Efficacy of Topical Blockade of Interleukin-1 in Experimental Dry Eye Disease

PURPOSE: To evaluate the therapeutic efficacy of topical interleukin-1 receptor antagonist (IL-1Ra) in the treatment of dry eye disease. DESIGN: Laboratory investigation. METHODS: Dry eye disease was induced in C57BL/6 female mice through exposure to a desiccating environment within a controlled environment chamber. Topical formulations containing 5% IL-1Ra, 1% methylprednisolone, 0.05% cyclosporin A, and a vehicle control containing carboxymethylcellulose sodium were applied after the induction of dry eye. Corneal fluorescein staining was performed by a masked observer in the different treatment groups. Immunohistochemical studies were undertaken to enumerate corneal CD11b+ cells, as well as to evaluate corneal lymphangiogenesis. Real-time polymerase reaction was used to quantify the expression of interleukin-1 beta in the cornea. RESULTS: A significant decrease in corneal fluorescein staining was observed after topical treatment with 5% IL-1Ra (P < .01), 1% methylprednisolone (P < .01), and 0.05% cyclosporin A (P < .03). Additionally, a significant decrease in the numbers of central corneal CD11b+ cells (P < .05), corneal lymphatic growth (P < .05), and corneal interleukin-1 beta expression (P < .003), compared with vehicle treated, were demonstrated only after treatment with 5% IL-1Ra and 1% methylprednisolone, and were absent after cyclosporin A treatment. CONCLUSIONS: Topical treatment with IL-1Ra is effective in ameliorating the clinical signs of the dry eye disease, as well as in reducing underlying inflammation. These effects are comparable with those resulting from treatment with topical methylprednisolone. Topical IL-1Ra may hold promise as a novel therapeutic strategy in the treatment of dry eye. (Am J Ophthalmol 2012; 154:63-71. (C) 2012 by Elsevier Inc. All rights reserved.)