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Terry G. Coursey, Drew Wassel, Alexander Quiambao, Aaron J Dockins, David G Dillion, James R Johnson, Lynsie M Morris, Mandy L Lambros, Rafal Farjo; Once-a-day Cyclosporine-A-MiDROPS™ for treatment of dry eye disease. Invest. Ophthalmol. Vis. Sci. 2018;59(9):4951.
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© ARVO (1962-2015); The Authors (2016-present)
To determine the efficacy of a once-a-day cyclopsporine A treatment formulated with our novel patented Microemulsion Drug Ocular Penetration System (MiDROPS™) (CsA-MiDROPS™) for treatment of dry eye disease.
CsA concentrations were determined by LC-MS/MS in ocular tissues of Dutch-Belted rabbits treated with Restasis®, 0.05 % CsA-MiDROPS™, or 0.1% CsA-MiDROPS™ twice per day for nine days. In order to assess tolerability, 50 μl of CsA-MiDROPS™ (0.1%) was applied to the eyes of New Zealand White rabbits twice per day for 14 days. Baseline, day seven, and day 14 examinations were conducted by a veterinarian ophthalmologist. Hackett-McDonald scoring (0-4) was used to assess corneal clarity, fluorescein staining, vascularization, hyperemia and chemosis of the ocular surface. In order to determine the efficacy of CsA-MiDROPS™ for treatment of DED, C57BL/6 mice were exposed to desiccating stress (DS) for 10 days. OGD cornea staining was used to quantify corneal permeability.
Pharmacokinetics studies indicate significantly increased drug concentration with CsA-MiDROPS™ compared to Restasis®. CsA levels were increased 2.6 fold in the palpebral conjunctiva (p > 0.0005), 3.1 fold (p > 0.0005) bulbar conjunctiva, and 1.7 fold (p > 0.0005) in the cornea compared to Restasis®. Significantly increased CsA concentrations were also observed in the sclera, lens, and RPE/choroid. No CsA was detected in blood serum. Tolerability studies indicate that CsA-MiDROPS™ is well tolerated, as Hackett-McDonald scores were 1 or less in all clinical parameters after the 14 day treatment. Experimental dry eye studies indicated that a once per day (QD) CsA-MiDROPS™ (0.1%) was superior to twice per day (BID) Restasis® in regards to corneal permeability (OGD- gray levels 1234 ± 123 for BID Restasis® vs. QD CsA-MiDROPS™ 645 ± 43; p > 0.005). QD CsA-MiDROPS™ was significantly reduced compared to the QD MiDROPS™ vehicle (p > 0.005).
Our results indicate that CsA-MiDROPS™ delivers more CsA to ocular tissues with minimal tolerability issues. Importantly, we demonstrate that QD CsA-MiDROPS™ is more effective than BID Restasis® in treatment of dry eye in our experimental model. The development of the CsA-MiDROPS™ product has the potential to significantly increase the efficacy and tolerability of CsA in the treatment of dry eye disease and offer a better alternative to Restasis®.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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