Four hundred myopic children randomly received atropine 0.02% (n = 138) or 0.01% (n = 142) in both eyes once-nightly or only wore single-vision spectacles (control group) (n = 120) for 2 years. Spherical equivalent refractive error (SER), axial length (AL), pupil diameter (PD), and amplitude of accommodation (AMP) were measured every 4 months. After 2 years, the SER changes were − 0.80 (0.52) D, − 0.93 (0.59) D and − 1.33 (0.72) D and the AL changes were 0.62 (0.29) mm, 0.72 (0.31) mm and 0.88 (0.35) mm in the 0.02% and 0.01% atropine groups and control group, respectively. There were significant differences between changes in SER and AL in the three groups (all P < 0.001). The changes in SER and AL in the 2nd year were similar to the changes in the 1st year in the three groups (all P > 0.05). From baseline to 2 years, the overall decrease in AMP and increase in PD were not significantly different in the two atropine groups, whereas the AMP and PD in the control group remained stable (all P > 0.05). 0.02% atropine had a better effect on myopia control than 0.01% atropine, and its effects on PD and AMP were similar to 0.01% atropine. 0.02% or 0.01% atropine controlled myopia progression and AL elongation synchronously and had similar effects on myopia control each year.

Three hundred and twenty-eight myopic children, randomized to use either 0.01% (N = 166) or 0.02% (N = 162) atropine were enrolled in this study. Gender, age, body mass index(BMI), parental myopia status, atropine concentration used, pupil diameter, amplitude of accommodation, spherical equivalent refractive error (SER), anterior chamber depth (ACD) and axial length (AL) were collected at baseline and 1 year after using atropine. Rapid AL elongation was defined as > 0.36 mm growth per year. Univariate analyses showed that children with rapid AL elongation tend to be younger, have a smaller BMI, use of 0.01% atropine, narrow ACD, lower SER, shorter AL, smaller change in pupil diameter between 1 year and baseline (all P < 0.05). Multivariate logistic regression analyses confirmed that rapid AL elongation was associated with children that were younger at baseline (P < 0.0001), use of 0.01% atropine (P = 0.04), a shorter baseline AL (P = 0.03) and a smaller change in pupil diameter between 1 year and baseline (P = 0.04). Younger children with shorter AL at baseline, less change in their pupil diameter with atropine treatment and using the lower of the two atropine concentrations may undergo rapid AL elongation over a 12 months myopia control treatment period.

To evaluate the e cacy of 0.01% atropine eye drops in preventing myopia shift and myopia onset in premyopic children. A prospective, randomized, double-masked, placebo-controlled, crossover trial was conducted over 13 months. Sixty premyopic children aged 6-12 years with cycloplegic spherical equivalent refraction (SER) > -0.75 D and ≤ + 0.50 D in both eyes were assigned in a 1:1 ratio to receive one drop of 0.01% atropine or placebo once nightly for 6 months (period 1), followed by a 1-month recovery period. Then, the 0.01% atropine group was crossed over to the placebo group, and the latter was crossed over to the 0.01% atropine group for another 6 months (period 2). The primary outcomes were changes in SER and axial length (AL), and the secondary outcomes were the proportion of myopia onset (SER ≤ -0.75D) and fast myopic shift (change in SER ≤ -0.25D) in the two periods. Generalized estimating equation (GEE) model performed statistically signi cant treatment effect of 0.01% atropine compared with placebo (p SER = 0.02, p AL < 0.001), with a mean SER and AL difference of 0.20D (-0.15 ± 0.26D vs. -0.34 ± 0.34D) and 0.11mm (0.17 ± 0.11mm vs. 0.28 ± 0.14mm) in period 1, and 0.17D (-0.18 ± 0.24D vs. -0.34 ± 0.31D) and 0.10mm (0.15 ± 0.15mm vs. 0.24 ± 0.11mm) in period 2. GEE model showed that the proportion of myopia onset (p = 0.004) and fast myopic shift (p = 0.009) were signi cantly lower in the 0.01% atropine group than that in the placebo group. The period effect was not statistically signi cant (all p > 0.05). 0.01% atropine signi cantly prevented myopic shift, axial elongation, and myopia onset in premyopic schoolchildren in central Mainland China.Conclusions: Within the limits of only two consecutive 6-month observation period, 0.01% atropine eye drops effectively prevented myopic shift, axial elongation, and myopia onset in premyopic children.Trial registration: This trial was registered in the Chinese Clinical Trial Registry (Registration number: ChiCTR2000034760). Registered 18 July 2020. What Is Known• Minimal studies on interventions for pre-myopia, despite the International Myopia Institute stating that preventing myopia is an "even more valuable target" for science and practice than reducing progression after onset.What Is New • 0.01% atropine eye drops may safely and effectively reduce the proportion of myopia onset and fast myopic shift in premyopic schoolchildren.

Background: To evaluate the additive effects of orthokeratology (OK) lenses and 0.01% atropine on slowing axial elongation in myopic children. Methods: A prospective, randomized, double-blinded, placebo-controlled trial was conducted over a 12-month period. Sixty children aged 8 to 12 years with spherical equivalent refraction from − 1.00 to -4.00 D who had been wearing OK lenses successfully for 2 months (as baseline) were randomly assigned in a 1:1 ratio to combination group (combination of OK lens and 0.01% atropine eye drops) and control group (combination of OK lens and placebo). The primary outcome was change in axial length, along with secondary outcomes including change in pupil diameter (PD) and accommodative amplitude (AMP) at 12 months (measured at 4-month intervals). Results: After 12 months, the overall axial elongation was 0.10 ± 0.14 mm and 0.20 ± 0.15 mm (p = 0.01) in the combination and control groups, respectively. The change in axial length in the two groups showed significant differences only in the first four months (median [Q1, Q3] (95% CI), -0.01 mm [-0.07, 0.05] (-0.06, 0.04) vs. 0.04 mm [0.00, 0.10] (0.02, 0.09); p = 0.04), but no difference thereafter. Multivariate linear regression analysis showed that the axial elongation was significantly slower in the combination group than in the control group (standard β = -0.10, p = 0.02). PD significantly increased by 0.45 mm [0.20, 0.68] at the 4th month visit (p < 0.001) and then remained stable in the combination group. The PD in the control group and AMP in the two groups remained stable from baseline to 12 months (all p > 0.05). Conclusion: The combination therapy was more effective than the OK lens alone in slowing axial elongation after 12 months of treatment, and mainly in the first 4 months. Trial registration: The First Affiliated Hospital of Zhengzhou University, ChiCTR2000033904. Registered 16/06/2020, http://www.chictr.org.cn/login.aspx?referurl=%2flistbycreater.aspx

To evaluate the efficacy of 0.01% atropine eye drops in preventing myopia shift and myopia onset in premyopic children. A prospective, randomized, double-masked, placebo-controlled, crossover trial was conducted over 13 months. Sixty premyopic children aged 6–12 years with cycloplegic spherical equivalent refraction (SER) > -0.75 D and ≤ + 0.50 D in both eyes were assigned in a 1:1 ratio to receive one drop of 0.01% atropine or placebo once nightly for 6 months (period 1), followed by a 1-month recovery period. Then, the 0.01% atropine group was crossed over to the placebo group, and the latter was crossed over to the 0.01% atropine group for another 6 months (period 2). The primary outcomes were changes in SER and axial length (AL), and the secondary outcomes were the proportion of myopia onset (SER ≤ -0.75D) and fast myopic shift (change in SER ≤ -0.25D) in the two periods. Generalized estimating equation (GEE) model performed statistically significant treatment effect of 0.01% atropine compared with placebo (pSER = 0.02, pAL < 0.001), with a mean SER and AL difference of 0.20D (-0.15 ± 0.26D vs. -0.34 ± 0.34D) and 0.11mm (0.17 ± 0.11mm vs. 0.28 ± 0.14mm) in period 1, and 0.17D (-0.18 ± 0.24D vs. -0.34 ± 0.31D) and 0.10mm (0.15 ± 0.15mm vs. 0.24 ± 0.11mm) in period 2. GEE model showed that the proportion of myopia onset (p = 0.004) and fast myopic shift (p = 0.009) were significantly lower in the 0.01% atropine group than that in the placebo group. The period effect was not statistically significant (all p > 0.05). 0.01% atropine significantly prevented myopic shift, axial elongation, and myopia onset in premyopic schoolchildren in central Mainland China. Conclusions: Within the limits of only two consecutive 6-month observation period, 0.01% atropine eye drops effectively prevented myopic shift, axial elongation, and myopia onset in premyopic children. Trial registration: This trial was registered in the Chinese Clinical Trial Registry (Registration number: ChiCTR2000034760). Registered 18 July 2020.