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Geographic atrophy is a leading cause of progressive, irreversible vision loss. The objectives of OAKS and DERBY were to assess the efficacy and safety of pegcetacoplan compared with sham treatment in patients with geographic atrophy.

IMPORTANCE: The identification of patients at risk of progressing from intermediate age-related macular degeneration (iAMD) to geographic atrophy (GA) is essential for clinical trials aimed at preventing disease progression. DeepGAze is a fully automated and accurate convolutional neural network–based deep learning algorithm for predicting progression from iAMD to GA within 1 year from spectral-domain optical coherence tomography (SD-OCT) scans. OBJECTIVE: To develop a deep-learning algorithm based on volumetric SD-OCT scans to predict the progression from iAMD to GA during the year following the scan. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study included participants with iAMD at baseline and who either progressed or did not progress to GA within the subsequent 13 months. Participants were included from centers in 4 US states. Data set 1 included patients from the Age-Related Eye Disease Study 2 AREDS2 (Ancillary Spectral-Domain Optical Coherence Tomography) A2A study (July 2008 to August 2015). Data sets 2 and 3 included patients with imaging taken in routine clinical care at a tertiary referral center and associated satellites between January 2013 and January 2023. The stored imaging data were retrieved for the purpose of this study from July 1, 2022, to February 1, 2023. Data were analyzed from May 2021 to July 2023. EXPOSURE: A position-aware convolutional neural network with proactive pseudointervention was trained and cross-validated on Bioptigen SD-OCT volumes (data set 1) and validated on 2 external data sets comprising Heidelberg Spectralis SD-OCT scans (data sets 2 and 3). MAIN OUTCOMES AND MEASURES: Prediction of progression to GA within 13 months was evaluated with area under the receiver-operator characteristic curves (AUROC) as well as area under the precision-recall curve (AUPRC), sensitivity, specificity, positive predictive value, negative predictive value, and accuracy. RESULTS: The study included a total of 417 patients: 316 in data set 1 (mean [SD] age, 74 [8]; 185 [59%] female), 53 in data set 2, (mean [SD] age, 83 [8]; 32 [60%] female), and 48 in data set 3 (mean [SD] age, 81 [8]; 32 [67%] female). The AUROC for prediction of progression from iAMD to GA within 1 year was 0.94 (95% CI, 0.92-0.95; AUPRC, 0.90 [95% CI, 0.85-0.95]; sensitivity, 0.88 [95% CI, 0.84-0.92]; specificity, 0.90 [95% CI, 0.87-0.92]) for data set 1. The addition of expert-annotated SD-OCT features to the model resulted in no improvement compared to the fully autonomous model (AUROC, 0.95; 95% CI, 0.92-0.95; P = .19). On an independent validation data set (data set 2), the model predicted progression to GA with an AUROC of 0.94 (95% CI, 0.91-0.96; AUPRC, 0.92 [0.89-0.94]; sensitivity, 0.91 [95% CI, 0.74-0.98]; specificity, 0.80 [95% CI, 0.63-0.91]). At a high-specificity operating point, simulated clinical trial recruitment was enriched for patients progressing to GA within 1 year by 8.3- to 20.7-fold (data sets 2 and 3). CONCLUSIONS AND RELEVANCE: The fully automated, position-aware deep-learning algorithm assessed in this study successfully predicted progression from iAMD to GA over a clinically meaningful time frame. The ability to predict imminent GA progression could facilitate clinical trials aimed at preventing the condition and could guide clinical decision-making regarding screening frequency or treatment initiation.

A common clinical phenotype of several neurodegenerative and systemic disorders including Alzheimer's disease and atherosclerosis is the abnormal accumulation of extracellular material, which interferes with routine cellular functions. Similarly, patients with age-related macular degeneration (AMD), the leading cause of vision loss among the aged population, present with extracellular lipid- and protein-filled basal deposits in the back of the eye. While the exact mechanism of growth and formation of these deposits is poorly understood, much has been learned from investigating their composition, providing critical insights into AMD pathogenesis, prevention, and therapeutics. We identified human osteopontin (OPN), a phosphoprotein expressed in a variety of tissues in the body, as a newly discovered component of basal deposits in AMD patients, with a distinctive punctate staining pattern. OPN expression within these lesions, which are associated with AMD disease progression, were found to co-localize with abnormal calcium deposition. Additionally, OPN puncta colocalized with an AMD risk-associated complement pathway protein, but not with apolipoprotein E or vitronectin, two other well-established basal deposit components. Mechanistically, we found that retinal pigment epithelial cells, cells vulnerable in AMD, will secrete OPN into the extracellular space, under oxidative stress conditions, supporting OPN biosynthesis locally within the outer retina. Finally, we report that OPN levels in plasma of aged (non-AMD) human donors were significantly higher than levels in young (non-AMD) donors, but were not significantly different from donors with the different clinical subtypes of AMD. Collectively, our study defines the expression pattern of OPN in the posterior pole as a function of disease, and its local expression as a potential histopathologic biomarker of AMD.

BackgroundThe macular central 1 mm diameter zone is crucial to patients’ visual acuity, but the long-term natural history of central sparing in eyes with geographic atrophy (GA) is unknown.MethodsWe manually segmented GA in 210 eyes with GA involving central 1 mm diameter zone (mean follow-up=3.8 years) in the Age-Related Eye Disease Study. We measured the residual area in central 1 mm diameter zone and calculated central residual effective radius (CRER) as square root of (residual area/π). A linear mixed-effects model was used to model residual size over time. We added a horizontal translation factor to each data set to account for different durations of GA involving the central zone.ResultsThe decline rate of central residual area was associated with baseline residual area (p=0.008), but a transformation from central residual area to CRER eliminated this relationship (p=0.51). After the introduction of horizontal translation factors to each data set, CRER declined linearly over approximately 13 years (r2=0.80). The growth rate of total GA effective radius was 0.14 mm/year (95% CI 0.12 to 0.15), 3.7-fold higher than the decline rate of CRER (0.038 mm/year, 95% CI 0.034 to 0.042). The decline rate of CRER was 53.3% higher in eyes with than without advanced age-related macular degeneration in the fellow eyes at any visit (p=0.007).ConclusionsCRER in eyes with GA declined linearly over approximately 13 years and may serve as an anatomic endpoint in future clinical trials aiming to preserve the central zone.

To investigate the topographic distribution of geographic atrophy (GA) and to identify an anatomic endpoint that correlates with visual acuity (VA) in eyes with GA.

In macula-wide analyses, spectral-domain (SD) optical coherence tomography (OCT) features including drusen volume, hyperreflective foci, and OCT-reflective drusen substructures independently predict geographic atrophy (GA) onset secondary to age-related macular degeneration (AMD). We sought to identify SD OCT features in the location of new GA before its onset.

To assess visual function outcomes to 48 weeks in patients with bilateral geographic atrophy (GA) secondary to age-related macular degeneration included in 2 interventional clinical trials: relationship to baseline lesion size, outcomes by baseline lesion characteristic subgroups, and correlation of visual function outcomes with GA area.

Outer retinal degenerations, including age-related macular degeneration (AMD), are characterized by photoreceptor and retinal pigment epithelium (RPE) atrophy. In these blinding diseases, macrophages accumulate at atrophic sites, but their ontogeny and niche specialization remain poorly understood, especially in humans. We uncovered a unique profile of microglia, marked by galectin-3 upregulation, at atrophic sites in mouse models of retinal degeneration and human AMD. In disease models, conditional deletion of galectin-3 in microglia led to phagocytosis defects and consequent augmented photoreceptor death, RPE damage, and vision loss, indicating protective roles. Mechanistically, Trem2 signaling orchestrated microglial migration to atrophic sites and induced galectin-3 expression. Moreover, pharmacologic Trem2 agonization led to heightened protection but in a galectin-3–dependent manner. In elderly human subjects, we identified this highly conserved microglial population that expressed galectin-3 and Trem2. This population was significantly enriched in the macular RPE-choroid of AMD subjects. Collectively, our findings reveal a neuroprotective population of microglia and a potential therapeutic target for mitigating retinal degeneration.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ajo.2009.04.018 Byline: Eleonora M. Lad (a), Tina Hernandez-Boussard (b), John M. Morton (b), Darius M. Moshfeghi (a) Abstract: To determine the incidence of retinopathy of prematurity (ROP) based on a national database and to identify baseline characteristics, demographic information, comorbidities, and surgical interventions. Author Affiliation: (a) Department of Ophthalmology, Stanford University School of Medicine, Stanford, California (b) Department of Surgery, Stanford University School of Medicine, Stanford, California Article History: Accepted 16 April 2009

To report the 1-year progression of visual impairment on psychophysical tests of visual function in patients with early and intermediate age-related macular degeneration (AMD).

Age-related macular degeneration (AMD) is a major cause of vision loss in the elderly. To better study the pathobiology of AMD, postmortem eyes offer an excellent opportunity to correlate optical coherence tomography (OCT) imaging characteristics with histopathology. However, postmortem eyes from autopsy present challenges to standard OCT imaging including opaque anterior segment structures and standard of care autopsy processing resulting in oblique views to the macula. To overcome these challenges, we report a custom periscope attached by a standard mount to an OCT sample arm and demonstrate high quality macular OCT acquisitions in autopsy-processed eyes.

The peripheral retina of the human eye offers a unique opportunity for assessment and monitoring of ocular diseases. We have developed a novel wide-field (>70°) optical coherence tomography system (WF-OCT) equipped with wavefront sensorless adaptive optics (WSAO) for enhancing the visualization of smaller (<25°) targeted regions in the peripheral retina. We iterated the WSAO algorithm at the speed of individual OCT B-scans (~20 ms) by using raw spectral interferograms to calculate the optimization metric. Our WSAO approach with a 3 mm beam diameter permitted primarily low- but also high- order peripheral wavefront correction in less than 10 seconds. In preliminary imaging studies in five normal human subjects, we quantified statistically significant changes with WSAO correction, corresponding to a 10.4% improvement in average pixel brightness (signal) and 7.0% improvement in high frequency content (resolution) when visualizing 1 mm (~3.5°) B-scans of the peripheral (>23°) retina. We demonstrated the ability of our WF-OCT system to acquire non wavefront-corrected wide-field images rapidly, which could then be used to locate regions of interest, zoom into targeted features, and visualize the same region at different time points. A pilot clinical study was conducted on seven healthy volunteers and two subjects with prodromal Alzheimer’s disease which illustrated the capability to image Drusen-like pathologies as far as 32.5° from the fovea in un-averaged volume scans. This work suggests that the proposed combination of WF-OCT and WSAO may find applications in the diagnosis and treatment of ocular, and potentially neurodegenerative, diseases of the peripheral retina, including diabetes and Alzheimer’s disease.

A prospective exploratory pilot study examined the test–retest reliability and feasibility of computerized alternative visual function studies in patients with dry, age-related macular degeneration to improve early outcome metrics used to track and treat this disease. These included low luminance visual acuity, cone-specific contrast, contrast sensitivity, and microperimetry.

To evaluate the diagnostic performance of emergency physicians’ interpretation of robotically acquired retinal optical coherence tomography images for detecting posterior eye abnormalities in patients seen in the emergency department.

AbstractAge-related macular degeneration (AMD), the leading cause of blindness in developed nations, has been associated with poor performance on tests of phonemic fluency. This pilot study sought to (1) characterize the relationship between phonemic fluency and resting-state functional brain connectivity in AMD patients and (2) determine whether regional connections associated with phonemic fluency in AMD patients were similarly linked to phonemic fluency in healthy participants. Behavior-based connectivity analysis was applied to resting-state, functional magnetic resonance imaging data from seven patients (mean age=79.9±7.5 years) with bilateral AMD who completed fluency tasks prior to imaging. Phonemic fluency was inversely related to the strength of functional connectivity (FC) among six pairs of brain regions, representing eight nodes: left opercular portion of inferior frontal gyrus (which includes Broca's area), left superior temporal gyrus (which includes part of Wernicke's area), inferior parietal lobe (bilaterally), right superior parietal lobe, right supramarginal gyrus, right supplementary motor area, and right precentral gyrus. The FC of these reference links was not related to phonemic fluency among 32 healthy individuals (16 younger adults, mean age=23.5±4.6 years and 16 older adults, mean age=68.3±3.4 years). Compared with healthy individuals, AMD patients exhibited higher mean connectivity within the reference links and within the default mode network, possibly reflecting compensatory changes to support performance in the setting of reduced vision. These findings are consistent with the hypothesis that phonemic fluency deficits in AMD reflect underlying brain changes that develop in the context of AMD.

The present study aimed to examine cost, demographics, and short-term complications associated with orbital fractures and their surgical repair in the inpatient population in the United States over a 7-year period.

The purpose of this study was to report a case of an impending central retinal artery occlusion with hypoperfusion in a moyamoya patient.

BACKGROUND AND OBJECTIVE:To determine whether the use of lidocaine gel before application of povidone-iodine affects endophthalmitis rates following intravitreal injections.PATIENTS AND METHODS:Retrospective consecutive case series of all intravitreal injections and post-intravitreal injection endophthalmitis cases at one institution from 2000 to 2009. A review of medical records of post-intravitreal injection endophthalmitis cases was performed to determine whether lidocaine gel was applied prior to povidone-iodine antisepsis and to analyze the clinical course and outcomes.RESULTS:A total of 8,802 intravitreal injections were administered during the study period. When no lidocaine gel was used prior to povidone-iodine antisepsis, four cases of endophthalmitis following 4,120 intravitreal injections (0.097%) were recorded. When 2% lidocaine gel was applied before povidone-iodine, four cases of endophthalmitis following 4,682 intravitreal injections (0.085%) were observed (A total of 8,802 intravitreal injections were administered during the study period. When no lidocaine gel was used prior to povidone-iodine antisepsis, four cases of endophthalmitis following 4,120 intravitreal injections (0.097%) were recorded. When 2% lidocaine gel was applied before povidone-iodine, four cases of endophthalmitis following 4,682 intravitreal injections (0.085%) were observed (P= 1.00, odds ratio = 1.12).CONCLUSION:The use of lidocaine gel prior to povidone-iodine antisepsis did not significantly alter post-intravitreal injection endophthalmitis rates.

Background and Objective:To report the 36-month experience of the Stanford University Network for Diagnosis of Retinopathy of Prematurity (SUNDROP) telemedicine initiative.Patients and Methods:Retrospective analysis of the SUNDROP archival data between December 1, 2005, and November 30, 2008, to evaluate this diagnostic technology for retinopathy of prematurity (ROP) screening. A total of 230 consecutively enrolled infants meeting ROP examination criteria were screened with the Ret-Cam II (Clarity Medical Systems, Pleasanton, CA) and evaluated by the SUNDROP reading center at Stanford University. Outcomes included referral-warranted ROP, treatment-warranted ROP, and anatomic outcomes.Results:In the initial 36-month period, the SUNDROP telemedicine initiative did not miss any treatment-warranted ROP. A total of 230 infants (460 eyes) were imaged, resulting in 1,059 examinations and 10,921 unique images. Ten infants were identified with referral-warranted ROP: nine underwent laser photocoagulation and one regressed spontaneously. The sensitivity was 100% with a specificity of 99.5%. No patient progressed to retinal detachment or other adverse outcomes.Conclusion:The SUNDROP telemedicine screening initiative for ROP has demonstrated high reliability for identification of treatment-warranted disease. All cases of treatment-warranted disease were captured. There were no adverse outcomes.

To assess baseline differences and longitudinal rate of change in retinal and choroidal imaging parameters between APOE ε4 carriers and non-carriers with normal cognition.

Purpose: Intravitreal injection is the most frequently performed eye procedure in the world and is an essential component in the management of sight-threating retinal diseases and conditions. Given the seriousness and range of diseases treated and the risks of the procedure, retina specialists must weigh the pros and cons of each individual treatment. Complexities guiding injection treatment are multifaceted and involve patient-history review, careful examination, diagnostic testing selection and interpretation, customized medical decision-making, and follow-up considerations.Methods: This article by the Intravitreal Injection Task Force Committee of the American Society of Retina Specialists documents the intricacies and necessary components of the intravitreal injection procedure.Results: By expert consensus, the task force further recommends ancillary services and decision-making that may accompany intravitreal injection visits, when appropriate, to monitor response to treatment, adjust treatment, and manage additional considerations in the same or fellow eye.Conclusions: Retina specialists can optimize safety and therapeutic outcomes with individualized consideration and customization of intravitreal injection treatment for each patient.