Comparative Efficacy and Safety of 37 Regimens of Anti-Vascular Endothelial Growth Factor for Neovascular Age-Related Macular Degeneration: A Network Meta-Analysis of Randomized Controlled Trials

Abstract

Background: Nowadays, there are more than forty therapeutic regimens of anti-vascular endothelial growth factor agents existing for neovascular age-related macular degeneration (nAMD), while numerous controversies exist regarding the ideal agent and optimum strategy. We aimed to give a comprehensive efficacy and safety ranking of these regimens by quantifying data from randomized controlled trials (RCT). Methods: Electronic database searches were conducted on PubMed, Embase and the Cochrane Central Register of Controlled Trials up to December 1, 2019 to identify relevant RCTs on different regimens of anti-VEGF agents for the treatment of nAMD. Two authors screened studies and extracted data independently. Primary outcomes were changes of best-corrected visual acuity (BCVA) for efficacy and the incidence of severe ocular adverse events (ADEs) for safety. The standardized mean difference (SMD), odds ratios (OR), their 95% credible intervals (CI), the surface under the cumulative ranking curves and the mean ranks of each outcome were estimated using network meta-analyses by Stata 14.0. Findings: We identified 47 RCTs, which included 17872 nAMD patients randomly assigned to 36 different therapeutic regimens of anti-VEGF agents or sham treatment. Ranibizumab 0.5mg (TE The combination of radiation, topical NSAIDs and photodynamic therapy might provide additional effect in terms of central retinal thickness (CRT) reduction; All these therapeutic regimens of different anti-VEGF agents do not significantly increase the risk of severe ocular or cardiocerebral vascular ADEs compared with sham treatment (P>0.05). Interpretation: Based on the currently available evidence base, T&E strategy showed top-level effect in terms of visual improvement and there is no significant difference in efficacy or safety between Ranibizumab, Bevacizumab and Aflibercept. The combination of topical NSAIDs provides additional effect in terms of CRT reduction and all the included regimens have acceptable risk of ADEs. Further study is worth to evaluate whether T&E strategy of anti-VEGF agents plus topical NSAIDs could achieve better efficacy than current regimens. Funding Statement: No funding was received for this research. Declaration of Interests: All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers' bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or nonfinancial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript. Ethics Approval Statement: This study was performed in accordance with the PRISMA guideline of network meta-analysis.