Longitudinal Assessment of Ellipsoid Zone Integrity, Subretinal Hyperreflective Material, and Sub-RPE Disease in Neovascular AMD

Abstract Purpose To longitudinally assess the effect of anti–vascular endothelial growth factor (VEGF) treatment on ellipsoid zone (EZ) integrity, subretinal hyperreflective material (SHRM), and the sub–retinal pigment epithelium (sub-RPE) compartment in eyes with neovascular age-related macular degeneration (nAMD). Design This study was a post hoc analysis of the OSPREY clinical trial, a prospective, double-masked, phase 2 study comparing brolucizumab 6 mg with aflibercept 2 mg over 56 weeks. Participants Participants with treatment-naive nAMD at the initiation of the trial were included in the analysis. Methods Eyes were evaluated with spectral domain optical coherence tomography (SD-OCT) at 4-week intervals in the OSPREY trial (n=81). SD-OCT scans collected from each visit were automatically. segmented using a proprietary, machine learning enabled higher-order feature-extraction platform for retinal layer, SHRM, and sub-RPE boundary lines, which were evaluated and corrected as needed by masked trained graders. The current analysis focused only on subjects evaluated with Cirrus (Zeiss) platform, n=28). Main Outcome Measures Outcome measures included change from baseline in EZ-RPE volume, EZ-RPE central subfield thickness (CST), total EZ attenuation, SHRM volume, SHRM CST, and total sub-RPE volume. The correlation between each of these measures and best corrected visual acuity (BCVA) at each visit was evaluated. Results EZ-RPE volume and EZ-RPE CST showed significant increases, and total EZ attenuation, SHRM volume, SHRM CST, and total sub-RPE volume showed significant decreases from baseline at each visit from Week 4–56 (P Conclusions EZ integrity, SHRM, and sub-RPE disease features in eyes with nAMD showed improvement as early as Week 4 of anti-VEGF treatment. EZ integrity measures and SHRM volume were predictors of visual acuity over the first year of treatment.