Clinical and Imaging Biomarkers Associated with Outer Retinal Atrophy Onset in Exudative Age-Related Macular Degeneration: A Real-Word Prospective Study

Introduction: Macular neovascularization (MNV) secondary to age-related macular degeneration (AMD) is well managed by anti-vascular endothelial growth factor (anti-VEGF) intravitreal injections. However, outer retinal atrophy represents an unavoidable occurrence detected during follow-up. Several imaging metrics have been proposed as clinically relevant in stratifying the risk of onset of outer retinal atrophy. The main goal of this study is to evaluate the impact of noninvasive imaging metrics on the assessment of outer retinal atrophy onset in a large cohort of eyes with neovascular AMD managed in a real-world setting. Methods: This study was a prospective, observational, case series. We included patients affected by newly diagnosed neovascular AMD, requiring anti-VEGF intravitreal injections. We collected clinical and imaging data, with a planned follow-up of 24 months. The multimodal imaging protocol included optical coherence tomography, optical coherence tomography angiography, and fundus autofluorescence. We collected noninvasive imaging metrics and we assessed the relationship with the morphological and functional outcome evaluated at 12-month and 24-month time points. Results: We included 370 eyes of 370 patients with exudative AMD (210 male; mean age 79 ± 8 years). MNV were classified as follows: type 1, 198 (54%); type 2, 89 (24%); polypoidal choroidal vasculopathy, 29 (7%); and type 3, 54 (15%). A total of 120 out of 370 eyes (33%) showed complete outer retinal atrophy at the end of the 2-year follow-up. The presence of intraretinal fluid, thinning of the Sattler choroidal layer, late anti-VEGF switch, the overall number of anti-VEGF injections, and the perfusion characteristics of the MNV were found to be the most relevant factors associated with the onset of outer retinal atrophy. The other collected metrics were found to be less clinically relevant, also showing no cumulative effect in the multivariate analysis (p > 0.05). Conclusions: We identified imaging metrics significantly associated with the 2-year risk onset of outer retinal atrophy. These metrics might pave the way for the development of future customized anti-VEGF treatment strategies.