Ten-year incidence, risk factors and progression rate of macular atrophy in neovascular age-related macular degeneration

Background: To evaluate the 10-year cumulative incidence, progression rates, and risk factors for macular atrophy (MA) in neovascular age-related macular degeneration (nAMD) patients receiving long-term anti-vascular endothelial growth factor (VEGF) therapy. Methods: Retrospective, multicenter, cohort study including 148 eyes from 140 nAMD patients treated with a pro-re-nata (PRN) anti-VEGF regimen and followed for ≥ 10 years. Annual multimodal imaging-including blue autofluorescence [BAF], spectral-domain optical coherence tomography [SD-OCT] and near-infrared reflectance-was reviewed to detect and quantify MA using RegionFinder. Kaplan-Meier analysis estimated cumulative MA incidence, while mixed-effects Cox and linear regressions identified risk factors and progression rates. Results: Baseline MA prevalence was 23.0%, increasing to 64.9% at 5 years and 79.8% at 10 years. Foveal involvement occurred in 47.4% of cases. Significant predictors for MA included baseline BCVA < 20/40 (HR = 1.50, p = 0.02), greater central subfield thickness (CST) fluctuations (HR = 1.04, p = 0.01), and more frequent submacular haemorrhages (HR = 1.34, p = 0.04). Type 3 macular neovascularization was associated with fovea-involving MA (HR = 2.03, p = 0.02). Mean MA size increased from 0.34 to 2.27 mm at 10 years, progressing at 0.20 mm/year (β = 0.15, p < 0.001). Eyes with incident MA exhibited faster progression (β = 0.03, p = 0.01) and worse BCVA decline compared to those with baseline MA (-1.96 vs. -1.42 letters/year, p < 0.001). Conclusions: nAMD patients treated with PRN anti-VEGF therapy demonstrated a high 10-year cumulative incidence of MA (79.8%), with poor baseline BCVA and CST fluctuations as key risk factors. Eyes with incident MA progressed faster and were associated with greater visual decline, suggesting a more visually impactful atrophy.