Juan Ding, OD, PhD

Short summary if you don’t have time:

Yes, low dose atropine can lower myopia risk if used in children without myopia in this Hong Kong study. However, even without it, 47% of the studied children did not develop myopia after 2 years. In those using 0.01% atropine, 54% did not develop myopia, and in those using 0.05% atropine, 72% did not develop myopia. A dose dependent effect of myopia prevention can be inferred. But whether to use atropine or what dose to use should be an individualized process.

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Official full text below

Recently, the University of Hong Kong published a paper [1] to study whether two different concentrations of low-dose atropine can prevent the development of myopia for children whose eyes are not yet myopic. This is a randomized double-blind study involving more than 400 children aged 4-9 years old with 0-1.00 diopters of hyperopia. About 1/3 received placebo, 1/3 used 0.05 % atropine once daily, and 1/3 used 0.01 % atropine eye drops once daily for two years, and the development of myopia was observed in these children. The study found no statistically significant difference using atropine 0.01% compared with placebo. In contrast, atropine at a concentration of 0.05% was able to delay the progression of myopia. After this article came out, many people had doubts. Wasn’t it shown that atropine at a concentration of 0.01% can control the growth of myopia? Why can’t it play a role in preventing myopia? So should we not use 0.01% atropine at all, but should use 0.05% instead?

To explore this issue, we need to understand the history of atropine used to control myopia.

It was discovered decades ago that 1 % atropine (note the high concentration) could slow down the progression of myopia. However, relatively high-quality evidence, such as a randomized, double-blind clinical study, was not published until 2006. In 2006, a clinical study conducted in Singapore confirmed that 1 % atropine was used for 2 years to effectively control myopia, reducing myopia by 7 7% [2]. Of course, its side effects are also very significant. 1% atropine is a common drug used to dilate pupils for fundus examination or for cycloplegic refraction. It can effectively dilate the pupils and completely paralyze the ciliary muscle of the eyes, so the eyes will be very light sensitive and blurry when looking at near objects. This side effect makes it unrealistic to use 1% atropine to control myopia. Almost no one can tolerate such side effects, especially considering that myopia control is done over many years, due to myopia progression naturally stops only between the ages of 16 and 18. Another disadvantage of 1% atropine for myopia control is that myopia progression actually rebounded remarkedly after discontinuation [3].

Later, scholars in Singapore did more randomized double-blind studies [4], they studied whether lower concentrations of atropine besides 1% atropine can also play a role in controlling myopia, which may have less severe side effects. They studied concentrations at 0.5%, 0.1%, and 0.01%. In this study, scholars found that the effect of atropine on controlling myopia is a concentration-related. That is to say, the higher the concentration, the better the effect of controlling myopia. But the side effects are also dose dependent. Another result that surprised them is that 0.01%, which is equivalent to diluting 1 % atropine 100 times, can still play a role in controlling myopia. And this concentration of atropine has almost no mydriatic (pupil dilating) effect and side effects. This study was also observed for two years.

At the third year, all children stopped using atropine, and the researchers wanted to see whether myopia would continue to grow. They found that after stopping the relatively high concentrations of atropine (0.5 % and 0.1 %), the myopia rebounded, that is to say, the speed of myopia progression increased faster than average myopic children. But surprisingly the 0.01% concentration of atropine showed no such phenomenon of rebound [5].

The study found that the side effects of atropine at a concentration of 0.01% are very low. Although there are some side effects of mydriasis and loss of accommodation, the vast majority of children are not disturbed, and they can still see normally.

This result suggests that although the concentration of 0.01% atropine is very low, it can effectively control myopia, and the side effects are also the lowest. It is conceivable that the safety is also the best. After this research was published, many countries in Asia began to use 0.01% atropine to control myopia in children. At the same time, people started to steer away from the relatively high concentration of atropine (a concentration greater than 0.1 %), because these high concentrations may not only have worse side effects, but also rebound after discontinuation.

However, at this time, there is no research on concentrations in between 0.1% and 0.01%. Will they also be effective in controlling myopia? How about the side effects? What about myopia rebound after discontinuation?

To answer these questions, researchers at the University of Hong Kong conducted research on this issue. They recruited children who had already developed myopia and randomly assigned them to placebo, 0.01%, 0.025%, and 0.05% concentrations of atropine once a day. Their research also found that the effect of atropine on controlling myopia has a dose dependent effect, and the higher the concentration, the better the effect of controlling myopia. The effect of atropine 0.025% and 0.05% in controlling myopia is better than that of 0.01% [6]. Reenforcing previous research, compared with placebo, atropine at a concentration of 0.01% can still control myopia. The researchers also tested the children’s accommodation and how pupil size was affected by these different concentrations of atropine. It turns out that it is also related to the concentration, that is to say, the higher the concentration, the greater the side effects. However, even atropine at a concentration of 0.05% is still tolerated by most children.

After the two-year study, they also stopped using the drug for a year to see if the myopia would rebound. This result is also related to the concentration of atropine. If the concentration is slightly higher, such as 0.05%, the rebound will be slightly more. Of course, this rebound is much smaller than the rebound of atropine with a higher concentration such as 0.1%, 0.5% and 1%. The lowest rebound is still 0.01% [7].

These results are actually quite consistent with the previous results in Singapore. Generally speaking, we know that the higher the concentration of atropine, the better the effect of controlling myopia, but even at a concentration of 0.01%, it is already effective. In terms of side effects, atropine at a concentration of 0.05% or lower are relatively easy to tolerate, and more than this concentration will be worse, and more children will not be able to tolerate it. Therefore, it is generally believed that atropine with a concentration of 0.05% or lower should used, and atropine with a higher concentration is not recommended. In particular, there are other means to control myopia, such as orthokeratology lenses, peripheral defocused spectacles, and soft multifocal contact lenses, so it is not necessary to insist on a high-concentration atropine, which will reduce quality of life. Since the long-term safety of atropine is still under study, it is important to minimize drug exposure, using a relatively low concentration and with the shortest duration possible. The rebound phenomenon after discontinuation also needs attention, as there may be many children who will not be able to use atropine all the years until they are 18. From this point of view, 0.01% concentration of atropine is still a good choice.

These previous studies were conducted on children who had already developed myopia. But more and more parents are asking, since low-concentration atropine can effectively control the growth of myopia, can I use it when my child is not yet myopic, so as to prevent my child from developing myopia, maybe he will never develop myopia?

The current study by the University of Hong Kong helped us answer this question. The data of this study tell us that the use of 0.01% and 0.05% atropine to prevent the development of myopia is relatively safe, and the side effects in these children are also relatively low, and most children can tolerate it. The effect of 0.05% concentration of atropine is significant. But they also found that 0.01% atropine was not much different vs controls. So should 0.01% concentration of atropine be abandoned?

We have to analyze this issue with logic. Though this new study unfortunately did not include the 0.02% concentration, a trend can be seen from the data that the effect on the prevention of myopia is dose dependent. Atropine at a concentration of 0.01% was actually better than placebo (Figure 1), though this result did not reach statistical significance. Myopia developed in 45.9% of the children given atropine 0.01% compared with 53% of the children given the placebo.

Figure 1. Myopia prevention by atropine. In the beginning, none of the children had myopic (the value was 0). As time went by, more and more children developed myopia. But the children who received 0.05% atropine had the lowest rate of myopia. The blue line is the placebo group, the black line is the 0.01 % atropine group, and the orange line is the 0.05 % atropine group. The chart comes from reference [1]

I think the results of this study are quite consistent with previous studies on myopic children, that is to say, the higher the concentration, the better the effect of atropine on controlling or preventing myopia. This is straightforward, logical, and supported by a lot of previous data. So the 0.01% is just a dose that is very low, that in certain population the effect is not significant enough. And this population happens to be one that even without any intervention, myopia does not develop in half the children, as shown by the placebo group. That is to say, even in the group of children who received atropine at a concentration of 0.05%, perhaps half of the children did not need to use it at all and would not develop myopia.

On the other hand, though 0.05% atropine is effective, it is not 100% effective. After two years of intervention, approximately 28.4% of children in the 0.05% atropine group were still myopic. So it is clear that 0.05% atropine can indeed reduce the risk of developing myopia within two years, but it cannot completely avoid the occurrence of myopia.

This is the conclusion of the research. There is naturally a big difference between real life and research. In the study, a child is randomly assigned to a treatment regimen for a time set by the study, say in this case two years. In real life, of course, it is impossible to apply a fixed method to a child, regardless of the effect of the method itself over years. For example, in real life, we may give a child 0.01% concentration of atropine to control myopia. If it is observed that the control effect is not very good, we will switch to other methods, such as increasing the concentration of atropine, or changing to orthokeratology lenses or soft multifocal contact lenses, instead of continuing to use the same method mechanically. Therefore, the enlightenment brought to us by a study is mainly the effect and safety of the treatment method itself. Based on this information, we can apply the methodology to treat patients. It is not an automatic copying of the research.

What we know so far is that the safety of low-concentration atropine between 0.01% and 0.05% is relatively good, and most children can tolerate the side effects. In children who are already myopic, it can control myopia, and the higher the concentration within this range, the better the control effect. We also know now that even in non-myopic children using these concentrations of atropine can reduce the risk of myopia development, a similar dose dependent effect can be inferred. But this does not mean that when children are not nearsighted, 0.05% concentration of atropine should be used to prevent myopia automatically. Consider that 47 % of children do not develop myopia within two years even without any medical intervention. If 0.05% concentration of atropine is blindly given to every child, this will increase unnecessary drug exposure to nearly half of the children.

For those children whose parents are myopic, and whose eye axial growth is relatively fast and hyperopia is declining rapidly, if the parents and children have a strong motivation to prevent the development of myopia, 0.05% can be considered in this scenario. But for a child with relatively stable hyperopia and normal eye axial growth, it is not necessary. It is safer to observe regularly and intervene only after changes are detected.

Even after children develop myopia, what kind of concentration to use is a personalized treatment process. Atropine at a concentration of 0.01% can indeed reduce the rate of myopia increase, which has been confirmed in many clinical trials. A more reasonable consideration is to use 0.01% concentration of atropine to control after the development of myopia, and observe regularly for six months to one year. If the effect is not good, then increase the concentration to 0.05% , add/or use other controls model. Because there are indeed many children who can get effective myopia control after using 0.01% concentration of atropine alone, with the least rebound effect and side effects. If you use a relatively high concentration directly without trying a low concentration first, you will not know whether the child can effectively control myopia with only a lower concentration, which is not conducive to reducing drug exposure.

As a parent, you can communicate with the doctor to formulate a personalized treatment plan that suits your child, instead of blindly following the trend and using atropine with a relatively high concentration for control.

To summarize the existing research results of atropine in controlling myopia: atropine can effectively control the growth of myopia, and this effect is related to the concentration, the higher the concentration, the better the effect. However, the higher the concentration, the greater the side effects, and the more rebound after discontinuation. At present, it is found that 0.01%, and 0.025% and 0.05% concentrations of atropine can effectively control the further growth of myopia. And their side effects are acceptable to most children. For prevention of myopia, 0.05% concentration of atropine can also be considered. Atropine at a concentration of 0.01% has no significant difference from placebo in the prevention of myopia in one study so far. But the current study is limited to children in Hong Kong, and the follow-up is only two years. In fact, for an individual child, what method to use to prevent or control myopia should be a personalized plan for the child and their family.

References

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• [4] Chia A, Chua WH, Cheung YB, 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: 347e354
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• [7] Yam JC, Zhang XJ, Zhang Y, Wang YM, Tang SM, Li FF, Kam KW, Ko ST, Yip BHK, Young AL, Tham CC, Chen LJ, Pang CP. Three-Year Clinical Trial of Low-Concentration Atropine for Myopia Progression (LAMP) Study: Continued Versus Washout: Phase 3 Report. Ophthalmology. 2022 Mar;129(3):308-321. doi: 10.1016/j.ophtha.2021.10.002. Epub 2021 Oct 7. PMID: 3462780 9.