Atropine for pre-myopia

Identifying children at risk of myopia can be straightforward, but management can be a challenge when it comes to balancing the benefits of treatment with the impact and likely compliance. New data on low-concentration atropine for pre-myopia presents an interesting and potentially appealing option for proactive management, where a lack of evidence exists otherwise for optical treatments. 

A child with pre-myopia has one or more risk factors for developing myopia such as:

• Lower baseline hyperopia than expected for their age
• A family history of myopia
• Visual environment factors which increase risk of myopia, such as reduced time spent outdoors and intensive near work habits.¹

The International Myopia Institute defines pre-myopia as “a refractive state of an eye of ≤ 0.75 D and > 0.50 D in children where a combination of baseline refraction, age, and other quantifiable risk factors provide a sufficient likelihood of the future development of myopia to merit preventative interventions.”² 

The balance of age and refraction in terms of myopia risk was determined by Zadnik et al,³ who found that the single best accurate predictor of childhood onset myopia before age 13 was the level of cycloplegic autorefraction at a younger age. These cut points are shown in the Table below.

Four studies have shown a potential role for low-concentration atropine in delaying onset in children at risk of myopia development. 

In a retrospective cohort study of 50 Chinese children aged 6-12 years, published in 2010, 0.025% atropine eye drops significantly reduced the myopic shift in pre-myopic children aged 6-12 to -0.14D/year, compared to -0.58D/year in the untreated control group. It was found that 21% of children in the atropine group experienced myopia onset compared to 54% in the control group, and fast myopic shifts occurred in 8% of the atropine group versus 58% of controls, demonstrating effectiveness in preventing myopia onset over a 12-month period. Axial length was not reported.⁴

A randomized case-control study published in 2022 evaluated 60 children in India aged 5-12 years (mean 7.7) years, half of whom had 0.01% atropine and half had no intervention. Before treatment, their progression rate was similar at around 0.70D/year. 

• After one year, the atropine group progressed -0.31D / 0.12mm compared to -0.76D / 0.21mm in the control group
• After two years, the atropine group had progressed a total of -0.60D / 0.21mm compared to -1.75D / 0.48mm in the control group.⁵

A crossover trial in China published in 2023 investigated atropine 0.01% in 60 pre-myopic children aged 6-12 (mean 8.6) years. In the first six months, the atropine group progressed -0.15D and 0.17mm compared to -0.34D and 0.28mm in the placebo group. There was one month without treatment, and then the groups were crossed over, with the second six months showing a similar effect. Within the limits of these two consecutive 6-month periods, atropine 0.01% reduced myopia onset and fast myopic shift.⁶

In the LAMP2 randomised clinical trial published in 2023, involving 474 Hong Kong Chinese children aged 4-9 (mean 6.8) years, atropine 0.05% and 0.01% were investigated for delaying myopia onset. Nightly use of 0.05% atropine eye drops significantly reduced the 2-year cumulative incidence of myopia to 28.4%, and fast myopic shift to 25.0%, compared to 53.0% and 53.9% respectively in the placebo group. In contrast, the 0.01% atropine group showed no significant difference from placebo, with a myopia incidence of 45.9% and a fast myopic shift of 45.1%. The study highlighted 0.05% atropine as effective in preventing early myopia onset.⁷

Currently, the key evidence-based intervention for pre-myopia is increasing time spent outdoors. Meta-analysis has shown the protective effect of outdoor time as reducing incident (onset) myopia by about half, with an increase of 1 hr/day or 7 hr/week resulting in a reduction of incident myopia by 45%. A handful of clinical trials have shown a pooled reduction in myopic shift of -0.30D over three years, although this data includes myopes and non-myopes.⁸ 

Aiming for at least 13 hours per week (around 2 hours per day) as a total amount of outdoor time places children out of the highest risk category,⁸ and recent research has shown this effect is most powerful in children aged 3 to 9 years, to reduce onset of myopia between ages 10 to 15 years.⁹

Which concentration is best? Taking these four studies in sum, these varying concentrations of atropine reduced the incidence of myopia and resulted in myopic shifts and axial length growth at around half the rate of the untreated children. The conflicting outcomes for the two recent randomized controlled trials, both undertaken in Chinese children, perhaps point to the benefit of stronger concentrations for younger children when treating pre-myopia. 

• Atropine 0.01% showed benefit in the study involving children with a mean age of 8.6 (range 6-12) years
• Atropine 0.05% (and not 0.01%) showed benefit in the study involving children with a mean age of 6.8 (range 4-9) years.

It is also important to note that atropine 0.01% was found to be effective in Indian pre-myopic children with a mean age of 7.7 (range 5-12 years). Just as the outcomes of atropine 0.01% for slowing myopia progression appear to be varying by ethnicity - with minimal effects for Asian children^10,11 but some effects found in children in North America¹² and in European children with blue eyes,¹³ the same could be true for pre-myopia treatment. 

Should you prescribe 0.025% as the best ‘mid way’ choice? There could be some sensibility in this, but there’s only the early retrospective study indicating efficacy. If your patient has lighter irides they could be more likely to suffer side effects,^14,15 although there is individual variation. For a slightly older child of Asian ethnicity, atropine 0.025% could be an effective choice to balance efficacy and side effects as well. 

It is a common challenge in myopia management - and in eye care or medicine in general - that we often don’t have the specific study to prove efficacy for that particular child's characteristics. We do have a sum of data now, though, indicating efficacy of low-dose atropine for delaying myopia onset in children at risk of myopia. The choice between this, and the alternative treatment of increasing outdoor time (or both!) will likely depend on the level of concern proactivity of the parents, as well as availability of atropine in your scope and setting of practice.