%0 Journal Article %J JAMA Ophthalmol %D 2013 %T Topical interleukin 1 receptor antagonist for treatment of dry eye disease: a randomized clinical trial %A Amparo, Francisco %A Dastjerdi, Mohammad H %A Okanobo, Andre %A Ferrari, Giulio %A Smaga, Leila %A Hamrah, Pedram %A Jurkunas, Ula %A Schaumberg, Debra A %A Dana, Reza %K Administration, Ophthalmic %K Adult %K Aged %K Boston %K Chi-Square Distribution %K Diagnostic Techniques, Ophthalmological %K Double-Blind Method %K Dry Eye Syndromes %K Female %K Fluorescein %K Fluorescent Dyes %K Humans %K Immunologic Factors %K Interleukin 1 Receptor Antagonist Protein %K Male %K Meibomian Glands %K Middle Aged %K Ophthalmic Solutions %K Predictive Value of Tests %K Prospective Studies %K Time Factors %K Treatment Outcome %X IMPORTANCE: 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. DESIGN AND SETTING: Prospective phase 1/2, randomized, double-masked, vehicle-controlled clinical trial. PARTICIPANTS: Seventy-five patients with refractory DED. INTERVENTIONS: 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. MAIN OUTCOMES AND MEASURES: 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 AND RELEVANCE: 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. %B JAMA Ophthalmol %V 131 %P 715-723 %8 2013 Jun %G eng %N 6 %1 http://www.ncbi.nlm.nih.gov/pubmed/23599118?dopt=Abstract %R 10.1001/jamaophthalmol.2013.195