@article {1363239, title = {Topical interleukin 1 receptor antagonist for treatment of dry eye disease: a randomized clinical trial}, journal = {JAMA Ophthalmol}, volume = {131}, number = {6}, year = {2013}, month = {2013 Jun}, pages = {715-723}, abstract = {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.}, keywords = {Administration, Ophthalmic, Adult, Aged, Boston, Chi-Square Distribution, Diagnostic Techniques, Ophthalmological, Double-Blind Method, Dry Eye Syndromes, Female, Fluorescein, Fluorescent Dyes, Humans, Immunologic Factors, Interleukin 1 Receptor Antagonist Protein, Male, Meibomian Glands, Middle Aged, Ophthalmic Solutions, Predictive Value of Tests, Prospective Studies, Time Factors, Treatment Outcome}, issn = {2168-6173}, doi = {10.1001/jamaophthalmol.2013.195}, author = {Amparo, Francisco and Dastjerdi, Mohammad H and Okanobo, Andre and Ferrari, Giulio and Smaga, Leila and Hamrah, Pedram and Jurkunas, Ula and Schaumberg, Debra A and Dana, Reza} }