Topical Cyclosporine A benefits and harms for Dry Eye Disease assessed in 58 RCTs, clarifying clinical uncertainty

Dry Eye Disease (DED) is a prevalent, multifactorial ocular condition characterized by a vicious cycle of inflammation, oxidative stress, and mitochondrial dysfunction on the ocular surface. This leads to tear film instability, ocular surface damage, and debilitating symptoms like dryness, itching, and foreign body sensation, significantly impairing quality of life. Topical cyclosporine A (CsA), an immunosuppressant, is a common treatment, targeting ocular surface inflammation. However, despite its widespread use and extensive clinical evaluation, persistent uncertainty surrounds its precise benefits and potential harms, necessitating a comprehensive, updated review.

This updated Cochrane review systematically assessed the benefits and harms of topical cyclosporine A for DED. Researchers conducted extensive searches across CENTRAL, MEDLINE, Embase, and other databases, last updated on March 17, 2026. They included 58 randomized controlled trials (RCTs) with 10,225 participants, comparing topical CsA against its vehicle, artificial tears, or alternative CsA formulations/concentrations. Primary outcomes included DED symptoms, ocular surface staining, tear production, tear film stability, artificial tear use, conjunctival goblet cell density, and discontinuation due to adverse events at 3 months. Risk of bias was assessed using RoB 1, and results were synthesized via meta-analysis where possible, calculating mean differences (MDs), standardized mean differences (SMDs), or risk ratios (RRs) with 95% confidence intervals (CIs), with evidence certainty assessed by GRADE.

The meta-analysis included 58 RCTs, encompassing 10,225 participants with Dry Eye Disease, with a median age of 53 years. The majority of studies (60%, or 35 of 58) originated from South Korea, the USA, and China. Follow-up periods typically spanned three months, ranging from three days to 12 months. The review aimed to quantify effects on key DED indicators, including DED symptoms, ocular surface staining, tear production, tear film stability, artificial tear use, conjunctival goblet cell density, and discontinuation rates due to adverse events. While the abstract details the comprehensive methodology and scope of the assessment, it does not present the specific quantitative results (MDs, SMDs, RRs, or CIs) regarding the benefits or harms of topical cyclosporine A across these outcomes. The review's objective was to provide clarity where "uncertainty remains regarding its benefits and harms." This extensive body of evidence was systematically evaluated to address this clinical gap.

The review systematically assessed 58 RCTs involving 10,225 DED patients, focusing on outcomes like DED symptoms, ocular surface staining, tear production, and adverse event discontinuation to clarify cyclosporine A's efficacy and safety profile.