Faculty Bibliography

Glaucoma is a chronic neurodegenerative disease of the visual system, and treatment is targeted toward lowering intraocular pressure. However, some patients fail to respond to treatment and their intraocular pressure levels remain high, risking continuous vision loss. Explainable machine learning provides a mechanism for both individual prognostication and the identification of factors associated with treatment outcome. Here, we used explainable machine learning to predict intraocular pressure for glaucoma patients receiving medication treatment. We accessed the UK Biobank to obtain information on 290 eyes from 161 participants who reported a diagnosis of glaucoma and were receiving treatment. Features were divided into three distinct datasets containing demographic data only, physiometabolic parameters and medication prescription data, and all data combined. We evaluated five machine learning techniques for each feature set in terms of their ability to predict intraocular pressure at a follow-up visit in a classification task. We then calculated SHapley Additive exPlanation (SHAP) values for the best performing model to determine feature importance, stability, and interactions. We found that eXtreme Gradient Boosting (XGBoost) outperformed all other models when trained and tested on the combined feature set with an area under receiver operating characteristic curve (AUC) of 0.708. Insulin-like growth factor 1 (IGF-1), low-density lipoprotein (LDL), and lymphocyte count ranked as the three most important features for this model. LDL and IGF-1 exhibited a low degree of global variability in contribution to the model output across all cross-validation repeats. SHAP values demonstrated the strongest interactions being between LDL and IGF-1. In summary, our studies indicated the importance of blood LDL and IGF-1 in contributing to the outcomes of intraocular pressure lowering treatment and demonstrated the ability of XGBoost to predict these outcomes.

PURPOSE/OBJECTIVE:To compare the long-term safety of MicroShunt implantation with trabeculectomy in eyes with primary open-angle glaucoma. DESIGN/METHODS:A 3-year observational extension of a 2-year prospective randomized trial. PARTICIPANTS/METHODS:The extension study enrolled 279 patients (217 MicroShunt, 62 trabeculectomy), with 256 (198 and 58, respectively) completing the month 60 visit. METHODS:This trial compared clinical outcomes of MicroShunt implantation with trabeculectomy, both augmented with mitomycin C. Adverse events (AEs), intraocular pressure (IOP), and IOP-lowering medication use were recorded 36, 48, and 60 months after initial randomization. MAIN OUTCOME MEASURES/METHODS:The primary outcome was the cumulative incidence of sight-threatening AEs. Secondary outcomes included all other AEs/complications, secondary interventions, and reductions in IOP and number of glaucoma medications. RESULTS:Rates of sight-threatening AEs were 2% (n = 4) in the MicroShunt group and 0% in the trabeculectomy group, with 1 eye each in the MicroShunt group having central retinal artery occlusion, choroidal hemorrhage (after placement of a glaucoma drainage device), progressive endothelial cell loss, and pseudophakic bullous keratopathy. Only 2 of the 4 sight-threatening AEs in the MicroShunt group were deemed related to the study device or procedure. Four eyes in the MicroShunt group experienced device erosion through the conjunctiva. Increased IOP requiring treatment was more frequent (26% vs. 8%, P = 0.0017), whereas hypotony (3% vs. 13%, P = 0.038), epiretinal membrane formation (2% vs. 8%; P = 0.028), and blepharoptosis (4% vs. 11%, P = 0.048) were less frequent in the MicroShunt group. Four patients in the trabeculectomy group required surgical revision for hypotony. Changes in endothelial cell density were similar in the MicroShunt (-19% ± 22%) and trabeculectomy (-19% ± 22%) groups, with a mean between-group difference of 0.1% (P = 0.98). In the mean ± standard deviation, IOP was reduced from 20.8 ± 4.9 mmHg at baseline to 14.2 ± 4.1 mmHg at month 60 in MicroShunt eyes (mean reduction, 5.5 mmHg [26%]) and from 20.1 ± 3.9 mmHg to 10.4 ± 3.7 mmHg in trabeculectomy eyes (mean reduction, 9.1 mmHg [45%]), with a between-group difference of -4.6 mmHg (P < 0.0001). CONCLUSIONS:Both filtering procedures demonstrated favorable safety profiles over 5 years. Most AEs through 5 years did neither necessitate reoperation nor result in vision-threatening complications. FINANCIAL DISCLOSURE(S)/BACKGROUND:Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

PURPOSE/OBJECTIVE:Anti-vascular endothelial growth factor medications are a cornerstone in the treatment of many macular diseases in modern ophthalmology. These medications accrue significant economic burdens to individuals and health systems, and recent data on health-system level practice patterns involving agent selection is lacking. We sought to examine utilization of intravitreal anti-VEGF agents from 2017 to 2023 across various payors and diagnoses in the United States in order to analyze trends in usage. METHODS:A retrospective cross-sectional study was performed. Data were obtained from the Epic Cosmos database, comprised of de-identified data from the electronic health record, Epic, of 238 million patients from all 50 states from January 1, 2017 to December 31, 2023. Encounters where a patient received an intravitreal injection in an ophthalmology clinic were categorized by intravitreal medication ordered, visit diagnosis, and primary insurance payor. The overall usage rates of each medication across different diagnoses and primary payor were compared. Total number of injections per year of anti-VEGF medication, the rate per 100000 ophthalmology encounters (OE), and the rate in different retinal conditions and with various insurance providers were the main outcome measures. RESULTS:From 2017-2023, there were 571,545 anti-VEGF injections administered, with 53.6% aflibercept 2 mg (306,247/571,545; 625.8/000 OE), 34.8% bevacizumab 1.25 mg (198,696/571,545; 414.7/100000 OE), 7.83% ranibizumab 0.3 mg and 0.5 mg (44,803/571,545; 99.2/100000 OE), and 3.43% faricimab 6 mg (19,624/571,545; 32.8/100000 OE). Brolucizumab 6 mg, ranibizumab-eqrn 0.5 mg, ranibizumab-nuna 0.5 mg, and aflibercept 8 mg accounted for <1% of all injections. From 2017-2023, the rate of aflibercept 2 mg increased from 361.3 injections/100000 OE to 913.1, bevacizumab increased from 274.1 to 538.1, and ranibizumab decreased from 92.4 to 64.0. The rate of faricimab increased from 37.9/100000 OE to 189.9 from 2022-2023. Patients with Medicare received aflibercept 2 mg at higher rates than bevacizumab (364.3/100000 OE vs 187.1, respectively) [t(6) = 5.67, p = 0.001] and faricimab (19.4/100000 OE), a pattern not seen in commercially insured [t(6)=2.07, p > 0.05] patients. Medicaid patients had a marginally significant difference in use of bevacizumab (M = 19.9/100000 OE, SD = 7.32) and aflibercept 2 mg (16.1/100000 OE, SD = 7.22) [t(6)]=2.95, p = 0.026]. CONCLUSIONS:Aflibercept 2 mg was the most common drug used overall from 2017-2023. Faricimab had the highest absolute and relative increase in utilization from 2022-2023. Patients with Medicare B or C were significantly more likely to receive aflibercept over bevacizumab.

BACKGROUND:Whole eye transplantation (WET) has long been looked to as a potential solution for the aesthetic and functional deficits caused by severe ocular pathology and trauma. Here, we describe the first successful combined face and whole eye transplantation (FT/WET), highlighting the logistical, ethical, and technical considerations that enabled this milestone. METHODS:A 46-year-old male with severe facial and ocular deficits underwent multidisciplinary evaluation and was deemed a candidate for FT/WET. Subsequently, a surgical algorithm was developed through rigorous preoperative planning and team based surgical simulations. This process focused on techniques that would allow for efficient graft procurement and inset, while simultaneously limiting trauma to the globe and its adnexa. RESULTS:Longitudinal monitoring demonstrated maintained graft viability throughout the postoperative period. Fluorescein angiography and ICG angiography confirmed robust retinal and choroidal perfusion. Diffusion-weighted MRI revealed structural preservation of the optic tracts, despite inner retinal atrophy. The patient has also experienced significant improvement in facial aesthetics and functionality with no episodes of graft rejection to date. CONCLUSIONS:This case demonstrates the feasibility of addressing deficits once deemed irreparable through advanced surgical techniques, preoperative planning, and multidisciplinary collaboration. Although functional vision recovery has not been observed, this innovation expands the reconstructive options available for patients with severe facial and ocular deficits, paving the way for future advancements in vascularized composite allotransplantation.

BACKGROUND:Healthcare is responsible for 8.5% of greenhouse gas emission in the United States. Physicians are becoming increasingly concerned about the climate crisis, particularly in the field of ophthalmology where there is a growing body of literature related to sustainability. Although emissions of cataracts surgery, one of the most performed surgical procedures in the world, have been quantified, modifications to practice have yet to be made. This study aims to uplift the perspectives of a diverse set of healthcare workers on implementing environmentally sustainable practices in the cataract surgery setting. METHODS:16 semi-structured interviews were conducted with professionals working in various direct patient care or administrative roles at a large health center to gain insight on implementing a variety of sustainability initiatives. We focused on initiatives related to supply reduction, reusable supplies, multi-dosing pharmaceuticals, and health system process and policy shifts. RESULTS:Participants most frequently identified infection prevention and control (IPC) concerns as a primary barrier to implementation. Additionally, the IPC department was most often cited as a key stakeholder in implementation. However, participants from this department did not share these same concerns. Additionally, participants most often cited that these initiatives would be successfully implemented by those providing direct patient care. CONCLUSIONS:Themes generated from the collection of responses underscore a broader discussion of disconnect between policy and practice in healthcare as a barrier to implementation of these initiatives and an opportunity in harnessing clinically led change to implement sustainable practices in a growing healthcare system.

PURPOSE/OBJECTIVE:To evaluate the association between socioeconomic status (SES; represented by a patient's neighborhood area deprivation index) and structural and functional measurements of the eye at initial presentation for those who eventually underwent trabeculectomy. DESIGN/METHODS:A retrospective cohort study. PARTICIPANTS/METHODS:We identify patients who underwent a trabeculectomy and had at least 1 OCT scan and 1 visual field (VF) test before undergoing surgery. Patients of any age with either progressing glaucoma or uncontrolled intraocular pressure, or both, who underwent a trabeculectomy and were a part of the DOMAIN cohort study were included. METHODS:We use a subject's first recorded OCT scan and VF test to obtain baseline structural and functional measurements. We next use patient addresses to determine their census block, which is then matched to the corresponding proxy for SES. Univariate and multivariate regressions controlling for race, age, and gender were used to analyze the associations between SES and structural and functional measurements at baseline. MAIN OUTCOME MEASURE/METHODS:The association between SES and structural and functional measures at baseline. RESULTS:Among the 154 eyes in the study, we find that living in an area with greater deprivation is associated with worse structural (larger cup volumes [CVs], thinner retinal nerve fiber layer, and ganglion cell-inner plexiform layer) and functional (lower visual field index [VFI] and mean deviation [MD]) measures at baseline. However, these associations only remained statistically significant in the multivariate analysis for CV, VFI, and MD after controlling for a patient's race, gender, and age. In addition, when comparing those living in the best and worst neighborhoods, we find that living in the area with the highest decile level of deprivation is associated with a 6.63 dB lower MD at presentation compared to those living in areas with the least deprivation. CONCLUSIONS:Lower SES is associated with worse optic nerve damage and VF performance at presentation for eyes that eventually undergo trabeculectomy surgery. FINANCIAL DISCLOSURE(S)/BACKGROUND:Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Neurofibroma can present in a myriad of body tissues, including, very rarely, in the sclera; a unique presentation that is described herein. We describe a case of a 21-year-old man with neurofibromatosis type 1, who presented with 2 weeks of a blue-gray scleral discoloration overlying a protrusion of the sclera. His presentation was initially concerning for scleritis; however, histopathological analysis revealed an epibulbar neurofibroma. Recognition of rare manifestations of neurofibromatosis is essential to properly diagnose and manage ocular findings in this condition.

PURPOSE/OBJECTIVE:To describe the clinical features, multimodal imaging findings, natural history, and treatment outcomes of acute outer retinopathy (AOR), which represents an expanded spectrum of acute annular outer retinopathy (AAOR). DESIGN/METHODS:Retrospective, observational, longitudinal, multicenter case series. PARTICIPANTS/METHODS:Twenty-three patients (15 female, 8 male) with a mean age of 41.8 ± 18.6 years (range: 14-86 years) and a mean follow-up duration of 3.7 ± 1.5 years (range: 1-12 years). METHODS:Clinical characteristics, multimodal imaging findings, laboratory evaluations, genetic testing, natural history, therapeutic management, and outcomes were reviewed and analyzed. MAIN OUTCOMES MEASURES/METHODS:Specific multimodal imaging signatures of AOR were identified, including findings from ophthalmoscopy, fundus autofluorescence (FAF), fluorescein angiography (FA), indocyanine green angiography (ICGA), and optical coherence tomography (OCT). Humphrey visual field testing, full-field electroretinography (ERG), and multifocal ERG were analyzed. Baseline features and the natural course of the disease were delineated. RESULTS:Thirty-eight eyes from 23 patients were analyzed. Presenting symptoms included photopsia (87%), blurred vision (57%), and scotoma (57%). On ophthalmoscopy, AOR was acutely characterized by yellow-greyish outer retinal lesions corresponding to hyperautofluorescent changes on FAF and the angular sign of Henle fiber layer hyperreflectivity (ASHH) on OCT. FAF imaging revealed ring-like hyperautofluorescent lesions surrounding the optic disc in 18% of eyes. Additional lesion patterns on FAF included perivenular (53%), sectoral (16%), and spot-like distributions (13%). FA and ICGA findings were mostly unremarkable. Lesion progression primarily occurred within the initial weeks following presentation and stabilized in size beyond this period in the majority of eyes. Over time, affected areas progressed to outer retinal atrophy with pigmentary changes. Foveal sparing was observed in 68% of the eyes. None of the therapeutic interventions appeared effective in halting the progression to complete outer retinal atrophy or preventing lesion enlargement. CONCLUSIONS:AOR is characterized by early photoreceptor disruption, evidenced by ASHH on OCT, leading to rapid outer retinal atrophy and subsequent degeneration of the retinal pigment epithelium within the damaged zones. Although distinct patterns of lesion distribution were observed, their consistent features on multimodal imaging support their inclusion within a unified disease spectrum termed acute outer retinopathy.