Glaucoma is the second leading cause of blindness worldwide. Certain types of glaucoma are directly related to the iris contour. For example, in primary angle closure glaucoma (ACG), the iris is positioned abnormally to the anterior. In my research project, I tried to reveal the mechanisms underlying iris contour abnormalities using a combination of computational and experimental studies.
The iris contour is determined by the balance of three forces: muscular contractions, iris elastic responses, and hydrodynamic forces. The iris muscular forces arise from activation of the iris constituent muscles while the elastic forces are the result of passive mechanical behavior of the iris. Unlike the other two forces that are generated by the iris, the hydrodynamic forces are caused by the continuous flow of the aqueous humor (AH) in the anterior eye. An accurate and predictive computational model, which could provide insights into pathophysiology of glaucoma and possibly lead to novel therapeutic strategies, must accounts for all of the three elements contributing to the iris contour. As part of the continues investigations in Dr. Barocas’s lab at the University of Minnesota, the main purposes of this study were (1) to characterize the passive mechanical properties of the iris, (2) to characterize iris-related risk factors to ACG using anterior segment optical coherence tomography (AS-OCT) technique, and (3) to develop a computational model of the iris-aqueous-humor interaction in the anterior eye during dilation. The iris is composed of three constituent components: the stroma, the sphincter iridis, and the dilator pupillae. To quantify the relative stiffness of different sections of the iris, mechanical indentation tests and histological analysis in combination with a three- dimensional finite element (FE) simulation were performed. The iris was divided into three regions and the indentation tests were performed on both anterior and posterior sides of porcine irides. The effective moduli and viscoelastic parameters for all regions were calculated. Three-dimensional anatomically accurate models of iris indentation were generated in ABAQUS, based on histological data. An inverse method was developed to determine depth-dependent elastic properties of the iris by comparing experimental results and FE predictions. The study outcomes supported the hypothesis that the posterior layer was the stiffest and produced larger force with increasing depth.
In addition to the differences in their passive stiffness, the iris constituent components also differ in their physiological function and/or pathophysiological roles. For example, there is clinical evidence that in high-risk patients, pupil dilation, caused by relaxation of sphincter iridis and contraction of dilator pupillae, can lead to acute ACG or exacerbate chronic ACG. To study such risk factors, experimental and computational studies were performed.
In the experimental study, twenty normal subjects underwent complete ophthalmic examination and AS-OCT in a controlled-light study. Dynamic changes of the anterior chamber and the iris configuration were captured during light-to-dark (dilation) and dark-to-light (constriction) conditions in a series of AS-OCT images. The relationship between iris parameters (like iris volume) and anterior chamber parameters (like anterior chamber angle and anterior chamber volume) with changes of pupil diameter were evaluated. We observed a decrease (increase) in iris volume and anterior chamber angle during dilation (constriction), and no significant change in anterior chamber volume. The results of this experimental study emphasized the idea that relative compressibility of the iris and dynamic pupillary block play important roles in angle closure mechanism.
Furthermore, a mathematical model of the anterior segment was developed to study ACG risk factors. In a fluid-solid interaction model of the anterior segment, the contribution of three anatomical and physiological factors (dilator thickness, AH blockage, and iris compressibility) to changes in anterior chamber angle during pupil dilation was investigated. The model predicted that iris bowing during dilation was driven primarily by posterior location of the dilator muscle and aqueous humor blockage. The model also predicted that the risk of ACG during dilation increased with iris incompressibility, a result consistent with several clinical observations.
University of Minnesota Ph.D. dissertation. February 2013. Major: Mechanical Engineering. Advisor: Victor H. Barocas. 1 computer file (PDF); x, 164 pages, appendices A-B.
Biomechanical characterization and computational modeling of the anterior eye.
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