Efficacy and Safety of Topical Cyclosporine A in Moderate-To-Severe Dry Eye Disease: An Updated Systematic Review with Meta-Analysis

Background: The increasing prevalence of dry eye disease (DED) and its inflammatory nature have attracted interest for treatment. Cyclosporine A (CsA) has been used to treat DED. This study aimed to provide a comprehensive and updated synthesis of evidence on the efficacy and safety of Cyclosporine A in treating moderate-to-severe DED. Methods: A systematic review and meta-analysis were conducted following the PRISMA guidelines. Randomised controlled trials (RCTs) comparing CsA with artificial tears were identified through systematic searches of PubMed, Embase, and Cochrane Library, up to 2024. Primary outcomes included tear breakup time, Schirmer’s test, fluorescein staining. Secondary outcomes include adverse events, ocular surface disease index, meibum expressibility, and goblet cell density. Meta-analyses were performed using a random effects model, and heterogenicity was evaluated using the I² statistic. Results: Fifteen RCTs involving 1683 participants were analysed. Pooled analysis revealed better outcomes of CsA in tear breakup time (SMD0.85, 95%CI 0.35 to 1.34), Schirmer’s test (SMD0.50, 95%CI 0.05 to 0.95), and fluorescein-staining (SMD0.74, 95%CI -1.14-0.34). CsA was associated with more adverse events than ATs (Risk Ratio (RR) 3.13, 95%CI 0.94 to 10.45), but the difference was not statistically significant. Secondary outcomes, including the OSDI score (SMD − 0.88; 95% CI -1.26 to -0.50) and goblet cell density (SMD 1.06; 95% CI 0.04 to 2.08), also favoured CsA, although confidence intervals indicated potential variability. Conclusion: Current evidence suggests that CsA is more effective than artificial tears in improving key clinical outcomes for moderate-to-severe DED treatment, although variability in effect sizes and a higher incidence of adverse events warrant careful interpretation. Future research should focus on longer-term studies to evaluate the role of CsA in delaying disease progression, optimising treatment duration, and addressing safety concerns.