Applications of topical immunomodulators enhance clinical signs of vernal keratoconjunctivitis (VKC) and atopic keratoconjunctivitis (AKC): a meta-analysis

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

Research output: Contribution to journalReview articlepeer-review


This meta-analysis aimed to review the safety and efficacy of topical cyclosporine A (CsA) and topical tacrolimus in allergic eye disease. A systematic search identified thirteen studies and a total of 445 patients for inclusion, making this the largest meta-analysis published on the subject. The current review was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Thirteen randomized control trials were included in the meta-analysis. Eleven studies used CsA as the treatment, and two used Tacrolimus. In total, 445 participants were included, of whom 76.6% were male. The mean age of participants across the included studies 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 more than 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 (I  = 61%, Q  = 30.76) in the outcome measure (P = 0.0021); therefore, a random-effect meta-analysis was also completed in which the pooled SMD was - 0.98 (95% CI [- 1.26, - 0.69], τ  = 0.16). This study affirms the current scientific community's stance that immunomodulators effectively treat clinical signs, including blepharitis, conjunctival hyperemia, edema, papillae, and corneal damage in severe ocular allergic disease.
Original languageEnglish
Article number157
Pages (from-to)157-177
Number of pages19
JournalInternational Ophthalmology
Issue number1
Early online date24 Mar 2024
Publication statusPublished - 24 Mar 2024

Bibliographical note

Copyright © The Author(s), under exclusive licence to Springer Nature B.V. 2024. This version of the article has been accepted for publication, after peer review and is subject to Springer Nature’s AM terms of use [], but is not the Version of Record and does not reflect post-acceptance improvements, or any corrections. The Version of Record is available online at:].


  • Keratoconjunctivitis - diagnosis - drug therapy
  • Conjunctiva
  • Cyclosporine
  • Allergic eye disease
  • Immunologic Factors
  • Female
  • Atopy
  • Keratoconjunctivitis
  • Vernal
  • Humans
  • Immunomodulators
  • Hyperemia
  • Adolescent
  • Male
  • Conjunctivitis, Allergic - diagnosis - drug therapy
  • Tacrolimus


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