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Myopia


The Myopia Research Group at the Singapore Eye Research Institute, in conjunction with the Singapore National Eye Centre and National University of Singapore, has been involved in various aspects of myopia research over the last 20 years. The group’s research focus is on five sub themes: Genetics, animal experimental models, epidemiology and community-based interventions, treatments to retard myopia progression and visually-disabling pathologic myopia. The aims of our group are to better understand the epidemiology, genetics, pathogenesis and public health implications of myopia, to develop and evaluate novel interventions to prevent or slow myopia progression in young children, and to formulate better management strategies for myopia-related complications in older adulthood. The multi-disciplinary team will address important key questions to tackle the epidemic of myopia.

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The Epidemiology Studies
Several large population-based studies have helped determine the prevalence of myopia in children, including the School Cohort of Refraction Myopia (SCORM) cohort which followed children aged 7-9 years for a period of 10 years, and the Strabismus Amblyopia and Refractive Error Singaporean preschool children (STARS), a cross-sectional study of children aged 6 months to 6 years. Data are also available from several adult studies including the Singapore Malay, Indian and Chinese eye studies (SIMES, SINDI, SCES) which provide information of myopic prevalence in Singaporeans aged >40 years. Early life data are available from the GUSTO birth cohort involving 1200 children in whom refractive status is measured at aged 3 years. Together, these studies provide us with great detail of the size of the myopic problem in Singapore, and an opportunity to study risk factors associated with myopia.

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Myopia and Genetics
Genetic studies in myopia show a complex interaction of multiple genetic influences. Our work with the international Consortium for Refractive Errors And Myopia (CREAM) has uncovered several novel genetics variants by meta-analyzing genome-wide association studies (GWAS) from more than 30 population-based studies in Europe, Asia, United State and Australia. The challenge now is to consolidate information to see if we could identify high risk children with genetic susceptibility for extreme myopia with the Singaporean Chinese population who will benefit from early interventions to retard the progression of myopia.

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The Biology of Myopia
Over the years, we have also studied the factors that influence myopia in our mouse and chick models. Our studies show that atropine reduces myopia progression in both pigmented and non-pigmented mice eyes, and that atropine may act on one or more muscarinic receptors to differentially regulate expression levels of specific receptors which in turn influence axial length and vitreous depth, the main morphological parameters associated with myopia.

Our muscarinic receptor knockout mouse study has provided in vivo evidence to support an important role for the M2/M3 muscarinic receptor in myopia development. The data indicate that the actions of the M2 receptor are mediated by changes in the expression of key extracellular matrix proteins, linking the functional role of M2 with scleral remodeling in myopia. The study also highlights the utility of the mouse as a model for myopia, particularly in conjunction with new technologies that can measure ocular dimensions and optical properties with high precision. Further mouse studies are needed to pinpoint and validate the downstream targets of M2 and to investigate the role of the M3 receptor subtype in myopia development.

More recently, we have also shown that manipulation of the chromaticity of light can also influence myopia progression with chicks raised in red/green environment becoming more myopic while those in blue/green light became more hyperopic. We intend to see if similar chromatic manipulation could also slow myopic progression in children.

Interventional Studies: Slowing, Stopping and Reversing Myopia
Researchers at SERI/SNEC have been exploring ways of slowing or stopping myopia using optical (eg. progressive add, bifocal and myopic defocus glasses) and pharmacological (eg. pirenzepine and atropine) interventions. Of these, results from the Atropine Treatment of Myopia (ATOM) studies have been most promising. There are 2 major ATOM studies, ATOM1 and ATOM2, involving a total of 800 subjects and testing a variety of doses of atropine over a 3-5 year periods. These studies suggest that even a low dose of atropine (0.01%) could slow myopia progression by 60% with no/minimal side-effects. This has translated into clinical practice with many clinicians locally and worldwide now converting to lower doses. More work still needs to be done to better understand the exact pharmacological mechanism of the medication, and to determine the best possible treatment regime. Low-dose atropine, however, has been one of the more exciting new developments in myopia management for some time.

There are, however, other novel optical (e.g. peripheral defocus optics or corneal modifying contact lenses) and pharmacological treatments which need to be explored. The role of different treatment modalities (either on its own or in combination) is still unclear and much work still needs to be done on the subject.

There are, however, other novel optical (eg. peripheral defocus optics or corneal modifying contact lenses) and pharmacological treatments which need to be explored. The role of different treatment modalities (either on its own or in combination) is still unclear and much work still needs to be done on the subject.

We do also know that environmental factors (such as the lack of outdoor activity and too much near work) may influence myopia onset and progression. Reasons for this are uncertain but it is believed that levels of light intensity, chromatics and frequency may be important. The FIT outdoor trial evaluated a weekend Park outdoor program. Novel school or family-based outdoor programs could help to stop or slow myopia onset and progression in our local Singaporean context. Steps have been made to undertake an exploratory randomized controlled study both locally and in conjunction with collaborators overseas.

Clinical Myopia
Eventually, this importance in this research is how it can be used clinically to prevent or slow myopia in childhood, minimize the subsequent impact on quality-of-life and quality-of-vision in adulthood (eg. through optical and surgical correction) and to manage any myopia-related complications which may occur in mid to late adulthood.
The myopic epidemic in Singapore started in the 1980s, and individuals from that generation of Singaporeans, with a prevalence of high myopia of 20-30%, are now entering their 5th decade when myopic complications (such as retinal detachment, macula neovascularization, schisis or atrophy, early cataracts and glaucoma) start to manifest.

Directions of Myopia Research
Our plans of the future include programs encompassing five sub themes: genetics, animal experimental models, epidemiology and community-based interventions, treatments to retard myopia progression and visually-disabling pathologic myopia to cover different aspects of myopia research. The epidemiological studies have already led to modification of behavior in the community and changes in national policies. Our proposed outdoor physical activity program will be integrated in schools and rolled out nationwide in conjunction with the Ministries of Education and Health (Health Promotion Board). The ATOM studies have led to changes in our clinical management of children with progressive myopia. There is still much that needs to be learnt and our hope is that we can continue in discover ever better ways to control and manage myopia and to evaluate the predictors and natural history of pathologic myopia.

  1. Saw SM, Katz J, Schein OD, Chew SJ, Chan TK. Epidemiology of myopia.

  2. Saw SM, Hong CY, Chia KS, Stone RA, Tan Dd. Nearwork and myopia in young children. Lancet. 2001; 357:390

  3. Chong YS, Liang Y, Gazzard G, Stone RA, Saw SM. Association between breastfeeding and likelihood of myopia in children. JAMA Journal of the American Medical Association. 2005; 293:3001-2

  4. Saw SM, Tong L, Chua WH, Koh D, Tan DTH, Katz J. Incidence and progression of myopia in Singapore school children. Invest Ophthalmol Vis Sci 2005;46:51-57.

  5. Tan DT, Lam DS, Chua WH, Shu-Ping DF, Crockett RS; Asian Pirenzepine Study Group. One-year multicenter, double-masked, placebo-controlled, parallel safety and efficacy study of 2% pirenzepine ophthalmic gel in children with myopia. Ophthalmol 2005;112(1):84-91.

  6. Luu CD, Lau AM, Koh AH, Tan D. Multifocal electroretinogram in children on atropine treatment for myopia. Br J Ophthalmol. 2005;89(2):151-3.

  7. Chua WH, Balakrishnan V, Chan YH, Tong L, Ling Y, Quah BL, Tan D. Atropine for the treatment of childhood myopia. Ophthalmology. 2006;113(12):2285-91.

  8. Tong L, Huang XL, Koh AL, Zhang X, Tan DT, Chua WH. Atropine for the treatment of childhood myopia. effect on myopia progression after cessation of atropine. Ophthalmol 2009;116(3):572-9.

  9. Samarawickrama C, Mitchell P, Tong L, Gazzard G, Lim L, Wong TY, Saw SM. Myopia-related optic disc and retinal changes in adolescent children from Singapore. Ophthalmol. 2011;118:2050-7.

  10. Morgan IG, Ohno-Matsui K, Saw SM. Myopia. Lancet. 2012; 379(9827):1739-48.

  11. Fan Q, Zhou X, Khor CC, Cheng CY, Goh LK, Sim X, Tay WT, Li YJ, Ong RT, Suo C, Cornes B, Ikram MK, Chia KS, Seielstad M, Liu J, Vithana E, Young TL, Tai ES, Wong TY, Aung T, Teo YY, Saw SM. Genome-wide meta-analysis of five Asian cohorts identifies PDGFRA as a susceptibility locus for corneal astigmatism. PLoS Genet. 2011; 7(12):e1002402.

  12. Low W, Dirani M, Gazzard G, Chan YH, Zhou HJ, Selvaraj P, Au Eong KG, Young TL, Mitchell P, Wong TY, Saw SM. Family history, near work, outdoor activity, and myopia in Singapore Chinese preschool children. Br J Ophthalmol. 2010;94(8):1012-6.

  13. Lim W, Kwan JL, Goh LK, Beuerman RW, Barathi VA. Evaluation of gene expression profiles and pathways underlying postnatal development in mouse sclera. Mol Vis. 2012;18:1436-48.

  14. Barathi VA, Weon SR, Tan QS, Lin KJ, Tong L, Beuerman RW. Transglutaminases(TGs) in ocular and periocular tissues: effect of muscarinic agents on TGs in scleral fibroblasts. PLoS One. 2011;6(4):e18326.

  15. Barathi VA, Beuerman RW. Molecular mechanisms of muscarinic receptors in mousescleral fibroblasts: Prior to and after induction of experimental myopia with atropine treatment. Mol Vis. 2011;17:680-92.

Head:

Key Team Members:

  • Prof Donald Tan
  • Prof Roger Beuerman
  • Prof Wong Tien Yin
  • A/Prof Cheng Ching-Yu
  • Dr Velachamy Amutha Barathi
  • Prof Terri Young
  • Prof Wallace Foulds
  • Dr Khor Chiea Chuen
  • Dr Victor Koh
  • Dr Qiao Fan
  • Dr Pavan K Verkicharla
  • Dr Dharani Ramamurthy
  • Dr Suan Pu

Contact Us: Prof Saw Seang Mei at saw.seang.mei@seri.com.sg