Abstract
Purpose :
To identify the potential of three approved dry-eye disease (DED) drugs to serve as reference compounds in the standardized SiccaSystemTM mouse experimental platform for experimental dry-eye disease.
Methods :
DED was induced in 10-week old male C57Bl/6J mice through exposure to a controlled desiccating environment (<15% humidity, 15 l/min airflow; SiccaSystemTM, K&P Scientific LLC) combined with transdermal scopolamine administration (ScopoDerm®, Novartis). Drugs were applied twice daily into both eyes (10 µl each). Three approved drugs were tested: 0.05% cyclosporine ophthalmic emulsion (Restasis®; Allergan Inc.), 1 mg/ml ophthalmic eye drop emulsion (Ikervis®; Santen Pharmaceutical Co. Ltd.) and 5% ophthalmic lifitegrast solution (Xiidra®; Shire plc). Fluorescein staining was used to quantify corneal surface damage; lacrimal gland pathology and the number of conjunctival goblet cells were quantified using histological analysis.
Results :
In a preventative treatment paradigm, Restasis® significantly reduced corneal fluorescein staining (n = 12; P < 0.01) and significantly decreased lacrimal gland pathology (n = 12; P < 0.01). Goblet cell number was 19.1% higher in Restasis®-treated eyes compared with vehicle, but this difference did not reach statistical significance (n = 12; P = 0.52). In a therapeutic treatment paradigm, Restasis® was able to partially reverse disease pathology, as determined by improved corneal fluorescein staining when compared with untreated eyes (n = 9; P < 0.05) or with vehicle (n = 9; P = 0.86). Ikervis® showed similar protection of the cornea as Restasis® when administered in the preventative therapeutic paradigm (n = 8; P = 0.99). In contrast, Xiidra® did not protect against DED-associated pathology. Specifically, Xiidra® did not improve fluorescein staining when administered preventatively (n = 8; P = 0.88) or therapeutically (n = 14; P = 0.45). Similarly, we did not observe any statistically significant effects on lacrimal gland pathology (n = 8; P = 0.62) or the number of conjunctival goblet cells (n = 8; P = 0.99).
Conclusions :
Cyclosporine-based formulations can be successfully used to decrease inflammatory pathology in the SiccaSystemTM desiccating environment and scopolamine administration murine DED model. In contrast, the effects of lifitegrast on dry eye-related pathology may be strain- and/or species-dependent.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.