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Jonathan B Jacobs, Richard W Hertle, Jeffrey Dunmire, Louis F Dell'Osso, Lauren A Dalvin, Dongsheng Yang, Michelle Evano-Chapman; Efficacy and Safety of Topical New Sodium Pump Inhibitor (NSPI) in Reducing Intraocular Pressure in a Canine Model. Invest. Ophthalmol. Vis. Sci. 2014;55(13):2889.
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To determine the ocular and systemic safety and efficacy of a new topical medication in canines to lower intraocular pressure. This additional effect was discovered during a study of an NSPI as a treatment for infantile nystagmus syndrome.
Following in vitro safety testing and IUCAC approval, we applied increasing concentrations of topical NSPI drops (0.002% to 0.7%) in two canines with normal intraocular pressures. Drops were applied routinely in both animals. We collected ophthalmic data including: rebound tonometry (ICARER), indirect ophthalmoscopic video fundus examination, and slit lamp and external inspection for surface and intraocular toxicity. We monitored for systemic toxicity with urine analysis and venous blood sampling for hematology, serum chemistries and liver function tests.
At the 0.7% concentration dose of NSPI there was minimal, reversible, conjunctival hyperemia, with no other ocular or systemic toxicity. At the 0.6% dose there was a sustained decrease in IOP of 40-60%. Pressure returned to—or near—normal by the following day, though after prolonged administration the rebound lessened.
Canines serve as an excellent model for human glaucoma. They share similar IOP, anterior segment anatomy and aqueous production, metabolism and egress physiology. We postulate an immediate decrease in aqueous production as the likely mechanism of the NSPI. This unique class of biologically acting agents may act directly on non-pigmented ciliary epithelial metabolism. Our study suggests that a new, potent, safe class of pharmacological agents has potential for topical treatment of human glaucoma.
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