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The current study investigated the anti-inflammatory effect of 0.1% tacrolimus eye drops for the treatment of therapeutic penetrating keratoplasty (TPK) for severe infectious keratitis during early disease stages and reported the long-term clinical outcomes. The present retrospective study included 20 eyes from patients diagnosed with severe keratitis who underwent TPK surgery. Patients were followed-up for up to 12-18 months. Tacrolimus eye drops were administered 4 times/day starting on the first day post-surgery. Glucocorticoid eye dro