Preclinical Efficacy Comparison of Cyclosporine Ophthalmic Solution 0.09% vs Cyclosporine Ophthalmic Emulsion 0.05% vs Ciclosporin Ophthalmic Emulsion 0.1% in a NOD Mouse Model of Dry Eye Disease.

Introduction: Cyclosporine ophthalmic solution 0.09% (CsA 0.09% sol) is approved to increase tear production in patients with keratoconjunctivitis sicca. This study evaluated the efficacy of CsA 0.09% sol vs cyclosporine ophthalmic emulsion 0.05% (CsA 0.05% eml) vs ciclosporin ophthalmic emulsion 0.1% (CsA 0.1% eml) in a NOD mice model.
Methods: Mice were randomized and administered placebo, CsA 0.09% sol twice daily, CsA 0.05% eml twice daily, CsA 0.09% sol once daily, or CsA 0.1% eml once daily in the conjunctival sac of both eyes for 60 days. Tear volume was measured with phenol red threads at baseline and 4 hours after treatment every 15 days. On day 58, the corneal surface was observed under a slit-lamp after staining with 3% lissamine green administered into the inferior lateral conjunctival sac. On day 61, mice were euthanized, globes excised, sliced into 4 µm sections in 3 areas per section, and stained. Total number of stained goblet cell/µm was counted, and the sum per eye was averaged. Lacrimal gland tissues were removed and interleukin (IL) 1-β cytokine levels estimated.
Results: Groups comprised 11 mice each, including an untreated normal and untreated diseased control group (7 groups total). CsA 0.09% sol twice daily significantly increased tear volume on day 30, 45, and 60 vs CsA 0.05% eml ( P <0.05, <0.001, <0.001, respectively) and vs CsA 0.1% eml on day 60 ( P <0.05); CsA 0.09% sol once daily significantly increased tear volume on day 45 vs CsA 0.05% eml ( P <0.05). Goblet cell density significantly increased with CsA 0.09% sol twice daily vs placebo and NOD control ( P <0.01 both). There was no significant difference in corneal staining and IL-1β levels with CsA 0.09% sol.
Conclusion: Sixty-day treatment with CsA 0.09% sol showed comparatively improved preclinical results vs CsA 0.05% eml and CsA 0.1% eml.
Competing Interests: Vinod Burade, Rishit Zalawadia, and Alpesh Patel are employees of Sun Pharmaceutical Industries, Ltd. Abayomi Ogundele is an employee of Sun Pharmaceutical Industries, Inc. The authors report no other conflicts of interest in this work.
(© 2020 Burade et al.)