Risk of Endophthalmitis Based on Cumulative Number of Anti-Vascular Endothelial Growth Factor Intravitreal Injections

To determine the risk of endophthalmitis in eyes undergoing intravitreal injections (IVIs) of anti-VEGF based on cumulative number of injections per eye.Retrospective cohort study.Patients from a single center undergoing IVIs of ranibizumab, aflibercept, or bevacizumab.Eyes were divided into quartiles based on injection number causative of endophthalmitis between January 1, 2011, and June 1, 2022.Interquartile clinical outcomes and cumulative risk of endophthalmitis per injection and per eye.A total of 43 393 eyes received 652 421 anti-VEGF injections resulting in 231 endophthalmitis cases (0.035% per injection, 1 in 2857), of which 215 were included. The cumulative endophthalmitis risk increased from 0.0018% (1 in 55 556) after 1 injection to 0.013% (1 in 7692) after 11 injections (0.0012 percentage point change), versus 0.014% (1 in 7143) after 12 injections to 0.025% (1 in 4000) after 35 injections (0.00049 percentage point change), versus 0.025% (1 in 4000) after 36 injections to 0.031% (1 in 3226) after 66 injections (0.00017 percentage point change), versus 0.031% (1 in 3226) after 63 injections to 0.033% (1 in 3030) after 126 injections (0.000042 percentage point change) (P < 0.001). Likewise, the cumulative endophthalmitis risk per eye increased from 0.028% (1 in 3571) to 0.20% (1 in 500) between injections 1 and 11 (0.018 percentage point change), versus 0.21% (1 in 476) to 0.38% (1 in 263) between injections 12 and 35 (0.0075 percentage point change), versus 0.38% (1 in 263) to 0.46% (1 in 217) between injections 36 and 66 (0.0026 percentage point change), versus 0.46% (1 in 217) to 0.50% (1 in 200) between injections 67 and 126 (0.00063 percentage point change) (P < 0.001).The cumulative endophthalmitis risk per injection and per eye increased with greater number of injections received but appeared to do so at a higher rate during earlier injections and at a lower rate further into the treatment course.Proprietary or commercial disclosure may be found after the references.