Tacrolimus Eye Drops as Adjunct Therapy in Severe Corneal Endothelial Rejection Refractory to Corticosteroids

Purpose: To evaluate the safety and efficacy of tacrolimus eye drops as adjunctive therapy in the treatment of severe corneal endothelial rejection after penetrating keratoplasty refractory to corticosteroids. Methods: In this prospective interventional case series, 11 eyes of 11 patients assessed for severe corneal endothelial rejection, with an inadequate response to topical, local, and systemic corticosteroids, were treated with either 0.01% or 0.05% tacrolimus eye drops 4 times daily. Improvement in signs of rejection, visual function, and development of complications were monitored. Results: The duration of steroid treatment before intervention was 8.1 ± 1.4 days (range = 7-11). Patients were subsequently administered topical tacrolimus 0.01% or 0.05% qid. The time to clinical improvement was 10.3 ± 3.4 days (range = 3-17). The time to rejection reversal was 27.8 ± 16.3 days (range = 7-52). After 3 months, 10 patients (90.8%) demonstrated clinical improvement, and complete restoration of graft clarity was achieved in 5 patients (45.4%). In responsive cases, steroid therapy was successfully tapered off after 60.2 ± 19.7 days (range = 36-93). The best spectacle-corrected visual acuity improved from 1.7 ± 0.9 to 0.8 ± 0.5 logMAR (P = 0.0016). Reported side effects included stinging on drop instillation and punctate epithelial keratopathy. Conclusions: Tacrolimus eye drops may be able to play an adjunctive therapeutic role in patients with severe corneal endothelial rejection refractory to conventional steroid treatment. Controlled studies are needed to further investigate the role of tacrolimus in this setting.