Timing and Determinants of Postinjection Endophthalmitis after First-Time Anti-VEGF Administration: A Retrospective National Study in the American Academy of Ophthalmology IRIS® Registry (Intelligent Research in Sight).

purposeTo investigate the epidemiology of postinjection endophthalmitis (PIE) after the first anti-VEGF administration and evaluate the association of sociodemographic and clinical factors with incidence, timing of onset, and presenting visual acuity (VA) using the IRIS® Registry (Intelligent Research in Sight).

designRetrospective cohort study.

participantsPatients with endophthalmitis after the first anti-VEGF injection in the IRIS Registry from 2016 to 2023.

methodsOnly the first anti-VEGF injection per eye was included. Exclusion criteria were cataract surgery during the study, intravitreal corticosteroids within 30 days before PIE, uveitis, or cystoid macular edema. Mean best VA was recorded within 100 days before anti-VEGF treatment and at the time of endophthalmitis diagnosis. Regression modeling evaluated associations between endophthalmitis and sociodemographic and clinical factors, and time to PIE. Linear regression assessed predictors of VA, and descriptive statistics were used to analyze time to onset.

main outcome measuresIncidence of PIE, time to symptom onset, and best VA at diagnosis.

resultsAmong 1 025 788 eyes treated, 600 (0.059%) developed endophthalmitis after the first anti-VEGF injection. Key risk factors included residence in US territories (odds ratio [OR] = 2.62; P = 0.038 vs. Northeast) and history of intravitreal corticosteroid injection (OR = 2.35; P = 0.004 vs. no history). The strongest protective factor was nonsmoking (OR = 0.71; P = 0.023 vs. smokers). The median time from injection to onset of PIE after the first anti-VEGF injection was 5 days (interquartile range: 3-8). The salient predictors of time to PIE included patient age (4.3 days sooner per decade older; P = 0.04), prior corticosteroid treatment (11.7 days sooner; P = 0.02), and a diagnosis of diabetic retinopathy (2.3 days sooner; P = 0.03). Baseline VA before PIE was the only significant predictor of VA at the time of PIE diagnosis (0.67, P < 0.001).

conclusionsPostinjection endophthalmitis after the first anti-VEGF injection was significantly associated with residence in US territories and prior intravitreal corticosteroid exposure, while nonsmoking status was protective. Most cases presented 3 to 8 days after anti-VEGF injection. Older age, history of prior corticosteroid treatment, and diabetic retinopathy were associated with earlier PIE. Baseline VA predicted VA at the time of PIE. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.