Monotherapy or combination therapy for myopia control: a structured narrative comparison of 12-month axial elongation

Purpose: To compare annual axial elongation in children treated with low-dose atropine (0.01%) combined with optical interventions versus higher-dose atropine (≥0.05%) monotherapy and to assess whether combination therapy provides a clinically meaningful advantage over single-agent pharmacologic treatment. Methods: We reviewed 62 clinical studies reporting 12-month axial elongation in 5769 children (median age 9.7 years, IQR 1.2) receiving myopia control interventions. Eligible studies included atropine monotherapy (0.01%, 0.05%, 0.5% and 1%) and combination therapies pairing 0.01% atropine with orthokeratology, peripheral defocus spectacle lenses, or multifocal contact lenses. The primary outcome was absolute axial elongation (mm/year) per treatment group. For contextual interpretation, a composite control group was constructed from 3,097 untreated children across 37 study arms. Results: Combination therapy was reported in 19 study arms (of which 16 East Asian) and high-dose atropine monotherapy in 8 study arms (of which 7 East Asian). Median axial elongation was 0.36mm/year (IQR 0.22) in untreated controls. Under 0.01% atropine monotherapy, elongation was 0.26mm/year (IQR 0.14), whereas under combination therapy, elongation was 0.15mm/year (IQR 0.11). In contrast, elongation was substantially lower with 0.5% and 1% atropine monotherapy: 0.08mm/year (IQR 0.35) and 0.03mm/year (IQR 0.23), respectively. Conclusion: Combination therapy using 0.01% atropine and optical interventions was associated with lower first-year axial elongation than low-dose atropine alone but does not match the effect of higher-dose atropine monotherapy. In children at higher risk of rapid progression, higher-dose atropine monotherapy (0.5% or 1%) may be considered within structured follow-up, balancing potential efficacy against tolerability and longer-term treatment planning.