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 severe dry eye disease. Design: Multicenter, randomized, double-masked, parallel-group, 6-month, vehicle-controlled. Participants: A total of 877 patients with defined moderate to severe dry eye disease (292 to 293 in each treatment group). Methods: Two identical clinical trials; patients were treated twice daily with 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, Schirmer 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 to treatment, treatment success, and daily use of artificial tears. Safety: occurrence of adverse events, best-corrected visual acuity, intraocular pressure, 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 concomitant artificial tears, and the physician's evaluation of global response to treatment). There was no dose-response effect. Both CsA treatments exhibited an excellent safety profile, and there were no significant topical or 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 yielding improvements in both objective and subjective measures. Topical CsA represents a new pharmacologically based treatment for dry eye disease that may provide significant patient benefits. (C) 2000 by the American Academy of Ophthalmology.