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Philippe Daull, Takashi Nagano, Shinji Okada, Emilie Gros, Laurence Feraille, Jean-Sebastien Garrigue; Efficacy of preservative-free cyclosporine emulsion eye drops in a mouse model of dry eye. Invest. Ophthalmol. Vis. Sci. 2019;60(9):292. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Dry eye disease (DED) is a multifactorial disease in which uncontrolled inflammation can lead to severe corneal epithelium lesions and symptoms of discomfort. Anti-inflammatory eye drops are effective in the management of DED clinical signs and inflammation. The aim of the present study was to compare the efficacy of two cyclosporine-based anti-inflammatory emulsions in a mouse model of dry eye with severe corneal epithelium lesions.
Six to 9-week-old female C57BL/6N mice with tail patches of scopolamine were housed in a controlled environment room to induce dry eye. At day three, 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 instilled in both eyes with: QD 0.1% CsA cationic emulsion (Ikervis, Santen, France), BID 0.05% CsA anionic emulsion (Restasis, Allergan, USA), or left untreated. A group of healthy mice with no experimental DED was used as control. Aqueous tear production and corneal epithelium lesions were assessed at baseline and day 3, 6, 10 and 14. At the end of the experimental period left eyes were sampled, fixed and stained with hematoxylin/Eosin/Safran for histology analysis of the ocular surface.
The PRT lacrimation test confirmed the scopolamine-induced decrease in tear secretion, which was maintained throughout the experiment. CFS scores were reduced (vs. dry eye baseline) by 10.4, 18.4, and 10.9% at day 6, 10, and 14, respectively with 0.1% CsA cationic Em (QD), while they were reduced by 2.6, 3.0, and 5.5% at day 6, 10, and 14, respectively with 0.05% CsA anionic Em (BID). Histology of the ocular surface confirmed that CsA treatments reduced the severity of DED-induced ocular lesions. In the DED untreated group, 7 out of 10 mice presented moderate to severe ocular lesions, while only 2 and 5 mice presented slight to moderate ocular lesions in the 0.1% CsA cationic Em (QD) and 0.05% CsA anionic Em (BID) groups, respectively.
This study demonstrates that both cyclosporine emulsions were effective at reducing CFS scores, with the 0.1% CsA (QD) cationic emulsion being significantly better than BID instillations of 0.05% CsA anionic emulsion. DED animals treated with the 0.1% CsA cationic emulsions also presented fewer DED-induced ocular surface lesions. These data confirmed the improved potency of CsA when formulated in a cationic emulsion.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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