title: Steroid-Sparing Effect of 0.1% Tacrolimus Eye Drop for Treatment of Shield Ulcer and Corneal Epitheliopathy in Refractory Allergic Ocular Diseases.
abstract: To evaluate the effects of 0.1% topical tacrolimus alone or in combination with steroids for the treatment of shield ulcers and corneal epitheliopathy in patients with refractory allergic ocular diseases.
  
  
  
  Open cohort study.
  
  
  
  Patients with refractory allergic conjunctivitis epitheliopathy, shield ulcers, or corneal plaques (N = 791).
  
  
  
  The 791 patients were treated with topical tacrolimus alone or in combination with topical or oral steroids. The effectiveness of the treatments was determined by a corneal epitheliopathy score during the 3-month follow-up period. The clinical signs were rated on a 4-grade scale. Corneal epitheliopathy with no corneal staining was graded as 0, and shield ulcers or plaques were graded as 3, the highest grade. The effects of tacrolimus with and without topical steroids on the epitheliopathy scores were assessed after adjustments for the severity of the clinical signs and characteristics.
  
  
  
  Changes in the corneal epitheliopathy score.
  
  
  
  Adjusted mean epitheliopathy score at the baseline was 1.73 (95% confidence interval [CI], 1.65-1.81) for patients treated with tacrolimus alone, and this was significantly reduced by -0.93 at 1 month. The reduction of the score by topical and oral steroids was -0.02 for fluorometholone, 0.02 for betamethasone, and -0.02 for oral steroids, and these reductions were not significant compared with the reduction effect of topical tacrolimus alone at -0.93. The 238 patients with shield ulcer (score 3) were analyzed with adjustments, and the mean epitheliopathy score at 1 month was reduced to 1.38 with tacrolimus alone (95% CI, 1.24-1.51), 1.41 (95% CI, 1.26-1.56) with adjuvant fluorometholone, and 1.46 (95% CI, 1.32-1.61) with adjuvant betamethasone. No significant difference was observed in the adjunctive topical steroids. The presence of severe palpebral conjunctival symptoms, including giant papillae, was a significant resisting factor for topical tacrolimus.
  
  
  
  The significant effects of topical tacrolimus alone on shield ulcers and corneal epitheliopathy suggest that it may be used without the need for steroids.
authors.affiliation: Division of Ophthalmology and Visual Science, Faculty of Medicine, Tottori University, Tottori, Japan. Electronic address: dm@grape.med.tottori-u.ac.jp.
authors.forename: Dai
authors.initials: D
authors.lastname: Miyazaki
authors.affiliation: Department of Ophthalmology, Kochi Medical School, Kochi, Japan.
authors.forename: Atsuki
authors.initials: A
authors.lastname: Fukushima
authors.affiliation: Department of Ophthalmology, Ehime University School of Medicine, Ehime, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Ohashi
authors.affiliation: Department of Ophthalmology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Ebihara
authors.affiliation: Department of Ophthalmology, Fukuoka University, School of Medicine, Fukuoka, Japan.
authors.forename: Eiichi
authors.initials: E
authors.lastname: Uchio
authors.affiliation: Okamoto Eye Clinic, Ehime, Japan.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Okamoto
authors.affiliation: Division of Ophthalmology, Department of Visual Sciences, Nihon University School of Medicine, Tokyo, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Shoji
authors.affiliation: Department of Ophthalmology, Tokyo Women's Medical University School of Medicine, Tokyo, Japan.
authors.forename: Etsuko
authors.initials: E
authors.lastname: Takamura
authors.affiliation: Nakagawa Eye Clinic, Osaka, Japan.
authors.forename: Yayoi
authors.initials: Y
authors.lastname: Nakagawa
authors.affiliation: Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Hokkaido, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Namba
authors.affiliation: Department of Ophthalmology, Tsurumi University Dental Hospital, Kanagawa, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Fujishima
mesh_terms: D000284:Administration, Oral; D000287:Administration, Topical; D000293:Adolescent; D001623:Betamethasone / Q000008:administration & dosage / Q000627:therapeutic use; D065095:Calcineurin Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D002648:Child; D015331:Cohort Studies; D003233:Conjunctivitis, Allergic / Q000175:diagnosis / Q000188:drug therapy*; D003320:Corneal Ulcer / Q000175:diagnosis / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D019573:Epithelium, Corneal / Q000187:drug effects* / Q000473:pathology; D005260:Female; D005469:Fluorometholone / Q000008:administration & dosage / Q000627:therapeutic use; D005938:Glucocorticoids / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D009883:Ophthalmic Solutions; D012189:Retrospective Studies; D016559:Tacrolimus / Q000008:administration & dosage / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D065095:Calcineurin Inhibitors; D005938:Glucocorticoids; D009883:Ophthalmic Solutions; D001623:Betamethasone; D005469:Fluorometholone; D016559:Tacrolimus