Real-World Outcomes of Switching to Aflibercept 8 mg in Previously Treated Neovascular Age-Related Macular Degeneration: A Systematic Review and Meta-Analysis

Background: Neovascular age-related macular degeneration (nAMD) remains a leading cause of irreversible central vision loss. Although anti-vascular endothelial growth factor (anti-VEGF) therapy has transformed management, pivotal trials enrolled exclusively treatment-naïve patients, leaving clinicians without pooled evidence to guide switching decisions in previously treated eyes. This systematic review and meta-analysis assessed real-world visual, anatomical, durability, and safety outcomes following switching to aflibercept 8 mg in previously treated nAMD. Methods: Following PRISMA 2020 guidelines, we searched PubMed, Embase, Web of Science, CENTRAL, Scopus, and Google Scholar through April 2026. Studies reporting switching to aflibercept 8 mg with change in best-corrected visual acuity (BCVA), central subfield thickness (CST), or treatment interval were included. Continuous outcomes were pooled using random-effects models with Hartung–Knapp–Sidik–Jonkman adjustment; proportions were estimated using generalized linear mixed models. Methodological quality was evaluated using the JBI Critical Appraisal Checklist for Case Series. Certainty of evidence was assessed using GRADE. The protocol was registered with PROSPERO (CRD420261371334). Results: Twenty-one studies met inclusion criteria. BCVA remained stable (WMD: −0.017 logMAR; 95% CI: −0.027 to −0.007; +0.83 ETDRS letters; I2 = 0%). CST decreased significantly (WMD: −21.5 µm; 95% CI: −29.3 to −13.7; I2 = 56.0%), and treatment intervals extended by +1.79 weeks (95% CI: +1.32 to +2.27; I2 = 74.3%). Intraretinal and subretinal fluid each resolved in 37.5% of eyes. Intraocular inflammation was rare across 9959 treated eyes, though this pool was not restricted to switched eyes, with no confirmed retinal vasculitis. Sensitivity analyses confirmed robustness across all co-primary estimates. GRADE certainty was low for BCVA and very low for CST and treatment interval. Conclusions: Low-certainty evidence suggests that switching to aflibercept 8 mg preserves visual acuity, while very-low-certainty evidence suggests reductions in central subfield thickness and modest extension of treatment intervals. Intraocular inflammation was rare, though safety denominators included non-switch eyes. These findings provide preliminary pooled estimates to inform switch decisions in previously treated eyes.