Effect of pilocarpine 4% in combination with latanoprost 0.005% or 8-iso Prostaglandin E₂ 0.1% on Intraocular pressure in laser-induced glaucomatous monkey eyes

Purpose: 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). Methods: Each of the two treatment groups was composed of the same eight monkeys with unilateral laser-induced glaucoma. Intraocular pressure (IOP) was measured hourly for 6 hours beginning at 9:00 AM on the baseline day (Thursday before treatment week) and on treatment days 1, 3, and 5 (Monday, Wednesday, and Friday). On all five treatment days, one drop of pilocarpine 4% was administered at 9:00 AM and 3:00 PM, and one drop of latanoprost 0.005% or 25 μL of 8-iso PGE₂ 0.1% was administered at 10:00 AM and 4:00 PM. Results: One hour after pilocarpine instillation on day 1, the reduction of IOP was similar (P > 0.90) in both treatment groups, 7.6 ± 1.1 mm Hg (mean ± standard error of the mean) in the latanoprost group and 7.4 ± 0.8 mm Hg in the 8-iso PGE₂ group. However, the IOP effects of the two treatment groups became significantly different (P < 0,05) beginning 2 hours after dosing with latanoprost or 8-iso PGE₂ on day 1. A difference (P < 0.05) between the two groups persisted at all subsequent measurements. The reduction of IOP lessened with repeated dosing in the latanoprost and 8-iso PGE₂ groups. Three hours after dosing with pilocarpine and two hours after dosing with the prostanoids, the IOP reduction was 8.3 ± 0.9 mm Hg in the latanoprost group and 9.9 ± 0.6 mm Hg in the 8-iso PGE₂ group on day 1, and 2.1 ± 1.0 mm Hg in the latanoprost group and 7.3 ± 0.9 mm Hg in the 8-iso PGE₂ group on day 5. Conclusions: The smaller reductions in IOP with pilocarpine and latanoprost than with pilocarpine and 8-iso PGE₂ show that pilocarpine blocks much more of the ocular hypotensive effect of latanoprost than of 8-iso PGE₂. The results also indicate that pilocarpine and latanoprost are mutually antagonistic. Enhancement of uveoscleral outflow appears to account for most of the ocular hypotensive effect of latanoprost and for much less of the ocular hypotensive effect of 8-iso prostaglandin E₂.