Topical Tacrolimus as Adjuvant Therapy to Corticosteroids in Acute Endothelial Graft Rejection After Penetrating Keratoplasty: A Randomized Controlled Trial

PURPOSE: To evaluate the efficacy of topical tacrolimus 0.05% as adjuvant therapy to corticosteroids in the treatment of acute endothelial rejection of a penetrating keratoplasty (PKP) graft. METHODS: Patients with the clinical diagnosis of acute endothelial rejection of a PKP graft were randomized into 2 groups-group 1: receiving topical tacrolimus 0.05% as adjuvant therapy to corticosteroid treatment and group 2: receiving only corticosteroid treatment. Main outcome measures were rejection reversal, time to rejection reversal, and recurrence of rejection. RESULTS: Thirty-one eyes of 31 patients (17 and 14 eyes in group 1 and 2, respectively) were included in the study. The rejection episode completely resolved in 88.2% of patients in group 1 and 85.7% of patients in group 2 [hazard ratio = 0.60, 95% confidence interval (CI) = 0.28-1.29, P = 0.191]. After adjusting for preoperative factors using the inverse-probability weighting method, the time to resolution of rejection was significantly shorter in group 1 than group 2 (average treatment effect = 16, 95% CI, 3.7-28.7, P = 0.013). The recurrence rate of rejection was significantly higher in group 2 (39.7, 95% CI, 12.8-92.6 per 1000 months of follow-up) than in group 1 (3.6, 95% CI, 0.05-19.9 likewise); risk ratio: 11.1, 95% CI, 1.3-95.0, P = 0.028. CONCLUSIONS: Topical tacrolimus 0.05% as an adjunct to steroids can hasten the resolution of endothelial rejection of a PKP graft and potentially decreases the recurrence of rejection. However, it may not improve rejection reversal success.