https://theses.gla.ac.uk/ Theses Digitisation: https://www.gla.ac.uk/myglasgow/research/enlighten/theses/digitisation/ This is a digitised version of the original print thesis. Copyright and moral rights for this work are retained by the author A copy can be downloaded for personal non-commercial research or study, without prior permission or charge This work cannot be reproduced or quoted extensively from without first obtaining permission in writing from the author The content must not be changed in any way or sold commercially in any format or medium without the formal permission of the author When referring to this work, full bibliographic details including the author, title, awarding institution and date of the thesis must be given Enlighten: Theses https://theses.gla.ac.uk/ [email protected] ACTIONS OF ANTICHOLINESTERASES CN VISUAL PERFORMANCE IN MAN AND THEIR ANTAGONISM BY ATROPINE A thesis submitted to the Uhiversity of Glasgow in Candidature for the degree of DOCTOR OF PHILOSOPHY in the Faculty of Medicine by CHRISTINE DIANE KAY from The Institute of Physiology The University Glasgow © C.D. Kay, 1989 July 1989 1 ProQuest Number: 10999368 All rights reserved INFORMATION TO ALL USERS The quality of this reproduction is dependent upon the quality of the copy submitted. In the unlikely event that the author did not send a com plete manuscript and there are missing pages, these will be noted. Also, if material had to be removed, a note will indicate the deletion. uest ProQuest 10999368 Published by ProQuest LLC(2018). Copyright of the Dissertation is held by the Author. All rights reserved. This work is protected against unauthorized copying under Title 17, United States C ode Microform Edition © ProQuest LLC. ProQuest LLC. 789 East Eisenhower Parkway P.O. Box 1346 Ann Arbor, Ml 48106- 1346 CONTENTS Page Contents .............. ............................... 2 List of tables ........................................... 7 List of figures ......................... .............. 8 Acknowledgements ........................................... 12 Summary 13 Introduction 17 Measurement of visual function; contrast-Sensitivity ... 18 Factors affecting the retinal image ... 22 Influence of cholinergic drugs on visual function ........ 29 Cholinergic mechanisms in the retina... .................... 29 Cholinergic influences in other parts of the visual pathway 32 Cholinergic pharmacology Nature and function of cholinesterase ................... 34 Mechanism of action of anticholinesterases .............. 35 A. Reversible anticholinesterases......................... 36 B. Irreversible anticholinesterases ................... 36 Actions of anticholinesterases in v i v o ................... 37 Historical review of physostigmine ................... 40 Effects of topically instilled physostigmine ............. 42 Development of organophosphorus nerve a g e n t s ............. 45 Effects of organophosphorus compounds on visual function .. .. 46 Protection of cholinesterase against irreversible inactivation 49 Cholinergic antagonists; atropine and hcmatropine ........ 51 Combination of atropine with muscarinic receptors ........ 51 Pharmacological effects of atropine ................... 54 Clinical uses of atropine ................... 54 Atropine as an antidote to organophosphorus poisoning ... 55 2 Effects of atropine on physical performance .............. 57 Effects of intramuscular atropine on visual performance ... 57 Aims of this study Part 1: A quantitative investigation of the effects of defocus, pupil diameter and spatial frequency on contrast sensitivity 58 Part 2: The effects of a single oral dose of pyridostigmine bromide on contrast sensitivity 59 Part 3: The effects of topical application of 0.25% physostigmine sulphate on visual performance ... 60 Part 4: The effect of an intramuscular dose of 2mg atropine sulphate on visual performance ......................... 61 Part 5: The effectiveness of prior administration of an intramuscular injection of atropine sulphate or instillation of hcmatropine eyedrops against physostigmine eyedrops........ 63 Methods 64 Apparatus (1) CRT D i s p l a y ........................................... 65 (2) Laser Display ................... 69 Other visual measurements ....... 72 S u b j e c t s ................................................ 73 Exclusions 73 Ethical consent ........................................... 74 Experiments performed................................. ... 74 Part 1: A quantitative investigation of the effects of defocus, pupil diameter and spatial frequency on contrast sensitivity 75 Part 2: The effects of a single oral dose of pyridostigmine bromide on contrast sensitivity 77 Part 3: The effects of topical application of 0.25% physostigmine sulphate on visual performance ......................... 78 3 Part 4: Ihe effect of an intramuscular dose of 2mg atropine sulphate on visual performance ......................... 80 General procedure ... 80 Experiment 1 81 (1) Reaction time and choice reaction time ............. 82 (2) Extraocular muscle balance ........................ 82 (3) Accommodation ..................................... 83 (4) Colour-matching ................... ... 83 (5) Stereoacuity .............. .. C.................. 84 (6) Visual acuity ..................................... 84 (7) Contrast sensitivity to a moving stimulus............. 85 Experiment 2 85 Part 5: Ihe effectiveness of prior administration of an intramuscular injection of atropine sulphate or instillation of homatropine eyedrops against physostigmine eyedrops........ 86 Data Analysis .......................................... 88 Results 89 Part 1: A quantitative investigation of the effects of defocus, pupil diameter and spatial frequency on contrast sensitivity 90 Contrast sensitivity to CRT display ................... 90 Pupil diameter ........................................... 90 Defocus ... ... ... ... ... ... ... ... ... 91 Quantitative analysis................................... 96 Contrast sensitivity to the laser display ............. 97 Part 2: The effects of a single oral dose of pyridostigmine bromide on contrast sensitivity ... .............. 99 Contrast sensitivity to CRT and laser displays Individual results ..................................... 99 Mean results .... ... ... ... ... ... ... ... 102 4 Part 3: Ihe effects of topical application of 0.25% physostigmine sulphate on visual performance ......................... 103 Contrast sensitivity to stationary grating patterns ........ 108 Contrast sensitivity to moving grating patterns ........ 109 Contrast sensitivity to laser interference fringes ........ 109 Possible genetic factors involved in sensitivity of accommodation to physostigmine ... ... ... ... ... ... ... ... 111 Part 4: The effect of an intramuscular dose of 2mg atropine sulphate on visual performance ... .............. 113 General effects of atropine ... • • • • • • 113 Pupil diameter and accommodation • • • • • • 114 Experiment 1 Reaction time and choice reaction time 115 Extraocular muscle balance ........ 115 Colour-matching................... 115 Stereoacuity .............. • • • • 117 Visual acuity ... ... ... ... ... ... ... ... 117 Contrast sensitivity to a moving grating pattern ........ 119 Experiment 2 Contrast sensitivity to a stationary grating pattern; CRT display Reproducibility of measurements ......................... 121 Effect of atropine ..................................... 121 Contrast sensitivity to the laser display ............. 122 Part 5: The effectiveness of prior administration of an intramuscular injection of atropine sulphate or instillation of homatropine eyedrops against physostigmine eyedrops ........ 123 Pre-treatment with atropine sulphate • • • • 123 Pupil diameter ................... 124 Accommodation ................... 126 5 Critical fusion frequency ............................... 127 Contrast sensitivity ..................................... 127 (a) Atropine 8 min prior to physostigmine..... ............. 128 (b) Atropine 124 min prior to physostigmine... ............. 131 Pre-treatment with hcmatropine hydrobromide eyedrops ... 134 Pupil d i a m e t e r ................... 134 Accommodation ........................................... 136 Contrast sensitivity ..................................... 139 Discussion ^' 141 Contrast sensitivity to the CRT display ................... 142 Contrast sensitivity to the laser display ............. 143 Hie ocular modulation transfer function................... 145 Reproducibility of the measurements ................... 146 Part 1: A quantitative investigation of the effects of defocus, pupil diameter and spatiai frequency on contrast sensitivity 148 Pupil d i a m e t e r ........................................... 148 Defocus ... ... ... ... ... ... ... ... ... 150 Quantitative analysis..................................... 154 Part 2: The effects of a single oral dose of pyridostigmine bromide on contrast sensitivity 155 Part 3: The effects of topical application of 0.25% physostigmine sulphate on visual performance ......................... 157 Part 4: The effect of an intramuscular dose of 2mg atropine sulphate on visual performance ......................... 163 Part 5: The effectiveness of prior administration of an intramuscular injection of atropine sulphate or instillation of hcmatropine eyedrops against physostigmine eyedrops........ 169 References ... ... ... ... ... ... ... ... ... 174 6 List of tables Table Page 1 Signs and symptoms of anticholinesterase