Atropine 0.05% for rapid progressive childhood myopia

The authors Saxena et al. have done a significant work to assess the effectiveness of 0.05% atropine for the control of myopia in children aged 6–12 years who had rapidly progressed (>0.75 D) in the last year.[1] They conducted a prospective single-arm (before and after) clinical trial for myopes who had -2.0 to -6.0 D refractive error at baseline and found that instillation of 0.05% atropine once at bedtime was effective in slowing the progression. The response to treatment was not related to the age of starting treatment, preexistent refractive error, earlier progression, gender, and family history of myopia. So far so good.

However, there are questions not completely answered. The authors have not presented (or did not have) the axial length data for the year before, before the 1-year period that is considered for comparison. The study is not a randomized controlled trial (RCT), where these confounders would have been taken care of. The study, though remarkable, needs a higher sample size than the 40 children presented. What is the difference between the two eyes of each child? Was the better eye or worse eye considered?

Would using 0.01% atropine, which is easily and cheaply available commercially, give the same result? The Atropine for the Treatment of Myopia (ATOM) 1 and ATOM 2 studies, well-planned RCTs with 2-year follow-up from Singapore, had demonstrated that atropine eye drops slowed the progression of myopia in Asian children.[2,3] The use of 1% atropine in ATOM 1 study had unacceptable mydriasis and cycloplegia, even if it slowed the progression. In the ATOM 2 study conducted a few years later, 0.5%, 0.1%, and 0.01% atropine were compared. It demonstrated that 0.1% and 0.01% atropine had better control for progression of myopia than 0.5% atropine, and 0.01% atropine was as effective as 0.1% atropine, more effective than 0.5% atropine, and had the least side effects of allergic conjunctivitis, dermatitis, loss of accommodation, challenges in near vision, and mydriasis and was thus considered the candidate of choice. A multicentric study in India demonstrated that instillation of 0.01% atropine in children slowed the progression of myopia in Indian children.[4] The progression was more in younger children, those with larger refractive error, and those with poor compliance.[4] Perhaps 0.05% would be more useful for such children.

The Low-concentration Atropine for Myopia Progression (LAMP) 1 study was an RCT from Hong Kong, in which 438 children aged 4–12 years with myopia of ≤-1.0 D and astigmatism ≤-2.5 D were randomly assigned to four groups: atropine eye drops administered at 0.05%, 0.025%, and 0.01% in three groups, respectively, and compared with placebo for a 1-year period.[5] The mean spherical equivalent change (mean ± standard deviation) was -0.27 ± 0.61 D, -0.46 ± 0.45 D, -0.59 ± 0.61 D, and -0.81 ± 0.53 D in the 0.05%, 0.025%, and 0.01% atropine groups, and placebo group, respectively; the outcome was as per the concentration.[5]

The LAMP 2 study, a robust RCT also from Hong Kong with a 2-year follow-up and a sample size of 474, which was conducted in non-myopic children aged 4–9 years investigated the incidence (new cases) of myopia in children instilled 0.05% or 0.01% atropine and compared the groups with placebo. The study found that 0.05% atropine was more effective than 0.01% atropine and placebo.[6] The 2-year cumulative incidence of myopia in the 0.05% atropine, 0.01% atropine, and placebo groups was 28.4% (33/116), 45.9% (56/122), and 53.0% (61/115), respectively, and the percentage of participants with fast myopic shift at 2 years was 25.0%, 45.1%, and 53.9%, respectively.[6]

So, 0.05% atropine is more effective than 0.01% atropine. To what segment, magnitude of myopia, age of onset, speed of progression, and paucity of compliance should it be recommended compared to 0.01%? There are national guidelines in India for the use of low-dose atropine, but they are for 0.01% atropine.[7] Only a robust multicentric RCT in the Indian setting will be able to answer this question. Otherwise, in children in whom 0.01% atropine does not seem to work, 0.05% atropine would be an option available. But what about the incremental cost? Perhaps the less infrequent side effects? All these questions would need to be answered before we recommend 0.05% as a panacea for rapid processors.

Excess near work, family history, and academic pressure are all known to contribute to myopia progression. Eye drops is just one missile in our armamentarium, albeit the easiest and cheapest one. It is the one most preferred by parents due to its ease of administration and cost compared to special spectacles and contact lenses. The authors Saxena et al. should be complemented for engaging this important aspect of myopia control.