title: Topical interleukin 1 receptor antagonist for treatment of dry eye disease: a randomized clinical trial.
abstract: OBJECTIVE
  The immunopathogenic mechanisms of dry eye disease (DED), one of the most common ophthalmic conditions, is incompletely understood. Data from this prospective, double-masked, randomized trial demonstrate that targeting interleukin 1 (IL-1) by topical application of an IL-1 antagonist is efficacious in significantly reducing DED-related patient symptoms and corneal epitheliopathy.
  
  
  OBJECTIVE
  To evaluate the safety and efficacy of treatment with the topical IL-1 receptor antagonist anakinra (Kineret; Amgen Inc) in patients having DED associated with meibomian gland dysfunction.
  
  
  METHODS
  Prospective phase 1/2, randomized, double-masked, vehicle-controlled clinical trial.
  
  
  METHODS
  Seventy-five patients with refractory DED.
  
  
  METHODS
  Participants were randomized to receive treatment with topical anakinra, 2.5% (n = 30), anakinra, 5% (n = 15), or vehicle (1% carboxymethylcellulose) (n = 30) 3 times daily for 12 weeks.
  
  
  METHODS
  Primary outcomes were corneal fluorescein staining (CFS), complete bilateral CFS clearance, dry eye-related symptoms as measured by the Ocular Surface Disease Index, tear film breakup time, and meibomian gland secretion quality.
  
  
  RESULTS
  Topical anakinra was well tolerated compared with vehicle, with no reports of serious adverse reactions attributable to the therapy. After 12 weeks of therapy, participants treated with anakinra, 2.5%, achieved a 46% reduction in their mean CFS score (P = .12 compared with vehicle and P < .001 compared with baseline); participants treated with anakinra, 5%, achieved a 17% reduction in their mean CFS score (P = .88 compared with vehicle and P = .33 compared with baseline); and patients treated with vehicle achieved a 19% reduction in their mean CFS score (P = .11). Complete bilateral CFS clearance was noted in 8 of 28 patients (29%) treated with anakinra, 2.5%, vs in 2 of 29 patients (7%) treated with vehicle (P = .03). By week 12, treatment with anakinra, 2.5%, and treatment with anakinra, 5%, led to significant reductions in symptoms of 30% and 35%, respectively (P = .02 and P = .01, respectively, compared with vehicle); treatment with vehicle led to a 5% reduction in symptoms.
  
  
  CONCLUSIONS
  Treatment with topical anakinra, 2.5%, for 12 weeks was safe and significantly reduced symptoms and corneal epitheliopathy in patients with DED. These data suggest that the use of an IL-1 antagonist may have a role as a novel therapeutic option for patients with DED. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00681109.
authors.affiliation: Department of Ophthalmology, Massachusetts Eye and Ear Infirmary (Drs Amparo, Dastjerdi, Okanobo, Ferrari, Hamrah, Jurkunas, and Dana and Ms Smaga), and Division of Preventive Medicine, Brigham and Women's Hospital (Dr Schaumberg), Harvard Medical School, Boston.
authors.forename: Francisco
authors.initials: F
authors.lastname: Amparo
authors.affiliation: Department of Ophthalmology, Massachusetts Eye and Ear Infirmary (Drs Amparo, Dastjerdi, Okanobo, Ferrari, Hamrah, Jurkunas, and Dana and Ms Smaga), and Division of Preventive Medicine, Brigham and Women's Hospital (Dr Schaumberg), Harvard Medical School, Boston.
authors.forename: Mohammad H
authors.initials: MH
authors.lastname: Dastjerdi
authors.affiliation: Department of Ophthalmology, Massachusetts Eye and Ear Infirmary (Drs Amparo, Dastjerdi, Okanobo, Ferrari, Hamrah, Jurkunas, and Dana and Ms Smaga), and Division of Preventive Medicine, Brigham and Women's Hospital (Dr Schaumberg), Harvard Medical School, Boston.
authors.forename: Andre
authors.initials: A
authors.lastname: Okanobo
authors.affiliation: Department of Ophthalmology, Massachusetts Eye and Ear Infirmary (Drs Amparo, Dastjerdi, Okanobo, Ferrari, Hamrah, Jurkunas, and Dana and Ms Smaga), and Division of Preventive Medicine, Brigham and Women's Hospital (Dr Schaumberg), Harvard Medical School, Boston.
authors.forename: Giulio
authors.initials: G
authors.lastname: Ferrari
authors.affiliation: Department of Ophthalmology, Massachusetts Eye and Ear Infirmary (Drs Amparo, Dastjerdi, Okanobo, Ferrari, Hamrah, Jurkunas, and Dana and Ms Smaga), and Division of Preventive Medicine, Brigham and Women's Hospital (Dr Schaumberg), Harvard Medical School, Boston.
authors.forename: Leila
authors.initials: L
authors.lastname: Smaga
authors.affiliation: Department of Ophthalmology, Massachusetts Eye and Ear Infirmary (Drs Amparo, Dastjerdi, Okanobo, Ferrari, Hamrah, Jurkunas, and Dana and Ms Smaga), and Division of Preventive Medicine, Brigham and Women's Hospital (Dr Schaumberg), Harvard Medical School, Boston.
authors.forename: Pedram
authors.initials: P
authors.lastname: Hamrah
authors.affiliation: Department of Ophthalmology, Massachusetts Eye and Ear Infirmary (Drs Amparo, Dastjerdi, Okanobo, Ferrari, Hamrah, Jurkunas, and Dana and Ms Smaga), and Division of Preventive Medicine, Brigham and Women's Hospital (Dr Schaumberg), Harvard Medical School, Boston.
authors.forename: Ula
authors.initials: U
authors.lastname: Jurkunas
authors.affiliation: Department of Ophthalmology, Massachusetts Eye and Ear Infirmary (Drs Amparo, Dastjerdi, Okanobo, Ferrari, Hamrah, Jurkunas, and Dana and Ms Smaga), and Division of Preventive Medicine, Brigham and Women's Hospital (Dr Schaumberg), Harvard Medical School, Boston.
authors.forename: Debra A
authors.initials: DA
authors.lastname: Schaumberg
authors.affiliation: Department of Ophthalmology, Massachusetts Eye and Ear Infirmary (Drs Amparo, Dastjerdi, Okanobo, Ferrari, Hamrah, Jurkunas, and Dana and Ms Smaga), and Division of Preventive Medicine, Brigham and Women's Hospital (Dr Schaumberg), Harvard Medical School, Boston.
authors.forename: Reza
authors.initials: R
authors.lastname: Dana
mesh_terms: D060433:Administration, Ophthalmic; D000328:Adult; D000368:Aged; D001900:Boston; D016009:Chi-Square Distribution; D003941:Diagnostic Techniques, Ophthalmological; D004311:Double-Blind Method; D015352:Dry Eye Syndromes / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D005260:Female; D019793:Fluorescein; D005456:Fluorescent Dyes; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage* / Q000009:adverse effects; D053590:Interleukin 1 Receptor Antagonist Protein / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008537:Meibomian Glands / Q000503:physiopathology; D008875:Middle Aged; D009883:Ophthalmic Solutions; D011237:Predictive Value of Tests; D011446:Prospective Studies; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D005456:Fluorescent Dyes; D007155:Immunologic Factors; D053590:Interleukin 1 Receptor Antagonist Protein; D009883:Ophthalmic Solutions; D019793:Fluorescein