Atropine has been the apparent hero of myopia management since the 2006 publication of the ATOM (atropine for the treatment of childhood myopia) study, which showed an 80% refractive and 100% axial length myopia controlling effect with 1% atropine compared to placebo.1 The significant side effects of mydriasis and cycloplegia, though, made it less than tolerable as a first line treatment for progressive myopia.
More recently, low dose (0.01%) atropine has become the new hero, on the basis of an evolving story in the literature. Firstly, the ATOM2 study in 2012 investigated 0.5%, 0.1% and 0.01% atropine for efficacy, and found that in both refractive and axial length control, the results appeared to be more impressive with greater concentrations.2 This study did not include a control group – as the story goes, the 0.01% atropine was meant to be the placebo. The plot twist was the ATOM2 five year study, published in 2016, which took the participants of the ATOM2 study and from year 2 to year 3, discontinued all treatment. Greater rebound effects were noted with the higher concentrations. Then, at the start of year 4, all remaining participants were recommenced on 0.01% atropine. The final picture at the end of year 5 showed that the children who had commenced on 0.01% atropine for two years, discontinued for a year, then commenced 0.01% again for another two years, had the lowest overall refractive progression.3 This low dose of atropine is much more clinically palatable, appearing to have a negligible side effect profile compared to higher concentrations.
The crown slips on 0.01% atropine
Newer analysis of the ATOM studies, though, has revealed that 0.01% atropine is not all it’s cracked up to be as a myopia management hero. In early 2018, Mark Bullimore and David Berntsen published a letter to the Editor of JAMA Ophthalmology4 evaluating the data on low dose (0.01%) atropine, pointing out the enormous mismatch between its efficacy for refractive versus axial length control. In secondary analysis – comparison to the historical ATOM1, 2006 study control group – the ATOM2 data showed a 59% refractive control effect but a -8% axial length control effect for 0.01% atropine. If axial length is a key risk factor for risk of myopia pathology and vision impairment5 then this must bring into question the clinical usefulness of low dose atropine, which is clinically popular, especially in ophthalmology-driven myopia management.
A study with a concurrent control group is the better method for assessing comparative efficacy. In mid-2018, the Low-Concentration Atropine for Myopia Progression (LAMP) was published online, with one year data again showing efficacy correlated with concentration.6 More studies are underway around the world, and in other ethnicities, as all of this cited data has been collected on children in Asian countries.
So which atropine concentration is best? Comparative efficacy and side effects are shown in the table above. As shown, 0.1% and 0.5% dilated the pupil by around 3mm and dramatically impaired near vision in the ATOM2 study – this makes these concentration an unpalatable option for school aged children who need comfortable near vision to learn. By comparison, 0.025% and 0.05% showed a small pupil dilation and minimal loss of accommodative amplitude in the LAMP study. Once again, 0.01% atropine looks pretty unimpressive as a first line therapy. There’s still a lot we need to learn about atropine, including any more subtle effects on binocular vision beyond amps of accommodation, ideal dosage schedules, treatment tapering and safe discontinuation. Perhaps it will work best in combination with optical treatments, as early research is beginning to indicate. For the moment, though, I’m personally sticking to optical treatments as first line therapy – as that myopia needs to be corrected anyway, and considering atropine as a secondary treatment, as outlined in our Clinical Decision Trees.
For a great summary of the ATOM1 and ATOM2 data in a clinician-accessible form, check out the June 2018 article written by Professor John Phillips of University of Auckland for the NZ Optics journal.