Discover the latest insights on using atropine for myopia control in children. Learn about atropine's optimal concentrations and its safety profile. Explore the effectiveness of standalone and combination therapies.Â
Did you recently learn that your child has myopia? Did your doctor suggest some treatment options to control myopia progression, including an eye drop called atropine? Myopia, commonly known as nearsightedness, has reached alarming prevalence rates globally, with figures nearly doubling over the past three decades.1 If left untreated, myopia can lead to vision-threatening complications, such as myopic macular degeneration, cataracts, glaucoma, and retinal detachment.2 Furthermore, myopia can significantly interfere with children’s ability to see clearly, enjoy sports, or perform well in school.
In this article, we deep dive into atropine, one of the most effective treatments for myopia control. We will explore what atropine is, its mechanisms of action, and the latest research findings on its efficacy and safety profile.
How does atropine work?
Atropine is an antimuscarinic and a subtype of an anticholinergic agent. The most well known effect of an atropine is it can paralyze the ciliary muscles and dilate one’s eyes. This action results in the inhibition of accommodation, preventing the eye from shifting its focus between distant and nearby objects. Essentially, it disrupts the eye's ability to "tune" itself to different viewing distances.2
Despite its well-established role in inhibiting accommodation, the results of numerous studies showed that atropine might exert its actions on myopia through mechanisms beyond accommodation. Studies conducted on animal models propose that atropine could alter retinal neurotransmission by acting on extraretinal muscarinic receptors possibly in the retinal pigment epithelium, choroid, or sclera. Through this action, it was found atropine may increase dopamine release.3
Dopamine that is produced in the retina was hypothesized to regulate refractive development and can impact the balance between eye growth and emmetropization - how the optical structure of the eye adjusts and develops to achieve normal vision.3Â
Current understanding of atropine for myopia control in children
Since its first documented recommendation for the control of myopia published in Glasgow Medical Journal in the 1910s, extensive research has been conducted, particularly in its application to control myopia in children.
Numerous studies have looked into different concentrations of atropine and explored combination therapies, such as atropine combined with myopia control contact lenses or glasses.
High concentration atropine: Effective but with trade-off
Two of the most important initial atropine studies conducted in the early 2000s were ATOM 1 and ATOM 2. The ATOM studies were the largest randomized controlled trials at that time, and they provided strong evidence that myopia progression could be controlled through pharmacological means such as topical atropine.4,5
In the first study (ATOM 1), they found that using high-concentration 1% atropine in one eye every day reduced myopia progression (refractive errors) by 77% compared to placebo. However, after stopping the treatment, the eyes with atropine progressed faster than the placebo group. This phenomenon is commonly referred to as “rebound”. The silver lining to this is that even though the atropine-treated eyes progressed faster after one year, these children’s eyes were still less nearsighted than the untreated ones after three years. In simpler words, high-concentration atropine slows down myopia progression even though there may be a slight rebound after stopping the treatment.4
In the second study (ATOM 2), researchers tried using lower concentrations of atropine (0.5%, 0.1%, and 0.01%) to assess the optimal concentration. Surprisingly, the group with 0.01% atropine, which was supposed to be the control group, slowed down refractive error progression by 59% with less rebound and fewer adverse events.5
What is the optimal low-concentration atropine?
Despite the favorable responses of atropine in refractive error progression, a detailed examination of the findings from the ATOM 2 study showed that the low concentration atropine did not appear to reduce the progression of eye axial length, a crucial factor in evaluating myopia.5Â
After several years of intense discussion, the LAMP study was published, providing valuable insights into the optimal low-concentration atropine for myopia control. In the landmark study, researchers compared various low concentrations of atropine (0.05%, 0.025%, and 0.01%) with a placebo group. The first year of the study highlighted the concentration-dependent effectiveness of these low-concentration atropine solutions. 0.05% proved to be the most effective in controlling both refractive error and axial elongation, with reductions of 66% and 51%, respectively. 0.025% showed the next best results, with reductions of 43% in refractive error and 29% in axial elongation. Although 0.01% exhibited a slight impact on axial length, it was not as effective, showing reductions of 27% and 12%, respectively.6
In the third year of the study, more valuable insights were obtained. About half of the children continued with one of the low-concentration atropine options, while the other half ceased treatment, This allowed us to investigate any rebound effects. Progression was faster in the non-treated groups, and the group that stopped 0.05% atropine displayed a clinically insignificant 'rebound' – merely 0.04mm of difference over one year. Furthermore, 0.05% remained the most effective, while 0.025% and 0.01% did not show a significant difference in total axial length change.7
Based on these results, many experts suggested 0.05% atropine should be the recommended concentration when used as monotherapy.
Combination therapy with 0.01% atropine
If 0.05% atropine is the optimal dose, what could be the role of 0.01% atropine in myopia control in children? Managing myopia progression involves addressing multiple risk factors, often requiring a combination of interventions. Ortho-K, specialized contact lenses, and myopia control eyeglasses act through the optical pathway, while atropine influences retinal neurotransmission. So, how well does 0.01% atropine do when combined with other treatments?
Research indicated that a combination treatment of low-concentration atropine (0.01%) and Ortho-K was highly effective – comparable to using high-concentration atropine monotherapy – in slowing myopia progression in children. Moreover, a 2-year study showed that the combination treatment of Ortho-K with an additional 0.01% atropine is 28% more effective than Ortho-K alone in reducing axial length progression.8
Another combination study revealed that combining 0.01% atropine with MiYOSMART myopia control glasses was highly effective. It provided an additional 25 - 28% reduction in both refractive errors and axial elongation progression than MiYOSMART alone.9
On the other hand, a small study assessed combining low-concentration atropine (0.01%) with the myopia control soft contact lens, MiSight. The findings indicated that the combined approach effectively curbed the progression of myopia. However, despite a numerical improved result compared to the efficacy of MiSight alone, the combined treatment did not attain statistical significance, precluding a conclusion that such combination treatment is more effective.10Â
The safety profile of atropineÂ
Numerous studies have investigated the effectiveness of low-concentration atropine in preventing or slowing down nearsightedness. To gain a more comprehensive understanding, let’s take a look at a meta-analysis of 19 studies involving 3,137 children that evaluated atropine's safety profile.11
In the atropine groups, a total of 308 adverse events were reported, resulting in an overall incidence of 12.7%. The predominant adverse effects included photophobia (25.1%), poor near visual acuity (7.5%), and allergy (2.9%).11
The incidence of atropine-induced adverse events exhibited variation based on drug concentration. High-dose atropine was associated with a higher occurrence of adverse effects, for example, a 43.1% incidence of photophobia compared to 6.3% for low-dose atropine.11
Long-term studies on atropine
Typically, myopia control treatment concludes once myopia stabilizes. This often extends over a period of more than 10 years. Naturally, questions arise regarding the availability of long-term studies to shed light on the efficacy and safety of its long-term use.
In a small 10-year study examining the long-term use of 0.05% atropine for myopia control, findings suggested that children who persisted in their treatment over 10 years exhibited slower myopic progression. Notably, no significant side effects were reported during this long-term study.12
The recently published Atropine Treatment Long-term Assessment Study (ATLAS) delved into the outcomes and safety of atropine use over a 20-year span for 17.8% of the participants in the ATOM1 study and a 10-year follow-up for 39.5% of those in the ATOM2 study. Even though, at the study's conclusion, participants using atropine eye drops for 2 to 4 years during childhood did not result in differences in refractive error, there was also no increased incidence of treatment or myopia-related ocular complications in the 1% atropine-treated group (the 20-year span group) vs the placebo group.13 On the other hand, what is interesting from the ATOM2 group is the incidence of myopic macular degeneration was 19.6%, 28.7%, and 38.1% in atropine groups 0.01%, 0.1%, and 0.5% respectively. The counterintuitive results -- a higher rate of eye complications in the higher concentration atropine -- were speculated that they might be due to a selection bias due to the percentage of participants included in the follow-up or a by-chance finding. Â Â
These findings imply that using atropine for a short period (2 to 4 years) may not result in improved long-term outcomes. However, for children who responded positively and persisted in treatment for over ten years, myopic progression was slower.Â
Key takeaways
Atropine was shown in many studies to be effective with a well-studied safety profile in slowing or stopping the progression of myopia in children. It can be used alone or in combination with other treatments, and various concentrations have been studied for their long-term safety and effectiveness. The recommended concentration for standalone use is 0.05%, while 0.01% has been shown to work well when combined with Ortho-K and myopia control glasses.
Before beginning any treatment, it is important to consult with an eye doctor to weigh the potential risks and benefits. It's important to note that atropine or a myopia control treatment is not a cure for myopia and maintaining good eye habits remains crucial. The key to successful myopia control lies in combining good eye habits with effective treatment, ultimately reducing the risk of vision-threatening complications in the future.
Related article:
1. Atropine eye drop: over a century of myopia control
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