A comprehensive analysis of Taiwan's National Health Insurance database involving over 1.2 million children has revealed complex safety signals for long-term atropine use in myopia control, with findings that both support and raise questions about the widespread practice of prescribing these drops to slow nearsightedness progression.
The retrospective cohort study, published in JAMA Ophthalmology and led by researchers from National Taiwan University Hospital, examined children aged 8-15 who were newly diagnosed with myopia between 2001 and 2015. Of the 606,923 children with myopia included in the analysis, 406,383 (67.0%) were prescribed atropine drops, reflecting the common use of this treatment in Taiwan for over two decades.
Myopia Increases Complication Risk
The study confirmed that myopia itself carries inherent risks, with children diagnosed with the condition showing a 49% higher risk of developing serious ocular complications compared to their non-myopic peers. The incidence of complications including cataracts, glaucoma, and maculopathy was 1.54 per 10,000 person-years in the myopia group versus 0.96 per 10,000 person-years in the non-myopia group (adjusted hazard ratio 1.49; 95% CI, 1.36-1.64).
However, when comparing children with myopia who received atropine treatment to those who did not, researchers found no overall difference in complication rates, with both groups showing identical incidence rates of 1.54 per 10,000 person-years (adjusted hazard ratio 1.05; 95% CI, 0.93-1.18).
Duration Versus Dosage Paradox
The study's most intriguing finding emerged when researchers examined treatment duration versus cumulative exposure. Children treated with atropine for 3-5 years showed a 50% increased risk of ocular complications, while those treated for more than five years demonstrated an 88% increase in risk, with glaucoma showing the most pronounced association.
Yet this apparent risk signal disappeared when researchers analyzed cumulative dosing rather than duration. "No increased risk was found among children with the highest quartile of cumulative atropine dose," the researchers reported, with an adjusted hazard ratio of 1.05 (95% CI, 0.89-1.25).
Myopia Severity as Confounding Factor
The relationship between treatment duration and complications became less clear when researchers accounted for high myopia. In children with severe myopia, the duration effect vanished entirely (adjusted hazard ratio 1.10; 95% CI, 0.56-2.19), suggesting that myopia severity rather than atropine exposure drives the observed associations.
Lead author Tzu-Hsun Tsai and colleagues noted that "long-term or higher-dose atropine drops are typically prescribed for children with earlier-onset or rapidly progressing myopia," indicating that treatment patterns may reflect disease severity rather than arbitrary clinical decisions.
Clinical Context and Global Implications
The findings carry particular significance given the global myopia epidemic, especially in East Asia where the condition affects growing numbers of children. Atropine drops, which work by blocking acetylcholine and relaxing ciliary muscles to dilate pupils, have shown promise in slowing myopia progression in some studies, though evidence remains mixed.
The researchers noted that despite widespread atropine use in Taiwan, "the prevalence of myopia and high myopia has continued to increase," raising questions about real-world effectiveness alongside safety considerations.
Study Limitations and Future Directions
The database analysis, while comprehensive with follow-up periods extending 10 years for over 70% of participants and 15 years for 40%, carries inherent limitations of retrospective observational studies. The absolute numbers of complications remained small, with 1,258 cases in the myopia group and 786 in the non-myopic control group.
The researchers concluded with measured caution: "The risk of ocular complications from myopia may exceed that associated with long-term atropine use. These findings support monitoring of children receiving atropine for myopia treatment if these results are confirmed by future studies that address the limitations of this investigation."
The study's mixed messages reflect the complexity of evaluating long-term safety in pediatric populations, where treatment decisions must balance potential benefits against uncertain risks. As the global medical community continues searching for effective myopia control strategies, these findings underscore the need for continued vigilance and research into the long-term consequences of interventions designed to protect children's vision.
