This article was originally published in a sponsored newsletter.

Intravitreal injections have, without a doubt, changed the landscape of retina practice. While the complication rate associated with intravitreal injections is low, multiple reports have analyzed endophthalmitis,^1-3 which is an area of concern with these injections. Factors including the usage or forgoing of topical antibiotic drops, speculum use, antiseptic choices, and mask use have been attributed to the development of endophthalmitis.^4,5

Many physicians presumed that the probability of developing endophthalmitis increased with the number of injections, but this correlation has not been explored fully. Despite controlling for factors linked to infection, some patients may develop endophthalmitis earlier than others, even when they have had similar control exercised over the above-mentioned factors.

Interestingly, a report of 43,393 eyes — which received 652,421 injections — assessed the cumulative risk of endophthalmitis.⁶ This was a single-center, retrospective study by Israilevich et al from Wills Eye Hospital. Patients received intravitreal injections of bevacizumab (Avastin; Genentech), ranibizumab (Lucentis; Genentech), or aflibercept (Eylea; Regeneron) for the treatment of retinal issues from January 1, 2011 to June 1, 2022, and developed endophthalmitis. Patients were excluded if their endophthalmitis developed in the setting of other intravitreal injection (such as steroids), or if it was attributable to a recent surgery, a corneal ulcer, or glaucoma-related causes.

The eyes were divided into 4 quartiles based on number of injections causative of endophthalmitis. They were analyzed using a 1-way analysis of variance for continuous variables and Pearson’s chi-square test or Fisher exact test for categorical variables. A plotted curve was used to illustrate the cumulative risk of endophthalmitis per eye.

Of the 43,393 eyes (651,421 injections), 231 developed endophthalmitis. Sixteen of these eyes were not assessed because they did not have a high enough number of injections to be included in the analysis. Based on the plotted curve, 4 linear sections were created and risk of endophthalmitis was calculated within each injection range. Statistics were calculated per injection and per eye. When analyzing the risk per injection, the authors found that the risk increased as follows:

Similarly, the cumulative risk per eye was calculated as follows:

The study found an overall risk of endophthalmitis of 0.035% (1 in 2,857 injections). There was also a higher risk of endophthalmitis with earlier injections, which decreased with more treatments. The risk of endophthalmitis, while low, did not increase in a linear manner with treatment, but rather changed with number of injections. The authors speculated that there may be patient-level factors that predispose patients to developing endophthalmitis earlier in their course of treatment, such as immune status, bacterial load of the conjunctiva, or lack of understanding around postinjection expectations, care, or both. The authors also concluded that more studies are necessary to further understand these results.⁶

References

1. Reibaldi M, Pulvirenti A, Avitabile T, et al. Pooled estimates of incidence of endophthalmitis after intravitreal injection of anti-vascular endothelial growth factor agents with and without topical antibiotic prophylaxis. Retina. 2018;38(1):1-11. doi:10.1097/iae.0000000000001583
2. Morioka M, Takamura Y, Nagai K, et al. Incidence of endophthalmitis after intravitreal injection of an anti-VEGF agent with or without topical antibiotics. Sci Rep. 2020 Dec;10(1):22122. doi:10.1038/s41598-020-79377-w
3. Stem MS, Rao P, Lee IJ, et al. Predictors of endophthalmitis after intravitreal injection: a multivariable analysis based on injection protocol and povidone iodine strength. Ophthalmol Retina. 2019 Jan;3(1):3-7. doi:10.1016/j.oret.2018.09.013
4. Shah CP, Garg SJ, Vander JF, et al. Outcomes and risk factors associated with endophthalmitis after intravitreal injection of anti-vascular endothelial growth factor agents. Ophthalmology. 2011 Oct;118(10):2028-2034. doi:10.1016/j.ophtha.2011.02.034
5. Patel SN, Hsu J, Sivalingam MD, et al. The impact of physician face mask use on endophthalmitis after intravitreal anti-vascular endothelial growth factor injections. Am J Ophthalmol. 2021 Feb;222:194-201. doi:10.1016/j.ajo.2020.08.013
6. Israilevich RN, Mansour H, Patel SN, et al. Risk of endophthalmitis based on cumulative number of anti-VEGF intravitreal injections. Ophthalmology. 2024 Jan. doi:10.1016/j.ophtha.2023.12.033

Sruthi Arepalli, MD is an assistant professor of vitreoretinal surgery and uveitis at Emory University in Atlanta, Georgia.