Efficacy and Safety of Anti-vascular Endothelial Growth Factor (VEGF) Agents in Diabetic Macular Edema

Diabetic macular edema (DME) is a leading cause of vision loss, with anti-vascular endothelial growth factor (VEGF) agents as standard therapy. However, comparative efficacy and safety remain debated. To evaluate anti-VEGF agents' efficacy/safety in DME by drug class, dosing, and baseline severity. A Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-compliant meta-analysis of 21 studies (2010-2024) was conducted. Random-effects models pooled mean differences (MD) for visual acuity (VA) and central retinal thickness. Subgroup analyses assessed anti-VEGF types, dosing regimens, and baseline severity. Aflibercept showed superior VA gains in severe DME (+8.2 letters; 95% CI: 6.1-10.3) compared with bevacizumab (+3.7 letters). Faricimab demonstrated non-inferiority to ranibizumab with extended dosing (every 16 weeks; +10.1 letters). Bevacizumab biosimilars were cost-effective but required more injections. Brolucizumab was associated with a higher risk of intraocular inflammation (RR = 2.1, 95% CI: 1.6-2.6). Monthly regimens outperformed PRN (MD: +2.5 letters, p < 0.001). Aflibercept remains optimal for severe DME, while faricimab reduces treatment burden. Safety and cost considerations favor individualized therapy. Heterogeneity was extremely high (I² = 97.19%), indicating substantial variability in treatment effects across studies, only partially explained by differences in drug class, dosing regimens, and baseline severity. This high heterogeneity underscores the need for personalized treatment approaches and cautious interpretation of pooled estimates.