Abstract
<jats:sec> <jats:title>Purpose:</jats:title> <jats:p>Endophthalmitis is a rare but severe complication of intravitreal injections that can result in significant vision loss. This systematic review and meta-analysis aimed to evaluate the efficacy of topical antibiotic prophylaxis in reducing endophthalmitis incidence, a topic of ongoing controversy and varied clinical practice worldwide.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods:</jats:title> <jats:p>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 intravitreal injections 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 risk of bias in nonrandomized studies of interventions tool. Data were pooled using a random-effects model. The protocol was registered in PROSPERO (CRD420251102460).</jats:p> </jats:sec> <jats:sec> <jats:title>Results:</jats:title> <jats:p> Twenty-two studies encompassing 5,834,932 intravitreal injections (3,426,671 with prophylaxis and 2,408,261 without) were included. Overall, no significant difference in endophthalmitis incidence was observed between groups ( <jats:italic toggle="yes">P</jats:italic> = 0.09). However, a subgroup analysis of antivascular endothelial growth factor injections showed a significantly higher risk of endophthalmitis in the antibiotic group (odds ratio, 1.56; 95% confidence interval, 1.03–2.36; I <jats:sup>2</jats:sup> = 31%; very low-certainty evidence). </jats:p> </jats:sec> <jats:sec> <jats:title>Conclusion:</jats:title> <jats:p>Topical antibiotic prophylaxis was not associated with a reduced risk of endophthalmitis and may increase the risk in patients receiving antivascular endothelial growth factor intravitreal injections. These findings suggest that the routine use of antibiotic prophylaxis for these injections is unwarranted.</jats:p> </jats:sec>