Abstract
PurposeCyclosporine A (Cs) has been used as effective topical therapy for inflammatory dry eye disease since more than a decade. However, due to its lipophilic character, Cs is formulated as emulsions or oily solutions for topical application. This experimental study aimed to test if the use of semifluorinated alkanes (SFAs) as a preservative-free, well-tolerated non-stinging or burning vehicle maintains or even improves the benefits of Cs in the topical therapy of dry-eye disease.MethodsDesiccating stress was applied to C57BL/6 mice for 14 consecutive days to induce experimental dry-eye. Cs dissolved in SFA (perfluorobutylpentane = F4H5with 0.5% Ethanol), F4H5 with 0.5% ethanol only, 0.05% Cs (Restasis®), and dexamethasone (Monodex®) were applied three times daily beginning either at day 4 or day 11 of desiccating stress for up to 3 weeks after end of dry-eye induction.ResultsIn comparison to other groups, Cs/F4H5 demonstrated high efficacy and earlier reduction of corneal staining. In this study, Cs/F4H5 had the ability to maintain conjunctival goblet cell density once applied on day 4. Flow cytometry analysis from cervical lymphnodes demonstrated a significantly lower CD4+ and CD8+ T-cells in the Cs/F4H5 group following 3 weeks of therapy than at baseline, but no difference in regulatory T cells from regional lymphnodes were seen.ConclusionsOverall, compared to a commercially available Cs formulation (Restasis®) and dexamethasone, Cs/F4H5 was shown to be equally effective but with a significantly faster therapeutic response in reducing signs of dry-eye disease in an experimental mouse model.
Highlights
Dry-eye disease (DED) is one of the most common disorders of the ocular surface, associated with dysfunction of the lacrimal functional unit, changes in tear fluid, corneal and conjunctival epitheliopathy, and consecutive inflammation [1, 2]
For T-cell and regulatory T-cell (Treg) analysis, single cell suspensions were stained with FITC-conjugated anti-CD8, antigen-presenting cell (APC)-conjugated anti-CD4, PE-conjugated antiCD25 and a FITCconjugated anti-FoxP3
Comparative group analysis for TPs 3–5 demonstrated that Cs/F4H5treated mice had a significantly stronger increase of tear production after Experimental dry eye (EDE) compared to F4H5, Restasis®, dexamethasone and the untreated control
Summary
Dry-eye disease (DED) is one of the most common disorders of the ocular surface, associated with dysfunction of the lacrimal functional unit, changes in tear fluid, corneal and conjunctival epitheliopathy, and consecutive inflammation [1, 2]. Lighter cases of DED and consecutive ocular discomfort are mainly managed with artificial tears, while therapeutic treatment of more severe and chronic cases of dry eye and underlying inflammation include topical steroids or cyclosporine (Cs), topical or oral antibiotics, topical autologous serum drops, and even systemic immunosupressives. Some of these therapeutic strategies cause a wide range of side-effects, e.g., cataract, glaucoma, or infections, and a strong burning sensation during topical application [3, 4]. As an alternative to existing formulations semifluorinated alkanes (SFAs) were introduced as a new delivery platform, enabling a simple and preservative-free formulation of Cs
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