A Model of the Mechanisms Underpinning Unconventional Aqueous Humor Outflow

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Abstract

PURPOSE. To develop a mathematical model of the unconventional outflow pathway. METHODS. The unconventional pathway is modeled as having two key components: the uveo-vortex and the trans-scleral pathways. The uveo-vortex pathway is modeled using Starling’s law and the trans-scleral flow using predominately hydrostatic forces. We include transcytosis from the choriocapillaris (CC) and collapsibility of the suprachoroidal space (SCS) as particular features. There is considerable uncertainty in a number of model parameter values, and we identify the most significant ones using sensitivity analysis. RESULTS. The model successfully generates a fluid flow from anterior to posterior in the choroidal tissue and the SCS, which also demonstrates many of the known physiological features, including the insensitivity of the unconventional flow to fluctuations in the IOP, albumin removal by the trans-scleral flow, and the CC as a net absorber of fluid from, and supplier of albumin to, the choroidal tissue. The model supports the two previously proposed mechanisms of the action of prostaglandin F2α analogues. CONCLUSIONS. We have developed a theoretical model of the unconventional aqueous outflow pathway that successfully captures its physiological features and elucidates the actions of prostaglandin F2α analogues and other drugs.

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Tweedy, J. H., Dvoriashyna, M., Crawshaw, J. R., Overby, D. R., Repetto, R., Roberts, P. A., … Foss, A. J. E. (2025). A Model of the Mechanisms Underpinning Unconventional Aqueous Humor Outflow. Investigative Ophthalmology and Visual Science, 66(4). https://doi.org/10.1167/iovs.66.4.75

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