title: Acoustic radiation force for noninvasive evaluation of corneal biomechanical changes induced by cross-linking therapy.
abstract: OBJECTIVE
  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.
authors: Department of Ophthalmology, Columbia University Medical Center, New York, New York USA (R.U., H.O.L., R.H.S.); and Frederic L. Lizzi Center for Biomedical Engineering, Riverside Research Institute, New York, New York USA (R.H.S.). ru2118@columbia.edu.
authors: Raksha
authors: R
authors: Urs
authors: Department of Ophthalmology, Columbia University Medical Center, New York, New York USA (R.U., H.O.L., R.H.S.); and Frederic L. Lizzi Center for Biomedical Engineering, Riverside Research Institute, New York, New York USA (R.H.S.).
authors: Harriet O
authors: HO
authors: Lloyd
authors: Department of Ophthalmology, Columbia University Medical Center, New York, New York USA (R.U., H.O.L., R.H.S.); and Frederic L. Lizzi Center for Biomedical Engineering, Riverside Research Institute, New York, New York USA (R.H.S.).
authors: Ronald H
authors: RH
authors: Silverman
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001696:Biomechanical Phenomena / Q000187:drug effects / Q000502:physiology; D003315:Cornea / Q000000981:diagnostic imaging* / Q000187:drug effects; D063171:Corneal Pachymetry / Q000379:methods; D003432:Cross-Linking Reagents / Q000494:pharmacology*; D004548:Elasticity / Q000187:drug effects; D054459:Elasticity Imaging Techniques / Q000379:methods*; D005500:Follow-Up Studies; D017319:Photosensitizing Agents / Q000494:pharmacology*; D011817:Rabbits; D012256:Riboflavin / Q000494:pharmacology*; D014467:Ultraviolet Therapy / Q000379:methods*; D014783:Viscosity / Q000187:drug effects
chemical_list: D003432:Cross-Linking Reagents; D017319:Photosensitizing Agents; D012256:Riboflavin
keywords: acoustic radiation force; cornea; cross-linking; elasticity; keratoconus; ultrasound