Background: Myopia (nearsightedness) is a growing global health concern, projected to affect 50% of the world population by 2050. Children with progressive myopia are at risk of serious ocular complications including myopic maculopathy, glaucoma, and retinal detachment. Low-dose atropine (0.05%) has shown efficacy in slowing myopia progression, and optical interventions such as bifocal spectacles may provide additional benefits by altering peripheral retinal defocus. Objective: This randomized controlled trial aims to compare the efficacy and effectiveness of atropine 0.05% monotherapy versus combination therapy (atropine 0.05% plus bifocal spectacles) in controlling myopia progression in children. Methods: Children aged 4-16 years with bilateral myopia (cycloplegic spherical equivalent between -1.00 D and -6.00 D) and documented recent progression (≥ -0.50 D in the preceding 12 months) will be randomized 1:1 to receive either atropine 0.05% eye drops once daily or atropine 0.05% plus bifocal spectacles. The primary outcome is change in spherical equivalent refraction over 12 months; the secondary outcome is change in axial length. Follow-up visits occur at 3, 6, 9, and 12 months. Conclusion: This study will provide evidence on whether adding bifocal correction to pharmacological therapy offers superior myopia control compared to atropine alone, informing clinical practice guidelines for pediatric myopia management.

Study Design and Setting:

This is a prospective, randomized, parallel-group, controlled trial conducted at the Department of Ophthalmology, Mayo Hospital, Lahore, Pakistan. The study is designed and reported in accordance with CONSORT (Consolidated Standards of Reporting Trials) guidelines. The total study duration is 12 months, with follow-up assessments scheduled at 3, 6, 9, and 12 months after baseline.

Sample Size Calculation:

Sample size was determined using G*Power software (version 3.1.9.4). A two-tailed independent-samples t-test was assumed with α = 0.05 and power = 0.95. The allocation ratio N1/N2 was set to 1. To detect a clinically meaningful difference in myopia progression between groups, a total of 210 participants are required, with 105 participants allocated to each treatment arm.

Randomization and Masking:

Eligible participants will be randomized in a 1:1 ratio to either the monotherapy group (atropine 0.05% alone) or the combination therapy group (atropine 0.05% plus bifocal spectacles). The randomization sequence will be generated using a computer-generated random number table. Allocation concealment will be maintained using sequentially numbered, opaque, sealed envelopes. Due to the nature of the interventions (eye drops vs. eye drops plus spectacles), masking of participants and care providers is not feasible. However, outcome assessors will be masked to group allocation.

Interventions:

Group A (Monotherapy): Participants receive atropine sulfate 0.05% ophthalmic solution. One drop is instilled in each eye once daily at bedtime. Parents or guardians are instructed on proper instillation technique, and compliance is monitored by counting returned empty bottles at each follow-up visit.

Group B (Combination Therapy): Participants receive atropine sulfate 0.05% ophthalmic solution (same dosage and regimen as Group A) PLUS bifocal spectacle correction. Bifocal spectacles are prescribed with the distance correction determined by cycloplegic refraction and a near addition of +2.00 D. Participants are instructed to wear spectacles during all waking hours.

Outcome Measures:

Primary Outcome: Change in spherical equivalent refraction (SER) from baseline to 12 months, measured using cycloplegic autorefraction. Cycloplegia is achieved with 1% cyclopentolate or 1% tropicamide administered 30 minutes prior to measurement.

Secondary Outcome: Change in axial length (AL) from baseline to 12 months, measured using optical biometry (e.g., IOLMaster or Lenstar). Three consecutive measurements are taken for each eye, and the mean value is used for analysis.

Safety Monitoring:

At each follow-up visit, participants are assessed for adverse events including:

Ocular: photophobia, blurred near vision, ocular irritation, conjunctival hyperemia, allergic reaction

Systemic: dry mouth, flushing, tachycardia, behavioral changes Adverse events are graded for severity and relationship to study intervention. Participants experiencing serious adverse events may be withdrawn from the study and referred for appropriate management.

Statistical Analysis:

All analyses will be performed using SPSS version 27 (IBM Corp., Armonk, NY, USA). Baseline characteristics will be summarized using descriptive statistics: mean and standard deviation for continuous variables, frequency and percentage for categorical variables. Normality of continuous data will be assessed using the Kolmogorov-Smirnov test. For between-group comparisons, independent t-tests will be used for normally distributed data; Mann-Whitney U tests will be used for non-normally distributed data. Within-group changes over time will be analyzed using repeated-measures ANOVA with Bonferroni correction for multiple comparisons. The primary analysis will be conducted on an intention-to-treat basis. A p-value < 0.05 will be considered statistically significant.

Ethical Considerations:

This study is conducted in accordance with the Declaration of Helsinki. Ethical approval has been obtained from the Institutional Review Board of The University of Faisalabad. Written informed consent is obtained from parents or legal guardians of all participants. Child assent is obtained when appropriate (age 7 years and above, depending on institutional policy). Participants and their families are informed of their right to withdraw from the study at any time without penalty or impact on their clinical care. Participant confidentiality is maintained throughout the study, and data are stored in a secure, password-protected database accessible only to authorized study personnel.

Inclusion Criteria:

• Children aged 4 to 16 years
• Bilateral myopia with cycloplegic spherical equivalent refraction between -1.00 D and -6.00 D in each eye
• Documented recent myopia progression of ≥ -0.50 D over the preceding 12 months
• Best-corrected visual acuity (BCVA) of at least 6/12 (Snellen) or equivalent in each eye
• Parent or guardian able and willing to provide written informed consent
• Child assent when applicable (age 7 years and above per institutional policy)

Exclusion Criteria:

• Ocular conditions affecting myopia progression: strabismus, amblyopia, significant astigmatism (>2.50 D), anisometropia (>2.50 D), cataract, glaucoma, uveitis, or history of ocular surgery
• Prior myopia-control treatment within 6 months (atropine, orthokeratology, multifocal contact lenses, pirenzepine)
• Known allergy or hypersensitivity to atropine or spectacle materials
• Systemic or neurodevelopmental disorders affecting cooperation or refractive development
• Inability to obtain accurate axial length or cycloplegic refraction measurements
• Parent or guardian refusal to provide informed consent