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Jean-Sebastien Garrigue, Cimbolini Nicolas, Karima Kessal, Emilie Gros, Virginie Mauro, Stefano Barabino, Christophe Baudouin, Philippe Daull; Comparative efficacy of preservative-free anti-inflammatory eye drops in a mouse model of dry eye. Invest. Ophthalmol. Vis. Sci. 2017;58(8):800.
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© ARVO (1962-2015); The Authors (2016-present)
Dry eye disease (DED) is a complex multifactorial disease with tear film instability and uncontrolled inflammation leading to corneal epithelium lesions and symptoms of discomfort. Anti-inflammatory eye drops are effective options for the management of DED clinical signs and inflammation. The aim of the present study was to compare the efficacy of different formulations in a mouse model of dry eye with severe corneal epithelium lesions.
Eight to 12-week-old female C57BL6 mice with tail patches of scopolamine (replaced every other days) were housed in controlled environment room to induce dry eye. At day three (dry eye baseline), following dry eye confirmation by corneal fluorescein staining (CFS, score 0-15) and phenol red thread (PRT) lacrimation test, the mice (n=10/gp) were either treated 3 times a day in both eyes with: 0.1% CsA cationic emulsion (Ikervis, Santen, France), 5% lifitegrast solution (Xiidra, Shire, USA), a cationic emulsion vehicle (CEv, Santen, France), 0.9% NaCl or left untreated. Aqueous tear production and corneal epithelium lesions were assessed at day 3, 6 and 10, while CD4+ and CD11b+ counts and inflammatory genes expression profile (NanoString mouse inflammatory codeset) in the cornea and conjunctiva were evaluated at the end of the treatment (day 10).
The PRT lacrimation test confirmed the scopolamine-induced decrease in tear secretion. At day 6, CFS score was reduced (vs. dry eye baseline) by 9.2, 18.5 and 22.8% with Xiidra, CEv and Ikervis, respectively. Interestingly, the cationic emulsion vehicle (CEv) was more effective than Xiidra at reducing the corneal epithelium lesions at day 6. CFS scores at day 10 decreased to 6.9±1.5, 8.7±2.2, and 6.9±1.8 at day 10 for Xiidra, CEv, and Ikervis, respectively, while saline treatment failed to reduce CFS. The expression profiles of inflammatory markers were differentially modulated by the anti-inflammatory eye drops (eg. IL6, CXCL1, CXCL10, CCL19, TNF). CD11b+ and CD4+ cell counts in the cornea were only slightly decreased by the anti-inflammatory eye drops.
This study indicates that the two anti-inflammatory formulations and the CEv are effective at reducing corneal epithelium lesions in a mouse model of DED, and represents good treatment options for the management of DED in patients.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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