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Maharajgunj Medical
Campus
IOM, Nepal
Bikash Sapko
B. Optometry
Interventions to Reduce
Myopia Progression in
Children
Objectives
• To find out the different interventions to reduce myopia
progression in children
• To determine the effectiveness of different interventions
to slow down the progression of myopia in children
Introduction
• Near-sightedness, also known as short-sightedness and myopia,
is a condition of the eye where light focuses in front of, instead
of on, the retina
• This causes distant objects to be blurry while close objects
appear normal
- "Facts About Refractive Errors". NEI. October 2010. Retrieved 30 July 2016
Prevalence
• Myopia: 22.9%
• High Myopia: 2.7%
• Estimated to be
- Myopia: 49.8%
- High Myopia: 9.8% by 2050
• Its prevalence is increasing at an alarming rate
- Holden BA, Fricke TR, Wilson DA, et al. Global prevalence of myopia and high myopia and temporal trends from 2000
through 2050. Ophthalmology. 2016;123(5):1036–1042.
Introduction
• There has been an increase in the prevalence of high myopia,
affecting up to 20% of secondary-school children in East Asian
populations
• It is also well recognized that myopia occurring at an earlier age
in childhood is associated with a higher degree of myopia in
adult life
- Fan DSP, LamDSC, Lam RF, et al. Prevalence, incidence, and progression of myopia of school children in Hong Kong. Invest
Ophthalmol Vis Sci. 2004;45:1071–1075.
- Zadnik K, Sinnott LT, Cotter SA, et al. Prediction of juvenile-onset myopia. JAMA Ophthalmol. 2015;133 (6):683–689.
Introduction
• In addition to the costs of optical correction, high myopia is
associated with significant ocular morbidity and visual disability
• Those with high myopia are at higher risk of developing sight
threatening complications such as degenerative retina changes,
early onset cataracts (in the 30-40 age range) and open-angle
glaucoma
- Saw SM, Gazzard G, Shih-Yen EC, Chua WH. Myopia and associated pathological complications. Ophthalmic Physiol Opt.
2005;25(5):381–391.
- Xu L, Wang Y, Wang S, et al. High myopia and glaucoma susceptibility the Beijing Eye Study. Ophthalmology.
2007;114(2):216–220.
Introduction
• As early as 1935, Sir Stewart Duke-Elder predicted that
environmental factors like excessive near work & lack of outdoor
activities influence myopia progression
• Since then, research has showed that environmental and genetic
factors play a role in myopia in addition to other active
interventions
- Duke-Elder S. The Practice of Refraction.2nd ed. Philadelphia,PA: P. Blakiston’s Son & Co.; 1935:105–106.
- Polling JR, Verhoeven VJ, Tideman JW, Klaver CC. Duke-Elder’s views on prognosis, prophylaxis, and treatment of myopia:
way ahead of his time. Strabismus. 2016;24(1):40–43.
Introduction
• In 2011, Walline et al. published a meta-analysis of 23 randomized
controlled trials (RCTs) assessing the effects of several interventions,
including pharmacological agents, spectacles, and contact lenses on
the progression of myopia in children
• Since then, there have been more trials evaluating similar or new
therapies
• Therapies could involve reducing environmental risk factors by
behavioral modification, or more active approaches such as the use of
optical devices (contact lenses and spectacles) and pharmacological
agents
- Walline JJ, Lindsley K, Vedula SS et al. Interventions to slow progression of myopia in children. Cochrane Database Syst
Rev. 2011;(12):CD004916.
Introduction
• Myopia control may take two forms:
- decrease of myopia progression or
- prevention of myopia onset
• Far more evidence regarding slowing of myopia progression is
available than preventing the onset of myopia
Introduction
• Environmental Considerations
- Time Spent Outdoors
- Near-Vision Activities
• Spectacles & Contact Lenses
- Gas-Permeable Contact Lens Wear
- Bifocal & Multifocal Spectacles
- Soft Bifocal Contact Lenses
- Orthokeratology
• Pharmacological Therapies
- Antimuscarinic Agents: Atropine & Pirenzepine
• Under Correction of Myopia
Interventions to Reduce Myopia
Progression
Environmental
Considerations
Time Spent Outdoors
• It has been postulated that:
- an increased level of light outdoors
- increases retinal dopamine production and release,
- alters gene expression in the retina,
- which in turn reduces axial elongation
• Rudnicka et al.(2016) found that children living in predominantly
urban environments have 2.6 times the risk of myopia compared
to children living in rural environments
- Feldkaemper M, Schaeffel F. An updated view on the role of dopamine in myopia. Exp Eye Res. 2013;114:106–119.
• Potential explanations include:
- more congested environment,
- greater emphasis on education, and as a result
- more near-vision work and
- fewer outdoor activities
- Rudnicka AR, Kapetanakis VV, Wathern AK, et al. Global variations and time trends in the prevalence of childhood
myopia, a systematic review and quantitative meta-analysis: implications for aetiology and early prevention [published
online ahead of print January 22, 2016]. Br J Ophthalmol. doi:10.1136/bjophthalmol2015-307724.
Time Spent Outdoors
• In a study involving 863 Australian children, children who were
myopic only spent an average of 16.3 hrs outdoors compared to
non-myopic children, who spent 21.0 hrs outdoors per week
• In Singapore, a study of 1249 adolescents showed that outdoor
physical activity appeared to be a protective factor for myopia
development in disease progression (P=0.008) but not indoor
sports (P=0.16)
- French AN, Morgan IG, Mitchell P et al. Risk factors for incident myopia in Australian schoolchildren: the Sydney
adolescent vascular and eye study. Ophthalmology. 2013;120:2100–2108.
- Dirani M, Tong L, Gazzard G, et al. Outdoor activity and myopia in Singapore teenage children. Br J Ophthalmol.
2009;93:997–1000.
Time Spent Outdoors
• In another study comparing 628 Singaporean and 124 Australian
school children, the prevalence of myopia was 3.3% in the
Australian children & 29.1% in Singaporean children
• The difference betwn the 2 groups of children was that the
Australian children spent a significant longer time outdoors
compared to Singaporean (13.8 vs 3.1 hrs per week)
- RoseKA,MorganIG, SmithW,etal. Myopia,lifestyle, and schooling in students of Chinese ethnicity in Singapore and
Sydney. Arch Ophthalmol. 2008;126:527–530.
Time Spent Outdoors
• A recent prospective interventional study was conducted in
school children aged 6 to 12 yrs in both rural and urban parts of
north western China
• The interventional group had two additional outdoor recess
programs of 20 mins each incorporated during school days
• Over the period of 1 yr, the mean uncorrected visual acuity for
the intervention group was significantly better than the control
group
Time Spent Outdoors
• The control group was 2.2 times (3.70% vs 8.50%, P=0.048)
more likely to develop myopia with a higher rate of progression
than the interventional group (-0.27±0.52 D/year vs -0.10 ±
0.65 D/year, P=0.005)
• Changes in axial length was also significantly lower following
the intervention group
• Hence, more time spent outdoors has been shown not only to
reduce the progression of myopia but also to prevent its onset
- Jin JX, Hua WJ, Jiang X, et al. Effect of outdoor activity on myopia onset and progression in school-aged children in
northeast China: the Sujiatun Eye Care Study. BMC Ophthalmol. 2015;15:73.
Time Spent Outdoors
Near-Vision Activities
• Several studies have shown a link between increased near vision
activities and myopia
• In a Singapore study, performing more than 20.5 hrs of reading
and writing a week was found to be positively associated with
myopia (OR 1.12, 95% CI 1.04-1.20, P=0.003)
- Quek TPL, Chua CG, Chong CS, et al. Prevalence of refractive errors in teenage high school students in Singapore.
Ophthalmic Physiol Opt 2004;24:47–55.
• In the Sydney myopia study, children aged 12 yrs who read at a
distance of less than 30 cm and continuously for more than 30
mins. were 2.5 and 1.5 times more likely to develop myopia,
respectively
• In a study conducted in Beijing high school students aged 16 to
18 yrs, a higher prevalence of myopia was associated with a
longer time spent on near work and a shorter near work
distance
- Ip JM, Saw SM, Rose KA, et al. Role of near work in myopia: findings in a sample of Australian school children. Invest
Ophthalmol Vis Sci. 2008;49:2903–2910.
- Wu LJ, You QS, Duan JL, et al. Prevalence and associated factors of myopia in high-school students in Beijing. PLoS
One. 2015;10(3):e0120764.
Near-Vision Activities
• A recent systemic review and meta-analysis of 27 cross-sectional
and cohort studies was performed to quantify the effect of near-
work activities on myopia in children
• They found that more time spent on near-work activities was
associated with a higher OR of myopia of 1.14 (95% CI 1.08-1.20)
- Huang HM, Chang DS, Wu PC. The association between near work activities and myopia in childrena systematic review
and meta-analysis. PLoS One. 2015;10(10):e0140419
Near-Vision Activities
Spectacles & Contact Lenses
Bifocal or Multifocal Spectacles
• The most investigated form of myopia control is bifocal or
multifocal spectacles
• Similar to under correction of myopic refractive error, multifocal
spectacles are thought to reduce accommodative effort or error
to slow the progression of myopia
• Most of the investigations find statistically significant slowing of
myopia progression with multifocal spectacles
• Few investigations find clinically meaningful slowing of myopia
progression
- Edwards MH, Li RW, Lam CS, et al. (2002)
- Yang Z, Lan W, Ge J, et al.(2009)
- Gwiazda J, Hyman L, Hussein M, et al. (2003)
- Fulk GW, Cyert LA, Parker DE. (2000)
- Correction of Myopia Evaluation Trial 2 (COMET 2, 2011)
- Hasebe S, Jun J, Varnas SR. (2014)
- Cheng D, Woo GC, Drobe B, et al. (2014)
- Berntsen DA, Sinnott LT, Mutti DO, et al. (2012)
Bifocal or Multifocal Spectacles
FIG. The percent slowing of myopia progression reported by various controlled
investigations of bifocal or multifocal spectacles myopia control studies. The length
(years) of the trial is indicated at the bottom of the data points for each study.
Bifocal or Multifocal Spectacles
• The largest randomized clinical trial reported that children
wearing multifocal spectacles progressed 0.20±0.08 D less than
children wearing single vision spectacles (P=0.004),
• But a difference of less than 0.25 D over 3 yrs is not clinically
meaningful
- Gwiazda J, Hyman L, Hussein M, et al. A randomized clinical trial of progressive addition lenses versus single vision
lenses on the progression of myopia in children. Invest Ophthalmol Vis Sci 2003;44:1492–1500
Bifocal or Multifocal Spectacles
• A recent clinical trial randomly assigned children to wear single
vision, executive bifocal, or executive bifocal with 3D base-in
prism spectacles
- the prism had no effect on myopia progression,
- but the executive bifocal slowed myopia progression
-2.06±0.13 D for single vision wearers
-1.25±0.10 D for the executive bifocal group (P<0.01) over 3 yrs,
- which is a 39% treatment effect that approaches clinical
meaningfulness
- Cheng D, Woo GC, Drobe B, et al. Effect of bifocal and prismatic bifocal spectacles on myopia progression in children:
three-year results of a randomized clinical trial. JAMA Ophthalmol 2014;132:258–264.
Bifocal or Multifocal Spectacles
• In the Cochrane database meta-analysis in 2011, Walline et al.
found from 8 studies that
- the use of progressive addition lenses (PALs) compared to
single-vision lenses (SVLs) was statistically significant in slowing
myopia progression,
- but to a clinically insignificant degree
• The evidence supports the benefit of bifocal spectacles was
limited and inconsistent across trials
- Walline JJ, Lindsley K, Vedula SS et al. Interventions to slow progression of myopia in children. Cochrane Database Syst
Rev. 2011;(12):CD004916.
Bifocal or Multifocal Spectacles
Soft Bifocal Contact Lenses
• Thought to work on the similar notion that myopic progression
can be slowed
- by inducing a peripheral myopic defocus,
- which slows the rate of axial elongation
• Soft bifocal contact lenses are of 2 types:
- center distance (add power in the
peripheral part of the contact lens) or
- center near (add power in the central
part of the contact lens)
• Only center distance contact lenses have been investigated for
myopia control
• On average, these contact lenses slow myopia progression by
46%
• Similar to the 43% slowing of myopia progression exhibited by
orthokeratology contact lenses
- Anstice NS, Phillips JR. (2011)
- Lam CS, Tang WC, Tse DY, et al. (2014)
- Walline JJ, Greiner KL, McVey ME, et al. (2013)
- Sankaridurg P, Holden B, Smith E III, et al. (2011)
- Aller TA, Liu M, Wildsoet CF. (2016)
Soft Bifocal Contact Lenses
Author Bifocal Design Add Power Study Design Bifocal Single Vision
Anstice
(10 mnths)
Concentric +2.00 Contralateral
control
-0.44±0.33 -0.69±0.38
Lam
(2yrs)
Concentric +2.50 Randomized -0.59±0.49 -0.79±0.56
Sankaridurg
(1 yr)
Progressive
add
+2.00 Prospective,
historical
control
-0.28±0.28 -0.84±0.47
Walline
(2 yrs)
Progressive
add
+2.00 Prospective,
historical
control
-0.51±0.06 -1.03±0.06
Aller TA
(1 yr)
Concentric +2.00 Randomized -0.22 ± 0.34 -0.79 ± 0.43
TABLE: Summary of Five Soft Bifocal Contact Lens Myopia Control studies
Result
Myopia Progression (D)
Soft Bifocal Contact Lenses
Orthokeratology
• Orthokeratology (ortho-K) contact lenses work by temporarily
reshaping the corneal surface when worn at night, mainly
through central epithelial thinning
• They have also been shown to be effective in reducing axial
elongation
- and are thought to work similarly to bifocal SCLs in achieving a
relative peripheral myopia
- which is thought to reduce myopia progression
- Hiraoka T, Kakita T, Okamoto F, Takahashi H, Oshika T. Long-term effect of overnight orthokeratology on axial
length elongation in childhood myopia: a 5-year follow-up study. Invest Ophthalmol Vis Sci. 2012;53 (7):3913–
3919.
- Santodomingo-Rubido J, Villa-Collar C, Gilmartin B, Gutiérrez-Ortega R. Myopia control with orthokeratology
contact lenses in Spain: refractive and biometric changes. Invest Ophthalmol Vis Sci. 2012;53(8):5060– 5065.
FIG. The percent slowing of myopia progression reported by various controlled
investigations of corneal reshaping contact lens myopia control studies.
The length (years) of the trial is indicated at the bottom of the data points for each
study.
Orthokeratology
• In a recent meta-analysis of 7 studies by Sun et al.,
- the combined results showed that the mean AL of the 218
subjects in the ortho-K group was 0.27 mm (95% CI 0.22-0.32)
less than that of 217 subjects in the control group after 2 yrs,
- corresponding to nearly a 45% decrease in myopic progression
- Sun Y, Xu F, Zhang T, et al. Orthokeratology to control myopia progression: a meta-analysis. PLoS One.
2015;10(4):e0124535.
Orthokeratology
Demerits of Ortho-K Lenses
• Findings from studies lacked a washout period
• Also did not evaluate the risk of myopia rebound after cessation
of ortho-K lenses
• Some studies also did not have post ortho-K refractive error data
• There is also no long-term data on the potential long-term ocular
effects of ortho-K wear
Orthokeratology
• Though there were no serious complications reported in
these studies,
- more than 100 cases of infective keratitis have been
reported in other independent studies
- including infections with pseudomonas and acanthamoeba
Published Reports Year No. of Cases
Sun X, Zhao H, Deng S, et al. 2006 28
Yepes N, Lee SB, Hill V, et al. 2005 3
Tseng CH, Fong CF, Chen WL, et al. 2005 3
Young AL, Leung AT, Cheng LL, et al. 2004 6
Xuguang S, Lin C, Yan Z, et al. 2003 4
Chan TC,LiEY, Wong, et al. 2014 23
Watt K, Swarbrick HA. 2005 50
Orthokeratology
• The American Academy of Ophthalmology published a report in
2008 evaluating the safety of ortho-K lenses
• It stated that these lenses put pts. at risk of vision-threatening
complications
• So a wide margin of safety should be built into ortho-K regimes
- Van Meter WS, Musch DC, Jacobs DS, et al. Safety of overnight orthokeratology for myopia: a report by the American
Academy of Ophthalmology. Ophthalmology. 2008;115:2301–2313
Orthokeratology
• The risk of infective keratitis in children using Ortho-K lenses
overnight (the majority of ortho-K wearers) is 13.9 per 10,000
wearers
• The risk is similar to the high risk reported in adults who wear
SCLs overnight
• And the risk-benefit ratio of Ortho-K lens wear for myopia
control in children belies the controversy of this approach
- Bullimore MA, Sinnott LT, Jones-Jordan LA. The risk of microbial keratitis with overnight corneal reshaping lenses. Optom
Vis Sci. 2013;90:937–944.
Orthokeratology
Pharmacological Therapies
Antimuscarinic Agents
• Although the specific mechanism of treatment effect for
antimuscarinic agents is unknown,
- it is known that their effective myopia control is not a result of
reduced accommodation
• Atropine is a nonspecific muscarinic receptor antagonist that
causes cycloplegia and mydriasis
- Troilo D, Gottlieb MD, Wallman J. Visual deprivation causes myopia in chicks with optic nerve section. Curr Eye Res
1987;6:993–999.
- McBrien NA, Stell WK, Carr B. How does atropine exert its anti-myopia effects? Ophthalmic Physiol Opt 2013;33:373–
378.
• From animal studies, it is thought to work either via a
neurochemical cascade, which begins with M1/4 receptors at the
retina level, or
• Directly on scleral fibroblasts by inhibiting the synthesis of
glycosaminoglycans via a non-muscarinic mechanism
• Schwahn et al. (2000) also found that
- atropine stimulated an increase in the amount of dopamine
released from retinal pigment epithelium (RPE) cells,
- which in turn might cancel out a retinal signal that controls eye
growth
• Pirenzepine is an M1-specific muscarinic receptor antagonist
• M1 receptors are highly concentrated in the retina and found
rarely on the ciliary body or iris
• So they cause far fewer cycloplegic and mydriatic-related
symptoms
• Both pirenzepine7 and atropine8 have been shown to slow
myopia progression
7- Siatkowski RM et al (2008), Tan DT, et al (2005)
8- Wu PC, et al (2011), Chua WH, (2006), Lee JJ, et al (2006), Chia A, et al (2012)
Pirenzepine
• In 2 RCTs, one conducted in Asia (Singapore, Hong Kong, and
Thailand) and one in the USA,
• Pirenzepine in the form of a 2% ophthalmic gel twice daily was
shown to reduce myopia progression by about 77% and 51%
respectively
• The main side effect resulting from ointment preparations of
pirenzepine was asymptomatic papillary conjunctivitis,
photophobia or blur while reading
- Siatkowski RM, Cotter SA, Crockett RS, et al. Two-year multicenter, randomized, double-masked, placebo-controlled,
parallel safety and efficacy study of 2% pirenzepine ophthalmic gel in children with myopia. J AAPOS 2008;12:332–339.
- Tan DT, Lam DS, Chua WH, et al. One-year multicenter, double-masked, placebo-controlled, parallel safety and efficacy
study of 2% pirenzepine ophthalmic gel in children with myopia. Ophthalmology 2005;112:84–91.
Study Study Design Duration Pirenzepine
Group
Placebo Group
Siatkowski RM,
et al (USA,
2008)
RCT 2 Years -0.58D -0.99D
(p=0.008)
Tan DT et al
(Asia, 2005)
RCT 1 Year -0.47D -0.84D
(p<0.01)
Result
Myopia Progression
Table: Summary of Two Pirenzepine Study on controlling Myopia Progression
The Atropine for the Treatment of
Childhood Myopia (ATOM) study
• ATOM 1 Study
• ATOM 2 Study
(ATOM 1) Study
• Parallel-group, placebo-controlled, randomized, double-masked
study
• Conducted in Singapore
• Included 400 children aged 6-12 years (mean age 9.2 years)
• With moderate myopia (-1.00 D to -6.00 D, mean -3.50 D)
• For 3 yrs (2-yrs treatment period and 1-yr washout period)
• The treatment group received atropine 1% at bed time in one
eye and no treatment in the other eye
- Chua WH, Balakrishnan V, Chan YH, et al. Atropine for the treatment of childhood myopia. Ophthalmology.
2006;113(12):2285–2291.
Result of ATOM 1 Study
• Over 2 yrs, there was a 77% reduction in the mean progression
of myopia (progression of-1.20 D+/0.69 in the placebo group and
-0.28D +/- 0.92 in the atropine group)
• There was also a strong correlation with reduction in axial length
in the atropine group
• There were no severe adverse effects associated with atropine
eye drops
• At 3 yrs, a significant rebound was seen for both the myopia
progression and axial elongation after cessation of atropine 1%
for 1 yr
- Tong L, Huang XL, Koh AL, Zhang X, Tan DT, Chua WH. Atropine for the treatment of childhood myopia: effect on myopia
progression after cessation of atropine. Ophthalmology. 2009;116(3):572–579.
ATOM 2 Study
• Conducted shortly after ATOM 1 study
• Aim: To compare the safety and efficacy of 3 lower doses of
atropine (0.5%, 0.1%, and 0.01%)
• Double-masked, randomized, controlled trial
• Included 400 children
• Age: 6-12 years
• Myopia worse than -2.00 D
• Children were randomized to receive either 0.5% atropine
(n=161), 0.1% (n=155), or 0.01% (n=84)
- Chia A, Chua WH, Cheung YB, et al. Atropine for the treatment of childhood myopia: safety and efficacy of 0.5%, 0.1%,
and 0.01% doses (Atropine for the Treatment of Myopia 2). Ophthalmology. 2012;119 (2):347–354.
• Both eyes were treated
• This was a 5-yr study that included 2 yrs of treatment, 1 yr of
washout, and 2 yrs where treatment was restarted in children
who continued to progress
• These children were retreated with only 1 dose of atropine
• The results showed a dose-related response with atropine and
myopia progression
• But these differences were clinically small (-0.30 +/0.60 D for
0.5%, -3.8 +/- 0.60 D for 0.1%, and -4.9 +/- 0.63 D for 0.01%)
Consolidating data from both ATOM 1 and ATOM 2,
• 0.01% atropine has similar efficacy compared to the higher concn
of 0.1% and 0.5%
• Side effects with atropine 0.01% were minimal compared to the
2 higher concn
• Negligible effect on accommodation (mean residual
accommodation was 11.8 D in the 0.01% group, compared to 6.8
D and 4 D in the 0.1% and 0.5% groups, respectively)
• Pupil size (0.8 mm and 1.2 mm difference from baseline in
mesopic and photopic condn, respectively, in the 0.01% group,
compared to 2.3 mm and 2.8 mm in the 0.1% group and 3.1 mm
and 3.6 mm in the 0.5% group, P<0.01)
• No effect on near VA in the 0.01% group (mean value of 20/20,
J1)
• During the washout period, children in the 0.01% atropine group
had minimal rebound (-0.87 +/- 0.52 D in the 0.5% group, -0.68
+/- 0.45 D in the 0.1% group, and -0.28 +/- 0.33 D in the 0.01%
group, P<0.01)
• No rebound seen for axial length in the 0.01% group
• The lower myopia progression in the 0.01% group persisted
during phase 3, with overall myopia progression and change in
axial elongation being the lowest in this group at the end of 5 yrs
• Another retrospective, case-controlled study conducted in the
USA
- to evaluate the effect of atropine 0.01% in the progression
of childhood myopia
- significant reduction in the rate of myopia progression was
found with minimal side effects
• Those who were on atropine had significantly lower rates of
myopia progression (-0.10 ± 0.60 D/year) than the controls (-0.60
± 0.40 D/year, P=0.001) and 75% of children in this group showed
slow progression (≤-0.25 D/year)
- Clark TY, Clark RA. Atropine 0.01% eyedrops significantly reduce the progression of childhood myopia. J Ocul Pharmacol
Ther. 2015;31(9):541–545.
• Another retrospective, case-controlled study conducted in
Taiwan
- to evaluate the use of slightly higher concn of atropine
(0.05% and 0.1%)
- found it to be effective in slowing the rate of myopia
progression
- However, there were no data on near blur, glare, or pupil size
• Compared to those who were untreated, the progression of
myopia was slower in the atropine group over 4.5 years (-0.23
D/year vs -0.86 D/year, P<0.01)
- Wu PC, Yang YH, Fang PC. The long-term results of using low-concentration atropine eye drops for controlling myopia
progression in schoolchildren. J Ocul Pharmacol Ther. 2011;27(5):461–466.
Under-correction of Myopia
• Under correction of myopia is thought to reduce the
accommodative effort or error (lag)
• Two randomized clinical trials conducted to determine whether
under correction of myopic refractive error slows myopia
progression reported differing results
• Adler and Millodot found that under correction of myopia by
approx. 0.50 D did not significantly affect myopia progression in
6 to 15 yr-old myopic children
- Adler D, Millodot M. The possible effect of undercorrection on myopic progression in children. Clin Exp Optom
2006;89:315–321.
• Chung et al. found that myopia progressed an average of -1.00 D
for 9 to 14-yr-old myopes under corrected by -0.75 D, compared
with -0.77 D for fully corrected myopes of the same age range
(P<0.01)
• Despite the differing results, the myopia control information is
the same: undercorrection of myopic refractive error by 0.50 to
0.75 D does not slow the progression of myopia
- Chung K, Mohidin N, O’Leary DJ. Undercorrection of myopia enhances rather than inhibits myopia progression. Vison
Res. 2002;42:2555–2559.
Under-correction of Myopia
Gas-Permeable Contact Lens Wear
• Several early studies of gas-permeable contact lens myopia
control reported slowing of myopia progression
• Two randomized clinical trials found no effect of gas-permeable
contact lens wear on myopia progression in children
- Walline JJ, Jones LA, Mutti DO, et al. A randomized trial of the effects of rigid contact lenses on myopia progression. Arch
Ophthalmol 2004;122: 1760–1766.
- Katz J, Schein OD, Levy B, et al. A randomized trial of rigid gas permeable contact lenses to reduce progression of
children’s myopia. Am JOphthalmol 2003;136:82–90.
• Katz et al. found no difference in myopia progression (P=0.64) or
axial elongation (P=0.38) over 2 yrs between children wearing
gas-permeable and soft contact lens wear
• Walline et al. reported gas-permeable contact lens wearers
progressed -1.56±0.95 D over 2 years compared with -2.19±0.89
D for single vision soft contact lens wearers (P<0.001)
• However, there was no difference in the amount of axial
elongation between the gas-permeable (0.81±0.51 mm) and
single vision (0.76±0.44 mm) contact lens wearers
Gas-Permeable Contact Lens Wear
• Most of the treatment effects were due to less change in corneal
curvature exhibited by the gas-permeable contact lens wearers
• Because the change in corneal curvature is assumed to be
temporary, it is concluded that gas-permeable contact lenses
should not be fit solely for myopia control
• Again, despite differing results, the conclusions are the same:
gas-permeable contact lens wear does not slow myopia
progression in children
Gas-Permeable Contact Lens Wear
Summary
• Environmental factors such as reduced time spent outdoors and
increased near-work activities have been shown to play a role in
myopia progression
• Of the approaches that have been discussed, all have shown to
slow myopia progression;
- in particular, atropine, ortho-K contact lenses, and soft bifocal
contact lenses have been shown to be most effective
• The relative risks of SCL wear, or overnight ortho-K rigid contact
lens wear are mainly related to sight threatening infectious
keratitis,
- need careful consideration if these CL approaches
become significant therapeutic modalities for myopia control
• From the ATOM trials, atropine has been shown to reduce
myopia progression and axial elongation in children in a dose-
related manner, up to 77% with atropine 1%,
- though there was a rebound phenomenon noted with higher
doses
Summary
• These eye drops were shown to be safe, with no serious adverse
events reported,
- though in higher doses they have limited practical use because
of pupil dilatation, loss of accommodation and near vision blur
• With atropine 0.01%, myopia progression is reduced by up to
50%, with minimal side effects on pupillary dilatation, near
vision, and accommodation
• More studies will need to be done to evaluate the appropriate
duration of treatment and also to decide when it is best to start,
stop, and restart treatment
Summary
• Each of these therapies is limited in variable extents by
- treatment compliance,
- potential side effects, and
- lack of long-term data
• They are likely to improve with further validation and longer-
term studies
• In addition, it would be interesting to evaluate the potential
additive effects of combination therapies on the progression of
myopia in future studies
Summary
Thankyou

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Interventions to Reduce Myopia Progression in Children (Journal Club) (healthkura.com)

  • 2. Interventions to Reduce Myopia Progression in Children
  • 3. Objectives • To find out the different interventions to reduce myopia progression in children • To determine the effectiveness of different interventions to slow down the progression of myopia in children
  • 4. Introduction • Near-sightedness, also known as short-sightedness and myopia, is a condition of the eye where light focuses in front of, instead of on, the retina • This causes distant objects to be blurry while close objects appear normal - "Facts About Refractive Errors". NEI. October 2010. Retrieved 30 July 2016
  • 5. Prevalence • Myopia: 22.9% • High Myopia: 2.7% • Estimated to be - Myopia: 49.8% - High Myopia: 9.8% by 2050 • Its prevalence is increasing at an alarming rate - Holden BA, Fricke TR, Wilson DA, et al. Global prevalence of myopia and high myopia and temporal trends from 2000 through 2050. Ophthalmology. 2016;123(5):1036–1042. Introduction
  • 6. • There has been an increase in the prevalence of high myopia, affecting up to 20% of secondary-school children in East Asian populations • It is also well recognized that myopia occurring at an earlier age in childhood is associated with a higher degree of myopia in adult life - Fan DSP, LamDSC, Lam RF, et al. Prevalence, incidence, and progression of myopia of school children in Hong Kong. Invest Ophthalmol Vis Sci. 2004;45:1071–1075. - Zadnik K, Sinnott LT, Cotter SA, et al. Prediction of juvenile-onset myopia. JAMA Ophthalmol. 2015;133 (6):683–689. Introduction
  • 7. • In addition to the costs of optical correction, high myopia is associated with significant ocular morbidity and visual disability • Those with high myopia are at higher risk of developing sight threatening complications such as degenerative retina changes, early onset cataracts (in the 30-40 age range) and open-angle glaucoma - Saw SM, Gazzard G, Shih-Yen EC, Chua WH. Myopia and associated pathological complications. Ophthalmic Physiol Opt. 2005;25(5):381–391. - Xu L, Wang Y, Wang S, et al. High myopia and glaucoma susceptibility the Beijing Eye Study. Ophthalmology. 2007;114(2):216–220. Introduction
  • 8. • As early as 1935, Sir Stewart Duke-Elder predicted that environmental factors like excessive near work & lack of outdoor activities influence myopia progression • Since then, research has showed that environmental and genetic factors play a role in myopia in addition to other active interventions - Duke-Elder S. The Practice of Refraction.2nd ed. Philadelphia,PA: P. Blakiston’s Son & Co.; 1935:105–106. - Polling JR, Verhoeven VJ, Tideman JW, Klaver CC. Duke-Elder’s views on prognosis, prophylaxis, and treatment of myopia: way ahead of his time. Strabismus. 2016;24(1):40–43. Introduction
  • 9. • In 2011, Walline et al. published a meta-analysis of 23 randomized controlled trials (RCTs) assessing the effects of several interventions, including pharmacological agents, spectacles, and contact lenses on the progression of myopia in children • Since then, there have been more trials evaluating similar or new therapies • Therapies could involve reducing environmental risk factors by behavioral modification, or more active approaches such as the use of optical devices (contact lenses and spectacles) and pharmacological agents - Walline JJ, Lindsley K, Vedula SS et al. Interventions to slow progression of myopia in children. Cochrane Database Syst Rev. 2011;(12):CD004916. Introduction
  • 10. • Myopia control may take two forms: - decrease of myopia progression or - prevention of myopia onset • Far more evidence regarding slowing of myopia progression is available than preventing the onset of myopia Introduction
  • 11. • Environmental Considerations - Time Spent Outdoors - Near-Vision Activities • Spectacles & Contact Lenses - Gas-Permeable Contact Lens Wear - Bifocal & Multifocal Spectacles - Soft Bifocal Contact Lenses - Orthokeratology • Pharmacological Therapies - Antimuscarinic Agents: Atropine & Pirenzepine • Under Correction of Myopia Interventions to Reduce Myopia Progression
  • 13. Time Spent Outdoors • It has been postulated that: - an increased level of light outdoors - increases retinal dopamine production and release, - alters gene expression in the retina, - which in turn reduces axial elongation • Rudnicka et al.(2016) found that children living in predominantly urban environments have 2.6 times the risk of myopia compared to children living in rural environments - Feldkaemper M, Schaeffel F. An updated view on the role of dopamine in myopia. Exp Eye Res. 2013;114:106–119.
  • 14. • Potential explanations include: - more congested environment, - greater emphasis on education, and as a result - more near-vision work and - fewer outdoor activities - Rudnicka AR, Kapetanakis VV, Wathern AK, et al. Global variations and time trends in the prevalence of childhood myopia, a systematic review and quantitative meta-analysis: implications for aetiology and early prevention [published online ahead of print January 22, 2016]. Br J Ophthalmol. doi:10.1136/bjophthalmol2015-307724. Time Spent Outdoors
  • 15. • In a study involving 863 Australian children, children who were myopic only spent an average of 16.3 hrs outdoors compared to non-myopic children, who spent 21.0 hrs outdoors per week • In Singapore, a study of 1249 adolescents showed that outdoor physical activity appeared to be a protective factor for myopia development in disease progression (P=0.008) but not indoor sports (P=0.16) - French AN, Morgan IG, Mitchell P et al. Risk factors for incident myopia in Australian schoolchildren: the Sydney adolescent vascular and eye study. Ophthalmology. 2013;120:2100–2108. - Dirani M, Tong L, Gazzard G, et al. Outdoor activity and myopia in Singapore teenage children. Br J Ophthalmol. 2009;93:997–1000. Time Spent Outdoors
  • 16. • In another study comparing 628 Singaporean and 124 Australian school children, the prevalence of myopia was 3.3% in the Australian children & 29.1% in Singaporean children • The difference betwn the 2 groups of children was that the Australian children spent a significant longer time outdoors compared to Singaporean (13.8 vs 3.1 hrs per week) - RoseKA,MorganIG, SmithW,etal. Myopia,lifestyle, and schooling in students of Chinese ethnicity in Singapore and Sydney. Arch Ophthalmol. 2008;126:527–530. Time Spent Outdoors
  • 17. • A recent prospective interventional study was conducted in school children aged 6 to 12 yrs in both rural and urban parts of north western China • The interventional group had two additional outdoor recess programs of 20 mins each incorporated during school days • Over the period of 1 yr, the mean uncorrected visual acuity for the intervention group was significantly better than the control group Time Spent Outdoors
  • 18. • The control group was 2.2 times (3.70% vs 8.50%, P=0.048) more likely to develop myopia with a higher rate of progression than the interventional group (-0.27±0.52 D/year vs -0.10 ± 0.65 D/year, P=0.005) • Changes in axial length was also significantly lower following the intervention group • Hence, more time spent outdoors has been shown not only to reduce the progression of myopia but also to prevent its onset - Jin JX, Hua WJ, Jiang X, et al. Effect of outdoor activity on myopia onset and progression in school-aged children in northeast China: the Sujiatun Eye Care Study. BMC Ophthalmol. 2015;15:73. Time Spent Outdoors
  • 19. Near-Vision Activities • Several studies have shown a link between increased near vision activities and myopia • In a Singapore study, performing more than 20.5 hrs of reading and writing a week was found to be positively associated with myopia (OR 1.12, 95% CI 1.04-1.20, P=0.003) - Quek TPL, Chua CG, Chong CS, et al. Prevalence of refractive errors in teenage high school students in Singapore. Ophthalmic Physiol Opt 2004;24:47–55.
  • 20. • In the Sydney myopia study, children aged 12 yrs who read at a distance of less than 30 cm and continuously for more than 30 mins. were 2.5 and 1.5 times more likely to develop myopia, respectively • In a study conducted in Beijing high school students aged 16 to 18 yrs, a higher prevalence of myopia was associated with a longer time spent on near work and a shorter near work distance - Ip JM, Saw SM, Rose KA, et al. Role of near work in myopia: findings in a sample of Australian school children. Invest Ophthalmol Vis Sci. 2008;49:2903–2910. - Wu LJ, You QS, Duan JL, et al. Prevalence and associated factors of myopia in high-school students in Beijing. PLoS One. 2015;10(3):e0120764. Near-Vision Activities
  • 21. • A recent systemic review and meta-analysis of 27 cross-sectional and cohort studies was performed to quantify the effect of near- work activities on myopia in children • They found that more time spent on near-work activities was associated with a higher OR of myopia of 1.14 (95% CI 1.08-1.20) - Huang HM, Chang DS, Wu PC. The association between near work activities and myopia in childrena systematic review and meta-analysis. PLoS One. 2015;10(10):e0140419 Near-Vision Activities
  • 23. Bifocal or Multifocal Spectacles • The most investigated form of myopia control is bifocal or multifocal spectacles • Similar to under correction of myopic refractive error, multifocal spectacles are thought to reduce accommodative effort or error to slow the progression of myopia
  • 24. • Most of the investigations find statistically significant slowing of myopia progression with multifocal spectacles • Few investigations find clinically meaningful slowing of myopia progression - Edwards MH, Li RW, Lam CS, et al. (2002) - Yang Z, Lan W, Ge J, et al.(2009) - Gwiazda J, Hyman L, Hussein M, et al. (2003) - Fulk GW, Cyert LA, Parker DE. (2000) - Correction of Myopia Evaluation Trial 2 (COMET 2, 2011) - Hasebe S, Jun J, Varnas SR. (2014) - Cheng D, Woo GC, Drobe B, et al. (2014) - Berntsen DA, Sinnott LT, Mutti DO, et al. (2012) Bifocal or Multifocal Spectacles
  • 25. FIG. The percent slowing of myopia progression reported by various controlled investigations of bifocal or multifocal spectacles myopia control studies. The length (years) of the trial is indicated at the bottom of the data points for each study. Bifocal or Multifocal Spectacles
  • 26. • The largest randomized clinical trial reported that children wearing multifocal spectacles progressed 0.20±0.08 D less than children wearing single vision spectacles (P=0.004), • But a difference of less than 0.25 D over 3 yrs is not clinically meaningful - Gwiazda J, Hyman L, Hussein M, et al. A randomized clinical trial of progressive addition lenses versus single vision lenses on the progression of myopia in children. Invest Ophthalmol Vis Sci 2003;44:1492–1500 Bifocal or Multifocal Spectacles
  • 27. • A recent clinical trial randomly assigned children to wear single vision, executive bifocal, or executive bifocal with 3D base-in prism spectacles - the prism had no effect on myopia progression, - but the executive bifocal slowed myopia progression -2.06±0.13 D for single vision wearers -1.25±0.10 D for the executive bifocal group (P<0.01) over 3 yrs, - which is a 39% treatment effect that approaches clinical meaningfulness - Cheng D, Woo GC, Drobe B, et al. Effect of bifocal and prismatic bifocal spectacles on myopia progression in children: three-year results of a randomized clinical trial. JAMA Ophthalmol 2014;132:258–264. Bifocal or Multifocal Spectacles
  • 28. • In the Cochrane database meta-analysis in 2011, Walline et al. found from 8 studies that - the use of progressive addition lenses (PALs) compared to single-vision lenses (SVLs) was statistically significant in slowing myopia progression, - but to a clinically insignificant degree • The evidence supports the benefit of bifocal spectacles was limited and inconsistent across trials - Walline JJ, Lindsley K, Vedula SS et al. Interventions to slow progression of myopia in children. Cochrane Database Syst Rev. 2011;(12):CD004916. Bifocal or Multifocal Spectacles
  • 29. Soft Bifocal Contact Lenses • Thought to work on the similar notion that myopic progression can be slowed - by inducing a peripheral myopic defocus, - which slows the rate of axial elongation • Soft bifocal contact lenses are of 2 types: - center distance (add power in the peripheral part of the contact lens) or - center near (add power in the central part of the contact lens)
  • 30. • Only center distance contact lenses have been investigated for myopia control • On average, these contact lenses slow myopia progression by 46% • Similar to the 43% slowing of myopia progression exhibited by orthokeratology contact lenses - Anstice NS, Phillips JR. (2011) - Lam CS, Tang WC, Tse DY, et al. (2014) - Walline JJ, Greiner KL, McVey ME, et al. (2013) - Sankaridurg P, Holden B, Smith E III, et al. (2011) - Aller TA, Liu M, Wildsoet CF. (2016) Soft Bifocal Contact Lenses
  • 31. Author Bifocal Design Add Power Study Design Bifocal Single Vision Anstice (10 mnths) Concentric +2.00 Contralateral control -0.44±0.33 -0.69±0.38 Lam (2yrs) Concentric +2.50 Randomized -0.59±0.49 -0.79±0.56 Sankaridurg (1 yr) Progressive add +2.00 Prospective, historical control -0.28±0.28 -0.84±0.47 Walline (2 yrs) Progressive add +2.00 Prospective, historical control -0.51±0.06 -1.03±0.06 Aller TA (1 yr) Concentric +2.00 Randomized -0.22 ± 0.34 -0.79 ± 0.43 TABLE: Summary of Five Soft Bifocal Contact Lens Myopia Control studies Result Myopia Progression (D) Soft Bifocal Contact Lenses
  • 32. Orthokeratology • Orthokeratology (ortho-K) contact lenses work by temporarily reshaping the corneal surface when worn at night, mainly through central epithelial thinning • They have also been shown to be effective in reducing axial elongation - and are thought to work similarly to bifocal SCLs in achieving a relative peripheral myopia - which is thought to reduce myopia progression - Hiraoka T, Kakita T, Okamoto F, Takahashi H, Oshika T. Long-term effect of overnight orthokeratology on axial length elongation in childhood myopia: a 5-year follow-up study. Invest Ophthalmol Vis Sci. 2012;53 (7):3913– 3919. - Santodomingo-Rubido J, Villa-Collar C, Gilmartin B, Gutiérrez-Ortega R. Myopia control with orthokeratology contact lenses in Spain: refractive and biometric changes. Invest Ophthalmol Vis Sci. 2012;53(8):5060– 5065.
  • 33. FIG. The percent slowing of myopia progression reported by various controlled investigations of corneal reshaping contact lens myopia control studies. The length (years) of the trial is indicated at the bottom of the data points for each study. Orthokeratology
  • 34. • In a recent meta-analysis of 7 studies by Sun et al., - the combined results showed that the mean AL of the 218 subjects in the ortho-K group was 0.27 mm (95% CI 0.22-0.32) less than that of 217 subjects in the control group after 2 yrs, - corresponding to nearly a 45% decrease in myopic progression - Sun Y, Xu F, Zhang T, et al. Orthokeratology to control myopia progression: a meta-analysis. PLoS One. 2015;10(4):e0124535. Orthokeratology
  • 35. Demerits of Ortho-K Lenses • Findings from studies lacked a washout period • Also did not evaluate the risk of myopia rebound after cessation of ortho-K lenses • Some studies also did not have post ortho-K refractive error data • There is also no long-term data on the potential long-term ocular effects of ortho-K wear Orthokeratology
  • 36. • Though there were no serious complications reported in these studies, - more than 100 cases of infective keratitis have been reported in other independent studies - including infections with pseudomonas and acanthamoeba Published Reports Year No. of Cases Sun X, Zhao H, Deng S, et al. 2006 28 Yepes N, Lee SB, Hill V, et al. 2005 3 Tseng CH, Fong CF, Chen WL, et al. 2005 3 Young AL, Leung AT, Cheng LL, et al. 2004 6 Xuguang S, Lin C, Yan Z, et al. 2003 4 Chan TC,LiEY, Wong, et al. 2014 23 Watt K, Swarbrick HA. 2005 50 Orthokeratology
  • 37. • The American Academy of Ophthalmology published a report in 2008 evaluating the safety of ortho-K lenses • It stated that these lenses put pts. at risk of vision-threatening complications • So a wide margin of safety should be built into ortho-K regimes - Van Meter WS, Musch DC, Jacobs DS, et al. Safety of overnight orthokeratology for myopia: a report by the American Academy of Ophthalmology. Ophthalmology. 2008;115:2301–2313 Orthokeratology
  • 38. • The risk of infective keratitis in children using Ortho-K lenses overnight (the majority of ortho-K wearers) is 13.9 per 10,000 wearers • The risk is similar to the high risk reported in adults who wear SCLs overnight • And the risk-benefit ratio of Ortho-K lens wear for myopia control in children belies the controversy of this approach - Bullimore MA, Sinnott LT, Jones-Jordan LA. The risk of microbial keratitis with overnight corneal reshaping lenses. Optom Vis Sci. 2013;90:937–944. Orthokeratology
  • 40. Antimuscarinic Agents • Although the specific mechanism of treatment effect for antimuscarinic agents is unknown, - it is known that their effective myopia control is not a result of reduced accommodation • Atropine is a nonspecific muscarinic receptor antagonist that causes cycloplegia and mydriasis - Troilo D, Gottlieb MD, Wallman J. Visual deprivation causes myopia in chicks with optic nerve section. Curr Eye Res 1987;6:993–999. - McBrien NA, Stell WK, Carr B. How does atropine exert its anti-myopia effects? Ophthalmic Physiol Opt 2013;33:373– 378.
  • 41. • From animal studies, it is thought to work either via a neurochemical cascade, which begins with M1/4 receptors at the retina level, or • Directly on scleral fibroblasts by inhibiting the synthesis of glycosaminoglycans via a non-muscarinic mechanism • Schwahn et al. (2000) also found that - atropine stimulated an increase in the amount of dopamine released from retinal pigment epithelium (RPE) cells, - which in turn might cancel out a retinal signal that controls eye growth
  • 42. • Pirenzepine is an M1-specific muscarinic receptor antagonist • M1 receptors are highly concentrated in the retina and found rarely on the ciliary body or iris • So they cause far fewer cycloplegic and mydriatic-related symptoms • Both pirenzepine7 and atropine8 have been shown to slow myopia progression 7- Siatkowski RM et al (2008), Tan DT, et al (2005) 8- Wu PC, et al (2011), Chua WH, (2006), Lee JJ, et al (2006), Chia A, et al (2012) Pirenzepine
  • 43. • In 2 RCTs, one conducted in Asia (Singapore, Hong Kong, and Thailand) and one in the USA, • Pirenzepine in the form of a 2% ophthalmic gel twice daily was shown to reduce myopia progression by about 77% and 51% respectively • The main side effect resulting from ointment preparations of pirenzepine was asymptomatic papillary conjunctivitis, photophobia or blur while reading - Siatkowski RM, Cotter SA, Crockett RS, et al. Two-year multicenter, randomized, double-masked, placebo-controlled, parallel safety and efficacy study of 2% pirenzepine ophthalmic gel in children with myopia. J AAPOS 2008;12:332–339. - Tan DT, Lam DS, Chua WH, et al. One-year multicenter, double-masked, placebo-controlled, parallel safety and efficacy study of 2% pirenzepine ophthalmic gel in children with myopia. Ophthalmology 2005;112:84–91.
  • 44. Study Study Design Duration Pirenzepine Group Placebo Group Siatkowski RM, et al (USA, 2008) RCT 2 Years -0.58D -0.99D (p=0.008) Tan DT et al (Asia, 2005) RCT 1 Year -0.47D -0.84D (p<0.01) Result Myopia Progression Table: Summary of Two Pirenzepine Study on controlling Myopia Progression
  • 45. The Atropine for the Treatment of Childhood Myopia (ATOM) study • ATOM 1 Study • ATOM 2 Study
  • 46. (ATOM 1) Study • Parallel-group, placebo-controlled, randomized, double-masked study • Conducted in Singapore • Included 400 children aged 6-12 years (mean age 9.2 years) • With moderate myopia (-1.00 D to -6.00 D, mean -3.50 D) • For 3 yrs (2-yrs treatment period and 1-yr washout period) • The treatment group received atropine 1% at bed time in one eye and no treatment in the other eye - Chua WH, Balakrishnan V, Chan YH, et al. Atropine for the treatment of childhood myopia. Ophthalmology. 2006;113(12):2285–2291.
  • 47. Result of ATOM 1 Study • Over 2 yrs, there was a 77% reduction in the mean progression of myopia (progression of-1.20 D+/0.69 in the placebo group and -0.28D +/- 0.92 in the atropine group) • There was also a strong correlation with reduction in axial length in the atropine group • There were no severe adverse effects associated with atropine eye drops • At 3 yrs, a significant rebound was seen for both the myopia progression and axial elongation after cessation of atropine 1% for 1 yr - Tong L, Huang XL, Koh AL, Zhang X, Tan DT, Chua WH. Atropine for the treatment of childhood myopia: effect on myopia progression after cessation of atropine. Ophthalmology. 2009;116(3):572–579.
  • 48. ATOM 2 Study • Conducted shortly after ATOM 1 study • Aim: To compare the safety and efficacy of 3 lower doses of atropine (0.5%, 0.1%, and 0.01%) • Double-masked, randomized, controlled trial • Included 400 children • Age: 6-12 years • Myopia worse than -2.00 D • Children were randomized to receive either 0.5% atropine (n=161), 0.1% (n=155), or 0.01% (n=84) - Chia A, Chua WH, Cheung YB, et al. Atropine for the treatment of childhood myopia: safety and efficacy of 0.5%, 0.1%, and 0.01% doses (Atropine for the Treatment of Myopia 2). Ophthalmology. 2012;119 (2):347–354.
  • 49. • Both eyes were treated • This was a 5-yr study that included 2 yrs of treatment, 1 yr of washout, and 2 yrs where treatment was restarted in children who continued to progress • These children were retreated with only 1 dose of atropine • The results showed a dose-related response with atropine and myopia progression • But these differences were clinically small (-0.30 +/0.60 D for 0.5%, -3.8 +/- 0.60 D for 0.1%, and -4.9 +/- 0.63 D for 0.01%)
  • 50. Consolidating data from both ATOM 1 and ATOM 2, • 0.01% atropine has similar efficacy compared to the higher concn of 0.1% and 0.5% • Side effects with atropine 0.01% were minimal compared to the 2 higher concn • Negligible effect on accommodation (mean residual accommodation was 11.8 D in the 0.01% group, compared to 6.8 D and 4 D in the 0.1% and 0.5% groups, respectively) • Pupil size (0.8 mm and 1.2 mm difference from baseline in mesopic and photopic condn, respectively, in the 0.01% group, compared to 2.3 mm and 2.8 mm in the 0.1% group and 3.1 mm and 3.6 mm in the 0.5% group, P<0.01)
  • 51. • No effect on near VA in the 0.01% group (mean value of 20/20, J1) • During the washout period, children in the 0.01% atropine group had minimal rebound (-0.87 +/- 0.52 D in the 0.5% group, -0.68 +/- 0.45 D in the 0.1% group, and -0.28 +/- 0.33 D in the 0.01% group, P<0.01) • No rebound seen for axial length in the 0.01% group • The lower myopia progression in the 0.01% group persisted during phase 3, with overall myopia progression and change in axial elongation being the lowest in this group at the end of 5 yrs
  • 52. • Another retrospective, case-controlled study conducted in the USA - to evaluate the effect of atropine 0.01% in the progression of childhood myopia - significant reduction in the rate of myopia progression was found with minimal side effects • Those who were on atropine had significantly lower rates of myopia progression (-0.10 ± 0.60 D/year) than the controls (-0.60 ± 0.40 D/year, P=0.001) and 75% of children in this group showed slow progression (≤-0.25 D/year) - Clark TY, Clark RA. Atropine 0.01% eyedrops significantly reduce the progression of childhood myopia. J Ocul Pharmacol Ther. 2015;31(9):541–545.
  • 53. • Another retrospective, case-controlled study conducted in Taiwan - to evaluate the use of slightly higher concn of atropine (0.05% and 0.1%) - found it to be effective in slowing the rate of myopia progression - However, there were no data on near blur, glare, or pupil size • Compared to those who were untreated, the progression of myopia was slower in the atropine group over 4.5 years (-0.23 D/year vs -0.86 D/year, P<0.01) - Wu PC, Yang YH, Fang PC. The long-term results of using low-concentration atropine eye drops for controlling myopia progression in schoolchildren. J Ocul Pharmacol Ther. 2011;27(5):461–466.
  • 54. Under-correction of Myopia • Under correction of myopia is thought to reduce the accommodative effort or error (lag) • Two randomized clinical trials conducted to determine whether under correction of myopic refractive error slows myopia progression reported differing results • Adler and Millodot found that under correction of myopia by approx. 0.50 D did not significantly affect myopia progression in 6 to 15 yr-old myopic children - Adler D, Millodot M. The possible effect of undercorrection on myopic progression in children. Clin Exp Optom 2006;89:315–321.
  • 55. • Chung et al. found that myopia progressed an average of -1.00 D for 9 to 14-yr-old myopes under corrected by -0.75 D, compared with -0.77 D for fully corrected myopes of the same age range (P<0.01) • Despite the differing results, the myopia control information is the same: undercorrection of myopic refractive error by 0.50 to 0.75 D does not slow the progression of myopia - Chung K, Mohidin N, O’Leary DJ. Undercorrection of myopia enhances rather than inhibits myopia progression. Vison Res. 2002;42:2555–2559. Under-correction of Myopia
  • 56. Gas-Permeable Contact Lens Wear • Several early studies of gas-permeable contact lens myopia control reported slowing of myopia progression • Two randomized clinical trials found no effect of gas-permeable contact lens wear on myopia progression in children - Walline JJ, Jones LA, Mutti DO, et al. A randomized trial of the effects of rigid contact lenses on myopia progression. Arch Ophthalmol 2004;122: 1760–1766. - Katz J, Schein OD, Levy B, et al. A randomized trial of rigid gas permeable contact lenses to reduce progression of children’s myopia. Am JOphthalmol 2003;136:82–90.
  • 57. • Katz et al. found no difference in myopia progression (P=0.64) or axial elongation (P=0.38) over 2 yrs between children wearing gas-permeable and soft contact lens wear • Walline et al. reported gas-permeable contact lens wearers progressed -1.56±0.95 D over 2 years compared with -2.19±0.89 D for single vision soft contact lens wearers (P<0.001) • However, there was no difference in the amount of axial elongation between the gas-permeable (0.81±0.51 mm) and single vision (0.76±0.44 mm) contact lens wearers Gas-Permeable Contact Lens Wear
  • 58. • Most of the treatment effects were due to less change in corneal curvature exhibited by the gas-permeable contact lens wearers • Because the change in corneal curvature is assumed to be temporary, it is concluded that gas-permeable contact lenses should not be fit solely for myopia control • Again, despite differing results, the conclusions are the same: gas-permeable contact lens wear does not slow myopia progression in children Gas-Permeable Contact Lens Wear
  • 59. Summary • Environmental factors such as reduced time spent outdoors and increased near-work activities have been shown to play a role in myopia progression • Of the approaches that have been discussed, all have shown to slow myopia progression; - in particular, atropine, ortho-K contact lenses, and soft bifocal contact lenses have been shown to be most effective
  • 60. • The relative risks of SCL wear, or overnight ortho-K rigid contact lens wear are mainly related to sight threatening infectious keratitis, - need careful consideration if these CL approaches become significant therapeutic modalities for myopia control • From the ATOM trials, atropine has been shown to reduce myopia progression and axial elongation in children in a dose- related manner, up to 77% with atropine 1%, - though there was a rebound phenomenon noted with higher doses Summary
  • 61. • These eye drops were shown to be safe, with no serious adverse events reported, - though in higher doses they have limited practical use because of pupil dilatation, loss of accommodation and near vision blur • With atropine 0.01%, myopia progression is reduced by up to 50%, with minimal side effects on pupillary dilatation, near vision, and accommodation • More studies will need to be done to evaluate the appropriate duration of treatment and also to decide when it is best to start, stop, and restart treatment Summary
  • 62. • Each of these therapies is limited in variable extents by - treatment compliance, - potential side effects, and - lack of long-term data • They are likely to improve with further validation and longer- term studies • In addition, it would be interesting to evaluate the potential additive effects of combination therapies on the progression of myopia in future studies Summary

Notas del editor

  1. degenerative retina changes (eg, retinal detachment, choroidal neovascularization, macular schisis and holes, myopic macular degeneration
  2. It is unknown whether this study found a strong effect because it was the only one to use executive bifocals or because it is the only one to limit participation to currently progressing myopic children
  3. Reason: reducing hyperopic blur during near work by reducing accommodation effort
  4. historical control A control group that is chosen from a group of patients who were observed at some time in the past or for whom data areavailable through records. Historical controls are used for comparison with subjects being treated or assessed concurrently
  5. Though the findings from these studies are promising, - they lacked a washout period, and
  6. Although pirenzepine provides effective myopia control with few side effects, it is not commercially available in an ophthalmic preparation in the United States.
  7. More importantly, the side effects experienced
  8. A cohort of 48 myopic children Age: 6 to 15, fully corrected- 23, undercorrected by 0.50D- 25 Retrospective study For 18 months
  9. 2 yr prospective study, 94 myopies of age 9-14, 47 experimental subjects myopia undercorrected by -0.75D