Myopia Research. Primary Care Treatment of Myopia 10/30/11. Prevalence. An Evidence-Based Approach. Mitchell Scheiman, OD

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1 Primary Care Treatment of Myopia An Evidence-Based Approach Mitchell Scheiman, OD 1 Myopia Research Prevalence US: 33% of individuals over the age of 12 years Taiwan, Honk Kong, Singapore: 60% to 80% High myopia (6D or >) associated with potential ocular disease and visual impairment Vitale S, Ellwein L, Cotch MF, Ferris FL III, Sperduto R. Prevalence of refractive error in the United States, Arch Ophthalmol 2008;126:

2 Myopia: Public Health Problem Predisposing factor for: Retinal detachment Myopic retinopathy Glaucoma May cause visual impairment Important to finding effective treatments that slow myopia progression and axial elongation 4 Why Does Myopia Progress? Excessive accommodation Near point stress Under accommodation Blur hypothesis Eye Shape Genetic factors Number of myopic parents Current Treatments Current Treatments Single vision lenses Contact lenses Refractive surgery Do not slow eye growth Do not retard physiological changes associated with excessive axial elongation 6 2

3 Lens Interventions to Slow Myopia Progression 7 Review of Study and their Implications for Clinical Practice Gwiazda J, Hyman L, Hussein M, Everett D, Norton TT, Kurtz D, Leske MC, Manny R, Marsh-Tootle W, Scheiman M., A randomized clinical trial of progressive addition lenses versus single vision lenses on the progression of myopia in children. Invest Ophthalmol Vis Sci Apr;44(4): STUDY DESIGN Randomized clinical trial Multicenter (4 centers) University of Alabama University of Houston New England College of Optometry Pennsylvania College of Optometry Double-masked Children/parents Optometrists 3

4 PRIMARY AIM To evaluate whether PAL's (Varilux Comfort, addition) slow the rate of juvenile- onset myopia vs single vision lenses (SVL) Progression is measured by cycloplegic autorefraction Axial length (A-scan ultrasonography) INCLUSION CRITERIA Ages 6-11 years at baseline Myopic spherical equivalent (SE) between D and D inclusive, in both eyes Astigmatism < 1.50 D Anisometropia < 1.0 D FOLLOW-UP VISITS Every six months for 3 years 4

5 Results Adjusted 3- Year Difference in Myopia Progression Between PAL and SVL Groups Ethnicity Difference (D) (PAL SVL) Asian 0.39 Afr.-American 0.31 Hispanic White 0.22 Mixed 0.14 OVERALL 0.20 COMET RESULTS Use of PAL s slowed the progression of myopia in COMET children by a small, statistically significant amount The effect was observed in the first year The size of the treatment effect remained similar and significant for the next 2 years 5

6 COMET RESULTS Larger treatment effect of PAL s in children with Lower vs higher baseline accommodative response at near Lower vs higher baseline myopia Results for axial length were similar to those for refractive error COMET RESULTS Secondary analysis: Children with larger accommodative lags and esophoria (N) using SVLs had the most progression at 3 years PALs slowed progression in this group by 0.64D COMET RESULTS This finding basis for COMET2 (PEDIG) Study has ended results to be published soon. 6

7 COMET RESULTS Also found that greater treatment effect for PALs with children: With closer reading distances Spending more time with near tasks had greater progression COMET RESULTS Ancillary COMET study also looked at the association between parental myopia and the progression of myopia Number of myopic parents was directly related to myopia progression among children wearing SVLs No myopic progressed: 1.80 D One myopic parent 2.00 D Two myopic parents 2.60 D In the PAL group, progression was not significantly related to the number of myopic parents and was about D overall Kurtz D, Hyman L, Gwiazda JE, et al. and COMET Group.Role of parental myopia in the progression of myopia and its interaction with treatment in COMET children. Invest Ophthalmol Vis Sci Feb;48(2): COMET RESULTS The number of myopic parents is a statistically significant risk factor for myopia progression in COMET children wearing SVLs PALs significantly reduced progression in children with 2 myopic parents 7

8 CONCLUSIONS The small magnitude of the treatment effect does not warrant a change in clinical practice COMET Guidelines for Treatment of Myopia PALs may slow the progression of myopia in subgroups of myopic children: Large accommodative lags in conjunction with near esophoria Lower amounts of myopia Close reading distance Children who spend more hours per week engaged in near work COMET Guidelines for Treatment of Myopia Important for optometrists to counsel families about risk factors: High accommodative lag/esophoria at near Close reading distances Spending considerable time engaged in near visual activities 2 myopic parents 8

9 COMET Guidelines for Treatment of Myopia PALs might be considered in the following situations: High lag of accommodation and esophoria at near Low amounts of myopia (less than 2.00 D) Child who holds reading material very close Child who spends a great deal of time engaged in near activities such as reading and computer use Child with two myopic parents Other Lens Intervention Study Hasebe, et al. Effect of progressive addition lenses on myopia progression in Japanese Children: A prospective, randomized, double-masked, crossover trial. IOVS 2008;49: Study Design 92 children 6-12 years -1.25D to -6D Randomized to 18 months of: PALs followed by SVLs SVLs followed by PALs Outcome measure Cycloplegic autorefraction 27 9

10 Results 18 month treatment effect of only 0.17D ± 0.05D. Not clinically meaningful Problem: Under corrected myopia by 0.75D 28 Results As in COMET: Children with larger accommodative lags had a larger treatment effect than those with smaller lags (0.61 vs D) Children who were esophoric or orthophoric at near had a larger treatment effect than those who were more exophoric (0.55 vs D). 29 Clinical Implications Similar to COMET (also small magnitude treatment effect) Does not support the long-term use of PALs for slowing the progression of myopia in all myopic patients 30 10

11 Latest Lens Intervention Study Cheng, D, Schmid,KL, Woo G, Drobe, B. Randomized Trial of Effect of Bifocal and Prismatic Bifocal Spectacles on Myopic Progression: Two- Year Results. Arch Ophthalmol. 2010;128(1): Study Design RCT of 135 myopic, Chinese Canadian children Myopia of 1.00 D with myopic progression of at least 0.50 D in the preceding year 32 Study Design Randomly assigned to: Single-vision lenses +1.50D ADD (executive bifocals) +1.50D ADD (executive bifocals) with 3 BI prism diopters at near Main Outcome measures (24 months): Cycloplegic auto refraction Axial length at 6-month intervals for 24 months 33 11

12 Results 97% completed the trial after 24 months Myopic progression averaged SVL: 1.55 D Bifocals: 0.96 D Bifocals and BI: 0.70D Axial length increased SVL: 0.62 mm Bifocals: 0.41 mm Bifocals and BI: 0.41mm 34 Results The treatment effect of bifocals (0.59 D) and prismatic bifocals (0.85 D) was significant (P.001) and both bifocal groups had less axial elongation (0.21 mm) than the single vision lens group (P.001). 35 Conclusions Bifocal lenses can moderately slow myopic progression in children with high rates of progression after 24 months Bifocal spectacles may be considered for slowing myopic progression in children with an annual progression rate of at least 0.50 D 36 12

13 Conclusions Authors: In our opinion, treatment effect of bifocal and prismatic bifocal lenses of 38% and 55%, is only modest effect Whether or not the effect tapers off will decide clinical significance. If treatment effects continued over time Could have a significant role in preventing the development of very high pathologic myopia 37 Conclusions Even benefit of 1-D myopia reduction could be useful. Therefore, the long-term effect of the treatment needs to be more rigorously analyzed. At the current stage, bifocal spectacles, as a myopia-control treatment, should be offered to myopic children with caution in clinical practice. Modest benefit of bifocals weighed against factors like: Increased cost of the lenses Cosmetic appearance 38 Pharmaceutical Agents Atropine Pirenzepine 39 13

14 ATROPINE 40 Atropine Study Shih (Taiwan) children 6 to 13 years old 3 treatment groups 0.5% atropine with multi-focals Multi-focals Single vision lenses Followed 18 months Shih YF, Hsiao CK, Chen CJ, Chang CW, Hung PT, Lin LL. An intervention trial on efficacy of atropine and multi-focal glasses in controlling myopic progression. Acta Ophthalmol Scand 2001;79:233-6 Atropine Study Shih (Taiwan) 18 months examination Atropine group: 0.41 D increase Multi-focal group: 1.19 D increase Single Vision Group: 1.40 D increase No progression of myopia 50% of atropine group <10% of multi-focal group <10% of single vision group 14

15 Atropine Study: Chua, et al. 2-year study of 400, 6- to 12-year-old myopic children in Singapore Different experimental paradigm Children randomly assigned to: Atropine With only one eye of each child treated with either 1% atropine or vehicle eye drops once nightly. Placebo-control group Chua WH, Balakrishnan V, Chan YH, Tong L, Ling Y, Quah BL, Tan D. Atropine for the treatment of childhood myopia. Ophthalmology 2006;113: Atropine Study: Chua, et al. Two-year progression in the atropine-treated eyes was found to be D, significantly less than progression in the control eyes (-1.20 D) Myopia progression in untreated eyes of both groups was similar to that of the control eyes 44 Conclusions This outcome meant that many children in the atropine group were anisometropic at the end of the study Study did not report follow-up data to indicate whether a rebound effect might have occurred Increased progression in the atropinetreated eyes after cessation of treatment 45 15

16 Cessation of Atropine Rebound effect? Amplitude of Accommodation? 46 Myopic Progression after Cessation of Atropine 400 Children 6-12 years old Myopia -1D to -6D Astigmatism 1.50D or less Tong, L et al. Atropine for the treatment of childhood myopia: Effect on myopia progression after cessation of atropine. Ophthalmol 2009; 116: Methods No intervention Subjects followed for up to 12 months after stopping 2 years of treatment in only 1 eye: 1% atropine Placebo drops 48 16

17 Myopia Progression After 12 Months of FU Atropine group -1.14D Placebo Group -0.38D P< Results After 3 Years 2 years of Tx, 1 Year FU Atropine group -4.29D Placebo Group -5.22D Amplitude of accommodation and near visual acuity returned to normal levels after cessation of atropine 50 Conclusions Higher rates of myopia progression after cessation of treatment Rebound effect Absolute myopia progression after 3 years significantly lower in atropine group compared to placebo group 51 17

18 Conclusions Not known whether rate of progression will plateau or continue unabated resulting in the myopia catching up with the control eyes 52 Atropine: Long Term Safety? Long term effects unknown Cataract formation? Retinal toxicity? Conclusions Atropine does slow progression of myopia Need more information about rebound effect 18

19 How does Atropine Work? By minimizing accommodative effort? Direct effects on sclera/retina? Animals studies show that muscarinic agents block axial elongation in chickens by acting on non-accommodative mechanisms 55 Conclusions Atropine used in many countries in Asia for slowing the progression of myopia Rarely used in the United States for this purpose Side effects associated with atropine (e.g., photophobia, cycloplegia) are considered by many clinicians to be unacceptable for long-term therapy 56 Pirenzepine 57 19

20 Background Pirenzepine, like atropine, is a muscarinic antagonist Less likely to produce mydriasis and cycloplegia Two clinical trials of pirenzepine have been conducted 1. Singapore/Hong Kong/Thailand 2. United States 58 US Pirenzepine Study Efficacy of 2% Pirenzepine Ophthalmic Gel in Myopic Children Two-year multicenter, randomized, double-masked, placebo-controlled, parallel safety and efficacy study of 2% pirenzepine ophthalmic gel in children with myopia., Siatkowski RM, Cotter SA, Crockett, RS, et al, U.S. Pirenzepine Study Group. J AAPOS Aug;12(4): Major Eligibility Criteria Healthy child, 8-12 years Myopia 0.75 to 4.00 D (SEQ) Astigmatism /anisometropia 1.00D BVA far and near 20

21 Conclusions 0.25 myopia reduction over 1 yr in healthy 8-12 yr children with moderate myopia Clinically significant? No safety concerns 2-Year Data Shows an increase in the size of the treatment effect from 0.30 to 0.41 between 1 and 2 years 62 Conclusion These results must be interpreted with caution since the study was designed as a 1-year study and only 84 of the originally enrolled 174 subjects (48%) agreed to continue for a second year 63 21

22 Singapore Study Myopia in children increased over a 1- year period by: 0.47 D for those using pirenzepine ophthalmic gel twice a day 0.70 D for those using it once a day 0.84 D for the control group Tan DT, Lam DS, Chua WH, Shu-Ping DF, Crockett RS. One-year multicenter, double-masked, placebo-controlled, parallel safety and efficacy study of 2% 64 pirenzepine ophthalmic gel in children with myopia. Ophthalmology 2005;112:84-91 Contact Lenses and Myopia Control Contact Lens and Myopia Progression Study CLAMP Study 116 subjects RGPs SCLs A randomized trial of the effects of rigid contact lenses on myopia progression. Walline JJ, Jones LA, Mutti DO, Zadnik K. Arch Ophthalmol Dec;122(12):

23 Results Corneal curvature steepened significantly less over 3 years in RGP group (0.62 ± 0.60 D) compared to soft lens group (0.88 ± 0.57 D, p = 0.01) 3-year axial elongation not significantly different between treatment groups 67 Summary Results suggest that the slowed myopia progression was mainly due to corneal flattening May be reversible with discontinuation of RGP lens wear No differences in axial elongation Most of the treatment effect occurring in the first year 68 Conclusions Authors concluded that RGP lenses should not be prescribed mainly for myopia control 69 23

24 SCLs/Myopia Progression Anecdotal reports and evidence from pilot studies have suggested that the use of soft contact lenses speeds up myopia progression Fulk GW, Cyert LA, Parker DE, West RW. The effect of changing from glasses to soft contact lenses on myopia progression in adolescents. Ophthalmic Physiol Opt 2003;23: SCLs/Myopia Progression RCT investigating effect of soft contact lenses on myopia progression in children reported no significant difference in progression between soft contact lens and spectacle wearers Walline JJ, Jones LA, Sinnott L, Manny RE, Gaume A, Rah MJ, Chitkara M, Lyons S. A randomized trial of the effect of soft contact lenses on myopia progression in children. Invest Ophthalmol Vis Sci 2008;49: Orthokeratology Corneal Refractive Therapy 72 24

25 Orthokeratology Corneal refractive therapy Limited quality research Need randomized clinical trial Possible problems Increasing number of reports of microbial keratitis associated with overnight wear of Ortho-k lenses LORIC (Cho) 35 children wore ortho-k lenses for 2 years Results compared to those from an historical control group of children wearing SVLs Cho, et al. Curr Eye Res The longitudinal orthokeratology research in children (LORIC) in Hong Kong: a pilot study on refractive changes and myopic control LORIC Reduction of 2.09D in ortho-k group 25

26 LORIC - Results Change in axial length rather than refractive error typically used as outcome measure Because of corneal flattening produced by the lenses Over 2-year period axial length in the orthokeratology group increased by 0.29 mm vs mm for the control group (significant difference) 76 Conclusions Well-designed study required Sufficient subject numbers Random assignment 77 Undercorrection of Myopia? Is this an effective approach for myopia control? 26

27 Studies Chung (Vis Res 2002) Adler (Clin Exp Optom 2006) 48 children 6 to 15 years Randomized to undercorrection (+0.50) or full correction Examined at 6, 12 and 18 months Undercorrection of myopia enhances rather than inhibits myopia progression. Chung K, Mohidin N, O'Leary DJ. Vision Res Oct; 42(22): Chung 94/ 106 (89%) myopic children aged 9 to 14 years completed 2 years of spectacle wear in SVLs ½ randomized to full correction ½ to under-correction ~ 0.75 D Chung Two-year progression in the fully corrected group was 0.77 D Significantly less than the 1.0 D in the under-corrected group (p < 0.01) 81 27

28 Adler 2006 Adler 48 children 6 to 15 years Randomized to undercorrection (+0.50) or full correction Examined at 6, 12 and 18 months The possible effect of undercorrection on myopic progression in children. Adler D, Millodot M. Clin Exp Optom Sep;89(5): Adler - Results Statistically significant INCREASE in myopic progression in undercorrected group (0.17D) Near phoria does not affect the results 83 Conclusion Evidence does not support the undercorrection of myopia to slow the progression of myopia 28

29 Other Factors Parental Myopia Outdoor Activity Near activity Urban environment 85 COMET: Parental Myopia 5-year progression for children with 0, 1, or 2 myopic parents for both treatment groups (PAL or SVL) Role of parental myopia in the progression of myopia and its interaction with treatment in COMET children., Kurtz D, Hyman L, Gwiazda JE, Manny R, Dong LM, Wang Y, Scheiman M; COMET Group., Invest Ophthalmol Vis Sci Feb;48(2): Single Vision Group # Myopic parents Mean Progression D D D 29

30 PAL Group # Myopic parents Mean Progression D D D Treatment Effect Subgroup with two myopic parents Five-year progression was 0.59 diopters less among children wearing PALs than among those wearing SVL Conclusions # of myopic parents is a statistically significant risk factor for myopia progression in children wearing SVL # of myopic parents is predictive of treatment effect of PALs versus SVLs 30

31 Effect of Parental Hx of Myopia on Children s Eye Size Children 5 to 16 years of age tested twice: baseline and 1 year later VA Cycloplegic autorefraction Axial length Parental history Lam, D, et al. The effect of parental history of myopia on children s eye size and growth. Invest Ophthalmol Vis Sci 2008;49: Results 4468 children examined twice Eye growth and myopic shift occurred more rapidly in children with stronger parental Hx (P<0.001) #$ of Parents with Myopia Increase in Axial Length Myopia Progression mm 0.22D mm 0.07D mm 0.02 D 92 Conclusions Parental Hx of myopia influences the growth rate of the eye 93 31

32 Outdoor Activity and Myopia Progression Rose, et al. Outdoor activity reduces the prevalence of myopia in children. Ophthalmol 2008;115: Study Design 1765, 6 year olds 2367, 12 year olds Examination Questionnaire Questions about: Near activities Mid-working distance Outdoor activities 95 Questionnaire Questions about: Near activities Drawing, homework, reading, handheld computer Mid-working distance Television, videogames, computer use Outdoor activities Playing outdoors, picnics, bicycle riding, bushwalking, outdoor sports 96 32

33 Results Average amount of time outdoors 2.35 hours per day Greater # of hours spent outdoors associated with less myopia Highly significant P< No significant influence of near work on refractive status 97 Impact of Outdoor Activities Substitution effect? More outdoor activity means less time for near work? Did not find this relationship Does not appear to be sports or physical activity Light Intensity? 98 Light Intensity 99 33

34 Light Intensity Light intensities higher outdoors Hypothesis 1: Pupils more constricted outdoors Would result in greater depth of field and less image blur Hypothesis 2: Dopamine acts as inhibitor of eye growth Dopamine release from retina known to be stimulated by light 100 Light Intensity Neither hypothesis has been tested 101 Clinical Implications Protective effect of time spent outdoors ODs should suggests increasing outdoor activity

35 Role of Near Work in Myopia Ip, J et al. Role of near work in myopia: Findings in a sample of Australian school children. Invest Ophthalmol Vis Sci 2008;49: Introduction Near work has been considered a risk factor for development of myopia Association of myopia with educational performance Association with close-work occupations 104 Why Would Near Work be a Factor? Older theory Increased accommodation Limited data to support this theory New theory Under accommodation Better research

36 Purpose Evaluate associations of myopia with near work Particular attention to variables such as: Duration of reading Type of reading activity Reading habits 106 Methods 65-item questionnaire that included information about near-work factors filled out by subjects 2353 children in study 107 Results In the children with: 2 myopic parents Parents reported close reading distances, the mean SER was 2.58 D In the children without myopic parents and no reported close reading distance, the mean SER was 0.65 D

37 Results Time spent in continuous reading (30 minutes) and parental reports of close reading distance (30cm) were associated with greater odds of myopia after adjustment for age, sex, ethnicity, school type, parental myopia, and outdoor activity 109 Discussion Behavioral Aspect of Reading Amount of reading not as important as close working distance In addition, continuous reading may be important 110 Clinical Implications Identification of close reading distance and continuous reading as possible risk factors for myopia in this study may have important public health significance Encourage children to read with the book at a further distance, and to take breaks between periods of continuous reading

38 Myopia and Urban Environment Ip, J, et al. Myopia and the urban environment: Findings in a sample of 12-yearold Australian school children. Invest Ophthalmol 2008;49: Introduction Geographic location may be important for childhood myopia Higher myopia prevalence reported in urban compared with rural areas Impact of urbanization, however, specifically reported in only one retrospective study 113 Purpose Evaluate impact of urbanization by examining association of childhood myopia with factors such as: Area of residence Type of residential housing Housing density In sample of school children living in different urban environments but attending the same schools

39 Methods 2367 children Parents completed 173-item questionnaire that collected detailed sociodemographic data Sydney divided into 5 different regions 115 Results Findings suggest that the children living in regions with higher population density were significantly more likely to have myopia Apartment-style housing was also significantly associated with myopia 116 Discussion Myopia on the rise in urbanized parts of the world Evidence supports hypothesis that certain features of the urban environment may influence the development of myopia in childhood Further work needed to characterize which aspects of urban living contribute to myopia 39

40 Clinical Implications Educate parents about risk factors 118 Summary of Myopia Research 119 Summary of Studies Study Tx Leung 1999 PAL vs SVL Leung 1999 PAL vs SVL Fulk Bifocal vs SVL Gwiazda 2003 PAL vs SVL Walline 2004 RGP vs SCL Shih 2001 Atropine vs multifocal Tan 2005 Pirenzepine vs placebo Siatkowski 2004 Pirenzepine vs placebo Cheng 2010 Bifocal, Bifocal with BI 0.59, 0.85 (BI) 40

41 Myopia Studies: Summary Atropine Significant reduction in progression Side effects/safety concerns? Pirenzepine Moderate effect Not available in USA Contact lenses No significant benefit Bifocals/Progressive lenses No significant benefit, except perhaps with high lag,and near esophoria Orthokeratology More research required Undercorrection No evidence to support its use Parental Myopia Significant relationship Outdoor activities Significant relationship Vision Therapy 121 Lack of quality research Myopia Tx: Issues to Consider Many statistically significant differences between experimental and control treatments for slowing the progression of myopia Most not considered clinically meaningful 122 Myopia Tx: Issues to Consider In part because many of the treatments are effective early on After initial months treatment effects may increase only minimally or not at all

42 Myopia Tx: Issues to Consider Possible solutions: Switching from one treatment to another when the first one no longer slows myopia progression Combining treatments Introducing periods of time (hours, days, or weeks) without any treatment 124 Myopia Tx: Issues to Consider Inclusion criteria for clinical trials typically are quite broad All treatments, especially lenses, are not likely to work for all myopes 125 Clinical Implications 42

43 Guidelines for Treatment of Myopia Educate parents Myopia with esophoria and poor accommodative response Treat with progressive lenses Two myopic parents, early onset of myopia Consider PALs Concern about very high myopia (history, early onset, rapid progression) Consider Atropine Educate about importance of outdoor activities/sports Patients with myopia and accommodative/binocular vision disorders Treat underlying problems Hope for slowing of myopia progression Other myopes Single vision lenses