Clinical

Topical Atropine for Myopia Management: The Latest Research

August 9, 2019

By Jianfeng Zhu, MD, Consultant Pediatric Ophthalmologist, Shanghai Eye Disease Prevention and Treatment Center, Visiting Research Scientist, Brien Holden Vision Institute

A network meta-analysis on myopia control found that use of atropine at different concentrations was significantly superior to other interventions (for example, progressive addition spectacle lenses, multifocal soft contact lenses, orthokeratology, more outdoor activities, etc.)1 Other reviews and meta-analysis similarly concluded that there was less myopic progression with atropine and that both the efficacy and adverse effects were dose-dependent.2, 3

Atropine is a non-selective muscarinic acetylcholine receptor antagonist (mAchR), and the underlying mechanisms by which it controls myopia progression remain unclear. Initially, it was thought that the drug acted via accommodative mechanisms. Later evidence suggested that the mechanism was via non-accommodative pathways,4 with some reports suggesting that atropine exerted its action via retinal amacrine cells and dopamine; when atropine binds to mAchR on the cells, they could release dopamine, which is considered to play a role in slowing myopia.5-7 Other studies reported that atropine could be directly acting on sclera8 and might play a role in inhibiting glycosaminoglycan production and, thus, eye growth. 9, 10

Of all the concentrations assessed, 1% (the highest concentration assessed) atropine used daily has the best efficacy for slowing myopia. However, the concentration is also associated with severe side effects that include photophobia, blurred near vision and worse vision-related quality of life. Additionally, on discontinuation of the drug, the magnitude of rebound observed was greatest with this concentration. Lower concentrations of atropine notably 0.01% was considered to be an effective concentration as there was still a significant slowing of myopia with respect to spherical equivalent, adverse effects were minimal, and there was less rebound after cessation. However, both ATOM2 and LAMP studies showed that while 0.01% atropine was beneficial over placebo as determined by change in spherical equivalent (SE), there was no benefit observed with the change in mean axial length (AL) 11,12. Therefore, 0.01% might not be the ideal dose of atropine for controlling axial myopia.

So, should we attempt a higher concentration? Shih et al. reported 0.5% atropine was the most effective for controlling myopia progression (-0.04±0.63D per year) compared with 0.25% (-0.45±0.55D per year) and 0.1% atropine (-0.47±0.91D per year), but they had not considered adverse effects with the various doses.13 In comparison, ATOM2 study confirmed the efficacy of 0.5% and 0.1% atropine to be superior to 0.01% but reported more severe adverse effects with higher concentrations.11 More recently, the LAMP study reported 0.05% to be the most effective dose for slowing myopia compared with 0.025% and 0.01% while not affecting vision-related quality of life.12 Lee et al. found similar efficacy of 0.05% atropine.14 In conclusion, based on these reported data, low concentration atropine (0.05% to 0.1%) atropine might be a desirable starting concentration. It should be noted that the frequency of atropine use in most clinical trials is once per day and this respect, the use of high-dose atropine at a reduced frequency might be an alternative way to lower the adverse effects while maintaining efficacy, but it remains to be explored.

When should one start atropine treatment for myopes? Most clinical trials showed atropine to exert a satisfactory effect for participants aged 4 to 16 years old. In control eyes, slowest myopia progression was observed in older children (>18 years) and the fastest progression occurred between 8 to 12 years.15 Thus it is advisable to commence at an age when progression is faster. However, younger age was also found to be a risk factor for poor atropine response,16 and additionally, early use of atropine on infant monkeys had an impact on anterior segment eye growth and emmetropization.17 Thus, caution should be exercised in very young children (possibly <4 years) with atropine. Although the majority of studies with atropine were aimed at children with moderate myopia (mean baseline SE ranging from -3.0D to -5.0D) a study found 0.5% atropine to be equally effective for low myopia (-0.5D to -2.0D).18 Additionally, 1% atropine was found to show better myopia control with low myopia (-0.5D to-2.0D) (SE change: 0.32±0.22D per year; AL change: -0.03±0.07mm)19 than moderate-high myopia (≥-3D) (SE change: 0.06±0.79D; AL change: 0.09±0.19mm).20 Thus, it appears that it would be beneficial to start a person on atropine at the onset of myopia. In terms of duration of treatment, the optimal length of treatment is not clear, although most recommend one to two years of active treatment. In Taiwan, use of atropine is continuous till late adolescence (around 15–18 years old), as myopia progression is considered to stabilize around this period.21

Is atropine useful for preventing the onset of myopia? Atropine at 0.025% atropine was effective in preventing myopia onset in pre-myopes (<+1.0D) (change of -0.14D ± 0.24D per year) compared with the control group (-0.58D ± 0.34D per year)22. However, this finding needs to be validated with further studies, and, clearly, the concentration should be as low as possible without the risk of adverse effects. At the other end of the spectrum, there have been very few studies that have assessed the efficacy of atropine in high myopia (worse than -6.0D). However, these found atropine to be efficacious in highly myopic eyes. Atropine at 0.5 % was effective in slowing high myopia in a small group of children compared to tropicamide,23 and in another study, high myopia patients benefited more from 0.125% atropine than low to moderate myopia.24 Thus, the use of atropine in high myopia might have been underestimated but requires further work.

In summary, in terms of benefit versus risk, atropine at concentrations ranging from 0.05 % to 0.1% might be a desirable starting point to initiate treatment. Although these concentrations are not free of side effects, they appear to be less severe and additionally show lesser rebound on discontinuation. Initiating therapy at the onset of myopia may provide greater control and therefore reduce the risk of the eye reaching higher levels of myopia. Although the optimal length of treatment is not clear, continuing treatment until after myopia is stabilized may be a useful strategy to reduce the risk of rebound. In addition, atropine appears to have a role in preventing or delaying the onset of myopia as well as controlling progression in high myopes, but this remains to be explored further.

References

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