Low-dose atropine for myopia in children: two years of experience
Children in Tel Aviv have been treated with nightly atropine drops, significantly slowing the progression of myopia.
Eighty-three children with rapidly progressing myopia have been treated with nightly atropine drops in Tel Aviv since January 2015. Their 2-year results were reported by Professor Yair Morad of the Assaf Herofeh Medical Centre at the recent European Society of Ophthalmology meeting in Barcelona.
Atropine drops can significantly slow the progression of myopia. Since this was demonstrated in the ‘atropine for the treatment of childhood myopia’ (ATOM) studies,1,2children have begun to receive treatment in clinics around the world.
ATOM1 and ATOM2
The ATOM1 study showed that 1% atropine administered nightly over a 2-year period slowed myopic progression by 77%.1ATOM2 went on to demonstrate that the effect was dose-dependent and that 0.01% was sufficient to significantly suppress myopia progression.2
A ‘rebound effect’ was evident in both studies: that is, myopia increased when the atropine treatment was stopped, to a greater extent in children who had received higher doses. The least rebound effect was seen with 0.1% atropine; patients receiving this dose had the least overall progression of myopia after 5 years (3 years after the end of treatment).3
Two years of 0.01% atropine treatment provided, after 5 years, a 50% reduction of myopia compared with the predicted value.4
2 years of treatment
The children treated in the Assaf Herofeh Medical Centre, all of whom were progressing by at least 0.75 D/year, were initially given 0.01% atropine drops in both eyes every night. After 6 months, their myopia had stopped progressing (≤0.25 D) in almost all cases.
“We were really amazed to see that after 6 months of treatment almost all children really stopped progressing,” Professor Morad said. “This is actually different from the study in Singapore [ATOM1], where the treatment did not have a profound effect in the first year.”
There were no side effects reported. The mean age of the children at the start of treatment was 9.2 years and their mean refraction was –4.7 D (range –3 to –12 D). Myopia was moderate in 88% and severe (>7 D) in the remaining 12%. Most of the children (72%) had myopic parents.
Only one child, who had a baseline refraction of –6.5 D and two parents with high myopia, continued to progress (by 0.75 D). His dose of atropine was increased to 0.05%.
After 12 months (n = 56), most of the patients were still progressing by 0.5 D or less; two children progressed by 0.75 D (relative to baseline) so were switched to 0.05% atropine.
After 18 months (n = 36), almost all the children had still not progressed more than 0.5 D; only three children progressed more than 0.75 D. And after 2 years (n = 16), 11 children had really stopped progressing, with a decrease of 0.5 D or less.
The remaining five children continued to progress by 1 or 1.25 D, but this is a great result, Professor Morad said, bearing in mind that all these children progressed by at least 0.75 D per year before treatment, and that some were progressing by 1.5 or even 2 D per year.
Myopia progression was reduced to <0.5 D per year in two of the three patients whose atropine dose was increased to 0.05%. One patient continued to progress but only by 1 D per year, which was still much better than the progression he had been experiencing before.
The mean progression across all the children was 0.32 D per year. There were no side effects or discomfort reported, even in those children who received 0.05% atropine.
The best responders were those who had low myopia and no family history. Those with high myopia and two myopic parents did not see such good results.
Outstanding questions
The most difficult question that remains unaddressed is when to stop the treatment, Professor Morad noted. In the ATOM studies, treatment was given for 2 years and then stopped. If the patient continued to progress by >0.5 D per year, treatment could be reinitiated.
“This seems like a sensible approach but there are other possibilities,” Professor Morad said. “Perhaps treatment should be continued until around 13 years of age, when myopia usually stops progressing.”
Another important consideration is cost. Atropine is not yet commercially available as 0.01% drops, so the treatment has to be prepared in a pharmacy-in Israel the cost varies from $20 to $80 per bottle, which could place a high burden on the parents.
Lastly, the long-term side effects are unknown. The studies from the 1970s that looked at 1% atropine showed no significant side effects except for difficulties in accommodation after prolonged treatment.
Professor Morad pointed out that the dose used in these children is much lower and no side effects were reported, which is “hopeful”.
Myopia
Myopia is common and its prevalence is increasing (for example, myopia prevalence, monitored in nearly 1 million people who were joining the Israeli army at the age of 18, increased from 20% in 1990 to 28% in 2002)5. The economic burden is huge, estimated at around 260 billion dollars annually worldwide.6
The main influence on myopia progression is genetics.7More than 20 genetic loci for myopia are known and a child whose parents are both myopic has six times the risk for myopia than a child with non-myopic parents.
It has recently been explored how time spent outdoors is firmly associated with less myopic refraction. A study from China showed that the prevalence of myopia significantly decreased, from 39% (control group) to 30%, in schoolchildren who had 40 minutes of outdoor activities every day.8
There are many studies showing a definite relation between near work and myopia progression. A meta-analysis of 27 such studies (25,025 children) showed that myopia increased by 2% for every hour of near work per week.9
Atropine drops
Atropine drops were first used to arrest myopia in the 1970s: they were initially believed to work by blocking accommodation. However, atropine prevents form myopia from developing in chicks when one eye is blocked, so this cannot be the mechanism.
Instead, it blocks receptors on the sclera, the scleral muscle and retina, and inhibits the thinning and stretching of the sclera that is characteristic of form myopia.
References
1. Chua WH, et al. Atropine for the treatment of childhood myopia. Ophthalmology. 2006;113:2285-2291.
2. Chia A, 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;119:347-354.
3. Tong L, et al. Atropine for the treatment of childhood myopia: effect on myopia progression after cessation of atropine. Ophthalmology. 2009;116:572-579.
4. Chia A, et al. Five-Year Clinical Trial on Atropine for the Treatment of Myopia 2: Myopia Control with Atropine 0.01% Eyedrops. Ophthalmology. 2016;123:391-399.
5. Dayan YB, et al. The changing prevalence of myopia in young adults: a 13-year series of population-based prevalence surveys. Investig. Opthalmology Vis. Sci. 2005;46:2760.
6. Smith TST, et al. Potential lost productivity resulting from the global burden of uncorrected refractive error. Bull. World Health Organ. 2009;87:431-437.
7. Cooke Bailey JN, et al. Advances in the genomics of common eye diseases. Hum. Mol. Genet. 2013;22:R59-R65.
8. He M, et al. Effect of Time Spent Outdoors at School on the Development of Myopia Among Children in China: A Randomized Clinical Trial. JAMA. 2015;314:1142.
9. Huang HM, Chang D-ST , Wu P-C. The Association between Near Work Activities and Myopia in Children-A Systematic Review and Meta-Analysis. PLoS One. 2015;10:e0140419.
Dr Professor Yair Morad, MD
Professor Morad works at Assaf Harofeh Medical Center, Tel Aviv University.
