Topical treatment with cyclosporine A eyedrops for inflammation of the surface of the eye

Atopic keratoconjunctivitis (AKC) is an inflammatory disorder of the ocular surface that can be suffered by 67.5% of atopic dermatitis patients. It is a chronic condition that often requires long-term treatment in order to avoid ocular complications that may lead to visual loss. This condition is frequently treated with steroid eyedrops, but long-term treatment with such drugs can produce severe side effects, such as the development of cataracts, glaucoma or severe infections of the eye. Topical treatment with cyclosporine A (CsA) eyedrops may be useful to control signs and symptoms of atopic keratoconjunctivitis, and to reduce the need for steroid eyedrops.

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.

Authors' conclusions: 

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.

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Background: 

Atopic keratoconjunctivitis (AKC) is a chronic ocular surface non-infectious inflammatory condition that atopic dermatitis patients may suffer at any time point in the course of their dermatologic disease and is independent of its degree of severity. AKC is usually not self resolving and it poses a higher risk of corneal injuries and severe sequelae. Management of AKC should prevent or treat corneal damage. Although topical corticosteroids remain the standard treatment for patients with AKC, prolonged use may lead to complications. Topical cyclosporine A (CsA) may improve AKC signs and symptoms, and be used as a corticosteroid sparing agent.

Objectives: 

To determine the efficacy and gather evidence on safety from randomised controlled trials (RCTs) of topical CsA in patients with AKC.

Search strategy: 

We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2012, Issue 6), MEDLINE (January 1946 to July 2012), EMBASE (January 1980 to July 2012), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to July 2012), Cumulative Index to Nursing and Allied Health Literature (CINAHL) (January 1937 to July 2012), OpenGrey (System for Information on Grey Literature in Europe) (www.opengrey.eu/), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov), the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en), the IFPMA Clinical Trials Portal (http://clinicaltrials.ifpma.org/no_cache/en/myportal/index.htm) and Web of Science Conference Proceedings Citation Index- Science (CPCI-S). We did not use any date or language restrictions in the electronic searches for trials. The electronic databases were last searched on 9 July 2012. We also handsearched the following conference proceedings: American Academy of Ophthalmology, Association for Research in Vision and Ophthalmology, International Council of Opthalmology and Societas Ophthalmologica Europaea from 2005 to July 2011.

Selection criteria: 

We included randomised controlled trials only.

Data collection and analysis: 

Two review authors independently extracted data. Due to the small number of studies and the diversity of outcome measures, interventions and participants, we presented results narratively.

Main results: 

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.

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