Search

To compare the effect of pilocarpine, an agent that reduces uveoscleral outflow, on the ocular hypotensive efficacy of latanoprost and 8-iso prostaglandin E2(PGE2).

• OBJECTIVE. —To evaluate the ocular effects of oxymetazoline hydrochloride, an α2 agonist, in cynomolgus monkeys and albino rabbits. METHODS. —Intraocular pressure was measured before and for 6 hours after application to glaucomatous monkey eyes. Outflow facility and aqueous flow rates were measured in normal monkey eyes. Uveoscleral outflow was measured in rabbit eyes. Ocular peak pulse volume was determined with the ocular blood flow system in normal and glaucomatous monkey eyes. RESULTS. —Single applications of ozymetazoline reduced (P<.001) intraocular pressure up to 6.0±1.0 mm Hg (mean±SEM). Enhancement of the ocular hypotensive effect was observed with 5-day twicedaily administration. Outflow facility was unaltered; aqueous flow rate was decreased (P<.001) by 39% in the treated eyes compared with baseline values; and uveoscleral outflow was increased (P<.005) by 56% in the treated eye. Peak pulse volume was unchanged. CONCLUSION. —Oxymetazoline reduces intraocular pressure by decreasing aqueous humor flow rates and increasing uveoscleral outflow. Oxymetazoline may have clinical potential as an ocular hypotensive drug.

• Selective α2-adrenergic agonists UK14304-18 and B-HT 920 were evaluated in the eyes of cynomolgus monkeys. In normal monkeys, unilateral topical application of 0.3%, 0.5%, or 1% UK14304-18 or B-HT 920 reduced (P<.05) intraocular pressure bilaterally up to 9.9±1.2 mm Hg (mean±SEM) and 8.4±1.4 mm Hg in treated and contralateral eyes, respectively. Five-day twice-daily 0.5% UK14304-18 administration reduced (P<.05) intraocular pressure up to 49% in eight glaucomatous monkeys. In eight normal monkeys, 0.5% B-HT 920 and 0.5% UK14304-18 produced no alterations in outflow facility. Following unilateral application of 0.5% B-HT 920 or 0.5% UK14304-18, fluorophotometrically measured aqueous humor production was reduced (P<.05) bilaterally up to 67% compared with baseline values. Also, 0.5% UK14304-18 reduced (P<.025) systolic and diastolic blood pressure. UK14304-18 and B-HT 920 seem to reduce intraocular pressure by decreasing aqueous production. They are potential new agents for the treatment of glaucoma.

Solutions of levoepinephrine borate were prepared in concentrations of 0.06%, 0.12%, 0.25%, 0.50%, 1.00%, and 2.00%. These solutions were applied to the right eye only for four to six weeks in a series of open-angle glaucomatous patients who were receiving 4% pilocarpine to both eyes. Although a small effect was noted with lower doses, no meaningful additional hypotensive response from epinephrine was noted until the concentration reached 0.50%. The maximal additive response occurred with 2.00% levoepinephrine. Although the combined effect of pilocarpine and epinephrine was greater than the maximal effect of either drug alone, it was less than the additive effects of both drugs. Parallelism of the epinephrine and pilocarpine/epinephrine dose-response curves suggests that both drugs act by similar mechanisms.

In vivo application of echothiophate iodide to cats' eyes resulted in approximately 70% inhibition of true cholinesterases (ChE) and 15% inhibition of pseudo-ChE in treated eyes. Contralateral untreated eyes, however, showed a similar magnitude of enzymatic inhibition. In both eyes, the acetyl-β-methylcholine bromide (MeCh) dose-response curve showed a 1 log unit increase in sensitivity, whereas the carbachol dose-response curves were unaltered. The latter finding indicates that the sensitivity of cholinergic receptors in this structure is unaltered by echothiophate. Results of the current study showed excellent correlation with previous in vitro studies of cat irides treated with echothiophate. Maximum enzymatic inhibition and shift in the dose-response curves was obtained after one day of treatment with echothiophate.

Elevation of intraocular pressure after the topical application of cyloplegic, though rarely noted in the normal population, is seen in some 25% of the open angle glaucomatous population. No positive cycloplegic provocative responses were elicited from a population of 58 normals. After three weeks of treatment with topically administered dexamethasone, however, a 19% incidence of positive cycloplegic provocative tests was found in this same group. No correlation was noted between poststeroid intraocular pressure and cyloplegic-induced pressure elevation, but a statistically significant, inverse correlation between positive cycloplegic responses and outflow facility was noted after steroid treatment. The phenomenon of cycloplegic-induced pressure elevation thus appears to be related more closely to impaired outflow facility than to pretesting intraocular pressure levels.

The effects on surface cholinesterases and contractility of intact cat irides treated with echothiophate iodide in vitro have been studied. Echothiophate, in contrast to diisopropylfluoro phosphate (DFP), more selectively inhibits true cholinesterases (ChE) than pseudo-ChE. Significant enzymatic inhibition is seen even with doses of echothiophate as low as 5 × 10-8 M, whereas DFP has little effect on these enzymes below 10-6 M concentration. The effects of echothiophate iodide on the acetyl-β-methylcholine dose-response curve and surface ChEs were completely reversed by in vitro treatment with pralidoxime chloride at 10-3 M.