Safety and Efficacy of 0.1% Cyclosporine Solutions in Dry Eye Syndrome: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

Purpose: Cyclosporine A (CsA) is a primary treatment for dry eye disease (DED). Ophthalmic solutions containing CsA are available in concentrations of 0.05%, 0.09%, and 0.1%. While 0.1% CsA solutions have been used to treat DED, their safety and effectiveness remains somewhat uncertain. Therefore, we conducted a meta-analysis to evaluate their safety and efficacy. Methods: We searched PubMed, Cochrane Database, Embase, and Web of Science for randomized controlled trials (RCTs) that compared 0.1% CsA solutions with their vehicle. Statistical analysis was performed using Review Manager 5.4.1. Results: We included six RCTs (2,170 patients) with follow-up periods ranging from 4 weeks to 6 months. A total of 1,119 patients (51.56%) with DED were treated with 0.1% CsA. The mean age of patients was 57.9 ± 4.8 years, with 79.7% being female. The total corneal fluorescein staining (tCFS) at last follow-up [mean differences (MD) -0.49; 95% confidence interval (CI) (-0.73, -0.24); P < 0.0001], at 4 weeks [MD -0.64; 95% CI (-1.07, -0.22); P = 0.003], and central corneal fluorescein staining (cCFS) [MD -0.19; 95% CI (-0.35, -0.03); P = 0.02] scores were lower in patients treated with 0.1% CsA compared with vehicle. The Lissamine Green conjunctival staining (LGCS) [MD -0.51; 95% CI (-0.78, -0.24); P = 0.0002] and ocular surface disease index (OSDI) scores [MD -3.04; 95% CI (-5.84, -0.23); P = 0.03] were lower in the 0.1% CsA group compared with vehicle. Adverse events associated with 0.1% CsA solution in the treatment of DED varied across studies, but were generally mild to moderate. Notably, similar events were also significantly present in the vehicle group, supporting the safety profile of this treatment. Conclusion: Ophthalmic 0.1% CsA seems safe for treating DED, and significantly reduced tCFS, cCFS, LGCS, and OSDI scores compared with vehicle solutions.