Myopia Management PERSPECTIVES

Evaluating efficacy of low-dose atropine for myopia management

Referenced papers:
  • CHAMP study – Efficacy and Safety of 0.01% and 0.02% Atropine for the Treatment of Pediatric Myopia Progression Over 3 Years: A Randomized Clinical Trial. Paper authors: Karla Zadnik et al.
  • PEDIG study – Low-Dose 0.01% Atropine Eye Drops vs Placebo for Myopia Control: A Randomized Clinical Trial. Paper authors: Michael X. Repka et al.
  • ATLAS study – Topical Atropine for Childhood Myopia Control: The Atropine Treatment Long-Term Assessment Study. Paper authors: Yong Li et al.

This report evaluates the role of low-dose atropine in myopia management in children, drawing on insights from the Childhood Atropine for Myopia Progression (CHAMP), Pediatric Eye Disease Investigator Group (PEDIG) and Atropine Treatment Long-term Assessment Study (ATLAS) projects.  These recent studies share some similarities in their goal of examining the effect on axial length of low-dose atropine, but as ever with myopia management studies, care must be taken when comparing results due to differences in study design (e.g. study duration) and individual limitations.

Importantly, CHAMP and PEDIG are among the first large-scale studies to examine the safety and efficacy of low-dose atropine in Western populations, a noteworthy shift from previous research predominantly conducted in Asian settings.  CHAMP examined two non-compounded, preservative-free atropine concentrations across North America and Europe over 36 months.  The use of non-compounded drug introduced a level of formulation consistency not seen in earlier studies. PEDIG focused on comparing 0.01% atropine with a placebo in the United States over 24 months, plus a 6-month observation period, further enhancing our understanding of its effectiveness in non-Asian populations.  ATLAS extends this overall body of research by assessing the long-term safety and effectiveness of topical atropine in controlling childhood myopia, by reviewing subjects who participated in both the Atropine Treatment of Myopia (ATOM1[1]) and ATOM2[2] trials up to two decades earlier.

What the Research Showed

CHAMP Trial Findings
The CHAMP study, a phase 3 clinical trial (a study conducted to determine if a product can be launched) across 27 clinical sites in North America and five countries in Europe, included 576 participants aged three to 17 years, with initial myopia ranging from -0.50 D to -6.00 D. It compared the efficacy of low-dose atropine (0.01% and 0.02%) against a placebo control group over 36 months. The study found that both concentrations significantly slowed myopia progression; interestingly, the 0.01% concentration demonstrated superior efficacy in reducing axial elongation and refractive error changes. However, it is important to contextualise these results: while statistically significant, the reductions in myopia progression were modest and lower than in a number of optical (e.g. orthokeratology or multifocal contact lens) and atropine studies.  The study also revealed that the preservative-free, low-dose atropine formulation used in the study had a favorable safety profile with participants showing good tolerance to both concentrations (0.01% and 0.02%), with minimal ocular side effects.

PEDIG Trial Findings
The PEDIG study, conducted from June 2018 to September 2022 across the United States, involved 187 children aged three to 12 years with initial myopia between -1.00DS and -6.00DS. It examined the impact of nightly 0.01% atropine eye drops versus a placebo over 24 months, followed by a six-month observation period. The study concluded that 0.01% atropine did not significantly slow myopia progression or axial elongation compared to the placebo, suggesting that this concentration may not be effective to manage myopia in some populations.  This finding contrasts with several studies conducted in East Asia, where low-dose atropine has shown significant efficacy. Potential reasons for these differing outcomes include racial and ethnic differences in response to atropine, iris pigmentation affecting drug efficacy, variations in study design, and differences in baseline myopia progression rates among populations. These factors are crucial for clinicians to consider when interpreting the effectiveness of low-dose atropine across diverse patient groups.

ATLAS Trial Findings
The ATLAS project collated long-term data from mainly Chinese subjects aged six to 12 years who took part in the ATOM1 and ATOM2 trials about 20 and 10 years earlier, respectively. About one quarter of the original trial participants were assessed for this new work; they had initially been treated with either a placebo or atropine between 0.01%, and 1.0% for two to four years. Results indicated no clear long-term benefits in refractive or axial length change across different atropine concentrations compared to controls, although these findings should be interpreted with caution due to selection bias, as a significant number of original participants were not included in the long-term follow-up because of logistical challenges and participant availability. Overall, rates of most adverse events did not differ between the various randomised groups which provides some assurance about the use of atropine for myopia management. One exception here was for myopic macular degeneration which increased significantly with increasing atropine concentration. However, the changes noted were largely retinal tessellation, which may not progress to vision loss.

Key Takeaways for Practising Eye Care Professionals

Adult female doctor ophthalmologist checking eye vision of young girl in modern clinic
  • The results and conclusions drawn from studies of low-dose atropine are varied, especially in Western/White populations.
  • The best concentration for the use of low dose atropine requires further research.
  • Long-term follow-up is essential to fully understand the efficacy and safety of atropine in managing myopia, as immediate treatment outcomes may not reflect sustained effects on axial length over a longer period. This is particularly important due to the association between axial length and the development of myopia-related pathologies.

Three Action Items for Practising Eye Care Professionals

  1. Stay informed about the evolving research on the use of low dose atropine to manage myopia.
  2. Consider that low-dose atropine does not offer day-to-day refractive correction, unlike contact lens and spectacle myopia management approaches.
  3. Engage in open discussions with patients and their families about the benefits and limitations of low-dose atropine for myopia management, ensuring informed decision-making and setting realistic expectations.

For the full-length articles, please visit here, here and here.

[1] Chua  W-H, Balakrishnan  V, Chan  Y-H,  et al.  Atropine for the treatment of childhood myopia.   Ophthalmology. 2006;113(12):2285-2291.

[2] Chia  A, Chua  W-H, Cheung  Y-B,  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.

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Mitigation
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Prepared by the World Council of Optometry Myopia Management Resource Committee 2023.
The World Council of Optometry Myopia Management Standard of Care initiative is a collaborative partnership between World Council of Optometry and CooperVision.

Soft Dual Focus or Multifocal Contact Lenses

Spectacle Lenses for Myopia Control

Orthokeratology

Atropine

When to wear it

Children who are physically active
Ideal for very young wearers
Children disliking glasses and/or inclined to not wearing them full-time

Considerations

Shown to improve confidence and ability to participate in activities.

Typically more availability for astigmats.

No wearing time during waking hours.

Optical correction is still needed.

* Excluding children frequently engaged in water sports.