Evidence on the Use of Topical Ciclosporin for Ocular Surface Disease: A Systematic Review and Meta-Analysis

To identify evidence on the use of topical CsA for ocular surface diseases (OSD).

A literature search was conducted following the preferred reporting items for systematic reviews and meta-analyses (PRISMA) through June 2023 via Cochrane Central Registries, Clinical Trials Registry, Grey literature and citation searching. Randomised clinical trials (RCTs) in which different concentrations of topical CsA were compared with one another or other topical therapies were included. Risk of bias was assessed following the Cochrane ROB2 standard tool. Meta-analysis was considered when data were sufficient. The certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE).

Five hundred and eight-three RCT publication titles were identified, of which 48 OSD RCTs were included. Thirty trials found significantly better efficacy with CsA irrespective of dose or concentration for OSD. The effect of CsA was comparable to artificial tears (AT), vehicle, fluorometholone 0.1%, tacrolimus 0.03% or diquafosol 3% only in 13 trials. Improved outcomes with CsA for symptoms (RCTs comprising 1107-patients) and clinical signs, including in ocular surface staining (2505-patients) and the average number of goblet cells (138-patients) were found. Inconsistency of treatment effect on symptoms and signs, particularly tear film function, was evident in some trials. Ten trials were judged to be at high risk of bias. The certainty of evidence was judged to be low to moderate, downgraded mostly for imprecision and risk of bias.

Topical CsA treatment effect on ocular surface symptoms and staining suggests that CsA may be superior to the vehicle, AT or other topical treatment alternatives for OSD.