Role of Topical Calcineurin Inhibitors During and After Fungal Keratitis: A Narrative Review

Purpose: To describe current data of topical calcineurin inhibitors (CIs) during fungal keratitis in combination with antifungal agents and after therapeutic penetrating keratoplasty (TPKP) for fungal keratitis as steroid-sparing anti-inflammatory medications. Methods: This narrative review was performed with a literature search conducted in PubMed. Full-text articles available in English with no date restrictions were used. Results: CIs attenuate T-lymphocyte activation, which is an important mechanism underlying host immune responses in fungal keratitis. Topical CIs are used off-label in a variety of ocular conditions, including in high-risk PKP to decrease risk of corneal graft rejection. In fungal keratitis, in vitro and experimental animal studies have demonstrated both additive and synergistic effects with cyclosporine A and tacrolimus in combination with antifungals. Retrospective data and community consensus further support the perceived clinical benefit of CIs during active fungal keratitis. Topical cyclosporine use in patients who undergo TPKP for fungal keratitis has demonstrated clinical efficacy as a steroid-sparing agent in both minimizing fungal recurrences while optimizing graft clarity rates. Conclusions: Although not yet widely adopted in clinical practice, topical CIs represent a promising potential solution to the clinical dilemma of balancing inflammation control while avoiding steroids in fungal keratitis. Based on data from both during fungal keratitis and after TPKP for fungal keratitis, there may be a role in early initiation of CIs.