Tacrolimus A Potential Alternative to Cyclosporine in Severe Vernal Keratoconjunctivitis

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A study supports the use of a calcineurin inhibitor for severe ocular allergies.

Clinicians can effectively use mast cell stabilizers as a first-line therapy for vernal keratoconjunctivitis, were, a study in The Journal of Allergy and Clinical Immunology, confirmed. It also shows that  tacrolimus  and cyclosporine had similar efficacy, making tacrolimus a viable alternative to cyclosporine in severe cases of this severe type of allergic conjunctivitis. 

The study, a systematic review and meta-analysis, was conducted using PubMed, Cochrane Library, Embase, and ScienceDirect databases included 45 studies — 27 randomized controlled trials and 18 prospective cohort studies — for a total of 1749 patients (78% men, mean age 11.2 years) in 12 different treatment classes. Those studies predominantly included results of mast cell stabilizers, cyclosporine, and tacrolimus, which were the most studied drugs. Researchers hoped to find the efficacy of treatments for VKC. 

They found that, overall, all clinical scores improved total symptom and sign score decreased for mast cell stabilizers (MCS, effect size -3.19, 95% CI -4.26 to -2.13), cyclosporine (-2.06, -2.72 to -1.40), and tacrolimus (-2.39, -3.36 to -1.43). 

The investigators reported no significant differences between treatment classes, concentration, age, gender, baseline activity scores, or atopy, and the sensitivity analyses also demonstrated similar results.

Both tacrolimus and cyclosporine are calcineurin inhibitors that inhibit T-lymphocyte activation and the release of inflammatory cytokines, the research explains. While research has reviewed the use of cyclosporine for ophthalmic use since the 1990s, the researchers say interest in tacrolimus is relatively new. It’s currently used in Japan for patients with vernal conjunctivitis who exhibit inadequate responses to anti-allergic agents.

The study’s limitations include the fact that only 3 drugs were compared — but only because other drugs weren’t often reported. In addition, inclusion criteria were not identical across studies, and seasonal influence was not controlled in most studies. “Another limitation of our meta-analysis is the lack of data on characteristics of patients such as history of previous treatments or duration of VKC, precluding further analyses. Finally, studies were mostly monocentric although all continents and all ethnicities were represented, favoring generalizability of our results,” the study says. 


Roumeau I, Coutu A, Navel V, et al. Efficacy of medical treatments for vernal keratoconjunctivitis: a systematic review and meta-analysis. J Allergy Clin Immunol. Published online April 2, 2021. doi:10.1016/j.jaci.2021.03.026.