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Keyton Clayson- PhD Dissertation.pdf (5.08 MB)

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Corneal Biomechanical Responses to Intraocular Pressure Using High Frequency Ultrasound Elastography: From Ex Vivo to In Vivo

Clayson, Keyton Leslie
http://orcid.org/0000-0002-6176-4835
http://rave.ohiolink.edu/etdc/view?acc_num=osu1574701032958196

Abstract Details

2019, Doctor of Philosophy, Ohio State University, Biophysics.
The cornea is the clear, front part of the eye, and its shape and transparency are essential for vision. In disease states, including keratoconus and glaucoma, the mechanical properties of the cornea may be altered and could contribute to the progression of eye disease. Current clinical devices cannot measure the mechanical properties of the cornea, but several approaches have been proposed. Most of these approaches either depend on external loading or only provide average responses that cannot delineate where pathologic changes are occurring. In this work, we utilize an ultrasound-based speckle tracking technique to characterize the mechanical response of the cornea during changes in intraocular pressure (IOP) in both ex vivo donor eyes and in living volunteers. The first two studies presented in this work identify how corneal hydration impacts the mechanical response of postmortem cornea. The 3D strain response of porcine corneas during ex vivo inflation testing at two different hydration states (untreated and dextran-treated) were obtained. Our results showed that the dextran-treated corneas showed an inflation response expected of a thin spherical shell, while the inflation response of untreated cornea was confounded with swelling during experimentation. As differences between hydration states were observed, a method was developed to restore and maintain physiological hydration in postmortem corneas during ex vivo experimentation using poloxamer 188 (P188), a synthetic macromolecule surfactant. Our results showed that P188 could return the cornea towards physiological hydration levels after treatment, and that inflation strains were significantly affected by the hydration level of the cornea. These results confirm the impact of hydration state on corneal mechanical response and suggest that P188 treatment may stabilize hydration near physiological levels during ex vivo experimentation. The third study investigated how corneoscleral biomechanical properties may impact glaucoma risk, and specifically, how these properties affect IOP spikes induced by rapid microvolumetric change. Porcine eyes were subjected to volumetric infusions before and after either 1) central cornea stiffening, 2) posterior sclera stiffening, or 3) changes in steady-state IOP. We found that the IOP spike magnitudes increased in all three cases, with corneal stiffening having a stronger effect than scleral stiffening, and steady-state IOP markedly increasing spike magnitude due to the increased “apparent” stiffness of the ocular shell. These results suggest that corneoscleral properties may represent additional pathways for understanding and managing glaucoma risk. The last two studies tested the feasibility of a new technique, termed ocular pulse elastography (OPE), to quantify corneal strains generated by naturally occurring pulsations of IOP using high-frequency ultrasound. Human cadaver globes with simulated ocular pulses were used to investigate the effects of physiological variations (baseline IOP, ocular pulse amplitude (OPA), and pulse frequency) and clinically relevant corneal crosslinking (CXL) on corneal strain. Variations in both baseline IOP and OPA had a significant influence on strain magnitude, while variations in pulse frequency within the normal human heartrate range did not. CXL treatment significantly reduced corneal strain magnitude, and the extent of strain reduction appeared to correlate with initial strain magnitude. An in vivo study including 41 healthy and 4 keratoconic volunteers was conducted to demonstrate the translational feasibility of the OPE technique. Our results showed that displacements obtained with the OPE technique were of cardiac origin, and strain magnitudes could be reasonably obtained in volunteers. These studies demonstrate that the OPE method may lead to a new clinical tool for safe and quick biomechanical evaluations of the cornea.
Jun Liu (Advisor)
Gunjan Agarwal (Committee Member)
Cynthia Roberts (Committee Member)
119 p.
Biomechanics; Biomedical Engineering; Biophysics; Medical Imaging; Ophthalmology
ultrasound speckle tracking; ultrasound elastography; high frequency ultrasound; biomechanics; cornea; ocular pulse; corneal deswelling; corneal hydration

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Citations

  • Clayson, K. L. (2019). Corneal Biomechanical Responses to Intraocular Pressure Using High Frequency Ultrasound Elastography: From Ex Vivo to In Vivo [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1574701032958196

    APA Style (7th edition)

  • Clayson, Keyton. Corneal Biomechanical Responses to Intraocular Pressure Using High Frequency Ultrasound Elastography: From Ex Vivo to In Vivo. 2019. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1574701032958196.

    MLA Style (8th edition)

  • Clayson, Keyton. "Corneal Biomechanical Responses to Intraocular Pressure Using High Frequency Ultrasound Elastography: From Ex Vivo to In Vivo." Doctoral dissertation, Ohio State University, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=osu1574701032958196

    Chicago Manual of Style (17th edition)

osu1574701032958196
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This open access ETD is published by The Ohio State University and OhioLINK.