Ocular Discomfort Upon Tear Drying by Jalaiah Prasad Varikooty A thesis presented to the University of Waterloo in fulfillment of the thesis requirement for the degree of Master of Science in Vision Science Waterloo, Ontario, Canada, 2003 ©Jalaiah Varikooty 2003 I hereby declare that I am the sole author of this thesis. This is a true copy of the thesis, including any required final revisions, as accepted by my examiners. I understand that my thesis may be made electronically available to the public. ii Ocular Discomfort Upon Tear Drying Abstract Purpose: Assess the relationship between tear film drying and sensation between blinks. Methods: MATLAB sampled a slitlamp video camera, a potentiometer and a microphone while subjects kept one eye open for as long as possible. 23 subjects rated the intensity of the ocular sensation while video and voice data were collected simultaneously. The tear drying on the cornea was measured. Results: The sensation was triphasic. Two linear functions described the latter 2 parts of the data (r ≥ 0.95). The correlation between TBUT and the elbow in the time-discomfort function was 0.72. Extent of tear film drying was linearly correlated to time (median correlation = 0.88). The correlation between the discomfort elbow and image elbow was 0.93 with single data pair for each subject. Analysis of sensation characteristics showed significant differences between itching and burning for both intensity and time (p = 0.03 and p = 0.02 respectively). Conclusions: Simultaneous recording of ocular surface appearance, discomfort intensity and attributes of sensation provide novel information about the development of discomfort during ocular surface drying. The rapid increase in discomfort proceeding blinking has been quantified and the relationship between the time course of drying and discomfort is elucidated. iii Acknowledgements I wish to express my sincere gratitude to my supervisor Dr. Trefford Lee Simpson for providing me the opportunity to pursue graduate studies at the School of Optometry. I will always be indebted to him for his valuable guidance, support and encouragement. His time and effort will always be remembered. I will always be grateful to the members of my advisory committee Dr. Desmond Fonn and Dr. Lyndon Jones for their feedback, advice and assistance. I would also like to express my deep sense of gratitude to Colin G. W. Campbell in the department of Information Systems and Technology, University of Waterloo for his invaluable help and technical assistance in the development of the “Comfortscope” instrument. I extend my personal thanks to the team at the Centre for Contact Lens Research for their excellent collegial encouragement. The technical support provided by Andrew Nowinski and Robin Jones is greatly acknowledged. A special thanks to all the people who agreed to participate as subjects during the experimental stage of this investigation. Thanks also to my fellow graduate students for their advice and the wonderful times we shared together. iv Dedication I dedicate this work to the Varikooty family, especially to my wife and children for their love, patience and constant moral support through all these years. v TABLE OF CONTENTS Ocular Discomfort Upon Tear Drying...................................................................................... i Abstract...............................................................................................................................iii Acknowledgements............................................................................................................. iv Dedication............................................................................................................................ v TABLE OF CONTENTS........................................................................................................ vi LIST OF FIGURES ............................................................................................................... xii LIST OF TABLES................................................................................................................ xiv LITERATURE REVIEW: ....................................................................................................... 1 1. Dry Eye and the Sensation of Ocular Dryness: .............................................................. 1 Cutaneous Dryness: What do we mean by the term Dry Skin?...................................... 2 Neural Mechanisms of Dry Skin Perception: .............................................................. 3 Peripheral Afferents of Mechanoreception and their Psychophysical Channels:.... 4 Relation of Intensity of Stimulus to Magnitude of Sensation:................................. 7 A Note about the evolution of the mucous surface to reduce the drag force:................. 8 2. Neural coding mechanisms of roughness in skin:........................................................... 9 Perception of Moving Stimuli in the Skin: ................................................................ 10 Molecular mechanisms of mechanosensation and its relevance to the ocular surface: .................................................................................................................................... 11 3. Epidemiology of Dry Eye, Dry Skin and Dry Mouth:.................................................. 15 Epidemiology of Dry Skin:........................................................................................... 15 Oral Dryness – What do we mean by the term Dry Mouth? ........................................ 16 Ocular Drying: What do we mean by the term Dry eye? ............................................. 18 The Epidemiology of Dry Mouth and Dry Eye (ICD-9 #375.15): ............................ 18 vi Factors Associated with Dry Eye:.............................................................................. 21 Epidemiology of Dry Eye and Ocular Irritation: ................................................... 22 4. Measurement of Ocular Discomfort: ............................................................................ 26 Suprathreshold Measurement of Ocular Discomfort:................................................... 27 Unidimensional Pain measurement: ............................................................................. 28 Discrete Categorical Scales: ...................................................................................... 29 Analysis of discrete category scales with equal distances:.................................... 30 Disadvantages of Category Scales with equal distances: ...................................... 30 Method of Successive Categories:......................................................................... 31 Disadvantages of the method of Successive Categories:....................................... 32 Determination of Category Values Independently: ............................................... 32 Formats of the Category Scales: ................................................................................ 33 Construction of Scales: .......................................................................................... 33 Direct Estimation techniques:................................................................................ 36 Comparative Methods:........................................................................................... 38 Thurstone’s method of equal appearing intervals:................................................. 38 Guttmann Scaling: ................................................................................................. 39 Paired Comparison Technique:.............................................................................. 40 Continuous Measure Scale:........................................................................................ 40 Bounded Continuous Scale:................................................................................... 41 The Unbounded continuous scales: ....................................................................... 42 Other Unidimensional Suprathreshold Scaling techniques: ...................................... 44 The Hedonic Pain Scales: ...................................................................................... 45 Multidimensional scaling:............................................................................................. 45 vii Computerized method of Pain assessment:................................................................ 47 5. Structure and function of the Tear Film:....................................................................... 49 The lipid layer of the tear film:..................................................................................... 49 Morphology of the meibomian gland: ....................................................................... 50 Regulation of the lipid layer secretion:...................................................................... 50 Composition and formation of the Lipid Layer:........................................................ 52 Functions of the Lipid Layer: .................................................................................... 55 The Prevention of Evaporation:............................................................................. 55 Surface Spreading Function:.................................................................................. 56 Compression and expansion of the lipid layer:...................................................... 57 The Aqueous-mucin layer