An evidence-based update on myopia and interventions to retard its progression Seo-Wei Leo, MBBS, FRCSEd(Ophth),a,b and Terri L. Young, MDc, ( J AAPOS 2011;15:181-189) AP.박미라 / R3이지명

Introduction Summarizes the current literature regarding myopia epidemiology Genetics & Twin study Animal model studies Interbvention Myopia is the most common human eye disorder in the world, affecting - 85%~ 90% of young adults in some Asian countries such as Singapore and Taiwan, - 25% ~ 50% of older adults in the United States and Europe.

Introduction With its increasing prevalence and earlier age of onset in recent birth cohorts, myopia now affects 33% of adults in the United States. Epidemiological studies about prevalence of myopia - in Western populations of preschool children : low(<5%) - in Asian children affecting of preschool children : 9% to 15% - in Singapore of primary school children : 29% - in a study of 10,000 Taiwanese school children : 6% in 6-year-olds, 70 % by age of 15 years.

Epidemiology Recent epidemiological data has identified outdoor activity as a key environmental determinant of myopia. In both Singaporean and Australian children, total time spent outdoors was associated with less myopic refraction. A comparative study of Chinese children in Singapore and Sydney also revealed a protective effect of outdoor activity. Previous reports of inner-city urban areas having higher odds of myopia than outer suburban areas : small to moderate environmental differences may affect myopia development 환경적 결정 요소

of myopia at an early age. Design: Cross-sectional study. Ophthalmology 2002;109: 2065–2071 © 2002 by the American Academy of Ophthalmology, Inc. Objective: To examine the risk factors for variations in ocular biometry parameters in Singapore Chinese children, a population with a known high prevalence rate of myopia at an early age. Design: Cross-sectional study. Participants: Children aged 7 to 9 years (n= 1453) from three schools in Singapore. Methods: AxL / vitreous chamber depth/ lens thickness/ ACD/ ref. / corneal curvature radius 을 측정. Q. of 독서량 for 1wk / parental myopia. Results: in males , taller children ► AC - deeper / in female, older, shorter children. ► corneal curvature - steeper Conclusions: * AXL, Vit. CD 의 증가 - associated with older age, male, 2권 이상의 독서 /wk , 키의 증가.부모의 myopia * ACD, corneal curvature, lens thickness. - not associated with 독서량 , 부모의 myopia. * Confirm that conventional risk factors for myopia associated the vitreous cavity, but ant. Seg. parameters (corneal curvature , lens thickness) may be unrelated postnatal growth control mechanisms. older, male, 2권 이상의 독서 /wk, taller, 부모 중 한명 이상 myopia. ► the AxL - longer & V.C–deeper early age 때 myopia의 prevalence rate 이 높다고 알려진 Singapore Chinese children 에서 ocular biometry parameters 에 영향을 주는 risk factor 를 알아보기 위한 .

Genetics of Ocular Refractive Components AL is estimated to be the greatest determinant of refractive error; heritability estimates for AL , most recently were reported to be 81% in a whole genome twin study in Australia. This study was the first to identify a locus on chromosome 5q, implicated in ocular AxL Pedigree and clinical data suggest that an AR gene is responsible for high myopia in a consanguineous Chinese family. Meta-analysis of Genomewide linkage in Caucasian (CAUC) and Old Order Amish (OOA), Jewish (ASHK), African American (AFRAM) families identify genomic regions that influence for refraction. heritability 유전률 염색체 5번 장완에 위치

Axial length is highly heritable.- influenced by one or more genes Ophthalmology 2008;115:1053–1057 © 2008 by the American Academy of Ophthalmology. Purpose: To estimate heritability and locate quantitative trait loci influencing axial length. Design: Classic twin study of MZ & DZ twins Participants: 893 명 .( from 460 families ) were recruited through the Twin Eye Study in Tasmania and the Brisbane Adolescent Twin Study (BATS) / AxL를 측정. Methods: Structural equation modeling was used to estimate genetic and environmental components of variation in AxL. Analysis of existing microsatellite marker genomewide linkage scan data was performed on 318 individuals from 142 BATS families. Results: The heritability estimate for AxL, adjusted for age and sex The highest multipoint logarithm of the odds (LOD) score observed was 3.40 on chromosome 5q. Additional regions were also identified on chromosome 6, chromosome 10, chromosome 14 Conclusion: Axial length is highly heritable.- influenced by one or more genes on the chromosome 5q, chromosome 6, chromosome 10, chromosome 14

Twin Studies provide the strongest conclusive evidence that myopia is inherited, as background contributions are diminished. Many studies have noted an increased concordance of refractive error & refractive components(AL, corneal curvature, lens power) in MZ twins compared to DZ twins. Most recently, Dirani and colleagues reported the first evidence for a genetic component in adult-onset myopia within a large cohort study of white twins. - estimated a high genetic contribution to AxL, AC depth, and angle opening distance in twins refractive error 굴절이상 refractive error 일치

a genetic component in adult-onset myopia. (Invest Ophthalmol Vis Sci. 2008;49:3324–3327) DOI:10.1167/iovs.07-1498 PURPOSE. part of the Genes in Myopia (GEM) twin study , large cohort of Caucasian twins 을 대상으로 To report the frequency of adult-onset myopia & quantify the genetic contribution in adult-onset myopia METHODS. All twins aged 18 years or older - participate in the GEM twin study through the Australian Twin Registry (ATR). including cycloplegic objective examination. A total of 1224 twins ( 690 MZ / 534DZ between 18 ~ 86 years of age ) into the GEM study. Adult-onset myopia was defined-first spectacle/contact lens correction at the age of 18 years or older. Myopia was defined as SE ≤ 0.50 D. RESULTS. A total of 96 twins (27.7%) (comprising 50 MZ and 46 DZ twins) : Adult-onset myopia A significantly higher MZ intrapair correlation (r = 0.61) compared with that in DZ twins (r = 0.16, P < 0.01) for SE was found in twins with adult-onset myopia. CONCLUSIONS. the GEM twin study is the first study of its kind to provide evidence to support a genetic component in adult-onset myopia.

Animal Models If irregularly expressed, could cause the eye to elongate and become myopic. The majority of myopia cases are not caused by defects in structural proteins, but by defects involving the control of structural proteins. ZENK is linked to an axial eye growth inhibitory signal. Hyperopic defocus, to stimulate eye growth that moves the retina toward the conjugate point. Myopic defocus, pushing the retina forward toward the myopic focal point. Later studies showed that animal eyes respond bidirectionally to a level of defocus greater than its distance from emmetropia.

Medication < Atropine Eye Drops > the Atropine in the Treatment of Myopia study (ATOM) was a randomized, doublemasked, placebo-controlled trial involving 400 Singapore children. It showed that 1% atropine eye drops instilled nightly in 1 eye over a 2-year period reduces myopic progression significantly in children by 77%(1.2D in the control group vs 0.28D in the atropine group). Finally, the optimal concentration and desired duration of drug application need to be established.

Medication < Pirenzepine 2% Gel> relatively selective for the M1 muscarinic receptor In the US pirenzepine 2% gel applied twice a day slowed myopia progression over 2 year (0.58 D vs 0.99 D) Currently development of pirenzepine as an anti-myopia therapeutic has ceased due to regulatory and financial obstacles.

Optical Treatment 1) Bifocals 2) Progressive Additional Lenses randomized, clinical trials in the US, Finland, and Denmark showed no significant slowing of myopia 2) Progressive Additional Lenses The use of progressive addition lenses has produced relatively small treatment effects- statistically significant , but not clinically meaningful. 3) Contact Lenses In the Contact Lens and Myopia Progression study, subjects were randomized to wear either RGP or soft contact lenses for 3 years. Results showed a statistically significant difference in myopia progression in the RGP (-1.56±0.95 D ) vs. soft lens group (-2.19±0.89 D) ( p< 0.001) with most of the treatment effect found in the first year In the absence of differences in axial elongation, the authors concluded that RGP lenses was not effective for myopia control.

Optical Treatment 4)Orthokeratology 5)Undercorrection There is still no evidence for long-term efficacy A gold standard randomized controlled trial with sufficient subject numbers still needs to be conducted to definitively determine. 5)Undercorrection Contrary to animal studies, myopic defocus speeds up myopia progression rather than retarding it. This means that myopes may have an abnormal mechanism for detecting the direction of optical defocus of the retinal image. 6)Part-Time Lens Wear Three-year refractive shifts were not significantly different among the 4 groups: (1) full-time wearers, (2) myopes who switched from distance to full-time wear, (3) distance wearers, (4) nonwearers.

Commercial Products and Techniques NeuroVision Although NeuroVision has been shown to improve unaided visual acuity and unaided contrast sensitivity in adults with low myopia, it does not alter refraction or accommodative amplitudes. 2) EyeRelax “EyeRelax” is a microscope-like device purported to improve the vision f there is no evidence that it can retard the progression of myopia. 3) “Vision Therapy Eyewear”/Pinhole Glasses A 10% to 20% improvement in vision—even elimination of myopia is advertised. However, there is no evidence that this can retard myopia progression.

Recommendations Future research should take into consideration the role of environmental factors to genetic influences, such as interactions of early-age nearwork or outdoor activity and genotype. 1% Aropine With regard to optical correction, current evidence suggests full correction. Peripheral refraction interventions to retard myopia progression may also be possible in the near future.

Design: Classic twin study of MZ & DZ twins Ophthalmology 2008;115:1053–1057 © 2008 by the American Academy of Ophthalmology. Purpose: To estimate heritability and locate quantitative trait loci influencing axial length. Design: Classic twin study of MZ & DZ twins Participants: 893 명 .( from 460 families ) were recruited through the Twin Eye Study in Tasmania and the Brisbane Adolescent Twin Study (BATS) ocular AxL. measured. Methods: Structural equation modeling was used to estimate genetic and environmental components of variation in axial length Analysis of existing microsatellite marker genomewide linkage scan data was performed on 318 individuals from 142 BATS families. Main Outcome Measure: Ocular AxL. Results: The heritability estimate for AxL, adjusted for age and sex The highest multipoint logarithm of the odds (LOD) score observed was 3.40 on chromosome 5q. Additional regions were also identified on chromosome 6, chromosome 10, chromosome 14 Conclusion: Axial length, a major endophenotype for refractive error, is highly heritable and is likely to be influenced by one or more genes on the long arm of chromosome 5.

older, male, 2권 이상의 독서 /wk, taller, 최소 한명 이상의 myopic 부모. Ophthalmology 2002;109: 2065–2071 © 2002 by the American Academy of Ophthalmology, Inc. Objective: To examine the risk factors for variations in ocular biometry parameters in Singapore Chinese children, a population with a known high prevalence rate of myopia at an early age. Design: Cross-sectional study. Participants: Children aged 7 to 9 years (n= 1453) from three schools in Singapore. Methods: A scan biometry, cycloplegic autorefraction 을 측정. Q. of regarding number of books read per week / night lighting/parental myopia. Main Outcome Measures: AxL / vitreous chamber depth/ lens thickness/ ACD/ refraction / corneal curvature radius Results: older, male, 2권 이상의 독서 /wk, taller, 최소 한명 이상의 myopic 부모. ► the AXL - longer & vitreous chambers –deeper Anterior chambers- deeper ► in males , taller children corneal curvature - steeper ► in female, older shorter children. Conclusions: AXL, Vit. CD 의 증가 - associated with older age, male, 2권 이상의 독서 /wk , 키의 증가.부모의 myopia ACD, corneal curvature, lens thickness.. - not associated with reading , 부모의 myopia Hx These findings confirm that conventional risk factors for myopia associated the vitreous cavity, but suggest that ant. Seg. parameters (corneal curvature , lens thickness) may be subject to unrelated postnatal growth control mechanisms. early age 때 myopia의 prevalence rate 이 높다고 알려진 Singapore Chinese children 에서 ocular biometry parameters 에 영향을 주는 risk factor 를 알아보기 위한 .