Neovascular Age-Related Macular Degeneration Treated with Aflibercept: Five-Year Follow-Up and Correlation with Optical Coherence Tomography Biomarkers in a Real-World Setting

Introduction: To evaluate long-term outcomes of neovascular age-related macular degeneration(nAMD) treatment with aflibercept in a treat-and-extend (T&E) regimen and explore correlations between optical coherence tomography (OCT) biomarkers and clinical evolution over 5 years in a real-world setting. Methods: This retrospective monocentric study included patients diagnosed with type 1 or type 2 nAMD at the University Magna Graecia of Catanzaro between 2016 and 2024. Inclusion criteria were treatment-naïve status, diagnosis confirmed by OCT and optical coherence tomography angiography (OCT-A), exclusive treatment with intravitreal aflibercept following a T&E regimen, and a minimum 5-year follow-up. Best-correct visual acuity (BCVA) and OCT were assessed at baseline, after the third injection, and yearly up to year 5 (seven time points). Evaluated OCT biomarkers included subretinal and intraretinal fluid (SRF, IRF), hyperreflective spots (HS), drusenoid pigment epithelial detachment (dPED), subretinal hyperreflective material (SHRM), outer retinal tubulations (ORT), onion sign, retinal pigment epithelium (RPE) tears, and subretinal fibrosis. Results: Among 59 cases, 57.6% were type 1 macular neovascularization (MNV) and 42.4% type 2. At the baseline, SRF was more common in type 1, SHRM in type 2. Central foveal thickness (CFT) decreased significantly in both groups after loading and remained stable. SRF decreased significantly in type 1 (p = 0.001), but not in type 2. dPED decreased in both groups, significantly in type 1 (p = 0.01). HS decreased in patients with type 1 MNV (p = 0.009). RPE tears were more frequent in type 2 (12%) and linked to BCVA loss. For type 2 MNV, ORT (p = 0.035) and subretinal fibrosis appeared from year 5 (p = 0.006). BCVA improved after loading in both groups, declined after year 2, and was better preserved in those with better visual acuity after the loading dose. Conclusions: Baseline SHRM in type 2 MNV may predict more IRF, ORT, and RPE tears over time. Type 1 MNV with baseline SRF often shows reduced HS and dPED but may develop subretinal fibrosis. BCVA gains after loading wane by year 5, and eyes needing ongoing treatment for persistent OCT biomarkers decline gradually in both subtypes (significant in type 1).