Study Describes Factors Associated with Endophthalmitis Following Anti-VEGF

Study shows many risks and determinants of post-injection endophthalmitis after first anti-VEGF injection. It was significantly associated with residing in the southern part of the US and prior intravitreal corticosteroid exposure, while non-smoking status was protective. Older age, history of prior corticosteroid treatment and diabetic retinopathy were associated with earlier presentation. Photo: Christine Sindt, OD. Click image to enlarge. While anti-VEGF treatments are very effective, each injection carries a rare but potentially vision-devastating risk of post-injection endophthalmitis if not treated promptly. In a recent study, researchers investigated the epidemiology of this complication after the first anti-VEGF administration using IRIS Registry (Intelligent Research in Sight) data. They found that most cases presented three to eight days following injection and were associated with residing in the southern US, prior intravitreal corticosteroid exposure, older age, history of prior corticosteroid treatment and diabetic retinopathy. The findings were reported in Ophthalmology Retina.Included were patients with endophthalmitis after the first anti-VEGF injection in the IRIS Registry from 2016-2023. Only the first injection per eye was included. Exclusion criteria were cataract surgery during the study, intravitreal steroids within 30 days prior to development of endophthalmitis, uveitis or cystoid macular edema. Mean best VA was recorded within 100 days prior to anti-VEGF treatment and at the time of endophthalmitis diagnosis. Regression modeling evaluated associations between endophthalmitis and sociodemographic and clinical factors and time to endophthalmitis.Among 1,025,788 eyes treated, 600 (0.059%) developed endophthalmitis after the first anti-VEGF injection. The median time from injection to the onset was five days, with most cases occurring between three and eight days. This is similar to previous studies that reported rates of 0.049% to 0.056%.Patients living in the southern United States are at an increased risk, possibly because of limited access to specialized care in some of these regions. “This could reflect immediate access to healthcare services or regional differences in healthcare-seeking behavior,” the authors explained in their paper. “Another possible explanation could be seasonal variation; prior studies had reported increased rates of post-cataract surgery endophthalmitis during hot and humid months, which may similarly influence the incidence and timing of post-injection endophthalmitis.” This finding suggests the need for targeted quality initiatives in underserved regions and further research into system-level factors influencing safety, the authors added.Another key risk factor is a history of intravitreal corticosteroid injection. This aligns with prior evidence that chronic corticosteroid use may confer local immunosuppression, increasing susceptibility to infection. “Our study suggests an additive effect, while some previous studies examined corticosteroids alone,” the authors noted in their paper.The strongest protective factor was non-smoking, with non-smokers demonstrating a significantly lower risk of post-injection endophthalmitis after first anti-VEGF injection compared to smokers. “This finding was supported by reports that smoking impaired ocular surface immunity and promoted inflammation, thereby increasing susceptibility to intraocular infections,” the authors explained in their paper. “Our data shows that smoking may be a modifiable patient risk factor, and counseling smokers about eye infection risks is warranted.”Additionally, bevacizumab use was associated with lower odds of endophthalmitis compared to aflibercept.Older patients tended to present with endophthalmitis sooner, which may reflect age-related alterations in immune function, though the possibility of residual confounding cannot be excluded, the authors noted in their paper.Similarly, patients with prior intravitreal corticosteroid use were more likely to experience earlier post-injection endophthalmitis possibly due to chronic corticosteroids’ known immunosuppressive effects increasing infection risk. “While direct evidence for intravitreal corticosteroids is limited, long-term use of oral corticosteroids, which have similar immunosuppressive effects, has been associated with an increased risk of infections,” the authors wrote in their paper.Patients with diabetic retinopathy were more likely to exhibit an earlier presentation of endophthalmitis after first anti-VEGF injection, which could be attributed to the impaired immune responses characteristic of the condition, which facilitated pathogen entry into the vitreous cavity and accelerated infection onset.No demographic or clinical characteristics were associated with presenting vision, indicating no differential impact of post-injection endophthalmitis across patient subgroups. This may reflect the rapid and severe clinical course of the condition, which overwhelms more modest effects related to patient characteristics or presentation timing.The authors noted that there were some limitations to this study. The retrospective, registry-based design relies on billing codes, which limits the ability to distinguish infectious endophthalmitis from sterile inflammation. Additionally, the study lacked data on microbiological cultures, specific injection techniques and other practice-level factors, such as environmental conditions or antiseptic preparation.Click here for the journal source. Ghauri SY, Ross C, Gilbert JB, et al. Timing and determinants of post-injection endophthalmitis after first-time anti-VEGF administration: a retrospective national study in the American Academy of Ophthalmology IRIS Registry (Intelligent Research in Sight). Ophthalmol Retina. March 18, 2026. [Epub ahead of print.]  This article was developed by the editorial staff in conjunction with experts in the field. In the process, AI may have been among the editorial tools used to meet the goals of human editors, who approved all content.