In the review by Foster and Jiang (2014), who summarised the incidence, prevalence, and progression of myopia, it is clear that myopia is an epidemic. Myopia can lead to significant and irreversible vision loss. This calls for urgent intervention of successful myopia control. According to the literature of the last decade, atropine eye drops proves to be one of the most effective treatments to limit myopia progression. The use of atropine for controlling myopia progression dates back to 1979 (Cheng and Hsieh, 2014), making it the oldest, and still most effective, pharmacological treatment (McBrien et al. 2013).
This literature review provides a summary of the usage, safety, and efficacy of atropine eye drops for myopia control. It was systemised by collecting information from the Cochrane, Star-Plus, International Myopia Institute, and Myopia Profile databases. Sources used were limited to recently published literature of the last decade (2010 to 2019). The study population in all referenced sources are all under the age of eighteen, with no specific race group.
Using atropine for myopia control
As a non-specific muscarinic antagonist, atropine relaxes accommodation by paralysing the ciliary muscles and dilating the pupil. This allows for increased ultraviolet exposure, which limits scleral growth and reducing axial length (Cheng and Hsieh, 2014). McBrien et al. (2013) agreed that the main limiting factor for myopia is inhibition of axial length growth, however it is still not clear whether the exact site of action of atropine in myopia control is on the retina, sclera or choroid. McBrien et al. (2013) supported the argument that myopia progression is not reduced by accommodation paralysis. This is supported by findings where myopia was reduced by atropine usage in chickens with striated ciliary muscles, which is not innervated by muscarinic receptors, and thus refers to a non-accommodative action.
Huang et al (2016) classifies atropine dosage into high-dose (1% & 0.5%), moderate-dose (0.1%) and low-dose (0.01%). There is clinical uncertainty regarding the most effective and safe dosage of atropine. It is influenced by a number of factors, such as the degree of myopia, age of starting treatment, duration of treatment, and when to cease atropine usage. According to the findings of Chia et al. (2016), a daily dose of 0.01% is the proposed dosage of atropine for myopia control in children between six and twelve years of age who show an annual myopic progression of 0.5 dioptres or more. Wu et al. (2019) also suggested a dosing regimen of once daily at bedtime. Children between the age of six and twelve years are the major and most common population group included in myopia control trials and studies. Wolffshohn et al. (2019) agreed that pharmaceutical myopia control treatment is most effective when started during this period. Wu et al. (2019) advocated a gradual increase of low-dose atropine with cautious routine follow up, monitoring for any side effects. This treatment regimen should be followed for a minimum of two years and can only be stopped if there is no or less than 0.25Dioptres of myopic progression. Atropine 0.01% can be restarted if the myopia progression proves to be more than this desirable end-point. Rebound myopia assessment should be done at least for one year after cessation of atropine treatment (Wolffsohn et al., 2019). Wolffsohn et al. (2019) suggested that clinical trials evaluating myopia control should be conducted over a minimum period of three years.
Wolffshohn et al. (2019) recommended a routine check-up every six months to evaluate the safety and efficacy of the treatment regimen. The same baseline tests should be conducted for accurate comparison and monitoring, of which axial length is a crucial parameter. Annual cycloplegic refraction and fundus examinations are advised. Wu et al. (2019) differed in the follow-up routine by referring to a three month follow up period and recommends cycloplegic refraction with every visit.
Safety of atropine for myopia control
The Cochrane review by Walline et al. (2011) made a general conclusion that atropine drops caused photophobia and affected near vision. This conclusion cannot be generalised as the review does not specify whether all the trials included in the study used the same percentage of atropine, neither does the review specify whether all trials used the same drop administration routine. However, Chia et el (2012) clarified that 1% atropine caused mydriasis and cycloplegia, whereby increased pupil size pose a risk for glare and harmful sunlight exposure, although these side effects were negligible in 0.01% atropine usage. Increased ultraviolet exposure through the dilated pupil enhances the risk for retinal solar damage and cataract formation (Cheng and Hsieh, 2014). As a preventative measure against photophobia, Wu et al. (2019) proposed the use of hats, sunglasses, and photochromic lenses. Patients on lower dosage atropine recover faster from pupil dilatation, paralysed accommodation, and blurry near vision during the rebound treatment phase (Chia et al. 2014). Yam et al. (2019) gathered evidence that low-dose atropine of 0.05%, 0.025%, and 0.01% is safe and well-tolerated regarding pupil dilatation, best-corrected distance and near vision, over a one year study period. Chia et al. (2012) reported dermatitis and allergic conjunctivitis in the administration of 0.5% and 0.1%. Kothari et al. (2018) concluded that allergy to atropine eye drops is most prevalent in high-dose atropine with ocular symptoms such as itching, burning, conjunctival hyperaemia, discharge, and periocular swelling. To reduce allergic reactions, punctal occlusion should be done after drop instillation, and excess drops should be wiped off the periocular skin. Atropine usage should be ceased until all symptoms have resolved, after which a lower concentration of atropine can be introduced. McBrien et al. (2013) referred to premature presbyopia as a side effect in long-term atropine treatment. Further elaboration on this was not found, and it is unclear if this side effect was linked to high or low dosage atropine. Light coloured irises have shown to be more causative of adverse effects (Gong et al., 2017).
Although uncommon, atropine usage does carry the risk of systemic complications such as dry mouth, face flush, headache, hypertension, constipation, difficulty urinating and central nervous interruptions (Wu et al., 2019).
Psychological effects can include bullying when peers notice dilated pupils (Wu et al., 2019).
Efficacy of using atropine for myopia control
The authors of the Cochrane review, Walline et al. (2011), concluded that atropine successfully limited myopia progression compared to other myopia control strategies in their randomised control trials which included: under-correction of myopia, progressive addition spectacle lenses, bifocal spectacle lenses, rigid gas permeable contact lenses, and soft multifocal contact lenses. These interventions were compared to single vision spectacle lenses, placebo or no treatment.
Chia et al. (2012) reviewed that 1% and 0.5% atropine showed more favourable control of myopia progression than 0.1% & 0.01%, but unfortunately due to reduced accommodative amplitude, additional costs were required for bifocal or multifocal spectacle lenses. The concentration-dependent response was found in high-dose atropine as well as in low dose atropine (Yam et al.,2019). This contradicts the findings of Gong et al. (2017), who suggested that atropine efficacy is dose-independent within the dosage range, although side effects were dose-dependent. Chia et al. (2016) reported 0.01% atropine to have a significant balance between efficacy and safety in controlling myopia in their long-term five-year study compared to Chia et al. (2012) with a shorter study term. Gong et al. (2017) agreed that low-dose atropine is safe and efficient in limiting myopia progression. Wu et al. (2019) referred to a successful treatment period of a minimum of two years. In the study of Yam et al. (2019), low-dose atropine of 0.05%, 0.025%, and 0.01% compared to placebo groups, showed to significantly reduce the spherical equivalent refractive error, proportional to the dosage, but with no significant statistical difference in limiting axial length. According to the Atropine for the Treatment of Myopia (ATOM 2) study of Chia et al. (2012) and Low-Concentration Atropine for Myopia Progression (LAMP) study of Yam et al. (2019) both indicate poor axial length control with atropine 0.01%, which questions the clinical usefulness of atropine 0.01%, as axial length control is crucial in myopia control.
As the low dosage atropine might be less efficient in controlling myopia progression compared to the higher dosages, Cheng and Hsieh (2014) suggested combining 0.125% atropine with auricular acupoint stimulation which reduces intraocular pressure and enhances micro-circulation around the eyes stimulating relaxation of the ciliary muscle. Wei et al. (2011) and Yeh (2012) reported that auricular acupuncture shows favourable results in controlling myopia, but only in a large study population in studies conducted over a period of one year or more. Wu et al. (2019) also advised low-dose atropine to be combined with increased outdoor time and limiting non-productive near work.
Chia et al. (2014) and Chia et al. (2016) both studied children between six and twelve years of age that used low-dose and high-dose atropine for two years and then ceased treatment for 1year. Their studies agreed that the rebound of myopic progression, after cessation of atropine treatment, was greater in the higher dose atropine group. Chia et al. (2014)’s statistics showed that myopic rebound progression is directly proportional to increased atropine dosage.
The most recent International Myopia Institute myopia control report by Wolffsohn et al. (2019) agreed with the above studies by Chia et al. 2012, 2014, and 2016. High-dose atropine can reduce myopia progression by 60%-80%, while low-dose atropine reduces myopia progression by 45%, but with increased safety and less rebound myopia after discontinuation.
Parental education plays a pivotal role in effective pharmacological treatment. Parents need to understand and be aware of myopia progression, its causes, associated risks, and treatment options. They need to be informed about investment in related costs and frequent check-ups required (McCrann et al., 2018). Optometrists and other eye care professionals form part of the guilty party, too, as they are not implementing and actively involved in atropine usage. This could possibly be due to the lack of consensus regarding the ultimate atropine dosage (Wolffsohn et al. 2016) and the availability of low-dose atropine.
Atropine eye drops are one of the most successful interventions to slow down myopia progression. The aim is to reduce axial length growth. High-dose atropine is more effective than low-dose atropine in achieving reduced myopia progression, but low-dose atropine results in less adverse effects. This review concludes that low-dose atropine is the best for efficacy and safety of children up until eighteen years of age, although best results were achieved between six and twelve years of age. Unfortunately, low-dose atropine is not readily available and require compounding pharmacies to provide this pharmaceutical combination.
Low-dose atropine for myopia control should be administered once daily at bedtime, for a minimum period of two years, with follow up appointments every six months. Atropine usage can be ceased when myopia progression is a quarter Dioptre or less. Rebound myopia should be assessed for at least one year after ceasing atropine treatment. Low-dose atropine should be the dose of choice in case of rebound myopia. It can be used in combination with other myopia control strategies to ensure increased efficacy. Side effects are rarely fatal and can be easily managed or reversed upon incidence.
Eye care professionals and parents should be kept well informed regarding atropine usage to achieve a compliant and successful trend for atropine myopia control.
The ideal atropine dose will provide the best balance between efficacy and safety of the concentration used on each individual. Gradual concentration increase can be done with close monitoring of side effects. Research is still unclear whether atropine administration will be safe to use twice daily for a minimum two year period. Further studies on the mechanism of atropine action are suggested, as controversy arises between sources. Limited sources are available showing the efficacy of atropine amongst international race groups, but large study populations are required.
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