Abstract
Purpose :
Increased iris pigmentation is one of the cosmetic adverse events caused by prostaglandin analogues (FP receptor agonists) used for the treatment of ocular hypertension and open-angle glaucoma. Omidenepag isopropyl (OMDI), a selective, non-prostaglandin, EP2 receptor agonist, is being developed as a new IOP-lowering topical agent for glaucoma. Here, we examined the effects of OMDI on iris pigmentation through repeated ocular administration in monkeys.
Methods :
Thirty microliters of 0.003% and 0.01% OMDI ophthalmic solution were topically administered to the left eye once daily for 39 weeks in 5 male and 5 female 3-4 year old cynomolgus monkeys (Macaca fascicularis). During the treatment period, photographs of the iris were taken by a digital fundus camera at week 13, 26 and 39 in order to macroscopically assess the prevalence of iris pigmentation. In a separate study, 30 μL of 0.005% latanoprost (FP receptor agonist) ophthalmic solution, a positive control, were topically administered to the left eye twice daily for 13 weeks in 6 male and 6 female 2-5 year old cynomolgus monkeys. Assessment of iris pigmentation in the monkeys treated with latanoprost was conducted at week 4, 8 and 13 using the same procedure described above.
Results :
Latanoprost caused iris color changes with pigmentation in 1/6 males and 4/6 females at week 13. In contrast, OMDI did not cause any color changes in the iris in all animals (0/5 males, 0/5 females) throughout week 39 of the instillation period. The prevalence rate of iris pigmentation was statistically different between the two groups by Chi-squared test.
Conclusions :
OMDI ophthalmic solution did not cause increased iris pigmentation in monkeys during long-term treatment, whereas latanoprost did. These results suggest that OMDI is an anti-glaucoma ophthalmic solution with no iris pigmentation concerns, unlike existing prostaglandin analogues.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.