EFFECT OF 8-ISO PROSTAGLANDIN E-2 ON AQUEOUS-HUMOR DYNAMICS IN MONKEYS

Objective: To evaluate the effects of 8-iso prostaglandin E-2 (8-iso P GE(2); prosta-5,13-dien-1-oic acid, 11,15-dihydroxy-9-oxo-,[5Z,8 beta- 11X,13E,15S]-) on the intraocular pressure (IOP), outflow facility, an d aqueous humor flow rates in normal monkeys and monkeys with glaucoma . Methods: The IOP was measured before and as long as 6 hours after th e topical application of 8-iso PGE2 to 1 eye of 6 normal monkeys and t o the glaucomatous eye of 8 monkeys with unilateral laser-induced glau coma. The pupil diameter was measured at the same times as the IOP mea surements in the normal monkeys. Tonographic outflow facility and fluo rophotometric flow rates of aqueous humor were measured in 6 normal mo nkeys before and after drug treatment. Results: In normal monkeys, a s ingle dose of 0.1% 8-iso PGE(2) reduced (P<.01) the IOP for 4 hours in the treated eyes with a maximum (mean +/- SEM) reduction of 3.2 +/-: 0.2 mm Hg, compared with the contralateral control eyes. The pupil siz e was smaller (P<.01) in the treated eyes by as much as 1.0 +/- 0.2 mm for 4 hours. In 8 glaucomatous monkey eyes, the application of 0.05% and 0.1% 8-iso PGE(2) reduced the IOP (P<.01) for as long as 2 and 5 h ours, respectively. The maximum reduction in the IOP was 4.6 +/- 0.8 m m Hg (0.05%) and 6.0 +/- 0.8 mm Hg (0.1%) compared with baseline measu rements. The magnitude and duration of the ocular hypotensive effect w ere enhanced with twice-a-day administration for 5 consecutive days. O utflow facility in normal monkey eyes was increased (P<.05) by 48% in the treated eyes, and aqueous humor flow was unchanged (P>.10), compar ed with vehicle-treated contralateral control eyes. Mild eyelid edema, conjunctival edema, hyperemia, and discharge appeared in some eyes tr eated with the 0.1% drug concentration. Conclusions: The use of 8-iso PGE(2) reduces the IOP in both normal and glaucomatous monkey eyes. An increase in outflow facility appears to account for most of the IOP r eduction in normal monkeys. Clinical Relevance: The application of 8-i so PGE(2) may have potential for the treatment of glaucoma as an outfl ow facility-increasing drug.