Endophthalmitis risk after intravitreal anti-vascular endothelial growth factor injection using prefilled versus vial-drawn syringes: An agent-specific systematic review and meta-analysis

Why clinicians should know about it

• Picked for Ophthalmology (paper of the day, 8 November 2026): Large safety analysis of intravitreal injection delivery

Abstract

Post-injection endophthalmitis is a rare, vision-threatening complication of intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy. Prefilled syringes may reduce contamination by eliminating point-of-care drug transfer, but prior pooled comparisons may be confounded by anti-VEGF agent, drug mix, and calendar era. We systematically reviewed anti-VEGF studies comparing prefilled with vial-drawn syringes (PROSPERO CRD420251090070). Fourteen comparative studies included 6.2 million injections; nine vial-only cohorts informed the temporal anchoring analysis. Using arm-based generalized linear mixed models, prefilled syringes were associated with lower endophthalmitis odds: the agent-matched odds ratio was 0.62 (95% CI 0.49-0.77) and the all-agent estimate 0.53 (0.43-0.65). Effects were concordant for ranibizumab (0.61) and aflibercept (0.58), with no significant between-agent difference, and culture-positive endophthalmitis was likewise lower with prefilled syringes (OR 0.33). The agent-matched absolute risk difference was approximately 1 fewer case per 10,000 injections. Findings were robust to small-study adjustment and persisted after linear calendar-year adjustment (OR, 0.60; 95% CI, 0.53-0.69), with no evidence of a linear year association (P=.93). Prefilled-syringe delivery is associated with approximately one-third lower odds of endophthalmitis than vials-consistent across agents, robust to bias adjustment, and calendar-years adjustments-while acknowledging the residual-confounding limits inherent to observational data.

Abstract as published, via PubMed.