Antibiotic Prophylaxis for Preventing Endophthalmitis After Intravitreal Injections: An Updated Systematic Review and Meta-Analysis

Purpose: Endophthalmitis is a rare but severe complication of intravitreal injections (IVIs) that can result in significant vision loss. This systematic review and meta-analysis aims to evaluate the efficacy of topical antibiotic prophylaxis in reducing endophthalmitis incidence, a topic of ongoing controversy and varied clinical practice worldwide. Methods: A systematic review and meta-analysis was conducted by searching PubMed, Embase, Cochrane, and Web of Science through July 2025. Studies comparing endophthalmitis incidence in IVIs with and without antibiotic prophylaxis were included; reviews, case reports, and studies lacking outcome data were excluded. Two reviewers independently screened studies, extracted data, and assessed risk of bias using the ROBINS-I tool. Data were pooled using a random-effects model. The protocol was registered in PROSPERO (CRD420251102460). Results: Twenty-two studies encompassing 5,834,932 IVIs (3,426,671 with prophylaxis and 2,408,261 without) were included. Overall, no significant difference in endophthalmitis incidence was observed between groups (p = 0.09). However, a subgroup analysis of anti-VEGF injections showed a significantly higher risk of endophthalmitis in the antibiotic group (Odds Ratio, 1.56; 95% CI, 1.03–2.36; I 2 = 31%; very low-certainty evidence). Conclusions: Topical antibiotic prophylaxis was not associated with a reduced risk of endophthalmitis and may increase the risk in patients receiving anti-VEGF IVIs. These findings suggest that the routine use of antibiotic prophylaxis for these injections is unwarranted.