Abstract: We found three RCTs with a total of 58 participants that were eligible for inclusion. There was significant variability between the trials in interventions, methodology and outcome measures and therefore we did not perform meta-analysis. One study reported on the use of 2% CsA in maize oil and two on the use of a commercial emulsion of 0.05% CsA. Of these three studies, one showed a beneficial effect of topical CsA in controlling signs and symptoms of AKC, one in controlling signs of AKC and one did not show evidence of an improvement. Only two studies analysed the effect of topical CsA in reducing topical steroid use; one showed a significant reduction in topical steroid use with CsA, but the other did not show evidence of this improvement. No serious adverse events were reported in the trials. This systematic review highlights the relative scarcity of controlled clinical trials assessing the efficacy of topical CsA therapy in AKC and suggests that evidence on the efficacy and safety of topical CsA treatment in patients with CsA remains limited. However, the data suggest that topical CsA may provide clinical and symptomatic relief in AKC and may help to reduce topical steroid use in patients with steroid-dependent or steroid-resistant AKC. No serious adverse events were reported. Reported adverse events in patients treated with topical CsA include intense stinging and eyelid skin maceration. One patient in the placebo group developed a severe allergic response to maize antigens. However, the total number of patients in the trials was too small to assess the safety of this treatment. Additional well-designed and powered RCTs of topical CsA in AKC are needed. Ideal study designs should include adequate randomisation and concealment of allocation; masking of participants, personnel and outcome assessors; adequate follow-up periods and minimisation of attrition bias; and comparison groups with similar clinical and epidemiologic characteristics. Samples should be large enough to provide sufficient statistical power to assess the safety of CsA and to detect clinically relevant treatment effect sizes of the primary outcomes. Analyses should be appropriate to the study’s design and outcome measures. Moreover, standardisation of outcome measures and follow-up periods across studies would be beneficial to maximise study comparability.

Plain-language summary: Three eligible studies with a total of 58 participants were included in this review. One study was conducted in the UK, one in Australia and one had multicentre sites in the UK and US. These studies varied significantly in interventions, methodology and reported outcomes. One study used 2% CsA in maize oil, and two used a commercial emulsion of 0.05% CsA. Of these three studies, two showed a beneficial effect of topical CsA in controlling signs of AKC, and one did not find evidence of this improvement. One study showed a beneficial effect of topical CsA in controlling symptoms of AKC, but the other two did not find evidence of this improvement. Only two studies analysed the effect of topical CsA in reducing topical steroid use; one showed a significant reduction in topical steroid use with CsA, but the other could not find evidence of this improvement. The data suggest that topical CsA may provide clinical and symptomatic relief in AKC and may help to reduce topical steroid use in patients with steroid-dependent or steroid-resistant AKC. Moreover, no serious adverse events were detected. However, this review has identified a need for more randomised controlled trials to provide further reliable evidence on the efficacy and safety of topical treatment with CsA eyedrops for patients with AKC. These trials should include larger samples of patients with AKC, and their follow-up periods should be long enough to draw conclusions on the long-term efficacy and safety of this therapy.