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Kathryn S Crawford, William H Garner, William Burns; Dioptin™: A novel pharmaceutical formulation for restoration of accommodation in presbyopes. Invest. Ophthalmol. Vis. Sci. 2014;55(13):3765.
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Dioptin™ ophthalmic formulation for presbyopia is under development with plans to enter clinical trials in 2014. Dioptin™ contains the proprietary active pharmaceutical ingredient, EV06 (lipoic acid choline ester), which is a prodrug of lipoic acid (LA), enhancing LA corneal permeability. Studies were conducted to establish drug tolerability and safety when applied topically in ophthalmic formulation.
Screening studies were conducted to determine the highest tolerated concentration when applied topically to rabbit eyes, in conjunction with bioanalysis of corneal, aqueous humor, and lens concentrations of EV06 and its metabolites. In a GLP rabbit study, animals were treated with topical 0, 1, 3 or 4% Dioptin solution three times daily for 90 consecutive days. Slit-lamp exams and fundoscopy were performed at pre-dose baseline and after 1, 30, and 90 days of dosing. Daily clinical observations, food consumption, body weights, clinical pathology, and toxicokinetics were performed. Full necropsy and ocular histopathology were also conducted.
Dioptin™ ophthalmic formulations were well tolerated in rabbit eyes. No dose-related ocular signs of toxicity were observed at any timepoint in the GLP study. Ophthalmic exams were normal, with the exception of mild (1+) conjunctival congestion and (1+) discharge observed in some of animals dosed with 3% or 4% Dioptin™ on the first day of dosing, which persisted throughout the dosing period, but did not worsen. No systemic effects or adverse events were reported. Plasma levels of EV06 were at or below the limits of detection, indicating rapid metabolism.
Dioptin™ is a promising new treatment for presbyopia, with the potential to restore several diopters of accommodation. In preclinical studies, EV06 has been shown to be effective at increasing lens elasticity through reduction of lens protein disulfides. The ophthalmic formulation is non-irritating, and systemic and ocular safety have been demonstrated in a 90 day GLP ocular toxicology study at topical doses up to 4% three times daily.
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