Complete RPE and outer retinal atrophy in patients receiving anti-VEGF treatment for neovascular age-related macular degeneration

IMPORTANCE: Neovascular age-related macular degeneration (nAMD) is a leading cause of blindness with several intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents available for its management such as aflibercept, bevacizumab, and ranibizumab. However, direct comparisons between these three agents among the same patient population are limited. OBJECTIVE: To assess the rate and growth of complete retinal pigment epithelium and outer retinal atrophy (cRORA) in eyes with nAMD treated with aflibercept, bevacizumab, and/or ranibizumab. METHOD: Retrospective cohort study of patients with treatment-naïve neovascular AMD seen at an academic hospital between October 2006 and February 2019. Study eyes were treated with intravitreal injections of aflibercept, bevacizumab, and/or ranibizumab and followed for two years. MAIN OUTCOMES AND MEASURES: cRORA prevalence, location, size, and growth rate. Eyes were imaged with Cirrus spectral domain optical coherence tomography (SD-OCT). Presence and size of cRORA were calculated using the FDA-approved Advanced RPE Analysis software. Linear regression models were used to correlate cRORA progression with baseline demographic and ocular characteristics, anti-VEGF drug, and number of injections. Unpaired t-tests, ANOVA, and linear regression models were computed with SAS 9.4. RESULTS: 197 eyes from 158 patients (mean age 78.9, 62.9% women) received an average of 13 anti-VEGF injections over 24 months. 22% developed new cRORA. Mean cRORA area increased from 1.71 mm(2) to 2.93 mm(2). At 24 months, eyes with 11+ injections had significantly less cRORA area (11+ injections, 4.02 mm(2); ≤ 10 injections, 2.46 mm(2); p = 0.01) and growth rate (11+ injections, 0.41 mm(2)/year; ≤ 10 injections, 1.05 mm(2)/year; p = 0.02). Choice of anti-VEGF drug yielded no significant difference in cRORA progression. CONCLUSIONS AND RELEVANCE: Treating nAMD with aflibercept, bevacizumab or ranibizumab demonstrated comparable cRORA development at 24 months. Number of injections inversely correlated with cRORA area and growth. These results warrant further investigation in the pathophysiology of cRORA in anti-VEGF treated eyes.