Radiotherapy for Neovascular Age-Related Macular Degeneration: A Systematic Review and Meta-Analysis

Anti-vascular endothelial growth factor (anti-VEGF) drugs have limitations in the treatment of neovascular age-related macular degeneration (nAMD). This study aims to evaluate the efficacy and safety of radiotherapy combined with anti-VEGF therapy versus anti-VEGF monotherapy in the treatment of nAMD.Methods: This systematic review and meta-analysis (PROSPERO registration number: CRD420251010811) searched PubMed, Embase, Cochrane, Web of Science, LILACS, ISRCTN registry, and ClinicalTrials.gov up to February 25, 2025. Two radiotherapy modalities were analyzed: epimacular brachytherapy (EBM) and stereotactic radiotherapy (SRT). The primary outcome was the proportion of participants who lost more than 15 Early Treatment Diabetic Retinopathy Study (ETDRS) letters at 12 and 24 months. A total of four studies were included, yielding 7 articles for meta-analysis.

For EBM combined with anti-VEGF therapy, compared with anti-VEGF monotherapy, there was a higher risk of losing more than 15 ETDRS letters at 12 months (relative risk [RR] 2.36, 95% confidence interval [CI] 1.49-3.74) and 24 months (RR 2.39, 95% CI 1.68-3.39). The difference in best-corrected visual acuity (BCVA) was 0.10 logarithm of the minimum angle of resolution (logMAR) (95% CI 0.05-0.15) at 12 months and 0.17 logMAR (95% CI 0.13-0.21) at 24 months. For SRT combined with anti-VEGF therapy, there was a greater risk of losing more than 15 ETDRS letters at 24 months (RR 1.75, 95% CI 1.12-2.74) compared with anti-VEGF monotherapy; however, the SRT group required 2.10 fewer ranibizumab injections than the sham-irradiation group (mean difference [MD] -2.10, 95% CI -2.97 to -1.22).

Epimacular brachytherapy (EBM) combined with anti-VEGF therapy may worsen patient outcomes and increase the risk of adverse events. In contrast, stereotactic radiotherapy (SRT) combined with anti-VEGF therapy does not improve visual acuity but can reduce the frequency of anti-VEGF injections, potentially alleviating the treatment burden for patients with nAMD.