Detecting Iris Stiffening and Its Significance in Certain Types of Glaucoma

Rouzbeh Amini, PhD
The University of Akron (Akron, OH)

Co-Principal Investigators

Syril K. Dorairaj, MD
Mayo Clinic (Jacksonville, FL)
Year Awarded:
2018
Grant Duration:
July 1, 2018 to June 30, 2020
Disease:
Glaucoma
Award Amount:
$150,000
Grant Reference ID:
G2018177
Award Type:
Standard
Award Region:
US Midwestern

In-Vivo Assessment of Human Iris Mechanical Properties

Summary

The shape of the iris and how it deforms in response to light (ie, pupil dilation or constriction) are important factors in understanding the mechanism of glaucoma. Similar to any other tissue that deforms (eg, blood vessels or skeletal muscles), if the iris is stiffer, it deforms differently, which has been the case in some glaucoma patients. Unlike previous studies, in which surgically removed pieces of the iris were used for quantifying the stiffness, we aim to combine noninvasive imagining techniques currently used in eye clinics with a novel computer model to estimate iris stiffness. We also aim to understand how stiffening of the iris affects the shape of its comprising cells during the pupil’s responses to light, because we believe that cellular-level deformation is an important factor in the regulation of activities in those cells. 

Details

The main goal of our project is to examine if, why, and how the iris becomes stiffer and consequently becomes abnormally deformed, in the eyes of certain groups of patients who suffer from angle-closure glaucoma.

The shape of the iris and how it deforms in response to light (the pupil either dilates or constricts) are important factors for understanding the mechanism of angle-closure glaucoma. Similar to any other tissue in the body that changes shape (eg, blood vessels or skeletal muscles), if the iris becomes stiffer, it will deform in a different way, as is the case for some angle-closure glaucoma patients. 

Unlike previous studies, in which surgically removed pieces of the iris were used to estimate the stiffness of the iris, we are using noninvasive imaging to measure the shape of the irises of volunteers as they respond to changes in light levels—employing optical coherence tomography (OCT), which is available in many clinical examination centers. Because we know from biomechanical studies in other eye tissues that tissue stiffening could be a result of aging, we are conducting studies to measure iris stiffness for healthy individuals of different ages, and comparing the results to measurements from angle-closure glaucoma patients of the same age. To do so, we construct a novel, patient-specific computer model to estimate the stiffness of the iris. Since it is known that this computational guessing process should be repeated many times to obtain an accurate and reliable value for the iris stiffness, we will use high-performance computers at the Ohio Supercomputer Center to run hundreds of simulations in less than a few minutes. 

Previous studies have shown that cells subjected to higher levels of deformation will produce proteins that make tissues stiffer. Another novel aspect of our project pertains to understanding how the iris becomes stiffer: we are using a model to simulate changes in the cellular-level deformation following light-induced changes in the iris, as we believe that deformation at this level is an important factor in regulating cellular activities that lead to the production of the proteins that can stiffen the iris.

Once our project is completed, the knowledge obtained regarding the relationship between iris tissue stiffening, iris cellular mechanical sensitivity, and the development of angle-closure glaucoma can be used to develop new treatment strategies. For example, if the iris becomes stiffer more rapidly with age in certain populations of patients, it may be possible to develop pharmacological agents that soften the iris by targeting the production of iris-stiffening proteins.

About the Researcher

Dr. Amini completed his PhD in biomedical engineering at the University of Minnesota in the field of ocular biomechanics and biotransport in 2010, and his dissertation was entitled, “Iris Biomechanics in Health and Disease.” He continued his research work on the mechanics of soft tissues as a postdoctoral trainee at the University of Pittsburgh’s Department of Bioengineering, where he held the Ruth L. Kirschstein National Research Service Award (NIH F32). Dr. Amini has served as an assistant professor in the Department of Biomedical Engineering at the University of Akron since August 2013. His research has been funded by the National Science Foundation, Akron Children’s Hospital, the Firestone Foundation, the American Heart Association, and the BrightFocus Foundation.

Personal Story

When I embarked upon my doctoral training in the fall of 2005, one of the first books that I read to obtain fundamental knowledge regarding my research project in eye biomechanics was Chandler and Grant's Glaucoma, edited by David L. Epstein, Rand Allingham, and Joel Schuman. This is how the introduction of this fascinating book begins:


The study of glaucoma can be clinically satisfying and intellectually stimulating. Yet, it is the most humbling of the disciplines, both because of our clinical failures but even more our lack of understanding. In truth, if one looks at the ophthalmic knowledge in the last century, the field of glaucoma has shown the least progress. 
 

 

For the past 13 years, understanding the pathophysiology of glaucoma as it pertains to the biomechanics of the anterior eye has been a major focus of my research efforts. Today, I agree even more with Dr. Epstein and his colleagues that the study of glaucoma is “the most humbling of the disciplines.” However, with the advent of high-performance computers and accurate non-invasive imaging techniques, we are now able to conduct novel studies to understand the pathophysiology of glaucoma that were not possible even 10 years ago. I have been fortunate to combine my engineering knowledge with the clinical expertise of my collaborators as we strive to find answers for some important questions: Why does angle-closure glaucoma develop in some people and not in others? Why are surgical treatments of angle-closure successful in some patients and not successful in others? How should we develop new treatment strategies for those patients who do not respond to any of our current treatment methods?

While I have always been determined to work hard to find answers to the above-mentioned questions, it was not until I visited the office of my clinical collaborator, Dr. Dorairaj, that I fully grasped the importance of our efforts. While the main purpose of my trip was to discuss our research plans, I witnessed how Dr. Dorairaj interacted with a few of his patients. During this day, a young lady in her twenties visited Dr. Dorairaj. She was nearly blind in one eye, and her sight in the other eye was rapidly deteriorating. Dr. Dorairaj examined her eyes and in an adroit and extremely polite manner explained that the most aggressive procedures had been performed for her and basically “there was nothing else to be done.” Of course, that was not what she had been hoping to hear, nor was it an answer that any physician wants to deliver to a patient. On that day, Dr. Dorairaj saved a few minutes after each patient visit for the two of us to discuss the cases. Prior to this young lady, most of our post-visit conversations were about the specific cases. This time, after she left, we just had a few somber moments, and then Dr. Dorairaj expressed his utmost frustration about why he feels so helpless when such cases are presented. He then looked at me and told me bluntly, “Rouzbeh, together, let’s solve the problem of angle-closure in our lifetime.”

While we are all motivated and excited about our research work, a major challenge for those of us conducting research in biomedical fields is securing continuous and sufficient funding. For our laboratory, the funding from BrightFocus Foundation could not have come at a better time. Thanks to the generosity of donors and the positive opinion of the scientific review committee, who found our study to be novel and significant, we are able to continue our research. I am now able to train a doctoral student who can dedicate 100 percent of her research efforts to this project. We hope that the knowledge gained from this funded project will help us to better understand the mechanism of angle-closure glaucoma and will motivate researchers to develop additional and/or alternative treatments to help glaucoma patients. 

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