Evaluating the Effects of Riboflavin/UV-A and Rose-Bengal/Green Light Cross-Linking of the Rabbit Cornea by Noncontact Optical Coherence Elastography

et al. 2018

Optom Vis Sci

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SIGNIFICANCE: Measured corneal biomechanical properties are driven by intraocular pressure, tissue thickness, and inherent material properties. We demonstrate tissue thickness as an important factor in the measurement of corneal biomechanics that can confound short-term effects due to UV riboflavin cross-linking (CXL) treatment. PURPOSE: We isolate the effects of tissue thickness on the measured corneal biomechanical properties using optical coherence elastography by experimentally altering the tissue hydration state and stiffness. METHODS: Dynamic optical coherence elastography was performed using phase-sensitive optical coherence tomography imaging to quantify the tissue deformation dynamics resulting from a spatially discrete, low-force air pulse (150-μm spot size; 0.8-millisecond duration; <10 Pa [<0.08 mmHg]). The time-dependent surface deformation is characterized by a viscoelastic tissue recovery response, quantified by an exponential decay constant—relaxation rate. Ex vivo rabbit globes (n = 10) with fixed intraocular pressure (15 mmHg) were topically instilled every 5 minutes with 0.9% saline for 60 minutes and 20% dextran for another 60 minutes. Measurements were made after every 20 minutes to determine the central corneal thickness (CCT) and the relaxation rates. Cross-linking treatment was performed on another 13 eyes, applying isotonic riboflavin (n = 6) and hyper-tonic riboflavin (n = 7) every 5 minutes for 30 minutes, followed by UV irradiation (365 nm, 3 mW/cm2) for 30 minutes while instilling riboflavin. Central corneal thickness and relaxation rates were obtained before and after CXL treatment. RESULTS: Corneal thickness was positively correlated (R2 = 0.9) with relaxation rates. In the CXL-treated eyes, iso-tonic riboflavin did not affect CCT and showed a significant increase in relaxation rates (+10%; P = .01) from2.29 ms−1 to 2.53 ms−1. Hypertonic riboflavin showed a significant CCT decrease (−31%; P = .01) from 618 μm to 429 μm but showed little change in relaxation rates after CXL treatment. CONCLUSIONS: Corneal thickness and stiffness are correlated positively. A higher relaxation rate implied stiffer material properties after isotonic CXL treatment. Hypertonic CXL treatment results in a stiffness decrease that offsets the stiffness increase with CXL treatment.

Section: Discussionmentioning

confidence: 99%

Effects of Thickness on Corneal Biomechanical Properties Using Optical Coherence Elastography

Vantipalli

et al. 2018

Optom Vis Sci

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“…However, application of spectral analysis of the elastic wave propagation (as a function of frequency) or time reversal wavelength tomography can reveal the depth-resolved micro-scale elasticity distribution in the cornea [33] and may be able to elucidate the depth-dependent changes in the elastic anisotropy of the cornea. Moreover, the depth-wise effects of CXL are not uniform as evidenced by various techniques such as Brillouin microscopy [53], USE [49], and OCE [54]. Our future work will involve investigating if there are any anisotropic characteristics of the depth-wise mechanical anisotropy as a function of IOP or after CXL.…”

Section: Discussionmentioning

confidence: 99%

Assessing the effects of riboflavin/UV-A crosslinking on porcine corneal mechanical anisotropy with optical coherence elastography

Han

et al. 2016

Biomed. Opt. Express

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In this work we utilize optical coherence elastography (OCE) to assess the effects of UV-A/riboflavin corneal collagen crosslinking (CXL) on the mechanical anisotropy of porcine corneas at various intraocular pressures (IOP). There was a distinct meridian of increased Young's modulus in all samples, and the mechanical anisotropy increased as a function of IOP and also after CXL. The presented noncontact OCE technique was able to quantify the Young's modulus and elastic anisotropy of the cornea and their changes as a function of IOP and CXL, opening new avenues of research for evaluating the effects of CXL on corneal biomechanical properties.

“…Similar to traditional elastographic techniques, OCE utilizes its parent imaging modality of OCT to detect externally induced displacements within tissue. Due to the high resolution and noncontact nature of OCT, OCE is particularly well suited for assessing the biomechanical properties of the cornea (Ford et al, 2011; Ford et al, 2014; Han et al, 2015b; Li et al, 2014a; Li et al, 2013; Li et al, 2014b; Qu et al, 2016; Singh et al, 2016a; Singh et al, 2016b; Singh et al, 2016c; Singh et al, 2015; Twa et al, 2014; Wang and Larin, 2014a, b). …”

Section: Introductionmentioning

confidence: 99%

Optical coherence elastography assessment of corneal viscoelasticity with a modified Rayleigh-Lamb wave model

Han

Journal of the Mechanical Behavior of Biomedical Materials

et al. 2017

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103

The biomechanical properties of the cornea play a critical role in forming vision. Diseases such as keratoconus can structurally degenerate the cornea causing a pathological loss in visual acuity. UV-A/riboflavin corneal collagen crosslinking (CXL) is a clinically available treatment to stiffen the cornea and restore its healthy shape and function. However, current CXL techniques do not account for pre-existing biomechanical properties of the cornea nor the effects of the CXL treatment itself. In addition to the inherent corneal structure, the intraocular pressure (IOP) can also dramatically affect the measured biomechanical properties of the cornea. In this work, we present the details and development of a modified Rayleigh-Lamb frequency equation model for quantifying corneal biomechanical properties. After comparison with finite element modeling, the model was utilized to quantify the viscoelasticity of in situ porcine corneas in the whole eye-globe configuration before and after CXL based on noncontact optical coherence elastography measurements. Moreover, the viscoelasticity of the untreated and CXL-treated eyes was quantified at various IOPs. The results showed that the stiffness of the cornea increased after CXL and that corneal stiffness is close to linear as a function of IOP. These results show that the modified Rayleigh-Lamb wave model can provide an accurate assessment of corneal viscoelasticity, which could be used for customized CXL therapies.