Myopia Management: Foresight for Short-sight?

Myopia Management:

Foresight for Short-sight?

65th Annual Rochester Ophthalmology Conference

March 26 – 27, 2021

Michael DePaolis, OD, FAAO

Associate Professor of Clinical Ophthalmology

Flaum Eye Institute / URMedicine

Michael DePaolis, OD, FAAOAssociate Professor of Clinical Ophthalmology

Flaum Eye Institute, University of Rochester Medical Center

Financial Disclosures

Clinical Investigator, Advisory Board, Speaker’s Bureau, Consultant

Alcon

Allergan

AMO

Bausch & Lomb

CooperVision

Euclid

J&J Vision Care

LenTechs

Paragon Vision Sciences

Shire

SynergEyes

Visionology

Optometric Editor, Primary Care Optometry News (SLACK, Inc) and Healio.com/optometry

Global myopiamuch ado about nothing or cause for concern?

Significance of myopia and its societal impact

Myopia as a risk factor for ocular disease

Identifying those at risk

Understand mechanisms of myopia progression … and its management

Pharmacologic & optical considerations

Environmental & lifestyle considerations

What do we tell our patients?

Significance of myopia and its societal impact

Global Prevalence: 1.5 billion myopes (2010) -> 5 billion (2050)

US Adult population (12-54 yoa): 25% in 1971 to 42% in 1999

Lifetime per capita cost of myopia care $21,000 (S) in Singapore

Uncorrected refractive error costs in direct/indirect loss of productivity ~ $200 billion (US) per year

WHO: currently 300 million “high” myopes today -> 1 billion in 2050

Myopia as a risk factor for ocular disease

Retinal tears & detachment (Scottish RD Study Group – Mitry, etal IOVS 2010) 53% primary idiopathic RRD’s in myopic eyes

Cataract (Blue Mountain Eye Study – Younan, etal IOVS 2002) High myopia & nuclear cataract (OR 3.3) & PSC (OR 4.4)

Glaucoma (Singapore Malay Eye Study – Perea, etal Arch Oph 2010) Moderate/high myopia 3x increased risk of POAG

Myopic macular degeneration (Hisayama Study – Asakuma, etal IOVS 2010) 5% of pathologic myopes with myopic retinopathy

Reducing myopia progression by 33% reduces

the frequency of high myopia by 73%

(Brennan, Con Lens & Ant Eye 2012)

Identifying those at risk – for myopia progression

Genetics 3131 Chinese children and their parents / grandparents Myopic parents increased odds ratio for myopia “diminished” with each generation

(Wu, etal Optom Vis Sci 1999)

Environmental considerations Pubmed / Medline meta-analysis of 80 worldwide studies Low levels of outdoor activities, near work, dim light, poor sleep, urban setting

(Grzybowski, etal BMC Ophth 2020)

Risk calculators: www.myopiaprofile.com or www.bhvi.org

Likelihood of high myopia? 443 children followed 12+ yr. Myopia onset at 7-8 yoa = 54% while 12 yoa = 1%

(Hu JAMA Ophth 2020)

http://www.myopiaprofile.com/

http://www.bhvi.org/

Understanding the mechanisms for myopia progression

Emmetropization mechanism Molecular signaling leading to choroid/scleral remodeling to coincide the retina with the eye’s focal plane

A time honored practice … Ancient Chinese periorbital acupressure (2,000 BC) William Bates, MD “Perfect Sight Without Eyeglasses” (1891) Robert Morrison, OD Time Magazine (November 1957)

Controlling axial length growth … and Rx Genetics Pharmacology Optics Environment & lifestyle

Pharmacologic regulation of myopia progression

Anti-muscarinic agents mechanism of action?

Does not appear to be ciliary body cholinergic receptor driven Does not appear to be retinal amacrine cell mediated May be mediated through

RPE cells – induced release of dopamine slowing AL Choroid – induced choroidal thickening slowing AL Sclera – reduced GAG production slowing AL

atropine non-selective muscarinic acetylcholine receptor antagonist (mAchR) studies in 1960’s looked at atropine to discourage over-accommodation no controls, adjunct bifocals, and poor compliance hampered trials ATOM 1 (atropine 1%) & ATOM 2 (atropine 0.5%, 0.1%, and 0.01%)


Chia, etal Ophth 2012 atropine 0.5% -> 75% reduction in myopia progression atropine 0.1% -> 68% reduction in myopia progression atropine 0.01% -> 59% reduction in myopia progression

Huang, etal Ophth 2016 meta-analysis of 30 RCTs – impact of atropine vs control in myopia control high dose (0.5-1.0%) atropine: AL -0.21 & Rx 0.68D moderate dose (0.1%) atropine: AL -0.21 & Rx 0.53D low dose (0.01%) atropine: AL -0.15 & Rx 0.53D

Yam, etal Oph 2019 Low concentration of atropine for myopia progression (LAMP) 438 myopic children randomized to receive 0.05%, 0.025%, and 0.01% atropine mean myopia progression @ 1 year: -0.27D, -0.46D, -0.59D, and -0.81D (control)

Best used as early as possible, but not before 4 yoa, and for 4-6 year treatment


Pirenzepine

selective M1/M4 muscarinic receptor antagonist (alpha-adrenogenic receptor)

less mydriasis and cycloplegia than atropine mydriasis <1mm up to 2% concentration (Bartlett, etal J Oc Pharm Th 2003)

2% gel bid x 1 year slowed progression 50% (Siatkowski, etal Arch Ophth 2004)

not commercially available

Would today’s delivery systems work?


7-methylxanthine

adenosine antagonist and caffeine metabolite

altered scleral collagen content & fibril size in rabbits (Trier, etal BJO 1999)

7-MX fed guinea pigs ~ 50% less axial elongation (Cui, etal Acta Ophth 2009)

slowed AL & Rx progression ~ 25% over 2 years (Trier, etal J Biol Dis Infor 2008)

effect diminishes when treatment discontinued

commercially available as an oral agent in Denmark

Proposed mechanisms for optical management of myopia progression

Can we optically manipulate retinal image shell shape (and AL) by modulating retinal (de)focus optically?

Myopic defocus effects are mediated by mechanisms that integrate visual signals in a local, regionally selective manner in primates (Smith,etal Opt & Vis Sci 2013)

Peripheral defocus regulates scleral / choroidal change more than does the fovea

Optical regulation of myopia progression

Single vision lenses

Numerous animal studies support regulation of AL via optical defocus Results less consistent in human studies Wear duration no significant impact on progression (Ong, etal Opt & Vis Sci 1999) UnderRx (0.75D) no impact on progression (Chung, etal Vis Res 2002)

Bifocals & Progressive Addition Lenses (PAL’s)

COMET Trial demonstrated 0.20D benefit for PAL’s vs SVL over 3 years Reduced accommodative lag with esophoria ~ 0.64D Lower baseline myopia ~ 0.44D Closer reading distance ~ 0.48D

Treatment by period effect (Hasebe, etal IOVS 2008)

Best used for early myopes with shorter reading distances and higher AC/A


Novel spectacle lenses

DIMS (Defocus Incorporated Multiple Segments) 9mm central Rx zone surrounded by array of defocus segments (+3.05D) reduced progression of SE by 52% & AL by 62% (Lam, etal B J Oph 2019) MiyoSmart (Hoya)

Light Diffusion Technology clear central Rx aperture with reduced contrast lens peripheral zone reduced progression of SE by 59-74% & AL by 33-50% 3 year 265 child CYPRESS study

(Rappon, etal ARVO 2019) SightGlass Vision (now Essilor / CooperVision)

Highly Aspheric Lenslet Target (HALT) Clear central Rx aperture surrounded by peripheral aspheric lenslets reduced progression of SE by 63% & AL by 64% (Black, etal mivision 2020). Stellest (Essilor)

Executive Prismatic Bifocals 51% myopia progression reduction with prism bifocals 39% myopia progressrion reduction with bifocals (Cheng, etal JAMA Oph 2014) 3pd BI prism in children with accommodative lag


Proposed mechanisms for myopia control with contact lenses

Manipulation of accommodative lag (Aller, etal Opt & Vis Sci 2016)

Reduced peripheral retinal hyperopic defocus (Sankaridurg, etal IOVS 2011)

Sustained myopic defocus (Back, etal (aaopt.org July 3, 2017)

Negative spherical aberration cancellation (Cheng, etal Opt & Vis Sci 2016)

Optimization of point images in front of or on retina (Bakaraju ARVO 2015)

Optimization of peripheral aberration profile (Yoo, etal Heliyon 2020)

Optical regulation of myopia progression with RGP CL’s

Contact Lens & Myopia Progression Study (CLAMP) (Walline, etal Arch Ophth 2004) 3 year treatment benefit of RGP CL due to corneal flattening No significant slowing of AL in RGP CL group

Longitudinal Ortho-K Research in Children (LORIC) (Cho, etal Curr Eye Res 2005) AL growth slowed 50% over 2 years in Ortho-K wearers

Retardation of Myopia in Orthokeratology (ROMIO) (Cho, etal IOVS 2012) 43% reduction in AL growth over 2 years in Ortho-K group 7-8 yoa with >1D progression per year: 65% control vs 20% Ortho-K

What about wearability ? (Santodomingo, etal Eye & Con Lens 2013) Children wearing ortho-K lenses overall QOL rating superior to controls Parents rated Ortho-K method and intention to continue superior to controls

Optical Regulation of myopia progression with RGP CL’s

Optical Regulation of myopia with rigid gas permeable contact lenses (RGPCL)

LO 11 yof

MRx (2018)

OD -1.75sph = 20/20

OS -1.75sph = 20/20

MRx (2019)

OD -3.00sph = 20/20

OS -3.00-0.25x180 = 20/20

MRx (6 mth s/p VST )

OD +0.25 – 0.25 x 25 = 20/20

OS +0.25 - -0.25 x 170 = 20/20


Is there an additive effect to ortho-keratology and low dose atropine?

Kinoshito, etal ARVO 2019 80 Japanese children randomized to OK or OK+A (O.01%) In children with lower myopia OK+A provided 38% greater myopia reduction In children with higher myopia OK+A provided 28% greater myopia reduction may be synergistic effect

Chen, etal Con Len & Ant Eye 2019 60 children with 2-year hx of OK – added 0.01% atropine in yr 2 mean AL progression 0.45mm/yr to 0.14mm/yr treatment option most marked in younger patients

Why additive effect? Separate mechanisms vs increased pupil size


Fundamentals of corneal reshaping Central corneal flattening Central epithelial migration

Is there an increased risk of Microbial keratitis (MK)?

23 cases of MK in Hong Kong (8 acanthamoeba) Chan, etal AJO 2014 37 cases of MK in North America (2 studies) Cope, etal Ophth 2016 Increased risk

Overnight wear Soaking in tap water Topping off solutions Delayed reporting Vijay, etal Eye & Con Lens (2015)


Do the benefits of orthokeratology (OK) outweigh risks?

8-12 yo lowest rates of infiltrates (CLAY) (Chalmers, etal Inv Oph & Vis Sci 2011)

Children wearing contact lenses are safer than adults (Bullimore Opt Vis Sci 2017)

MK in OK (Bullimore Opt Vis Sci 2019) 1,000 children and adults representing 2600 patient wearing years 2 cases of MK in children yielding risk of 14 per 10,000 wearing years

Benefits of OK? better uncorrected vision better options for corrected vision (including refractive surgery) less prevalence of high myopia (and attending pathology)

on average, controlling myopia by 1 D reduces risk of myopic maculopathy by40%, glaucoma by 20%, and visual impairment by 20% (Bullimore & Brennan)

Optical regulation of myopia progression with SOFT CL’s

Peripheral Defocus Novel design reduced Rx progression & AL ~ 33% (Holden, etal IOVS 2011)

Annual Design Bifocal (Distance center / Peripheral near) Reduced Rx progression 50% & AL 29% (Walline, etal Opt Vis Sci 2013)

Simultaneous (Concentric Rings) Reduced Rx progression 25% & AL 28% (Lam, etal BJO 2014)

Positive Spherical Aberration Induction Reduced Rx progression & AL at 6m, but not 1 yr (Cheng, etal Opt Vis Sci 2016)

Extended Depth of Focus (EDOF) Reduced Rx progression 95% over prior lens (Cooper, etal Eye & Con Lens 2017) Small sample size, no control cohort, no AL

Optical regulation of myopia progression with SOFT CL’s

MiSight Bifocal Soft Lens For Myopia Control (CooperVision) Center distance annular concentric ring design daily disposable 109 myopic children 3-yr randomized trial MiSight slowed AL by 52% & Rx by 59% vs controls

Chamberlain, etal Optom Vis Sci 2019

NaturalVue Multifocal (VTI) Center distance EDOF design daily disposable Retrospective case series of 32 myopic children with 5-24 mo follow-up Reduced annualized mean progression from 0.85D to to 0.04D.

Cooper, etal Eye Cont Lens 2018

Regulation of myopia progression -environmental & lifestyle considerations

Is time outdoors important?

Bejing Myopia study – less time outdoors correlated withgreater AL and AL/CC over 1-year period (Guo, etal PLoS One 2013)

Meta-analysis found 2% reduced odds of myopiaper additional hour spent outdoors

(Sherwin, etal Ophth 2012)

Avon Longitudinal study – time outdoors, not activity,important (Guggenheim, etal IOVS 2012)

Time outdoors more protective in preventing myopiaOptimal amount? 11 hours per week


What about near point activity and screen time (vs green time) ?

Near point activity ….

Nearpoint activities with high accommodative demand promote myopia (You, etal PLoS One 2016)

More rapid myopia progression with shorter reading distance (Hsu, etal BJO 2017)

Myopic students ~2x smartphone data consumption as non-myopic peers(Mccrann, etal Clin Exp Optom 2021).


Does lighting play a role?

Violet light (360-400nm) in chick model appears inhibitory to AL growth

VL blocking spectacles and CL’s associated with increased AL changes(Torii, etal EBioMed 2017)

VL blocking phakic IOL’s associated with increased AL and Rx(Torii, etal Scien Rep 2017)

11 hr/wk @ 1,000+ lux is protective for myopia(Wu, etal Ophth 2018)

Should we recommend blue blocking computer glasses to adolescents?

Regulation of myopia – how should we monitor?

Refraction either wet (1% cyclogyl) or damp (1% tropicamide x2)

Topography Corneal power (radius and thickness) is relatively stable throughout growth Monitor important in all management forms and essential in OK

Axial Length strong correlation between AL and amount of myopia, but not linear or constant

1D change = 0.28mm in 6-7 yo, 0.32mm in 12-13 yo, 0.38mm in adults AL varies by age, gender, and descent Absolute AL of little benefit Trend analysis more important (0.10mm/yr vs 0.23mm/yr)

Biometry of choice? MyopiaMaster (Oculus) Lenstar Myopia (HS)

Regulation of myopia progression … the 1,000 ft view

Assumption: Prime years for progression from8-16 yoa @ rate of 0.75D per year

Outdoor time / near point activity / proper lighting 10 – 20% reduced rate of progression

Bifocal / Progressive Addition Spectacles 20 – 25% reduced rate of progression

Overnight Orthokeratology (RGPCL) 40 – 45% reduced rate of progression

Soft contact lenses (SCL’s) 45 – 50% reduced rate of progression

Pharmacologic 60 – 75% reduced rate of progression* * Single vision Rx controls

Myopia management and what to tell parents (patients) …

Myopia prevalence increasing worldwide – more than genetics involved

Area of significant interest – emerging evidence-based recommendations

Time outdoors, optimizing near point activities, and proper lighting important considerations

Pharmacologic and optical strategies exist – to slow, not stop, progression

Worthy pursuit as aim to enter adulthood as a mild or moderate myope

Documents

Myopia Management: Foresight for Short-sight?