Myopia – can we prevent it?

12th March 2023, Dr Chee L Khoo

Myopia, especially high myopia is associated with increased risk of irreversible blinding conditions, including myopic retinopathy, retinal detachment, choroidal neovascularisation, and glaucoma (1-4) leading to a heavy cost burden on individuals and communities (5). So, it makes sense to see whether we could prevent or delay the onset of myopia or at least slow its progression. Various interventions have been tried including under-correction, progressive addition lenses, contact lenses, pirenzepine gel, and increased outdoor activity. However, the results of these interventions have been disappointing or positive results of marginal clinical significance. The most promising attempt in slowing the progression is topical atropine. Let’s look at the evidence thus far.

Myopia is irreversible once it has developed and the earlier its onset, the greater the likelihood of high myopia (spherical equivalent indicated more myopia than −6.00 D) occurring later in life (6-8). Prevention of myopia potentially can improve long term outcomes. A 2016 review predicted that approximately half of the world’s population will have myopia by 2050, with 10% being high myopia (9). In China, the prevalence of myopia reaches 5.2% in children aged 6 years, nearly 70% in seventh-grade students, and exceeds 80% in university students.  A randomised trial in China found that increasing outdoor class time by 40 minutes daily reduced the 3-year cumulative incidence of myopia from 39.5% to 30.4% in first-grade children (10).

So, does topical atropine reduce slow progression of myopia? If it does, what is the lowest dose to do the job? What is the optimal age to begin the intervention? Well, evidence have slowly evolved over the last 15 years:

ATOM1 (2006)(11)

346 children aged 6 to 12 years with refractive error of spherical equivalent -1.00 to -6.00 diopters (D) and astigmatism of -1.50 D or less were randomised to receive either 1% atropine or vehicle eye drops once nightly for 2 years. Only 1 eye of each subject was chosen through randomisation for treatment. After 2 years, the mean progression of myopia and of axial elongation in the placebo-treated control eyes was -1.20+/-0.69 D and 0.38+/-0.38 mm, respectively. In the atropine-treated eyes, myopia progression was only -0.28+/-0.92 D, whereas the axial length remained essentially unchanged compared with baseline (-0.02+/-0.35 mm).

Topical atropine was well tolerated and effective in slowing the progression of low and moderate myopia and ocular axial elongation in Asian children. But 1% topical atropine came with visual side effects resulting from cycloplegia and mydriasis.

ATOM2 (2012)(12)

400 children aged 6-12 years with myopia of at least -2.0 diopters (D) and astigmatism of -1.50 D or less were randomised to receive either  0.5%, 0.1%, and 0.01% atropine to be administered once nightly to both eyes for 2 years.

After 2 years, atropine 0.01% has minimal side effects compared with atropine at 0.1% and 0.5%, but retains comparable efficacy in controlling myopia progression.

LAMP (1) (2018) (13)

A total of 438 children aged 4 to 12 years with myopia of at least −1.0 diopter (D) and astigmatism of −2.5 D or less were randomised to 0.05%, 0.025%, and 0.01% atropine eye drops, or placebo eye drop, respectively, once nightly to both eyes for 1 year. The 0.05%, 0.025%, and 0.01% atropine eye drops reduced myopia progression along a concentration-dependent response. All concentrations were well tolerated without an adverse effect on vision-related quality of life. Of the 3 concentrations used, 0.05% atropine was most effective in controlling SE progression and AL elongation over a period of 1 year.

LAMP2 (2023) (14)

This is the most recent in the evolution of the evidence. LAMP2 is a placebo-controlled, double-masked trial conducted at the Chinese University of Hong Kong Eye Centre enrolled 474 non-myopic children aged 4 – 9 years with cycloplegic spherical equivalent between +1.00 D to 0.00 D and astigmatism less than −1.00 D. Participants were assigned at random to the 0.05% atropine (n = 160), 0.01% atropine (n = 159), and placebo (n = 155) groups and had eyedrops applied once nightly in both eyes over 2 years.

Among children aged 4 to 9 years without myopia, nightly use of 0.05% atropine eyedrops compared with placebo resulted in a significantly lower incidence of myopia and lower percentage of participants with fast myopic shift at 2 years. There was no significant difference between 0.01% atropine and placebo.

This is a significant finding. Atropine 0.05% have resulted in a reduction in incidence of myopia. Children receiving this treatment had a significantly lower cumulative incidence of myopia and lower percentage who developed a myopic shift of at least 1.00 diopter relative to children in the placebo and 0.01% atropine groups.

In summary, low dose atropine (0.05%) seems to be efficacious in both reducing the progression of myopia in children from about 5-6 years old as well as reducing the incidence of myopia with minimal adverse effects. There remain a number of questions:

  • In the LAMP2 trial, about 20% of participants were excluded because they already have myopia. How early should atropine be initiated?
  • Most of the trials went on for 2 years. What happens when atropine is stopped? How long do we need to continue with atropine?
  • Most of the studies are done on Asian participants. Are these findings applicable to non-Asians?

References:

  1. Saw  SM, Gazzard  G, Shih-Yen  EC, Chua  WH.  Myopia and associated pathological complications.   Ophthalmic Physiol Opt. 2005;25(5):381-391. doi:10.1111/j.1475-1313.2005.00298
  2. Wong  TY, Ferreira  A, Hughes  R, Carter  G, Mitchell  P.  Epidemiology and disease burden of pathologic myopia and myopic choroidal neovascularization: an evidence-based systematic review.   Am J Ophthalmol. 2014;157(1):9-25.e12.
  3. Mitchell  P, Hourihan  F, Sandbach  J, Wang  JJ.  The relationship between glaucoma and myopia: the Blue Mountains Eye Study.   Ophthalmology. 1999;106(10):2010-2015. doi:10.1016/S0161-6420(99)90416-5
  4. Liang  YB, Friedman  DS, Wong  TY,  et al; Handan Eye Study Group.  Prevalence and causes of low vision and blindness in a rural chinese adult population: the Handan Eye Study.   Ophthalmology. 2008;115(11):1965-1972. doi:10.1016/j.ophtha.2008.05.030
  5. Smith  TS, Frick  KD, Holden  BA, Fricke  TR, Naidoo  KS.  Potential lost productivity resulting from the global burden of uncorrected refractive error.   Bull World Health Organ. 2009;87(6):431-437. doi:10.2471/BLT.08.055673
  6. Chua  SY, Sabanayagam  C, Cheung  YB,  et al.  Age of onset of myopia predicts risk of high myopia in later childhood in myopic Singapore children.   Ophthalmic Physiol Opt. 2016;36(4):388-394. doi:10.1111/opo.12305
  7. Pärssinen  O, Kauppinen  M.  Risk factors for high myopia: a 22-year follow-up study from childhood to adulthood.   Acta Ophthalmol. 2019;97(5):510-518. doi:10.1111/aos.139648.
  8. Fang  Y, Yokoi  T, Nagaoka  N,  et al.  Progression of myopic maculopathy during 18-year follow-up.   Ophthalmology. 2018;125(6):863-877. doi:10.1016/j.ophtha.2017.12.005
  9. 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. doi:10.1016/j.ophtha.2016.01.006
  10. He  M, Xiang  F, Zeng  Y,  et al.  Effect of time spent outdoors at school on the development of myopia among children in china: a randomized clinical trial.   JAMA. 2015;314(11):1142-1148. doi:10.1001/jama.2015.10803
  11. 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. doi: 10.1016/j.ophtha.2006.05.062. Epub 2006 Sep 25. PMID: 16996612.
  12. 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.
  13. Yam JC, Jiang Y, Tang SM, et al. 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.
  14. Yam  JC, Zhang  XJ, Zhang  Y,  et al.  Effect of low-concentration atropine eyedrops vs placebo on myopia incidence in children: the LAMP2 randomized clinical trial.   JAMA. 2023;329(6):472-481.