Topical Immunomodulators Improve Clinical Signs of Vernal Keratoconjunctivitis and Atopic Keratoconjunctivitis: A Meta-Analysis

Nir Erdinest, Dror Ben Ephraim Noyman, Naomi London, Yair Morad, Nadav Levinger, David Landau, Itay Lavy, Abraham Solomon, Shehzad Naroo

Research output: Preprint or Working paperPreprint


Objective: Topical immunomodulators cyclosporine A (CsA) and tacrolimus have been added in recent years to the armament to control severe chronic allergic ocular diseases such as atopic keratoconjunctivitis (AKC) and vernal keratoconjunctivitis (VKC). This meta-analysis summarizes the randomized controlled trials (RCTs) that utilized topical immunomodulators, to examine their effectiveness at decreasing clinical signs as assessed by clinicians in severe allergic eye disease.

Methods: A systematic search identified thirteen studies and a total of 445 patients for inclusion, making this the largest meta-analysis published on the subject.

Results: Thirteen RCTs were included. Eleven studies used Cyclosporine A as the treatment, and two used Tacrolimus. In total, 445 participants were included, 76.6% were male. The mean age of the participants was 14 years. All studies reported clinical signs as evaluated by an examining clinician. Signs were usually assessed by anatomical region, with the most common regions being the conjunctiva and the cornea, and the most common signs assessed were hyperemia and papillae. Three studies accounted for over 50% of the meta-analysis's weight. Effect size (d) ranged from -2.37 to -0.03, negative values favoring immunomodulators. Fixed Effect Meta-Analysis returned an SMD of -0.81 (95% CI: [-0.98, -0.65]). However, there was significant heterogeneity (I2=61%, Qw=30.76) in the outcome measure (P=0.0021); therefore, a random-effect meta-analysis was also completed where the pooled SMD was -0.98 (95% CI: [-1.26, -0.69], τ2 = 0.16).

Conclusions: This study affirms that immunomodulators effectively treat clinical signs, including blepharitis, conjunctival hyperemia, edema, papillae, and corneal damage in severe ocular allergic disease.
Original languageEnglish
Publication statusPublished - 1 Jul 2022


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