Comparative Outcomes of Systemic Immunomodulatory Therapy Versus Local Corticosteroid Therapy in Chronic Noninfectious Uveitis

Purpose Chronic uveitis is a significant cause of visual impairment. Although initial therapy relies on corticosteroids, patients with chronic inflammation often require systemic immunomodulatory therapy (IMT) or local sustained-release steroids. However, comparative long-term outcomes of these treatment approaches remain unclear.Methods This retrospective cohort study used the TriNetX Network to identify adults (ages ≥ 18 years) with chronic uveitis treated with systemic IMT or local corticosteroid therapy. Baseline characteristics were balanced using propensity score matching (PSM). Incidence of ocular outcomes including intraocular pressure (IOP)-lowering medication use, glaucoma, incisional glaucoma surgery, cataract surgery, cystoid macular edema (CME), and epiretinal membrane (ERM) were assessed at 1, 2, and 3 years. Outcome proportions were compared between groups using risk ratios (RR), with p < 0.05 considered statistically significant.Results Of 4,683 patients meeting inclusion criteria (1,273 on local therapy; 3,410 on systemic IMT), 1,087 patients remained per group after PSM. By 3 years, patients treated with local therapy had a higher cumulative incidence of IOP-lowering medication use (12.9% vs 6.9%; RR 1.88, p < 0.001), glaucoma (8.2% vs 3.1%; RR 2.60, p < 0.001), incisional glaucoma surgery (2.3% vs 1.1%; RR 2.19, p = 0.03), and cataract surgery (7.7% vs 3.5%; RR 2.24, p < 0.001) compared with systemic IMT. Rates of newly diagnosed CME (8.3% vs 2.5%; RR 3.37, p < 0.001) and ERM (8.9% vs 4.4%; RR 2.04, p < 0.001) were likewise higher in the local therapy group.Conclusion Local corticosteroid therapy was associated with a higher cumulative incidence of complications compared to systemic IMT in patients with chronic uveitis.