Switching to aflibercept among patients with treatment-resistant neovascular age-related macular degeneration: a systematic review with meta-analysis

PURPOSE To systematically review anatomical and functional outcomes subsequent to switching from bevacizumab/ranibizumab to aflibercept monotherapy in patients with treatment-resistant neovascular age-related macular degeneration (nAMD). DESIGN Systematic review and meta-analysis. METHODS Medline, PubMed, Embase, and Cochrane databases were searched up to July 2016 for available scientific literature which met inclusion criteria. Eligible studies reported visual and anatomical outcomes with at least 6 months of follow-up among patients with nAMD and persistent or resistant exudative fluid despite previous anti-vascular endothelial growth factor (VEGF) therapy (bevacizumab and/or ranibizumab) and were switched to aflibercept monotherapy. Mean changes in best-corrected visual acuity (BCVA) and central retinal thickness (CRT) were pooled using random-effects models with 95% confidence intervals (CIs). RESULTS Of 82 papers reviewed, 28 studies met inclusion criteria of this review. Pooled results showed a small mean improvement in BCVA at 6 and 12 months following switching (1.11 letters, 95% CI -0.25 to 2.46, P=0.17 and 0.63 letters, 95% CI -0.26 to 1.52, P=0.17, respectively). There was a significant improvement in mean CRT following switching (-61.90 µm, 95% CI -77.10 to -46.80, P<0.001 and -50.00 µm, 95% CI -63.20 to -36.80, P<0.001 at 6 and 12 months, respectively). CONCLUSION Pooled analysis demonstrated significantly improved anatomical outcomes; however, visual function remained stable, having a comparable effect to other anti-VEGF agents in preservation of vision. These patients had poorly responsive chronic disease with limited potential for visual recovery. Switching to aflibercept with frequent monitoring may be a suitable option for patients who have developed treatment resistance.