Efficacy of Conversion to Aflibercept for Diabetic Macular Edema Previously Refractory to Bevacizumab or Ranibizumab: A Meta-analysis of High-Quality Nonrandomized Studies.

Background: Aflibercept has been widely used in treating diabetic macular edema (DME). However, the effect of aflibercept in treating DME refractory to bevacizumab or ranibizumab has not been well established. Objective: To assess the therapeutic effect of switching from bevacizumab or ranibizumab to aflibercept in the treatment of refractory DME. Methods: Relevant studies were searched from 3 databases: the Cochrane Library, PubMed, and Web of Science. Data on changes in best-corrected visual acuity (BCVA), central macular thickness (CMT), and adverse events within the follow-up period were collected and pooled using weighted mean differences (WMDs) with corresponding 95% CIs in a random effects model. The between-study heterogeneity was tested using the χ² test and the I2 statistic, and funnel plots were used to evaluate the publication bias. Results: A total of 11 nonrandomized trials met the inclusion criteria and were included in the meta-analysis. Our studies showed significant improvements in the BCVA (WMD = 100.55; 95% CI = 68.46 to 132.63; P < 0.01) and reduction in CMT (WMD = 0.09; 95% CI = 0.03 to 0.14; P < 0.01) after switching to aflibercept. Although a large amount of heterogeneity was detected in the CMT results among these studies, the sensitivity analyses showed the reliability and stability of our results. Conclusion and Relevance: There were significant improvements in both visual and anatomical outcomes after switching from bevacizumab or ranibizumab to aflibercept, without risk of adverse events. Thus, switching therapy may be a safe and effective treatment for patients with refractory DME.