Myopia Control from Evidence to Implementation

Transcription

1 Myopia Control from Evidence to Implementation Mark A. Bullimore, MCOptom, PhD, FAAO Earl Smith III, OD, PhD, FAAO Alan N. Glazier, OD Please silence all mobile devices and remove items from chairs so others can sit. Unauthorized recording of this session is prohibited.

2 Observations Relevant to Treatment Strategies for Myopia Earl L. Smith III, O.D., Ph.D. College of Optometry, University of Houston Conflicts of Interest: Patents related to anti-myopia lens designs Consultant for Treehouse Eyes and SightGlass Vision, Inc. Research Support: Supported by funds from NIH grants NEI & NEI 07551, the Brien Holden Vision Institute, and the UH Foundation.

3 Why Worry About Myopia? Myopia is very common. The prevalence and severity of myopia is increasing. Myopia reduce the quality of life Myopia has a substantial economic burden. Myopia can reduce the quality of life, interfere with learning, and limit career choices.

4 Ocular Sequelae of Myopia Posterior Subcapsular Cataract Idiopathic Retinal Detachment Myopic Macular Degeneration Open-Angle Glaucoma (Curtin, 1985) Myopia is a leading cause of permanent blindness. The prevalence and risk of pathology increase with both the degree of myopia and axial elongation. Relative risk of ocular pathology associated with myopia. Jones et al, 2019

5 Refractive development is guided by optical defocus. Effects of Imposed Defocus D Ametropia (D) D Expected Ametropia +3.0 D 0.0 D -3.0 D -6.0 D Age (days)

6 Refractive Development is Regulated by Local Retinal Mechanisms. Full-Field Diffuser Clear Lens Nasal-Field Diffuser Clear Lens Ametropia (D) Temporal Field Nasal Field Fellow Eye Treated -6 Eye Temporal Field Nasal Field Eccentricity (deg)

7 Local Retinal Mechanisms Full-Field vs. Nasal-Field FD

8 Visual signals from the fovea are not essential for vision-dependent refractive development. Unrestricted Vision Diffuser -3.0 D lenses Laser Normal Emmetropization Form-Deprivation Myopia Lens Compensation Ametropia (D)

9 Peripheral Visual Signals Can Dominate Central Refractive Development Lens or Diffuser Deprived / Defocused deg (4 8 mm aperture) Unrestricted Entrance pupil Deprived / Defocused 8 Peripheral FD 8 Hyperopic Defocus 8 Myopic Defocus Ametropia (D) Controls FD Periphery Controls -3D Full Field -3D Periphery Controls +3D Full Field +3D Periphery

10 Simultaneous Competing Defocus

11 Simultaneous Competing Defocus Vision Through a Concentric Bifocal

12 Effects of Simultaneous Defocus Tse et al Dual-Focus Lenses Lens Powers: +3 D / plano (n=7) and -3 D / plano (n=7) These Fresnel lenses produce two distinct focal planes across the visual field.

13 Myopic Defocus vs Unrestricted Vision +3 D / Plano Lenses (50 : 50 area ratio) Longitudinal Refractive Error End of Treatment 8 8 Ametropia (D) Age (days) Normals +3 D Full Field +3D / Pl Refractive development was dominated by the positive-powered portion of the lens.

14 Dual Focus Lenses Effects of Varying Surface Areas 0.4 mm Dual-focus lenses produce two distinct focal planes simultaneously across the visual field. The relative strengths of the image planes reflect the relative surface areas devoted to the two power zones.

15 Dual Focus Lenses Effects of Varying Surface Areas +3 Pl 6 Ametropia (D) Plano lens single vision 0 Controls "18:82" "25:75" "33:66" "50:50" FF +3D Area Ratio (+3:pl) Even when the positive portion of the lens is 4.5 times smaller than the plano portion, the eye develops hyperopia.

16 6 Ametropia (D) 4 2 FF +3D % -3D 50% -3D Controls FF -3D % +3D 100% +3D Area Devoted to Powered Component In primates, the mechanism regulating ocular growth does not appear to average the defocus signals produced by dual-focus lenses.

17 Optical Interventions Animal models tell us: 1) that ocular growth and the refractive state of the eye are regulated by defocus. Hyperopic defocus accelerates axial growth; myopic defocus can reduce axial growth. 2) peripheral vision, probably as a result of spatial summation, can dominate central refractive development. Optical treatment strategies for myopia that take into account the periphery are more likely to be successful.

18 The visiondependent mechanisms that regulate eye growth are located entirely within the eye, operate in a regionally selective manner, and function independently of the rest of the nervous system. Emmetropization Cascade

19 Outdoor Activities Reduce the Risk of Becoming Myopic. Jones et al., 2007 One of the most powerful and potentially significant epidemiologic observations. Replicated in multiple locations around the planet.

20 Why does time outdoors reduce the risk for myopia? Ambient Lighting Levels are much higher outdoors. Outdoors Overcast day Outside Shade Direct Sunlight Office for Detailed Work Indoors Public Areas Normal Office Work Areas Illuminance (lux)

21 High Ambient Lighting & FDM in Monkeys Longitudinal Anisometropia 4 Normal Lighting ~ 350 lux 4 High Ambient Lighting ~ 25,000 lux 2 2 Anisometropia (D) (treated eye - fellow eye) n = 18 n = Age (days) Age (days) Exposed to elevated lighting for 6 hours per day Smith et al., 2012 Controls ± 2 SD

22 Dopamine Antagonist & High Light Levels Form-Deprivation Myopia Chickens Ashby & Schaeffel, 2010 Dopamine antagonists block the protective effects of high ambient lighting on form-deprivation myopia.

23 High Light Levels & Hyperopic Defocus Negative Lens Compensation Chickens Control Eyes Tree Shrews Control Eyes -7 D Lens 15,000 lux -7 D Lens 500 lux -5 D Lens 200 lux -5 D Lens 15,000 lux Ashby & Schaeffel, 2010 Norton & Siegwart, 2013 High ambient light levels retard the development of lens-induced myopia in chicks and tree shrews.

24 High Light Levels & Hyperopic Defocus Lens-Induced Anisometropia (-3D) 2 Normal Lighting ~ 350 lux 2 High Ambient Lighting ~ 25,000 lux 1 Normals ± 2 SD 1 Anisometropia (D) (treated eye - fellow eye) Mean ± SD Mean ± SD Age (days) Age (days)

25 High Light Levels & Optical Defocus Interocular Differences in Vitreous Chamber Depth Infant Monkeys Reared with -3 D of Imposed Anisometropia 350 lux vs 25,000 lux High ambient lighting did not alter the rate of axial compensation for imposed defocus in infant monkeys.

26 Conclusions The FDM results suggest that the protective effects of outdoor activities against myopia in children are probably in part due to exposure to the higher light levels normally encountered in outdoor environments. The failure of elevated lighting levels to alter the time course (at least in monkeys) or end point for negative lens compensation indicates that defocus signals can override the effects of high ambient lighting.

27 Emmetropization Cascade Ambient Lighting Intensity Pupil Size

28 Why does time outdoors reduce the risk for myopia? Indoor scenes are dominated by long-wavelength light. Fluorescent Light Horizontal position (pixels) Foulds et al., 2014

29 Ambient Light: Spectral Composition Longitudinal Chromatic Aberration Because the eye s refracting power varies with wavelength, the eye s effective refractive state varies with wavelength (i.e., the defocus signal regulating eye growth varies with wavelength).

30 Spectral Composition & Emmetropization Chickens Reared for 7 Days in Quasi-Monochromatic Light Seidemann & Schaeffel, 2002 Ametropia (D) Individual Refractions Average Refractions N = 10 P < Blue 430 nm Red 615 nm Blue 430 nm Red 615 nm Variations in the spectral composition of ambient lighting can alter emmetropization (1.26 ± 0.54 D difference vs predicted 1.50 D difference based on LCA).

31 Spectral Composition & Emmetropization Guinea Pigs (Liu et al., 2011) Chickens (Fould et al., 2014) 430 nm Broad Band 477 nm 530 nm 641 nm Predicted Δ = 1.47 D Observed Δ = 4.72 D Predicted Δ = 1.18 D Observed Δ = 7.38 D The eye does not necessarily compensate for changes in refractive error produced by LCA. Progressive nature suggests that growth is unregulated.

32 Narrow-Band, Long-Wavelength Ambient Lighting Melanopsin Green cones Red cones Red LEDs Red Light Subject Groups Controls (n=7) Unrestricted Vision Blue cones Monocular FD (n=7) LP Occlusion Foil Monocular -3 D (n=6) Monocular +3 D (n=7) Red LEDs = 630 ± 20 nm (solid black line) Avg Illuminance = 480 lux.

33 Anisometropia (D) (treated eye - fellow eye) Effects of Long-Wavelength Light Anisometropias in Infant Monkeys Form Deprivation White Light D Aniso White Light Normal Mean ± 2 SD D Aniso White Light Anisometropia (D) (Treated eye - fellow eye) Form Deprivation Red Light Age (Days) D Aniso Red Light +3 D Aniso Red Light Age (Days) Normal Mean ± 2 SD Age (Days) In monkeys red ambient lighting 1) prevents form-deprivation and defocusinduced myopia and 2) augments the hyperopia produced by myopic defocus.

34 Effects of Long-Wavelength Light Changes in Absolute Refractive Errors in Control Eyes Change in Ametropia (D) Normal 25%-75% Fellow eyes white light Normal Median Fellow eyes red light Age (Days) Change in Ametropia (D) FD White Light Age (Days) D White Light +3D White Light Age (Days) Controls Red Light FD Red Light -3D Red Light +3D Red Light Age (Days) The control eyes of monkeys reared in narrow-band red ambient lighting develop progressive hyperopia.

35 Effects of Long-Wavelength Light End of Treatment Ametropias Ametropia (D) 10 A. Lens-Reared Monkeys B. Diffuser-Reared Monkeys Normals Red Controls normal median filled symbols = treated eyes open symbols = control eyes +3D-White +3D-Red -3D-White -3D-Red Normals FD-White FD-Red In monkeys red ambient lighting prevents form-deprivation myopia and defocus induced myopia, but not defocus induced hyperopia. Ametropia (D)

36 Effects of Long-Wavelength Light Axial Dimensions Choroidal Thickness Change (µm) 60 Right or Treated Eye Left or Control Eye Normal Monkeys Choroidal Thickness Red Light Controls -3D Red Light Age (days) FD Red Light +3D Red Light Age (days) Ametropia vs Vitreous Chamber/Corneal Radius Ametropia (D) RL Controls +3D-RL -3D-RL FD-RL filled symbols = treated eyes open symbols = fellow eyes VC/CR Ratio r 2 = 0.73 The hyperopic errors were associated with sustained increases in choroidal thickness and reduced vitreous chamber elongation.

37 Conclusions In non-human primates, narrow-band, longwavelength lighting resulted in progressive axial hyperopia and prevented both FDM and defocusinduced myopia. Neither blue cone signals nor melanopsin signaling is necessary to produce hyperopia or to prevent visiondependent myopia. Chromatic cues play a major role in vision-dependent emmetropization in primates. Luminance contrast signals are effective in guiding emmetropization for myopic defocus.

38 Why does red ambient lighting produce hyperopia? Longitudinal Chromatic Aberration Myopic Defocus It is possible that the eye can extract sign of defocus information by comparing excitation levels between long versus short wavelength mechanisms. Under red lighting the excitation strength for long wavelengths would be much stronger than that associated with short wavelengths.which could be misinterpreted as chronic myopic defocus.

39 Ambient Lighting Spectral Composition Emmetropization Cascade Ambient Lighting Intensity Pupil Size

40 Clinical Implications Too Many Contradictory Results In animal models, long-wavelength lighting. results in axial myopia in fish, chickens, and Guinea pigs, but axial hyperopia in tree shrew and monkeys (or no effect in monkeys; Liu et al., 2014). does not prevent vision-induced myopia in chicks, but it does in monkeys. In humans, Torii et al. (2017) claimed that violet light ( nm) suppressed myopia progression. However, Zhao et al. (2017) found that eliminating short-wavelength light had no effect on progression.

41 Why does time outdoors reduce the risk for myopia? Indoor and outdoor scenes have very different dioptric topographies. Outdoor Scene Dioptric Demand Indoor Scene Dioptric Demand Flitcroft, 2012 When an emmetrope is outdoors virtually the entire visual field is in focus, which provides a strong signal to reduce axial growth.

42 Why does time outdoors reduce the risk for myopia? Indoor and outdoor scenes have very different dioptric topographies. Charman, 2011 Dioptric demands for 100 deg field You can experience high degrees of hyperopic defocus that are irregularly distributed across the visual field.

43 Emmetropization Cascade Ambient Lighting 1) Spectral Composition 2) Intensity Pupil Size Adenosine receptors expression modulated by vision.

44 Adenosine Receptor Antagonists Caffeine and 7-methlxanthine (7-MX), a metabolite of caffeine, are non-selective adenosine receptor antagonists. 7-MX does not have the arousal effects of caffeine Common dietary sources are coffee, cacao, and chocolate. The expression of adenosine receptors in the retina, choroid and sclera is altered by form deprivation (Cui et al., 2010). Oral administration of 7-MX increases the concentration of collagen and collagen fibril diameter In the posterior sclera and reduces FDM in guinea pigs and chickens (Trier et al., 1999; Cui et al., 2011).

45 Effects of Adenosine Receptor Antagonists 6.0 Normal Monkeys Lens-Reared Controls Lens-Reared Adenosine Antagonists Ametropia (D) Normal Average 0.0 Adenosine antagonists, both oral 7-MX and topical caffeine, inhibit lensinduced myopia, enhance lens-induced hyperopia and promote hyperopia in fellow control eyes.

46 Choroid Thickness Changes Normal vs 7-mx and Caffeine Treated Monkeys 7-MX or Caffeine -3 D 7-MX or Caffeine +3 D Choroidal Thickness Change (µm) Age (days) Age (days) 7-MX Treated Eyes 7-MX Fellow Eyes Normal Monkeys Caffeine Treated Eyes Caffeine Fellow Eyes

47 Axial Nature of Ametropias End of Treatment: Treated vs Control Monkeys 10 7-MX Monkeys 10 Caffeine Monkeys 8 8 Ametropia (D) r 2 = r 2 = Caffeine monkeys Lens-reared controls VC / CR Ratio -2 Caffeine monkeys Lens-reared controls VC / CR Ratio Both eyes of the 7-MX- and caffeine-treated monkeys exhibited slower vitreous chamber elongation rates and were more hyperopic than normals and lens-reared controls

48 No Observed Ocular or Systemic Adverse Effects of 7-MX or Caffeine Pupil size (7-MX: 3.78 ± 0.42 mm; caffeine: 3.74 ± 0.22 mm vs Normals: 3.95 ± 0.53 mm) IOP (7-MX: 11.4 ± 1.6 mm Hg; caffeine: 10.4 ± 0.9 mm Hg vs Normals: 11.7 ± 2.0 mm Hg) Ocular surface abnormalities No observed changes in general behavior or health (serum caffeine levels = 154 to 249 ng/ml) OCT images show normal retinal anatomy Normal Control 7-MX treated Eye Caffeine- treated Eye

49 Conclusions In primates, the daily systemic administration of 7-MX or topical instillation of 1.4% caffeine eye drops (BID): increases choroidal thickness reduces overall axial growth rates reduces the compensating myopia normally produced by imposed hyperopic defocus promotes hyperopia in both lens-treated and fellow eyes These results suggest that adenosine receptor antagonists have therapeutic potential in efforts to slow myopia progression. The site and mechanism of action that are responsible for the reductions in axial elongation are unknown. The pattern of results suggest that components in the emmetropization cascade are involved.

50 Myopia Control: An Evidence Based Approach Mark A. Bullimore, MCOptom, PhD, FAAO

51 Disclosure Statement: Consulting and Speaking: Acucela Alcon Amorphex Apellis Carl Zeiss Meditec CooperVision Euclid Systems Eyenovia Genentech J&J Vision Novartis Tear Film Innovations Research Support: Bausch + Lomb Paragon Vision Sciences Ownership: Ridgevue Publishing Ridgevue Technologies Ridgevue Vision ridgevue.com

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53 Myopia Control Summary -19% -7% 18% 35% 42% 52% 81% Undercorrection Bifocal / PAL Pirenzepine Soft Bifocal GP Spectacles OK Atropine Slide Courtesy of Jeff Walline

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55 Weighing the Evidence Center for Evidence-Based Management:

56 Studies to be Discussed Emphasis on randomized clinical trials Some important studies used historical controls Contralateral studies not discussed Before and after studies not discussed Axial length data vs. refractive error

57 Spectacle Lenses Underminussing makes it worse Multifocals offer some benefit

58 Two Large-Scale PAL Trials Edwards et al. (2002) Single vision = 1.26 D PALs = 1.12 D Treatment effect = 11% COMET (Gwiazda et al., 2003) Single vision = 1.48 D PALs = 1.28 D Treatment effect = 13% Refractive error (D) BF SV Myopia Progression (D) BF SV Baseline 6 mo 12 mo 18 mo 24 mo Baseline 1 year 2 year 3 year Visit Visit

59 Executive Bifocals (Cheng et al., 2014) Randomized clinical trial of 135 myopic Chinese Canadian children Randomly assigned to: single-vision lenses +1.50D executive bifocals D executive with 3 Δ base-in in segment Mean 3-year progression: Single-vision = 2.06 D Bifocal = 1.25 D Prism bifocal = 1.01 D

60 Executive Bifocals (Cheng et al., 2014) Randomized clinical trial of 135 myopic Chinese Canadian children Randomly assigned to: single-vision lenses +1.50D executive bifocals D executive with 3 Δ base-in in segment Mean 3-year progression: Single-vision = 0.82 mm Bifocal = 0.57 mm Prism bifocal = 0.54 mm Treatment Effect: Bifocal = 31% Prism bifocal = 34%

61 Mechanisms of Myopia and Control 1997 Accommodative Lag Theory Under-accommodation during near work Image focused behind retina at fovea Relative hyperopia stimulates eye growth Treat with plus at near: bifocals, PALs 2017 Peripheral Refraction Theory Shorter off-axis eye length Image focused behind retina in periphery Relative hyperopia stimulates eye growth Treat with plus in periphery

62 Mechanisms of Myopia and Control 1997 Accommodative Lag Theory Under-accommodation during near work Image focused behind retina at fovea Relative hyperopia stimulates eye growth Treat with plus at near: bifocals, PALs 2017 Peripheral Refraction Theory Shorter off-axis eye length Image focused behind retina in periphery Relative hyperopia stimulates eye growth Treat with plus in periphery

63 Why Care About Peripheral Refractive Errors? Smith III (2010)

64 Why Care About Peripheral Refractive Errors? Refractive development regulated by visual feedback Fovea not essential for vision-dependent growth When conflicting signals exist peripheral signals can dominate central Peripheral optical errors can alter central refractive development Clinical studies

65 PALs vs. Executives COMET (Gwiazda et al., 2003) Single vision = 1.48 D PALs = 1.28 D Treatment effect = 13% Cheng et al. (2014) Single-vision = 2.06 D Bifocal = 1.25 D Treatment effect = 39% Myopia Progression (D) Baseline 1 year 2 year 3 year Visit BF SV

66 Putting Plus in the Periphery Corneal reshaping with ortho-k Multizone contact lenses Spectacle lens with add in all meridians

67 Putting Plus in the Periphery Corneal reshaping with ortho-k Multizone contact lenses Spectacle lens with add in all meridians

68 Contact Lenses Soft Lenses: no effect Conventional RGPs: no effect Orthokeratology: promising

69 RGP Lenses: The CLAMP Study 3 year randomized masked clinical trial 116 children aged 8-11 years randomized to RGPs or soft lenses Run-in period to limit drop-out 7%

70 Orthokeratology (Ortho-K) Temporary reduction in myopia AKA: Corneal reshaping Corneal Refractive Therapy Vision Shaping Treatment Produced by flat-fitting rigid contact lens Photo courtesy of Jeff Walline

71 Reverse-geometry lens designs Secondary curve steeper than base curve Computer-assisted videokeratography Highly gas permeable materials Potential for overnight wear Ortho-K: the Revolution

72 Who Wears Ortho-K Lenses? Frequency Age at Fitting (years) Bullimore et al. (2009)

73 Ortho-K: Myopia Control Supported by case series Ortho-k slows axial length growth Cho et al. (2005) Walline et al. (2009)

74 Myopia Control with Ortho-K (Cho et al., 2005) Corneal reshaping contact lenses = mm Spectacle wearers = mm (p = 0.01) 46% Axial Length

75 Myopia Control with Ortho-K (Walline et al., 2009) 56%

76 Myopia Control with Ortho-K (Cho and Cheung, 2012) 43%

77 43%

78 Putting Plus in the Periphery Corneal reshaping with ortho-k Multizone contact lenses Results from Brien Holden Vision Institute 34% reduction in progression of myopia relative to spectacle comparison group 33% reduction in axial elongation Spectacle lens with add in all meridians

79 Contact Lens Reducing Peripheral Hyperopia 33%

80 Multifocal Soft Contact Lenses 29%

81 Multifocal Soft Contact Lenses 31%

82 Multifocal Soft Contact Lenses 31%

83 Multifocal Soft Contact Lenses 39%

84 Multifocal Soft Contact Lenses >70%

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86 0%!0.25% 0.7" 0.6" Control" Test" Increase(in(Myopia((D)(!0.5%!0.75%!1% Control% Axial&Elonga+on&(mm)& 0.5" 0.4" 0.3" 0.2"!1.25% Test% 0.1"!1.5% 0% 12% 24% 36% Follow4Up((months)( " 0" 12" 24" 36" Follow1Up&(months)& Change in Axial Length (mm) Control Test Change in Refractive Error (D)

87 Putting Plus in the Periphery Corneal reshaping with ortho-k Contact lens with small optical zone Spectacle lens with add in all meridians

88 PALs vs. Executives COMET (Gwiazda et al., 2003) Single vision = 1.48 D PALs = 1.28 D Treatment effect = 13% Cheng et al. (2014) Single-vision = 2.06 D Bifocal = 1.25 D Treatment effect = 39% Myopia Progression (D) Baseline 1 year 2 year 3 year Visit BF SV

89 Putting Plus in the Periphery Corneal reshaping with ortho-k Contact lens with small optical zone Spectacle lens with add in all meridians Results from Brien Holden Vision Institute 15% reduction in progression compared to control group 30% reduction in younger children with at least one myopic parent

90 Spectacle Lens with Plus Periphery 15%

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92 59% 58%

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94 Pharmaceutical Approaches Beta Blockers: Ineffective Atropine: Most effective of current options Designer atropine

95 Effect of Atropine Myopia progression at 2 years in ATOM1 (N = 400) 0.28 D in 1% group 77% 1.20 D in placebo group Mean myopia progression at 2 years in ATOM2 (N = 400) 0.30 D in 0.5% group 75% 0.38 D in 0.1% group 68% 0.49 D in 0.01% group 61%

96 Effect of Atropine Concentration Chia et al. (2012)

97 Effect of Atropine Concentration

98 How Does Atropine Control Myopia? Effective in controlling experimental myopia in chicks Chicks have striated, not smooth, ciliary muscle Action on muscarinic receptors in retina Atropine is non-selective muscarinic antagonist Selective muscarinic antagonist could target M 1 receptors in retina

99 Pirenzepine Selective anti-muscarinic One-year randomized trial of 174 children

100 Pirenzepine Clinical Trial 51%

101 Pirenzepine Clinical Trial Stinging, pupil dilation and short term blurring

102 Effect of Atropine Concentration

103 Effect of Atropine Concentration Chia et al. (2012)

104 Clinical Research Pearl 1: Do the Data Agree? Spherical Equivalent Control = 1.20 D Mean myopia progression at 2 years in ATOM2 (N = 400) 0.30 D in 0.5% group 75% 0.38 D in 0.1% group 68% Axial Length Control = 0.38 mm Mean myopia progression at 2 years in ATOM2 (N = 400) 0.27 mm in 0.5% group 29% 0.28 mm in 0.1% group 25% 0.49 D in 0.01% group 61% 0.41 mm in 0.01% group WTF?

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107 Effect of Atropine Concentration

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109 Myopia Control: Why Should We Care? Disability Better surgical candidate Risk of cataract, retinal detachment, glaucoma

110 61

111 Myopia Control: What Are You Waiting For? Directions?

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113 Myopia Control: What Are You Waiting For? Is there a downside? Reduction in vision? Risk of infection?

114 Visual Acuity in Ortho-K

115 VA with Myopia Control Soft Lens

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117 What is Risk of Contact Lens Wear? Incidence shown in cases per 10,000 years What is risk of soft lens wear in children? What is risk for overnight ortho-k in children? From Stapleton et al. (2008)

118 Microbial Keratitis in Overnight Ortho-K Patients with at least three months of documented lens wear Resulted in sample of 1317 patients 640 adults (49%) 677 children (51%) 2,599 patient years of wear 1,164 in adults 1,435 in children Frequency Age at Fitting (years)

119 Comparison Risk of microbial keratitis with overnight corneal reshaping lenses is similar to that with other overnight modalities: 7.7 per 10,000 years 90% CI: In children 13.9 per 10,000 years 95% CI:

120

121 Soft Contact Lens Myopia Control Growing list of publications of myopia control using multifocal SCLs in children Only 1 of 9 report any safety outcomes

122 The Safety of Soft Contact Lenses in Children Incidence of CIEs much lower in 8-12 year olds than in adults No reported cases of MK in over 2,000 prospective and 400 retrospective patient years of lens wear Behavior increases incidence in older children Daily disposable SCLs may reduce risk corneal infiltrative events in all patients

123 Age is a significant non-linear factor Incidence (per 10,000 patient years) Iritis Microbial keratitis CLARE w/o infiltrates CLARE w/infiltrates CLPU Infiltrative keratitis Age Range (years)

124 Effect of Age: Behavior, not Biology Incidence (per 10,000 patient years) Iritis Microbial keratitis CLARE w/o infiltrates CLARE w/infiltrates CLPU Infiltrative keratitis Age Range (years)

125 Incidence (per 10,000 pa/ent years) Incidence of Symptomatic CIEs Error bars = 95% CI Adults Prospective (age range, years) Retrospective Prospective

126 Myopia Prevention: The Final Frontier?

127 Can we Predict which Child Develops Myopia? Best predictors: Less than D at age 6 Parental history of myopia

128 CLEERE Study D and 0 myopic parents D and 1 myopic parent < D and 2 myopic parents More likely to become myopic < D and 0 myopic parents < D and 1 myopic parent < D and 2 myopic parents

129 What Environment Factors Affect Myopia Onset and Progression? Outdoor activity protects Near work has little impact

130 Outdoor Activities

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132 Once Child at Risk is Identified, How Do We Prevent? Behavior Interventions

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134 Outdoor Activity Halves Incidence of Myopia

135 Myopia Prevention: The Next 10 Years Clinical trials in at-risk children Low dose Atropine Corneal reshaping Multifocal soft lenses Outside Classroom lighting

136 Weighing the Evidence Center for Evidence-Based Management:

137 Clinical Research Pearl 2: Beware of the anecdote

138 One swallow does not a summer make

139 Clinical Research Pearl 2A: The First Study Clinical study of Progressive Addition Lenses (PALs): 32 children with single vision lenses Mean myopic progression over 2 years 1.23 D 22 wore PALs with D add: 0.76 D 38% 14 wore PALs with D add : 0.66 D 46%

140 Two Large-Scale PAL Trials Edwards et al. (2002) Single vision = 1.26 D PALs = 1.12 D Treatment effect = 11% COMET (Gwiazda et al., 2003) Single vision = 1.48 D PALs = 1.28 D Treatment effect = 13% Refractive error (D) BF SV Baseline 6 mo 12 mo 18 mo 24 mo Visit Myopia Progression (D) Baseline 1 year 2 year 3 year Visit BF SV

141 Clinical Research Pearl 3: Preliminary Data are..preliminary One year data show 37% reduction in myopia progression

142 Clinical Research Pearl 3: Preliminary Data are..preliminary One year data show 37% reduction in myopia progression COMET (Gwiazda et al., 2003) Single vision = 1.48 D PALs = 1.28 D Treatment effect = 13% Myopia Progression (D) BF SV Baseline 1 year 2 year 3 year Visit

143 Clinical Research Pearl 3A: Myopia control loses effect over time

144 Clinical Research Pearl 3A: Myopia control loses effect over time

145 Clinical Research Pearl 3A: Myopia control loses effect over time

146 Moving Forward Rapidly evolving field Stay alert and educated

147 Marketing Your Myopia Control Practice Alan Glazier, OD, FAAO, Dipl., ABO Disclosure Statement: VTI (Naturalvue) Johnson & Johnson Vision Care MyopiaInstitute.com

148 Marketing Your Myopia Control Practice In Office Marketing

149 Marketing Your Myopia Control Practice In Office Marketing Educating Staff

150 Marketing Your Myopia Control Practice In Office Marketing Educating Staff Educating Parents Most Don t Know Anything Can Be Done They Talk..and They Refer Chickens and Ping Pong Balls Working Distance/Digital Device use Myopia is a Disease

151 Myopia Calculator www. Calculator.brienholdenvision.org Demo to predict progression-customized for: Current Rx Current Age Mode of correction

152 Myopia Calculator www. Calculator.brienholdenvision.org

153 Marketing Your Myopia Control Practice In Office Marketing Educate Staff Educating Parents Community Events Asian Sunday Schools Local Primary School Nurses Health Fairs

154 Marketing Your Myopia Control Practice In Office Marketing Educate Staff Educating Parents Community Events Asian Sunday Schools Local Primary School Nurses Health Fairs Incentivizing Patients for Referrals

155 Marketing Your Myopia Control Practice In Office Marketing Educate Staff Educating Parents Community Events Asian Sunday Schools Local Primary School Nurses Health Fairs Incentivizing Patients for Referrals Social Media Content Creation is Key!

156 What Is Content?

157 Content (def.) The Information and Experience(s) Directed Towards an End-User or Audience.What the End-User Derives Value From

158

159 Quizzes Games Humor Charity Contests Polling Vlogging

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161 Marketing Your Myopia Control Practice Search Optimization First Organic Listing

162 MyopiaInstitute.com

163 Search Optimization MyopiaInstitute.com Myopia Control

164 Search Optimization MyopiaInstitute.com Myopia Control

165 Pricing Premium Service Charge What Training and Expertise are Worth What the Market Will Bear Guarantees/Warranties/Replacement Lenses Fees Global? How Do They Differ From Fees Charged for Standard Contact Lens Services? Accepting Insurance Not Succumbing to OLSE

166 Why Add a Myopia Control Specialty? New Standard of Care Emerging Offer Therapy, Not Cause or Crutch Increased Revenue Non-Covered Service Referrals Others are actively trying to usurp optometry s core competence treating myopia; don t let them

167 Informed Consent General Info Orthokeratology, also known as Vision Shaping, CRT and OrthoK is a procedure where rigid gas permeable plastic medical devices are utilized while sleeping to temporarily reduce or eliminate refractive error throughout the course of ones waking hours

168 Informed Consent Candidacy Most patients with Rx s under diopters may get several hours to several days of reduced prescription and this may eliminate the need for corrective eyewear for a good part of the day. to achieve maximum results, patients must sleep in the lenses for 8 hours or more..

169 Complications Pain Redness Tearing Irritation Discharge Abrasions Vision Distortions Infection Informed Consent

170 Care Hand Washing Lens Cleaning Avoiding Water Annual Follow Up Required Informed Consent

171 Informed Consent Complications What to Do If Pain, Photophobia or Both Occur and Last After Lenses Removed You Must Return to Eye Doctor ASAP Most Times Scratches Discuss Infectious Keratitis Cell Phone

172 Informed Consent I have been informed and understand risks associated with extended wear orthokeratology lenses I understand how orthokeratology will temporarily reduce the need for prescription eyewear; I understand that it will not permanently improve myopia or astigmatism I understand that fees for orthokeratology fitting and materials are refundable in full if the devices are unsuccessful in correcting vision and only for that reason

173 Considerations of Using Off-Label Product: Atropine Cross Sensitivity Dry Mouth Dry Eyes Constipation Drowsiness Dizziness Confusion Hallucinations Hemodynamic effects (Anti-Cholinergic) Tachycardia Arrhythmia Sudden Death

174 Considerations of Using Off-Label Product: Atropine Avoid in patients already on anti cholinergics such as allergy meds

175 Considerations of Using Off-Label Product: Ortho-K Cost Quality Efficacy Reproducibility Increased risk of infectious keratitis B+L and Paragon have FDA approval for temporary reduction of myopia Thus any claims to patients regarding control of myopia progression is an off-label use of an FDA-approved device

176 Case Report 10 YO AM OD: = X 002; OS: = X 180 FINAL RX: OD, OS 20/20 OU

177 Case Report Good centration of treatment zones Optic zone smaller than pupillary border How much and how quickly does peripheral plus ramp up from visual axis? i.e. How much peripheral myopic defocus is being created? Smaller optical zones used if necessary to increase myopia control

178 How To Get Started With Myopia Control Methods American Academy of Orthok and Myopia Control (AAOMC) Meeting

179 What to Do on Monday (Low Hanging Fruit) Join MyopiaInstitute.com Make Sure Your Google Business Page is Filled Out Up Your Social Media and SEO Game Talk to Parents Talk to Staff