A meta-analysis on the use of atropine for myopia control.pdf

https://www.google.com/
Modified slide deck of Dr. Stacey Sau

https://www.who.int/blindness/causes/MyopiaReportforWeb.pdf

Myopia
▷Risks and complications associated:
o Retinal detachment
o Cataract
o Glaucoma
o Choroidal neovascularization
o Myopic degenerative changes
▷Retinopathy secondary to high myopia
- second most frequent cause of low vision and
blindness among adults
Yam JC, Jiang Y, Tang SM, Law AKP, Chan JJ, Wong E, Ko ST, Young AL, Tham CC, Chen LJ, Pang CP. Low-Concentration Atropine
for Myopia Progression (LAMP) Study: A Randomized, Double-Blinded, Placebo-Controlled Trial of 0.05%, 0.025%, and 0.01% Atropine
Eye Drops in Myopia Control. Ophthalmology. 2018 Jul 6. pii: S0161-6420(18)30285-9.

Treatment methods for myopia
▷Eyeglasses that undercorrect
▷Multifocal eyeglasses
▷Novel lens eyeglasses design
▷Various contact lens therapies such as
bifocal or multifocal contact lenses or
orthokeratology
▷Topical timolol and topical antimuscarinic
agents (pirenzepine and atropine)
Pineles SL, Kraker RT, VanderVeen DK, Hutchinson AK, Galvin JA, Wilson LB, Lambert SR. Atropine
for the Prevention of Myopia Progression in Children. Ophthalmology. 2017 Dec;124(12):1857-1866.
doi: 10.1016/j.ophtha.2017.05.032. Epub 2017 Jun 29. PMID: 28669492

Conclusion:
Antimuscarinic agents are the most likely effective treatment to
slow myopia progression.

Atropine eyedrops
▷Non-selective muscarinic antagonist
▷No ideal approach as to the
concentration and duration of
atropine treatment for the control of
myopia progression
▷Adverse effects: photophobia and
blurred near vision.
Gong Q, Janowski M, Luo M, Wei H, Chen B, Yang G, Liu L. Efficacy and Adverse Effects of Atropine in Childhood Myopia: A
Meta-analysis. JAMA Ophthalmol. 2017 Jun 1;135(6):624-630. doi: 10.1001/jamaophthalmol.2017.1091.

AAO updates
▷ Atropine in the Treatment of Myopia Studies (ATOM1 and
ATOM2)
○ 0.01% atropine once daily for 1 to 2 years
○ Higher doses = largest rebound myopic progression
after discontinuation
○ Singapore
▷ Clark and Clark (2015): retrospective case-control study
○ 0.01% atropine effective for reducing myopia
progression
○ US

Objective
To determine the efficacy of atropine in
reducing the rate of myopia
progression and increase in axial
length among myopic children who
were treated with atropine ophthalmic
drops ranging from 0.01% to 1%
versus control based on data from
published literature.

Methodology
Types of studies
➢Randomized controlled trials
➢Prospective interventional controlled trials
Types of participants
➢Pediatric patients aged 4 to 14 years old
➢With myopia on cycloplegic refraction
(cyclopentolate or tropicamide) regardless of
degree.

Methodology
Types of interventions
➢Daily topical administration of atropine eyedrops,
(regardless of concentration)
➢Controls may consist of placebo, alternate treatment,
or observation.
Types of outcome measures
➢Mean difference of rate of myopia progression in
diopters per year
➢Mean difference of increase in axial length in
millimeters

Search methods
➢PubMed, Embase, Google Scholar, Herdin,
and Cochrane
➢Free text search and Medical Subject
Headings (MeSH) were done up to
November 2018.
➢Search terms atropine and myopia
progression
➢Studies published in English

Fig 1. PRISMA flow diagram of the literature search

Table 1. Characteristics of studies included in the meta-analysis.
Study Country
Type of
study
Population
(age)
Degree of
myopia
Intervention Control
Number of
eyes
(intervention)
Number of
eyes
(control)
Outcomes
assessed
Follow-up
period
Yen
(1989)13
Taiwan RCT 6-14 -0.5 to -4.0D 1% atropine
every other day
Placebo (Saline) 32 32 Myopic
progression
1 year
Shih
(1999)8
Taiwan RCT 6-13 -0.5 to -6.75D 0.5% atropine
nightly
0.25% atropine
nightly
0.1% atropine
nightly
0.5% tropicamide
nightly
0.5% atropine:
41
0.25%
atropine: 47
0.1% atropine:
49
49 Myopic
progression
2 years
Shih
(2001)9
Taiwan RCT 6-13 mean baseline
myopia -3.28 to
-3.34D
0.5% atropine
nightly +
multifocal
lenses
Multifocal lenses 66 61 Myopic
progression,
axial length
1.5 years
Chua
(2006)14
Singapore RCT 6-12 -1.0 to -6.0D
and <1.5D
astigmatism
1% atropine
daily
Placebo (0.5%
hydroxypropyl
methylcellulose)
166 190 Myopic
progression,
axial length
2 years
Fan
(2007)15
Hong Kong Interventiona
l non-
randomized
study
5-10 -3.0D or more 1% atropine
daily
No intervention 23 23 Myopic
progression,
axial length
1 year
8 RCTs and 2 prospective interventional non-randomized studies
1,229 children aged 4 to 14 years.
Baseline cycloplegic refraction ranged from -0.5 to -6.75 D
Follow-up period 1 to 2 years

Chia
(2012)7
Singapore RCT 6-12 at least -2.0D
and <1.5D
astigmatism
0.5% atropine
nightly
0.1% atropine
nightly
0.01%
atropine
nightly
Placebo (0.5%
hydroxypropyl
methylcellulose)
0.5% atropine:
139
0.1% atropine:
141
0.01%
atropine: 75
190 Myopic
progression,
axial length
2 years
Yi
(2015)16
China RCT 7-12 -1.0 and -6.0D 1% atropine
nightly
Hypromellose +
dextran +
glycerol (Tears
Naturale Free)
62 62 Myopic
progression,
axial length
1 year
Lee
(2016)11
Taiwan Intervention
al non-
randomized
study
6-12 less than
-3.0D
0.125%
atropine
0.25%
atropine
No intervention 0.125%
atropine: 32
0.25%
atropine: 12
12 Myopic
progression
1 year
Wang
(2017)17
China RCT mean:
9.1
(interventio
n); 8.7
(control)
-0.5 to -2.0D 0.5% atropine Hypromellose +
dextran +
glycerol (Tears
Naturale Free)
54 55 Myopic
progression
1 year
Yam
(2018)4
Hong Kong RCT 4-12 at least -1.0D
and ≤-2.5D
astigmatism
0.05%
atropine
nightly
0.025%
atropine
nightly
0.01%
atropine
nightly
0.9% sodium
chloride
0.05%
atropine: 102
0.025%
atropine: 91
0.01%
atropine: 97
93 Myopic
progression,
axial length
1 year

RESULTS
Cochrane’s Review Manager 5.3 software
Pooled mean difference (PMD)

Anatomy of a Forest Plot
Line of No Effect
Intervention Control
O
O

Line of No Effect
Intervention
Control

Study or
subgrou
p
Intervention Total Control Total Weight Mean
Difference
Study A Mean +/- SD Mean +/-
SD
% Result (95%
CI)
Study B
Subtotal
Line of No Effect
Intervention
Control

Fig 3. Forest Plot of Atropine vs Control for Myopia Progression [D/Year]
with Subgroup Analysis by Concentration

Fig 4. Forest Plot of Atropine vs Control for Myopia Progression [D/Year] with Subgroup Analysis
by Study Methodology

Fig 5. Forest Plot of Atropine vs Control for Increase in Axial Length
[mm] with Subgroup Analysis by Concentration

Fig 6. Forest Plot of Atropine vs Control for Increase in Axial Length [mm]
with Subgroup Analysis by Study Methodology

Fig 7. Forest Plot of Sensitivity Analysis for Atropine vs Control for Myopia
Progression [D/Year] with Subgroup Analysis by Concentration

Fig 8. Forest Plot of Sensitivity Analysis for Atropine vs Control for Myopia
Progression [D/Year] with Subgroup Analysis by Study Methodology

Conclusions
Sau et al 2021 (Papers until 2018)
Atropine is
effective in
reducing myopia
progression and
decreasing axial
elongation.
Effect size
decreases as the
concentration of
atropine decrease,
but the 0.01%
subgroup had
equivocal results.

Discussion and Conclusion
▷ Atropine is effective in reducing myopia progression and
decreasing axial elongation.
▷ Effect size decreases as the concentration of atropine
decrease, with the 0.01% subgroup having equivocal results.
▷ Meta-analysis by Song et al (2011): dose-response
relationship between atropine and myopia progression.
○ Did not have a 0.01% subgroup since low dose atropine
was not yet being studied at that time.

Gong et al (2017)
Categorized the
different
concentrations of
atropine as to low
dose (0.01%),
moderate dose
(greater than 0.01% to
less than 0.5%) and
high dose (0.5% to
1.0%).
Li et al (2014)
Analyzed overall
effects
Lowest dose
included was
0.025%
Huang et al (2016)
Divided the
concentration of
atropine into low
(0.01%), moderate
(0.1%), and high
dose (0.5% and 1%)
No significant difference in slowing myopia
progression among various doses of
atropine

Recommendation
▷More randomized controlled trials are needed to
assess the efficacy of low dose atropine
specifically 0.01%, 0.025% and 0.05%.
▷Axial elongation should also be included as an
outcome measure in all future studies.

LAMP 2018 (Yam et al)
• Atropine 0.05% more effective
than 0.025, 0.01, placebo
AOK 2019 (Tan et al)
N=65, 1 month follow-up, p=0.003
AOK: -0.05 +/- 0.05 mm;
OK: -0.02 +/- 0.03 mm
Li FF, Yam JC. Low-Concentration Atropine Eye Drops for Myopia Progression. Asia Pac J Ophthalmol (Phila). 2019 Sep-
Oct;8(5):360-365. doi: 10.1097/APO.0000000000000256. PMID: 31478936; PMCID: PMC6784858.
Low-dose Atropine for Myopia Progression (LAMP)

Yam JC, Jiang Y, Tang SM, Law AKP, Chan JJ, Wong E, Ko ST, Young AL, Tham CC, Chen LJ, Pang CP. Low-Concentration
Atropine for Myopia Progression (LAMP) Study: A Randomized, Double-Blinded, Placebo-Controlled Trial of 0.05%, 0.025%, and
0.01% Atropine Eye Drops in Myopia Control. Ophthalmology. 2019 Jan;126(1):113-124. doi: 10.1016/j.ophtha.2018.05.029. Epub
2018 Jul 6. PMID: 30514630.
Low-dose Atropine for Myopia Progression (LAMP)
0.05% 0.025% 0.01% Placebo
Myopia Progression (D) -0.27 -0.46 -0.59 -0.81
Axial length (mm) 0.2 0.29 0.36 0.4
Pupillary Size (mm)
Photopic
Mesopic
1.03
0.58
0.76
0.43
0.49
0.23
0.13
0.02
Loss of accommodative
amplitude (D) 1.98 1.61 0.26 0.32

Placebo group
from Year 1
• Given Atropine 0.05%
Group 0.05%.
0.025%, 0.01%
• Stayed in same
regimen
Yam JC, Li FF, Zhang X, Tang SM, Yip BHK, Kam KW, Ko ST, Young AL, Tham CC, Chen LJ, Pang CP. Two-Year Clinical Trial of
the Low-Concentration Atropine for Myopia Progression (LAMP) Study: Phase 2 Report. Ophthalmology. 2020 Jul;127(7):910-919.
doi: 10.1016/j.ophtha.2019.12.011. Epub 2019 Dec 21. PMID: 32019700.
Low-dose Atropine for Myopia Progression (LAMP) 2
CONCLUSION: 0.05% remained the
most effective concentration in slowing
myopia progression.

Li FF, Zhang Y, Zhang X, Yip BHK, Tang SM, Kam KW, Young AL, Chen LJ, Tham CC, Pang CP, Yam JC. Age
Effect on Treatment Responses to 0.05%, 0.025%, and 0.01% Atropine: Low-Concentration Atropine for Myopia
Progression Study. Ophthalmology. 2021 Aug;128(8):1180-1187. doi: 10.1016/j.ophtha.2020.12.036. Epub 2021
Jan 8. PMID: 33422558.
Conclusion:
• Younger age poorer response.
• Younger age required highest
concentration (0.05%).

Wang S, Wang J, Wang N. Combined Orthokeratology with Atropine for Children with
Myopia: A Meta-Analysis. Ophthalmic Res. 2021;64(5):723-731. doi: 10.1159/000510779.
Epub 2020 Aug 11. PMID: 32781450.
Conclusion: OrthoK + A0.01% more
effective than orthoK alone in slowing
axial length elongation

Khanal S, Phillips JR. Which low-dose atropine for myopia control? Clin Exp Optom. 2020
Mar;103(2):230-232. doi: 10.1111/cxo.12967. Epub 2019 Sep 5. PMID: 31489714; PMCID:
PMC7065125.
“Initiating 0.01% atropine
treatment…would
inevitably delay
implementation of an
effective dose.”

References:
1. Gong Q, Janowski M, Luo M, Wei H, Chen B, Yang G, Liu L. Efficacy and Adverse Effects of Atropine in Childhood Myopia:
A Meta-analysis. JAMA Ophthalmol. 2017 Jun 1;135(6):624-630. doi: 10.1001/jamaophthalmol.2017.1091.
2. Pineles SL, Kraker RT, VanderVeen DK, Hutchinson AK, Galvin JA, Wilson LB, Lambert SR. Atropine for the Prevention of
Myopia Progression in Children. Ophthalmology. 2017 Dec;124(12):1857-1866. doi: 10.1016/j.ophtha.2017.05.032. Epub
2017 Jun 29. PMID: 28669492.
3. Song YY, Wang H, Wang BS, Qi H, Rong ZX, Chen HZ. Atropine in ameliorating the progression of myopia in children with
mild to moderate myopia: a meta-analysis of controlled clinical trials. J Ocul Pharmacol Ther. 2011 Aug;27(4):361-8. doi:
10.1089/jop.2011.0017. Epub 2011 Jun 7.
4. Yam JC, Jiang Y, Tang SM, Law AKP, Chan JJ, Wong E, Ko ST, Young AL, Tham CC, Chen LJ, Pang CP. Low-
Concentration Atropine for Myopia Progression (LAMP) Study: A Randomized, Double-Blinded, Placebo-Controlled Trial of
0.05%, 0.025%, and 0.01% Atropine Eye Drops in Myopia Control. Ophthalmology. 2018 Jul 6. pii: S0161-6420(18)30285-9.
doi:10.1016/j.ophtha.2018.05.029.
5. Li SM, Wu SS, Kang MT, Liu Y, Jia SM, Li SY, Zhan SY, Liu LR, Li H, Chen W, Yang Z, Sun YY, Wang N, Millodot M.
Atropine slows myopia progression more in Asian than white children by meta-analysis. Optom Vis Sci. 2014
Mar;91(3):342-50. doi: 10.1097/OPX.0000000000000178.
6. Walline JJ, Lindsley K, Vedula SS, Cotter SA, Mutti DO, Twelker JD. Cochrane Database Syst Rev. 2011 Dec 7;
(12):CD004916. doi: 10.1002/14651858.CD004916.pub3. PMID: 22161388
7. Chia A, Chua WH, Cheung YB, Wong WL, Lingham A, Fong A, Tan D. 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
Feb;119(2):347-54. doi: 10.1016/j.ophtha.2011.07.031. Epub 2011 Oct 2.
8. Shih YF, Chen CH, Chou AC, Ho TC, Lin LL, Hung PT. Effects of different concentrations of atropine on controlling myopia
in myopic children. J Ocul Pharmacol Ther. 1999 Feb;15(1):85-90.
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glasses in controlling myopic progression. Acta Ophthalmol Scand. 2001 Jun;79(3):233-6.

References:
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Collaboration’s tool for assessing risk of bias in randomised trials BMJ 2011; 343:d5928 [accessed November 24, 2018]
https://www.ncbi.nlm.nih.gov/books/NBK132494/bin/appf-fm1.pdf
11. Lee CY, Sun CC, Lin YF, Lin KK. Effects of topical atropine on intraocular pressure and myopia progression: a prospective
comparative study. BMC Ophthalmol. 2016 Jul 19;16:114. doi: 10.1186/s12886-016-0297-y.
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2011]. The Cochrane Collaboration, 2011. Available from www.handbook.cochrane.org [accessed November 21, 2018]
13. Yen MY, Liu JH, Kao SC, Shiao CH. Comparison of the effect of atropine and cyclopentolate on myopia. Ann Ophthalmol.
1989 May;21(5):180-2, 187.
14. Chua WH, Balakrishnan V, Chan YH, Tong L, Ling Y, Quah BL, Tan D. Atropine for the treatment of childhood myopia.
Ophthalmology. 2006 Dec;113(12):2285-91. Epub 2006 Sep 25. PMID: 16996612
15. Fan DS, Lam DS, Chan CK, Fan AH, Cheung EY, Rao SK. Topical atropine in retarding myopic progression and axial length
growth in children with moderate to severe myopia: a pilot study. Jpn J Ophthalmol. 2007 Jan-Feb;51(1):27-33. Epub 2007
Feb 9.
16. Yi S, Huang Y, Yu SZ, Chen XJ, Yi H, Zeng XL. Therapeutic effect of atropine 1% in children with low myopia. J AAPOS.
2015 Oct;19(5):426-9. doi: 10.1016/j.jaapos.2015.04.006. Epub 2015 Jul 27. PMID: 26228967
17. Wang YR, Bian HL, Wang Q. Atropine 0.5% eyedrops for the treatment of children with low myopia: A randomized controlled
trial. Medicine (Baltimore). 2017 Jul;96(27):e7371. doi: 10.1097/MD.0000000000007371.

1. Li FF, Yam JC. Low-Concentration Atropine Eye Drops for Myopia Progression. Asia Pac J
Ophthalmol (Phila). 2019 Sep-Oct;8(5):360-365. doi: 10.1097/APO.0000000000000256. PMID:
31478936; PMCID: PMC6784858.
2. Yam JC, Jiang Y, Tang SM, Law AKP, Chan JJ, Wong E, Ko ST, Young AL, Tham CC, Chen LJ,
Pang CP. Low-Concentration Atropine for Myopia Progression (LAMP) Study: A Randomized,
Double-Blinded, Placebo-Controlled Trial of 0.05%, 0.025%, and 0.01% Atropine Eye Drops in
Myopia Control. Ophthalmology. 2019 Jan;126(1):113-124. doi: 10.1016/j.ophtha.2018.05.029.
Epub 2018 Jul 6. PMID: 30514630.
3. Yam JC, Li FF, Zhang X, Tang SM, Yip BHK, Kam KW, Ko ST, Young AL, Tham CC, Chen LJ,
Pang CP. Two-Year Clinical Trial of the Low-Concentration Atropine for Myopia Progression
(LAMP) Study: Phase 2 Report. Ophthalmology. 2020 Jul;127(7):910-919. doi: 10.1016/
j.ophtha.2019.12.011. Epub 2019 Dec 21. PMID: 32019700.
4. Li FF, Zhang Y, Zhang X, Yip BHK, Tang SM, Kam KW, Young AL, Chen LJ, Tham CC, Pang CP,
Yam JC. Age Effect on Treatment Responses to 0.05%, 0.025%, and 0.01% Atropine: Low-
Concentration Atropine for Myopia Progression Study. Ophthalmology. 2021
Aug;128(8):1180-1187. doi: 10.1016/j.ophtha.2020.12.036. Epub 2021 Jan 8. PMID: 33422558.
5. Wang S, Wang J, Wang N. Combined Orthokeratology with Atropine for Children with Myopia: A
Meta-Analysis. Ophthalmic Res. 2021;64(5):723-731. doi: 10.1159/000510779. Epub 2020 Aug
11. PMID: 32781450.
6. Khanal S, Phillips JR. Which low-dose atropine for myopia control? Clin Exp Optom. 2020
Mar;103(2):230-232. doi: 10.1111/cxo.12967. Epub 2019 Sep 5. PMID: 31489714; PMCID:
PMC7065125.
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Atropine Eyedrops for Preventing Myopia Progression

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