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Baohe Tian, MD; Rong-Fang Wang, MD; Steven M. Podos, MD; Paul L. Kaufman, MD

Arch Ophthalmol. 2004;122:1171-1177.

Objectives  To determine if low concentrations of H-7 (1-[5-isoquinoline sulfonyl]-2-methyl piperazine) topically applied to the eye increases outflow facility and decreases intraocular pressure (IOP) without affecting the cornea in monkeys, and to evaluate if the effect of H-7 on IOP is pressure dependent.

Methods  Single or multiple doses of 5% H-7 or vehicle (20 µL) were administered topically to opposite eyes of normal monkeys. A single dose of 2% H-7 or vehicle (50 µL) was administered to the glaucomatous eye of monkeys with laser-induced unilateral glaucoma, with vehicle on day 1 and H-7 on day 2.

Results  In normotensive eyes, 1 dose of 5% H-7 maximally decreased IOP by a mean ± SEM of 2.5 ± 1.0 mm Hg (–16.7% ± 5.5%) at 3 hours. Higher baseline IOP and repeated dosing were associated with greater IOP reduction. Outflow facility was increased, but central corneal thickness was not affected. In glaucomatous eyes, 1 dose of 2% H-7 maximally decreased IOP by a mean ± SEM of 5.8 ± 0.6 mm Hg (–16.9% ± 1.6%) at 2 hours.

Conclusions  Five percent H-7 increases outflow facility and decreases IOP, but does not affect corneal thickness. Multiple doses of H-7 induce greater reduction of IOP than a single dose. The effect of H-7 on IOP may be pressure dependent.

Clinical Relevance  Multiple topical treatments with low doses of H-7 or analogues may substantially reduce outflow resistance in the hypertensive eye without meaningfully affecting the cornea.

From the Department of Ophthalmology and Visual Sciences, University of Wisconsin–Madison Medical School (Drs Tian and Kaufman); and Department of Ophthalmology, Mount Sinai School of Medicine, New York, NY (Drs Wang and Podos). Dr Kaufman has a proprietary interest in a patent related to H-7, which is held by the University of Wisconsin–Madison Alumni Research Foundation.

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