Cyclosporine in uveitis: a game changer or a risky choice? A systematic review and meta-analysis of its efficacy and safety.

Uveitis, an inflammation of the uveal tract, can lead to severe ocular complications and vision loss if left untreated. Cyclosporine has gained recognition as an effective immunosuppressive therapy, particularly as a steroid-sparing agent. This study aims to evaluate the efficacy and safety of cyclosporine in managing various types of uveitis, assess its safety profile and associated adverse effects, and compare its therapeutic effectiveness to other treatment options. Systematic review and meta-analysis were conducted on PubMed, Science Direct, Dimensions and Google Scholar databases through 7 February 2025. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed, and the Population, Intervention, Comparison, Outcomes, Study Design framework was observed with the inclusion criteria. Eligible studies included randomised controlled trials, cohort studies and case series that assessed cyclosporine use for any form of uveitis. Outcomes included improvement in visual acuity, inflammation control, remission rates and adverse events (nephrotoxicity, hypertension, fatigue). Risk of bias was assessed using the Cochrane RoB 2 tool for Randomized Control Trials and Risk of Bias for the Non-Randomized Interventional studies for non-randomised studies. Quality was evaluated using the Joanna Briggs Institute Critical Appraisal Checklist for case-control studies for case series studies evaluation, and Newcastle-Ottawa Scale for cohort studies. A total of 57 703 studies were identified through database searching. After removal of duplicates and application of inclusion and exclusion criteria, 16 studies encompassing 943 patients were included in the final analysis. The meta-analysis demonstrated that cyclosporine therapy resulted in significant visual acuity improvement or stabilisation in approximately 79% of patients (event rate=0.879; 95% CI 0.832 to 0.914; p<0.0001; I²=0%), reflecting a robust and consistent therapeutic benefit. Control of intraocular inflammation was achieved in approximately 77% of patients (event rate=0.767; 95% CI 0.705 to 0.818; p<0.0001; I²=0%), underscoring cyclosporine's efficacy in managing inflammatory activity. However, complete disease remission was achieved in only about 43% of patients (event rate=0.43; 95% CI 0.39 to 0.48; p=0.044), indicating that while cyclosporine effectively controls disease activity, it does not consistently induce long-term remission. Adverse effects were common and clinically significant. Fatigue was the most frequently reported adverse event, affecting approximately 65% of patients. Nephrotoxicity, indicated by elevated serum creatinine, was observed in 57% of patients, highlighting the critical need for regular renal monitoring during therapy. Hypertension developed in about 21% of patients, necessitating periodic blood pressure assessment. Importantly, heterogeneity across the studies for all major outcomes was negligible (I²=0%), and publication bias was assessed as minimal, lending further credibility to the pooled estimates. Cyclosporine demonstrates significant efficacy in the management of non-infectious uveitis, improving visual acuity in approximately 79% of patients and achieving inflammation control in 77%. However, complete remission was attained in only 43% of cases. Adverse events, notably nephrotoxicity (57%) and hypertension (21%), were frequent and highlight the need for careful monitoring. These findings affirm cyclosporine's role as an effective steroid-sparing immunosuppressive agent for vision preservation, though its long-term use requires individualised risk-benefit evaluation. CRD42025644344.