Actions of Anticholinesterases on Visual Performance in Man and Their Antagonism by Atropine

Kay, Christine Diane (1989) Actions of Anticholinesterases on Visual Performance in Man and Their Antagonism by Atropine. PhD thesis, University of Glasgow.

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This work investigates the effects of the anticholinesterases physostigmine and pyridostigmine and the cholinergic antagonists atropine and homatropine on the human visual system. The antagonism between these classes of drug is also assessed. Anticholinesterases cause pupillary constriction and an increase in accommodation. As a means of simulating their effects in a controlled situation, a systematic study was performed to determine the effects of artificial pupils and defocusing lenses on visual performance. This was assessed by measuring contrast sensitivity for the detection of sinusoidal grating patterns. Contrast sensitivity was measured in 12 subjects for a range of spatial frequencies (0.5-38 c/deg), for pupil diameters 2 - 8mm and for defocuses of +1 to +4 D, following homatropine eyedrops. Changes in pupil diameter, without any compensation for the change in retinal illumination, had no significant effect on contrast sensitivity, except at 0.5 and 1 c/deg when a significant reduction occurred with the 2mm pupil. This suggests that the expected improvement in optical quality associated with smaller pupil diameters had been annulled by the accompanying reduction in retinal illumination. On the other hand, defocus caused an appreciable reduction in contrast sensitivity at spatial frequencies higher than the peak of the contrast sensitivity function (3 c/deg) and a smaller reduction below the peak. With increasing defocus a downwards parallel shift of the contrast sensitivity function above the peak was observed. Each dioptre of defocus reduced contrast sensitivity by about 50% at spatial frequencies higher than peak and 19% at spatial frequencies lower than peak in the homatropinised eye. The decrements were slightly less in the natural eye. An oral dose of 60mg pyridostigmine bromide which causes at least a 20% inhibition of blood cholinesterase, caused a small but significant increase of 7% in contrast sensitivity to stationary oscilloscopegenerated grating patterns over 3-38 c/deg, for a group of 13 subjects. This was attributed to an increase in ocular quality due to the small reduction in pupil diameter. Contrast sensitivity to laser interference fringes observed in the Maxwellian view, were unchanged after pyridostigmine. It is concluded that pyridostigmine may be used as a pre-treatment against organophosphorus anticholinesterases without adverse effects on stationary visual function. Instillation of 0. 25% physostigmine sulphate eyedrops in 12 subjects caused a sustained miosis, a transient increase of near point accommodation and amplitude of involuntary accommodation. This last effect was maximal at 30 min and subsided by 90 min, though its amplitude varied greatly between subjects from +0.5D to +10D. Comparisons between two families of three siblings suggested involvement of a genetic trait in the amplitude of response of the ciliary body to physostigmine. Contrast sensitivity to externally-viewed oscilloscope grating patterns was transiently reduced after physostigmine and correlated with the increase in amplitude of accommodation. Physostigmine had a transient deleterious effect on contrast sensitivity to laser interference fringes, particularly at higher spatial frequencies, which was not affected by defocus of the image. Physostigmine also caused a prolonged reduction in contrast sensitivity to low spatial frequency grating patterns. Since the control eye showed no miosis, systemic absorption of physostigmine seems improbable. This suggests that there is a direct effect from trans-comeal absorption of physostigmine on the retinal neurones. The effects of a single intramuscular injection of 2mg atropine sulphate on visual performance were studied in 13 subjects. The well known actions of atropine on heart rate, secretion of saliva, dilatation of pupils and reduction in the amplitude of accommodative range, were observed. However, visual acuity, stereoacuity, red-green colour balance and reaction time to a visual stimulus were unaffected by atropine, although extra-ocular muscle balance was transiently changed. There was no significant change in contrast sensitivity to stationary sinusoidal gratings of spatial frequencies 1-30 c/deg for oscilloscope-generated patterns and laser interference fringes. However, contrast sensitivity to low spatial frequency (1-5 c/deg) grating patterns phase-reversed at 5.5 Hz showed a sustained reduction over six hours post-injection. Thus, it is concluded that atropine has an adverse effect on movement detection but not on stationary visual function. (Abstract shortened by ProQuest.).

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Keywords: Pharmacology
Date of Award: 1989
Depositing User: Enlighten Team
Unique ID: glathesis:1989-77835
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 14 Jan 2020 11:53
Last Modified: 14 Jan 2020 11:53

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