Optical Changes during Normal Emmetropization, Lens-induced Myopia and its Recovery in the Young Chick Eye by Zheng Shao A thesis presented to the University of Waterloo in fulfillment of the thesis requirement for the degree of Master of Science in Physics and Vision Science Waterloo, Ontario, Canada, 2015 ©Zheng Shao 2015 AUTHOR'S DECLARATION This thesis consists of material all of which I authored or co-authored: see Statement of Contributions included in the 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 Statement of Contributions This thesis has been written in a manuscript format. I would like to acknowledge the names of my co- authors who contributed to the research described in this thesis, these include: Kaitlin Bunghardt, Marsha L Kisilak, Dr. Elizabeth L. Irving, and Dr. Melanie CW Campbell. Please reference the beginning of each Chapter for details for contributions of authors. iii Abstract In human eyes, the at-birth hyperopoic defocus gradually decreases to mild hyperopia or emmetropia at around age 6. Studies on refractive development suggest somewhat complex mechanisms at work between eye power and length. Myopia occurs as a result of failure of normal emmetroipzation. Myopia is linked with various ocular pathologies and is now considered an independent risk factor of a range of ocular diseases. Therefore, myopia research is essential. The substantially increasing prevalence of myopia has particularly attracted researchers’ attention. Any improvement in the understanding of the mechanisms of normal emmeropization and myopia development has the potential to introduce interventions that can limit or prevent myopia incidence and/or progression. The eye power calculation presented is simpler than other approaches and provides an accurate power variation during normal emmetropization without the need for ex vivo measurements. Eye power calculation during normal growth showed a decrease in eye power and that the small difference between the rate of change in eye power and that of dioptric eye length, gives a decrease in MOR. When we modify the eye power calculation with one additional assumption, it can to be applied to myopic eyes. During emmetropization to hyperopoic defocus (LIM) and its recovery, eye power calculations based on different additional assumptions confirm a change in the optics, either in the positions of cardinal points or in the focal length, depending on the assumptions used. Changes in curvatures of the ocular surfaces remain to be assessed. Emmetropization is an active mechanism; it appears to be driven by values of angular blur due to defocus which are above the level of the cone photoreceptor resolution during emmetropization. Angular blur reaches a level similar to cone spacing at the completion of emmetropization. Rates of change in optical axial length (OAL), corneal radius and the lens power are proportional to angular iv blur, causing blur to reduce significantly. Angular blur varies linearly with MOR and its rate of change. After emmetropization, the constant angular blur and slightly increasing linear blur suggest that eye growth might be relatively uniform. The links between rates of change in OAL, corneal radius and the lens power during and after emmetropizaton may be related to a common signaling molecule or via passive mechanisms. During LIM and recovery from it, VCD is a main contributor to changes in mean ocular refraction. However, the relative change in the front of the eye (represented by anterior cornea to back lens distance) is proportional to the relative change in OAL and is important to overall OAL changes compared to the control eye. The change in eye power in relation to the change in eye length is important to normal emmetropization. The optics also changes during LIM and the recovery from it. In addition, in normal growth, a direct link between the changes in ocular parameters and retinal blur is shown. Since many of these results are consistent with findings during emmetropization in children, the link between the changes in ocular parameters and retinal blur may be important to understanding normal development and development of myopia in human. v Acknowledgements It has been my good fortune to have the advice and guidance of many talented people. I would like to take this opportunity to express my utmost gratitude to: My incredible supervisor, Dr. Melanie Campbell, whose patience, intelligence, diligence and erudition profoundly had an everlasting impact on me both academically and personally. My kindhearted committee members, Dr. Elizabeth Irving, whose earnest and sagacity enlightened my thoughts, and Dr. Donna Strickland, whose humorous and cheerful spirits softened my impressions on authority figures to foster better communication skills. My excellent colleagues, Ian Andrews, Kaitlin Bunghardt, Si Chen, Laura Emptage, Heqing Huang, Marsha Kisilak, Reza Khanbabaie, Rachel Redekop, Namrata Shah, Olivia Stanley, and Kevin Tuck (alphabetically ordered by last name), whose friendliness and assistance eased my nerves and sailed along with this project. My easygoing English tutors, Navjot Rai and Zara Wong, and friend, Fang Liu, whose encouragement and persuasion urged me on to knock at the door to this journey, and my grammatical- stickler ESL instructor, Mrs. Pat Skinner, whose maddening attention to writing drove me to finally learn to punctuate prose. My elegant friend, Carol Cameron, and her little buddy, Huey, whose selfless time and care sheltered my loneliness and longing for a nearby family. My invincible partner, Yexiang Zhang, whose persistence and carefulness prompted me to meld intellectual prowess with determination and inspiration. Last but not least, those people who established and regulated the following awards/scholarships, International Masters Student Award, Marie Curie Graduate Student Award, Graduate Research Studentship, Science Graduate Experience Award, enabled me to stay; Dr. Shoufa Lin and associates, whose efforts of initializing the China 2+2 program that brought me here to Canada; and my fellow classmates, whose companionship motivated me throughout the past years. This is the end of a two-year journey but the beginnings of an even more fruitful one. vi Dedication “Faith is the bird that feels the light and sings when the dawn is still dark.” ― Rabindranath Tagore I lovingly dedicate this thesis to my mom, for finding me the light, whenever it was far away, and to my family, for reminding me the lyrics, no matter what had happened. vii Table of Contents AUTHOR'S DECLARATION ............................................................................................... ii Statement of Contributions ................................................................................................... iii Abstract ................................................................................................................................... iv Acknowledgements ................................................................................................................ vi Dedication .............................................................................................................................. vii Table of Contents ................................................................................................................. viii List of Figures ........................................................................................................................ xii List of Tables ......................................................................................................................... xv Chapter 1 Introduction........................................................................................................ 1-1 1.1 Emmetropization and Myopia ...................................................................................... 1-1 1.1.1 Optical Changes during Normal Emmetrpoization ............................................... 1-1 1.1.2 Myopia Development in Human Eyes ................................................................... 1-3 1.1.3 Emmetropization and Myopia Studies in the Chick Model .................................. 1-5 1.1.3.1 Experimental Myopia ................................................................................... 1-7 1.1.3.2 Possible Mechanism of Experimental Myopia ........................................... 1-8 1.1.4 Motivations ............................................................................................................ 1-8 1.2 Thesis overview.......................................................................................................... 1-11 Chapter 2 Review of Techniques ...................................................................................... 2-13 2.1 Introduction ................................................................................................................ 2-13 2.1.1 In vivo Measurements .......................................................................................... 2-14 2.1.1.1 Refractive Error, Corneal Curvature and Dimensions ........................... 2-14 2.1.1.2 Experimental Conditions ........................................................................... 2-15 2.1.2 Ex vivo Measurements ......................................................................................... 2-16 2.1.2.1 Radii of Curvatures and Dimensions