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Andy Whitlock, Laura Belen, Jennifer Brackett, Burkhard Blank; Evaluation of a Topical Cis-urocanic acid in a Murine CAE™ Model of Dry Eye Disease. Invest. Ophthalmol. Vis. Sci. 2013;54(15):902. doi: https://doi.org/.
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The goal of this study was to test the potential of Cis-urocanic acid (Cis-UCA) in a topical formulation as a treatment for dry eye.
The study employed a murine model of dry eye disease that combines of environmental and pharmacologic induction of pathologic signs of disease. Cis-UCA was provided by the sponsor as a clear solution at concentrations of 0.0, 0.5, 1.0, and 2.5%. Restasis®, dry eye treatment (scopolamine and chamber only), and naive (room air) controls were included in the study as well. Mice were dosed topically three times a day in both eyes for a total of 22 days. Animals received 3 days of prophylactic topical treatment (no scopolamine or chamber) and 14 days of dry eye treatment (with scopolamine and chamber).Fluorescein staining evaluations were performed using Ora’s novel Micron III imaging system at various time points throughout the study. Corneal images were evaluated using Ora’s proprietary clinical scale as well as a custom image analysis algorithm.
1.0%Cis-UCA was most effective in reducing corneal fluorescein staining as compared to vehicle and the dry eye treatment controls. Throughout the study duration, the average staining of all the eyes in the group was maintained at about 8 units, whereas the vehicle and dry eye treatment groups steadily increased to a maximum average staining of approximately 12 units by Day 17. The average corneal staining for mice in the 1.0%Cis-UCA treatment group was statistically lower than both the vehicle and the dry eye treatment group (p<0.05 for both). The 0.5 and 2.5% Cis-UCA groups did not show a statistically significant reduction in staining values versus either control. Restasis®, which was included in the experiment as a clinical comparator, showed no statistical separation throughout the experiment and did not provide a significant reduction in corneal staining at Day 17.
Topical treatment with 1% Cis-UCA significantly reduced corneal staining in a pre-clinical model of dry eye disease. This concentration was superior to both higher or lower concentrations, suggesting that the dosing range used in this study provided an optimal compound concentration for topical ocular therapy. The 1% Cis-UCA formulation was superior to the positive comparator at all data points, providing further support for its potential as a therapy for dry eye disease.
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