In Vivo Corneal Stiffness Mapping by the Stress-Strain Index Maps and Brillouin Microscopy

Abstract The study of corneal stiffness in vivo has numerous clinical applications such as the measurement of intraocular pressure, the preoperative screening for iatrogenic ectasia after laser vision correction surgery and the diagnosis and treatment of corneal ectatic diseases such as keratoconus. The localised aspect of the microstructure deterioration in keratoconus leading to local biomechanical softening, corneal bulging, irregular astigmatism and ultimately loss of vision boosted the need to map the corneal stiffness to identify the regional biomechanical failure. Currently, two methods to map the corneal stiffness in vivo are integrated into devices that are either already commercially available or about to be commercialised: the stress-strain index (SSI) maps and the Brillouin Microscopy (BM). The former method produces 2D map of stiffness across the corneal surface, developed through numerical simulations using the corneal shape, its microstructure content, and the deformation behaviour under air-puff excitation. It estimates the whole stress-strain behaviour, making it possible to obtain the material tangent modulus under different intraocular pressure levels. On the other hand, BM produces a 3D map of the corneal longitudinal modulus across the corneal surface and thickness. It uses a low-power near-infrared laser beam and through a spectral analysis of the returned signal, it assesses the mechanical compressibility of the tissue as measured by the longitudinal modulus. In this paper, these two techniques are reviewed, and their advantages and limitations discussed.

[1]  Bernardo T. Lopes,et al.  In Vivo Biomechanical Changes Associated With Keratoconus Progression , 2022, Current eye research.

[2]  Bernardo T. Lopes,et al.  Evaluation of corneal biomechanical behavior in vivo for healthy and keratoconic eyes using the stress–strain index , 2022, Journal of cataract and refractive surgery.

[3]  Bernardo T. Lopes,et al.  Clinical Validation of the Automated Characterization of Cone Size and Center in Keratoconic Corneas. , 2021, Journal of refractive surgery.

[4]  Matthew R. Ford,et al.  Depth-resolved Corneal Biomechanical Changes Measured Via Optical Coherence Elastography Following Corneal Crosslinking , 2021, Translational vision science & technology.

[5]  K. Larin,et al.  Compressional Optical Coherence Elastography of the Cornea , 2021, Photonics.

[6]  Bernardo T. Lopes,et al.  Review of Ex-vivo Characterisation of Corneal Biomechanics , 2021 .

[7]  Bernardo T. Lopes,et al.  Stress–Strain Index Map: A New Way to Represent Corneal Material Stiffness , 2021, Frontiers in Bioengineering and Biotechnology.

[8]  Bernardo T. Lopes,et al.  Fibril density reduction in keratoconic corneas , 2021, Journal of the Royal Society Interface.

[9]  S. Yun,et al.  In vivo measurement of shear modulus of the human cornea using optical coherence elastography , 2020, Scientific Reports.

[10]  Bernardo T. Lopes,et al.  Characterization of cone size and centre in keratoconic corneas , 2020, Journal of the Royal Society Interface.

[11]  F. Hafezi,et al.  Quasi-Static Optical Coherence Elastography to Characterize Human Corneal Biomechanical Properties , 2020, Investigative ophthalmology & visual science.

[12]  Matthew R. Ford,et al.  Depth-Dependent Corneal Biomechanical Properties in Normal and Keratoconic Subjects by Optical Coherence Elastography , 2020, Translational vision science & technology.

[13]  S. Yun,et al.  Brillouin Spectroscopy of Normal and Keratoconus Corneas. , 2019, American journal of ophthalmology.

[14]  S. Yun,et al.  Spatially-resolved Brillouin spectroscopy reveals biomechanical abnormalities in mild to advanced keratoconus in vivo , 2019, Scientific Reports.

[15]  Bernardo T. Lopes,et al.  Determination of Corneal Biomechanical Behavior in-vivo for Healthy Eyes Using CorVis ST Tonometry: Stress-Strain Index , 2019, Front. Bioeng. Biotechnol..

[16]  F. Hafezi,et al.  Biomechanical Impact of Localized Corneal Cross-linking Beyond the Irradiated Treatment Area. , 2019, Journal of refractive surgery.

[17]  A. Elsheikh,et al.  Analysis of X-ray scattering microstructure data for implementation in numerical simulations of ocular biomechanical behaviour , 2019, PloS one.

[18]  Matthew R. Ford,et al.  Live human assessment of depth-dependent corneal displacements with swept-source optical coherence elastography , 2018, PloS one.

[19]  S. Yun,et al.  The influence of hydration on different mechanical moduli of the cornea , 2018, Graefe's Archive for Clinical and Experimental Ophthalmology.

[20]  Seok Hyun Yun,et al.  Brillouin microscopy: assessing ocular tissue biomechanics , 2018, Current opinion in ophthalmology.

[21]  Sheldon J. J. Kwok,et al.  Effects of Corneal Hydration on Brillouin Microscopy In Vivo , 2018, Investigative ophthalmology & visual science.

[22]  J. Jester,et al.  Evolution of the vertebrate corneal stroma , 2018, Progress in Retinal and Eye Research.

[23]  S. Yun,et al.  Spatially-resolved Brillouin spectroscopy reveals biomechanical changes in early ectatic corneal disease and post-crosslinking in vivo. , 2018, 1802.01055.

[24]  D. O’Brart,et al.  A review of keratoconus: Diagnosis, pathophysiology, and genetics. , 2017, Survey of ophthalmology.

[25]  Giuliano Scarcelli,et al.  Mechanical outcome of accelerated corneal crosslinking evaluated by Brillouin microscopy. , 2017, Journal of cataract and refractive surgery.

[26]  W. Dupps,et al.  Biomechanical Diagnostics of the Cornea , 2017, International ophthalmology clinics.

[27]  Bernardo T. Lopes,et al.  Detection of Keratoconus With a New Biomechanical Index. , 2016, Journal of refractive surgery.

[28]  K. Meek,et al.  Corneal structure and transparency , 2015, Progress in Retinal and Eye Research.

[29]  S. Yun,et al.  In vivo biomechanical mapping of normal and keratoconus corneas. , 2015, JAMA ophthalmology.

[30]  M. Fink,et al.  In vivo evidence of porcine cornea anisotropy using supersonic shear wave imaging. , 2014, Investigative ophthalmology & visual science.

[31]  S. Yun,et al.  Biomechanical characterization of keratoconus corneas ex vivo with Brillouin microscopy. , 2014, Investigative ophthalmology & visual science.

[32]  William J Dupps,et al.  Biomechanics of corneal ectasia and biomechanical treatments. , 2014, Journal of cataract and refractive surgery.

[33]  Stéphane Roux,et al.  3D static elastography at the micrometer scale using Full Field OCT. , 2013, Biomedical optics express.

[34]  Michael W. Belin,et al.  Dynamic ultra high speed Scheimpflug imaging for assessing corneal biomechanical properties , 2013 .

[35]  Brian Derby,et al.  Scanning Acoustic Microscopy for Mapping the Microelastic Properties of Human Corneal Tissue , 2013, Current eye research.

[36]  Giuliano Scarcelli,et al.  Brillouin microscopy of collagen crosslinking: noncontact depth-dependent analysis of corneal elastic modulus. , 2013, Investigative ophthalmology & visual science.

[37]  S. Yun,et al.  Brillouin optical microscopy for corneal biomechanics. , 2012, Investigative ophthalmology & visual science.

[38]  Pilhan Kim,et al.  In vivo measurement of age-related stiffening in the crystalline lens by Brillouin optical microscopy. , 2011, Biophysical journal.

[39]  C. Boote,et al.  The use of X-ray scattering techniques to quantify the orientation and distribution of collagen in the corneal stroma , 2009, Progress in Retinal and Eye Research.

[40]  K. Meek,et al.  Corneal collagen—its role in maintaining corneal shape and transparency , 2009, Biophysical Reviews.

[41]  S. Tuft,et al.  A study of corneal thickness, shape and collagen organisation in keratoconus using videokeratography and X-ray scattering techniques. , 2007, Experimental eye research.

[42]  S. Yun,et al.  Confocal Brillouin microscopy for three-dimensional mechanical imaging. , 2007, Nature photonics.

[43]  Craig Boote,et al.  Mapping collagen organization in the human cornea: left and right eyes are structurally distinct. , 2006, Investigative ophthalmology & visual science.

[44]  Michael J. Doughty,et al.  Assessment of the Number of Lamellae in the Central Region of the Normal Human Corneal Stroma at the Resolution of the Transmission Electron Microscope , 2005, Eye & contact lens.

[45]  D. Luce Determining in vivo biomechanical properties of the cornea with an ocular response analyzer , 2005, Journal of cataract and refractive surgery.

[46]  Craig Boote,et al.  Collagen fibrils appear more closely packed in the prepupillary cornea: optical and biomechanical implications. , 2003, Investigative ophthalmology & visual science.

[47]  C. Roberts The cornea is not a piece of plastic. , 2000, Journal of refractive surgery.

[48]  J. Randall,et al.  The measurement and interpretation of Brillouin scattering in the lens of the eye , 1982, Proceedings of the Royal Society of London. Series B. Biological Sciences.

[49]  J. Randall,et al.  Brillouin scattering, density and elastic properties of the lens and cornea of the eye , 1980, Nature.

[50]  J. Randall,et al.  Brillouin scattering in systems of biological significance , 1979, Philosophical Transactions of the Royal Society of London. Series A, Mathematical and Physical Sciences.

[51]  J. White,et al.  Phonons and the elastic moduli of collagen and muscle , 1977, Nature.

[52]  L. Brillouin Diffusion de la lumière et des rayons X par un corps transparent homogène - Influence de l'agitation thermique , 1922 .