Biomed Pharmacother. 2026 Feb 5;196:118881. doi: 10.1016/j.biopha.2025.118881. Online ahead of print.
ABSTRACT
INTRODUCTION: Neovascular age-related macular degeneration (nAMD) is a leading cause of irreversible vision loss in older adults. Intravitreal anti-vascular endothelial growth factor (VEGF) agents-including Aflibercept, Ranibizumab, Bevacizumab, Brolucizumab, and Faricimab-are the mainstay of therapy. However, their comparative efficacy and safety remain uncertain. This study aimed to compare the visual and systemic outcomes of these agents to inform clinical decision-making.
METHODS: A systematic search of PubMed, Embase, Scopus, and Web of Science from inception to September 2025 identified randomized controlled trials (RCTs) and observational studies comparing at least two anti-VEGF agents in nAMD. Eligible studies reported outcomes of best-corrected visual acuity (BCVA) change, visual gain ≥ 15 letters, mortality, or arteriothrombotic events. Risk of bias was assessed using Cochrane Risk of Bias 2 (RoB 2) and Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I) tools. A frequentist network meta-analysis estimated mean differences (MD) and odds ratios (OR) with 95 % confidence interval (CI). The protocol was registered in PROSPERO (CRD42025631298).
RESULTS: Sixteen studies involving 6758 participants (follow-up 3-24 months) met the inclusion criteria. For BCVA improvement, Aflibercept had the highest surface under the cumulative ranking curve (SUCRA) ranking (0.80), although all agents showed similar mean differences that were not statistically significant: aflibercept (MD 0.80; 95 % CI -1.20-2.80), Ranibizumab (0.64; -1.87-3.15), Bevacizumab (0.60; -2.02-3.22), Faricimab (2.20; -0.69-5.09), and Brolucizumab (4.20; -5.97-14.36). The larger point estimate for Brolucizumab reflects imprecision rather than superior visual efficacy. Mortality was lowest with Aflibercept (risk ratio (RR) 0.76; 95% CI 0.41-1.55). For arteriothrombotic events, no statistically significant differences were observed between anti-VEGF agents. Comparisons between Aflibercept and Bevacizumab (RR 1.11; 95% CI 0.60-2.07), aflibercept and Ranibizumab (RR 0.77; 95% CI 0.49-1.21), and Bevacizumab and Ranibizumab (RR 0.88; 95% CI 0.60-1.30) showed wide confidence intervals, reflecting substantial imprecision. Certainty of evidence (GRADE) ranged from moderate to low.
CONCLUSION: All anti-VEGF agents stabilize or improve vision in nAMD. Aflibercept may provide the most favorable efficacy-safety balance, Faricimab offers promising durability, and Brolucizumab demonstrates large visual gains with potential safety concerns. Further head-to-head and long-term real-world studies are needed to optimize individualized treatment strategies.
PMID:41650530 | DOI:10.1016/j.biopha.2025.118881
