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      Numerical model of optical coherence tomographic vibrography imaging to estimate corneal biomechanical properties

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          Abstract

          Most techniques measuring corneal biomechanics in vivo are biased by side factors. We demonstrate the ability of optical coherence tomographic (OCT) vibrography to determine corneal material parameters, while reducing current prevalent restrictions of other techniques (such as intraocular pressure (IOP) and thickness dependency). Modal analysis was performed in a finite-element (FE) model to study the oscillation response in isolated thin corneal flaps/eye globes and to analyse the dependency of the frequency response function on: corneal elasticity, viscoelasticity, geometry (thickness and curvature), IOP and density. The model was verified experimentally in flaps from three bovine corneas and in two enucleated porcine eyes using sound excitation (100–110 dB) together with a phase-sensitive OCT to measure the frequency response function (range 50–510 Hz). Simulations showed that corneal vibration in flaps is sensitive to both, geometrical and biomechanical parameters, whereas in whole globes it is primarily sensitive to corneal biomechanical parameters only. Calculations based on the natural frequency shift revealed that flaps of the posterior cornea were 0.8 times less stiff than flaps from the anterior cornea and cross-linked corneas were 1.6 times stiffer than virgin corneas. Sensitivity analysis showed that natural vibration frequencies of whole globes were nearly independent from corneal thickness and IOP within the physiological range. OCT vibrography is a promising non-invasive technique to measure corneal elasticity without biases from corneal thickness and IOP.

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          Most cited references19

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          Determining in vivo biomechanical properties of the cornea with an ocular response analyzer.

          David Luce (2005)
          To study the results of an ocular response analyzer (ORA) to determine the biomechanical properties of the cornea and their relationship to intraocular pressure (IOP). Reichert Inc., Depew, New York, USA. The ORA (Reichert) makes 2 essentially instantaneous applanation measurements that permit determination of corneal and IOP effects. Measurements of several populations indicate that corneal hysteresis, a biomechanical measure, varied over a dynamic range of 1.8 to 14.6 mm Hg and was only weakly correlated with corneal thickness (r(2)=0.12); this is related to the observation that some subjects with relatively thick corneas have less-than-average corneal hysteresis. Corneal hysteresis changes diurnally, presumably as a result of hydration changes. Keratoconus, Fuchs' dystrophy, and post-LASIK patients demonstrated low corneal hysteresis. The corneal hysteresis biomechanical measure may prove valuable for qualification and predictions of outcomes of refractive surgery and in other cases in which corneal biomechanics are important.
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            Brillouin optical microscopy for corneal biomechanics.

            The mechanical properties of corneal tissue are linked to prevalent ocular diseases and therapeutic procedures. Brillouin microscopy is a novel optical technology that enables three-dimensional mechanical imaging. In this study, the feasibility of this noncontact technique was tested for in situ quantitative assessment of the biomechanical properties of the cornea. Brillouin light-scattering involves a spectral shift proportional to the longitudinal modulus of elasticity of the tissue. A 532-nm single-frequency laser and a custom-developed ultrahigh-resolution spectrometer were used to measure the Brillouin frequency. Confocal scanning was used to perform Brillouin elasticity imaging of the corneas of whole bovine eyes. The longitudinal modulus of the bovine corneas was compared before and after riboflavin corneal collagen photo-cross-linking. The Brillouin measurements were then compared with conventional stress-strain mechanical test results. High-resolution Brillouin images of the cornea were obtained, revealing a striking depth-dependent variation of the elastic modulus across the cornea. Along the central axis, the Brillouin frequency shift varied gradually from 8.2 GHz in the epithelium to 7.5 GHz near the endothelium. The coefficients of the down slope were measured to be approximately 1.09, 0.32, and 2.94 GHz/mm in the anterior, posterior, and innermost stroma, respectively. On riboflavin collagen cross-linking, marked changes in the axial Brillouin profiles (P < 0.001) were noted before and after cross-linking. Brillouin imaging can assess the biomechanical properties of cornea in situ with high spatial resolution. This novel technique has the potential for use in clinical diagnostics and treatment monitoring.
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              Brillouin microscopy of collagen crosslinking: noncontact depth-dependent analysis of corneal elastic modulus.

              Corneal collagen crosslinking (CXL) is designed to halt the progression of keratoconus and corneal ectasia by inducing corneal stiffening. However, it currently is difficult to monitor and evaluate CXL outcome objectively due to the lack of suitable methods to characterize corneal mechanical properties. We validated noncontact Brillouin microscopy to quantify corneal mechanical properties before and after CXL. CXL was performed on fresh porcine eyes using various presoaking times and light doses, with or without epithelial debridement. From Brillouin maps of corneal elastic modulus, stiffness and average modulus of anterior, middle, and posterior stroma were analyzed. Corneal stiffening index (CSI) was introduced as a metric to compare the mechanical efficacy of a given CXL protocol with respect to the standard protocol (30-minute riboflavin presoak, 3 mW/cm² ultraviolet illumination for 30 minutes). Brillouin corneal stiffness increased significantly (P 0.98). Compared to the standard epi-off procedure, a typical epi-on procedure resulted in a third of stiffness increase in porcine corneas (CSI = 33). Brillouin microscopy allowed imaging and quantifying CXL-induced mechanical changes without contact in a depth-dependent manner at high spatial resolution. This technique may be useful to evaluate the mechanical outcomes of CXL procedures, to compare different crosslinking agents, and for real-time monitoring of CXL in clinical and experimental settings.
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                Author and article information

                Journal
                J R Soc Interface
                J R Soc Interface
                RSIF
                royinterface
                Journal of the Royal Society Interface
                The Royal Society
                1742-5689
                1742-5662
                6 December 2014
                6 December 2014
                : 11
                : 101
                : 20140920
                Affiliations
                [1 ]Instituto de Óptica, Consejo Superior de Investigaciónes Cientificas , Madrid, Spain
                [2 ]Wellman Center for Photomedicine and Harvard Medical School, Massachusetts General Hospital , Boston, MA, USA
                Author notes
                Article
                rsif20140920
                10.1098/rsif.2014.0920
                4223913
                25320067
                245c0228-d7c7-420d-b730-c7b816b21336

                © 2014 The Authors. Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited.

                History
                : 17 August 2014
                : 22 September 2014
                Categories
                1004
                124
                25
                26
                Research Articles
                Custom metadata
                December 6, 2014

                Life sciences
                non-contact,corneal biomechanical properties,vibrography,corneal natural frequencies

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