Myopia control in children: Atropine efficacy not proportional to dose

Use of atropine in the treatment of children with myopia helps slow refraction changes and axial elongation, although the drug’s efficacy is not proportional to dose, according to the results of a network meta-analysis.

Specifically, the most efficacious atropine concentrations were 1%, 0.5%, and 0.05%, with the latter being ranked as having the greatest benefit in terms of overall myopia progression, the investigators said.

“Higher-dose atropine ranked as a better intervention in slowing down refraction changes and axial elongation than did lower-dose atropine. Among moderate-dose (0.02–0.25%) atropine, 0.05 percent showed comparable efficacy to that of high-dose atropine and was ranked third in terms of [delaying] refraction changes and second [with respect to] slowing axial elongation,” they added.

The network meta-analysis included 30 pairwise comparisons from 16 placebo-controlled or head-to-head trials. The total population comprised 3,272 children with short-sightedness who had receive treatment for at least a year. The investigators ranked eight atropine concentrations (1%, 0.5%, 0.25%, 0.1%, 0.05%, 0.025%, 0.02%, and 0.01%) according to the primary outcome measures of mean annual changes in refraction (dioptres [dpt]/year [yr]) and axial length (AXL, millimetres [mm]/yr).

Compared with control, three atropine concentrations emerged as most beneficial with regard to delaying changes in refraction and axial length: 1% (mean difference [MD] 0.81 dpt/yr, 95 percent confidence interval [CI], 0.58–1.04; MD, –0.35 mm/yr, 95 percent CI, –0.46 to –0.25), 0.5% (MD, 0.70 dpt/yr, 95 percent CI, 0.40–1.00; MD, –0.23 mm/yr, 95 percent CI, –0.38 to –0.07), and 0.05% (MD, 0.62 dpt/yr, 95 percent CI, 0.17–1.07; MD, –0.25 mm/yr, –0.44 to –0.06). [Ophthalmology 2021;doi:10.1016/j.ophtha.2021.10.016]

For overall myopia progression, the 0.05% dose came out as the most efficacious (relative risk [RR], 0.39, 95 percent CI, 0.27–0.57), followed by the 1% dose (RR, 0.43, 95 percent CI, 0.33–0.56).

In terms of safety, the ranking probability for adverse effects (eg, photopic/mesopic pupil diameter and accommodation amplitude) tended to follow a dose-related order. However, this trend was not evident for distance best-corrected visual acuity (BVCA).

Atropine is a nonselective muscarinic antagonist that has been studied widely in recent years as an option for myopia control. The optimal concentration, according to the investigators, should be the one with the best balance between efficacy and safety. [Ophthalmology 2016;123:697-708]

Since progressive high myopia is a risk factor for open-angle glaucoma, cataract, myopic macular degeneration, and other complications that can lead to irreversible visual impairment later in life, a treatment to effectively put brakes on myopia progression in children are needed. [JAMA Ophthalmol 2016;134:1355-1363; BMC Ophthalmol 2020;20:1-8]

Aside from pharmacological treatment, other approaches are employed to slow down the progression of myopia. These include increased outdoor activity, reduced near work, peripheral defocusing lenses, and orthokeratology contact lenses. [Eye Contact Lens 2016;42:3-8]

“In any case, myopia is now the leading cause of preventable blindness in children and adolescents, which makes it an urgent public health issue… [O]ur network meta-analysis [showed] strong evidence that atropine treatment in children with myopia [is effective at delaying progression],” the investigators stated.

They underscored a need for well-supported evidence on ranking probabilities for near BCVA and/or acceptability to better establish the risk/benefit ratios of different atropine concentrations.

Myopia is the most common eye disease in children and adolescents in East Asia and is declared to have already reached a pandemic level. The eye disorder is projected to affect 4.8 billion people worldwide by the year 2050, which means that in 30 years, about half of the world population will be short-sighted. [Nature 2015;519:276; Prog Retin Eye Res 2018;62:134-149; Ophthalmology 2016;123:1036-1042]