Topical Cyclosporine A in the Treatment of Dry Eye: A Systematic Review and Meta-analysis

Purpose:Cyclosporine A (CsA) is considered a potentially effective treatment for dry eye syndrome (DES), which is now one of the most common ocular problems whose exact mechanism is unknown. Because randomized controlled trials (RCTs) reported to date have shown varying results in the efficacy and safety of CsA in different types of DES, we conducted a systematic review and meta-analysis of RCTs on CsA versus placebo in treating DES to evaluate the treatment efficacy and safety of CsA.Methods:We searched for RCTs published after 1990, in MEDLINE, EMBASE, the Cochrane library, and ClinicalTrials.gov. The RCTs that were included compared topical CsA and placebo for DES treatment by evaluating scores of ocular surface disease index, tear break-up time, or Schirmer test. Cochrane risk of bias tool was used for assessing the risk of bias.Results:We included 12 RCTs involving 3034 eyes of 1660 participants. We observed statistically significant improvements on scores of break-up time (standardized mean difference [SMD], 0.80; 95% confidence interval [CI], 0.13-1.46; I-2 = 95%) and scores of Schirmer test with anesthesia (SMD, 0.78; 95% CI, 0.09-1.46; I-2 = 97%) after treatment with topical CsA. Scores of ocular surface disease index (SMD, 0.77; 95% CI, -1.05 to 2.58; I-2 = 98%) and scores of Schirmer test without anesthesia (SMD, 0.08; 95% CI, -0.11 to 0.27; I-2 = 0%) were not improved. Adverse events (odds ratio [OR], 1.61; 95% CI, 1.28-2.02; I-2 = 21%) were observed.Conclusions:Topical CsA could be an effective treatment for DES, especially for DES associated with conjunctival injury. Further RCTs with larger sample sizes for different clinical types of DES are warranted to determine the efficacy and limitation for different clinical types of DES.