Myopia: Professor Chris Hammond St Thomas Hospital, London Dept Twin Research & Genetic Epidemiology

Transcription

1 Myopia: Cause and Cure Professor Chris Hammond St Thomas Hospital, London Dept Twin Research & Genetic Epidemiology

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3 Common! Cost Complications Why study myopia? Retinal detachment Myopic maculopathy Glaucoma Cataract

4 Click Myopic to edit Maculopathy Master title style Vogphanit et al >-1 D (control) -1 to -3 D -3 to -5 D -5 to -7 D -7 to -9 D <= -9D Flitcroft DI. Prog Ret Eye Res. Nov 2012; 31: /3/2014 4

5 Click Retinal to edit Detachment Master title style Ogawa & Tanaka >-1 D (control) -1 to -3 D -3 to -5 D -5 to -7 D -7 to -9 D <= -9D Eye Disease Control Study >-1 D (control) -1 to -3 D -3 to -8 D Flitcroft DI. Prog Ret Eye Res. Nov 2012; 31: /3/2014 5

6 The epidemiology of myopia increasing rapidly in some areas varies between populations associated with urbanisation, education and IQ... outdoor activity is protective

7 Click to edit Taiwan Master title style appears to be increasing Lin LL. Ann Acad Med Singapore. 2004;33: /3/2014 7

8 Click to USA edit NHANES Master title style Vitale, S. et al. Arch Ophthalmol 2009;127: /3/2014 8

9 E 3 Consortium 33 studies Epidemiological cohorts Case-control studies Up to 124,000 participants Myopia Prevalence 15 studies, 61,000 participants meta-analysis: 24.3% (95% CI ) age-standardised European prevalence: 30.6%( )

10 Click Age and to edit Myopia Master Prevalence title style Williams KM et al, in review 11/3/

11 Click to Cohort edit Master Effect? title style 11/3/

12 Cohort effect

13 Effect of Education 15% higher education born pre 1940 compared to 32% born after 1940 Does this explain increased myopia prevalence? Williams KM et al, in review

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15 varies between populations Morgan I. Prog Retin Eye Res. 2005;24:1-38

16 Outdoor activity Rose KA et al, Ophthalmology 2008:

17 Outdoor Activity Chinese children age 6-7 Myopia: 3.3% Sydney, 29.7% Singapore Similar parental myopia (70%) Similar reading amounts Outdoor activity: 13.7 hrs a week cf 3.1 Rose KA et al, Arch Ophth 2008; 126:

18 The population distribution of Click to edit Master title style refractive error: a complex trait Spherical Equivalent (Dioptres) Twin studies: refractive error 80% heritable 11/3/

19 Genome-Wide Association Studies Single Nucleotide Polymorphism (SNP): marker of genetic variation in DNA Gene 19

20 GWAS: all the rage!

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24 CREAM international meta-analysis Verhoeven et al, Nature Genetics 2013

25 26 loci Neurotransmission: GRIA4, GJD2, RASGRF1 Ion Transport: KCNQ5, CD55, CHNRG Retinoic acid: RDH5, RORB, CYP26A1 ECM remodelling LAMA2, BMP2 Eye development: SIX4, PRSS56, CHD7 Loci explain 3-4% of variation

26 23andWe myopia GWAS have you been diagnosed with nearsightedness approximately what age were you diagnosed? 26,000 myopes, 17,000 non-myopes

27 23andMe GWAS Kiefer et al, PLoS Genetics 2013

28 Click CREAM to edit Master vs 23andMe title style 11/3/2014 Wojciechowski R & Hysi PG. PLoS Genet

29 What have GWAS taught us? Myopia is not AMD! Many genes of small effect Analogous to height: 40 SNPs, 5% of variation Size is important! Large meta-analyses finding same results Still unexplained heritability Is this useful for personal prediction?

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31 Click to edit Master title style Who to treat? 11/3/

32 Myopia Progression fastest in... The earlier the onset Myopia before age 8 = -6D by adulthood Children with myopic parents Most significant risk factor of all Children who have high IQ, school achievement, read lots, less time outdoors.. NB significant proportion of myopia is adultonset

33 How fast do myopes progress? control SVL arms in RCTs Deng L et al, ARVO 2012

34 Principles of treatments Close work theory Accommodation must be bad Accommodation lag in myopes Animal models Muscarinic antagonists (eg atropine) work in animal models Peripheral retina Monkey ablation experiments Myopes prolate cf oblate eyes built up environment causes hyperopic defocus Light

35 Principles of treatments Close work theory UNDERCORRECT/BIFOCALS/PALS Accommodation must be bad Accommodation lag in myopes Animal models Muscarinic antagonists (eg atropine) work in animal models Peripheral retina Monkey ablation experiments Myopes prolate cf oblate eyes built up environment causes hyperopic defocus Light

36 Undercorrect or fully correct? 94 Malaysian myopes 9-14 years randomised to full or undercorrection (+0.75D, to 6/12) Stopped 2 years cf 3: faster progression in undercorrected Chung K et al. Vision Res 2002;42:2555-9

37 Progressive add lenses Hong Kong Progressive Lens Myopia Control Study 138 PAL, 160 SVL for 2 years (ages 7-10) Progression SVL, PAL Edwards MH et al. IOVS 2002; 43: Correction of Myopia Evaluation Trial (COMET) 469 USA myopes (ages 6-11) Progression 1.48 SVL, PAL Gwiazda J et al. IOVS 2003;44:

38 Overall Myopia Progression: All PALs, Bifocals, Multifocals

39 Principles of treatments Close work theory BIFOCALS/PALS Accommodation must be bad Accommodation lag in myopes Animal models ATROPINE/PIRENZEPINE Muscarinic antagonists (eg atropine) work in animal models Peripheral retina Monkey ablation experiments Myopes prolate cf oblate eyes built up environment causes hyperopic defocus Light

40 Click to edit Atropine Master title style ATOM Study 200 children randomized to atropine one eye or placebo 2 yr study <0.5D progression: 66% atropine, 16% placebo Myopia progression difference 0.92D (76%) No side effects reported Chua WH et al, Ophthalmology 2006; 113: /3/

41 Atropine ctd... BUT one year post-cessation Progression -1.1D atropine eyes, -0.39D placebo?related to cycloplegia Overall progression -0.95D versus -1.58D Dilute Atropine Atropine 0.5% -0.30±0.60 Atropine 0.1% -0.38±0.60 Atropine 0.01% -0.49±0.63 Tong L et al, Ophthalmology 2009; 116: Chia A et al, Ophthalmology 2012; 119:

42 Pirenzepine Relatively selective M1-muscarinic antagonist Asia trial: 353 children 6-12 years Baseline mean 2.3D Progression 0.47D PIR b.d., PIR od, placebo Tan DT et al Ophthalmology 2005; 112: USA trial: 174 children 8-12 years Baseline mean 2.10D Progression 0.26D PIR bd, -0.53D placebo Siatkowski et al Arch Ophth 2004; 122:

43 Overall Myopia Progression: Pharmaceutical Agents

44 Principles of treatments Close work theory BIFOCALS/PALS/DENMARK(!) Accommodation must be bad Accommodation lag in myopes Animal models ATROPINE/PIRENZEPINE Muscarinic antagonists (eg atropine) work in animal models Peripheral retina CL/VFCL/ORTHO-K Monkey ablation experiments Myopes prolate cf oblate eyes built up environment causes hyperopic defocus Light

45 Rigid Contact Lens CLAMP study 116 children randomized to RGP vs SCL 3-year follow-up Progression -1.56D RGP, -2.19D SCL Zadnik et al. Arch Ophth 2004; 122:

46 Overall Myopia Progression: Contact Lenses

47 Click to Varifocal edit Master CLs title style Sankaridurg et al, IOVS 2011;12: /3/

48 Overall Myopia Progression: Novel Lenses

49 Overall Axial Length Progression: Non-randomized Ortho-K Studies

50 Click to Orthokeratology edit Master title style 11/3/2014 Cho P. Invest Ophthalmol Vis Sci. 2012;53:

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52 Principles of treatments Close work theory BIFOCALS/PALS/DENMARK(!) Accommodation must be bad Accommodation lag in myopes Animal models ATROPINE/PIRENZEPINE Muscarinic antagonists (eg atropine) work in animal models Peripheral retina VFCL/ORTHO-K Monkey ablation experiments Myopes prolate cf oblate eyes built up environment causes hyperopic defocus Light GOAL STUDY/CLASSROOM

53 GOAL Study 1 hour/day extra outdoors after school Some reduction in myopia incidence Awaiting final results

54 Conclusions Myopia is becoming more common Probably multifactorial: earlier education, lack of outdoor activity, urbanisation Genetics identifying new pathways Hopefully new treatments in future No proven highly effective treatments Atropine (but side-effects) best Ortho-K interesting Combination? (eg dilute atropine and VFCL) Send the children out to play!

55 Click Acknowledgements to edit Master title style Guide Dogs for the Blind Association National Institutes of Health, USA 11/3/