Risk of post-injection endophthalmitis peaks within the first three injections of anti-vascular endothelial growth factor therapy: A nationwide registry-based study

Purpose

To report the incidence of post-injection endophthalmitis (PIE) and the cumulative risk associated with repeated injections of intravitreal anti-vascular endothelial growth factor (anti-VEGF).

Methods

We employed nationwide registries in Denmark to include all individuals aged ≥40 years who received at least one intravitreal anti-VEGF injection in 2007–2022. Our primary endpoint PIE was identified using specific diagnostic codes for endophthalmitis and procedure codes for vitreous biopsy within 10 days prior to and 120 days post-injection. Patients were stratified according to the underlying diagnoses for which they received the treatment. The relative risk (RR) for PIE was calculated between groups based on the number of injections received by the patients.

Results

We identified 60 825 patients who received intravitreal anti-VEGF treatment during study time, with a median age of 77.2 years and females constituting 58.1%. We identified 232 cases of PIE after 1 051 549 injections during follow-up, resulting in an incidence of 0.022% [95% CI 0.019%–0.025%]. Despite a linear growth in annual anti-VEGF use, the incidence remained stable at 0.020% [95% CI 0.017%–0.023%] from 2013 to 2022. Compared to patients receiving 1–3 injections, RR for patients receiving 4–20, 21–40, and >40 injections were 0.46 [95% CI 0.34–0.63], 0.32 [95% CI 0.21–0.50], and 0.54 [95% CI 0.36–0.81], respectively. Findings were similar across the different diagnoses.

Conclusions

Based on 16 years of nationwide registry data, this study identified a low and stable incidence of PIE. Notably, the highest risk of endophthalmitis was within the first three anti-VEGF injections.