Combined effects of H7 and pilocarpine on anterior segment physiology in monkey eyes

To determine, in monkey eyes in vivo if low doses of the cholinergic agonist pilocarpine (PILO) can enhance the outflow facility responses to a maximal dose of the serine-threonine kinase inhibitor H7 without producing apparent miosis and/or excessive accommodation.

Outflow facility was determined by two-level constant pressure perfusion in living monkeys after 24.5 microM phenylephrine (PE) bilaterally (stimulates the iris dilator without influencing the iris sphincter, ciliary muscle, or outflow facility, and facilitates the measurement of miosis and accommodation), 24.5 microM PE + 300 microM H7 (maximal outflow facility-effective dose) bilaterally, or 24.5 microM PE + 300 microM H7 +/- 2 or 10 microM PILO (2 microM PILO alone does not significantly increase outflow facility or accommodation but moderately constricts the pupil; 10 microM PILO is a threshold outflow facility-effective dose) in opposite eyes. Pupil diameter (Vernier calipers) and accommodation (coincidence refractometer) were measured essentially concurrently.

Outflow facility in the PE + H7 + 10 microM PILO eyes was 73% higher than that in the PE + H7 eyes (n = 6; p < 0.05). Accommodation was greater (n = 4; 2.6 vs. 0.6 D; p < 0.05) and pupil diameter was smaller (n = 6; 3.4 vs. 7.6 mm; p < 0.02) in the former than in the latter. No significant difference in outflow facility, accommodation or pupil diameter was observed between the PE + H7 + 2 microM PILO eyes and the PE + H7 eyes.

In living monkeys, 10 microM PILO, but not 2 microM PILO, enhances the 300 microM H7-induced increase in outflow facility with only approximately 3 diopters of accommodation, whereas 300 microM H7 partially inhibits the 2 microM PILO-induced, but not the 10 microM PILO-induced miosis. This suggests that, although the miosis following the threshold facility-effective dose of PILO cannot be reduced by combination with the maximal facility-effective dose of H7, the combination may at least benefit young glaucoma or ocular hypertension patients who are bothered by PILO-induced myopia more than by miosis.