Geographic Atrophy Progression Research Articles

Structural OCT and OCT angiography biomarkers associated with the development and progression of geographic atrophy in AMD.

Geographic atrophy (GA) is an advanced, irreversible, and progressive form of age-related macular degeneration (AMD). Structural optical coherence tomography (OCT) and OCT angiography (OCTA) have been largely used to characterize this stage of AMD and, more importantly, to define biomarkers associated with the development and progression of GA in AMD. Articles pertaining to OCT and OCTA biomarkers related to the development and progression of GA with relevant key words were used to search in PubMed, Researchgate, and Google Scholar. The articles were selected based on their relevance, reliability, publication year, published journal, and accessibility. Previous reports have highlighted various OCT and OCTA biomarkers linked to the onset and advancement of GA. These biomarkers encompass characteristics such as the size, volume, and subtype of drusen, the presence of hyperreflective foci, basal laminar deposits, incomplete retinal pigment epithelium and outer retinal atrophy (iRORA), persistent choroidal hypertransmission defects, and the existence of subretinal drusenoid deposits (also referred to as reticular pseudodrusen). Moreover, biomarkers associated with the progression of GA include thinning of the outer retina, photoreceptor degradation, the distance between retinal pigment epithelium and Bruch's membrane, and choriocapillaris loss. The advent of novel treatment strategies for GA underscores the heightened need for prompt diagnosis and precise monitoring of individuals with this condition. The utilization of structural OCT and OCTA becomes essential for identifying distinct biomarkers associated with the initiation and progression of GA.

Clinical Characteristics and Progression of Pachychoroid and Conventional Geographic Atrophy

PurposeTo elucidate the clinical characteristics and progression rates of pachychoroid and conventional geographic atrophy (GA). DesignRetrospective, multicenter, observational study. ParticipantsA total of 173 eyes from 173 patients (38 eyes with pachychoroid GA and 135 with conventional GA) from six university hospitals in Japan were included. All patients were Japanese, aged ≥ 50 years and with fundus autofluorescence (FAF) images having analyzable image quality. A total of 101 eyes (22 with pachychoroid GA and 79 with conventional GA) were included in the follow-up group. MethodsThe studied eyes were classified as having pachychoroid or conventional GA; the former was diagnosed if the eye had features of pachychoroid and no drusen. The GA area was semi-automatically measured on FAF images, and the GA progression rate was calculated for the follow-up group. Multivariable linear regression analysis was used to determine whether the rate of GA progression was associated with GA subtype. Main Outcome MeasuresClinical characteristics and progression rates of pachychoroid and conventional GA. ResultsThe pachychoroid GA group was significantly younger (70.3 vs. 78.7 years, P < 0.001), more male-dominant (89.5 vs. 55.6 %, P < 0.001), and had better best-corrected visual acuity (0.15 vs. 0.40 in logarithm of the minimum angle of resolution, P = 0.002), thicker choroid (312.4 vs. 161.6 μm, P < 0.001), higher rate of unifocal GA type (94.7 vs. 49.6%, P < 0.001), and smaller GA area (0.59 vs. 3.76 mm2, P < 0.001) than the conventional GA group. In the follow-up group, the mean GA progression rate (square-root transformation) was significantly lower in the pachychoroid GA group than in the conventional GA group (0.11 vs 0.27 mm/year, P < 0.001). ConclusionsDemographic and ocular characteristics differed between GA subtypes. The progression rate of pachychoroid GA, adjusted for age and baseline GA area, was significantly lower than that of conventional GA. Japanese patients with conventional GA showed characteristics and progression rates similar to those in Caucasian populations. Some characteristics of GA in Japanese population differ from those in Caucasian populations, which may be due to the inclusion of pachychoroid GA.

Phenotypic characterization of predictors for development and progression of geographic atrophy using optical coherence tomography.

To evaluate the impact of optical coherence tomography (OCT) phenotypes preceding atrophy related to age-related macular degeneration (AMD) on the progression of atrophic lesions. In this observational retrospective cohort study, a total of 70 eyes of 60 consecutive patients with intermediate AMD with a minimum follow-up of 24 months were included. The atrophy was quantified using fundus autofluorescence, also considering the directionality of atrophy as centrifugal and centripetal progression rates.Main outcome measures were geographic atrophy (GA) progression rate (mm2/year) and square root-transformation GA (mm2/year). The best-fit model for GA (OR: 1.81, p<0.001) and square root-transformation GA (OR: 1.36, p<0.001) areas revealed that the main baseline predictor was the presence of an RPE-basal lamina-(BL)-Bruch's membrane (BrM) splitting. Large drusen at baseline appeared protective for the GA area lesion expansion over time (OR: 0.52, p<0.001) when considered with other confounders. A thin RPE-BL-BrM splitting without evidence of neovascularization on OCT angiography likely represents an OCT signature for late basal laminar deposits. Identifying this phenotype can help identify individuals with a higher risk of rapid progression and atrophy expansion.

Choroidal signal hypertransmission on optical coherence tomography imaging: Association with development of geographic atrophy in age-related macular degeneration.

To examine the association between large choroidal signal hypertransmission ≥250 μm (LHyperT) on optical coherence tomography (OCT) with the risk of developing geographic atrophy (GA) and compare this risk with those associated with nascent geographic atrophy (nGA). Two hundred and eighty eyes from 140 participants with bilateral large drusen and without late age-related macular degeneration (AMD) or nGA at baseline underwent OCT imaging and colour fundus photography (CFP) at 6-monthly intervals up to 5 years. OCT scans were graded for the presence of LHyperT and nGA, and CFPs were graded for the presence of GA. The five-year incidence of LHyperT and nGA were 37% and 27% respectively (p = 0.003), and the two-year probability of their progression to GA were 17% and 40%, respectively (p = 0.002). LHyperT and nGA explained 81% and 91% of the variance in the time to develop GA, respectively (p = 0.032), and they were both associated with a significantly higher rate of GA development compared to eyes without these lesions (adjusted hazard ratio = 110.8 and 183.2, respectively; p < 0.001 for both). LHyperT and nGA were both high-risk features for GA development, but the latter showed a higher rate of GA progression and explained a significantly greater proportion of the variance in the time to develop GA. As such, nGA may be a more robust surrogate endpoint than LHyperT for the conventional clinical endpoint of CFP-defined GA for intervention trials in the early stages of AMD.

Patient acceptability of intravitreal complement inhibitors in geographic atrophy (GA): protocol for a UK-based cross-sectional study

IntroductionGeographic atrophy (GA) is the advanced form of the non-neovascular (‘dry’) type of age-related macular degeneration (AMD). Previously untreatable, complement inhibitors delivered by regular intravitreal injections have recently been demonstrated...

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

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. Parallel-group, multicenter, randomized phase II clinical trial. Participants aged ≥ 55 years without diabetes who had GA from atrophic AMD in ≥ 1 eye. 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. 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. 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. 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. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Advancements in the treatment of geographic atrophy: focus on pegcetacoplan in age-related macular degeneration

Geographic atrophy (GA) is a progressive form of age-related macular degeneration characterized by the degeneration of retinal pigment epithelial cells and photoreceptor death. The dysregulation of the complement cascade has been implicated in GA progression. This review provides a comprehensive overview of the pathophysiology of age-related macular degeneration and GA, discusses current therapeutic options, and focuses on the recent breakthrough drug, pegcetacoplan (SYFOVRE). Pegcetacoplan is a complement inhibitor that selectively targets the C3 complement protein, effectively modulating complement activation. Clinical trials, including the OAKS and DERBY studies, have demonstrated the efficacy of SYFOVRE in reducing the growth of GA lesions compared to placebo. The FDA approval of SYFOVRE as the first and only definitive therapy for GA marks a significant milestone in the management of this debilitating condition. The review also explores potential future treatment strategies, including immune-modulating agents and ocular gene therapy. While SYFOVRE offers new hope for GA patients, further research is needed to evaluate its long-term benefits, safety profile, and optimal treatment regimens.

Multimodal imaging and deep learning in geographic atrophy secondary to age-related macular degeneration.

Geographic atrophy (GA) secondary to age-related macular degeneration is among the most common causes of irreversible vision loss in industrialized countries. Recently, two therapies have been approved by the US FDA. However, given the nature of their treatment effect, which primarily involves a relative decrease in disease progression, discerning the individual treatment response at the individual level may not be readily apparent. Thus, clinical decision-making may have to rely on the quantification of the slope of GA progression before and during treatment. A panel of imaging modalities and artificial intelligence (AI)-based algorithms are available for such quantifications. This article aims to provide a comprehensive overview of the fundamentals of GA imaging, the procedures for diagnosis and classification using these images, and the cutting-edge role of AI algorithms in automatically deriving diagnostic and prognostic insights from imaging data.

A Deep-Learning Algorithm to Predict Short-Term Progression to Geographic Atrophy on Spectral-Domain Optical Coherence Tomography

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. 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. 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. 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). 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. 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). 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.

Novel Fractal-Based Sub-RPE Compartment OCT Radiomics Biomarkers Are Associated With Subfoveal Geographic Atrophy in Dry AMD.

The purpose of this study was to quantitatively characterize the shape of the sub-retinal pigment epithelium (sub-RPE, i.e., space bounded by RPE and Bruch's membrane) compartment on SD-OCT using fractal dimension (FD) features and evaluate their impact on risk of subfoveal geographic atrophy (sfGA) progression. This was an IRB-approved retrospective study of 137 subjects with dry age-related macular degeneration (AMD) with subfoveal GA. Based on sfGA status at year five, eyes were categorized as "Progressors" and "Non-progressors". FD analysis allows quantification of the degree of shape complexity and architectural disorder associated with a structure. To characterize the structural irregularities along the sub-RPE surface between the two groups of patients, a total of 15 shape descriptors of FD were extracted from the sub-RPE compartment of baseline OCT scans. The top four features were identified using minimum Redundancy maximum Relevance (mRmR) feature selection method and evaluated with Random Forest (RF) classifier using three-fold cross validation from the training set (N = 90). Classifier performance was subsequently validated on the independent test set (N = 47). Using the top four FD features, a RF classifier yielded an AUC of 0.85 on the independent test set. Mean fractal entropy (p-value = 4.8e-05) was identified as the most significant biomarker; higher values of entropy being associated with greater shape disorder and risk for sfGA progression. FD assessment holds promise for identifying high-risk eyes for GA progression. With further validation, FD features could be potentially used for clinical trial enrichment and assessments for therapeutic response in dry AMD patients.

Treatment of dry age-related macular degeneration: A review.

Age-related macular degeneration is a global disease with a significant societal impact. The advent of anti-vascular endothelial growth factor therapy (anti-VEGF) has revolutionised the treatment of neovascular age-related macular degeneration (nAMD). Dry age-related macular degeneration (dAMD) is being investigated for possible therapeutic options. The therapeutic categories undergoing clinical trials include complement pathway inhibitors, visual cycle modulators, reduction of toxic byproducts, antioxidative therapy, neuroprotective agents, laser therapy, surgical options, gene therapy, stem cell therapy, and miscellaneous treatments. Two intravitreal anti-complement factors (pegcetacoplan and avacincaptad pegol) have recently shown phase 3 clinical trial evidence of a reduction in the growth of geographic atrophy. In this review, we provide an update on treatment options currently undergoing clinical research trials for the management of dAMD and preventing the progression of Geographic Atrophy (GA).

Evaluating the Effects of C3 Inhibition on Geographic Atrophy Progression from Deep-Learning OCT Quantification: A Split-Person Study.

To evaluate the effect pegcetacoplan, a C3 and C3b inhibitor, on the rate of progression of geographic atrophy (GA) as assessed by spectral domain optical coherence tomography (SD-OCT) using a split-person study design and deep-learning quantification. A post hoc analysis of phase 2 FILLY trial data comparing study (treated monthly, treated every other month and sham-treated) and fellow (untreated) eyes in a split-person study design was performed. This analysis included 288 eyes from 144 patients with bilateral GA from the FILLY phase 2 trial (Clinical Trials identifier: NCT02503332). Only patients with bilateral GA and without evidence of choroidal neovascularisation in either eye were included. Patient study eyes were treated with sham injections or with pegcetacoplan monthly (PM) or every other month (PEOM) for 12months. SD-OCT scans of study and fellow eyes taken at baseline and 12months were used for the analysis. The main outcomes were the annual change in the area of retinal pigment epithelial and outer retinal atrophy (RORA), its constituent features (photoreceptor degeneration [PRD], retinal pigment epithelium [RPE] loss, hypertransmission) and intact macula as compared to the untreated fellow eye. Annual GA growth was reduced in eyes treated with PM versus untreated fellow eyes for OCT features, including RORA (study eye 0.792 vs. fellow eye 1.13 mm2; P = 0.003), PRD (0.739 vs. 1.23 mm2; P = 0.015), RPE-loss (0.789 vs. 1.17 mm2; P = 0.007) and intact macula (- 0.735 vs. - 1.29 mm2; P = 0.011). Similar (but not statistically significant) trends were observed with the PEOM treatment or when GA was quantified with fundus autofluorescence (FAF). The sham treatment demonstrated no effect. Pearson correlation coefficients showed concordance in the enlargement rate of GA between the study and fellow eyes in the sham (R = 0.64) and PEOM (R = 0.68) groups, but not in the PM group (R = 0.21). Pegcetacoplan-treated eyes demonstrated a reduction in spatial GA progression compared to their untreated counterparts. This effect was more evident on OCT than with FAF. Clinical Trials identifier: NCT02503332.

Monitoring of the progression of geographic atrophy with optical coherence tomography

With the prospect of available therapy for geographic atrophy in the near future and consequently increasing patient numbers, appropriate management strategies for the clinical practice are needed. Optical coherence tomography (OCT) as well as automated OCT analysis using artificial intelligence algorithms provide optimal conditions for assessing disease activity as well as the treatment response for geographic atrophy through a rapid, precise and resource-efficient evaluation.

Clinical Characteristics and Progression of Geographic Atrophy in a Japanese Population

To elucidate the clinical characteristics and progression rate of geographic atrophy (GA) associated with age-related macular degeneration (AMD) in a Japanese population. Retrospective, multicenter, observational study. A total of 173 eyes from 173 patients from six university hospitals in Japan were included. Of 173 study eyes, 101 eyes from 101 patients were included in the follow-up group. All patients were Japanese, aged ≥ 50 years, and had definite GA associated with AMD in at least one eye. The GA area was measured semi-automatically using fundus autofluorescence (FAF) images. In the follow-up group followed for more than six months with FAF images, the GA progression rate was calculated by two methods: mm2/year and mm/year using the square-root transformation (SQRT) strategy. Simple and multiple linear regression analyses were used to identify the baseline factors associated with the GA progression rate. Clinical characteristics of GA and the GA progression rate. The mean age was 76.8 ± 8.8 years and 109 (63.0%) were males. Sixty-two (35.8%) patients had bilateral GA. The mean GA area was 3.06 ± 4.00 mm2 (1.44 ± 1.00 mm [SQRT]). Thirty-eight eyes (22.0%) were classified as having pachychoroid GA. Drusen and reticular pseudodrusen were detected in 115 (66.5%) and 73 eyes (42.2%), respectively. The mean subfoveal choroidal thickness was 194.7 ± 105.5 μm. In the follow-up group (follow-up period: 46.2 ± 28.9 months), the mean GA progression rate was 1.01 ± 1.09 mm2/year (0.23 ± 0.18 mm/year [SQRT]). In the multivariable analysis, baseline GA area [SQRT] (P=0.002) and the presence of reticular pseudodrusen (P<0.001) were significantly associated with a greater GA progression rate [SQRT]. Certain clinical characteristics of GA in Asian populations may differ from those in Caucasians. Asian patients with GA showed male-dominance and relatively thicker choroid than Caucasian patients. There was a group with GA without drusen but with features of pachychoroid. The GA progression rate in this Asian population was relatively lower than that in Caucasians. Large GA and reticular pseudodrusen were associated with a greater GA progression rate.

WITHDRAWN: Pegcetacoplan in the treatment of geographic atrophy.

Ahead of Print article withdrawn by publisher.

EE305 Cost Burden of Geographic Atrophy and Visual Impairment/Blindness in US Elderly Patients

Geographic atrophy (GA) is an advanced form of age-related macular degeneration that can lead to irreversible visual impairment (VI) and blindness. This study quantified the cost burden of GA and GA progression to VI or blindness.

Progression Dynamics of Early versus Later Stage Atrophic Lesions in Nonneovascular Age-Related Macular Degeneration Using Quantitative OCT Biomarker Segmentation

To investigate the progression of geographic atrophy (GA) secondary to non-neovascular age-related macular degeneration (AMD) in early and later stage lesions using AI-based precision tools. Retrospective analysis of an observational cohort study. Seventy-four eyes of forty-nine patients with at least one complete retinal pigment epithelial and outer retinal atrophy (cRORA) lesion secondary to AMD were included. Patients were divided between recently developed cRORA and lesions with advanced disease status. Patients were prospectively imaged by spectral domain optical coherence tomography (SD-OCT) volume scans. The study period encompassed 18 months with scheduled visits every 6 months. Growth rates of recently to cRORA converted lesions were compared with lesions in an advanced disease status using mixed effect models. The progression of retinal pigment epithelial loss (RPEL) was considered the primary endpoint. Secondary endpoints consisted of external limiting membrane disruption (ELMD) and ellipsoid zone loss (EZL). These pathognomonic imaging biomarkers were quantified using validated deep learning algorithms. Further the EZ/RPE-Loss ratio was analysed in both study cohorts. Mean [95%CI] square root progression of recently converted lesions was 79.676[-77.140 - 236.493], 68.219[-101.210 - 237.648) and 84.825[-124.816 - 294.467] mm/half year for RPEL, ELML and EZL respectively. Mean square root progression of advanced lesions was 131.737[-22.574 - 286.047], 129.964[-36.666 - 296.594] and 116.837[-90.556 - 324.301] mm/half year for RPEL, ELML and EZL respectively. RPEL (p=0.038) and ELMD (p=0.026) progression showed significant differences between the two study cohorts. Further recent converters had significantly (p<0.001) higher EZ/RPE-Loss ratios in all time points compared to patients in an advanced disease status (1.716 [1.135 - 2.296] versus 1.153 [0.576 - 1.729]). Early cRORA lesions have a slower growth rate in comparison to atrophic lesions in advanced disease stages. Differences in growth dynamics may play a crucial role in understanding the pathophysiology of non-neovascular AMD and for the interpretation of clinical trials in GA. Individual disease monitoring using AI-based quantification paves the way towards optimized GA management.

Astellas to buy eye drug developer Iveric

Japan’s Astellas Pharma has agreed to buy Iveric Bio, a developer of treatments for retinal diseases, for about $5.9 billion. Iveric’s lead product is avacincaptad pegol, a protein inhibitor that may slow the progression of geographic atrophy, an advanced form of age-related macular degeneration. The US Food and Drug Administration accepted Iveric’s new drug application for the molecule in February, and Astellas expects a decision on it by Aug. 19.

Clinical validation for automated geographic atrophy monitoring on OCT under complement inhibitory treatment

Geographic atrophy (GA) represents a late stage of age-related macular degeneration, which leads to irreversible vision loss. With the first successful therapeutic approach, namely complement inhibition, huge numbers of patients will have to be monitored regularly. Given these perspectives, a strong need for automated GA segmentation has evolved. The main purpose of this study was the clinical validation of an artificial intelligence (AI)-based algorithm to segment a topographic 2D GA area on a 3D optical coherence tomography (OCT) volume, and to evaluate its potential for AI-based monitoring of GA progression under complement-targeted treatment. 100 GA patients from routine clinical care at the Medical University of Vienna for internal validation and 113 patients from the FILLY phase 2 clinical trial for external validation were included. Mean Dice Similarity Coefficient (DSC) was 0.86 ± 0.12 and 0.91 ± 0.05 for total GA area on the internal and external validation, respectively. Mean DSC for the GA growth area at month 12 on the external test set was 0.46 ± 0.16. Importantly, the automated segmentation by the algorithm corresponded to the outcome of the original FILLY trial measured manually on fundus autofluorescence. The proposed AI approach can reliably segment GA area on OCT with high accuracy. The availability of such tools represents an important step towards AI-based monitoring of GA progression under treatment on OCT for clinical management as well as regulatory trials.

Progression of Geographic Atrophy: Retrospective Analysis of Patients from the IRIS® Registry (Intelligent Research in Sight)

To evaluate disease progression and associated vision changes in patients with geographic atrophy (GA) secondary to age-related macular degeneration (AMD) in 1 eye and GA or neovascular AMD (nAMD) in the fellow eye using a large dataset from routine clinical practice. Retrospective analysis of clinical data over 24 months. A total of 256 635 patients with GA from the American Academy of Ophthalmology (Academy) IRIS® Registry (Intelligent Research in Sight) Registry (January 2016 to December 2017). Patients with ≥ 24 months of follow-up were grouped by fellow-eye status: Cohort 1, GA:GA; Cohort 2, GA:nAMD, each with (subfoveal) and without subfoveal (nonsubfoveal) involvement. Eyes with history of retinal disease other than AMD were excluded. Sensitivity analysis included patients who were managed by retina specialists and had a record of imaging within 30 days of diagnosis. Change in visual acuity (VA), occurrence of new-onset nAMD, and GA progression from nonsubfoveal to subfoveal. In total, 69 441 patients were included: 44 120 (64%) GA:GA and 25 321 (36%) GA:nAMD. Otherwise eligible patients (57 788) were excluded due to follow-up < 24 months. In both GA:GA and GA:nAMD cohorts, nonsubfoveal study eyes had better mean (standard deviation) VA at index (67 [19.3] and 66 [20.3] letters) than subfoveal eyes (59 [23.9] and 47 [26.9] letters), and 24-month mean VA changes were similar for nonsubfoveal (-7.6 and-6.2) and subfoveal (-7.9 and-6.5) subgroups. Progression to subfoveal GA occurred in 16.7% of nonsubfoveal study eyes in the GA:GA cohort and 12.5% in the GA:nAMD cohort. More new-onset study-eye nAMD was observed in the GA:nAMD (21.6%) versus GA:GA (8.2%) cohorts. Sensitivity analysis supported the robustness of the observations in the study. This retrospective analysis describes the natural progression of GA lesions and the decline in VA associated with the disease. Proprietary or commercial disclosure may be found after the references.