Abstract
Purpose: :
Many studies have used carbachol iontophoresis (CARB-ionto) or topical pilocarpine eye drops to pharmacologically stimulate accommodation in Rhesus monkeys. These methods hinder ocular measurements at the time of drug application, provide inconsistent results, and have a slow time-course. Here, the utility, safety, time-course, stability and repeatability of intravenous pilocarpine (iv-PILO) and CARB-ionto stimulated accommodation are compared.
Methods: :
Experiments were performed under anaesthesia on 5 previously iridectomized monkeys aged 10 to 16 years. In 3 monkeys, accommodation was stimulated with CARB-ionto in 5 successive experiments and refraction measured with a Hartinger coincidence refractometer. In separate experiments, accommodation was stimulated using a 5 mg/kg bolus of iv-PILO given over 30 seconds followed by a continuous infusion of 20 mg/kg/hr for 5.5 minutes in 3 successive experiments with the same monkeys as well as in single experiments with 2 additional monkeys. Accommodation was reversed with 0.15 mg/kg i.v. glycopyrrolate. Refraction was measured continuously with photorefraction with initial and final refraction measurements also made with the Hartinger. In subsequent iv-PILO experiments with each monkey, accommodative changes in lens equatorial diameter were measured continuously with video-image analysis.
Results: :
Maximum accommodation of 3 monkeys was mean ± SD: 14.0 ± 3.4; range: 9.9 - 20.7 D with CARB-ionto (5 repeats) and 11.0 ± 1.4; 8.8 - 13.0 D with iv-PILO stimulation (3 repeats). The average of the standard deviations of maximum accommodation from each monkey was 1.8 ± 1.8 D from 5 CARB-ionto experiments and 0.6 ± 0.40 from 3 iv-PILO experiments. The average latency to the start of the response after CARB-ionto administration was 9.6 ± 6.5; 0.8 - 20.8 minutes with a time constant of 15.6 ± 13.5; 2.6 - 47.3 minutes. The average latency after iv-PILO administration was 18.8 ± 1.4; 15.2 - 20.6 seconds with a time constant of 11.6 ± 4.4; 6.8 - 18.9 seconds, followed by a stable refractive nadir. There were no adverse side-effects of any kind. During iv-PILO stimulated accommodation in 5 monkeys, lens diameters decreased by 0.54 ± 0.09; 0.42 - 0.62 mm with a rate of change of 0.05 ± 0.01; 0.04 - 0.06 mm/D.
Conclusions: :
Intravenous administration of pilocarpine produces a 90 times faster accommodative response than carbachol iontophoresis with more consistent and stable accommodative changes as indicated by smaller standard deviations from multiple experiments. Relatively rapidly occurring, safe, repeatable ocular accommodative responses can be measured continuously, unhindered, using intravenous pilocarpine stimulation in anesthetized rhesus monkeys.