Efficacy of switching therapy to aflibercept for patients with persistent diabetic macular edema: a systematic review and meta-analysis

BACKGROUND: To evaluate functional and anatomical consequences of switching anti-vascular endothelial growth factor (anti-VEGF) therapy from bevacizumab and/or ranibizumab to aflibercept intravitreal injection for the treatment of persistent diabetic macular edema (DME). METHODS: Analysis of switching treatment in patients with persistent DME was performed using a literature search across multiple databases (PubMed, Medline, EMBASE, Cochrane Library and Web of Science) prior to May 2019. Therapeutic effect parameters, including mean change of best-corrected visual acuity (BCVA) and central macular thickness (CMT), were extracted from baseline to different follow-up times post initial injections. The quality of studies was assessed with the Downs and Black checklist. Data pertaining to ocular and systemic safety adverse events (SAEs) were collected as well as subgroup analysis stratified by pre-switch anti-VEGF reagents. All results were analyzed and pooled using random-effects models with 95% confidence intervals (CI). RESULTS: Fourteen studies involving 489 eyes met the inclusion criteria. The mean differences in BCVA were significantly improved at 1, 2 and 3 months with −0.11 logMAR (P=0.016), −0.22 logMAR (P<0.001) and −0.24 logMAR (P<0.01), respectively. Vision gain was also assessed following the aflibercept injection with a mean change of −0.10 logMAR (P<0.001) at 6 months and −0.08 logMAR (P=0.01) at 12 months. CMT reduction was significant from baseline with a mean decrease of 80.52 µm (P<0.001) at 1 month, 89.6 µm (P<0.013) at 2 months, 113.88 µm (P<0.001) at 3 months and 125.12 µm (P<0.001) at 6 months. Mean CMT continued to decline by 75.70 µm (P<0.001) at 12 months as well. CONCLUSIONS: This meta-analysis indicated the comparable efficacy and safety of a conversion treatment to aflibercept in cases of unsatisfactory responses to other anti-VEGF drugs. Switching treatment produces significant advantage for vision acuity recovery and macular edema improvement among persistent DME patients.