Myopia

Animal Models to Clinical Trials

This page intentionally left blank

vi Foreword

related to why humans become myopic. Given that every few years a new group of animals is added to the myopia zoo, all compensating for defocus imposed by spectacle lenses, how likely is it that humans are different?

Were the etiology of human myopia simple this controversy would have been resolved by now. But many human diseases, such as cardiovascular disease and diabetes, have a complex etiology, involving both genetic and behavioral components. How do they differ from myopia? One reason may be that these diseases can be effectively treated without fully understanding their underlying causes, whereas in the case of myopia, understanding the cause of the myopia may well be necessary because simply correcting the myopia may reinstate the conditions that caused the myopia in the first place, thereby setting in motion a positive feedback loop, resulting in an iatrogenic worsening of the myopia. Indeed, some of the possible treatments (scleral reinforcement, daily atropine administration) might be worse than the disease, at least for otherwise healthy children with mild myopia.

Only now are we beginning to appreciate and measure in children the parameters likely to be important indicators of the initiation and progression of the myopia development. For example, what is the refractive status of the retinal periphery and how is it affected by visual experience? Does the periphery become hyperopic relative to the fovea as a cause or consequence of the fovea becoming myopic? Does intensive reading first affect the central or peripheral refractions? How much of the variability in peripheral refractions is a function of eye-shape at birth vs the visual surroundings, and how do these interact? If medical students are more likely to become myopic than athletes, is this due to the total amount of reading or to the duration of episodes of reading? Or to the amount of time outdoors? If the latter, is the relevant factor the absence of hyperopic or myopic defocus at the fovea or in the periphery, or perhaps the enhanced stimulation of dopamine by bright light? These are issues that can be studied in both humans and animals, but require experimental manipulations more difficult than those that have been attempted to date.

An unfortunate consequence of the complicated, multifactorial, nature of the control of eye growth and development of refractive state is that the field of research has been nearly completely divided into those doing animal research and those doing human research. My dear friend and colleague, the late Sek-Jin Chew, was an exception. He studied muscarinic receptors in different ocular tissues to understand why atropine reduced myopic progression. He studied the blinking of chicks to understand whether brief pulses of increased intraocular pressure would affect ocular

vii Foreword

elongation. And he raised mice wearing a diffuser over one eye under his bed to explore whether mice might be a useful animal model for myopia research because of the variety of genetic manipulations available. When he returned from New York to Singapore he initiated both epidemiological and animal research that led to Singapore becoming one of the world’s leading centers of myopia research. We hope this volume will be a step in the direction of bringing together the fields of animal and epidemiological research into the etiology of myopia.

Josh Wallman

Department of Biology

City University of New York

USA

Professor Sek-Jin Chew

xDedication

S$20 million as a five-year grant from the NMRC. At the same time, he set up the SERI laboratories in the National University of Singapore (NUS) and built up a team of researchers and support staff from scratch, opening myopia research clinics. On top of that, he was seeing an increasing number of patients, recruiting school children for his myopia trials, as well as establishing successful links and clinical trials with top industry firms such as Bausch and Lomb, CIBA Vision, and others, which continue to this day.

However, I believe that it was not his brilliant academic achievements or his lightning speed in getting things done that has touched our lives the most. I believe all of us will best remember Sek-Jin for his fearless courage, his boundless optimism in coping with his brain tumour, his total devotion to his work, in spite of his terminal condition, his genuine friendship, and the interest and concern shown to even the most junior medical students.

In recognition of his work in myopia research, Sek-Jin was appointed to a number of international organisations. He was Vice President of the Myopia International Research Foundation and the Director of its AsiaPacific headquarters, based in Singapore. He was also appointed Visiting Professor at the City University of New York and the New York Eye and Ear Infirmary, as well as Visiting Scientist at the Rockefeller University. Sek-Jin was also awarded the SNEC Gold Medal Award in 1997 and the SNEC International Gold Medal posthumous Award in recognition of his achievements internationally.

In his short lifespan, Sek-Jin published over 50 papers. He also made more than 150 presentations, mainly in the field of myopia research, in regional and international conferences, and in particular at the world’s foremost research meeting.

Sek-Jin played a pivotal role in establishing links between SNEC and top universities in the USA, such as Harvard with its strong emphasis in myopia research, and Johns Hopkins University in a collaborative myopia study on RGP lens. He was constantly bringing in top scientists from the USA, UK, Australia, Japan, Taiwan, and China, just to name a few, to create opportunities to start new areas of collaboration into the 21st century.

Donald T.H. Tan

FRCSG, FRCSEd, FRCOphth, FAMS

Medical Director, Singapore National Eye Centre

Chairman, Singapore Eye Research Institute

Professor of Ophthalmology

Yong Loo Lin School of Medicine

National University of Singapore

xi Dedication

“My dear friend and colleague, the late Sek-Jin Chew, was an exception. He studied muscarinic receptors in different ocular tissues to understand why atropine reduced myopic progression. He studied the blinking of chicks to understand whether brief pulses of increased intraocular pressure would affect ocular elongation. And he raised mice wearing a diffuser over one eye under his bed to explore whether mice might be a useful animal model for myopia research because of the variety of genetic manipulations available. When he returned from New York to Singapore, he initiated both epidemiological and animal research that led to Singapore becoming one of the world’s leading centers of myopia research.”

Professor Josh Wallman

Department of Biology

City College, CUNY, USA

“Dr Sek-Jin Chew who was also my student, was my friend and a leader of research at the National University of Singapore. We founded the Singapore Eye Research Institute (SERI) of which he was the founding deputy director. Sek-Jin’s intense interest in myopia has made Singapore one of the world’s leading centers for myopic studies.”

Professor Arthur S.M. Lim

Founding Chairman

Singapore Eye Research Institute

“I first met Sek-Jin here in Singapore at the WOC in 1988; he had a dream to become the first clinician-scientist in Singapore and to establish an eye research institute here. He achieved both goals in a remarkably short-time and it is a great honor for all of us to recognize that his dream has taken root and grown. Sek and Esther were married while he worked in my lab in the US and they became dear friends.

Roger W. Beuerman

Singapore Eye Research Institute

Duke-NUS

SRP Neuroscience and Behavioral Disorders

Yong Loo Lin School of Medicine

National University of Singapore

xii Dedication

“Despite the onset of a fatal illness, he continued to direct the institute, organize its programmes, and produce a flood of ideas to encourage his team.”

Dr J.F. Cullen

Royal College of Surgeons of Edinburgh Newsletter

No. 55, Singapore 1999

“There are a lot of capable people, but few are both capable and respectable like Sek-Jin…. He was visionary, selfless, and both a good team leader and team player. One of his favorite quotes was, ‘Let’s work together.”’

Professor Dennis Lam

Chairman

Department of Ophthalmology

and

Visual Sciences of the Chinese University of Hong Kong

Hong Kong

Sek-Jin was a dedicated and highly motivated researcher who did not spare himself even when he knew that a brain tumour threatened his long-term future. He directed SERI up until his life was cruelly cut short. Together in New York, Glasgow and in Singapore, Sek-Jin and I put together a plan for what became the Singapore Eye Research Institute. It is a sadness that he was not spared to see the flowering of the seed that was planted at that time.

Wallace S. Foulds, CBE, MD, ChM

DSc (Hon), FRCS (Eng & Glasg), FRCOphth

Singapore Eye Research Institute

Singapore

University of Glasgow

United Kingdom

xiv Message

far, they would not survive. In contrast, Chinese scholars, craftsmen and artists engaged in near work survived. This might explain why, over the generations, myopia has become prevalent among the Chinese.

There are many studies to slow down the progress of myopia — eye exercises, eye massages, avoidance of prolonged reading, use of Atropine, use of large letters on white or black boards in school and a host of other methods.

Many have sought alternatives to the use of spectacles. Contact lenses became popular but their use is not without problems. In fact, the use of soft lenses can lead to infection which has caused blindness. When the patient is 20-year or older, his vision can be improved with surgery, the most popular of which is the use of the excimer laser. More recently, LASIK — where a thin layer of the cornea is lifted before the application of laser — has been used. There are now several new lasers and methods of refractive surgery being introduced. This book addresses myopia and I believe that readers will find it useful in their understanding of the condition.

I am delighted that this publication is dedicated to one of the world’s most enthusiastic researchers on myopia — the late Dr Sek-Jin Chew who was also my student, my friend and a leader of research at the National University of Singapore. We founded the Singapore Eye Research Institute (SERI) of which he was the founding deputy director. Sek Jin’s intense interest in myopia has made Singapore one of the world’s leading centres for myopic studies.

While we wait for research to give us more answers, this book is a useful guide for anyone wishing to learn more about myopia.

Professor Arthur Lim, MD (Hon), FRCS

Founding Chairman

Singapore Eye Research Institute

xvi Contents

xvii Contents

This page intentionally left blank