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B Tian, PL Kaufman; Effects Of 5% Topical H-7 On Outflow Facility, Intraocular Pressure And Corneal Thickness In Monkey Eyes . Invest. Ophthalmol. Vis. Sci. 2002;43(13):4064.
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Purpose: To determine if a single or multiple treatments with 5% topical H-7 will increase outflow facility and decrease introcular pressure (IOP) without affecting corneal thickness in normal monkey eyes. Methods: 20µl of 5% H-7 or saline was administered topically to opposite eyes twice daily for 2.5-5.5 days in 2 groups of cynomolgus monkeys (G1 & G2). IOP was measured by Goldmann tonometry before and after a single and/or 5 or 7 doses of H-7/vehicle in G1 and G2. Corneal thickness was measured by ultrasonic pachymetry before and after 5 doses of H-7/vehicle in G1. Outflow facility was measured by 2-level constant pressure perfusion 2 hr and 2 months after 11 doses of H-7/vehicle in G2. Results: After a single dose of H-7 in G1, IOP decreased from 13.57±0.77 (s.e.m.) to 10.21±1.37 mmHg within 4 hr. After adjustment for baseline and contralateral control IOP, the maximal hypotension of 2.50±0.98 mmHg occurred at hr 3 (n=7; P<0.05). Monkeys (n=2) that had higher baseline IOP appeared to have a stronger response to H-7 than monkeys (n=5) with lower baseline IOP (baseline: 16 vs. 12.5 mmHg; maximal hypotension: 5.67±1.33 vs. 1.53±0.63 mmHg, P<0.02). After the 5th dose of H-7 in G1, IOP decreased by 5.67±1.07 mmHg (n=3; P<0.05) at hr 6, while IOP reduction at this time point was only 2.67±1.26 mmHg (P<0.2) following a single dose in the same monkeys. Central corneal thickness was not affected from 1-6 hr after 5 doses of H-7 in G1 (n=6). After the 7th dose of H-7 in G2, IOP decreased from 10.71±0.71 to 7.94±0.62 mmHg within 2 hr, with a maximal hypotension of 3.08±0.78 mmHg at hr 1 (n=8; P<0.01) and a minimum hypotension of 1.52±0.39 at hr 6 (P<0.01). Outflow facility was significantly increased by 31±11% 2-3 hr after the 11th dose in G2 (n=8; P<0.025). Conclusion: 5% H-7 administered topically increases outflow facility and decreases IOP, but does not affect corneal thickness in living monkeys. Multiple doses of H-7 seem to induce greater hypotension than a single dose. Monkeys with higher baseline IOP appear to have greater response to H-7 than those with lower baseline IOP. This study suggests that multiple treatments with low topical doses of H-7 or analogues may reduce outflow resistance in the glaucomatous eye with elevated IOP without meaningfully affecting the cornea.
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