RISK FACTORS FOR EARLY-ONSET MYOPIA IN SINGAPORE CHINESE PRESCHOOL CHILDREN LOW CONG JIN WILSON (B.Sc.(Hons.), NUS) A THESIS SUBMITTED FOR THE DEGREE OF MASTER OF SCIENCE DEPARTMENT OF EPIDEMIOLOGY AND PUBLIC HEALTH NATIONAL UNIVERSITY OF SINGAPORE 2011 ACKNOWLEDGEMENTS My heartfelt appreciation goes towards my supervisor, Prof Saw Seang Mei who not only had introduced me into the realm of epidemiological research, but also provided umpteen encouragement, mentorship and guidance in my quest for a postgraduate education I thank her for believeing in my capabilities and passion towards research I would also like to extend my gratitude to my co-supervisor, Prof Wong Tien Yin for his superb support and timely critical review of my work I also thank him for motivating me to continue striving for excellence I am extremely grateful to Dr Dharani Ramamurthy for vetting my thesis, Mr Brendon Zhou and Ms Lin Xiaoyu for their statistical support, Ms Eunice Lo for her fantastic secretariat assistance, and all my friends and collegues at EPH for providing much encouragement, laughters and joy, and a great working environment Much credit and thanks also goes towards the current and past clinical and administrative staffs of STARS for their help and hard work in recruitment and collection of clinical data, without which my thesis would have certainly not existed The voluntary participation of all the subjects in the STARS is sincerely appreciated I acknowledge the funding of STARS by National Medical Research Council, Singapore (NMRC/1009/2005) Last but not least, I would like to thank my family for their tolerance, understanding and support i TABLE OF CONTENTS ACKNOWLEDGEMENTS i TABLE OF CONTENTS .ii SUMMARY iv LIST OF TABLES .vii LIST OF FIGURES ix CHAPTER LITERATURE REVIEW 1.1 Introduction 1.2 Background 1.2.1 Refractive Components of the Eyes and Relation to Myopia .1 1.2.2 Emmetropisation .2 1.2.3 Animal Models of Myopia 1.2.4 Genes and Environment 1.2.5 Definition of Myopia in Epidemiologic Studies 1.2.6 Axial Length and Myopia .5 1.2.7 Complications of High and Pathologic Myopia 1.2.8 Public Health and Socioeconomic Impact of Myopia 1.3 Prevalence of Myopia 1.3.1 Methodology of the literature search 1.3.2 Myopia Prevaence among Asian Children .8 1.3.3 Myopia Prevalence among Non-Asian Children 11 1.3.4 Myopia Prevalence Among Singaporean Adults 12 1.4 Distribution of Ocular Biometry 14 1.4.1 Axial Length 14 1.5 Risk Factors for Development of Myopia and Elongation of Axial Length15 1.5.1 Methodology of the Literature Search 15 1.5.2 Family History of Myopia 18 1.5.3 Near work Activities and Parameters 20 1.5.4 Outdoor Activity and Physical Activity 22 1.5.5 Stature 25 1.5.6 Birth Parameters 27 1.5.7 Parental Smoking History .28 1.5.8 Breastfeeding 29 1.6 Conclusion 30 1.6.1 Summary of Current Literature 30 CHAPTER 60 OBJECTIVES 60 2.1 Primary Aims .60 2.2 Secondary Aims 60 CHAPTER 61 METHODOLOGY 61 3.1 Study Design 61 3.2 Study Population 61 3.2.1 Sampling Frame 61 3.2.2 Eligibility 65 3.2.3 Study Approval .65 3.2.4 Recruitment 66 3.2.5 Response Rate .67 ii 3.3 Clinic Visit 68 3.3.1 Refractive Error Measurements 68 3.3.2 Biometry Measurements .73 3.3.3 Risk Factor Assessment 74 3.4 Questionnaires 75 3.4.1 Demographics and Socioeconomic Factors 75 3.4.2 Family History of Myopia 76 3.4.3 Near work Activities .76 3.4.4 Outdoor Activity 77 3.4.5 Birth Parameters 78 3.4.6 History of Parental Smoking .78 3.5 Definitions 79 3.6 Data Management 79 3.6.1 Data Collection and Entry 79 3.6.2 Confidentiality 80 3.7 Data Analysis .81 CHAPTER 82 RESULTS 82 4.1 Characteristics and Demographics of the Study Population 82 4.1.1 Age and Gender 82 4.1.2 Axial Length, Spherical Equivalent and Myopia 82 4.1.3 Social Economic Status .85 4.2 Risk Factors for Myopia Analysis .86 4.2.1 Parental History of Myopia 87 4.2.2 Stature 92 4.2.3 Outdoor Activity 101 4.2.4 Near work 107 4.2.5 Family History, Near Work, Outdoor Activity, and Myopia in Singapore Chinese Preschool Children 121 4.2.6 Parental History of Smoking .124 4.2.7 Birth Parameters 140 CHAPTER 154 DISCUSSION 154 5.1 Risk Factors for Myopia 155 5.1.1 Family History of Myopia 155 5.1.2 Body Stature 159 5.1.3 Near work 162 5.1.4 Outdoor Activity 166 5.1.5 Parental Smoking 169 5.1.6 Birth Parameters 172 5.2 Implications of study Results 174 5.3 Strengths and Limitations 177 5.3.1 Strengths .177 5.3.2 Limitations 178 5.4 Conclusions 181 CHAPTER 183 PUBLICATIONS .183 REFERENCES 214 LIST OF APPENDICES 226 iii SUMMARY Background: Both genes and environments are known to play important roles in the onset and development of myopia Family history of myopia is a major risk factor for myopia and ocular biometry and represents a surrogate for genetic or shared environmental factors However, current evidence also suggests that environmental factors such as near work and outdoor activity are implicated in the development of myopia and longer axial length (AL) Height and birth weight are potential risk factors for myopia and ocular biometry Objectives: The primary aim is to investigate the risks factors for myopia and ocular biometry in Singapore Chinese preschool children aged to 72 months The secondary aims include assessment of the association of family history of myopia, near work, outdoor activity, stature, birth parameters, and parental smoking with myopia and ocular biometry Methodology: A population-based cross-sectional study, with disproportionate random sampling by 6-month age groups, was conducted to determine the prevalence of and risk factors for myopia in a representative sample of 3009 Singaporean Chinese preschool children aged to 72 months living in the South-Western and Western part of Singapore Spherical equivalent refraction (SER) was measured using cycloplegic autorefraction or streak retinoscopy AL was obtained monocularly using non-contact partial coherence interferometry (IOL Master) Height and weight were assessed by standard protocols Information on family history of iv myopia, near work and outdoor activities, birth parameters and parental smoking were determined by comprehensive questionnaires Results: Children with two myopic parents were more likely to be myopic (adjusted odds ratio (OR) = 1.91; 95% confidence interval (CI) = 1.38 - 2.63), and were found to have a 0.35 diopters (D) (95% CI = -0.47 - -0.22) more myopic SER and a 0.16 mm (95% CI = 0.08 - 0.24) longer AL than children without myopic parents For each cm increase in height, the SER was more myopic by 0.01 D and AL longer by 0.02 mm Neither near work nor outdoor activity was associated with myopia The proportion of children with myopia was significantly less than among those whose mothers ever smoked compared to those whose mothers never smoked (7.6% vs 11.8%, p = 0.047) Birth weight was associated with longer AL (regression coefficient = 0.26; 95% CI = 0.18 - 0.33) Conclusion: Our study found an association of family history of myopia with prevalence of myopia, more myopic refraction and longer AL in Singaporean Chinese preschool children aged to 72 months Height was associated with more myopic SER and longer AL Birth parameters were associated with longer AL Maternal smoking appeared to reduce the risk of myopia in this very young group of children Key lifestyle factors such as near work and outdoor activity were not significantly associated with myopia in this study which might be due to the lesser amount of nearwork or outdoor activity performed This contradicts the association between myopia and near work or outdoor activity found in older children reported by previous studies in which the findings suggest that the cumulative effects of near work and outdoor activity may only influence the development of myopia in older v children aged more than years during the school years In summary, genetic factors may play a more substantial role in the development of early-onset myopia as compared to environmental factors vi LIST OF TABLES Table Prevalence of Myopia in Children in Asia .34 Table Prevalence of Myopia in Children in Non-Asian Countries 39 Table Prevalence of Myopia in Singaporean Adults 42 Table Family History/Parental Myopia as Risk Factor for Myopia in Children in Asia 43 Table Family History/Parental Myopia as Risk Factor for Myopia in Children in Non-Asian Countries .45 Table Near work as Risk factor For Myopia in Children in Asia 47 Table Near work as Risk Factor For Myopia in Children in Non-Asian Countries 49 Table Outdoor as Risk Factor of Myopia in Children .51 Table Stature and Anthropometric Parameters as Risk Factor for Myopia in Children 53 Table 10 Stature and Anthropometric Parameters as Risk Factor for Myopia in Adults 54 Table 11 Birth Parameters as Risk Factor for Myopia in Children 56 Table 12 Parental Smoking as Risk Factor For Myopia .57 Table 13 Breastfeeding as Risk Factor For Myopia .59 Table 14 Detectable odds ratios for different numbers of cases of a particular condition and prevalence of a particular risk factor using the remaining cohort as controls 65 Table 15 Characteristics of the Study Population by Gender and Age .82 Table 16 Characteristics of the Study Population by Ocular biometry and Spherical Equivalent 84 Table 17 Proportion of Children with Myopia by Ocular biometry and Spherical Equivalent 85 Table 18 Characteristics of the Study Population by Social Economic Status 86 Table 19 Proportion of Children with Myopia by Social Economic Status 86 Table 20 Characteristics of the Study Population by Parental Myopia 87 Table 21 Proportion of Children with Myopia by Parental Myopia 88 Table 22 Ocular Biometry and Spherical Refraction by Parental Myopia 90 Table 23 Characteristics of the Study Population by Stature .94 Table 24 Proportion of Children with Myopia by Stature 95 Table 25 Ocular Biometry and Spherical Refraction by Stature 99 Table 26 Characteristics of the Study Population by Outdoor Activity .102 Table 27 Proportion of Children with Myopia by Outdoor Activity 103 Table 28 Ocular Biometry and Spherical Refraction by Outdoor Activity 105 Table 29 Characteristics of the Study Population by Near work Activity 109 Table 30 Proportion of Children with Myopia by Near work Activity 112 Table 31 Ocular Biometry and Spherical Refraction by Near work Activity 117 Table 32 Risk factors Associated with Myopia among Singapore Chinese Preschool Children .122 Table 33 Risk Factors Associated with Spherical Equivalent Refraction among Singapore Chinese Preschool Children 123 Table 34 Factors predictive of Axial Length among Singapore preschool children 124 Table 35 Characteristics of the Study Population by Parental Smoking 125 Table 36 Proportion of Children with Myopia by Parental Smoking .130 vii Table 37 Ocular Biometry and Spherical Refraction by Parental Smoking .134 Table 38 Association of Smoking by Either Parent with Myopia in Children 137 Table 39 Association of Smoking by Each Parent with Myopia in Children 138 Table 40 Association of Smoking by Mother during Child’s Life and Low Birth Weight with Myopia in Children 140 Table 41 Characteristics of the Study Population by Birth Parameters 143 Table 42 Proportion of Children with Myopia by Birth Parameters 144 Table 43 Ocular Biometry and Spherical Refraction by Birth Parameters .148 Table 44 Association of Myopia with Quartiles of Birth Parameters .151 Table 45 Association of Myopia with Clinical Definitions of Birth Parameters (Normal and High versus Low Range) 152 Table 46 Association of Myopia with Clinical Definitions of Birth Parameters (Low and High versus Normal Range) 153 Table 47: Singapore Census of Population 2010 (Dwelling Types by Combined income, Education and STARS Recruitment Areas) 181 viii LIST OF FIGURES Figure Flowchart for Pubmed (Medline) Search on the Prevalence of Myopia in Children Figure Prevalence of myopia (SER at least -0.5 D) across different age groups in Singapore 13 Figure Flowchart for Pubmed (Medline) search on risk factors for myopia 17 Figure Multivariable-adjusted odds ratios (adjusted for gender, ethnicity, parental myopia, parental employment, and education) for myopia by reported average daily hours spent on near-work versus outdoor activities in 12-year-olds Australians 24 Figure Study Areas of the STARS Study 62 Figure Sampling Frame and Response Rate 63 Figure Distribution of Axial length among Singapore Chinese Preschool Children 83 Figure Distribution of Spherical Equivalent among the Right Eyes of Singapore Chinese Preschool Children .84 Figure Prevalence of Myopia in Children among History of Parental Myopia .88 Figure 10 Mean Axial Length in Children among Parental Myopia 89 Figure 11 Mean Spherical Equivalent among Parental Myopia 91 Figure 12 Distribution of Height among Singapore Chinese Preschool Children 93 Figure 13 Distribution of Weight among Singapore Chinese Preschool Children 93 Figure 14 Distribution of BMI among Singapore Chinese Preschool Chinese 94 Figure 15 Scatter Plot of Height and Axial Length 96 Figure 16 Scatter Plot of Weight and Axial Length 98 Figure 17 Prevalence of Myopia among Children whose Mothers ever Smoked during the Child’s Life .128 Figure 18 Prevalence of Myopia in Children who had at least One Parent who ever Smoked .129 Figure 19 Distribution of Birth Weight among Singapore Chinese Preschool Children 141 Figure 20 Distribution of Birth Length among Singapore Chinese Preschool Children 141 Figure 21 Distribution of Birth Head Circumference among Singapore Chinese Preschool Children 142 Figure 22 Distribution of Gestational Age among Singapore Chinese Preschool Children 142 ix 276 277 278 279 Appendix D 280 281 282 283 284 285 286 287 288 289 290 ... among Singapore Chinese Preschool Children 93 Figure 13 Distribution of Weight among Singapore Chinese Preschool Children 93 Figure 14 Distribution of BMI among Singapore Chinese Preschool Chinese. .. Factor for Myopia in Children in Non-Asian Countries .45 Table Near work as Risk factor For Myopia in Children in Asia 47 Table Near work as Risk Factor For Myopia in Children in Non-Asian... to smoking during pregnancy and childhood may protect against myopia in children Breastfeeding appears to protect against myopia in Singapore children but this finding requires validation in other