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Myopia and eye disease: From correlation to causation
James Loughman1, Mark A Bullimore2, Ian Flitcroft3
1Centre for Eye Research Ireland, School of Physics, Clinical and Optometric Sciences, Technological University Dublin, Dublin, Ireland.
Abstract:
Myopia is increasingly recognised as a risk factor strongly linked to visual impairment and sight-threatening ocular disease rather than a simple refractive state. The assumption of causality to these secondary effects underpins myopia control and its long-term public health value. This review considers epidemiologic, longitudinal, mechanistic, interventional, natural-experiment, and genetic evidence to evaluate causality based on Bradford Hill's nine criteria: strength, consistency, specificity, temporality, biological gradient, plausibility, coherence, experiment, and analogy. The graded dose-response relationship between myopia and visual impairment has been demonstrated across multiple populations. Similar patterns are shown for a range of myopia-related ocular diseases. Risks for myopic maculopathy and rhegmatogenous retinal detachment rise steeply with increasing refractive error and axial length, following reproducible log-linear dose-response patterns. Associations with primary open-angle glaucoma are more modest but consistent, supported by longitudinal and genetic causal-inference analyses, though diagnostic overlap in highly myopic eyes complicates interpretation. Cataract relationships are subtype-specific, with the strongest evidence for posterior subcapsular cataract; nuclear cataract associations require caution given lens-induced refractive shifts. The criteria for biological plausibility and the related concept of coherence are strong: axial elongation produces predictable remodelling of sclera, choroid, retina and optic nerve head that can be directly related to clinical phenotypes. Experimental evidence is mostly indirect but also supportive, and analogy with other axial-length-modifying conditions lends further support. Overall, convergent evidence across all of Bradford Hill's criteria supports a causal role of myopia in the major myopia-associated ocular diseases and justifies myopia management as a strategy to limit lifetime axial elongation.
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