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Raksha Urs, Harriet Lloyd, Ronald Silverman; In Vivo Evaluation of Corneal Biomechanical Properties After Corneal Collagen Cross-linking Therapy. Invest. Ophthalmol. Vis. Sci. 2013;54(15):1616.
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Collagen cross-linking therapy (CXL) is emerging as a treatment option for keratoconus. This procedure strengthens the biomechanical properties of the cornea by cross-linking the collagen bonds. However, biomechanical tests, to evaluate CXL outcome, have been performed only on ex vivo tissue. In vivo, the efficacy of the treatment is verified by assessing vision quality. The objective of this project is to demonstrate an in vivo technique to determine difference in biomechanical strength of the cornea after CXL.
CXL procedure was performed on the right eyes of 6 rabbits. The left eyes were used as controls. Acoustic Radiation Force (ARF) was used to assess corneal stiffness in vivo, once before treatment (Baseline BL) and weekly for four weeks after treatment (W1-W4). Cornea was exposed to ARF using a single element transducer (25 MHz central frequency; 6 mm aperture; 18 mm focal length; Panametrics V324-SU). The beam sequence consisted of 20 pushing tonebursts of 400 μs duration (80% duty cycle). Imaging impulses were interleaved in the dead time to allow the same transducer to acquire radiofrequency data during the push mode to image corneal displacement. Acoustic power levels were within FDA-specified levels for ophthalmic safety. Displacement of the front and back surfaces of the cornea were used to determine the change in corneal thickness and strain. ARF induced strain was fit to the Kelvin-Voigt model to determine the elastic modulus. The average moduli were calculated for the six rabbits, for each of the five time points (BL, W1-W4).
At the end of four weeks, ARF measurements showed an increase of average elastic modulus by 33% in the treated eye, and 3% in the control eye. Paired t-tests revealed statistically significant differences between treated and untreated eyes from W1-W4 (p=0.0005, 0.04, 0.0007, 0.006). There was no significant difference between right and left eyes before treatment (p=0.95).
Our findings demonstrate statistically significant differences in stiffness between control and CXL-treated rabbit corneas in vivo based on axial stress/strain measurements obtained using ARF. The capacity to non-invasively monitor corneal stiffness offers the potential for clinical monitoring of CXL. Longer term studies will be required to elucidate the effectiveness of this non-invasive technique.
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