Tomographic Biomarkers Predicting Progression to Fibrosis in Treated Neovascular Age-Related Macular Degeneration: A Multimodal Imaging Study

PURPOSE:To describe the photoreceptor-retinal pigment epithelium (RPE) interface changes and to analyze the relationships between these features and hyperreflective material (HRM) with scarring and atrophy at the macula of patients with neovascular age-related macular degeneration (nAMD). DESIGN:Retrospective single-center observational study. PARTICIPANTS:A total of 150 eyes from 144 patients with naive nAMD were included. METHODS:All patients had OCT (HRA-OCT Spectralis, Heidelberg Engineering, Heidelberg, Germany) at baseline and at 1, 3, 6, and 12 months. Macular scar and macular atrophy (MA) were determined on multimodal imaging, including color fundus (CF) and near-infrared imaging at baseline and month 12 (M12). MAIN OUTCOME MEASURES:Change in HRM type (undefined and well-defined) and location, development of fibrotic or nonfibrotic macular scar, MA, and best-corrected visual acuity (BCVA) at M12. RESULTS:At baseline, eyes with fibrin on CF had thicker and wider HRM on OCT that correlated strongly with presence of undefined HRM. The proportion of eyes with undefined HRM fell dramatically by month 1 but well-defined HRM increased. At M12 defined HRM was strongly associated with macular scar (chi-square, 82.1; P < 0.001). Ordinal regression showed that both the thickness and the width of HRM were significant risk factors for development of fibrotic scar (P < 0.001 and P = 0.02) but not nonfibrotic scars (P = 0.67 and P = 0.65). Fibrotic macular scar (P = 0.001) but not nonfibrotic scar (P = 0.129) negatively affected visual acuity at M12. Ordinal regression showed that the risk factors for progression to MA were reticular pseudodrusen and thinner HRM (P = 0.017 and P = 0.028, respectively). MA negatively affected BCVA at M12 (P < 0.001). CONCLUSION:Our study supports the role of HRM as an important biomarker for the evolution of macular scar and atrophy in patients with nAMD undergoing treatment with anti-VEGF therapies. Undefined HRM can resolve with treatment, whereas well-defined HRM likely contains vascular complexes and fibrotic elements.