Faculty Bibliography

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.

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".

We present a case of a 7-year-old boy who was presented with a small medial subperiosteal orbital abscess (SPOA) and trace superior phlegmon and who was initially treated with intravenous (IV) antibiotics, corticosteroids, and observation. After clinical resolution and discharge, the patient returned with superior migration of his abscess requiring surgical drainage. Potential factors leading to readmission are discussed, including the anti-inflammatory and immunosuppressant effects of steroids, and presence of early surgical indictors such as bony dehiscence and proptosis. This case highlights the need for careful consideration of initial imaging and presence of a non-medial phlegmon prior to initiation of steroids.

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.

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.

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.

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).

Traditionally, surgical head immobilization for neurobiological research with large animals is achieved using stereotaxic frames. Despite their widespread use, these frames are bulky, expensive, and inflexible, ultimately limiting surgical access and preventing research groups from practicing surgical approaches used to treat humans. Here, we designed a mobile, low-cost, three-pin skull clamp for performing a variety of neurosurgical procedures on non-human primates. Modeled after skull clamps used to operate on humans, our system was designed with added adjustability to secure heads with small or irregular geometries for innovative surgical approaches. The system has six degrees of freedom with skull pins attached to setscrews for independent, fine-tuned depth adjustment. Unlike other conventional skull clamps which require additional mounting fixtures, our system has an integrated tray with mounting bracket for easy use on most operating room tables. Our system has successfully secured primate heads in the supine and lateral position, allowing surgeons to match surgical approaches currently practiced when operating on humans. The system also expands the opportunity for researchers to utilize imaged-guided robotic surgery techniques. Overall, we hope that our system can serve as an adaptable, affordable, and robust surgery platform for any laboratory performing neurobiological research with large animal models.