Twice-daily atropine held a clearer two-year signal than nightly dosing in childhood myopia
Childhood myopia control usually turns on one biologic problem: the eye is still growing when it should be slowing down. In this randomized trial, 0.01% atropine used twice daily produced a stronger two-year effect than the same concentration given once nightly, with slower axial elongation and less refractive worsening across the full follow-up period. The comparison matters because the usual clinical question is not whether atropine can help at all, but whether dose timing and exposure frequency change the size of the effect enough to matter in practice.
Children aged 6 to 13 years with post-cycloplegic spherical equivalent refraction between −0.75 and −6.00 D were randomized 1:1 during the first year to nightly dosing or twice-daily dosing. The first phase set up the head-to-head efficacy comparison, while the second year functioned as a real-world extension without randomization. In the full two-year follow-up, 20 participants remained in the nightly group and 28 in the twice-daily group. Those numbers are modest, and they frame how cautiously the findings need to be read, even when the direction of effect is biologically coherent.
Over two years, adjusted axial length increased by 0.523 mm in the nightly group and 0.372 mm in the twice-daily group. The adjusted between-group difference was −0.132 mm, with a 95% confidence interval from −0.246 to −0.019 and a P value of 0.023. For myopia care, axial length is not a cosmetic measure; it is a proxy for the structural stretch that tracks future risk. A smaller gain in axial length implies a slower march toward the longer eye phenotype that drives progressive myopia.
Refractive change told a similar story. Adjusted spherical equivalent progression reached −1.087 D in the nightly group and −0.447 D in the twice-daily group over two years, with an adjusted difference of 0.640 D and a P value below 0.001. Even without overreading the magnitude, the pattern is hard to ignore: more frequent atropine exposure was associated with materially less refractive drift over the study period. In a pediatric clinic, that can translate into fewer prescription changes, less rapid progression into higher myopia, and a potentially smaller lifetime burden from myopia-related ocular complications.
Why atropine frequency may matter in a growing eye
Atropine’s role in myopia control is tied to the eye’s growth signaling, not simple pupil dilation alone. By modulating muscarinic pathways in ocular tissues, atropine appears to influence the cascade that drives axial elongation. More frequent dosing could plausibly maintain a steadier pharmacologic effect across the day, limiting the biologic windows in which the eye resumes growth signaling. The trial does not prove mechanism, but the clinical pattern fits that framework.
This is also where the distinction between control and convenience becomes clinically relevant. Once-daily regimens are easier for families to remember, yet lower exposure may leave less suppression of the growth process that myopia control is trying to interrupt. Twice-daily dosing raises a practical adherence question, but the available efficacy signal suggests that the extra exposure can buy better structural and refractive control over two years.
The study’s design helps, and it also limits how far the results can be stretched. Randomization occurred in the first year, then the extension became a real-world follow-up without random allocation. The second year therefore cannot isolate whether the lack of added benefit was driven by treatment saturation, adherence drift, attrition, or a true plateau in atropine effect. The absence of a significant between-group difference during Phase II is still informative. It suggests the major efficacy separation occurred earlier, not as a steadily widening gap across the second year.
The second year did not widen the gap
During Phase II, no significant between-group differences emerged in axial length change or spherical equivalent change, with P values of 0.916 and 0.247, respectively. That quiet second-year result matters because it tempers any temptation to frame twice-daily atropine as producing ever-increasing benefit over time. The advantage was visible over the full two-year interval, but the extension itself did not add measurable separation.
In practical terms, that pattern raises a familiar pediatric ophthalmology question: should the treatment plan be judged by early suppression of progression rather than by expectations of cumulative superiority year after year? The answer cannot be written from this dataset alone, but the data clearly indicate that the two regimens did not keep diverging in the extension phase. If anything, the study suggests that the first year carried most of the observable difference.
Small follow-up numbers narrow the certainty window
The study was funded by Tianjin-based science and medical discipline programs, with the funder having no role in study design, conduct, analysis, interpretation, manuscript preparation, or publication decisions. That independence supports the credibility of the work, but the more important limitation remains the small number of children completing two years of follow-up. A 20-patient nightly group and a 28-patient twice-daily group can generate a useful signal, yet they cannot settle dosing strategy for broad pediatric practice on their own.
No competing interests were declared. The trial therefore arrives as a focused clinical comparison rather than a commercially shaped signal. Even so, the clinical question it raises is larger than the sample: how much dosing intensity is enough to slow myopia progression without making family routines unnecessarily burdensome? This study leans toward twice-daily administration for stronger control over two years, but the second-year extension leaves open whether the same advantage would persist in a larger, fully randomized cohort.
A longer and larger trial would need to answer whether the early benefit holds across broader populations, whether adherence changes the real-world value of twice-daily therapy, and whether the modest structural advantage seen here translates into clinically meaningful differences later in childhood or adolescence. Until then, the cleanest reading is narrow and direct: 0.01% atropine given twice daily slowed myopia progression more than nightly dosing over two years, while the extra year of nonrandomized follow-up did not show a new efficacy gain.