Risk of Endophthalmitis After Cataract Surgery in Immunosuppressed Patients

Background and Objectives: The aim of this study was to determine whether systemic immunosuppression increases postoperative endophthalmitis risk following cataract surgery and to characterize risk differences across immunosuppressant medication classes. Patients and Methods: Retrospective cohort study using the TriNetX federated health research network identified 422,786 immunosuppressed patients (medication exposure within 90 days pre-surgery) and 263,913 non-immunosuppressed patients undergoing cataract surgery. After 1:1 propensity score matching for age, sex, race, diabetes, ethnicity, autoimmune diagnosis, year of surgery, and prior intravitreal injections, 208,935 patients remained per cohort. Patients were identified using International Classification of Diseases, Tenth Revision (ICD-10) and Current Procedural Terminology (CPT) codes, with medications categorized as corticosteroids, classic non-biologic immunosuppressants, small molecule inhibitors, or biologic immunomodulators. Endophthalmitis outcomes were assessed at 1 to 42 days (acute), 43 to 365 days (delayed onset), and 1 to 90 days postoperatively. Results: Immunosuppressed patients showed significantly elevated 90-day endophthalmitis risk (odds ratio [OR] 1.77, 95% CI 1.42–2.21, P < .0001; risk difference 0.128%). Risk elevation persisted for acute (OR 1.86, 95% CI 1.52–2.24, P < .0001) and delayed (OR 2.07, 95% CI 1.51–2.84, P < .0001) timeframes. Classic non-biologic immunosuppressants demonstrated strongest association (OR 5.03, 95% CI 3.97–6.37, P < .0001), followed by systemic corticosteroids (OR 1.77, 95% CI 1.40–2.23, P < .0001). Small molecule inhibitors showed non-significant trends. Biologic immunomodulators demonstrated a lower observed risk for acute endophthalmitis (OR 0.58, 95% CI 0.41–0.81, P = .0015). Conclusion: Systemic immunosuppression significantly increases acute and delayed-onset postoperative endophthalmitis risk following cataract surgery, with substantial variation across medication classes. Classic immunosuppressants and corticosteroids confer the highest risk, whereas biologic immunomodulators do not appear to increase risk.