Efficacy of nightly 0.01% atropine in controlling myopia progression in Lebanese children: A 24-month retrospective cohort study

Abstract

BACKGROUND

Children’s eyes are under siege. Pediatric myopia is escalating into one of the defining public health crises of this generation with mounting rates of high myopia that bring catastrophic sequelae including retinal detachment, glaucoma and irreversible myopic maculopathy. Low-dose atropine has stepped forward as a compelling pharmacological countermeasure. Yet an enormous evidence gap persists. Middle Eastern populations remain dramatically underrepresented in the literature. Lebanon has no published data whatsoever.

AIM

To investigate the efficacy of nightly 0.01% atropine eye drops in controlling myopia progression in Lebanese children aged 4-12 years.

METHODS

This retrospective cohort study enrolled 70 eyes from 36 pediatric patients (mean age 7.89 ± 2.59 years; 50% female; all Lebanese nationals of Arab ethnicity). Thirty-five eyes received nightly 0.01% atropine. Thirty-five eyes received standard spectacle correction alone. Follow-up extended across 24 months. Cycloplegic retinoscopy using cyclopentolate 1% determined refraction at every visit. The primary outcome was change in spherical equivalent refraction. Secondary outcomes included best-corrected visual acuity (logMAR) and adverse effects in the atropine group. Repeated measures analysis of variance via SPSS v26 conducted all analyses.

RESULTS

Both groups showed myopic progression throughout the follow-up window. The atropine cohort demonstrated significantly slower spherical equivalent refraction advancement at 6 months [0.26 ± 0.29 diopters (D) vs 0.51 ± 0.46 D; P = 0.008] and at 18 months (0.18 ± 0.25 D vs 0.37 ± 0.32 D; P = 0.009) relative to controls. Inter-period differences at 12 months (P = 1.00) and 24 months (P = 0.071) did not reach statistical significance. Best-corrected visual acuity held steady across both cohorts. No adverse effects were documented in the atropine arm.

CONCLUSION

Nightly 0.01% atropine was associated with significantly slower myopic progression at multiple timepoints in Lebanese children. The tolerability profile was exemplary. These findings extend support for low-dose atropine as a viable myopia management approach in the Middle Eastern pediatric population. Prospective randomized studies remain essential to consolidate these results.

Key Words: Myopia; Atropine; Pediatric myopia; Myopia control; Low-dose atropine; Myopia progression

Core Tip: This is the first study to evaluate nightly 0.01% atropine for myopia control in Lebanese children. Over 24 months atropine-treated eyes demonstrated statistically significantly slower myopic progression than spectacle-only controls at multiple timepoints. No adverse effects were recorded. These findings extend existing evidence to the underrepresented Middle Eastern region. They support low-dose atropine as a safe, accessible and effective option for pediatric myopia management in Lebanon.

INTRODUCTION

Myopia is winning, across the globe it is steadily tightening its grip on the eyes of children and adolescents at an unprecedented pace. Recent meta-analyses project that nearly half the world’s population will have myopia by 2050. Up to 10% of those will develop high myopia which carries catastrophic ophthalmologic consequences including retinal detachment, glaucoma and irreversible myopic maculopathy leading to permanent vision loss[1,2]. The stakes could not be higher.

Multiple strategies have entered the arena. Overnight orthokeratology lenses have demonstrated the capacity to retard axial elongation compared with single-vision spectacle correction[3]. Multifocal soft contact lenses have similarly shown efficacy in curbing progression[4]. Increased outdoor activity has emerged as a protective behavioral intervention against both myopia onset and its worsening[5]. The therapeutic landscape is rich. Yet no single approach has achieved universal adoption.

Among pharmacological interventions, topical atropine has attracted the most rigorous scientific scrutiny. High-concentration preparations (e.g., 1%) can arrest progression but produce intolerable side effects including photophobia and accommodative paresis that severely compromise quality of life[6]. Low-dose atropine (0.01% to 0.05%) retains meaningful efficacy while sidestepping these problems with remarkable consistency. The Low-Concentration Atropine for Myopia Progression trial confirmed that all three tested concentrations (0.01%, 0.025% and 0.05%) significantly curtailed myopic advancement and were well tolerated by participants[7]. The landmark Atropine for the Treatment of Myopia (ATOM) 2 trial in Singapore similarly validated the superiority of 0.01% atropine over higher doses on both efficacy and tolerability grounds[8].

Here lies the problem. The overwhelming preponderance of this evidence derives from East Asian or multiethnic Western cohorts. A study conducted in Lebanon found that more than half of medical trainees were myopic which starkly illustrates the local burden of this condition[9]. Neighboring Middle Eastern nations have started producing their own datasets. A double-blind randomized trial from Iran confirmed that atropine eye drops significantly reduced myopic progression vs a non-treated control group[10]. A retrospective observational study from Turkey similarly reported meaningful myopia control with low-dose atropine relative to alternative strategies[11]. Lebanon nonetheless remains conspicuously absent from this regional evidence base. No published study has evaluated low-dose atropine for myopia control in Lebanese children. Given that environmental and genetic factors may modulate atropine’s mechanism of action and that ethnic variability in treatment response is well documented in the literature[12], region-specific data are not merely desirable. They are indispensable.

The purpose of this study was therefore to investigate the effect of nightly 0.01% atropine eye drops on myopia progression in Lebanese children aged 4-12 years through a retrospective cohort design. We compared children treated with atropine to those managed with spectacle correction alone, measuring changes in spherical equivalent refraction (SER) over 24 months. We hypothesized that atropine-treated children would demonstrate significantly slower myopia progression with minimal side effects.

MATERIALS AND METHODS

Study design and setting

This retrospective cohort study was based on a review of pediatric patient files from two sites in Lebanon: A hospital-based ophthalmology department (site 1) and a private ophthalmology clinic (site 2). Refraction measurements at each site were performed by different clinician operators using their respective autorefractometers, constituting a potential source of between-site measurement variability that is acknowledged in the limitations. The study was conducted in accordance with the principles of the Declaration of Helsinki and relevant Good Clinical Practice guidelines. Institutional ethical review approval was obtained prior to data access. A STROBE checklist has been completed and is provided as a supplementary submission document.

Participants

Inclusion criteria: (1) Age 4-12 years at baseline; (2) Baseline myopia ≤ -1.00 diopters (D) and ≥ -8.00 D SER; (3) Minimum 12 months of documented follow-up data available; and (4) Lebanese nationality. The atropine group comprised children in whom the treating clinician had initiated nightly 0.01% atropine eye drops based on clinical judgment - typically informed by the degree of myopia, evidence of prior progression on existing records, and parental preference or request. The control group comprised age-eligible Lebanese children attending the same clinical settings for routine spectacle correction follow-up, who met all inclusion and exclusion criteria and had not received any myopia control intervention.

Exclusion criteria: Prior ocular surgery; known ocular pathology (e.g., strabismus, corneal disease); systemic conditions affecting refraction; use of other myopia control treatments (orthokeratology, multifocal lenses); anisometropia > 1.00 D; astigmatism > 2.50 D at baseline; prior history of any myopia control intervention; or incomplete refraction records at one or more follow-up visits.

Data collection

Cycloplegic retinoscopy defined refraction at every visit. Cycloplegia was achieved with cyclopentolate 1% eye drops administered as two instillations five minutes apart. Refraction measurements were obtained 30 minutes to 45 minutes after the second drop. Extracted data included baseline and serial measurements of SER (in diopters), cylinder values, best-corrected visual acuity (BCVA) and patient demographics (age and sex). Measurements were recorded at baseline and at 6-month intervals within a window of ± 2 months across the 24-month follow-up. BCVA was converted to logMAR for all statistical analyses. Parental history of myopia, near-work habits, outdoor activity levels and parental consanguinity were not systematically captured in the clinical records. These variables could therefore not be included as covariates in the analysis.

Outcome measures

The primary outcome was the change in SER from baseline to 24 months. Secondary outcomes included change in BCVA (logMAR) from baseline to 24 months and the occurrence of adverse effects (photophobia, near-vision difficulty, or systemic effects) in the atropine group.

Sample size calculation

Minimum sample size was calculated using G*Power software (version 3.1), with an effect size of 0.641, an alpha error of 0.05, and a power of 0.80. A minimum of 31 eyes per group (62 total) was required to detect a statistically significant difference in myopia progression between groups.

Statistical analysis

Data were analyzed using SPSS software (version 26; IBM Corp., Armonk, NY, United States). The primary analysis compared inter-period SER change (ΔSER) between groups at each 6-month interval using repeated measures analysis of variance. Statistical significance was set at P < 0.05. Results are expressed as mean ± SD. The biostatistical approach was reviewed by a qualified biomedical statistician.

RESULTS

Study population

A total of 70 eyes from 36 pediatric patients were included (mean age 7.89 ± 2.59 years; 50% female). All 36 patients were Lebanese nationals of Arab ethnicity, with Arabic as their primary language. A proportion of patients contributed data from both eyes, while others contributed data from one eye only (based on unilateral eligibility per the exclusion criteria), accounting for the discrepancy between the number of eyes (70) and patients (36). Thirty-five eyes were allocated to the atropine group and 35 to the control group. Eighteen patients (50%) were female and 18 (50%) were male. No systemic comorbidities were documented in any included participant. Family history of myopia and parental consanguinity were not systematically recorded in the available clinical records. They could not therefore be assessed.

Baseline SER values differed significantly between groups (atropine: 3.99 ± 1.50 D vs control: 2.71 ± 0.98 D; P < 0.001). The atropine group entered the study with greater myopia at baseline. This imbalance is a recognized limitation of the retrospective non-randomized design. It is addressed in detail in the Discussion. Sex-stratified analysis of SER progression was not feasible given the sample size constraints. This remains a priority for future investigation.

Primary outcome: Change in SER

Repeated measures analysis of variance confirmed that both groups experienced significant myopic progression at all time points (P < 0.001 for each). However, the atropine group consistently demonstrated a smaller rate of SER progression (Table 1). Inter-period ΔSER was significantly lower in the atropine group at the 0-6 months interval (0.26 ± 0.29 D vs 0.51 ± 0.46 D; P = 0.008) and the 12-18 months interval (0.18 ± 0.25 D vs 0.37 ± 0.32 D; P = 0.009). The inter-period differences at 6-12 months (P = 1.00) and 18-24 months (P = 0.071) did not reach statistical significance. Absolute SER values at each time point are presented in Table 2.

Table 1 Inter-period change in spherical equivalent refraction between the atropine and control groups (mean ± SD, diopters).

Time interval	Control group (n = 35)	Atropine group (n = 35)	P value
0-6 months vs baseline	0.51 ± 0.46	0.26 ± 0.29	0.008b
6-12 months	0.31 ± 0.29	0.31 ± 0.34	1.00
12-18 months	0.37 ± 0.32	0.18 ± 0.25	0.009b
18-24 months	0.42 ± 0.31	0.29 ± 0.24	0.071

^bP < 0.01 vs control group.

Table 2 Absolute spherical equivalent refraction values at each time point for the atropine and control groups (mean ± SD, diopters).

Time interval	Control group (n = 35)	Atropine group (n = 35)	P value
Baseline	2.71 ± 0.98	3.99 ± 1.50	< 0.001b
6 months	3.22 ± 1.07	4.24 ± 1.49	0.003b
12 months	3.54 ± 1.09	4.52 ± 1.44	0.003b
18 months	3.91 ± 1.13	4.73 ± 1.50	0.015a
24 months	4.33 ± 1.25	5.01 ± 1.49	0.057

^aP < 0.05 vs control group.

^bP < 0.01 vs control group.

Secondary outcomes

BCVA remained stable in both groups throughout the 24-month follow-up period, with no statistically significant changes detected. No adverse effects - including photophobia, near-vision difficulty, or systemic events - were reported in any atropine-treated patient during the study period.

DISCUSSION

This study evaluated the effectiveness of nightly 0.01% atropine eye drops in slowing myopic progression in Lebanese children over 24 months. Atropine treatment was associated with a significantly slower rate of progression at two of four inter-period intervals (0-6 months and 12-18 months), with no adverse effects. To our knowledge, this represents the first study to provide efficacy data for low-dose atropine specifically in the Lebanese population.

Our findings are broadly consistent with landmark trials conducted in East Asian populations. The ATOM 2 trial reported a 50% reduction in myopia progression over a 5-year period with 0.01% atropine in Singaporean children[8,13]. The Low-Concentration Atropine for Myopia Progression trial demonstrated significant progression control across all three low-dose concentrations tested and reported no adverse effect on visual acuity[7,14,15]. More recently, the Pediatric Eye Disease Investigator Group ATOM study in a predominantly non-Asian population similarly found that 0.01% atropine reduced progression relative to placebo, though the effect was modest[16,17]. Our results align with this growing multinational evidence base by demonstrating that the same dosage is active in a Middle Eastern cohort. The neighboring regional data from Iran[10] and Turkey[11] further support the potential generalizability of atropine-based myopia control across Middle Eastern and Eastern Mediterranean populations, with the present Lebanese cohort adding a further data point to this evidence landscape. These findings are concordant with published expert consensus recommendations endorsing low-dose atropine as a safe and effective front-line intervention for pediatric myopia control[18].

An important methodological consideration in this study is the significant baseline SER imbalance between groups (P < 0.001), with the atropine group presenting with greater myopia at entry. This imbalance is a recognized limitation of retrospective, non-randomized designs and likely reflects prescriber selection bias - clinicians may have preferentially initiated atropine in children with faster-progressing or more severe myopia. Because this would tend to bias results against the atropine group (i.e., against demonstrating a beneficial effect), the observed efficacy signal may represent a conservative estimate. The possibility that regression to the mean contributed to the observed slower progression in the atropine group also cannot be excluded in the absence of statistical adjustment for baseline values, even though the direction of the baseline imbalance would ordinarily work against, rather than in favor of, the atropine group. Nonetheless, the absence of randomization means that unmeasured confounders cannot be excluded as contributors to the observed differences, and these findings should be interpreted with appropriate caution. Future prospective, randomized studies in this population are essential to confirm these findings with greater internal validity.

Parental myopia is one of the most powerful and consistently validated predictors of childhood myopic progression. A large-scale investigation by Tang et al[19] in the Hong Kong Children Eye Study encompassing 2055 trios demonstrated that having two myopic parents conferred an approximately 11-fold heightened risk of myopia vs a mere 1.2-fold increase attributable to reading time. This underscores the dominant role of heritable susceptibility over behavioral factors. The present study did not systematically collect parental refractive status data. This omission represents a meaningful potential confounding variable. Future studies in this population must document parental myopia as a covariate. This is especially pertinent given Lebanon’s rates of consanguinity and family structure which may amplify genetic contributions to myopic susceptibility.

The wide age range enrolled (4 years to 12 years) introduces acknowledged heterogeneity. Myopia onset and progression kinetics vary substantially across this developmental window. Earlier-onset myopia generally portends greater eventual severity and faster progression. Age-stratified analyses would be needed to determine whether the treatment effect of 0.01% atropine differs by age at initiation as existing evidence suggests[7,17]. The present sample size precluded such stratification. Future studies must enroll larger cohorts to enable meaningful subgroup analysis.

Parental consanguinity is prevalent in certain Middle Eastern populations including Lebanon. It may shape the genetic architecture of myopia susceptibility and progression in ways not yet fully characterized. This factor was not assessed in the present study. It warrants dedicated systematic investigation in future regional research on pediatric myopia.

The non-significant inter-period differences at 6 months to 12 months (P = 1.00) and 18 months to 24 months (P = 0.071) require discussion. The complete absence of between-group difference at 12 months is notable. It may reflect natural developmental variability in progression rates across different growth phases. Alternatively it may represent a transient waning of atropine efficacy with prolonged use followed by renewed therapeutic activity. This oscillatory pattern has been observed in other low-dose atropine trials[7,15]. A simpler explanation is also plausible: The small sample size and limited statistical power may render individual inter-period comparisons susceptible to random fluctuation. The borderline P = 0.071 at the 18 months to 24 months interval is clinically meaningful. It may represent a genuine treatment effect that the study was underpowered to confirm. These findings reinforce the urgent need for larger well-powered studies with extended follow-up in this population.

The primary endpoint of the study (overall SER change from baseline to 24 months) did not achieve uniform statistical significance across all intervals. Conclusions regarding atropine efficacy should therefore be stated with precision. The available data support an association between nightly 0.01% atropine and decelerated myopia progression at specific timepoints. They do not definitively establish that atropine uniformly and comprehensively slows progression across the entire 24-month observation window in this cohort.

Visual acuity stability throughout the study and the complete absence of adverse effects in the atropine arm are clinically consequential findings. High atropine concentrations reliably produce photophobia and accommodative paresis[6]. The 0.01% preparation appears to circumvent these problems entirely. This tolerability profile is consistent with the broader literature[17] and renders nightly 0.01% atropine a pragmatically attractive therapeutic option. It is considerably less burdensome than orthokeratology (which demands nightly rigid lens wear) or multifocal contact lenses (which present fitting and comfort challenges in very young children)[3,4].

The primary limitation of this study is its retrospective design paired with a modest sample size (70 eyes from 36 patients). The cohort exceeded the pre-specified power calculation threshold. Larger cohorts nonetheless remain necessary for subgroup analyses stratified by age, sex and baseline severity. The absence of axial length measurements represents a secondary limitation. Axial elongation is a more mechanistically informative primary outcome measure. It would enable direct comparison with studies reporting axial length data[16]. The 24-month observation period also precludes evaluation of rebound myopia upon atropine discontinuation which has been described in long-term investigations[13]. Finally, the dual-site design with different operators and instruments introduces measurement variability that the retrospective analytical framework could not control.

CONCLUSION

The evidence points in one direction. Nightly 0.01% atropine eye drops were associated with significantly decelerated myopia progression at multiple timepoints over 24 months in Lebanese children. Visual acuity remained stable throughout. No adverse effects were observed. While the primary 24-month endpoint did not achieve uniform statistical significance across every inter-period interval, these findings substantively extend the emerging Middle Eastern evidence base for low-dose atropine. They support further clinical investigation of this agent in pediatric myopia management in Lebanon. Prospective randomized controlled trials with larger sample sizes, axial length outcome measures, parental myopia documentation and extended follow-up periods are needed to confirm and build upon these results.