Volume 33, Issue 8 pp. 1417-1426
Original Research

Acoustic Radiation Force for Noninvasive Evaluation of Corneal Biomechanical Changes Induced by Cross-linking Therapy

Raksha Urs PhD

Corresponding Author

Raksha Urs PhD

Department of Ophthalmology, Columbia University Medical Center, New York, New York USA

Address correspondence to Raksha Urs, PhD, Department of Ophthalmology, Columbia University Medical Center, 160 Fort Washington Ave, Room 711C, New York, NY 10032 USA.Search for more papers by this author
Harriet O. Lloyd MS

Harriet O. Lloyd MS

Department of Ophthalmology, Columbia University Medical Center, New York, New York USA

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Ronald H. Silverman PhD

Ronald H. Silverman PhD

Department of Ophthalmology, Columbia University Medical Center, New York, New York USA

Frederic L. Lizzi Center for Biomedical Engineering, Riverside Research Institute, New York, New York USA

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First published: 01 August 2014
Citations: 9

Supported by the American Institute of Ultrasound in Medicine Endowment for Education and Research

Abstract

Objectives

To noninvasively measure changes in corneal biomechanical properties induced by ultraviolet-activated riboflavin cross-linking therapy using acoustic radiation force (ARF).

Methods

Cross-linking was performed on the right eyes of 6 rabbits, with the left eyes serving as controls. Acoustic radiation force was used to assess corneal stiffness before treatment and weekly for 4 weeks after treatment. Acoustic power levels were within US Food and Drug Administration guidelines for ophthalmic safety. Strain, determined from ARF-induced displacement of the front and back surfaces of the cornea, was fit to the Kelvin-Voigt model to determine the elastic modulus (E) and coefficient of viscosity (η). The stiffness factor, the ratio of E after treatment to E before treatment, was calculated for treated and control eyes. At the end of 4 weeks, ex vivo thermal shrinkage temperature analysis was performed for comparison with in vivo stiffness measurements. One-way analysis of variance and Student t tests were performed to test for differences in E, η, the stiffness factor, and corneal thickness.

Results

Biomechanical stiffening was immediately evident in cross-linking–treated corneas. At 4 weeks after treatment, treated corneas were 1.3 times stiffer and showed significant changes in E (P= .006) and η (P= .007), with no significant effect in controls. Corneal thickness increased immediately after treatment but did not differ significantly from the pretreatment value at 4 weeks.

Conclusions

Our findings demonstrate a statistically significant increase in stiffness in cross-linking–treated rabbit corneas based on in vivo axial stress/strain measurements obtained using ARF. The capacity to noninvasively monitor corneal stiffness offers the potential for clinical monitoring of cross-linking therapy.

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