Estimating outflow facility through pressure dependent pathways of the human eye.

David W Smith,Bruce S Gardiner

doi:10.1371/journal.pone.0188769

David W Smith, Bruce S Gardiner

Open Access

https://doi.org/10.1371/journal.pone.0188769

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Journal: PloS one	Publication Date: Dec 20, 2017
Citations: 6	License type: CC BY 4.0

Affiliation: University of Western Australia, Murdoch University

Abstract

We develop and test a new theory for pressure dependent outflow from the eye. The theory comprises three main parameters: (i) a constant hydraulic conductivity, (ii) an exponential decay constant and (iii) a no-flow intraocular pressure, from which the total pressure dependent outflow, average outflow facilities and local outflow facilities for the whole eye may be evaluated. We use a new notation to specify precisely the meaning of model parameters and so model outputs. Drawing on a range of published data, we apply the theory to animal eyes, enucleated eyes and in vivo human eyes, and demonstrate how to evaluate model parameters. It is shown that the theory can fit high quality experimental data remarkably well. The new theory predicts that outflow facilities and total pressure dependent outflow for the whole eye are more than twice as large as estimates based on the Goldman equation and fluorometric analysis of anterior aqueous outflow. It appears likely that this discrepancy can be largely explained by pseudofacility and aqueous flow through the retinal pigmented epithelium, while any residual discrepancy may be due to pathological processes in aged eyes. The model predicts that if the hydraulic conductivity is too small, or the exponential decay constant is too large, then intraocular eye pressure may become unstable when subjected to normal circadian changes in aqueous production. The model also predicts relationships between variables that may be helpful when planning future experiments, and the model generates many novel testable hypotheses. With additional research, the analysis described here may find application in the differential diagnosis, prognosis and monitoring of glaucoma.

Highlights

Glaucoma is the most significant cause of irreversible blindness world-wide, with some 70 million people affected [1]
We develop the theory and governing equations using the new nomenclature, and employing various published experimental data, solve the model equations to make estimates of the three key parameters governing outflow facility in the new theoretical model, namely: (i) the hydraulic outflow conductance for the whole eye, CTSL, describing membrane outflow properties (ii) an exponential decay constant α-1 for the whole eye, which describes the rate of decrease of local outflow and outflow facility with increasing intraocular pressure (IOP), and (iii), the IOP denoted pT, at which there is no pressure dependent flow to or from the eye
Using published pressure-volume curves, ocular rigidity estimates and pressure-time curves for in vivo human eye, we work through Examples 1 to 5, estimating model parameters and outflow facility using Eq (23)

Summary

Introduction

Glaucoma is the most significant cause of irreversible blindness world-wide, with some 70 million people affected [1]. While glaucoma is a group of diseases, there is a crucially important association between the initiation and progression of glaucoma, and raised intraocular pressure (IOP). It is hypothesized that raised IOP (or elevation of the pressure gradient across the optic nerve head [2, 3]) can directly lead to optic nerve neuropathy. One postulated mechanism driving optic nerve neuropathy is the disruption of axonal transport at the optic nerve head, which leads to retinal ganglion cell degeneration and loss of vision [4, 5]. The only proven treatment of glaucoma is reduction of IOP [1, 6]

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