Abstract
Purpose :
Keratoconjunctivitis sicca (KCS) is a complex disease of the ocular surface characterized by ocular surface inflammation and impaired tear production. OTX-101 0.09%, a novel nanomicellar formulation of cyclosporine A, is approved to increase tear production in patients with KCS. In a preclinical study, we evaluated the effect of OTX-101 0.09% vs cyclosporine ophthalmic emulsion 0.05% (reference) on tear volume.
Methods :
NOD.B10.H2b (NOD) mice who spontaneously develop Sjogren’s syndrome with reduced tear production were randomized and administered 10 µL OTX-101 twice daily (BID), OTX-101 once daily (QD), placebo BID, or reference BID in the conjunctival sac for 60 days. Phenol red-impregnated cotton threads measured tear volume at baseline (day −1) and 4 hours after treatment on days 15, 30, 45, and 60. Mice were lightly anesthetized with isoflurane and a phenol red-impregnated cotton thread was inserted into the lateral canthus for 60 seconds and the wetted length was measured and recorded.
Results :
Each treatment group, including an NOD disease control and a normal control group that each received no treatment, consisted of 11 mice. The baseline mean (standard deviation [SD]) wetting length (mm) for the normal control, NOD control, placebo, OTX-101 BID, reference BID, and OTX-101 QD was 4.8 (2.2), 4.9 (1.6), 4.9 (1.3), 5.0 (1.3), 4.7 (1.2), and 4.7 (1.0), respectively. OTX-101 QD significantly improved tear production mean change from baseline (SD) vs reference at day 45; 5.6 (3.7) vs 2.3 (3.7, P <0.05). OTX-101 BID significantly improved tear production mean change from baseline (SD) vs reference at days 45 and 60; 6.5 (3.6) vs 2.3 (3.7), and 7.9 (4.3) vs 4.1 (2.7), respectively (P <0.01 for both). Both OTX-101 QD and OTX-101 BID significantly improved tear production at day 60 vs placebo (P <0.01 and P <0.001, respectively).
Conclusions :
OTX-101 BID 0.09% led to superior changes from baseline in tear volume vs cyclosporine ophthalmic emulsion 0.05% and placebo through 60 days of treatment in NOD mice demonstrating tear production deficiency and dry eye phenotype.
This is a 2020 ARVO Annual Meeting abstract.