A Balancing Act: Low-Dose Atropine Significantly Slows Pediatric Myopia Progression Without a Clinically Meaningful Risk of Rebound (Accelerated Myopia Progression Following Treatment Cessation)
Author(s)
Jelena Jovanovic, DPhil1, Maria Zacharioudaki, BSc, MSc2, Georgios Papadakis, PhD3, Marilena Kalatzi, BSc, MSc3, Nagarjuna Mulkalapalli, M.S. (Pharm.)4, Frederic Ernst, AttorneyatLaw, MBAHealthEconomics5, Thom de Milliano, BSc, MSc6.
1IQVIA, London, United Kingdom, 2IQVIA, Munich, Germany, 3IQVIA, Athens, Greece, 4IQVIA, Gurugram, India, 5Santen Pharmaceuticals, Munich, Germany, 6Santen, Geneva, Switzerland.
1IQVIA, London, United Kingdom, 2IQVIA, Munich, Germany, 3IQVIA, Athens, Greece, 4IQVIA, Gurugram, India, 5Santen Pharmaceuticals, Munich, Germany, 6Santen, Geneva, Switzerland.
OBJECTIVES: Paediatric myopia is a growing public health concern with adolescent prevalence projected to reach 47% by 2050. Approved interventions for controlling paediatric myopia and associated long-term complications are limited in the European Union. We evaluated comparative efficacy and safety of low-dose atropine (LDA) versus other pharmacological, optical or light interventions for slowing paediatric myopia progression.
METHODS: Randomised control trials (RCTs) were identified in a systematic literature review (SLR). Evidence from eligible RCTs was synthesized in a Bayesian random-effects network meta-analysis (NMA). Heterogeneity was examined through subgroup analyses and network meta-regressions (NMR). A hierarchical NMA for class effects was used to enhance precision while preserving the interpretability of individual interventions for decision-making.
RESULTS: SLR identified 117 RCTs of 24 active interventions. Twenty-two RCTs were excluded due to heterogeneity or high risk of bias. LDA (<0.1%) was superior versus inactive control in slowing myopia progression measured by spherical equivalent refraction (SER) or axial elongation for at least two years, in a dose-dependent manner. Although less effective than moderate-dose (MDA, 0.1% to <0.5%) or high-dose atropine (HDA, ≥0.5%) during active treatment, a year after treatment cessation patients on LDA showed no evidence of a clinically meaningful rebound effect, while children previously treated with MDA or HDA progressed faster than children who had never received active treatment. Repeated low-level red-light alone or with orthokeratology (ORTHOK) and LDA+ORTHOK were most effective in controlling myopia although their comparative rebound effect was not assessed due to lack of data. NMRs identified baseline SER, baseline progression, geography and race as effect modifiers albeit with borderline significance.
CONCLUSIONS: LDA significantly slows progression of paediatric myopia versus control over two years of treatment without a clinically meaningful rebound effect or safety concerns associated with MDA or HDA. These findings may inform guidelines and decision making to expand access to effective myopia control options.
METHODS: Randomised control trials (RCTs) were identified in a systematic literature review (SLR). Evidence from eligible RCTs was synthesized in a Bayesian random-effects network meta-analysis (NMA). Heterogeneity was examined through subgroup analyses and network meta-regressions (NMR). A hierarchical NMA for class effects was used to enhance precision while preserving the interpretability of individual interventions for decision-making.
RESULTS: SLR identified 117 RCTs of 24 active interventions. Twenty-two RCTs were excluded due to heterogeneity or high risk of bias. LDA (<0.1%) was superior versus inactive control in slowing myopia progression measured by spherical equivalent refraction (SER) or axial elongation for at least two years, in a dose-dependent manner. Although less effective than moderate-dose (MDA, 0.1% to <0.5%) or high-dose atropine (HDA, ≥0.5%) during active treatment, a year after treatment cessation patients on LDA showed no evidence of a clinically meaningful rebound effect, while children previously treated with MDA or HDA progressed faster than children who had never received active treatment. Repeated low-level red-light alone or with orthokeratology (ORTHOK) and LDA+ORTHOK were most effective in controlling myopia although their comparative rebound effect was not assessed due to lack of data. NMRs identified baseline SER, baseline progression, geography and race as effect modifiers albeit with borderline significance.
CONCLUSIONS: LDA significantly slows progression of paediatric myopia versus control over two years of treatment without a clinically meaningful rebound effect or safety concerns associated with MDA or HDA. These findings may inform guidelines and decision making to expand access to effective myopia control options.
Conference/Value in Health Info
2025-11, ISPOR Europe 2025, Glasgow, Scotland
Value in Health, Volume 28, Issue S2
Code
CO1
Topic
Clinical Outcomes, Study Approaches
Topic Subcategory
Comparative Effectiveness or Efficacy
Disease
Pediatrics, Sensory System Disorders (Ear, Eye, Dental, Skin)