiMEWDS") that may be seen in association with clinical manifestations disruptive to the choriocapillaris-Bruch membrane-retinal pigment epithelium complex.
PMID: 34432725
ISSN: 1539-2864
CID: 5175512
Consensus Recommendation for Mouse Models of Ocular Hypertension to Study Aqueous Humor Outflow and Its Mechanisms
Due to their similarities in anatomy, physiology, and pharmacology to humans, mice are a valuable model system to study the generation and mechanisms modulating conventional outflow resistance and thus intraocular pressure. In addition, mouse models are critical for understanding the complex nature of conventional outflow homeostasis and dysfunction that results in ocular hypertension. In this review, we describe a set of minimum acceptable standards for developing, characterizing, and utilizing mouse models of open-angle ocular hypertension. We expect that this set of standard practices will increase scientific rigor when using mouse models and will better enable researchers to replicate and build upon previous findings.
PMCID:8842499
PMID: 35129590
ISSN: 1552-5783
CID: 5156372
A mysterious myopic surprise [Case Report]
A 73-year-old man with an ocular history of inactive age-related macular degeneration and chronic angle-closure glaucoma (CACG) in both eyes recently underwent femtosecond laser-assisted cataract surgery/phacoemulsification and intraocular lens (IOL) implantation with simultaneous Hydrus microstent (Ivantis, Inc.) implantation in the left eye. Although there was some reported subincisional iris prolapse due to intraoperative floppy iris, the case was otherwise uneventful according to the referring surgeon. Two months postoperatively, he was referred to our office for a myopic surprise of approximately 2.0 diopters (D) in the left eye (Figure 1JOURNAL/jcrs/04.03/02158034-202202000-00022/figure1/v/2022-01-26T192641Z/r/image-tiff). Of note, he has a distant history of acute ACG and complicated cataract surgery in the right eye with a failed trabeculectomy. He subsequently had laser peripheral iridoplasty to pull the iris away from the angle in the right eye (Figure 2JOURNAL/jcrs/04.03/02158034-202202000-00022/figure2/v/2022-01-26T192641Z/r/image-tiff). His topical intraocular pressure (IOP)-lowering medications at presentation included dorzolamide-timolol 1 drop twice daily in the left eye and 1 drop of timolol in the right eye once daily. His past medical history is significant for hypertension and benign prostatic hyperplasia, and his oral medications include Tamsulosin (Flomax), Irbasartan (Avapro), and Atenolol. On examination, he had an UCDVA of 20/20 in the right eye and 20/80 in the left eye, and a BCDVA of 20/20 in the right eye and 20/25 in the left eye. His manifest refraction was plano in the right eye and 1.50 -0.75 × 90 in the left eye. IOP measured 19 mm Hg in the right eye and 26 mm Hg in the left eye. Pupil examination revealed a nonreactive pupil in the right eye and a round sluggish pupil in the left eye without an obvious relative afferent pupillary defect. Extraocular motility and confrontational visual fields were full in both eyes. On slitlamp examination, pertinent findings included the following: 1+ corneal guttata without edema in both eyes; anterior chambers were shallow but adequate in both eyes with scattered peripheral anterior synechiae in the right eye and a uniformly shallow but adequate chamber in the left eye; there was no cell or flare in either eye. Iris findings included a surgical pupil with a fibrotic pupillary membrane, laser iridoplasty scars with scattered temporal transillumination defects (TIDs) in the right eye, and 2.5 clock hours of TIDs and a patent peripheral iridotomy at 1 o'clock in the left eye; lens examination revealed centered posterior chamber IOLs with open posterior capsules in both eyes and lens pitting in the left eye. Pertinent findings on dilated fundus examination included a cup-to-disc ratio of 0.3 in both eyes with good neuroretinal rims and macular examination revealed medium-sized drusen with pigment clumping in both eyes and no active choroidal neovascular membranes. The remainder of the examination was unremarkable. What is the etiology of this myopic surprise? What diagnostic testing will help confirm the diagnosis and what are the best management options for this patient?
PMID: 35082239
ISSN: 1873-4502
CID: 5333722
A Preliminary Evaluation of Students' Learning and Performance Outcomes in an Accelerated 3-Year MD Pathway Program
Background/UNASSIGNED:Little outcome data exist on 3-year MD (3YMD) programs to guide residency program directors (PDs) in deciding whether to select these graduates for their programs. Objective/UNASSIGNED:To compare performance outcomes of 3YMD and 4-year MD (4YMD) students at New York University Grossman School of Medicine. Methods/UNASSIGNED:In 2020, using the Kirkpatrick 4-level evaluation model, outcomes from 3 graduating cohorts of 3YMD students (2016-2018) were compared with the 4YMD counterparts. Results/UNASSIGNED:=.03), other metrics and overall intern ratings did not differ by pathway. Conclusions/UNASSIGNED:Exploratory findings from a single institution suggest that 3YMD students performed similarly to 4YMD students in medical school and the first year of residency.
PMCID:8848877
PMID: 35222827
ISSN: 1949-8357
CID: 5174042
Relationship between mean follow-up intraocular pressure, rates of visual field progression and current target intraocular pressure guidelines
AIMS/OBJECTIVE:To investigate if eyes presenting intraocular pressure (IOP) within the limits of current guideline-driven target IOP indeed experience slow rates of glaucomatous visual field (VF) progression. METHODS:A total of 8598 24-2 VF tests from 603 eyes from the African Descent and Glaucoma Evaluation Study with manifest glaucoma were included. The sample was split into three groups based on baseline VF mean deviation (MD): G1 (better than -5.0Â dB), G2 (-5.0 to -10Â dB) and G3 (worse than -10Â dB). We investigated the relationship between existing target IOP guidelines and rates of MD progression in these groups. RESULTS:For stable eyes, the medians and IQR of the mean follow-up IOP were G1=15.0Â mmHg (IQR: 13.1 to 17.7), G2=13.2Â mmHg (IQR: 11.6 to 14.3) and G3=11.9Â mmHg (IQR: 10.1 to 13.8) (p<0.01). When considering the mean follow-up IOP within the limits proposed by current guidelines, the median MD slopes were: -0.20Â dB/y (IQR: -0.43 to -0.02) for G1<21Â mmHg, -0.19Â dB/y (IQR: -0.51 to -0.01) for G2<18Â mmHg and -0.15Â dB/y (IQR: -0.47 to 0.05) for G3<15Â mmHg (p=0.63). There were no significant differences between racial groups. CONCLUSION/CONCLUSIONS:In a sample of patients with manifest glaucoma, despite substantial variability between eyes, adherence to treatment guidelines helped slow the rates of global VF progression at various stages of disease. TRIAL REGISTRATION NUMBER/BACKGROUND:clinicaltrials.gov Identifier: NCT00221923.
PMID: 33130556
ISSN: 1468-2079
CID: 4663832
Classification of Presbyopia by Severity
There are close to two billion individuals globally living with presbyopia. In spite of its ubiquitous and progressive nature, there is no widely accepted, formal guideline or consensus statement on the classification of presbyopia by degree of severity. A panel of leading eye care professionals representing both optometrists and ophthalmologists convened virtually to discuss and document their combined assessments from the body of literature and clinical practice expertise in this commentary. In light of emerging therapies, classifying presbyopia by mild, moderate, or advanced severity may help provide consistency of diagnosis among eye care providers and may aid in managing patient expectations with different treatment options.
PMID: 34709607
ISSN: 2193-8245
CID: 5042612
Correction to: Classification of Presbyopia by Severity
PMID: 34800262
ISSN: 2193-8245
CID: 5049842
Improved Prognostic Precision in Uveal Melanoma through a Combined Score of Clinical Stage and Molecular Prognostication
Introduction/UNASSIGNED:Prognosis of uveal melanoma (UM) is assessed using clinical staging or molecular testing. Two modalities often used for prognostication are the American Joint Committee on Cancer (AJCC) staging and a tumor gene expression profile (GEP), the outcomes of which are often discordant. This article discusses a total risk score created to combine the discordant information from both sources. Methods/UNASSIGNED:A retrospective case series was conducted of all patients presenting with UM over 6 years to 2 referral centers. Each tumor was classified using the AJCC and the GEP. A total risk score was calculated for each patient using results from both AJCC and GEP. Kaplan-Meier analysis of metastasis-free survival was used to compare groups. Results/UNASSIGNED:A total of 294 patients were included in the study. Kaplan-Meier estimates showed significant curve separation between individual AJCC and GEP risk groups. The combined total risk score provided an accurate estimate of prognosis that incorporated results from both AJCC and GEP. Conclusions/UNASSIGNED:Clinical staging and molecular prognostication of UM can be discordant. There is important information provided by each system that is not provided by the other. The total risk score provides a simple method to combine information from both AJCC stage and the GEP class in order to provide patients and care teams with a more complete understanding of metastatic risk.
PMCID:8914271
PMID: 35356606
ISSN: 2296-4681
CID: 5191142
The association between bariatric surgery and cataract: a propensity score-matched cohort study
BACKGROUND:Obesity is considered a risk factor for cataracts. The association between weight loss and a cataract among patients with obesity has not been assessed to date. OBJECTIVES/OBJECTIVE:To assess the association between weight loss following bariatric surgery and cataracts. SETTING/METHODS:Nationwide Swedish healthcare registries between 2006 and 2019. METHODS:We performed a population-based cohort study. Patients aged 40-79 years who underwent bariatric surgery were matched on their propensity score (PS) to up to 2 patients with obesity ("unexposed patients"). Cox proportional hazard regression analyses calculated hazard ratios (HRs) and 95% confidence intervals (CIs) of developing cataracts following bariatric surgery, compared with unexposed patients. Subgroup analyses by age, sex, bariatric surgery type, and duration of follow-up were conducted. RESULTS:In total, 22,560 bariatric surgery patients were PS-matched to 35,523 unexposed patients. The risk of cataracts was decreased in bariatric surgery patients compared with unexposed patients (HR .71, 95% CI .66-.76). We observed the lowest risk of cataracts among bariatric surgery patients aged 40-49 years (HR .52, 95% CI .44-.75) but a null result for patients aged ≥60 years. Gastric bypass or duodenal switch were associated with decreased risks of cataracts, whereas sleeve gastrectomy yielded a null result. Subgroups of sex and duration of follow-up showed no evidence of effect modification (hazards were proportional throughout follow-up). CONCLUSION/CONCLUSIONS:Our results suggest that substantial weight loss following bariatric surgery is associated with a decreased risk of cataracts, especially if bariatric surgery was performed before age 60.
PMID: 34863672
ISSN: 1878-7533
CID: 5484682
PACK-CXL vs. antimicrobial therapy for bacterial, fungal, and mixed infectious keratitis: a prospective randomized phase 3 trial
BACKGROUND:Infectious keratitis is a major cause of global blindness. We tested whether standalone photoactivated chromophore corneal cross-linking (PACK-CXL) may be an effective first-line treatment in early to moderate infectious keratitis, compared with standard antimicrobial treatment. METHODS:This is a randomized, controlled, multinational phase 3 clinical trial. Participants in five centers in Egypt, India, Iran, Israel, and China, aged ≥ 18 years, with infectious keratitis of presumed bacterial, fungal, or mixed origin, were randomly assigned (1:1) to PACK-CXL, or antimicrobial therapy. Outcomes measures included healing, defined as time to re-epithelialization of the corneal epithelial defect in the absence of inflammatory activity in the anterior chamber and clearance of stromal infiltrates. Treatment success was defined as the complete resolution of signs of infection. RESULTS:Between July 21, 2016, and March 4, 2020, participants were randomly assigned to receive PACK-CXL (n = 18) or antimicrobial therapy per American Academy of Ophthalmology (AAO) guidelines (n = 21). No participants were lost to follow-up. Four eyes were excluded from the epithelialization time analysis due to treatment failure: two in the antimicrobial therapy group, and two in the PACK-CXL group. Success rates were 88.9% (16/18 patients) in the PACK-CXL group and 90.5% (19/21 patients) in the medication group. There was no significant difference in time to complete corneal re-epithelialization (P = 0.828) between both treatment groups. CONCLUSIONS:PACK-CXL may be an alternative to antimicrobial drugs for first-line and standalone treatment of early to moderate infectious keratitis of bacterial or fungal origin. Trial registration This trial is registered at ClinicalTrials.gov, trial registration number: NCT02717871.
PMCID:8742313
PMID: 34996516
ISSN: 2326-0254
CID: 5484712
Ultra-Widefield Indocyanine Green Angiography Reveals Patterns of Choroidal Venous Insufficiency Influencing Pachychoroid Disease
Purpose/UNASSIGNED:To compare patterns of choroidal venous drainage in eyes with pachychoroid disease to those of healthy subjects using ultra-widefield indocyanine green angiography (UWF ICGA). Methods/UNASSIGNED:Patients with pachychoroid disease and healthy controls were recruited at two referral centers. UWF ICGA images were used to evaluate the proportion of the postequatorial fundus drained by major vortex vein systems in each quadrant and to study the incidence and topography of choroidal vascular hyperpermeability (CVH) and intervortex venous anastomoses. Widefield swept-source optical coherence tomography (SS-OCT) was used to evaluate choroidal thickness at the posterior pole in eyes with pachychoroid disease. Results/UNASSIGNED:Fifty-two pachychoroid eyes and 26 healthy eyes were evaluated. Eyes with pachychoroid disease showed a significant within-subject variance in the proportion of the postequatorial fundus drained by each vortex vein system (range, 4.1%-48.1%; P < 0.0001) that was not seen in controls (range, 17.3%-31.7%; P = 0.11). CVH was present in all pachychoroid disease eyes and three of 26 controls. Intervortex venous anastomoses were present in 46 of 52 pachychoroid disease eyes and nine of 26 control eyes. Vortex vein systems with large drainage areas showed greater density of CVH spots. SS-OCT demonstrated asymmetric choroidal drainage in the macula of 59% of pachychoroid eyes. CVH and intervortex venous anastomoses were more prominent in areas showing maximal choroidal thickness. Conclusions/UNASSIGNED:In eyes with pachychoroid disease, imbalanced choroidal venous drainage with congestion of specific vortex vein systems may contribute to a state of choroidal venous insufficiency characterized by regional choroidal thickening, CVH and remodeling of venous drainage routes.
PMID: 35019945
ISSN: 1552-5783
CID: 5118762
In Vivo Sublayer Analysis of Human Retinal Inner Plexiform Layer Obtained by Visible-Light Optical Coherence Tomography
Purpose/UNASSIGNED:Growing evidence suggests that dendrite retraction or degeneration in a subpopulation of the retinal ganglion cells (RGCs) may precede detectable soma abnormalities and RGC death in glaucoma. Visualization of the lamellar structure of the inner plexiform layer (IPL) could advance clinical management and fundamental understanding of glaucoma. We investigated whether visible-light optical coherence tomography (vis-OCT) could detect the difference in the IPL sublayer thicknesses between small cohorts of healthy and glaucomatous subjects. Method/UNASSIGNED:We imaged nine healthy and five glaucomatous subjects with vis-OCT. Four of the healthy subjects were scanned three times each in two separate visits, and five healthy and five glaucoma subjects were scanned three times during a single visit. IPL sublayers were manually segmented using averaged A-line profiles. Results/UNASSIGNED:The mean ages of glaucoma and healthy subjects are 59.6 ± 13.4 and 45.4 ± 14.4 years (P = 0.02.) The visual field mean deviations (MDs) are -26.4 to -7.7 dB in glaucoma patients and -1.6 to 1.1 dB in healthy subjects (P = 0.002). Median coefficients of variation (CVs) of intrasession repeatability for the entire IPL and three sublayers are 3.1%, 5.6%, 6.9%, and 5.6% in healthy subjects and 1.8%, 6.0%, 7.7%, and 6.2% in glaucoma patients, respectively. The mean IPL thicknesses are 36.2 ± 1.5 µm in glaucomatous and 40.1 ± 1.7 µm in healthy eyes (P = 0.003). Conclusions/UNASSIGNED:IPL sublayer analysis revealed that the middle sublayer could be responsible for the majority of IPL thinning in glaucoma. Vis-OCT quantified IPL sublayers with good repeatability in both glaucoma and healthy subjects.
PMID: 35024761
ISSN: 1552-5783
CID: 5118912
Rossiiskii oftal'mologicheskii zhurnal. 2022:15(1):122-127. DOI: 10.21516/2072-0076-2022-15-1-122-127
Primary choroidal melanoma followed by two metachronous ipsilateral ocular metastases
Purpose. To describe two ipsilateral, metachronous, ocular choroidal melanoma metastases. Material and methods. A 64-year-old choroidal melanoma patient was initially treated with palladium-103 ophthalmic plaque brachytherapy which induced local control of the primary cancer. Seven years later, ophthalmic findings of a second, ipsilateral, discrete choroidal melanoma prompted restaging which revealed new hepatic and nodal metastases. Systemic immunotherapy (ipilimumab 3 mg/kg with nivolumab 1 mg/kg IV every 3 weeks 4 doses) resulted in intraocular tumor regression and was followed by maintenance nivolumab 480 mg IV every 4 weeks with follow-up ophthalmic examinations. Results. Three years after initiation of systemic immunotherapy, the patient was found to have a second ipsilateral local recurrence of choroidal melanoma. It presented with retinal detachment, uveitis, and optic neuritis. Then, due to its anterior uveal location, extrascleral tumor extension was amenable to a diagnostic biopsy. Overall, 3 years after onset of metastatic uveal melanoma and 2 months after her second ocular metastasis, the patient died. This was 10 years after the initial diagnosis of choroidal melanoma. Conclusions. Metastatic choroidal melanoma can present twice in the same eye as the primary tumor. Ophthalmic and systemic examinations allowed for immunotherapy to affect initial systemic regression, vision sparing, and globe salvage.
SCOPUS:85131874444
ISSN: 2072-0076
CID: 5314962
BACILLARY LAYER DETACHMENT OVERLYING REDUCED CHORIOCAPILLARIS FLOW IN ACUTE IDIOPATHIC MACULOPATHY
PURPOSE/OBJECTIVE:To report new multimodal imaging features that enhance our understanding of the inflammatory and ischemic nature of acute idiopathic maculopathy (AIM) and to correlate structural and functional changes due to a reversible initial choroidal ischemia over a clinical course of 3.5 months. METHODS:A 31-year-old man presented with acute central vision loss in his right eye due to coxsackievirus-associated AIM. Serial multimodal retinal imaging including confocal true color fundus photography, blue-light fundus autofluorescence (BAF), near-infrared reflectance (NIR), spectral domain optical coherence tomography and swept-source optical coherence tomography (SD-OCT + SS-OCT), and en face SS-OCT angiography (SS-OCTA) were performed over a 3.5-month follow-up. Eidon true color confocal scanner camera (Centervue, Padova, Italy) was used for color and BAF imaging. Near-infrared reflectance and SD-OCT images were obtained with the Heidelberg Spectralis OCT (HRA2 + OCT; Heidelberg Engineering, Heidelberg, Germany). For SS-OCT and en face SS-OCT and SS-OCTA images, the PLEX Elite 9,000 (Carl Zeiss Meditec, Inc, Dublin, CA) was used. Central alterations in choriocapillaris flow were analyzed with SS-OCTA using the University of Washington choriocapillaris (CC) flow deficit quantification algorithm available through the ARI Network. Flow deficit area and density values were analyzed and compared between the first and last examinations. Corresponding en face OCT imaging was used to distinguish true flow defects from artifacts secondary to shadowing. RESULTS:In the acute stage of AIM, a bacillary layer detachment appearing as a yellow-grayish foveal elevation surrounded by a hypopigmented parafoveal ring was evident in a Bull's eye configuration, corresponding to a hyperreflective ring upon NIR and a hyperautofluorescent ring with BAF. SD + SS-OCT showed mostly intraretinal fluid consistent with a bacillary layer detachment in conjunction with a thickened inner choroid. At presentation, SS-OCTA demonstrated a marked reduction of choriocapillaris flow signal. At 1 week, early resolution of retinal fluid was followed by restoration of the ellipsoid zone at 5 weeks, while restoration of the interdigitation zone and reduction in retinal pigment epithelium/Bruch membrane complex thickening occurred more slowly. Swept-source OCT angiography showed a gradual, but incomplete, recovery of inner choroidal flow signal at 3.5-month follow-up. CONCLUSION/CONCLUSIONS:Acutely, AIM may present with a photoreceptor splitting foveal bacillary layer detachment associated with a marked reduction in inner choroidal flow signal on SS-OCTA. Thereafter, restoration of the outer retinal layers and gradual normalization of choroidal flow signal appear to support the often-benign nature of the disease.
PMID: 31764886
ISSN: 1937-1578
CID: 4215652
Response to RE: Bacillary Layer Detachment Due to Macular Neovascularization
PMID: 34173360
ISSN: 1539-2864
CID: 4925932
Acute Idiopathic Maculopathy
[S.l.] : Springer International Publishing, 2022
pp. 3807-3813
ISBN: 9783030426330
CID: 5500932
Keratoconus concordance in monozygotic twins before and after combined CXL/PRK (Athens Protocol) using Scheimflung and OCT tomography
PUPOSE/UNASSIGNED:To describe the concordance of keratoconus expression in two pairs of monozygotic twins before and after a combined CXL/PRK procedure. SETTING/METHODS:Private Ambulatory Eye Surgery Unit. DESIGN/METHODS:Retrospective Interventional Twin Study. METHODS:Two pairs of male monozygotic twins with keratoconus (KCN) were studied retrospectively. Improvement of flattest (k1) and steepest (k2) keratometry, Index of Height Decentration (IHD), corneal thickness at thinnest point and corneal epithelial thickness measured by AS-OCT and Scheimpflug tomography was compared between respective eyes of monozygotic twin siblings 1 to 5 years after the application of combined corneal cross linking (CXL) and topography guided photorefractive keratectomy (PRK) of part of the refractive error (the Athens Protocol). RESULTS:Significant improvement was noted in all the keratometric indices of all 8 eyes after the combined CXL/PRK procedure.The difference in k1, k2, IHD corneal thickness at thinnest point and corneal epithelial thickness percentage improvement between the right eyes of each pair of twins was statistically significant 1 and 5 years post-operatively (P < .05). Statistically significant discordance in the aforementioned parameters percentage improvement was likewise observed between the left eyes of each pair of twins (P < .05). CONCLUSIONS:Although a genetic predisposition in KCN is well documented, the discordance in keratometric indices improvement after a CXL/PRK procedure between respective eyes of monozygotic twins suggests that environmental influences may contribute to the disease expression as well. Variable degree of synergy in a combined CXL/PRK procedure may also explain the aforementioned discordant improvement.
PMID: 34091554
ISSN: 1873-4502
CID: 4905952
Network-Aware 5G Edge Computing for Object Detection: Augmenting Wearables to “See” More, Farther and Faster
Advanced wearable devices are increasingly incorporating high-resolution multi-camera systems. As state-of-the-art neural networks for processing the resulting image data are computationally demanding, there has been a growing interest in leveraging fifth generation (5G) wireless connectivity and mobile edge computing for offloading this processing closer to end-users. To assess this possibility, this paper presents a detailed simulation and evaluation of 5G wireless offloading for object detection in the case of a powerful, new smart wearable called VIS4ION, for the Blind-and-Visually Impaired (BVI). The current VIS4ION system is an instrumented book-bag with high-resolution cameras, vision processing, and haptic and audio feedback. The paper considers uploading the camera data to a mobile edge server to perform real-time object detection and transmitting the detection results back to the wearable. To determine the video requirements, the paper evaluates the impact of video bit rate and resolution on object detection accuracy and range. A new street scene dataset with labeled objects relevant to BVI navigation is leveraged for analysis. The vision evaluation is combined with a full-stack wireless network simulation to determine the distribution of throughputs and delays with real navigation paths and ray-tracing from new high-resolution 3D models in an urban environment. For comparison, the wireless simulation considers both a standard 4G-Long Term Evolution (LTE) sub-6-GHz carrier and high-rate 5G millimeter-wave (mmWave) carrier. The work thus provides a thorough and detailed assessment of edge computing for object detection with mmWave and sub-6-GHz connectivity in an application with both high bandwidth and low latency requirements.
SCOPUS:85126309496
ISSN: 2169-3536
CID: 5189272
Multiple Evanescent White Dot Syndrome
[S.l.] : Springer International Publishing, 2022
pp. 4193-4208
ISBN: 9783030426330
CID: 5500952
LONG-TERM VISUAL ACUITY PRESERVATION IN SORSBY FUNDUS DYSTROPHY WITH CORTICOSTEROID TREATMENT
PURPOSE/OBJECTIVE:To describe the long-term findings of a patient with Sorsby fundus dystrophy treated with corticosteroids and propose a mechanism by which the results were obtained. METHODS:Comprehensive ophthalmologic examination with multimodal imaging to include optical coherence tomography and optical coherence tomography angiography was used to evaluate a patient with Sorsby fundus dystrophy treated with intravitreal triamcinolone. RESULTS:A 35-year-old woman presented in 2003 with aggressive macular neovascularization in both eyes; her visual acuity was 20/25 in the right and 20/400 in the left eye. She previously had photodynamic therapy without apparent benefit. She was then treated with photodynamic therapy and an intravitreal injection of 4 mg of triamcinolone, which caused the neovascularization to become inactive. She was eventually switched to an intravitreal injection of triamcinolone 4 mg every 3 to 4 months in the right eye. She had no further treatment in the left eye because of extensive scarring. After 15 1/2 years of treatment, her visual acuity in the right eye was 20/20. Optical coherence tomography showed a large, low-level, irregular elevation of the retinal pigment epithelium. optical coherence tomography angiography revealed widespread macular neovascularization, and the choriocapillaris showed extensive loss. The patient had a TIMP-3 mutation, c.610A>T (p.Ser204Cys). CONCLUSION/CONCLUSIONS:TIMP3 has numerous effects including controlling vascular endothelial growth factor signaling and tumor necrosis factor alpha production. Corticosteroids have the potential to modulate both cytokines. This is the longest reported treatment follow-up of Sorsby fundus dystrophy with macular neovascularization, and the patient retained excellent visual acuity.
PMID: 31764885
ISSN: 1937-1578
CID: 4237552
Idiopathic Polypoidal Choroidal Vasculopathy
[S.l.] : Springer International Publishing, 2022
pp. 3645-3661
ISBN: 9783030426330
CID: 5501082
Cycloablation
[S.l.] : Springer International Publishing, 2022
pp. 2463-2479
ISBN: 9783030426330
CID: 5500652
Comprehensive Glaucoma Imaging
[S.l.] : Springer International Publishing, 2022
pp. 2099-2119
ISBN: 9783030426330
CID: 5500852
Pachydermoperiostosis Presenting With Vision Loss Secondary to Severe Phlyctenular Keratoconjunctivitis
PURPOSE/OBJECTIVE:To report a case of severe phlyctenular keratoconjunctivitis in a patient with pachydermoperiostosis (PDP). METHODS:A 29-year-old Hispanic man presented with a 1-year history of vision loss in the right eye and redness, photophobia, and pain in both eyes. Associated symptoms included enlargement of his hands and feet for 3 years, acne, and joint pain. Examination was notable for severe meibomian gland dysfunction, corneal and limbal phlyctenules in both eyes, and central stromal scarring of the right cornea. He had cystic acne of the face and a coarse, wrinkled forehead and scalp. Examination of his hands and feet revealed clubbing of the digits. RESULTS:The patient had an extensive laboratory workup that was significant for elevated erythrocyte sediment rate and C-reactive protein. X-ray of his hands and feet revealed diffuse periosteal hyperostosis with diffuse bone expansion. The patient was diagnosed with PDP with severe meibomian gland dysfunction, phlyctenular keratoconjunctivitis, and corneal scarring. His pain and photophobia resolved with medical management of the phlyctenular keratoconjunctivitis but decreased vision in the right eye persisted because of neovascularization and scarring of the cornea. CONCLUSIONS:We report a rare case of phlyctenular keratoconjunctivitis associated with PDP. To our knowledge, this is the first case of PDP to initially present with vision loss.
PMID: 33758137
ISSN: 1536-4798
CID: 4822672
Positive sparse signal denoising: What does a CNN learn
Convolutional neural networks (CNNs) provide impressive empirical success in various tasks; however, their inner workings generally lack interpretability. In this paper, we interpret shallow CNNs that we have trained for the task of positive sparse signal denoising. We identify and analyze common structures among the trained CNNs. We show that the learned CNN denoisers can be interpreted as a nonlinear locally-adaptive thresholding procedure, which is an empirical approximation of the minimum mean square error estimator. Based on our interpretation, we train constrained CNN denoisers and demonstrate no loss in performance despite having fewer trainable parameters. The interpreted CNN denoiser is an instance of a multivariate spline regression model, and a generalization of classical proximal thresholding operators.
SCOPUS:85126695279
ISSN: 1070-9908
CID: 5189762
A Kalman Filter Framework for Simultaneous LTI Filtering and Total Variation Denoising
This paper proposes a Kalman filter framework for signal denoising that simultaneously utilizes conventional linear time-invariant (LTI) filtering and total variation (TV) denoising. In this approach, the desired signal is considered to be a mixture of two distinct components: a band-limited (e.g., low-frequency component, high-frequency component) signal and a sparse-derivative signal. An iterative Kalman filter/smoother approach is formulated where zero-phase LTI filtering is used to estimate the band-limited signal and TV denoising is used to estimate the sparse-derivative signal.
SCOPUS:85137881823
ISSN: 1053-587x
CID: 5330652
BREGMAN PLUG-AND-PLAY PRIORS
[S.l.] : IEEE Computer Society, 2022
pp. 241-245
ISBN: 9781665496209
CID: 5423792
Scanning interferometric near-infrared spectroscopy
In diffuse optics, quantitative assessment of the human brain is confounded by the skull and scalp. To better understand these superficial tissues, we advance interferometric near-infrared spectroscopy (iNIRS) to form images of the human superficial forehead blood flow index (BFI). We present a null source-collector (S-C) polarization splitting approach that enables galvanometer scanning and eliminates unwanted backscattered light. Images show an order-of-magnitude heterogeneity in superficial dynamics, implying an order-of-magnitude heterogeneity in brain specificity, depending on forehead location. Along the time-of-flight dimension, autocorrelation decay rates support a three-layer model with increasing BFI from the skull to the scalp to the brain. By accurately characterizing superficial tissues, this approach can help improve specificity for the human brain.
PMID: 34951892
ISSN: 1539-4794
CID: 5147262
Parallel interferometric Diffusing Wave Spectroscopy (iDWS) with Time-of-Flight Discrimination
[S.l.] : Optica Publishing Group (formerly OSA), 2022
pp. ?-?
ISBN: 9781557528209
CID: 5329222
Emergency and Initial Management of Anterior Segment and Adnexal Trauma
[S.l.] : Springer International Publishing, 2022
pp. 663-697
ISBN: 9783030426330
CID: 5501012
Tumors of the Cornea and Conjunctiva
[S.l.] : Springer International Publishing, 2022
pp. 405-430
ISBN: 9783030426330
CID: 5501022
Insect Fungus Metarhizium robertsii Is a Rare Causative Agent of Keratitis
PURPOSE/OBJECTIVE:This study aimed to describe a case of keratitis secondary to Metarhizium robertsii, a soil-dwelling fungus with typical insect pathogenicity. METHODS:A Case report. RESULTS:A 58-year-old man with a ocular history of soft contact lens overwear, poor contact lens hygiene, and ocular exposure to ground well water supplying his house was referred to our university practice for a central corneal ulcer with 40% thinning. Same-day rapid microscopic detection with Giemsa stain identified the presence of many hyphae elements, and he was ultimately diagnosed with M. robertsii keratitis. The patient's course involved severe and progressive corneal thinning that stabilized over a 3-month course of antifungal therapy. CONCLUSIONS:Metarhizium robertsii seems more aggressive than other forms of fungal keratitis; therefore, this infection may be watched more closely with the risk for quick progressive corneal thinning, even while on antifungal management.
PMID: 34870624
ISSN: 1536-4798
CID: 5116842
Targeted Neoadjuvant Intra-arterial Chemotherapy in Lacrimal Gland Adenoid Cystic Carcinoma: A Histological Correlation Using Apoptotic Tumor Markers
Neoadjuvant intra-arterial cytoreductive chemotherapy is used for the treatment of lacrimal gland adenoid cystic carcinomas (ACC) to improve outcomes in this condition with an otherwise dismal prognosis. We share our experience in the management of an advanced case of ACC using a novel, highly targeted intra-arterial cytoreductive chemotherapy delivery technique involving both the internal and external carotid circulation, with an attempt to correlate the effect histologically. Refinement of the chemotherapy delivery using the tumor's vascular anatomy and appropriate blood vessel selection may lead to future globe sparing procedures without compromising survival.
PMID: 34652309
ISSN: 1537-2677
CID: 5138252
Teprotumumab and Hearing Loss: Case Series and Proposal for Audiologic Monitoring
PURPOSE/OBJECTIVE:To present a protocol for audiologic monitoring in the setting of teprotumumab treatment of thyroid eye disease, motivated by 4 cases of significant hearing loss, and review the relevant literature. METHODS:Cases of hearing loss in the setting of teprotumumab were retrospectively elicited as part of a multi-institutional focus group, including oculoplastic surgeons, a neurotologist and an endocrinologist. A literature review was performed. RESULTS:An aggregate of 4 cases of teprotumumab-associated hearing loss documented by formal audiologic testing were identified among 3 clinicians who had treated 28 patients. CONCLUSIONS:Teprotumumab may cause a spectrum of potentially irreversible hearing loss ranging from mild to severe, likely resulting from the inhibition of the insulin-like growth factor-1 and the insulin-like growth factor-1 receptor pathway. Due to the novelty of teprotumumab and the lack of a comprehensive understanding of its effect on hearing, the authors endorse prospective investigations of hearing loss in the setting of teprotumumab treatment. Until the results of such studies are available, the authors think it prudent to adopt a surveillance protocol to include an audiogram and tympanometry before, during and after infusion, and when prompted by new symptoms of hearing dysfunction.
PMID: 34085994
ISSN: 1537-2677
CID: 4892082
Neurophotonic tools for microscopic measurements and manipulation: status report
PMCID:9047450
PMID: 35493335
ISSN: 2329-423x
CID: 5215772
Competition law and pricing among biologic drugs: the case of VEGF therapy for retinal diseases
Neovascular age-related macular degeneration (AMD) is a progressive eye disease and is a leading cause of vision loss in the Western world. Vascular endothelial growth factor inhibitors have become a mainstay of treatment for this disease. Currently, treatment options include three originator biologics with approvals for neovascular AMD (aflibercept, ranibizumab, and brolucizumab-dbll) and one biologic that is commonly used off-label for the condition (bevacizumab). In the USA, Medicare spending on these drugs consistently surpassed $4 billion per year between 2015 and 2019, driven by high prices and varying off-label use of bevacizumab, which is substantially cheaper than the other biologics used to treat neovascular AMD. In this article, we discuss how legal reform can improve market competition for biologic drugs, using AMD therapies as a case study. We chose this group of drugs for their significant contribution to Medicare spending, the price difference between approved therapies and intravitreal bevacizumab, and because there currently exists a large biosimilar pipeline with many drug candidates in the final stage of development. We propose mechanisms for anticipating and facilitating the market introduction of biosimilars, as well as changes to the pricing model in Medicare that can promote use of cost-effective therapies. Reforms such as empowering Medicare to negotiate drug prices may help ensure that introduction of new biologics and biosimilars for AMD will lower spending and increase patient access.
PMCID:8863367
PMID: 35211322
ISSN: 2053-9711
CID: 5175182
Urology Practice Acquisitions by Private Equity Firms from 2011-2021
INTRODUCTION/BACKGROUND:Private equity firms have recently acquired several large urology practices in the United States. As little is known about these acquisitions, we sought to characterize trends in urology practice consolidation. METHODS:We compiled urology practice acquisition data via financial databases, news outlets, practice websites, and Internet keyword search for the time period January 1, 2011 through March 15, 2021. For each acquisition, we determined the acquiring group, number of employed urologists, practice locations, and status of ancillary services (pathology, radiology, or surgery centers). We estimated workforce effects based on the 2019 American Urological Association workforce census. RESULTS:We identified 69 independent practice acquisitions in the study period, including 19 (28.4%) by hospital systems, 7 (10.4%) by multispecialty physician groups, 23 (34.3%) by urology practices, and 20 (29.9%) by private equity-backed platforms. Private equity firms initially targeted large urology practices (mean of 60.8±32.6 urologists) with ownership of ancillary services and consolidated local market share through acquisitions of smaller practices (mean of 15.9±14.5 urologists). As of March 2021, we estimate that 7.2% of private practice urologists in the U.S. were employed by one of 5 private equity-backed platforms; over 25% of all urologists practicing in New Jersey and Maryland are employed by a private equity-backed platform. CONCLUSIONS:Private equity acquisitions have accelerated to become a dominant form of urology practice consolidation in recent years and have achieved significant market influence in certain regions. Future research should assess the impact of private equity investment on practice patterns, health outcomes, and expenditures.
PMID: 37145557
ISSN: 2352-0787
CID: 5542242
Combination Cataract Extraction, Goniotomy, Ahmed Valve and Retrobulbar tube in a patient with bilateral Uveitic Glaucoma and Cogan's Syndrome [Case Report]
PMID: 34325883
ISSN: 1943-4693
CID: 4949992
Auto-Trabeculotomy Secondary to Blunt Force Trauma
PMID: 35067276
ISSN: 2589-4196
CID: 5333712
Reply to Comment on: Individualized Corneal Cross-Linking With Riboflavin and UV-A in Ultrathin Corneas: The Sub400 Protocol [Comment]
PMID: 34237318
ISSN: 1879-1891
CID: 5484592
The link between Keratoconus and posterior segment parameters: An updated, comprehensive review
Keratoconus (KCN) has been typically known as a disorder with effects limited to the cornea. Because of this viewpoint, less attention has been devoted to its effects on the posterior segment structures. We aimed to provide a comprehensive review of the literature to understand the potential link between KCN and posterior segment structures and their functions. It is clear from the extensive evidence in the literature that KCN can be associated with morphological and functional changes in different parts of the posterior segment. It is worth noting that anatomical changes have been not only noted in several layers of the retina but also in the optic nerve head and the choroid. Several mechanisms have been proposed to explain this observation, including incidents induced by oxidative stress in keratoconic corneas and retinal adaptions to the distorted image that lands on the retina. Consequently, when KCN has been diagnosed, it seems practical to consider assessing the retinal and choroidal profile using optical coherence tomography and potentially functional abnormalities through electrophysiology procedures.
PMID: 34890805
ISSN: 1937-5913
CID: 5484692
Reduction of Artificial Tears and Use of Adjunctive Dry Eye Therapies After Lifitegrast Treatment: Evidence from Clinical and Real-World Studies
Purpose/UNASSIGNED:To assess the frequency of patients reducing the use of artificial tears (ATs) among patients with dry eye disease (DED) following lifitegrast treatment. Patients and Methods/UNASSIGNED:Two independent analyses were performed using the data from the 1-year, randomized, multicenter, Phase 3 SONATA trial and a noninterventional, real-world evidence (RWE) study conducted in patients with DED who were treated with lifitegrast in the United States and Canada. In SONATA, patients who had used ATs in the lifitegrast and placebo groups were included. The RWE study reviewed patients' electronic medical records, prescribing patterns, and practices of physicians throughout the survey. These data were then used to compare the proportion of patients using ATs in the 6-month pre-index period versus the 12-month post-index period. Results/UNASSIGNED:Of 293 patients (lifitegrast, n=195; placebo, n=98) from SONATA, 107 (lifitegrast, n=64; placebo, n=43) used ATs during the on-therapy period while 186 (lifitegrast, n=131; placebo, n=55) did not. Of those not using ATs, the proportion of patients in the lifitegrast group at any time was higher (~67% [n=131]) versus placebo (~56% [n=55]); this was the case at all study time-points (Days 90, 180, 270, and 360). The RWE study included 600 patient charts (US, n=550; Canada, n=50); 75.5% (n=453) reported AT use. There was ~40% decrease in the proportion of patients using ATs as adjunct DED therapy to lifitegrast in the post-index period (n=273) versus those in the pre-index period (n=453). Conclusion/UNASSIGNED:The findings show that the reliance on AT use can be gradually reduced with lifitegrast treatment, eventually leading to a reduction in disease burden.
PMCID:8965331
PMID: 35368241
ISSN: 1177-5467
CID: 5219482
Hyalocyte origin, structure, and imaging [Review]
ISI:000850877000001
ISSN: 1746-9899
CID: 5388602
Hyalocytes in proliferative vitreo-retinal diseases
INTRODUCTION/UNASSIGNED:Hyalocytes are sentinel macrophages residing within the posterior vitreous cortex anterior to the retinal inner limiting membrane (ILM). Following anomalous PVD and vitreoschisis, hyalocytes contribute to paucicellular (vitreo-macular traction syndrome, macular holes) and hypercellular (macular pucker, proliferative vitreo-retinopathy, proliferative diabetic vitreo-retinopathy) diseases. AREAS COVERED/UNASSIGNED:imaging of human hyalocytes. EXPERT OPINION/UNASSIGNED:Hyalocytes are important in early pathophysiology, stimulating cell migration and proliferation, as well as subsequent membrane contraction and vitreo-retinal traction. Targeting hyalocytes early could mitigate advanced disease. Ultimately, eliminating the role of vitreous and hyalocytes may prevent proliferative vitreo-retinal diseases entirely.
PMCID:9718005
PMID: 36466118
ISSN: 1746-9899
CID: 5382952
Delayed Detection of Predominantly Pericentral Hydroxychloroquine Toxicity in a Dominican Patient [Case Report]
PURPOSE/UNASSIGNED:To describe delayed detection of pericentral hydroxychloroquine (HCQ) toxicity. METHODS/UNASSIGNED:67-year-old Dominican woman with rheumatoid arthritis on HCQ presented for examination. RESULTS/UNASSIGNED:Spectral-domain optical coherence tomography (SD-OCT) demonstrated bilateral cystoid macular edema with parafoveal attenuation of the external limiting membrane (ELM) and the ellipsoid zone (EZ). ELM and EZ disruption was present in inferior macula. While subtle superior defects were present on 10-2 visual fields, superior pericentral defects were noted on 24-2 testing. Hyperautofluorescence along inferior arcades corresponded to SD-OCT and visual fields. Examination 2 years prior demonstrated nonspecific points of depression on 10-2 visual fields and normal central SD-OCT findings. EZ and ELM disruption was present in the perifoveal inferior macula. CONCLUSIONS/UNASSIGNED:Early pericentral distribution of HCQ toxicity is not limited to Asian patients. Detecting pericentral HCQ toxicity involves reviewing entire macular cube on OCT. When OCT changes are suspected on parafoveal OCT B-scans, visual field testing with 24-2 may be more sensitive than 10-2.
PMCID:9976029
PMID: 37007920
ISSN: 2474-1272
CID: 5504452
Comparison of Global and Hemifield Rates of Visual Field (VF) Progression in Glaucoma [Meeting Abstract]
ISI:000844401303257
ISSN: 0146-0404
CID: 5533882
Toward Precision Medicine in ADHD
Attention-Deficit Hyperactivity Disorder (ADHD) is a complex and heterogeneous neurodevelopmental condition for which curative treatments are lacking. Whilst pharmacological treatments are generally effective and safe, there is considerable inter-individual variability among patients regarding treatment response, required dose, and tolerability. Many of the non-pharmacological treatments, which are preferred to drug-treatment by some patients, either lack efficacy for core symptoms or are associated with small effect sizes. No evidence-based decision tools are currently available to allocate pharmacological or psychosocial treatments based on the patient's clinical, environmental, cognitive, genetic, or biological characteristics. We systematically reviewed potential biomarkers that may help in diagnosing ADHD and/or stratifying ADHD into more homogeneous subgroups and/or predict clinical course, treatment response, and long-term outcome across the lifespan. Most work involved exploratory studies with cognitive, actigraphic and EEG diagnostic markers to predict ADHD, along with relatively few studies exploring markers to subtype ADHD and predict response to treatment. There is a critical need for multisite prospective carefully designed experimentally controlled or observational studies to identify biomarkers that index inter-individual variability and/or predict treatment response.
PMCID:9299434
PMID: 35874653
ISSN: 1662-5153
CID: 5276162
Participant Engagement and Symptom Improvement: Aripiprazole Tablets with Sensor for the Treatment of Schizophrenia
Purpose/UNASSIGNED:, comprising an ingestible event-marker sensor embedded in aripiprazole tablets, wearable sensor patches, and a smartphone application) reduced the incidence of psychiatric hospitalizations relative to oral standard-of-care antipsychotics. This analysis explored the relationship between AS engagement by participants and changes in participant performance and symptom-severity measures assessed by clinical raters. Participants and Methods/UNASSIGNED:This post hoc analysis used prospectively collected clinical data from a phase 3b clinical trial (NCT03892889). Outpatients had schizophrenia, were aged 18-65 years, and had ≥ 1 psychiatric hospitalization in the previous 48 months. Participants were grouped by study completion status and a k-means clustering algorithm based on AS utilization, resulting in 3 groups: discontinued (discontinued AS before month 3 of the study); moderate engagement (completed 3 months, used AS intermittently); and high engagement (completed 3 months, used AS regularly). Baseline to end-of-study differences for the Clinical Global Impression Scale (Severity of Illness and Improvement of Illness scales), Personal and Social Performance Scale, and Positive and Negative Syndrome Scale were calculated. Results/UNASSIGNED:< 0.05) and demonstrated significantly more improvement in symptoms than participants with less engagement. Conclusion/UNASSIGNED:Participants who completed 3 months of the study and had higher AS engagement experienced significantly greater improvement in their end-of-study clinical assessments versus participants who did not complete 3 months. Improvement may be related to more-consistent medication intake and better engagement with a digital health system.
PMCID:9342879
PMID: 35923658
ISSN: 1177-889x
CID: 5288172
Healthcare Provider Engagement with a Novel Dashboard for Tracking Medication Ingestion: Impact on Treatment Decisions and Clinical Assessments for Adults with Schizophrenia
Purpose/UNASSIGNED:Schizophrenia is a severe, chronic condition accounting for disproportionate healthcare utilization. Antipsychotics can reduce relapse rates, but the characteristics of schizophrenia may hinder medication adherence. A phase 3b open-label clinical trial used aripiprazole tablets with sensor (AS; includes pills with ingestible event-marker, wearable sensor patches and smartphone application) in adults with schizophrenia. This post hoc analysis explored how healthcare providers' (HCPs) usage of a dashboard that provided medication ingestion information impacted treatment decisions and clinical assessments. Patients and Methods/UNASSIGNED:) effect sizes. Results/UNASSIGNED:To ensure sufficient opportunity for AS engagement, 113 participants who completed ≥3 months on study were analyzed. HCPs most often accessed dashboard data regarding medication ingestion and missed doses. HCPs recommended adherence counseling and participant education most often. Participants whose HCPs used the dashboard more and recommended adherence counseling and participant education (n=61) improved significantly more than participants with less dashboard-active HCPs (n=49) in CGI-I mean score (2.9 versus 3.4 [p=0.004]), total PANSS (mean change: -9.2 versus -3.1 [p=0.0002]), PANSS positive subscale (-3.2 versus -1.5 [p=0.003]), PANSS general subscale (-4.3 versus -1.2 [p=0.02]), and Marder factor for negative symptoms (-1.9 versus 0.0 [p=0.03]). Most HCPs found the dashboard easy to use (74%) and helpful for improving conversations with participants about their treatment plan and progress (78%). Conclusion/UNASSIGNED:This provider dashboard may facilitate discussions with patients about regular medication-taking, which can improve patient outcomes.
PMCID:9343256
PMID: 35928793
ISSN: 1176-6328
CID: 5288302
The Development and Clinical Application of Innovative Optical Ophthalmic Imaging Techniques
The field of ophthalmic imaging has grown substantially over the last years. Massive improvements in image processing and computer hardware have allowed the emergence of multiple imaging techniques of the eye that can transform patient care. The purpose of this review is to describe the most recent advances in eye imaging and explain how new technologies and imaging methods can be utilized in a clinical setting. The introduction of optical coherence tomography (OCT) was a revolution in eye imaging and has since become the standard of care for a plethora of conditions. Its most recent iterations, OCT angiography, and visible light OCT, as well as imaging modalities, such as fluorescent lifetime imaging ophthalmoscopy, would allow a more thorough evaluation of patients and provide additional information on disease processes. Toward that goal, the application of adaptive optics (AO) and full-field scanning to a variety of eye imaging techniques has further allowed the histologic study of single cells in the retina and anterior segment. Toward the goal of remote eye care and more accessible eye imaging, methods such as handheld OCT devices and imaging through smartphones, have emerged. Finally, incorporating artificial intelligence (AI) in eye images has the potential to become a new milestone for eye imaging while also contributing in social aspects of eye care.
PMCID:9279625
PMID: 35847772
ISSN: 2296-858x
CID: 5278832
MALT Lymphoma Presenting with Peripheral Ulcerative Keratitis [Case Report]
Objective/UNASSIGNED:To report a case of ocular mucosa-associated lymphoid tissue (MALT) lymphoma presenting with peripheral ulcerative keratitis. Methods/UNASSIGNED:A 58-year-old man with a history of vitreous syneresis in both eyes and glaucoma presented with an abnormal, painful sensation of the left eye and mild hyperemia. Physical examination revealed peripheral ulcerative keratitis superiorly and a salmon-colored lesion in the superior conjunctiva. Results/UNASSIGNED:The differential diagnosis of superior corneal thinning includes collagen vascular disease, Terrien's marginal degeneration, infectious keratitis, and other forms of peripheral keratitis. Our patient was diagnosed with conjunctival MALT lymphoma by surgical excision of the mass, and the peripheral ulcerative keratitis may be related to this diagnosis. Conclusion/UNASSIGNED:Although rare, this case demonstrates a peripheral keratitis possibly related to the underlying disease of MALT lymphoma. The patient is being treated with local radiation treatment.
PMCID:9477148
PMID: 36120701
ISSN: 1179-142x
CID: 5335252
Endophthalmitis, Visual Outcomes, and Management Strategies in Eyes with Intraocular Foreign Bodies
Purpose/UNASSIGNED:Ocular trauma with intraocular foreign body (IOFB) can have devastating visual consequences. Management and antimicrobial strategies remain variable due to the infrequency and heterogeneity of presentation. Our goal was to identify risk factors for endophthalmitis and poor visual outcomes in cases of IOFB and investigate management strategies. Patients and Methods/UNASSIGNED:A retrospective chart review was conducted in 88 eyes of 88 patients suffering traumatic injury with IOFB at the University of Michigan between January 2000 and December 2019. Medical records were reviewed to characterize the injuries and IOFBs as well as how clinical presentation and treatment modalities were associated with outcomes. Results/UNASSIGNED:Delayed presentation (P=0.016) and organic IOFB (P=0.044) were associated with development of endophthalmitis. Retinal detachment (P=0.012), wound length greater than 5 mm (P=0.041), and poor presenting visual acuity (P=0.003) correlated with poor final visual outcome. Antibiotic prophylaxis was given to all patients, though agents and routes of delivery varied. Endophthalmitis developed in 4.9% of the eyes after initial management, with primary and secondary removal of posterior segment IOFBs associated with similar rates of endophthalmitis (P=1.000). Conclusion/UNASSIGNED:Poor presenting visual acuity and severity of injury, as measured by large wound and retinal detachment, correlate with poor visual outcome. Prompt globe closure and antimicrobial prophylaxis are critical for infection prevention. In cases where IOFB removal and globe closure cannot be performed concurrently, primary globe closure with aggressive antibiotic prophylaxis offers a reasonable alternative to prevent endophthalmitis.
PMCID:9078426
PMID: 35535124
ISSN: 1177-5467
CID: 5214232
Bleb Management Following Trabeculectomy and Glaucoma Drainage Device Implantation
While treatment options available to patients with glaucoma are expanding, trabeculectomy and glaucoma drainage device implantation (GDI) remain a mainstay in glaucoma surgical care. This article reviews key aspects of bleb management following trabeculectomy and GDI surgery. Basics of postoperative management of trabeculectomy and GDIs are reviewed, as well as how to manage complications such as early and late bleb leaks, fibrosis, bleb dysesthesia and the hypertensive phase. In general, careful surgical technique, close postoperative monitoring and appropriate intervention can help patients achieve safe outcomes and long-term control of intraocular pressure
Copyright
Copyright
EMBASE:2022279103
ISSN: 1756-1752
CID: 5510222
Ophthalmic imaging for the diagnosis and monitoring of glaucoma: A review [Review]
ISI:000751336000001
ISSN: 1442-6404
CID: 5242742
Progression of functional and structural glaucomatous damage in relation to diurnal and nocturnal dips in mean arterial pressure
BACKGROUND/UNASSIGNED:Systemic hypoperfusion plays a pivotal role in the pathogenesis of primary open-angle glaucoma (POAG). Extreme dips in mean arterial pressure (MAP) due to high 24-h variability are associated with POAG, however, whether this is driven by diurnal or nocturnal dips remains undocumented. We aimed this study to investigate the association of POAG damage with variability and dips in the diurnal and nocturnal MAP. METHODS/UNASSIGNED:We conducted a retrospective longitudinal study that included 110 POAG patients who underwent 24-h ambulatory blood pressure monitoring. Our outcomes included (i) functional [visual field defects expressed as mean deviation (MD)] and (ii) structural (optic disc cupping obtained from cup-to-disc ratio) glaucoma damage. MAP variability independent of the mean (VIMmap) was computed for diurnal and nocturnal MAP. Dips were the five diurnal and three nocturnal lowest drops in MAP. We also calculated the night-to-day ratio. We applied mixed models to evaluate the progression of visual field defects and optic disc cupping in relation to diurnal and nocturnal MAP measures. RESULTS/UNASSIGNED:≤ 0.022). CONCLUSION/UNASSIGNED:Progression of glaucoma damage in POAG associates with high variability and extreme dips in the diurnal MAP. Structural glaucoma damage seems more vulnerable to nocturnal hypotension. Ambulatory blood pressure monitoring allows the assessment of sporadic diurnal and persistent nocturnal hypotension episodes. These phenotypes might offer an opportunity to improve the risk-stratification of open-angle glaucoma (OAG).
PMCID:9705350
PMID: 36457809
ISSN: 2297-055x
CID: 5383712
Comparison Between the Recommendations of Glaucoma Specialists and OCT Report Specialists For Further Ophthalmic Evaluation in a Community-Based Screening Study
PURPOSE/OBJECTIVE:To compare glaucoma referral patterns between glaucoma and OCT report specialists and to determine what influence, if any, a designated OCT reading could have on glaucoma specialist judgments. DESIGN/METHODS:Retrospective exploratory study. SUBJECTS/METHODS:449 eyes (239 individuals) from high-risk NYC neighborhoods screened as part of a mobile van glaucoma screening study from July 2017 to October 2017 were included. METHODS:All participants underwent comprehensive testing including visual acuity, commercial OCT imaging, gonioscopy, intraocular pressure, frequency doubling testing, and funduscopic assessment. Three glaucoma specialists independently evaluated all collected data to determine if further glaucoma workup referral was recommended. Two OCT report specialists evaluated just the OCT image for each eye using the commercial report as well as a specialized customized report. In phase 2, the glaucoma specialists then re-evaluated a subset of these eyes, this time with an OCT report specialist's judgments made available. MAIN OUTCOME MEASURE/METHODS:Comparison of glaucoma specialist referrals made by glaucoma specialists versus OCT report specialists. RESULTS:Inter-grader agreement between glaucoma specialists was 60% (k= 0.42) and report specialists was 95% (k= 0.77). There was agreement between a single OCT report specialist and the consensus (2 of 3) glaucoma specialists in 74% of eyes (k= 0.32). 25% of eyes studied were referred for further glaucoma evaluation by the glaucoma specialists alone and 1% of eyes were referred for further glaucoma workup by only the report specialist. With the addition of the report specialist's judgments, referral pattern changes varied by glaucoma specialist, but overall agreement increased to 85% (κ=0.53). CONCLUSIONS:There was a fair level of agreement regarding glaucoma referral recommendations between glaucoma specialists with access to comprehensive screening data and those made by OCT report specialists with access to only OCT data. Overall agreement increased when the designated OCT evaluation was made available to the glaucoma specialists. These results may aid in the design of future large-scale glaucoma screening studies.
PMID: 35688330
ISSN: 2589-4196
CID: 5248562
Ocular disorders
[S.l.] : Cambridge University Press, 2022
pp. 524-535
ISBN: 9781108942751
CID: 5298122
Acute conjunctivitis
Thorofare NJ : SLACK, 2022
pp. -
ISBN: 9781630917746
CID: 5295172
Medical and surgical management of corneal hydrops
[S.l.] : Elsevier, 2022
pp. -
ISBN: 9780323759786
CID: 5295182
Ophthalmic Pathology Of Preeclampsia
Treasure Island FL : StatPearls Publishing, 2022
pp. ?-
ISBN:
CID: 5294432
Retrobulbar Hematoma
Treasure Island FL : StatPearls Publishing, 2022
pp. -
ISBN:
CID: 5294442
The effect of cross-linking procedure on corneal wavefront aberrations in patients with keratoconus
ISI:000917751100009
ISSN: 0042-8450
CID: 5485372
Festschrift aus Anlass der Verleihung des Georg Friedrich Gotz-Preises 2002, 24. Oktober 2002
Zurich : Universitaat Zürich. Medizinische Fakultat, 2022
Extent: 47 p.
ISBN:
CID: 5485482
Corneal Cross-Linking at the Slit Lamp
Cham, Switzerland : Springer, 2022
pp. 149-157
ISBN: 9783030845063
CID: 5485492
Corneal Cross-Linking in Ultrathin Corneas
Cham, Switzerland : Springer, 2022
pp. 159-165
ISBN: 9783030845063
CID: 5485502
Corneal Cross-linking in Thin Corneas: From Origins to State of the Art
ORIGINAL:0016953
ISSN: 2752-5473
CID: 5519272
ASGARD - Adverse events and safety in glaucoma patients: assessing reports on eye drops [Meeting Abstract]
ISI:000752424500092
ISSN: 1755-375x
CID: 5499032
Health-related quality of life in glaucoma and ocular hypertension: utility values and disease severity [Meeting Abstract]
ISI:000844401305004
ISSN: 0146-0404
CID: 5499042
Five-year visual field outcomes of the HORIZON trial [Meeting Abstract]
ISI:000844437006147
ISSN: 0146-0404
CID: 5499052
Occam versus Hickam [Case Report]
A 23-year-old man presented with new onset horizontal diplopia 5 months after a left orbital floor fracture. Examination revealed bilateral abduction deficits and disc swelling. Urgent MRI and MRI showed no significant abnormalities in the CNS. Lumbar puncture revealed a minimally elevated opening pressure and significant leukocytosis. Additional CSF testing revealed probable Lyme meningitis. The patient responded to a course of oral doxycycline, with rapid resolution of his diplopia, abduction deficits, and disc edema.
PMID: 35718026
ISSN: 1879-3304
CID: 5524252
Geographic Distribution and Trends of Self-Reported Visual Impairment in 2010-2019 [Meeting Abstract]
ISI:000844437006005
ISSN: 0146-0404
CID: 5524322
Subcutaneous tocilizumab for active thyroid eye disease refractory to orbital radiation and systemic steroids in tobacco smokers
PURPOSE/OBJECTIVE:Tocilizumab (TCZ) through intravenous infusion has been shown to effectively treat active thyroid eye disease (TED) refractory to systemic steroids. TCZ is also available as a self-administered subcutaneous injection, but data demonstrating the efficacy of this formulation are limited. This study investigated the efficacy and safety of subcutaneous TCZ (SC-TCZ) for the treatment of active, moderate-to-severe TED in smokers. MATERIALS AND METHODS/METHODS:This retrospective clinical case series evaluated the clinical outcomes and adverse effects of SC-TCZ when taken for a minimum of 4 months by patients with moderate-to-severe TED and a current or recent history of cigarette smoking. RESULTS:Three patients received SC-TCZ every 1-2 weeks (4.6-11.2 mg/kg/month). The average pre-to-posttreatment clinical activity score reduction was 5.4, and proptosis was reduced by an average of 2.0 mm. No serious adverse effects were reported. CONCLUSION/CONCLUSIONS:SC-TCZ may be a useful and effective therapy for treating challenging cases of inflammatory TED and offers a safe alternative to office or hospital-based infusions. Further studies are needed to better understand optimal dosing regimens and relative efficacy compared to monthly TCZ infusions and other immunotherapies.
PMCID:8988969
PMID: 35399969
ISSN: 2211-5072
CID: 5533972
