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

Vinod Burade,¹ Rishit Zalawadia,¹ Alpesh Patel,¹ Abayomi Ogundele<sup>2

1</sup>Sun Pharmaceutical Industries Limited, Vadodara, Gujarat, India; ²Sun Pharmaceutical Industries, Inc, Princeton, NJ, USA

Correspondence: Abayomi Ogundele
Sun Pharmaceutical Industries, Inc, Princeton, NJ, USA
Tel +1 (609) 720-5389
Email Abayomi.Ogundele@sunpharma.com

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.

Keywords: cyclosporine A, goblet cell density, keratoconjunctivitis sicca, preclinical, tear production