Safety and Efficacy of Low-Dose Atropine Eyedrops for the Treatment of Myopia Progression in Chinese Children

Abstract

IMPORTANCEBecause studies have suggested that atropine might slow the progression of myopia in children, randomized clinical trials are warranted to understand this potential causal relationship.OBJECTIVE To evaluate the efficacy and safety of atropine, 0.01%, eyedrops on slowing myopia progression and axial elongation in Chinese children. DESIGN, SETTING, AND PARTICIPANTSThis was a randomized, placebo-controlled, double-masked study. A total of 220 children aged 6 to 12 years with myopia of −1.00 D to −6.00 D in both eyes were enrolled between April 2018 and July 2018 at Beijing Tongren Hospital, Beijing, China. Cycloplegic refraction and axial length were measured at baseline, 6 months, and 12 months. Adverse events were also recorded.INTERVENTIONS Patients were randomly assigned in a 1:1 ratio to atropine, 0.01%, or placebo groups to be administered once nightly to both eyes for 1 year.MAIN OUTCOMES AND MEASURES Mean changes and percentage differences in myopia progression and axial elongation between atropine, 0.01%, or placebo groups. RESULTSOf 220 participants, 103 were girls (46.8%), and the mean (SD) age was 9.64 (1.68) years. The mean (SD) baseline refractive error and axial length were -2.58 (1.39) D and 24.59 (0.87) mm. Follow-up at 1 year included 76 children (69%) and 83 children (75%) allocated into the atropine, 0.01%, and placebo groups, respectively, when mean myopia progression was −0.49 (0.42) D and −0.76 (0.50) D in the atropine, 0.01%, and placebo groups (mean difference, 0.26 D; 95% CI, 0.12-0.41 D; P < .001), with a relative reduction of 34.2% in myopia progression. The mean (SD) axial elongation in the atropine, 0.01%, group was 0.32 (0.19) mm compared with 0.41 (0.19) mm in the placebo group (mean difference, 0.09 mm; 95% CI, 0.03-0.15 mm; P = .004), with relative reduction of 22.0% in axial elongation. Fifty-one percent and 13.2% of children progressed by at least 0.50 D and 1.00 D in the atropine, 0.01%, group, compared with 69.9% and 34.9% in the placebo group. No serious adverse events related to atropine were reported.CONCLUSIONS AND RELEVANCE While the clinical relevance of the results cannot be determined from this trial, these 1-year results, limited by approximately 70% follow-up, suggest that atropine, 0.01%, eyedrops can slow myopia progression and axial elongation in children and warrant future studies to determine longer-term results and potential effects on slowing sight-threatening pathologic changes later in life.

Risk factors for rapid axial length elongation with low concentration atropine for myopia control

“…It is well established that there is slowing of physiological change in AL in older children 19 We also found that the children with 0.01% atropine had a more rapid AL elongation and a worse myopic control effect than 0.02% atropine 13 . Other reports have also found a concentration-dependent response in myopia control with low concentration atropine 6,10,12,14 . Side effects and adverse effects are reportedly similar in 0.01% and 0.02% atropine 13,20 , suggesting that if children using 0.01% atropine are not achieving adequate myopia control, changing to the 0.02% concentration could be considered.…”

“…In a one year study of Korean myopic children 10 , the AL elongation was about 0.44 ± 0.32mm, 0.30 ± 0.24mm and 0.23 ± 0.25mm in 0.01%, 0.025% and 0.05% atropine, respectively. In a study of Chinese myopic children 14 , the AL elongation after one year was about 0.32 ± 0.19mm and 0.41 ± 0.09mm in 0.01% atropine and placebo, respectively. By comparison, in the present study the AL elongation was 0.36 ± 0.19mm with 0.01% and 0.30 ± 0.22mm with 0.02% atropine, 0.02% atropine had a better effect on myopia control than 0.01% atropine 13 .…”

“…This was consistent with three other studies which explored the same relationship between baseline age and AL increase in myopic children using atropine and whose baseline profiles were similar to the current study. Joachimsen et al 11 , Wei et al 14 and Lee et al 18 found that younger children in German, mainland China and Taiwan may still progress quickly while using 0.01%, 0.01% and 0.05% atropine, respectively. It is well established that there is slowing of physiological change in AL in older children 19 We also found that the children with 0.01% atropine had a more rapid AL elongation and a worse myopic control effect than 0.02% atropine 13 .…”

“…Studies have found a concentration-dependent response in myopia control with low concentration atropine 6,10,12,13 . In the ATOM2 study 5,6 , the change in axial length (AL) and change in spherical equivalent refractive error (SER) were not synchronous, such that in the absence of change in SER, AL changed during use of 0.01% atropine. Conversely, a number of studies, including our previous study found that low concentration atropine reduced myopia progression not only through refractive changes, but also through control of axial elongation 10,[12][13][14][15] . Meanwhile, myopia progression in children varies by race/ethnicity, and East/Southeast Asian children undergo more rapid myopia progression than white children 16,17 .…”

“…Many studies have shown that low concentrations of atropine can control the progression of myopia in children with good efficacy, minimal side effects, convenient use, and slight rebound effects after discontinuation [5][6][7] . Conversely, it has been observed that low concentration atropine has not effectively controlled myopia in all children [5][6][7][8][9][10][11][12][13][14][15] .…”