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Jean-Sebastien Garrigue, Philippe Daull, Laurence Feraille, Stefano Barabino; Comparative efficacy of cyclosporine eye drop formulations in a mouse model of dry eye. Invest. Ophthalmol. Vis. Sci. 2016;57(12):421.
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© ARVO (1962-2015); The Authors (2016-present)
Dry eye disease (DED) is a complex multifactorial disease with both inflammation and tear film instability recognized as its core mechanism. Topical steroids are effective in treating inflammation but may have important secondary effects. The aim of the present study was to compare the efficacy of various CsA 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, 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: 0.05% CsA (Restasis, Allergan, USA), 0.1% CsA (Ikervis, Santen, France), 1% CsA oil solution, and 0.5% loteprednol etabonate (Lotemax, Baush+Lomb, USA), or left untreated. Aqueous tear production and CFS score were assessed during the treatment period, while CD4+ and CD11b+ counts on flat mounted cornea were evaluated at the end of the experiment (at day 10).
The PRT lacrimation test confirmed the scopolamine-induced decrease in tear secretion, even though the tear reduction was significant only for the Ikervis group. After 7 days of treatment, the CFS score was reduced (vs. dry eye baseline) by 21, 31, and 44% with Restasis, Ikervis, and the 1% CsA oil solution, respectively. CFS scores at day 3 decreased to 7.8±1.3, 7.3±1.4, and 5.9±1.3 at day 10 for Restasis, Ikervis and the 1% CsA oil solution, respectively. By contrast 0.5% Loteprednol etabonate was not able to decrease CFS. No statistically significant dose dependent CFS reduction was observed with the three CsA formulations. CD11b+ and CD4+ cell counts were slightly decreased both in central and peripheral cornea by Restasis and Ikervis when compared to the untreated control.
This study indicates that the three CsA formulations are effective at reducing corneal epithelium lesions in a mouse model of severe DED, and represents good treatment options for the management of DED in patients. The study also suggests that no strict dose dependent relationship exists, since Ikervis (0.1% CsA) is not statistically different from the 1% CsA oil solution.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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