title: A Clinical Trial Comparing the Safety and Efficacy of Topical Tacrolimus versus Methylprednisolone in Ocular Graft-versus-Host Disease.
abstract: To evaluate the safety and efficacy of topical tacrolimus 0.05% versus topical methylprednisolone 0.5% in patients with ocular graft-versus-host disease (GVHD).
  
  
  
  Phase 1/2 prospective, randomized, double-masked clinical trial.
  
  
  
  Eighty eyes of 40 patients diagnosed with chronic ocular GVHD were enrolled.
  
  
  
  Forty patients with ocular GVHD were randomized; 24 patients were treated with topical tacrolimus 0.05% and 16 patients were treated with topical methylprednisolone 0.5% twice daily for 10 weeks, in addition to continuing their baseline treatment regimen.
  
  
  
  Safety was evaluated based on occurrence of adverse events. Tolerability was assessed based on subject reports of discomfort after drop instillation. Intraocular pressure (IOP) was monitored. The main efficacy end points were corneal fluorescein staining (CFS), tear film break-up time (TBUT), Schirmer test results, 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).
  
  
  
  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 2 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 with baseline (P < 0.001). Reduction in OSDI score achieved statistical significance with tacrolimus (27% reduction; P = 0.02), but was marginal with methylprednisolone (32% reduction; P = 0.06). Expression of ICAM-1 by ocular surface epithelium decreased significantly in both groups (tacrolimus, P = 0.003; methylprednisolone, P = 0.008), whereas HLA-DR expression decreased significantly 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).
  
  
  
  Topical tacrolimus 0.05% is safe, generally well tolerated, and effective for the treatment of ocular GVHD without the hypertensive effects of topical corticosteroids.
authors.affiliation: Cornea Service, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts; Department of Ophthalmology and Visual Sciences, Paulista School of Medicine, Federal University of São Paulo-UNIFESP, São Paulo, Brazil; Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts.
authors.forename: Tulio B
authors.initials: TB
authors.lastname: Abud
authors.affiliation: Cornea Service, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts; Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts.
authors.forename: Francisco
authors.initials: F
authors.lastname: Amparo
authors.affiliation: Cornea Service, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts.
authors.forename: Ujwala S
authors.initials: US
authors.lastname: Saboo
authors.affiliation: Cornea Service, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts; Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts.
authors.forename: Antonio
authors.initials: A
authors.lastname: Di Zazzo
authors.affiliation: Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts.
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Dohlman
authors.affiliation: Cornea Service, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts.
authors.forename: Joseph B
authors.initials: JB
authors.lastname: Ciolino
authors.affiliation: Cornea Service, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts; Cornea Service, New England Eye Center, Department of Ophthalmology, Tufts Medical Center, Tufts University School of Medicine, Boston, Massachusetts.
authors.forename: Pedram
authors.initials: P
authors.lastname: Hamrah
authors.affiliation: Cornea Service, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts; Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts. Electronic address: reza_dana@meei.harvard.edu.
authors.forename: Reza
authors.initials: R
authors.lastname: Dana
mesh_terms: D000287:Administration, Topical; D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000009:adverse effects; D003229:Conjunctival Diseases / Q000188:drug therapy*; D003316:Corneal Diseases / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D011446:Prospective Studies; D016559:Tacrolimus / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D000893:Anti-Inflammatory Agents; D007166:Immunosuppressive Agents; D016559:Tacrolimus; D008775:Methylprednisolone