Comparative efficacy and safety of Ranibizumab and Aflibercept for neovascular age-related macular degeneration: a systematic review and meta-analysis.

BACKGROUND

Ranibizumab and Aflibercept are widely used anti-VEGF agents for treating neovascular age-related macular degeneration (nAMD). This meta-analysis compares their efficacy, anatomical outcomes, treatment burden, and safety profiles.

METHODS

A systematic search of PubMed, Cochrane, and Google Scholar yielded 1,734 unique records. After screening and applying eligibility criteria, 11 studies were included. Primary outcomes were changes in best-corrected visual acuity (BCVA), central retinal thickness (CRT), proportion of dry retina, and injection frequency. Subgroup analyses and funnel plots assessed heterogeneity and publication bias.

RESULTS

Aflibercept showed a trend toward greater BCVA improvement compared with Ranibizumab, although the difference did not reach statistical significance (MD: 3.87 letters; 95% CI: -0.47 to 8.21; p = 0.07; I2 = 97%). Similarly, CRT reduction tended to favor Aflibercept (MD: -85.35 µm; 95% CI: -178.45 to 7.75; p = 0.09), but with substantial heterogeneity. The proportion of dry retina was significantly higher with Aflibercept (MD: 18.74%; 95% CI: 15.20 to 22.28; p < 0.001), with no heterogeneity (I2 = 0%). Although Aflibercept was associated with fewer injections (MD: -0.91; 95% CI: -1.67 to -0.15; p = 0.02), this finding was accompanied by substantial heterogeneity (I2 = 93%) and should be interpreted cautiously given the variability in study design, patient populations, and treatment regimens across included studies. Moreover, although the reduction in injection frequency was statistically significant, its magnitude was modest and its clinical importance remains uncertain given the high heterogeneity and very low certainty of evidence.

CONCLUSIONS

Both agents demonstrated comparable visual efficacy for nAMD. No statistically significant differences were observed for BCVA improvement or CRT reduction, and the available evidence does not establish clear superiority of either treatment. Although differences in dry retina outcomes and injection frequency were observed, these findings should be interpreted cautiously because of substantial heterogeneity, mixed study designs, and predominantly low-certainty evidence. Further standardized head-to-head studies are required to clarify the clinical relevance of these observations.

CLINICAL TRIAL NUMBER: Not applicable.