Timing of Height Growth Peaks and Axial Elongation in Atropine-Treated Myopic Children

Timing of Height Growth Peaks and Axial Elongation in Atropine-Treated Myopic Children | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Timing of Height Growth Peaks and Axial Elongation in Atropine-Treated Myopic Children Dongheon Surl, Jinu Han, Yuri Seo This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8776737/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 20 You are reading this latest preprint version Abstract Purpose To investigate the association between systemic height growth rate and ocular axial elongation rate in atropine-treated children with myopia, and to explore whether the timing of height growth may serve as a prognostic factor for treatment response. Methods Children with myopia ( 1 year were included. Participants were classified into a control group (no atropine) and an atropine group (0.05% nightly, initiated for axial elongation ≥ 0.4 mm/year). Axial elongation and height growth rates were calculated for each inter-visit interval. Peak growth ages were defined as those with the greatest inter-visit changes. Subgroup analyses in the atropine group were based on the median peak height growth age (10.45 years) and median annual axial elongation rate (0.23 mm/year). Results A total of 139 eyes from 70 children were analyzed (56 control, 83 atropine-treated). Height growth rate and axial elongation rate were not significantly correlated in either group. In the atropine group, peak height growth age showed marginal bimodality (P = 0.051) and correlated strongly with peak axial elongation age (r = 0.86, P < 0.01). Children with earlier height growth peaks had greater annual axial elongation (0.27 ± 0.17 vs. 0.15 ± 0.12 mm/year; P < 0.01) despite identical dosing. Conclusions Among atropine-treated children, earlier systemic growth peaks were associated with faster axial elongation. Monitoring height growth timing may help identify rapid ocular growth periods and optimize treatment strategies. Myopia progression Axial elongation Atropine treatment Height growth peak Pediatric ocular development Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 INTRODUCTION Myopia is a growing global public health concern, with increasing prevalence and earlier onset among children ( 1 – 4 ). Among various interventions to slow myopia progression, low-concentration atropine eye drops have shown efficacy in reducing ocular axial elongation—a key factor associated with disease progression and long-term ocular complications ( 5 – 7 ). In clinical practice, decisions regarding the initiation or adjustment of atropine therapy are often guided by the rate of axial elongation, which can be measured quickly and noninvasively, without requiring cycloplegia ( 8 ). However, axial elongation is not always predictable at the time of initial diagnosis or during early follow-ups. We hypothesized that the rate of systemic physical growth—specifically, height velocity—might parallel the rate of ocular axial elongation in children. Prior studies have explored associations between ocular axial length and anthropometric parameters, such as height, body mass index (BMI), and foot size ( 9 – 13 ). While some reported positive correlations between stature or growth velocity and axial length, others failed to establish consistent or predictive relationships. These discrepancies may stem from differences in study design, age ranges, ethnicity, or lack of treatment stratification. Despite widespread use of atropine in clinical settings, no study has examined whether systemic growth markers can predict axial elongation in children undergoing pharmacological treatment. Given that 25%–42% of atropine-treated children are classified as non-responders in previous trials, identifying predictors of treatment response remains an important unmet need ( 14 – 17 ). If systemic growth trajectories—such as the timing or velocity of height spurts—can indicate future axial elongation, clinicians may better anticipate periods of rapid myopia progression. This could facilitate prognostic discussions with families regarding and optimize the timing of treatment initiation or adjustment. Additionally, understanding whether certain growth characteristics are linked to reduced responsiveness to atropine could support personalized management strategies for pediatric myopia. Rather than examining a direct causal relationship between systemic growth and ocular axial elongation, this study aimed to characterize the overall relationship between axial elongation rate and systemic height growth patterns, and to further explore whether the timing of somatic growth is associated with inter-individual variability in axial elongation among children undergoing atropine treatment. METHODS This retrospective cohort study included children with myopia under 15 years of age who underwent serial ocular biometry and anthropometric assessments at a minimum of three clinic visits over a period exceeding 1 year. Participants were classified into two groups: a control group with no atropine treatment, and an atropine group prescribed 0.05% atropine once nightly, initiated due to axial elongation of ≥ 0.4 mm/year and the absence of contraindications such as cardiac or respiratory conditions ( 18 ). The baseline visit for the atropine group was defined as the time of treatment initiation. Inclusion criteria required a myopic refraction of less than − 0.50 D and astigmatism less than − 2.5D at the initial visit, along with complete ocular biometric and anthropometric data for all visits, including axial length, anterior chamber depth, lens thickness, white-to-white distance, keratometry, central corneal thickness, height, weight, and BMI. Exclusion criteria included a history of retinopathy of prematurity, congenital cataract, amblyopia or strabismus requiring treatment, neurological or syndromic disorders, or prior use of orthokeratology lenses. Children who received growth hormone therapy or gonadotropin-releasing hormone analogs for precocious puberty were excluded due to potential alterations in natural growth patterns. Children in the control group wore single-vision spectacles only. Participants using orthokeratology lenses, myopia control spectacles, or soft contact lenses were excluded. The primary outcome was the axial elongation rate. Axial elongation and height growth rates were calculated between visits by dividing the change in axial length or height by the time interval, expressed in millimeters per month (mm/month) and centimeters per month (cm/month), respectively. Axial length was measured using optical biometry (IOLMaster 700, Carl Zeiss Meditec, Germany), and height was measured at each visit using a wall-mounted stadiometer, with children barefoot and standing upright. All anthropometric and ocular measurements were obtained on the same visit day. For subgroup comparisons, an average annual axial elongation rate was calculated for each eye by dividing the total axial length change by the total follow-up duration, expressed in millimeters per year (mm/year) to facilitate interpretation. Peak ages for height growth and axial elongation were defined as the visit age corresponding to the greatest change rate between two consecutive visits. Subgroup analyses were conducted within the atropine. Participants were divided into early or late peak growth subgroups based on whether their peak occurred before or after the median age. Comparisons of annual axial elongation rates were made between these groups. Participants were also stratified into high or low axial elongation subgroups using the median annual axial elongation rate as the threshold. Peak ages for height and axial elongation were then compared across subgroups. Statistical analyses were performed using R software (version 4.3.0). Baseline characteristics were compared using independent t-tests. Linear mixed-effects models were used to evaluate the associations between height velocity and axial elongation while accounting for repeated measures. Height was treated as a subject-level variable, while axial elongation was analyzed at the eye level using mixed-effects models with subject-level random effects. To control for age-related variations, participants were stratified into quartiles based on visit age (Q1: ≤ 8.92 years; Q2: 8.93–10.45 years; Q3: 10.46–11.77 years; Q4: ≥ 11.78 years), and these strata were incorporated into graphical and modeling analyses. Distributional characteristics of peak ages were assessed using the Shapiro-Wilk test (normality), Levene’s test (homogeneity of variance), Kolmogorov–Smirnov test (distributional differences), and Hartigan’s dip test (modality). Skewness and kurtosis were also calculated to assess distributional shape. Pearson’s correlation was used to evaluate the association between height peak age and axial elongation peak age. A p-value < 0.05 was considered statistically significant. This study was approved by the Institutional Review Board of Yongin Severance Hospital, Yongin, South Korea (approval number: 2024-0339-001), and conducted in accordance with the Declaration of Helsinki. The author declares no conflicts of interest. RESULTS A total of 139 eyes from 70 children were included in the analysis (56 eyes in the control group and 83 eyes in the atropine group). Baseline biometric and anthropometric characteristics are summarized in Table 1. At the initial visit, there were no significant differences in height, weight, BMI, or ocular biometry measurements between the two groups, except for axial length and spherical equivalent. Initial axial length was significantly longer in atropine group compared to the control group (24.76 ± 1.03 mm vs. 24.18 ± 0.98 mm, P < 0.01). Initial spherical equivalent was also significantly more myopic in the atropine group (-3.19 ± 1.89D vs.-2.11 ± 1.85D, P < 0.01). Comparison of biometric and anthropometric change rates revealed significantly lower axial elongation in the atropine group (0.018 ± 0.014 mm/month vs. 0.024 ± 0.011 mm/month, P < 0.01), while corneal diameter (white-to-white) increased more in the atropine group than in the control group (0.003 ± 0.007 mm/month vs. − 0.001 ± 0.008 mm/month, P < 0.01). No significant differences were observed for other parameters between the groups (Supplementary Table 1). Because age is known to affect both height growth and axial elongation ( 19 – 21 ), the influence of age on height growth rate was evaluated before analyzing its relationship with axial elongation. In the control group, height growth rate decreased significantly with age (β = − 0.028 cm/month per year, P = 0.012); Supplementary Fig. 1. In contrast, no significant association was observed in the atropine group (β = 0.004 cm/month per year, P = 0.716), suggesting more heterogeneous somatic growth trajectories among atropine-treated children. The association between height growth rate and axial elongation rate was evaluated using linear mixed-effects models while adjusting for age (Fig. 1 ). In the atropine group, height growth rate was not significantly associated with axial elongation (β = − 0.021 mm/month per cm/month, P = 0.726). Axial elongation rate showed a modest but significant decrease with age (β = − 0.011 mm/month per year, P = 0.011), although this association was no longer significant after adjusting for both age and height growth rate (P = 0.942). In the control group, axial elongation rate also decreased significantly with age (β = − 0.048 mm/month per year, P = 0.003), while the effect of height growth rate remained non-significant (β = − 0.537 mm/month per cm/month, P = 0.123). After adjusting for age, the interaction term between height growth rate and age was also not statistically significant (P = 0.182). To account for age-related variation in growth patterns, data points in Fig. 1 were stratified by visit age quartiles (Q1: ≤ 8.92 years, Q2: 8.93–10.45 years, Q3: 10.46–11.77 years, Q4: ≥ 11.78 years), showing that the lack of association between height and axial elongation persisted across age groups. In conclusion, height growth rate showed no significant association with axial elongation rate in either group even after adjusting for age. Our initial hypothesis was that axial elongation rate would be associated with height growth rate. However, as shown in Fig. 1 , this association was not observed. To further investigate this discrepancy, we analyzed the distribution of peak ages for height growth rate and axial elongation rate in each group. The peak age was defined as the visit age at which the greatest change rate occurred for each eye. The distributions are shown in Fig. 2 . In the control group, the peak ages for both height growth and axial elongation rates were normally distributed (Shapiro–Wilk test, P = 0.106 and 0.376, respectively), and nearly identical (11.09 ± 1.92 years vs. 11.03 ± 2.16 years), with no significant difference between them (paired t-test, P = 0.62). These results suggest a synchronized pattern of systemic height and ocular axial growth in the absence of atropine treatment. Conversely, the atropine group showed a broader distribution of peak ages for height growth, with marginal evidence for bimodality (Hartigan’s dip test, P = 0.051). Although the distribution did not show two sharply separated peaks, visual inspection of Fig. 2 reveals a flattened central portion and a wide spread of peak ages, suggesting heterogeneity in growth timing among treated children. The distribution of axial elongation peak age in the atropine group appeared similarly variable, though statistical tests supported approximate unimodality (Shapiro-Wilk test: P = 0.478; Hartigan’s dip test: P = 0.091). The two most prominent peak ages for height growth in the atropine group were 8.81 and 10.75 years, while those for axial elongation were 9.77 and 11.5 years. Despite the appearance of multiple peaks, the mean peak age of axial elongation was 10.59 ± 2.1 years, representing the central tendency. Summary statistics, including skewness, kurtosis, and results of normality and variance tests, are provided in Supplementary Table 2. To further explore variability in peak growth timing within the atropine group, participants were categorized as “early growth peak (n = 42)” and “late growth peak (n = 41)” based on the median peak age of height growth (10.45 years). A strong positive correlation was observed between peak height growth age and peak axial elongation age in the atropine group (r = 0.86, P < 0.01; Fig. 3 ). Earlier peak height growth was associated with earlier axial length elongation, suggesting close alignment in the timing of systemic and ocular growth spurt. Axial elongation rate per year was also compared between the two subgroups. The early height growth peak group exhibited a significantly faster axial elongation rate than the late growth peak group (0.27 ± 0.17 mm/year vs. 0.15 ± 0.12 mm/year, P < 0.01; Fig. 4 ). A similar pattern was observed when the groups were defined by axial length peak age (median = 10.28 years), with the early peak group showing faster elongation (0.27 ± 0.17 mm/year vs. 0.15 ± 0.12 mm/year, P < 0.01), although the bimodality of axial elongation peak age did not reach statistical significance. This subgroup analysis is presented in Supplementary Fig. 2, based on the bimodal pattern observed in Fig. 2 . To further assess the relationship between growth timing and myopia progression in the atropine group, participants were stratified by the median axial elongation rate (0.21 mm/year). The high axial elongation rate group (n = 41) showed significantly earlier peak ages than the low-rate group (n = 42) for both height growth (9.66 ± 1.91 vs. 11.06 ± 1.82 years, P < 0.001) and axial elongation (9.6 ± 2.11 vs. 11.05 ± 1.72 years, P < 0.001). However, within each subgroup, the timing of height growth and axial elongation did not differ significantly (P = 0.85 for high-rate group; P = 0.56 for low-rate group), suggesting that systemic height and ocular axial growth remained synchronized regardless of the overall rate of elongation (Fig. 5 ). DISCUSSION We hypothesized that the rate of axial elongation would increase in parallel with systemic height growth rate and that this association could influence the efficacy of atropine in suppressing axial elongation. However, no significant correlation between axial elongation rate and systemic height growth rate was found in either the atropine or control groups (Fig. 1 ). To investigate this discrepancy, we analyzed the distributions of peak age for height growth and axial elongation. In the control group, the peak ages for height growth and axial elongation were closely synchronized (11.09 ± 1.92 vs. 11.03 ± 2.16 years), both following a unimodal, normal distribution. In contrast, the atropine group showed a suggestive bimodal pattern for the peak age of height growth, which was visually mirrored in the distribution of axial elongation peak age, although statistical tests did not confirm significant bimodality (Fig. 2 ). Subgroup analyses were conducted within the atropine-treated group (Figs. 3 , 4 , and 5 ). Earlier onset of height growth spurts was strongly associated with earlier axial elongation peaks (r = 0.86, P < 0.01; Fig. 3 ). Moreover, patients with an earlier height growth peak exhibited significantly faster annual axial elongation compared to those with later height growth peaks (P < 0.01; Fig. 4 ). When participants were stratified by axial elongation rate, those with higher elongation rates demonstrated significantly earlier peak ages for both height growth and axial elongation compared to those with lower elongation rates (Fig. 5 ). Notably, within each group, the peak ages of height growth and axial elongation remained closely synchronized (Fig. 5 ). These findings suggest that the temporal pattern of systemic growth—specifically, the timing of the height growth spurt—is more closely aligned with axial elongation than with overall growth velocity, regardless of atropine treatment. Importantly, the absence of a significant linear association between age and axial elongation rate in the atropine-treated cohort should not be interpreted as age-independent ocular growth. Rather, this finding likely reflects the heterogeneity of growth trajectories and the modifying effects of atropine treatment, which may obscure a simple age-related pattern within this clinically selected population. Interestingly, while both height growth rate and axial elongation rate followed unimodal distributions in the control group, the atropine group exhibited bimodal patterns for both parameters—even though the bimodality in axial elongation did not reach statistical significance. This pattern is likely not a direct consequence of atropine treatment but may reflect heterogeneity in underlying growth trajectories that could influence treatment response. Given the retrospective nature of this study, group classification was based on real-world clinical decisions: children with myopia of less than − 0.50 D were followed longitudinally, and those demonstrating axial elongation ≥ 0.4 mm/year were initiated on atropine treatment, forming the atropine group, while those with slower progression comprised the control group. Within the atropine group, patients with later height growth peaks exhibited peak ages (10.75 years for height growth and 11.5 years for axial elongation) similar to those observed in the control group (11.09 and 11.03 years, respectively). In contrast, patients with earlier height growth peaks demonstrated markedly earlier timing for both height growth (9.77 years) and axial elongation (8.81 years). This heterogeneity likely contributed to the lack of a consistent linear relationship between height growth rate and axial elongation rate. Nevertheless, a strong positive correlation was observed between the timing of height growth peak and axial elongation peak within the atropine group (r = 0.86, P < 0.01), indicating that systemic and ocular growth spurts tended to occur in close temporal proximity, regardless of whether the peak occurred early or late (Fig. 3 ). Although the control group also demonstrated close alignment between systemic and ocular growth peaks—evidenced by nearly identical mean peak ages and unimodal distributions—there was no significant correlation between the magnitude of height change and axial elongation rate (Fig. 1 ). These findings suggest that while the timing of systemic and ocular growth is often synchronized, the extent of growth in height and axial length is not necessarily correlated. Another clinically important finding is that, within the atropine group, children with earlier height growth peaks showed significantly greater annual axial elongation than those with later growth peaks, despite receiving the same atropine concentration and dosing frequency (Fig. 4 ). This suggests that early-onset systemic growth may be associated with reduced responsiveness to atropine in suppressing axial elongation. To further assess the predictive value of height growth peak timing, we performed a subgroup analysis based on axial elongation rate. When participants were stratified into high and low axial elongation rate groups, those in the high-rate group demonstrated significantly earlier peak ages for both height growth and axial elongation compared to the low-rate group (Fig. 5 ). Notably, within each subgroup, the timing of height and axial elongation peaks remained closely synchronized, with no significant difference between the two. These findings indicate that children who experience an earlier systemic growth spurt may be more likely to exhibit faster axial elongation and diminished response to atropine treatment, underscoring the potential of height growth peak age as a clinically meaningful marker for predicting treatment outcomes in pediatric myopia management. Previous studies have demonstrated that ocular axial elongation often coincides with periods of accelerated physical growth during childhood, suggesting a temporally synchronized relationship between systemic and ocular development ( 9 , 11 , 22 ). Specifically, earlier onset of peak height velocity has been associated with earlier axial elongation and earlier myopia onset, highlighting the importance of growth timing as a risk factor for myopia progression ( 9 ). However, these studies were limited to observational designs and did not assess whether growth patterns may influence responsiveness to pharmacologic interventions such as atropine ( 9 , 11 , 12 ). In the present study, we analyzed a clinically defined cohort in which children with documented rapid axial elongation were treated with uniform atropine therapy. Among these treated children, those with earlier height growth peaks showed significantly earlier axial elongation peaks and greater annual axial elongation, despite receiving identical atropine concentrations and regimens. This finding suggests that early biological maturation may be associated with attenuated responsiveness to atropine in suppressing ocular growth. Additionally, the bimodal distribution of growth peak ages—observed exclusively in the atropine group—likely reflects underlying heterogeneity in systemic growth trajectories that may have influenced treatment initiation timing. While previous reports have examined anthropometric correlates of axial length in adult populations ( 10 ) or identified behavioral and biometric predictors of myopia progression without accounting for treatment exposure ( 13 ), our study provides a unique perspective by linking physiologic growth patterns with both axial elongation timing and treatment efficacy in a pediatric population with myopia. Axial elongation and linear height growth are governed by multifactorial biological processes, yet they involve distinct mechanisms. Axial elongation is driven by factors such as scleral remodeling regulated by endoplasmic reticulum stress pathways, biomechanical forces including ciliary muscle activity, and genetic predisposition ( 23 – 26 ). These elements collectively contribute to progressive ocular elongation and the development of myopia. In contrast, height growth is regulated by endocrine signals, genetic factors, and environmental influences. Given these mechanistic differences, parallel progression of axial and height growth is not inherently expected. Nevertheless, several longitudinal studies have consistently reported a positive association between increases in height and axial length during childhood, particularly during early school age and preadolescence ( 11 , 22 , 27 , 28 ). This phenotypic correlation appears to be largely explained by shared genetic influences, as supported by twin studies attributing up to 89% of the covariance to genetic factors ( 29 ). Additionally, hormonal mediators such as growth hormone and insulin-like growth factor I—both of which regulate skeletal growth—have been proposed to influence axial elongation through their effects on ocular tissues ( 30 ). While these associations are most prominent during periods of rapid physical development, the relationship tends to weaken after the age of 10–12 years, as growth in both stature and eye size decelerates ( 11 , 31 ). These findings suggest that although axial and height growth share overlapping developmental windows and regulatory signals, the extent of their interdependence is limited and modulated by age and individual variability. These factors may have constrained the present study’s ability to more clearly delineate the relationship between height growth and axial elongation. This study had some additional limitations. First, its retrospective design and real-world clinical setting may introduce selection bias—particularly in assigning patients to the atropine group based on documented rapid axial elongation. Notably, the absence of a control group comprising children with axial elongation ≥ 0.4 mm/year who did not receive atropine limited our ability to isolate treatment effects from inherent growth tendencies. This comparison was not feasible due to the retrospective design of the study. Second, although height and axial length were measured repeatedly over time, other relevant variables—such as pubertal stage, hormonal markers, and genetic factors—were not assessed. Third, while we adopted axial elongation ≥ 0.4 mm/year as the clinical threshold for initiating atropine therapy, this objective cut-off may not fully reflect the broader range of clinical considerations that guide treatment decisions in real-world practice. Fourth, we acknowledge that identification of peak axial elongation age may be influenced by visit schedules and the timing of atropine initiation. However, because follow-up intervals rarely exceeded 6 months, the potential imprecision in peak age estimation is unlikely to exceed approximately 3 months. Despite these limitations, the study benefits from a well-characterized longitudinal dataset with serial biometric and anthropometric measurements, allowing for precise identification of peak growth timing. The inclusion of a pharmacologically treated cohort further enabled evaluation of not only the temporal relationship between systemic and ocular growth but also its potential influence on treatment responsiveness. By quantitatively analyzing individualized growth trajectories, this study provides novel insights into the dynamic interplay between physical development and myopia control and supports the clinical utility of height growth peak timing as a potential biomarker for guiding atropine treatment in pediatric populations. In conclusion, these findings underscore the importance of monitoring the timing of systemic growth spurts in the management of pediatric myopia. Height growth peak age may serve as a practical biomarker for identifying children at risk of rapid axial elongation despite atropine treatment. Given the close temporal alignment observed between systemic and ocular growth peaks, even children with delayed height growth spurts may experience later-onset axial elongation, reinforcing the need for continued biometric monitoring beyond the early years. Clinicians may consider integrating growth trajectory assessments into routine care and adjusting the timing or intensity of atropine therapy based on each child’s individualized growth pattern. Conclusions Systemic height growth rate was not linearly associated with axial elongation rate in children with myopia, regardless of atropine treatment. However, among atropine-treated children, the timing of systemic growth, particularly the age at peak height growth, was closely aligned with the timing of axial elongation and associated with greater annual axial elongation. Children with earlier height growth peaks exhibited faster axial elongation despite receiving identical atropine regimens. These findings suggest that monitoring height growth timing may help identify periods of increased risk for rapid axial elongation and support individualized management of pediatric myopia. Declarations Ethics approval and consent to participate This study was approved by the Institutional Review Board of Yongin Severance Hospital, Yongin, South Korea (approval number: 2024-0339-001), and the need for consent to participate was waived by the board. This study was performed in accordance with the tenets of the Declaration of Helsinki. Consent for publication Not applicable. Data availability statement The datasets generated during and/or analyzed during the current study are available from the corresponding author upon reasonable request. Competing interests All contributors affirm that they have no financial relationship or other associations with any entity or organization that could influence the content of this dissertation. Funding This research was supported by a 2024 research grant from Yonsei University College of Medicine (grant number 4-2024-0098). Author contributions D.S. contributed to interpretation of the data and drafting of the manuscript. J.H. contributed to drafting and critical revision of the manuscript. Y.S. contributed to the conceptualization and design of the study, acquisition, analysis, and interpretation of the data, supervision, funding acquisition, and drafting and critical revision of the manuscript. All authors read and approved the final manuscript and agree to be accountable for all aspects of the work. Acknowledgements We would like to thank Editage (www.editage.co.kr) for English language editing. References Lee SS, Lingham G, Sanfilippo PG, Hammond CJ, Saw SM, Guggenheim JA, et al. Incidence and Progression of Myopia in Early Adulthood. JAMA Ophthalmol. 2022;140(2):162–9. Holden BA, Fricke TR, Wilson DA, Jong M, Naidoo KS, Sankaridurg P, et al. Global Prevalence of Myopia and High Myopia and Temporal Trends from 2000 through 2050. Ophthalmology. 2016;123(5):1036–42. Cheung N, Lee SY, Wong TY. Will the Myopia Epidemic Lead to a Retinal Detachment Epidemic in the Future? JAMA Ophthalmol. 2021;139(1):93–4. Surl D, Seo Y, Han J. Trends in myopia prevalence among late adolescents in South Korea: a population-level study and future projections up to 2050. BMJ Open Ophthalmol. 2024;9(1). Ha A, Kim SJ, Shim SR, Kim YK, Jung JH. Efficacy and Safety of 8 Atropine Concentrations for Myopia Control in Children: A Network Meta-Analysis. Ophthalmology. 2022;129(3):322–33. Li FF, Yam JC. Low-Concentration Atropine Eye Drops for Myopia Progression. Asia-Pacific J Ophthalmol (Philadelphia Pa). 2019;8(5):360–5. Li Y, Yip M, Ning Y, Chung J, Toh A, Leow C, et al. Topical Atropine for Childhood Myopia Control: The Atropine Treatment Long-Term Assessment Study. JAMA Ophthalmol. 2024;142(1):15–23. Wolffsohn JS, Kollbaum PS, Berntsen DA, Atchison DA, Benavente A, Bradley A, et al. IMI - Clinical Myopia Control Trials and Instrumentation Report. Investig Ophthalmol Vis Sci. 2019;60(3):M132–60. Yip VC, Pan CW, Lin XY, Lee YS, Gazzard G, Wong TY, et al. The relationship between growth spurts and myopia in Singapore children. Investig Ophthalmol Vis Sci. 2012;53(13):7961–6. Shinojima A, Kurihara T, Mori K, Iwai Y, Hanyuda A, Negishi K, et al. Association between ocular axial length and anthropometrics of Asian adults. BMC Res Notes. 2021;14(1):328. Chen S, Guo Y, Han X, Yu X, Chen Q, Wang D et al. Axial Growth Driven by Physical Development and Myopia among Children: A Two Year Cohort Study. J Clin Med. 2022;11(13). Kearney S, Strang NC, Cagnolati B, Gray LS. Change in body height, axial length and refractive status over a four-year period in caucasian children and young adults. J optometry. 2020;13(2):128–36. Li W, Tu Y, Zhou L, Ma R, Li Y, Hu D, et al. Study of myopia progression and risk factors in Hubei children aged 7–10 years using machine learning: a longitudinal cohort. BMC Ophthalmol. 2024;24(1):93. Lee LC, Hsieh MW, Chen YH, Chen PL, Chien KH. Characteristics of responders to atropine 0.01% as treatment in Asian myopic children. Sci Rep. 2022;12(1):7380. Usmani E, Callisto S, Chan WO, Taranath D. Real-world outcomes of low-dose atropine therapy on myopia progression in an Australian cohort during the COVID-19 pandemic. Clin Exp Ophthalmol. 2023;51(8):775–80. Kothari M, Rathod V. Efficacy of 1% atropine eye drops in retarding progressive axial myopia in Indian eyes. Indian J Ophthalmol. 2017;65(11):1178–81. Zadnik K, Schulman E, Flitcroft I, Fogt JS, Blumenfeld LC, Fong TM, et al. Efficacy and Safety of 0.01% and 0.02% Atropine for the Treatment of Pediatric Myopia Progression Over 3 Years: A Randomized Clinical Trial. JAMA Ophthalmol. 2023;141(10):990–9. Bullimore MA, Brennan NA. Efficacy in Myopia Control: The Low-Concentration Atropine for Myopia Progression (LAMP) Study. Ophthalmology. 2023;130(7):771–2. Kim JH, Yun S, Hwang SS, Shim JO, Chae HW, Lee YJ, et al. The 2017 Korean National Growth Charts for children and adolescents: development, improvement, and prospects. Korean J Pediatr. 2018;61(5):135–49. Li T, Jiang B, Zhou X. Axial length elongation in primary school-age children: a 3-year cohort study in Shanghai. BMJ open. 2019;9(10):e029896. Zhang S, Chen Y, Li Z, Wang W, Xuan M, Zhang J, et al. Axial Elongation Trajectories in Chinese Children and Adults With High Myopia. JAMA Ophthalmol. 2024;142(2):87–94. Tao L, Wang C, Peng Y, Xu M, Wan M, Lou J, et al. Correlation Between Increase of Axial Length and Height Growth in Chinese School-Age Children. Front Public Health. 2021;9:817882. Ikeda S-i, Kurihara T, Jiang X, Miwa Y, Lee D, Serizawa N et al. Scleral PERK and ATF6 as targets of myopic axial elongation of mouse eyes. Nat Commun. 2022;13(1). Bhattacharya S, Meng Z-Y, Yang L, Zhou P. Ciliary muscles contraction leads to axial length extension——The possible initiating factor for myopia. PLoS ONE. 2024;19(4). Jonas JB, Jonas RA, Bikbov MM, Wang YX, Panda-Jonas S, Myopia. Histology, clinical features, and potential implications for the etiology of axial elongation. Prog Retin Eye Res. 2023;96. Jonas JB, Spaide RF, Ostrin LA, Logan NS, Flitcroft I, Panda-Jonas S. IMI—Nonpathological Human Ocular Tissue Changes With Axial Myopia. Invest Opthalmology Visual Sci. 2023;64(6). Wang D, Ding X, Liu B, Zhang J, He M. Longitudinal Changes of Axial Length and Height Are Associated and Concomitant in Children. Invest Opthalmology Visual Sci. 2011;52(11). Yang M-L, Huang C-Y, Hou C-H, Lin K-K, Lee J-S. Relationship of lifestyle and body stature growth with the development of myopia and axial length elongation in Taiwanese elementary school children. Indian J Ophthalmol. 2014;62(8). Zhang J, Hur Y-M, Huang W, Ding X, Feng K, He M. Shared Genetic Determinants of Axial Length and Height in Children. Arch Ophthalmol. 2011;129(1):63–8. Bourla DH, Laron Z, Snir M, Lilos P, Weinberger D, Axer-Siegel R. Insulinlike growth factor I affects ocular development: a study of untreated and treated patients with Laron syndrome. Ophthalmology. 2006;113(7):e11971–5. Northstone K, Guggenheim JA, Howe LD, Tilling K, Paternoster L, Kemp JP, et al. Body Stature Growth Trajectories during Childhood and the Development of Myopia. Ophthalmology. 2013;120(5):1064–e731. Additional Declarations No competing interests reported. Supplementary Files Supplemenatary.docx Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 01 Apr, 2026 Reviews received at journal 23 Mar, 2026 Reviews received at journal 13 Mar, 2026 Reviews received at journal 11 Mar, 2026 Reviewers agreed at journal 09 Mar, 2026 Reviewers agreed at journal 07 Mar, 2026 Reviews received at journal 07 Mar, 2026 Reviews received at journal 05 Mar, 2026 Reviews received at journal 05 Mar, 2026 Reviewers agreed at journal 04 Mar, 2026 Reviewers agreed at journal 02 Mar, 2026 Reviewers agreed at journal 27 Feb, 2026 Reviewers agreed at journal 26 Feb, 2026 Reviewers agreed at journal 26 Feb, 2026 Reviewers agreed at journal 25 Feb, 2026 Reviewers invited by journal 25 Feb, 2026 Editor invited by journal 05 Feb, 2026 Editor assigned by journal 04 Feb, 2026 Submission checks completed at journal 04 Feb, 2026 First submitted to journal 03 Feb, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8776737","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":597627744,"identity":"e095ebc3-6ab8-429d-bffb-f872e4eabb41","order_by":0,"name":"Dongheon Surl","email":"","orcid":"","institution":"Yongin Severance Hospital","correspondingAuthor":false,"prefix":"","firstName":"Dongheon","middleName":"","lastName":"Surl","suffix":""},{"id":597627745,"identity":"1797bd2f-a9fc-4e95-9bcb-340447cf7ed2","order_by":1,"name":"Jinu Han","email":"","orcid":"","institution":"Severance Hospital","correspondingAuthor":false,"prefix":"","firstName":"Jinu","middleName":"","lastName":"Han","suffix":""},{"id":597627746,"identity":"ea124ca4-cbad-46f0-9e33-1f204680eb22","order_by":2,"name":"Yuri Seo","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAqklEQVRIiWNgGAWjYNCCCgYGAxK1nCFZC2MbKVoMbh9/+ODjvMOJ2/kPMH74QZSWcznGhjO3HU7cOSOBWbKHKC1neNikeYFaNtxgYJAmzmFn2J//5p0D1HL+APNvIrUwmDHzNgC1HEhgI84WyTM8xpIzjqUbb7iR2GZJlF/4zrA//PChxlp2w/nDh28QFWIKB8BUMxAzNhDlLgZ5iLo64lSPglEwCkbByAQA6b822RgvaWcAAAAASUVORK5CYII=","orcid":"","institution":"Gangnam Severance Hospital","correspondingAuthor":true,"prefix":"","firstName":"Yuri","middleName":"","lastName":"Seo","suffix":""}],"badges":[],"createdAt":"2026-02-03 13:54:14","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8776737/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8776737/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":103732051,"identity":"c483c9ea-d376-4799-9c3c-5993bb6b6e39","added_by":"auto","created_at":"2026-03-02 09:19:45","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":306672,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eAssociation between height change and axial elongation by treatment group\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eScatter plots and linear regression lines illustrate the relationship between height change and axial length change per visit in the control and atropine groups. Data points are grouped by visit age quartiles to account for age-related effects (Q1: ≤ 8.92 years, Q2: 8.93–10.45 years, Q3: 10.46–11.77 years, Q4: ≥ 11.78 years), and lines represent linear regression fits. Linear mixed-effects modeling, incorporating visit age as an interaction term, confirmed no significant association between height velocity and axial elongation in either group (P \u0026gt; 0.05). Stratification by age quartiles and inclusion of age in the model indicate that height change alone does not predict ocular growth, regardless of age.\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-8776737/v1/8771c5b8db5f77eb2c0754b2.png"},{"id":103732046,"identity":"a69d933a-314a-404f-ab8e-158837ce25b2","added_by":"auto","created_at":"2026-03-02 09:19:44","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":297141,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eDistribution of individual peak ages of height growth and axial elongation by group\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe peak age was defined as the visit age at which the highest rate of change occurred, adjusting for visit interval. Each panel displays the distribution of peak ages for height growth (left) and axial elongation (right). In each histogram, gray bars represent the atropine group and white bars (unfilled) represent the control group. Overlaid density plots show smoothed distribution, with solid lines for the control group and dotted lines for the atropine group. In the control group, both height growth and axial elongation peak ages followed a unimodal, approximately normal distribution (peaks at 11.09 and 11.03 years, Shapiro–Wilk test, P = 0.172 and 0.406, respectively; solid line). In the atropine group, height growth peak age demonstrated marginal evidence of bimodality (Hartigan’s dip test, P = 0.051; dotted line), with two distinct peaks at 8.81 and 10.75 years. Axial elongation peak age in the atropine group also showed a visually broader distribution (peaks at 9.77 and 11.5 years), although statistical tests did not confirm bimodality (Hartigan’s dip test, P = 0.562; Shapiro–Wilk P = 0.511).\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-8776737/v1/d451acd8f0def103fab9d82d.png"},{"id":104399923,"identity":"4cc95b8c-d75e-4d0f-9908-9132a1c1cb0f","added_by":"auto","created_at":"2026-03-11 12:08:10","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":195011,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eCorrelation between peak age of height growth and axial elongation in the atropine group\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eScatter plots show a strong positive correlation between the peak age of height growth and the peak age of axial elongation in atropine-treated children (Pearson r = 0.86, P \u0026lt; 0.01). This synchrony was consistent regardless of whether the growth peak occurred earlier or later than the median peak age of height growth (10.45 years).\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-8776737/v1/63d97da4194dc75cb90b7efb.png"},{"id":103732048,"identity":"33594fd4-d558-4435-badf-5d7185aae5f9","added_by":"auto","created_at":"2026-03-02 09:19:44","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":154285,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eComparison of total axial length elongation rate between early and late growth peak subgroups in the atropine group\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBox plots compare axial elongation rate (mm/year) between children with early and late height growth peaks, classified based on the median height growth peak age (10.45 years). Eyes from early growth peak group (n = 42) exhibited significantly faster axial elongation than those from the late group (0.27 ± 0.17 mm/year vs. 0.15 ± 0.12 mm/year, P \u0026lt; 0.01).\u003c/p\u003e","description":"","filename":"Figure4.png","url":"https://assets-eu.researchsquare.com/files/rs-8776737/v1/b8638f93932ffb6b45342451.png"},{"id":103732050,"identity":"468ce600-c5ce-4008-93f7-6577e62c104a","added_by":"auto","created_at":"2026-03-02 09:19:44","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":198302,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eComparison of peak age for height growth rate and axial elongation rate between high and low axial elongation rate subgroups in the atropine group\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBox plot illustrates the timing of height growth and axial elongation peaks in eyes stratified by axial elongation rate (cutoff = 0.21 mm/year, n = 41 for high group; n = 42 for low group). Both height and axial elongation peaks occurred significantly earlier in the high axial elongation rate group (height peak age: 9.66 ± 1.91 years vs. 11.06 ± 1.82 years; axial elongation peak age: 9.6 ± 2.11 years vs. 11.05 ± 1.72 years, P \u0026lt; 0.001 for both comparisons). However, within each group, the temporal difference between systemic height and ocular axial length growth peak timing was not statistically significant (P = 0.85 for high group; P = 0.56 for low group), indicating synchronized growth patterns regardless of elongation rate.\u003c/p\u003e","description":"","filename":"Figure5.png","url":"https://assets-eu.researchsquare.com/files/rs-8776737/v1/b6fbf730ec85db62bb1464e9.png"},{"id":104410590,"identity":"e5cad7e3-a422-4f12-90a6-7f163ff2d1b4","added_by":"auto","created_at":"2026-03-11 12:52:55","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1708782,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8776737/v1/8916684e-5c6a-498b-93fc-8af1b1fe063e.pdf"},{"id":104399991,"identity":"38f37276-d6d3-4fa3-9584-5d445ec9bf70","added_by":"auto","created_at":"2026-03-11 12:08:26","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":2730909,"visible":true,"origin":"","legend":"","description":"","filename":"Supplemenatary.docx","url":"https://assets-eu.researchsquare.com/files/rs-8776737/v1/5de8f41d8939272f2f601630.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Timing of Height Growth Peaks and Axial Elongation in Atropine-Treated Myopic Children","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eMyopia is a growing global public health concern, with increasing prevalence and earlier onset among children (\u003cspan additionalcitationids=\"CR2 CR3\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). Among various interventions to slow myopia progression, low-concentration atropine eye drops have shown efficacy in reducing ocular axial elongation\u0026mdash;a key factor associated with disease progression and long-term ocular complications (\u003cspan additionalcitationids=\"CR6\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). In clinical practice, decisions regarding the initiation or adjustment of atropine therapy are often guided by the rate of axial elongation, which can be measured quickly and noninvasively, without requiring cycloplegia (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). However, axial elongation is not always predictable at the time of initial diagnosis or during early follow-ups.\u003c/p\u003e \u003cp\u003eWe hypothesized that the rate of systemic physical growth\u0026mdash;specifically, height velocity\u0026mdash;might parallel the rate of ocular axial elongation in children. Prior studies have explored associations between ocular axial length and anthropometric parameters, such as height, body mass index (BMI), and foot size (\u003cspan additionalcitationids=\"CR10 CR11 CR12\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). While some reported positive correlations between stature or growth velocity and axial length, others failed to establish consistent or predictive relationships. These discrepancies may stem from differences in study design, age ranges, ethnicity, or lack of treatment stratification.\u003c/p\u003e \u003cp\u003eDespite widespread use of atropine in clinical settings, no study has examined whether systemic growth markers can predict axial elongation in children undergoing pharmacological treatment. Given that 25%\u0026ndash;42% of atropine-treated children are classified as non-responders in previous trials, identifying predictors of treatment response remains an important unmet need (\u003cspan additionalcitationids=\"CR15 CR16\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIf systemic growth trajectories\u0026mdash;such as the timing or velocity of height spurts\u0026mdash;can indicate future axial elongation, clinicians may better anticipate periods of rapid myopia progression. This could facilitate prognostic discussions with families regarding and optimize the timing of treatment initiation or adjustment. Additionally, understanding whether certain growth characteristics are linked to reduced responsiveness to atropine could support personalized management strategies for pediatric myopia.\u003c/p\u003e \u003cp\u003eRather than examining a direct causal relationship between systemic growth and ocular axial elongation, this study aimed to characterize the overall relationship between axial elongation rate and systemic height growth patterns, and to further explore whether the timing of somatic growth is associated with inter-individual variability in axial elongation among children undergoing atropine treatment.\u003c/p\u003e"},{"header":"METHODS","content":"\u003cp\u003eThis retrospective cohort study included children with myopia under 15 years of age who underwent serial ocular biometry and anthropometric assessments at a minimum of three clinic visits over a period exceeding 1 year. Participants were classified into two groups: a control group with no atropine treatment, and an atropine group prescribed 0.05% atropine once nightly, initiated due to axial elongation of \u0026ge;\u0026thinsp;0.4 mm/year and the absence of contraindications such as cardiac or respiratory conditions (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). The baseline visit for the atropine group was defined as the time of treatment initiation.\u003c/p\u003e \u003cp\u003eInclusion criteria required a myopic refraction of less than \u0026minus;\u0026thinsp;0.50 D and astigmatism less than \u0026minus;\u0026thinsp;2.5D at the initial visit, along with complete ocular biometric and anthropometric data for all visits, including axial length, anterior chamber depth, lens thickness, white-to-white distance, keratometry, central corneal thickness, height, weight, and BMI. Exclusion criteria included a history of retinopathy of prematurity, congenital cataract, amblyopia or strabismus requiring treatment, neurological or syndromic disorders, or prior use of orthokeratology lenses. Children who received growth hormone therapy or gonadotropin-releasing hormone analogs for precocious puberty were excluded due to potential alterations in natural growth patterns. Children in the control group wore single-vision spectacles only. Participants using orthokeratology lenses, myopia control spectacles, or soft contact lenses were excluded.\u003c/p\u003e \u003cp\u003eThe primary outcome was the axial elongation rate. Axial elongation and height growth rates were calculated between visits by dividing the change in axial length or height by the time interval, expressed in millimeters per month (mm/month) and centimeters per month (cm/month), respectively. Axial length was measured using optical biometry (IOLMaster 700, Carl Zeiss Meditec, Germany), and height was measured at each visit using a wall-mounted stadiometer, with children barefoot and standing upright. All anthropometric and ocular measurements were obtained on the same visit day. For subgroup comparisons, an average annual axial elongation rate was calculated for each eye by dividing the total axial length change by the total follow-up duration, expressed in millimeters per year (mm/year) to facilitate interpretation. Peak ages for height growth and axial elongation were defined as the visit age corresponding to the greatest change rate between two consecutive visits.\u003c/p\u003e \u003cp\u003eSubgroup analyses were conducted within the atropine. Participants were divided into early or late peak growth subgroups based on whether their peak occurred before or after the median age. Comparisons of annual axial elongation rates were made between these groups. Participants were also stratified into high or low axial elongation subgroups using the median annual axial elongation rate as the threshold. Peak ages for height and axial elongation were then compared across subgroups.\u003c/p\u003e \u003cp\u003eStatistical analyses were performed using R software (version 4.3.0). Baseline characteristics were compared using independent t-tests. Linear mixed-effects models were used to evaluate the associations between height velocity and axial elongation while accounting for repeated measures. Height was treated as a subject-level variable, while axial elongation was analyzed at the eye level using mixed-effects models with subject-level random effects. To control for age-related variations, participants were stratified into quartiles based on visit age (Q1: \u0026le; 8.92 years; Q2: 8.93\u0026ndash;10.45 years; Q3: 10.46\u0026ndash;11.77 years; Q4: \u0026ge; 11.78 years), and these strata were incorporated into graphical and modeling analyses. Distributional characteristics of peak ages were assessed using the Shapiro-Wilk test (normality), Levene\u0026rsquo;s test (homogeneity of variance), Kolmogorov\u0026ndash;Smirnov test (distributional differences), and Hartigan\u0026rsquo;s dip test (modality). Skewness and kurtosis were also calculated to assess distributional shape. Pearson\u0026rsquo;s correlation was used to evaluate the association between height peak age and axial elongation peak age. A p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e \u003cp\u003e This study was approved by the Institutional Review Board of Yongin Severance Hospital, Yongin, South Korea (approval number: 2024-0339-001), and conducted in accordance with the Declaration of Helsinki. The author declares no conflicts of interest.\u003c/p\u003e"},{"header":"RESULTS","content":"\u003cp\u003eA total of 139 eyes from 70 children were included in the analysis (56 eyes in the control group and 83 eyes in the atropine group). Baseline biometric and anthropometric characteristics are summarized in Table\u0026nbsp;1. At the initial visit, there were no significant differences in height, weight, BMI, or ocular biometry measurements between the two groups, except for axial length and spherical equivalent. Initial axial length was significantly longer in atropine group compared to the control group (24.76\u0026thinsp;\u0026plusmn;\u0026thinsp;1.03 mm vs. 24.18\u0026thinsp;\u0026plusmn;\u0026thinsp;0.98 mm, P\u0026thinsp;\u0026lt;\u0026thinsp;0.01). Initial spherical equivalent was also significantly more myopic in the atropine group (-3.19\u0026thinsp;\u0026plusmn;\u0026thinsp;1.89D vs.-2.11\u0026thinsp;\u0026plusmn;\u0026thinsp;1.85D, P\u0026thinsp;\u0026lt;\u0026thinsp;0.01). Comparison of biometric and anthropometric change rates revealed significantly lower axial elongation in the atropine group (0.018\u0026thinsp;\u0026plusmn;\u0026thinsp;0.014 mm/month vs. 0.024\u0026thinsp;\u0026plusmn;\u0026thinsp;0.011 mm/month, P\u0026thinsp;\u0026lt;\u0026thinsp;0.01), while corneal diameter (white-to-white) increased more in the atropine group than in the control group (0.003\u0026thinsp;\u0026plusmn;\u0026thinsp;0.007 mm/month vs. \u0026minus;\u0026thinsp;0.001\u0026thinsp;\u0026plusmn;\u0026thinsp;0.008 mm/month, P\u0026thinsp;\u0026lt;\u0026thinsp;0.01). No significant differences were observed for other parameters between the groups (Supplementary Table\u0026nbsp;1).\u003c/p\u003e \u003cp\u003eBecause age is known to affect both height growth and axial elongation (\u003cspan additionalcitationids=\"CR20\" citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e), the influence of age on height growth rate was evaluated before analyzing its relationship with axial elongation. In the control group, height growth rate decreased significantly with age (β = \u0026minus;\u0026thinsp;0.028 cm/month per year, P\u0026thinsp;=\u0026thinsp;0.012); Supplementary Fig.\u0026nbsp;1. In contrast, no significant association was observed in the atropine group (β\u0026thinsp;=\u0026thinsp;0.004 cm/month per year, P\u0026thinsp;=\u0026thinsp;0.716), suggesting more heterogeneous somatic growth trajectories among atropine-treated children.\u003c/p\u003e \u003cp\u003eThe association between height growth rate and axial elongation rate was evaluated using linear mixed-effects models while adjusting for age (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). In the atropine group, height growth rate was not significantly associated with axial elongation (β = \u0026minus;\u0026thinsp;0.021 mm/month per cm/month, P\u0026thinsp;=\u0026thinsp;0.726). Axial elongation rate showed a modest but significant decrease with age (β = \u0026minus;\u0026thinsp;0.011 mm/month per year, P\u0026thinsp;=\u0026thinsp;0.011), although this association was no longer significant after adjusting for both age and height growth rate (P\u0026thinsp;=\u0026thinsp;0.942). In the control group, axial elongation rate also decreased significantly with age (β = \u0026minus;\u0026thinsp;0.048 mm/month per year, P\u0026thinsp;=\u0026thinsp;0.003), while the effect of height growth rate remained non-significant (β = \u0026minus;\u0026thinsp;0.537 mm/month per cm/month, P\u0026thinsp;=\u0026thinsp;0.123). After adjusting for age, the interaction term between height growth rate and age was also not statistically significant (P\u0026thinsp;=\u0026thinsp;0.182). To account for age-related variation in growth patterns, data points in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e were stratified by visit age quartiles (Q1: \u0026le; 8.92 years, Q2: 8.93\u0026ndash;10.45 years, Q3: 10.46\u0026ndash;11.77 years, Q4: \u0026ge; 11.78 years), showing that the lack of association between height and axial elongation persisted across age groups. In conclusion, height growth rate showed no significant association with axial elongation rate in either group even after adjusting for age.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eOur initial hypothesis was that axial elongation rate would be associated with height growth rate. However, as shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, this association was not observed. To further investigate this discrepancy, we analyzed the distribution of peak ages for height growth rate and axial elongation rate in each group. The peak age was defined as the visit age at which the greatest change rate occurred for each eye. The distributions are shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eIn the control group, the peak ages for both height growth and axial elongation rates were normally distributed (Shapiro\u0026ndash;Wilk test, P\u0026thinsp;=\u0026thinsp;0.106 and 0.376, respectively), and nearly identical (11.09\u0026thinsp;\u0026plusmn;\u0026thinsp;1.92 years vs. 11.03\u0026thinsp;\u0026plusmn;\u0026thinsp;2.16 years), with no significant difference between them (paired t-test, P\u0026thinsp;=\u0026thinsp;0.62). These results suggest a synchronized pattern of systemic height and ocular axial growth in the absence of atropine treatment.\u003c/p\u003e \u003cp\u003eConversely, the atropine group showed a broader distribution of peak ages for height growth, with marginal evidence for bimodality (Hartigan\u0026rsquo;s dip test, P\u0026thinsp;=\u0026thinsp;0.051). Although the distribution did not show two sharply separated peaks, visual inspection of Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e reveals a flattened central portion and a wide spread of peak ages, suggesting heterogeneity in growth timing among treated children. The distribution of axial elongation peak age in the atropine group appeared similarly variable, though statistical tests supported approximate unimodality (Shapiro-Wilk test: P\u0026thinsp;=\u0026thinsp;0.478; Hartigan\u0026rsquo;s dip test: P\u0026thinsp;=\u0026thinsp;0.091). The two most prominent peak ages for height growth in the atropine group were 8.81 and 10.75 years, while those for axial elongation were 9.77 and 11.5 years. Despite the appearance of multiple peaks, the mean peak age of axial elongation was 10.59\u0026thinsp;\u0026plusmn;\u0026thinsp;2.1 years, representing the central tendency. Summary statistics, including skewness, kurtosis, and results of normality and variance tests, are provided in Supplementary Table\u0026nbsp;2.\u003c/p\u003e \u003cp\u003eTo further explore variability in peak growth timing within the atropine group, participants were categorized as \u0026ldquo;early growth peak (n\u0026thinsp;=\u0026thinsp;42)\u0026rdquo; and \u0026ldquo;late growth peak (n\u0026thinsp;=\u0026thinsp;41)\u0026rdquo; based on the median peak age of height growth (10.45 years). A strong positive correlation was observed between peak height growth age and peak axial elongation age in the atropine group (r\u0026thinsp;=\u0026thinsp;0.86, P\u0026thinsp;\u0026lt;\u0026thinsp;0.01; Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Earlier peak height growth was associated with earlier axial length elongation, suggesting close alignment in the timing of systemic and ocular growth spurt.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eAxial elongation rate per year was also compared between the two subgroups. The early height growth peak group exhibited a significantly faster axial elongation rate than the late growth peak group (0.27\u0026thinsp;\u0026plusmn;\u0026thinsp;0.17 mm/year vs. 0.15\u0026thinsp;\u0026plusmn;\u0026thinsp;0.12 mm/year, P\u0026thinsp;\u0026lt;\u0026thinsp;0.01; Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). A similar pattern was observed when the groups were defined by axial length peak age (median\u0026thinsp;=\u0026thinsp;10.28 years), with the early peak group showing faster elongation (0.27\u0026thinsp;\u0026plusmn;\u0026thinsp;0.17 mm/year vs. 0.15\u0026thinsp;\u0026plusmn;\u0026thinsp;0.12 mm/year, P\u0026thinsp;\u0026lt;\u0026thinsp;0.01), although the bimodality of axial elongation peak age did not reach statistical significance. This subgroup analysis is presented in Supplementary Fig.\u0026nbsp;2, based on the bimodal pattern observed in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eTo further assess the relationship between growth timing and myopia progression in the atropine group, participants were stratified by the median axial elongation rate (0.21 mm/year). The high axial elongation rate group (n\u0026thinsp;=\u0026thinsp;41) showed significantly earlier peak ages than the low-rate group (n\u0026thinsp;=\u0026thinsp;42) for both height growth (9.66\u0026thinsp;\u0026plusmn;\u0026thinsp;1.91 vs. 11.06\u0026thinsp;\u0026plusmn;\u0026thinsp;1.82 years, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and axial elongation (9.6\u0026thinsp;\u0026plusmn;\u0026thinsp;2.11 vs. 11.05\u0026thinsp;\u0026plusmn;\u0026thinsp;1.72 years, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). However, within each subgroup, the timing of height growth and axial elongation did not differ significantly (P\u0026thinsp;=\u0026thinsp;0.85 for high-rate group; P\u0026thinsp;=\u0026thinsp;0.56 for low-rate group), suggesting that systemic height and ocular axial growth remained synchronized regardless of the overall rate of elongation (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eWe hypothesized that the rate of axial elongation would increase in parallel with systemic height growth rate and that this association could influence the efficacy of atropine in suppressing axial elongation. However, no significant correlation between axial elongation rate and systemic height growth rate was found in either the atropine or control groups (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). To investigate this discrepancy, we analyzed the distributions of peak age for height growth and axial elongation. In the control group, the peak ages for height growth and axial elongation were closely synchronized (11.09\u0026thinsp;\u0026plusmn;\u0026thinsp;1.92 vs. 11.03\u0026thinsp;\u0026plusmn;\u0026thinsp;2.16 years), both following a unimodal, normal distribution. In contrast, the atropine group showed a suggestive bimodal pattern for the peak age of height growth, which was visually mirrored in the distribution of axial elongation peak age, although statistical tests did not confirm significant bimodality (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Subgroup analyses were conducted within the atropine-treated group (Figs.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e, \u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e, and \u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e). Earlier onset of height growth spurts was strongly associated with earlier axial elongation peaks (r\u0026thinsp;=\u0026thinsp;0.86, P\u0026thinsp;\u0026lt;\u0026thinsp;0.01; Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Moreover, patients with an earlier height growth peak exhibited significantly faster annual axial elongation compared to those with later height growth peaks (P\u0026thinsp;\u0026lt;\u0026thinsp;0.01; Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). When participants were stratified by axial elongation rate, those with higher elongation rates demonstrated significantly earlier peak ages for both height growth and axial elongation compared to those with lower elongation rates (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e). Notably, within each group, the peak ages of height growth and axial elongation remained closely synchronized (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThese findings suggest that the temporal pattern of systemic growth\u0026mdash;specifically, the timing of the height growth spurt\u0026mdash;is more closely aligned with axial elongation than with overall growth velocity, regardless of atropine treatment. Importantly, the absence of a significant linear association between age and axial elongation rate in the atropine-treated cohort should not be interpreted as age-independent ocular growth. Rather, this finding likely reflects the heterogeneity of growth trajectories and the modifying effects of atropine treatment, which may obscure a simple age-related pattern within this clinically selected population.\u003c/p\u003e \u003cp\u003eInterestingly, while both height growth rate and axial elongation rate followed unimodal distributions in the control group, the atropine group exhibited bimodal patterns for both parameters\u0026mdash;even though the bimodality in axial elongation did not reach statistical significance. This pattern is likely not a direct consequence of atropine treatment but may reflect heterogeneity in underlying growth trajectories that could influence treatment response. Given the retrospective nature of this study, group classification was based on real-world clinical decisions: children with myopia of less than \u0026minus;\u0026thinsp;0.50 D were followed longitudinally, and those demonstrating axial elongation\u0026thinsp;\u0026ge;\u0026thinsp;0.4 mm/year were initiated on atropine treatment, forming the atropine group, while those with slower progression comprised the control group.\u003c/p\u003e \u003cp\u003eWithin the atropine group, patients with later height growth peaks exhibited peak ages (10.75 years for height growth and 11.5 years for axial elongation) similar to those observed in the control group (11.09 and 11.03 years, respectively). In contrast, patients with earlier height growth peaks demonstrated markedly earlier timing for both height growth (9.77 years) and axial elongation (8.81 years). This heterogeneity likely contributed to the lack of a consistent linear relationship between height growth rate and axial elongation rate. Nevertheless, a strong positive correlation was observed between the timing of height growth peak and axial elongation peak within the atropine group (r\u0026thinsp;=\u0026thinsp;0.86, P\u0026thinsp;\u0026lt;\u0026thinsp;0.01), indicating that systemic and ocular growth spurts tended to occur in close temporal proximity, regardless of whether the peak occurred early or late (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Although the control group also demonstrated close alignment between systemic and ocular growth peaks\u0026mdash;evidenced by nearly identical mean peak ages and unimodal distributions\u0026mdash;there was no significant correlation between the magnitude of height change and axial elongation rate (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). These findings suggest that while the timing of systemic and ocular growth is often synchronized, the extent of growth in height and axial length is not necessarily correlated.\u003c/p\u003e \u003cp\u003eAnother clinically important finding is that, within the atropine group, children with earlier height growth peaks showed significantly greater annual axial elongation than those with later growth peaks, despite receiving the same atropine concentration and dosing frequency (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). This suggests that early-onset systemic growth may be associated with reduced responsiveness to atropine in suppressing axial elongation. To further assess the predictive value of height growth peak timing, we performed a subgroup analysis based on axial elongation rate. When participants were stratified into high and low axial elongation rate groups, those in the high-rate group demonstrated significantly earlier peak ages for both height growth and axial elongation compared to the low-rate group (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e). Notably, within each subgroup, the timing of height and axial elongation peaks remained closely synchronized, with no significant difference between the two. These findings indicate that children who experience an earlier systemic growth spurt may be more likely to exhibit faster axial elongation and diminished response to atropine treatment, underscoring the potential of height growth peak age as a clinically meaningful marker for predicting treatment outcomes in pediatric myopia management.\u003c/p\u003e \u003cp\u003ePrevious studies have demonstrated that ocular axial elongation often coincides with periods of accelerated physical growth during childhood, suggesting a temporally synchronized relationship between systemic and ocular development (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e). Specifically, earlier onset of peak height velocity has been associated with earlier axial elongation and earlier myopia onset, highlighting the importance of growth timing as a risk factor for myopia progression (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). However, these studies were limited to observational designs and did not assess whether growth patterns may influence responsiveness to pharmacologic interventions such as atropine (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). In the present study, we analyzed a clinically defined cohort in which children with documented rapid axial elongation were treated with uniform atropine therapy. Among these treated children, those with earlier height growth peaks showed significantly earlier axial elongation peaks and greater annual axial elongation, despite receiving identical atropine concentrations and regimens. This finding suggests that early biological maturation may be associated with attenuated responsiveness to atropine in suppressing ocular growth. Additionally, the bimodal distribution of growth peak ages\u0026mdash;observed exclusively in the atropine group\u0026mdash;likely reflects underlying heterogeneity in systemic growth trajectories that may have influenced treatment initiation timing. While previous reports have examined anthropometric correlates of axial length in adult populations (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e) or identified behavioral and biometric predictors of myopia progression without accounting for treatment exposure (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e), our study provides a unique perspective by linking physiologic growth patterns with both axial elongation timing and treatment efficacy in a pediatric population with myopia.\u003c/p\u003e \u003cp\u003eAxial elongation and linear height growth are governed by multifactorial biological processes, yet they involve distinct mechanisms. Axial elongation is driven by factors such as scleral remodeling regulated by endoplasmic reticulum stress pathways, biomechanical forces including ciliary muscle activity, and genetic predisposition (\u003cspan additionalcitationids=\"CR24 CR25\" citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e). These elements collectively contribute to progressive ocular elongation and the development of myopia. In contrast, height growth is regulated by endocrine signals, genetic factors, and environmental influences. Given these mechanistic differences, parallel progression of axial and height growth is not inherently expected. Nevertheless, several longitudinal studies have consistently reported a positive association between increases in height and axial length during childhood, particularly during early school age and preadolescence (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThis phenotypic correlation appears to be largely explained by shared genetic influences, as supported by twin studies attributing up to 89% of the covariance to genetic factors (\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e). Additionally, hormonal mediators such as growth hormone and insulin-like growth factor I\u0026mdash;both of which regulate skeletal growth\u0026mdash;have been proposed to influence axial elongation through their effects on ocular tissues (\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e). While these associations are most prominent during periods of rapid physical development, the relationship tends to weaken after the age of 10\u0026ndash;12 years, as growth in both stature and eye size decelerates (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e). These findings suggest that although axial and height growth share overlapping developmental windows and regulatory signals, the extent of their interdependence is limited and modulated by age and individual variability. These factors may have constrained the present study\u0026rsquo;s ability to more clearly delineate the relationship between height growth and axial elongation.\u003c/p\u003e \u003cp\u003eThis study had some additional limitations. First, its retrospective design and real-world clinical setting may introduce selection bias\u0026mdash;particularly in assigning patients to the atropine group based on documented rapid axial elongation. Notably, the absence of a control group comprising children with axial elongation\u0026thinsp;\u0026ge;\u0026thinsp;0.4 mm/year who did not receive atropine limited our ability to isolate treatment effects from inherent growth tendencies. This comparison was not feasible due to the retrospective design of the study. Second, although height and axial length were measured repeatedly over time, other relevant variables\u0026mdash;such as pubertal stage, hormonal markers, and genetic factors\u0026mdash;were not assessed. Third, while we adopted axial elongation\u0026thinsp;\u0026ge;\u0026thinsp;0.4 mm/year as the clinical threshold for initiating atropine therapy, this objective cut-off may not fully reflect the broader range of clinical considerations that guide treatment decisions in real-world practice. Fourth, we acknowledge that identification of peak axial elongation age may be influenced by visit schedules and the timing of atropine initiation. However, because follow-up intervals rarely exceeded 6 months, the potential imprecision in peak age estimation is unlikely to exceed approximately 3 months.\u003c/p\u003e \u003cp\u003eDespite these limitations, the study benefits from a well-characterized longitudinal dataset with serial biometric and anthropometric measurements, allowing for precise identification of peak growth timing. The inclusion of a pharmacologically treated cohort further enabled evaluation of not only the temporal relationship between systemic and ocular growth but also its potential influence on treatment responsiveness. By quantitatively analyzing individualized growth trajectories, this study provides novel insights into the dynamic interplay between physical development and myopia control and supports the clinical utility of height growth peak timing as a potential biomarker for guiding atropine treatment in pediatric populations.\u003c/p\u003e \u003cp\u003eIn conclusion, these findings underscore the importance of monitoring the timing of systemic growth spurts in the management of pediatric myopia. Height growth peak age may serve as a practical biomarker for identifying children at risk of rapid axial elongation despite atropine treatment. Given the close temporal alignment observed between systemic and ocular growth peaks, even children with delayed height growth spurts may experience later-onset axial elongation, reinforcing the need for continued biometric monitoring beyond the early years. Clinicians may consider integrating growth trajectory assessments into routine care and adjusting the timing or intensity of atropine therapy based on each child\u0026rsquo;s individualized growth pattern.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eSystemic height growth rate was not linearly associated with axial elongation rate in children with myopia, regardless of atropine treatment. However, among atropine-treated children, the timing of systemic growth, particularly the age at peak height growth, was closely aligned with the timing of axial elongation and associated with greater annual axial elongation. Children with earlier height growth peaks exhibited faster axial elongation despite receiving identical atropine regimens. These findings suggest that monitoring height growth timing may help identify periods of increased risk for rapid axial elongation and support individualized management of pediatric myopia.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e This study was approved by the Institutional Review Board of Yongin Severance Hospital, Yongin, South Korea (approval number: 2024-0339-001), and the need for consent to participate was waived by the board. This study was performed in accordance with the tenets of the Declaration of Helsinki.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e Not applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability statement\u003c/strong\u003e The datasets generated during and/or analyzed during the current study are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e All contributors affirm that they have no financial relationship or other associations with any entity or organization that could influence the content of this dissertation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e This research was supported by a 2024 research grant from Yonsei University College of Medicine (grant number 4-2024-0098).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e D.S. contributed to interpretation of the data and drafting of the manuscript. J.H. contributed to drafting and critical revision of the manuscript. Y.S. \u0026nbsp;contributed to the conceptualization and design of the study, acquisition, analysis, and interpretation of the data, supervision, funding acquisition, and drafting and critical revision of the manuscript. All authors read and approved the final manuscript and agree to be accountable for all aspects of the work.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e We would like to thank Editage (www.editage.co.kr) for English language editing.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eLee SS, Lingham G, Sanfilippo PG, Hammond CJ, Saw SM, Guggenheim JA, et al. Incidence and Progression of Myopia in Early Adulthood. JAMA Ophthalmol. 2022;140(2):162\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHolden BA, Fricke TR, Wilson DA, Jong M, Naidoo KS, Sankaridurg P, et al. Global Prevalence of Myopia and High Myopia and Temporal Trends from 2000 through 2050. Ophthalmology. 2016;123(5):1036\u0026ndash;42.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCheung N, Lee SY, Wong TY. Will the Myopia Epidemic Lead to a Retinal Detachment Epidemic in the Future? JAMA Ophthalmol. 2021;139(1):93\u0026ndash;4.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSurl D, Seo Y, Han J. Trends in myopia prevalence among late adolescents in South Korea: a population-level study and future projections up to 2050. BMJ Open Ophthalmol. 2024;9(1).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHa A, Kim SJ, Shim SR, Kim YK, Jung JH. Efficacy and Safety of 8 Atropine Concentrations for Myopia Control in Children: A Network Meta-Analysis. Ophthalmology. 2022;129(3):322\u0026ndash;33.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLi FF, Yam JC. Low-Concentration Atropine Eye Drops for Myopia Progression. Asia-Pacific J Ophthalmol (Philadelphia Pa). 2019;8(5):360\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLi Y, Yip M, Ning Y, Chung J, Toh A, Leow C, et al. Topical Atropine for Childhood Myopia Control: The Atropine Treatment Long-Term Assessment Study. JAMA Ophthalmol. 2024;142(1):15\u0026ndash;23.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWolffsohn JS, Kollbaum PS, Berntsen DA, Atchison DA, Benavente A, Bradley A, et al. IMI - Clinical Myopia Control Trials and Instrumentation Report. Investig Ophthalmol Vis Sci. 2019;60(3):M132\u0026ndash;60.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYip VC, Pan CW, Lin XY, Lee YS, Gazzard G, Wong TY, et al. The relationship between growth spurts and myopia in Singapore children. Investig Ophthalmol Vis Sci. 2012;53(13):7961\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShinojima A, Kurihara T, Mori K, Iwai Y, Hanyuda A, Negishi K, et al. Association between ocular axial length and anthropometrics of Asian adults. BMC Res Notes. 2021;14(1):328.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChen S, Guo Y, Han X, Yu X, Chen Q, Wang D et al. Axial Growth Driven by Physical Development and Myopia among Children: A Two Year Cohort Study. J Clin Med. 2022;11(13).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKearney S, Strang NC, Cagnolati B, Gray LS. Change in body height, axial length and refractive status over a four-year period in caucasian children and young adults. J optometry. 2020;13(2):128\u0026ndash;36.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLi W, Tu Y, Zhou L, Ma R, Li Y, Hu D, et al. Study of myopia progression and risk factors in Hubei children aged 7\u0026ndash;10 years using machine learning: a longitudinal cohort. BMC Ophthalmol. 2024;24(1):93.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLee LC, Hsieh MW, Chen YH, Chen PL, Chien KH. Characteristics of responders to atropine 0.01% as treatment in Asian myopic children. Sci Rep. 2022;12(1):7380.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eUsmani E, Callisto S, Chan WO, Taranath D. Real-world outcomes of low-dose atropine therapy on myopia progression in an Australian cohort during the COVID-19 pandemic. Clin Exp Ophthalmol. 2023;51(8):775\u0026ndash;80.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKothari M, Rathod V. Efficacy of 1% atropine eye drops in retarding progressive axial myopia in Indian eyes. Indian J Ophthalmol. 2017;65(11):1178\u0026ndash;81.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZadnik K, Schulman E, Flitcroft I, Fogt JS, Blumenfeld LC, Fong TM, et al. Efficacy and Safety of 0.01% and 0.02% Atropine for the Treatment of Pediatric Myopia Progression Over 3 Years: A Randomized Clinical Trial. JAMA Ophthalmol. 2023;141(10):990\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBullimore MA, Brennan NA. Efficacy in Myopia Control: The Low-Concentration Atropine for Myopia Progression (LAMP) Study. Ophthalmology. 2023;130(7):771\u0026ndash;2.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKim JH, Yun S, Hwang SS, Shim JO, Chae HW, Lee YJ, et al. The 2017 Korean National Growth Charts for children and adolescents: development, improvement, and prospects. Korean J Pediatr. 2018;61(5):135\u0026ndash;49.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLi T, Jiang B, Zhou X. Axial length elongation in primary school-age children: a 3-year cohort study in Shanghai. BMJ open. 2019;9(10):e029896.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhang S, Chen Y, Li Z, Wang W, Xuan M, Zhang J, et al. Axial Elongation Trajectories in Chinese Children and Adults With High Myopia. JAMA Ophthalmol. 2024;142(2):87\u0026ndash;94.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTao L, Wang C, Peng Y, Xu M, Wan M, Lou J, et al. Correlation Between Increase of Axial Length and Height Growth in Chinese School-Age Children. Front Public Health. 2021;9:817882.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eIkeda S-i, Kurihara T, Jiang X, Miwa Y, Lee D, Serizawa N et al. Scleral PERK and ATF6 as targets of myopic axial elongation of mouse eyes. Nat Commun. 2022;13(1).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBhattacharya S, Meng Z-Y, Yang L, Zhou P. Ciliary muscles contraction leads to axial length extension\u0026mdash;\u0026mdash;The possible initiating factor for myopia. PLoS ONE. 2024;19(4).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJonas JB, Jonas RA, Bikbov MM, Wang YX, Panda-Jonas S, Myopia. Histology, clinical features, and potential implications for the etiology of axial elongation. Prog Retin Eye Res. 2023;96.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJonas JB, Spaide RF, Ostrin LA, Logan NS, Flitcroft I, Panda-Jonas S. IMI\u0026mdash;Nonpathological Human Ocular Tissue Changes With Axial Myopia. Invest Opthalmology Visual Sci. 2023;64(6).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang D, Ding X, Liu B, Zhang J, He M. Longitudinal Changes of Axial Length and Height Are Associated and Concomitant in Children. Invest Opthalmology Visual Sci. 2011;52(11).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYang M-L, Huang C-Y, Hou C-H, Lin K-K, Lee J-S. Relationship of lifestyle and body stature growth with the development of myopia and axial length elongation in Taiwanese elementary school children. Indian J Ophthalmol. 2014;62(8).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhang J, Hur Y-M, Huang W, Ding X, Feng K, He M. Shared Genetic Determinants of Axial Length and Height in Children. Arch Ophthalmol. 2011;129(1):63\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBourla DH, Laron Z, Snir M, Lilos P, Weinberger D, Axer-Siegel R. Insulinlike growth factor I affects ocular development: a study of untreated and treated patients with Laron syndrome. Ophthalmology. 2006;113(7):e11971\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNorthstone K, Guggenheim JA, Howe LD, Tilling K, Paternoster L, Kemp JP, et al. Body Stature Growth Trajectories during Childhood and the Development of Myopia. Ophthalmology. 2013;120(5):1064\u0026ndash;e731.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-ophthalmology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"boph","sideBox":"Learn more about [BMC Ophthalmology](http://bmcophthalmol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/boph","title":"BMC Ophthalmology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Myopia progression, Axial elongation, Atropine treatment, Height growth peak, Pediatric ocular development","lastPublishedDoi":"10.21203/rs.3.rs-8776737/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8776737/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003eTo investigate the association between systemic height growth rate and ocular axial elongation rate in atropine-treated children with myopia, and to explore whether the timing of height growth may serve as a prognostic factor for treatment response.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eChildren with myopia (\u0026lt;\u0026thinsp;15 years) who underwent serial ocular biometry and anthropometric measurements over \u0026ge;\u0026thinsp;3 visits spanning\u0026thinsp;\u0026gt;\u0026thinsp;1 year were included. Participants were classified into a control group (no atropine) and an atropine group (0.05% nightly, initiated for axial elongation\u0026thinsp;\u0026ge;\u0026thinsp;0.4 mm/year). Axial elongation and height growth rates were calculated for each inter-visit interval. Peak growth ages were defined as those with the greatest inter-visit changes. Subgroup analyses in the atropine group were based on the median peak height growth age (10.45 years) and median annual axial elongation rate (0.23 mm/year).\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eA total of 139 eyes from 70 children were analyzed (56 control, 83 atropine-treated). Height growth rate and axial elongation rate were not significantly correlated in either group. In the atropine group, peak height growth age showed marginal bimodality (P\u0026thinsp;=\u0026thinsp;0.051) and correlated strongly with peak axial elongation age (r\u0026thinsp;=\u0026thinsp;0.86, P\u0026thinsp;\u0026lt;\u0026thinsp;0.01). Children with earlier height growth peaks had greater annual axial elongation (0.27\u0026thinsp;\u0026plusmn;\u0026thinsp;0.17 vs. 0.15\u0026thinsp;\u0026plusmn;\u0026thinsp;0.12 mm/year; P\u0026thinsp;\u0026lt;\u0026thinsp;0.01) despite identical dosing.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eAmong atropine-treated children, earlier systemic growth peaks were associated with faster axial elongation. Monitoring height growth timing may help identify rapid ocular growth periods and optimize treatment strategies.\u003c/p\u003e","manuscriptTitle":"Timing of Height Growth Peaks and Axial Elongation in Atropine-Treated Myopic Children","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-03-02 09:19:39","doi":"10.21203/rs.3.rs-8776737/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-04-01T06:51:40+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-23T05:23:15+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-13T10:16:17+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-11T07:08:27+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"158820879907238951319908356630075049875","date":"2026-03-09T15:42:53+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"108287541918724666533411363992808152572","date":"2026-03-08T01:28:31+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-07T14:01:58+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-05T12:03:40+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-05T11:30:52+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"320103390379132560940587371866536455764","date":"2026-03-04T10:28:33+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"60765659349465666489530445969808884238","date":"2026-03-02T06:58:48+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"238677858813709791168699573975556538324","date":"2026-02-27T07:28:10+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"327577003178776023971495096451507346684","date":"2026-02-26T14:44:37+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"162786036721994085445601783764486648822","date":"2026-02-26T11:44:38+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"13616422909315941585171657737396843870","date":"2026-02-25T08:39:35+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-02-25T06:53:11+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-02-05T05:26:14+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-02-05T00:21:54+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-02-05T00:20:33+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Ophthalmology","date":"2026-02-03T13:16:34+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-ophthalmology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"boph","sideBox":"Learn more about [BMC Ophthalmology](http://bmcophthalmol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/boph","title":"BMC Ophthalmology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"b5b223f3-afb3-4171-9641-715eaff7a758","owner":[],"postedDate":"March 2nd, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-05-15T13:54:22+00:00","versionOfRecord":[],"versionCreatedAt":"2026-03-02 09:19:39","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8776737","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8776737","identity":"rs-8776737","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}