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

February 2024 

Matt R. Starr, MD
Vitreoretinal Surgery
Mayo Clinic
Rochester, MN


Rachel N. Israilevich, MD, Hana Mansour, MD, Samir N. Patel, MD, Sunir J. Garg, MD FACS, Michael A. Klufas, MD, Yoshihiro Yonekawa, MD, Carl D. Regillo, MD FACS, Jason Hsu, MD. Risk of Endophthalmitis Based on Cumulative Number of Anti-Vascular Endothelial Growth Factor Intravitreal Injections. Ophthalmology. Jan 3 2024;doi:10.1016/j.ophtha.2023.12.033

This article by Israilevich and colleagues evaluated the risk of developing endophthalmitis following intravitreal injections and how that risk changed with the cumulative number of intravitreal anti-vascular endothelial growth factor (VEGF) injections over time.  The authors nicely identify that there are countless articles and meta-analyses that have described the risk for endophthalmitis with each injection, but there is limited data on the cumulative risk after receiving intravitreal injections over many years.

This was a single center retrospective study of all eyes that receiving intravitreal injections (bevacizumab, ranibizumab, and aflibercept) that developed endophthalmitis during a 10 year study period. Other causes of endophthalmitis were excluded and only eyes with historical data available were included (ie, outside referrals). To identify the rate of endophthalmitis with cumulative injections, a plotted curve was made to display the cumulative risk of endophthalmitis per eye, calculated as the percentage of all eyes that developed endophthalmitis at the time of , or before, a given injection number.

During the study period, there were more than 650,000 anti-VEGF injections performed on nearly 43,000 eyes with 215 eyes developing endophthalmitis. The authors describe the eyes that developed endophthalmitis with the majority being treated for wet macular degeneration and treated with aflibercept or ranibizumab with S. epidermidis being the primary culture positive organism. The rate of endophthalmitis at this center was 1 in 2,857 per injection (0.035%). The cumulative risk of endophthalmitis per injection increased from 0.0018% – 0.013% or 1 in 55,556 – 1 in 7,692 injections for the first 1-11 injections and rose to 0.025% – 0.031% or 1 in 4000 – 1 in 3,226 injections during injection numbers 63-126 (p < 0.001). The cumulative risk of endophthalmitis per eye was 0.028% – 0.20% or 1 in 3,571 – 1 in 500 for the first 1-11 injections and increased to 0.47% – 0.50% or 1 in 217 – 1 in 200 injections for injection numbers 67 – 126 (p < 0.001).

The authors conclude that there is a higher cumulative risk of endophthalmitis with each subsequent injection earlier on in the disease treatment that lowers with injections done later on in the disease course. Suggesting a nonlinear relationship with infection risk over time which contrasts previous work of a much smaller study of 88,000 injections which described a linear pattern. The authors postulate there may be patient specific factors that were not elucidated which may explain why some patients develop infections while some do not as well as the mislabeling of noninfectious inflammation as endophthalmitis earlier in the disease course. Certainly more work to identify any specific differences and risk profiles are warranted, but this study sheds light on this interesting topic of the cumulative risk of endophthalmitis with subsequent intravitreal injections.