A semifluorinated alkane (F4H5) as novel carrier for cyclosporine A: a promising therapeutic and prophylactic option for topical treatment of dry eye

Cyclosporine 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. Desiccating 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 (RestasisA (R)), and dexamethasone (MonodexA (R)) 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. In 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. Overall, compared to a commercially available Cs formulation (RestasisA (R)) 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

Long-Term Safety and Efficacy of a Water-Free Cyclosporine 0.1% Ophthalmic Solution for Treatment of Dry Eye Disease: ESSENCE-2 OLE

The ESSENCE-2 Open-Label Extension study aimed to demonstrate long-term safety, tolerability, and efficacy of a novel water-free, nonpreserved topical cyclosporine 0.1% ophthalmic solution (US brand name VEVYE) for patients with dry eye disease (DED). This was a Phase 3, prospective, multicenter, open-label, clinical study. All patients received cyclosporine 0.1% ophthalmic solution and dosed each eye twice a day for 52 weeks. Primary safety end points were ocular and nonocular adverse events (AEs). Secondary safety end points included visual acuity, biomicroscopy, intraocular pressure, and dilated fundoscopy. Efficacy end points, such as total corneal fluorescein staining (tCFS) score (National Eye Institute [NEI] Scale), ocular symptoms (visual analog scale [VAS]), and Schirmer tear test, were also assessed. A total of 202 patients were enrolled from the ESSENCE-2 study. At week 52, 175 patients (86.6%) completed ESSENCE-2 open-label extension. A total of 55 patients (27.5%) reported 74 ocular treatment-emergent adverse events (TEAEs). The most common ocular AE was instillation site pain (6.5%), which was of mild intensity in all cases. Patients showed statistically significant improvements in all prespecified efficacy end points compared with baseline at each visit. Corneal staining improvements were early and stabilized over time while tear production improved continuously. Symptomatology improvement followed these effects with scores reaching a minimum after 1 year of treatment. The water-free cyclosporine 0.1% ophthalmic solution was safe and well tolerated during long-term use. The results demonstrated sustained 1-year efficacy, in both signs and symptoms of DED, and may help understand short and long-term healing dynamics in a predominant inflammatory DED population