Faculty Bibliography

PURPOSE/OBJECTIVE:To develop imaging and consensus-based guidelines on the application of multimodal imaging in multiple evanescent white dot syndrome (MEWDS). DESIGN/METHODS:Consensus agreement guided by literature, and an expert committee using a nominal group technique (NGT). METHODS:The expert committee employed a structured NGT with multiple rounds of discussion, conflict resolution, and anonymous voting to: (1) establish imaging criteria for diagnosing and monitoring MEWDS using color fundus photography (CFP), optical coherence tomography (OCT), fundus autofluorescence (FAF), fundus fluorescein angiography (FFA), indocyanine green angiography (ICGA), and OCT angiography (OCTA); and (2) develop consensus-based recommendations for assessing specific characteristics in patients with MEWDS. These formal recommendations were derived from a structured NGT using illustrative cases of MEWDS and were further voted upon by the entire task force. RESULTS:The diagnosis of acute MEWDS is supported by distinct multimodal features on CFP, multi-focal disruption of the ellipsoid/interdigitation zone with overlying outer retinal hyper-reflectivity with OCT, and hyper-autofluorescent spots with FAF (short-wave blue/green). In complex cases, wreath-like lesions on FFA and the absence of early hypofluorescence on ICGA help differentiate MEWDS from other chorioretinopathies. The lack of specific choroidal changes on OCT and preserved signal on OCTA on retinal and inner choroidal slabs also aid in diagnosis. CONCLUSIONS:Multimodal imaging is essential for diagnosing MEWDS and differentiating it from other non-infectious uveitis types, extending the Standardization of Uveitis Nomenclature (SUN) classification. These imaging criteria enable detailed assessment of disease activity and offer valuable insights into MEWDS pathogenesis.

Allergic contact dermatitis (ACD) is a delayed-type IV hypersensitivity response driven by innate and adaptive immune cells. While specific immune regulations of these cell types are amply elucidated, their regulations by extracellular matrix (ECM) components and T cell mediated adaptive immunity in ACD remains unclear. Lumican and biglycan are ECM proteoglycans abundant in the dermis and lymph node, known to regulate innate immune myeloid cells, but have not been investigated in lymphoid cell regulations in ACD. By immunohistology we localized lumican and biglycan in skin biopsies of psoriatic patients. Using wild type (WT), lumican and biglycan knockout mice, we investigated CD4⁺T cell infiltration, activation and proliferation in the skin and draining lymph node (dLN) of CHS-challenged mice by immunohistochemistry and flow cytometry. We used the OT-II adoptive transfer model to test antigen specific CD4⁺T cell activation. We assessed interactions of the proteoglycans with LFA-1 on T cells by confocal microscopy. Compared to WTs, the knockouts showed severe ear inflammation, with increased CD4⁺T cells infiltration in the dermis. CHS-challenged knockout mice dLN showed increased T-bet, STAT1 and -STAT4 signaling, indicating enhanced Th1 commitment and proliferation. We found that WT lymph node fibroblastic reticular cells (FRCs) secrete lumican, biglycan and decorin, a related proteoglycan, while none are expressed by naive or activated T cells. Lumican and biglycan interact with LFA-1 on T cell surfaces, and in vitro all three proteoglycans suppress CD4⁺T cell activation. Secreted by dLN FRCs, lumican, biglycan, and possibly decorin interact with LFA-1 on CD4⁺T cells to restrict its activation and reduce dermatitis severity.

PURPOSE/OBJECTIVE:To characterize the clinical and multimodal imaging features of central bouquet hemorrhage (CBH) with Henle fiber layer (HFL) involvement in highly myopic eyes, and to investigate the relationships between hemorrhage characteristics, reabsorption time, and visual outcomes. METHODS:Multicenter, retrospective analysis of highly myopic eyes with CBH involving the HFL, confirmed by optical coherence tomography (OCT). RESULTS:Eighteen eyes from 18 subjects were included for analysis. The mean age of the cohort was 39 ± 13.7 years (range: 17-69) and 61% of subjects were female. Mean refractive error was -14.8 ± 3.14 diopters (range: -9 D to -22 D). All eyes demonstrated a combined CBH with HFL component, while a subretinal component was present in 83.3% of cases. Myopic choroidal neovascularization (CNV) was excluded in all eyes using optical coherence tomography angiography (OCTA) or dye-based angiography (fluorescein or indocyanine green). No correlation was observed between hemorrhage size and visual outcomes or reabsorption time. Hemorrhage cleared after a mean of 2.63 months, and the radial HFL hemorrhage component resolved first. All eyes showed improvement in visual acuity from baseline. Persistent OCT alternations after resolution of hemorrhage included ellipsoid zone disruption (88.9%) and hyperreflective changes in HFL (77.8%). Anti-VEGF injections were administered to 6 eyes (33.3%) and did not correlate with a significant visual or anatomical benefit. CONCLUSION/CONCLUSIONS:CBH with HFL involvement in high myopia was associated with significantly improved visual outcomes from baseline but structural alterations can persist after clinical resolution. The size of the hemorrhage did not correlate with resorption time, and anti-VEGF treatment did not affect outcome. These findings provide new insights into the natural history and management of nonneovascular CBH in highly myopic eyes.

PURPOSE/OBJECTIVE:To assess whether slit-scanning specular microscopy (CellChek C; Konan Medical) can repeatedly image the same corneal location using anatomic landmarks (posterior corneal rings and corneal undulations) and unique cells identified during imaging. METHODS:A total of 203 eyes (113 patients) with and without corneal pathology were imaged to assess the prevalence of anatomic landmarks. A subcohort of 20 healthy eyes was used to identify unique cells adjacent to anatomic landmarks. Landmarks were then used to locate the same cells on repeat imaging approximately 1 week later. Endothelial cell density (ECD), coefficient of variation, and percent hexagonality were calculated. Intraclass correlation coefficient and 95% limits of agreement were used to measure variability and reproducibility of imaging. RESULTS:Approximately 91% of eyes had either posterior corneal rings or undulations present. Undulations were more common than posterior corneal rings in both healthy and diseased corneas. Among subcohort eyes, unique cells were found adjacent to anatomic landmarks in 100% of eyes. Landmarks were used to reimage the same cells in 75% of eyes. There was minimal variation in ECD, coefficient of variation, and hexagonality; intraclass correlation coefficient and 95% confidence intervals were 0.891 [0.715-0.962], 0.612 [0.179-0.849], and 0.793 [0.499-0.925], respectively. The 95% limits of agreement for ECD was -359.9-260.98. CONCLUSIONS:Landmarks identified with slit-scanning specular microscopy allowed reliable reimaging of the same endothelial location, providing a powerful tool to better understand the role of the peripheral endothelium in health and disease.

PURPOSE/UNASSIGNED:The purpose of this study was to assess the utility of artificial intelligence (AI) assisted analysis of anterior segment optical coherence tomography (AS-OCT) imaging of the device-cornea joint in predicting outcomes of an intrastromal synthetic cornea device in a rabbit model. METHODS/UNASSIGNED:Sixteen rabbits underwent intrastromal synthetic cornea implantation. Baseline anterior lamellar thickness was established using AS-OCT intraoperatively. Monthly postoperative clinical examinations and AS-OCT imaging were performed, focusing on the peri-optic zone. A convolutional neural network was trained using a subset of manually marked images to automatically detect anterior lamellar tissue. Images were aligned manually using reference coordinates. The tissue volume data were evaluated as both absolute volume and percentage change from baseline using AI. RESULTS/UNASSIGNED:Sixteen rabbits were observed for 6 (n = 8) and 12 (n = 8) months. Mild focal anterior lamella thinning without retraction was seen near tight sutures in 2 rabbits (2/8) in the 6-month cohort, whereas 2 rabbits (2/8) in the 12-month cohort showed mild focal retraction from the optic stem with thinning. AI-assisted AS-OCT image analyses detected tissue volume reduction up to 3 months before clinical examination, with a reliable threshold of 5% change in tissue volume. CONCLUSIONS/UNASSIGNED:AI-assisted AS-OCT can detect peri-prosthetic tissue loss and predicting postoperative complications following an intrastromal synthetic cornea implantation in a rabbit model. Further studies are warranted to explore its clinical utility in human patients. TRANSLATIONAL RELEVANCE/UNASSIGNED:AI-assisted monitoring of peri-optic corneal tissue volume may be a useful screening modality to detect subclinical thinning after artificial corneal implantation and inform clinical decision making.

PRECISE/UNASSIGNED:In this article, we describe the development of validated software that automates cost-effectiveness analyses of minimally invasive glaucoma surgeries based on modifications to robust mathematical models of glaucoma progression and management discussed in previous literature. PURPOSE/OBJECTIVE:To develop a validated application to streamline use of cost-effectiveness (CE) in clinical management and investigations of minimally invasive glaucoma surgeries (MIGS) in the United States. DESIGN/METHODS:Automated cost-utility analysis adapted from Markov models described in prior literature. PARTICIPANTS/METHODS:Patients of ages 65 years and greater with mild to moderate primary open-angle glaucoma irrespective of concurrent visually significant cataract. METHODS:Markov models simulating glaucoma progression through 37 states and death were constructed based on previous CE models of minimally invasive trabecular meshwork stents. These states represent combinations of various glaucoma severity (mild, moderate, advanced, and severe/blind) with differences in clinical management, including use of up to 4 medications, selective laser trabeculoplasty, or incisional surgery. These are not mutually exclusive and are based on decisions related to the rate of thinning of the retinal nerve fiber layer. Rather than using fixed sets of transition probabilities for specific surgical interventions, new transition probabilities are dynamically derived based on the expected reduction in intraocular pressure related to visual field mean deviation decline. In addition to the generic MIGS arm, two comparison arms (cataract-surgery or medications-only) are included. Medication reduction, whole costs, and utilities are modifiable inputs in the model. Optimal and worst-case results are determined by uncomplicated or complicated (secondary surgical intervention required/medication nonadherence) intervention outcomes. The model was entirely re-implemented in R and validated by comparing results to TreeAge data. MAIN OUTCOME MEASURES/METHODS:Total costs, quality adjusted life years (QALY), and incremental cost-effectiveness ratio (ICER). RESULTS:An optimal-case 35-year CE-analysis of the implantation of Hydrus and iStent inject devices provided values of costs and QALY that were similar to prior data (R vs. TreeAge): Hydrus (Cost: $50446.53 vs. $48026.13; QALY: 12.18 vs. 12.26), iStent inject (Cost: $52323.43 vs. $49599.86; QALY: 12.13 vs. 12.21), cataract (Cost: $54150.56 vs. $54409.25; QALY: 12.03 vs. 12.04). Trends of ICER over time were also very similar. CONCLUSIONS:Novel software is available to aid in CE analyses of MIGS with modifiable inputs and outcomes of interest. Such a tool makes CE more accessible for use in clinical management decisions and may guide future investigation.

PURPOSE/UNASSIGNED:To report a case of delayed diagnosis of a pituitary tumor impacting vision. The patient had undergone bilateral cataract surgery with multifocal lenses, and even an intraocular lens (IOL) exchange for persistent visual dissatisfaction, which was ultimately due to the tumor and not the visually significant cataracts or the intra-ocular lens. METHODS/UNASSIGNED:Single case report and narrative review. RESULTS/UNASSIGNED:An 81-year-old male patient presented with visually significant nuclear sclerotic cataracts that were consistent with his chief complaint of decreased visual acuity and colors not being vivid. About one month after uneventful sequential cataract phacoemulsification with multifocal IOL insertion, he complained of bilateral visual dissatisfaction, primarily with color and contrast issues. This was attributed to his non-adaption to the bilateral multifocal intra-ocular lenses. A unilateral IOL exchange of the multifocal lens to a monofocal lens occurred without complication. Still, the persistence of visual dissatisfaction after a unilateral IOL exchange prompted consultation with neuro-ophthalmology where he was diagnosed with a pituitary macroadenoma. CONCLUSION/UNASSIGNED:Prior to performing an IOL exchange in patients with persistent visual dissatisfaction after multifocal lens placement, other causes of visual dissatisfaction should be thoroughly investigated.

PURPOSE/OBJECTIVE:To develop consensus nomenclature amongst international retinal specialists for the distinctive optical coherence tomography (OCT) finding of a lesion originating from the retinal capillary bed, measuring ≥100 µm in size, and characterized by a hyperreflective wall with a hyporeflective lumen. METHODS:A comprehensive literature search was performed from inception to January 2024 on three databases to elicit publications reporting on relevant vascular abnormalities and corresponding nomenclature. A panel of retinal specialists with expertise in this topic reviewed the list of candidate terms and proposed other names for the lesion of interest. A refined list was then incorporated into a Delphi survey, which was distributed to the general membership of the International Retinal Imaging Society (IntRIS). Consensus was defined as at least 70% agreement amongst participants. RESULTS:An expert panel (n=11) reviewed candidate names for the lesion, with poor agreement noted amongst panel members regarding the relevant nomenclature. In the first Delphi survey, (n=70 IntRIS members), the need for a unified nomenclature was highlighted and two leading candidate names were established: large retinal capillary aneurysm (LRCA, n=38, 54.3%) and retinal capillary macroaneurysm (n=14, 20.0%). A second follow-up survey (n=54 IntRIS members) established LRCA (n=44, 81.5%) as the consensus term to identify the OCT vascular abnormality. CONCLUSION/CONCLUSIONS:This Delphi project reached consensus on a unifying term, large retinal capillary aneurysm, for a specific and signature OCT lesion. Identification of this characteristic OCT finding and adoption of this term may facilitate diagnosis, guide therapeutic decisions, and improve clinical and scientific communication.

PURPOSE/OBJECTIVE:To evaluate anti-vascular endothelial growth factor (VEGF) treatment patterns and long-term visual acuity (VA) outcomes in retinal vein occlusion (RVO) in routine clinical practice. DESIGN/METHODS:Retrospective observational study of the Vestrum Health Retina database. SUBJECTS/METHODS:Treatment-naïve eyes with a diagnosis of macular edema secondary to branch RVO (BRVO) or central RVO (CRVO) between January 2014 and November 2021. METHODS:Patient eyes were identified in the database using International Classification of Diseases, Clinical Modification codes, and free text searches of Vestrum's 'Exam Findings' field for macular edema. Eyes included for analysis were required to have ≥ 1 intravitreal anti-VEGF injection and ≥ 3 months of follow-up. MAIN OUTCOME MEASURES/METHODS:Treatment patterns and VA outcomes up to 60 months (5 years) of follow-up. Mean VA change stratified by the tertile of the number of anti-VEGF injections received over 60 months. RESULTS:22 365 BRVO and 18 064 CRVO eyes were included in the analysis; ∼70% had ≥ 12 months follow-up and ∼10% had ≥ 60 months follow-up. The mean number of anti-VEGF injections for BRVO and CRVO, respectively, were 6.9 and 7.0 in year 1 and 3.7 and 3.9 in year 5. Mean VA gains from baseline for BRVO and CRVO, respectively, were 11.5 and 9.7 Early Treatment Diabetic Retinopathy Study letters at month 12 and 8.2 and 5.3 letters at month 60. BRVO and CRVO eyes with fewer injections (tertile 1) tended to have lower VA gains compared with eyes that received more injections (tertile 3). Of available eyes at 60 months, 68% of BRVO and 71% of CRVO eyes had received ≥ 1 anti-VEGF injection in year 5 of follow-up. Overall, 24% of BRVO and 5% of CRVO eyes received focal/grid-pattern laser, whereas 14% of both BRVO and CRVO eyes received intravitreal corticosteroids at any time during follow-up over 60 months. CONCLUSIONS:In this retrospective analysis of the Vestrum database, VA gains were observed after anti-VEGF treatment. These were lower in patients with longer follow-up times and higher in patients who received a higher number of injections, suggesting a need for long-term monitoring of eyes with RVO.