Purpose
To evaluate the safety and efficacy of topical tacrolimus 0.05% vs. topical methylprednisolone 0.5% in patients with ocular graft-versus-host disease (GVHD).
Design
Phase I/II, prospective, randomized, double-masked clinical trial.
Subjects
Eighty eyes from 40 patients diagnosed with chronic ocular GVHD were enrolled.
Methods
Forty patients with ocular GVHD were randomized; 24 patients were treated with topical tacrolimus 0.05% and 16 patients with topical methylprednisolone 0.5% twice a day for 10 weeks, in addition to continuing their baseline treatment regimen.
Main Outcome Measures
Safety was evaluated based on occurrence of adverse events. Tolerability was assessed based on subjects’ reports of discomfort after drop instillation. Intraocular pressure (IOP) was monitored. The main efficacy endpoints were: corneal fluorescein staining (CFS), tear break-up time (TBUT), Schirmer test, and expression of the ocular surface inflammatory markers human leukocyte antigen-DR (HLA-DR) and intercellular adhesion molecule-1 (ICAM-1). Symptoms were evaluated using the Ocular Surface Disease Index (OSDI).
Results
After 10 weeks of treatment, no major adverse events occurred in either treatment group, and there was no significant difference in the composite tolerability scores between the two groups (P=0.06). However, burning sensation was more pronounced with tacrolimus (P=0.002). Topical tacrolimus was more effective than methylprednisolone in reducing the CFS score at week 10 (55% vs. 23% reduction, respectively; P=0.01), and achieved significant improvement in TBUT when compared to baseline (P<0.001). OSDI score reduction achieved statistical significance with tacrolimus (27% reduction; P=0.02) but was marginal with methylprednisolone (32% reduction; P=0.06). ICAM-1 expression by ocular surface epithelium decreased significantly in both groups (tacrolimus P=0.003; methylprednisolone P=0.008), while HLA-DR expression significantly decreased only in the tacrolimus group (P=0.03). Schirmer test scores did not change significantly in either group during the study; IOP increased significantly with methylprednisolone at week 10 (P=0.04).
Conclusions
Topical tacrolimus 0.05% is safe, generally well tolerated and effective for the treatment of ocular GVHD, without the hypertensive effects of topical corticosteroids.