Objectives: The aim of this study was to evaluate the comparative effectiveness of anti-vascular endothelial growth factor therapy in the treatment of diabetic macular edema (DME).

Methods: Searches focused on reports concerning treatment of DME with aflibercept, bevacizumab, pegaptanib, or ranibizumab published between January 2000 and June 30, 2012, with comparisons to laser photocoagulation, sham injection, or other control (e.g., triamcinolone). Effectiveness was based on best-corrected visual acuity (BCVA), in terms of letters gained. Direct meta-analyses were conducted on BCVA for each anti-vascular endothelial growth factor (VEGF) agent; indirect comparisons also were performed for each anti-VEGF pair.

Results: A total of fifteen randomized controlled trials (eleven fair- or good-quality) and eight observational studies were included. No direct comparative studies were identified. Improvement in visual acuity versus control was seen with all agents (range: 4–9 letters); outcomes were consistent across multiple timepoints. Meta-analyses showed no statistically significant and/or consistent differences between agents in BCVA changes or the percentage of patients gaining more than ten letters. No discernible differences in the potential harms of anti-VEGFs, including ocular events, MI, stroke, and other cardiovascular events, as well as death, were noted between aflibercept, pegaptanib, and ranibizumab. Data on harms for bevacizumab were underreported.

Conclusions: All anti-VEGF agents are effective in improving visual acuity in comparison to laser photocoagulation. Evidence is insufficient to distinguish the performance of any single anti-VEGF agent over others. The safety of bevacizumab remains the greatest element of uncertainty.