Two multicenter, randomized studies of the efficacy and safety of cyclosporine ophthalmic emulsion in moderate to severe dry eye disease

Objective: To compare the efficacy and safety of cyclosporin A ([CsA] 0.05% and 0.1% ophthalmic emulsions) to vehicle in patients with moderate to sev ere dry eye disease. Design: Multicenter, randomized, double-masked, parallel-group, 6-month, ve hicle-controlled. Participants: A total of 877 patients with defined moderate to severe dry e ye disease (292 to 293 in each treatment group). Methods: Two identical clinical trials; patients were treated twice daily w ith either CsA, 0.05% or 0.1%, or vehicle. The results of these two trials were combined for analysis. Main Outcome Measures: Efficacy: corneal and interpalpebral dye staining, S chirmer tear test (with and without anesthesia), tear break-up time, Ocular Surface Disease Index (OSDI), facial expression, patient subjective rating scale, symptoms of dry eye, investigator's evaluation of global response t o treatment, treatment success, and daily use of artificial tears. Safety: occurrence of adverse events, best-corrected visual acuity, intraocular pre ssure, biomicroscopy, and blood trough CsA concentrations. Results: Treatment with CsA, 0.05% or 0.1%, gave significantly (P less than or equal to 0.05) greater improvements than vehicle in two objective signs of dry eye disease (corneal staining and categorized Schirmer values). CsA 0.05% treatment also gave significantly greater improvements (P < 0.05) in three subjective measures of dry eye disease (blurred vision, need for con comitant artificial tears, and the physician's evaluation of global respons e to treatment). There was no dose-response effect. Both CsA treatments exh ibited an excellent safety profile, and there were no significant topical o r systemic adverse safety findings. Conclusions: The novel ophthalmic formulations CsA 0.05% and 0.1% were safe and effective in the treatment of moderate to severe dry eye disease yield ing improvements in both objective and subjective measures. Topical CsA rep resents a new pharmacologically based treatment for dry eye disease that ma y provide significant patient benefits. (C) 2000 by the American Academy of Ophthalmology.