ACCOMMODATIVE AQUEOUS REGULATION: A REFRACTIVE-STATE-DEPENDENT FRAMEWORK LINKING PRESBYOPIA TO GLAUCOMA SUBTYPES

Glaucoma is a multifactorial optic neuropathy in which intraocular pressure is the principal modifiable risk factor but not the whole of the disease. Three recurring observations in the epidemiology and pharmacology of open-angle glaucoma, each of which has several possible explanations, together motivate a mechanistic question: open-angle glaucoma incidence rises steeply across the presbyopic decades, glaucoma risk is increased in myopia, and the intraocular pressure of some normal-tension eyes falls in response to muscarinic agonists. This review develops, and then critically grades, the hypothesis that these observations are connected by the mechanical role that accommodation may play in the regulation of aqueous dynamics. The proposal, termed accommodative aqueous regulation (AAR), is that the cyclic ciliary-muscle engagement delivered to the anterior segment during ordinary accommodation contributes to the regulation of aqueous humour, principally by conditioning conventional (trabecular) outflow, the accommodative outflow mechanism (AOM), and that its progressive loss at presbyopia is one contributory, refractive-state-dependent factor in the outflow deterioration that predisposes susceptible eyes to glaucoma. The claim is deliberately limited. The mechanism is offered as a threshold-lowering modifier acting in susceptible eyes within a multifactorial disease, not as a necessary or sufficient cause, and the mapping of refractive state onto glaucoma subtype, associating emmetropia with high-tension open-angle disease, hyperopia with angle-closure, and high myopia with the normal-tension phenotype, is presented as a probabilistic tendency rather than a rule that any individual eye must obey. Established physiology is separated from hypothesis at every step. The mechanical coupling of the ciliary muscle to a mechanosensitive outflow apparatus is supported; the central claim, that ordinary accommodative cycling conditions outflow across a lifetime and that its loss contributes to glaucoma, remains untested and is graded as such. We conclude by specifying the experiments that would confirm or refute it.