Ocular or Visual Effects in Healthy Volunteers

Graham and Cook (1984) studied the effects of PB on multiple psychomotor parameters (see earlier discussions of neuromuscular effects and behavioral and cognitive function) as well as visual performance in 24 healthy male volunteers. In a double-blind, placebo-controlled, crossover study comparing 5 days of treatment with 30 mg of oral PB or placebo three times daily, investigators tested a number of visual function parameters, including spatial resolution by contrast sensitivity; neural transit time by steady-state visual evoked response; visual acuity by Snellen eye chart; and depth perception by biopter test. Testing was performed on days 4 and 5 of treatment and again 3 days after cessation of treatment. Interestingly, on days 4 and 5, subjects receiving PB had significant improvement in tests of depth perception compared to subjects on placebo. No significant drug-related effect on stationary visual acuity, contrast sensitivity, or stereopsis was noted. The drug regimen produced the expected level of inhibition of plasma ChE. However large differences between individuals in inhibition (range = −21.7 to +8.3 percent) were observed. Regression analyses were performed to determine the relationship between individual differences in ChE inhibition and study variables. These analyses indicated that as the level of enzyme inhibition increased, performance on tests of visual acuity decreased while depth perception improved.

Borland and colleagues (1985) investigated the effect of 3 days of oral PB at 30 mg every 8 hours on visual function and visual–motor coordination. Four healthy men between the ages of 19 and 27 participated in this double-blind, placebo-controlled, crossover study. After PB treatment, the mean critical flicker fusion threshold was significantly raised, an improvement in performance compared to that of subjects on placebo. PB-treated subjects performed dynamic visual acuity tasks with fewer missed responses than those on placebo. Visual– motor coordination was impaired with PB. No effect of PB was seen on pupillary diameter, static visual acuity, macular threshold, or kinetic perimetry. The authors suggest that the mild but statistically significant improvement in some visual performance tests was due to an increase in the level of arousal caused by increased stimulation of CNS cholinoceptive sites. The mild decrease in visual–motor coordination was attributed to either the peripheral anticholinesterase activity of the drug or a direct nicotinic action on the neuromuscular junction.

Also using a placebo-controlled, double-blind, crossover design, Kay and Morrison (1988) studied the effects on vision of a single 60-mg oral dose of PB in 14 male volunteers 18–40 years of age. In the first of a two-part experiment, contrast sensitivity to stationary oscilloscope-generated gratings showed a small but significant increase of 7 percent, which was attributed to a small reduction in pupillary diameter. Secondly, contrast sensitivity to laser interference fringes was tested, and with this method, which bypasses the optic media, no effect of PB was found. The authors concluded that PB could be used as a pretreatment for chemical warfare agents without a deleterious effect on stationary visual function.

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