Intergrader Agreement in Grading Optical Coherence Tomography Morphologic Features in Eyes With Intermediate Nonexudative Age-Related Macular Degeneration.

Purpose: To determine the reliability of a nine-point summary scale for grading intermediate age-related macular degeneration (AMD) image morphologic features based on the Early Treatment Diabetic Retinopathy Study (ETDRS) grid. Methods: Two trained graders independently divided spectral domain-optical coherence tomography (SD-OCT) scans into nine subfields and then graded each subfield for the presence of intraretinal hyperreflective foci (HRF), reticular pseudodrusen (RPD), and incomplete or complete retinal pigment epithelium and outer retinal atrophy (iRORA or cRORA). Grading results were assessed by summing the subfield grades into a nine-point summary score and also by using an eye-level binary grade for presence of the finding in any subfield. Gwet's first-order agreement coefficient (AC1) was calculated to assess intergrader agreement. Results: Images of 79 eyes from 52 patients were evaluated. Intergrader agreement was higher when the OCT grades were summarized with a nine-point summary score (Gwet's AC1 0.92, 0.89, 0.99, and 0.99 for HRF, RPD, iRORA, and cRORA, respectively) compared with the eye-level binary grade (Gwet's AC1 0.75, 0.76, 0.97, and 0.96 for HRF, RPD, iRORA, and cRORA, respectively), with significant differences detected for HRF and RPD. Conclusions: The use of a nine-point summary score showed higher reliability in grading when compared to the binary subfield- and eye-level data, and thus may offer more precise estimation of AMD disease staging. Translational Relevance: These findings suggest that a nine-point summary score could be a useful means of disease staging by using findings on OCT in clinical studies of AMD.

Implementation Mapping of the Collaborative University of California Teleophthalmology Initiative (CUTI): A Qualitative Study Using the Exploration, Preparation, Implementation, and Sustainment (EPIS) Framework.

Background This study aimed to investigate the rationale, barriers, and facilitators of teleretinal camera implementation in primary care and endocrinology clinics for diabetic retinopathy (DR) screening across University of California (UC) health systems utilizing the Exploration, Preparation, Implementation, and Sustainment (EPIS) framework. Methodology Institutional representatives from UC Los Angeles, San Diego, San Francisco, and Davis participated in a series of focus group meetings to elicit implementation facilitators and barriers for teleophthalmology programs within their campuses. Site representatives also completed a survey regarding their program's performance over the calendar year 2022 in the following areas: DR screening camera sites, payment sources and coding, screening workflows including clinical, information technology (IT), reading, results, pathologic findings, and follow-up, including patient outreach for abnormal results. Focus group and survey results were mapped to the EPIS framework to gain insights into the implementation process of these programs and identify areas for optimization. Results Four UC campuses with 20 active camera sites screened 7,450 patients in the calendar year 2022. The average DR screening rate across the four campuses was 55%. Variations between sources of payment, turn-around time, image-grading structure, image-report characteristics, IT infrastructure, and patient outreach strategies were identified between sites. Closing gaps in IT integration between data systems, ensuring the financial sustainability of the program, and optimizing patient outreach remain primary challenges across sites and serve as good opportunities for cross-institutional learning. Conclusions Despite the potential for long-term cost savings and improving access to care, numerous obstacles continue to hinder the widespread implementation of teleretinal DR screening. Implementation science approaches can identify strategies for addressing these challenges and optimizing implementation.

Biomechanic, proteomic and miRNA transcriptional changes in the trabecular meshwork of primates injected with intravitreal triamcinolone.

Although biomechanical changes of the trabecular meshwork (TM) are important to the pathogenesis of glucocorticoids-induced ocular hypertension (GC-OHT), there is a knowledge gap in the underlying molecular mechanisms of the development of it. In this study, we performed intravitreal triamcinolone injection (IVTA) in one eye of 3 rhesus macaques. Following IVTA, we assessed TM stiffness using atomic force microscopy and investigated changes in proteomic and miRNA expression profiles. One of 3 macaques developed GC-OHT with a difference in intraocular pressure of 4.2 mmHg and a stiffer TM with a mean increase in elastic moduli of 0.60 kPa versus the non-injected control eye. In the IVTA-treated eyes, proteins associated with extracellular matrix remodeling, cytoskeletal rearrangement, and mitochondrial oxidoreductation were significantly upregulated. The significantly upregulated miR-29b and downregulated miR-335-5p post-IVTA supported the role of oxidative stress and mitophagy in the GC-mediated biomechanical changes in TM, respectively. The significant upregulation of miR-15/16 cluster post-IVTA may indicate a resultant TM cell apoptosis contributing to the increase in outflow resistance. Despite the small sample size, these results expand our knowledge of GC-mediated responses in the TM and furthermore, may help explain steroid responsiveness in clinical settings.

Factors Involved in Anti-VEGF Treatment Decisions for Neovascular Age-Related Macular Degeneration: Insights from Real-World Clinical Practice.

Background: Anti-vascular endothelial growth factor (anti-VEGF) agents are widely prescribed for the treatment of neovascular age-related macular degeneration (nAMD). Although studies have investigated patient choice of anti-VEGF agent, little is known regarding factors that influence physician preference of anti-VEGF agent for their patients. Objective: To describe physician rationale and challenges in prescribing anti-VEGF treatments for patients with nAMD. Methods: Data were drawn from the Adelphi Real World nAMD Disease Specific Programme™, a cross-sectional survey with retrospective data capture of physicians and their patients with nAMD in the United States between October 2021 and May 2022. Physicians (n = 56) reported data for up to 13 consecutively consulting patients (n = 451), including current anti-VEGF treatments used, factors affecting physicians' choice of anti-VEGF agent and treatment strategy, and restrictions on specific agents. Results: Most physicians prefer employing a "treat-and-extend" treatment strategy, over "fixed interval" or "pro re nata" strategies. However, in routine clinical practice, "treat-and-extend" was reported for less than half of nAMD-diagnosed eyes. Top factors influencing physician choice of anti-VEGF agent and treatment strategy included maximizing clinical benefit (eg visual acuity gains and fluid control), patient convenience, and reducing out-of-pocket costs. However, physicians also reported facing substantial roadblocks in prescribing their choice of anti-VEGF agent, including restrictions on approved agents and gaps in insurance coverage. Persistent fluid was the most common physician-selected reason for switching a patient away from an anti-VEGF agent. Conclusion: Physicians face barriers to prescribing their preferred anti-VEGF agents in real-world healthcare settings. Overcoming these challenges may improve treatment outcomes for patients with nAMD.

People with wet age-related macular degeneration (wet AMD) have problems with their eyesight that can lead to blindness if left untreated. Eye doctors (ophthalmologists) use a class of medicine called anti-VEGF agents to treat people with wet AMD. However, eye doctors often face challenges in prescribing their anti-VEGF agent of choice. We surveyed eye doctors to determine the reasons why they preferred some anti-VEGF agents over others, as well as the barriers to prescribing these anti-VEGF agents. Eye doctors reported that they usually choose a specific anti-VEGF agent because it leads to better vision, has lower cost for people with wet AMD, or may reduce the number of appointments needed for people with wet AMD. Eye doctors also noted that they face challenges in treating people with wet AMD, including restrictions and limited insurance coverage for certain anti-VEGF agents. Solving these problems could help eye doctors use their medicine of choice and improve eyesight even more when they treat people with wet AMD.

Performance of Automated Machine Learning in Predicting Outcomes of Pneumatic Retinopexy.

Purpose: Automated machine learning (AutoML) has emerged as a novel tool for medical professionals lacking coding experience, enabling them to develop predictive models for treatment outcomes. This study evaluated the performance of AutoML tools in developing models predicting the success of pneumatic retinopexy (PR) in treatment of rhegmatogenous retinal detachment (RRD). These models were then compared with custom models created by machine learning (ML) experts. Design: Retrospective multicenter study. Participants: Five hundred and thirty nine consecutive patients with primary RRD that underwent PR by a vitreoretinal fellow at 6 training hospitals between 2002 and 2022. Methods: We used 2 AutoML platforms: MATLAB Classification Learner and Google Cloud AutoML. Additional models were developed by computer scientists. We included patient demographics and baseline characteristics, including lens and macula status, RRD size, number and location of breaks, presence of vitreous hemorrhage and lattice degeneration, and physicians' experience. The dataset was split into a training (n = 483) and test set (n = 56). The training set, with a 2:1 success-to-failure ratio, was used to train the MATLAB models. Because Google Cloud AutoML requires a minimum of 1000 samples, the training set was tripled to create a new set with 1449 datapoints. Additionally, balanced datasets with a 1:1 success-to-failure ratio were created using Python. Main Outcome Measures: Single-procedure anatomic success rate, as predicted by the ML models. F2 scores and area under the receiver operating curve (AUROC) were used as primary metrics to compare models. Results: The best performing AutoML model (F2 score: 0.85; AUROC: 0.90; MATLAB), showed comparable performance to the custom model (0.92, 0.86) when trained on the balanced datasets. However, training the AutoML model with imbalanced data yielded misleadingly high AUROC (0.81) despite low F2-score (0.2) and sensitivity (0.17). Conclusions: We demonstrated the feasibility of using AutoML as an accessible tool for medical professionals to develop models from clinical data. Such models can ultimately aid in the clinical decision-making, contributing to better patient outcomes. However, outcomes can be misleading or unreliable if used naively. Limitations exist, particularly if datasets contain missing variables or are highly imbalanced. Proper model selection and data preprocessing can improve the reliability of AutoML tools. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Surgical Drainage of Large Macular Cystoid Spaces in Coats Disease.

Purpose: To describe an option of surgically draining large macular cystoid spaces in a patient with Coats disease. Methods: A case and its findings were analyzed. Results: A standard pars plana vitrectomy was performed to aspirate large macular cystoid spaces using a subretinal cannula with intraoperative optical coherence tomography guidance. Because of the viscous nature of the chronic fluid and lipid exudates, the contents of the large cystoid spaces were drained through a retinotomy using a soft-tipped aspiration cannula. Postoperative follow-up after surgical drainage showed immediate resolution of the macular cystoid spaces and gradual resolution of the dense subfoveal exudates over 1 year. Although surgical intervention led to the eventual resolution of the macular edema and exudates, visual recovery was limited by the chronicity of the condition. Conclusions: Surgical drainage of large macular cystoid spaces in Coats disease can be achieved in eyes that are refractory to medical management. Earlier surgical intervention in select cases may allow for visual rehabilitation.

A Novel Predictive Model Utilizing Retinal Microstructural Features for Estimating Survival Outcome in Patients with Glioblastoma.

Glioblastoma is a highly aggressive brain tumor with poor prognosis despite surgery and chemoradiation. The visual sequelae of glioblastoma have not been well characterized. This study assessed visual outcomes in glioblastoma patients through neuro-ophthalmic exams, imaging of the retinal microstructures/microvasculature, and perimetry. A total of 19 patients (9 male, 10 female, average age at diagnosis 69 years) were enrolled. Best-corrected visual acuity ranged from 20/20-20/50. Occipital tumors showed worse visual fields than frontal tumors (mean deviation - 14.9 and - 0.23, respectively, p < 0.0001). Those with overall survival (OS) < 15 months demonstrated thinner retinal nerve fiber layer and ganglion cell complex (p < 0.0001) and enlarged foveal avascular zone starting from 4 months post-diagnosis (p = 0.006). There was no significant difference between eyes ipsilateral and contralateral to radiation fields (average doses were 1370 cGy and 1180 cGy, respectively, p = 0.42). A machine learning algorithm using retinal microstructure and visual fields predicted patients with long (≥ 15 months) progression free and overall survival with 78% accuracy. Glioblastoma patients frequently present with visual field defects despite normal visual acuity. Patients with poor survival duration demonstrated significant retinal thinning and decreased microvascular density. A machine learning algorithm predicted survival; further validation is warranted.

SUPRACHOROIDAL SPACE INJECTION TECHNIQUE: Expert Panel Guidance.

PURPOSE: To develop professional guidelines for best practices for suprachoroidal space (SCS) injection, an innovative technique for retinal therapeutic delivery, based on current published evidence and clinical experience. METHODS: A panel of expert ophthalmologists reviewed current published evidence and clinical experience during a live working group meeting to define points of consensus and key clinical considerations to inform the development of guidelines for in-office SCS injection. RESULTS: Core consensus guidelines for in-office SCS injection were reached and reported by the expert panel. Current clinical evidence and physician experience supported SCS injection as a safe and effective method for delivering retinal and choroidal therapeutics. The panel established consensus on the rationale for SCS injection, including potential benefits relative to other intraocular delivery methods and current best practices in patient preparation, pre- and peri-injection management, SCS-specific injection techniques, and postinjection management and follow-up. CONCLUSION: These expert panel guidelines may support and promote standardization of SCS injection technique, with the goal of optimizing patient safety and outcomes. Some aspects of the procedure may reasonably be modified based on the clinical setting and physician judgment, as well as additional study.

Teleophthalmology provides earlier eye care access for patients with newly-diagnosed diabetes.

Purpose: Timely diagnosis of diabetic retinopathy is important in preventing vision loss. This study aims to determine if remote retinal imaging enables earlier eye care access among newly-diagnosed diabetic patients. Design: Retrospective cohort study. Methods: Using the OptumLabs® Data Warehouse - a longitudinal, real-world dataset containing deidentified administrative claims and electronic health record (EHR) data, we included 968 846 adults with newly diagnosed type 2 diabetes and at least 1 year of continuous enrollment. We compared time from initial diabetes diagnosis to first eye exam by remote screening or in-person eye exam. Results: We found that at year 1 after diagnosis, 5459 (0.56%) patients underwent remote imaging and 208 023 (21.5%) underwent in-person exam. The mean (95% CI) time to eye exam was 3.48 (3.38-3.58) months for remote imaging and 4.22 (4.20-4.23) months for in-person visits (p < 0.0001). Interestingly, 27.5% of remote screenings were performed on the same day of diabetes diagnosis. Excluding same-day encounters, mean time to eye exam was 4.80 (4.68-4.91) months for remote imaging and 4.85 (4.83-4.86) months for in-person eyecare (p = 0.4). Conclusions: Thus, teleophthalmology may enable earlier eye care access among patients with newly-diagnosed diabetes, primarily with same-day screenings. Increased adoption of teleretinal screening may enable earlier detection of diabetic retinopathy and prevent vision loss.

METformin for the MINimization of Geographic Atrophy Progression (METforMIN): A Randomized Trial.

Purpose: Metformin use has been associated with a decreased risk of age-related macular degeneration (AMD) progression in observational studies. We aimed to evaluate the efficacy of oral metformin for slowing geographic atrophy (GA) progression. Design: Parallel-group, multicenter, randomized phase II clinical trial. Participants: Participants aged ≥ 55 years without diabetes who had GA from atrophic AMD in ≥ 1 eye. Methods: We enrolled participants across 12 clinical centers and randomized participants in a 1:1 ratio to receive oral metformin (2000 mg daily) or observation for 18 months. Fundus autofluorescence imaging was obtained at baseline and every 6 months. Main Outcome Measures: The primary efficacy endpoint was the annualized enlargement rate of the square root-transformed GA area. Secondary endpoints included best-corrected visual acuity (BCVA) and low luminance visual acuity (LLVA) at each visit. Results: Of 66 enrolled participants, 34 (57 eyes) were randomized to the observation group and 32 (53 eyes) were randomized to the treatment group. The median follow-up duration was 13.9 and 12.6 months in the observation and metformin groups, respectively. The mean ± standard error annualized enlargement rate of square root transformed GA area was 0.35 ± 0.04 mm/year in the observation group and 0.42 ± 0.04 mm/year in the treatment group (risk difference = 0.07 mm/year, 95% confidence interval = -0.05 to 0.18 mm/year; P = 0.26). The mean ± standard error decline in BCVA was 4.8 ± 1.7 letters/year in the observation group and 3.4 ± 1.1 letters/year in the treatment group (P = 0.56). The mean ± standard error decline in LLVA was 7.3 ± 2.5 letters/year in the observation group and 0.8 ± 2.2 letters/year in the treatment group (P = 0.06). Fourteen participants in the metformin group experienced nonserious adverse events related to metformin, with gastrointestinal side effects as the most common. No serious adverse events were attributed to metformin. Conclusions: The results of this trial as conducted do not support oral metformin having effects on reducing the progression of GA. Additional placebo-controlled trials are needed to explore the role of metformin for AMD, especially for earlier stages of the disease. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Choroidal Changes in Rhesus Macaques in Aging and Age-Related Drusen.

Purpose: Choroidal vascular changes occur with normal aging and age-related macular degeneration (AMD). Here, we evaluate choroidal thickness and vascularity in aged rhesus macaques to better understand the choroid's role in this nonhuman primate model of AMD. Methods: We analyzed optical coherence tomography (OCT) images of 244 eyes from 122 rhesus macaques (aged 4-32 years) to measure choroidal thickness (CT) and choroidal vascularity index (CVI). Drusen number, size, and volume were measured by semiautomated annotation and segmentation of OCT images. We performed regression analyses to determine any association of CT or CVI with age, sex, and axial length and to determine if the presence and volume of soft drusen impacted these choroidal parameters. Results: In rhesus macaques, subfoveal CT decreased with age at 3.2 µm/y (R2 = 0.481, P < 0.001), while CVI decreased at 0.66% per year (R2 = 0.257, P < 0.001). Eyes with soft drusen exhibited thicker choroid (179.9 ± 17.5 µm vs. 162.0 ± 27.9 µm, P < 0.001) and higher CVI (0.612 ± 0.051 vs. 0.577 ± 0.093, P = 0.005) than age-matched control animals. Neither CT or CVI appeared to be associated with drusen number, size, or volume in this cohort. However, some drusen in macaques were associated with underlying choroidal vessel enlargement resembling pachydrusen in human patients with AMD. Conclusions: Changes in the choroidal vasculature in rhesus macaques resemble choroidal changes in human aging, but eyes with drusen exhibit choroidal thickening, increased vascularity, and phenotypic characteristics of pachydrusen observed in some patients with AMD.

Impact of Prophylactic Ranibizumab to Prevent Neovascular Age-Related Macular Degeneration on Eyes With Intermediate Age-Related Macular Degeneration.

Purpose: The purpose of this study was to determine the impact of prophylactic ranibizumab (PR) injections given every 3 months in eyes with intermediate nonexudative age-related macular degeneration (AMD) on drusen volume, macular layer thicknesses, and progression of geographic atrophy (GA) area over 24 months in the PREVENT trial. Methods: This post hoc analysis of the prospective PREVENT trial compared eyes with intermediate AMD randomized to PR versus sham injections to determine rates of conversion to neovascular AMD over 24 months. Drusen area and volume, macular thickness and volume, and retinal layer thicknesses were measured on spectral-domain optical coherence tomography images and analyzed. Masked grading of GA area and subretinal drusenoid deposits (SDDs) using fundus autofluorescence images was performed. Results: There were no statistical differences in drusen area and volumes between groups, and similar reductions in central subfield thickness, mean cube thickness, cube volume, and retinal sublayer thickness from baseline to 24 months (P = 0.018 to < 0.001), with no statistical differences between groups in any of these anatomic parameters. These findings were not impacted by the presence or absence of SDD. Among the 9 eyes with GA in this study, mean GA growth rate from baseline to 24 months was 1.34 +/- 0.79 mm2/year after PR and 1.95 +/- 1.73 mm2/year in sham-treated eyes (P = 0.49), and similarly showed no statistical difference with square root transformation (P = 0.61). Conclusions: Prophylactic ranibizumab given every 3 months did not appear to affect drusen volume, macular thinning, or GA progression in eyes with intermediate AMD. Translational Relevance: This work investigates the impact of PR on progressive retinal degeneration in a clinical trial.

Barriers to Implementation of Teleretinal Diabetic Retinopathy Screening Programs Across the University of California.

Aim: To describe barriers to implementation of diabetic retinopathy (DR) teleretinal screening programs and artificial intelligence (AI) integration at the University of California (UC). Methods: Institutional representatives from UC Los Angeles, San Diego, San Francisco, Irvine, and Davis were surveyed for the year of their program's initiation, active status at the time of survey (December 2021), number of primary care clinics involved, screening image quality, types of eye providers, image interpretation turnaround time, and billing codes used. Representatives were asked to rate perceptions toward barriers to teleretinal DR screening and AI implementation using a 5-point Likert scale. Results: Four UC campuses had active DR teleretinal screening programs at the time of survey and screened between 246 and 2,123 patients at 1-6 clinics per campus. Sites reported variation between poor-quality photos (<5% to 15%) and average image interpretation time (1-5 days). Patient education, resource availability, and infrastructural support were identified as barriers to DR teleretinal screening. Cost and integration into existing technology infrastructures were identified as barriers to AI integration in DR screening. Conclusions: Despite the potential to increase access to care, there remain several barriers to widespread implementation of DR teleretinal screening. More research is needed to develop best practices to overcome these barriers.

Retinal Aneurysms in Myopic Traction Maculopathy.

This case report describes retinal telangiectatic vessels and aneurysms in a woman aged 23 years with a history of pathologic myopia.

Real-World Experience Using Intravitreal Brolucizumab Alone or in Combination with Aflibercept in the Management of Neovascular Age-Related Macular Degeneration.

Purpose: To evaluate real-world experience using intravitreal brolucizumab (IVBr), alone or in combination with aflibercept, in eyes with neovascular age-related macular degeneration (nAMD) treated previously with other inhibitors of VEGF (anti-VEGF). Methods: This was a retrospective study of all eyes with nAMD treated with IVBr on a treat-and-extend protocol at a single center. Best-corrected visual acuity (BCVA), optical coherence tomography (OCT) at baseline and final visit, and drug-related adverse events were analyzed. Eyes with recurrent macular fluid on IVBr every 8 weeks were treated with a combination therapy alternating between IVBr and aflibercept every month. Results: Among 52 eyes (40 patients) on IVBr, all had been previously treated with other anti-VEGF therapy, with 73% having persistent macular fluid. After a mean follow-up of 46.2±27.4 weeks on IVBr, the mean treatment interval for intravitreal therapy increased to 8.8±2.1 weeks on IVBr from a baseline of 6.1±3.1 weeks (p<0.001). Macular fluid decreased and BCVA was stable/improved in 61.5% of eyes on IVBr. Ten eyes with increased macular fluid on IVBr monotherapy when extended to every 8 weeks were treated with combination therapy alternating between IVBr and aflibercept every 4 weeks. In these eyes, 80% had improved macular fluid on OCT and 70% stable or improved BCVA after a median follow-up of 53 weeks on combination therapy. Mild intraocular inflammation developed in four eyes, all occurring on IVBr monotherapy, and none had associated vision loss. Conclusion: In the real world, IVBr used to treat eyes with nAMD previously treated with other anti-VEGF therapies appears to be well tolerated and associated with an improvement in macular fluid, stabilization of BCVA, and/or increase in intravitreal treatment interval. Combination therapy alternating between IVBr and aflibercept monthly appears to be well tolerated and can be considered for eyes with macular fluid on IVBr every 8 weeks.

Predictors of As-Needed Ranibizumab Injection Frequency in Patients With Macular Edema Following Retinal Vein Occlusion.

PURPOSE: To evaluate spectral-domain optical coherence tomography (SD-OCT) biomarkers associated with ranibizumab injection frequency after 7 monthly doses in the prospective, multicenter SHORE study for macular edema due to retinal vein occlusion (RVO). DESIGN: Prospective phase IV clinical trial data. METHODS: Post hoc analysis of 95 patients who received 7 monthly doses of ranibizumab followed by either pro re nata (PRN) or nonrandomized monthly injections from months 7-15 in eyes with macular edema secondary to RVO. Baseline SD-OCT biomarkers assessed include central subfield thickness (CST), epiretinal membrane presence, intraretinal and subretinal fluid, hyperreflective foci, disorganization of retinal inner layers (DRIL), and disruption of the external limiting membrane, ellipsoid zone, or interdigitation zone. Univariate and multivariable regression analyses evaluated the association between SD-OCT biomarkers and ranibizumab injection frequency. RESULTS: Mean age of patients was 65.3 (SD, 12.7) years. Overall, 57.9% had BRVO/HRVO and 42.1% of eyes had CRVO. Mean BCVA improved (+17.5 [SD, 1.2] Early Treatment of Diabetic Retinopathy Study [ETDRS] letters) during the 7-month fixed dosing period, remaining stable from baseline (+20.1 [SD, 1.5] ETDRS letters) during the PRN phase from months 7-15. The mean number of PRN injections was 4.32 (SD, 2.35). On multivariate regression, greater baseline DRIL (ß = 0.021, P = .0275) and higher CST at month 3 (ß = 0.01, P < .001) were associated with a higher total number of PRN injections. CONCLUSION: Greater baseline DRIL and higher CST at 3 months after starting ranibizumab treatment are associated with more frequent ranibizumab injections in PRN-treated patients with macular edema due to RVO.

A Spontaneous Nonhuman Primate Model of Myopic Foveoschisis.

Purpose: Foveoschisis involves the pathologic splitting of retinal layers at the fovea, which may occur congenitally in X-linked retinoschisis (XLRS) or as an acquired complication of myopia. XLRS is attributed to functional loss of the retinal adhesion protein retinoschisin 1 (RS1), but the pathophysiology of myopic foveoschisis is unclear due to the lack of animal models. Here, we characterized a novel nonhuman primate model of myopic foveoschisis through clinical examination and multimodal imaging followed by morphologic, cellular, and transcriptional profiling of retinal tissues and genetic analysis. Methods: We identified a rhesus macaque with behavioral and anatomic features of myopic foveoschisis, and monitored disease progression over 14 months by fundus photography, fluorescein angiography, and optical coherence tomography (OCT). After necropsy, we evaluated anatomic and cellular changes by immunohistochemistry and transcriptomic changes using single-nuclei RNA-sequencing (snRNA-seq). Finally, we performed Sanger and whole exome sequencing with focus on the RS1 gene. Results: Affected eyes demonstrated posterior hyaloid traction and progressive splitting of the outer plexiform layer on OCT. Immunohistochemistry showed increased GFAP expression in Müller glia and loss of ramified Iba-1+ microglia, suggesting macro- and microglial activation with minimal photoreceptor alterations. SnRNA-seq revealed gene expression changes predominantly in cones and retinal ganglion cells involving chromatin modification, suggestive of cellular stress at the fovea. No defects in the RS1 gene or its expression were detected. Conclusions: This nonhuman primate model of foveoschisis reveals insights into how acquired myopic traction leads to phenotypically similar morphologic and cellular changes as congenital XLRS without alterations in RS1.

Teleophthalmology Using Remote Retinal Imaging During the COVID-19 Pandemic.

Introduction: Lower insurance reimbursements have limited the financial sustainability of remote eye screening programs. Greater utilization and insurance coverage for teleophthalmology screening during the coronavirus disease 2019 (COVID-19) pandemic in 2020 may enhance awareness and expand remote retinal imaging services. This retrospective cross-sectional study evaluates utilization and insurance coverage for remote retinal imaging in the United States in 2020. Methods: We analyzed teleretinal imaging utilization and insurance payments from January 1 to December 31, 2020, using the Optum Labs Data Warehouse, a comprehensive national database of deidentified administrative claims for commercial and Medicare Advantage enrollees in the United States. We evaluated frequency of claims and insurance payment for services using the Current Procedural Terminology codes 92227 and 92228 for remote eye imaging by any provider, and 92250 for fundus photography by non-eye care providers. Results: The use of remote retinal imaging in the United States declined rapidly during the initial COVID-19 lockdown from 3,627 claims in February 2020 to 1,414 claims in April 2020, but returned to 3,133 claims by December 2020, similar to mean prepandemic levels in 2019 (2,841 ± 174.8 claims). The proportion of insurance payments for remote imaging increased temporarily from 47.4% in February to 56.7% in April, and then returned to 45.9% in December of 2020. Discussion: Utilization of remote retinal imaging declined steeply, while the insurance coverage increased during the initial COVID-19 lockdown in 2020, but returned to prepandemic levels by end of the year. Changes in utilization and relaxed restrictions on insurance reimbursements for teleophthalmology during the COVID-19 pandemic were not sustained.