Biomechanical properties of the keratoconic cornea: a review

There has been a recent surge of interest in assessing corneal biomechanical properties due to potential clinical applications, particularly in the early detection of keratoconus (KC). This review discusses the effects of keratoconus on the biomechanical properties of the cornea and the current techniques used to detect these changes both in the laboratory and clinical setting. Specific structural changes occurring in the corneal stroma as part of the disease process can be linked to alterations in the viscous and elastic properties of the cornea in keratoconus. Although there are extensive ex vivo studies using techniques such as extensometry and inflation testing to analyse the biomechanical properties of the normal cornea, few have investigated the keratoconic cornea using the same methods. There are a number of ex vivo studies that confirm the effectiveness of collagen cross-linking in increasing Young's modulus in healthy corneas. Recently, research has focussed on measuring corneal biomechanical parameters in vivo using two commercially available instruments: the Ocular Response Analyser (ORA) and the CorVis ST (CST). Both instruments analyse the dynamic behaviour of the cornea, when temporarily deformed by an air puff; however, the outputs of these instruments are not directly comparable due to differences in the characteristics of the air puff and output parameters. Studies using these instruments have reported significant differences between keratoconic and healthy corneas; however, neither instrument can currently be used in isolation to reliably diagnose keratoconus. Further research analysing the outputs of these instruments may enhance their diagnostic capabilities.

[1]  D. Touboul Biomechanics in keratoconus , 2012 .

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

[3]  C. Foster,et al.  Ocular rigidity in keratoconus. , 1978, American journal of ophthalmology.

[4]  Trevor Sherwin,et al.  Laser scanning in vivo confocal analysis of keratocyte density in keratoconus. , 2008, Ophthalmology.

[5]  E. Sarchielli,et al.  Effects of riboflavin/UVA corneal cross‐linking on keratocytes and collagen fibres in human cornea , 2010, Clinical & experimental ophthalmology.

[6]  Zsolt Bor,et al.  UV absorbance of the human cornea in the 240- to 400-nm range. , 2002, Investigative ophthalmology & visual science.

[7]  A. Proia,et al.  Histopathological Variation in Keratoconus , 1992, Cornea.

[8]  Renato Ambrósio,et al.  Ocular response analyzer measurements in keratoconus with normal central corneal thickness compared with matched normal control eyes. , 2010, Journal of refractive surgery.

[9]  Mostafa Naderi,et al.  Biomechanical parameters of the cornea after collagen crosslinking measured by waveform analysis , 2010, Journal of cataract and refractive surgery.

[10]  A. A. Antonov,et al.  Determination of corneal elasticity coefficient using the ORA database. , 2010, Journal of refractive surgery.

[11]  Matthew R. Ford,et al.  Method for optical coherence elastography of the cornea. , 2011, Journal of biomedical optics.

[12]  C. Teng Electron Microscope Study of The Pathology of Keratoconus: Part I* , 1963 .

[13]  William J Dupps,et al.  Discriminant value of custom ocular response analyzer waveform derivatives in keratoconus. , 2014, Ophthalmology.

[14]  E. Spörl,et al.  Untersuchungen zur Verfestigung der Hornhaut am Kaninchen , 2000, Der Ophthalmologe.

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

[16]  S. Greenstein,et al.  In Vivo Biomechanical Changes After Corneal Collagen Cross-linking for Keratoconus and Corneal Ectasia: 1-Year Analysis of a Randomized, Controlled, Clinical Trial , 2012, Cornea.

[17]  M. Boulton,et al.  Diurnal variations in human corneal thickness. , 1996, The British journal of ophthalmology.

[18]  B. Becker,et al.  Research into the pathogenesis of keratoconus. A new syndrome: low ocular rigidity, contact lenses, and keratoconus. , 1970, Archives of ophthalmology.

[19]  G. A. Limb,et al.  Matrix metalloproteinases in disease and repair processes in the anterior segment. , 2002, Survey of ophthalmology.

[20]  C. McGhee 2008 Sir Norman McAlister Gregg Lecture: 150 years of practical observations on the conical cornea – what have we learned? , 2009, Clinical & experimental ophthalmology.

[21]  Steven E. Wilson,et al.  Bowman's Layer Structure and Function: Critical or Dispensable to Corneal Function? A Hypothesis , 2000, Cornea.

[22]  Steven E. Wilson,et al.  Biomechanics and wound healing in the cornea. , 2006, Experimental eye research.

[23]  Jun Liu,et al.  A quantitative ultrasonic spectroscopy method for noninvasive determination of corneal biomechanical properties. , 2009, Investigative ophthalmology & visual science.

[24]  C. McMonnies Assessing Corneal Hysteresis Using the Ocular Response Analyzer , 2012, Optometry and vision science : official publication of the American Academy of Optometry.

[25]  S. Klyce,et al.  Is keratoconus a true ectasia? An evaluation of corneal surface area. , 2000, Archives of ophthalmology.

[26]  Walton Nosé,et al.  Corneal biomechanical metrics and anterior segment parameters in mild keratoconus. , 2010, Ophthalmology.

[27]  G. Wollensak,et al.  Long‐term biomechanical properties of rabbit cornea after photodynamic collagen crosslinking , 2009, Acta ophthalmologica.

[28]  S. Yun,et al.  In vivo Brillouin optical microscopy of the human eye , 2012, Optics express.

[29]  J. Jonas,et al.  Prevalence and associations of keratoconus in rural maharashtra in central India: the central India eye and medical study. , 2009, American journal of ophthalmology.

[30]  E. Spörl,et al.  Biomechanische Zustand der Hornhaut als neuer Indikator für pathologische und strukturelle Veränderungen , 2009, Der Ophthalmologe.

[31]  Sanjay V. Patel,et al.  Keratocyte density in keratoconus. A confocal microscopy study(a). , 2002, American journal of ophthalmology.

[32]  C. Danielsen,et al.  Tensile mechanical and creep properties of Descemet's membrane and lens capsule. , 2004, Experimental eye research.

[33]  A. Daxer,et al.  Collagen fibril orientation in the human corneal stroma and its implication in keratoconus. , 1997, Investigative ophthalmology & visual science.

[34]  S. Sel,et al.  Interlamellar cohesion after corneal crosslinking using riboflavin and ultraviolet A light , 2011, British Journal of Ophthalmology.

[35]  Antonela Ljubic Keratoconus and Its Prevalence in Macedonia , 2009 .

[36]  J. Alió,et al.  Corneal biomechanical properties in normal, post‐laser in situ keratomileusis, and keratoconic eyes , 2007, Journal of cataract and refractive surgery.

[37]  P R Greene,et al.  Comparison of mechanical properties of keratoconus and normal corneas. , 1982, Experimental eye research.

[38]  M Matallana,et al.  Does Bowman's layer determine the biomechanical properties of the cornea? , 1992, Refractive & corneal surgery.

[39]  J L Ojeda,et al.  The three‐dimensional microanatomy of the rabbit and human cornea. A chemical and mechanical microdissection‐SEM approach , 2001, Journal of anatomy.

[40]  H. Oxlund,et al.  Biomechanical properties of keratoconus and normal corneas. , 1980, Experimental eye research.

[41]  I. Avni,et al.  Can We Measure Corneal Biomechanical Changes After Collagen Cross-Linking in Eyes With Keratoconus?-A Pilot Study , 2009, Cornea.

[42]  G. Wollensak,et al.  Crosslinking treatment of progressive keratoconus: new hope , 2006, Current opinion in ophthalmology.

[43]  G. Conrad,et al.  Effects of Ultraviolet-A and Riboflavin on the Interaction of Collagen and Proteoglycans during Corneal Cross-linking* , 2011, The Journal of Biological Chemistry.

[44]  Min Gao,et al.  Corneal Biomechanical Assessment Using Corneal Visualization Scheimpflug Technology in Keratoconic and Normal Eyes , 2014, Journal of ophthalmology.

[45]  J. Krachmer,et al.  Keratoconus and related noninflammatory corneal thinning disorders. , 1984, Survey of ophthalmology.

[46]  Rex D. Hamilton,et al.  Corneal biomechanical measurements before and after laser in situ keratomileusis , 2008, Journal of cataract and refractive surgery.

[47]  J. Wollensak,et al.  Biochemical studies on human corneal proteoglycans —a comparison of normal and keratoconic eyes , 2004, Graefe's Archive for Clinical and Experimental Ophthalmology.

[48]  C. McMonnies The possible significance of the baropathic nature of keratectasias , 2013, Clinical & experimental optometry.

[49]  R. Barbucci Integrated biomaterials science , 2002 .

[50]  J. Kalenak More ocular elasticity? , 1991, Ophthalmology.

[51]  D. Weiss,et al.  Confocal in vivo microscopy and confocal laser-scanning fluorescence microscopy in keratoconus. , 1996, German journal of ophthalmology.

[52]  S. Marcos,et al.  Contributing factors to corneal deformation in air puff measurements. , 2013, Investigative ophthalmology & visual science.

[53]  W. Schief,et al.  Biomechanically Coupled Curvature Transfer in Normal and Keratoconus Corneal Collagen , 2006, Eye & contact lens.

[54]  W K McEwen,et al.  Immediate rigidity of an eye. I. Whole, segments and strips. , 1970, Experimental eye research.

[55]  B. Seitz,et al.  Morphological and Immunohistochemical Changes After Corneal Cross-Linking , 2013, Cornea.

[56]  Donald V. Rosato,et al.  Plastics Institute of America Plastics Engineering, Manufacturing & Data Handbook , 2001 .

[57]  Allan Luz,et al.  Corneal‐thickness spatial profile and corneal‐volume distribution: Tomographic indices to detect keratoconus , 2006, Journal of cataract and refractive surgery.

[58]  Jun Liu,et al.  Measurement of corneal changes after collagen crosslinking using a noninvasive ultrasound system , 2010, Journal of cataract and refractive surgery.

[59]  M. O'Keefe,et al.  Corneal Hysteresis and Corneal Resistance Factor in Keratoectasia: Findings Using the Reichert Ocular Response Analyzer , 2008, Ophthalmologica.

[60]  B. Calvo,et al.  Biomechanical property analysis after corneal collagen cross-linking in relation to ultraviolet A irradiation time , 2011, Graefe's Archive for Clinical and Experimental Ophthalmology.

[61]  Eberhard Spoerl,et al.  Biomechanical evidence of the distribution of cross‐links in corneastreated with riboflavin and ultraviolet A light , 2006, Journal of cataract and refractive surgery.

[62]  William J Dupps,et al.  Surface wave elastometry of the cornea in porcine and human donor eyes. , 2007, Journal of refractive surgery.

[63]  A. Elsheikh,et al.  Assessment of the epithelium's contribution to corneal biomechanics. , 2008, Experimental eye research.

[64]  A. Pérez-Escudero,et al.  Corneal biomechanical changes after collagen cross-linking from porcine eye inflation experiments. , 2010, Investigative ophthalmology & visual science.

[65]  T. Sherwin,et al.  Morphological changes in keratoconus: pathology or pathogenesis , 2004, Clinical & experimental ophthalmology.

[66]  Theo Seiler,et al.  Thermomechanical Behavior of Collagen-Cross-Linked Porcine Cornea , 2004, Ophthalmologica.

[67]  F. Raiskup,et al.  Detection of biomechanical changes after corneal cross-linking using Ocular Response Analyzer software. , 2011, Journal of refractive surgery.

[68]  P. McDonnell,et al.  Changes in corneal curvature at different excimer laser ablative depths. , 1991, American journal of ophthalmology.

[69]  T. Seiler,et al.  Collagen Fiber Diameter in the Rabbit Cornea After Collagen Crosslinking by Riboflavin/UVA , 2004, Cornea.

[70]  D. Gatinel,et al.  Biomechanical properties of keratoconus suspect eyes. , 2010, Investigative ophthalmology & visual science.

[71]  Jonas S. Friedenwald,et al.  Contribution to the Theory and Practice of Tonometry , 1937 .

[72]  T. Seiler,et al.  Stress‐strain measurements of human and porcine corneas after riboflavin–ultraviolet‐A‐induced cross‐linking , 2003, Journal of cataract and refractive surgery.

[73]  William J Dupps,et al.  Hysteresis: new mechanospeak for the ophthalmologist. , 2007, Journal of cataract and refractive surgery.

[74]  S. Marcos,et al.  Dynamic OCT measurement of corneal deformation by an air puff in normal and cross-linked corneas , 2012, Biomedical optics express.

[75]  D. Patel,et al.  In vivo confocal microscopy analyses of corneal microstructural changes in a prospective study of collagen cross-linking in keratoconus. , 2014, Ophthalmology.

[76]  A. Kanai,et al.  [Quantitative analysis of collagen fiber in keratoconus]. , 1990, Nippon Ganka Gakkai zasshi.

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

[78]  D. Schwartz,et al.  An in vitro intact globe expansion method for evaluation of cross-linking treatments. , 2010, Investigative ophthalmology & visual science.

[79]  Terry Magnuson,et al.  Lumican Regulates Collagen Fibril Assembly: Skin Fragility and Corneal Opacity in the Absence of Lumican , 1998, The Journal of cell biology.

[80]  R. T. Hart,et al.  The optic nerve head as a biomechanical structure: a new paradigm for understanding the role of IOP-related stress and strain in the pathophysiology of glaucomatous optic nerve head damage , 2005, Progress in Retinal and Eye Research.

[81]  Ahmed Elsheikh,et al.  Comparative study of corneal strip extensometry and inflation tests , 2005, Journal of The Royal Society Interface.

[82]  T. Seiler,et al.  Riboflavin/ultraviolet-a-induced collagen crosslinking for the treatment of keratoconus. , 2003, American journal of ophthalmology.

[83]  Mathias Fink,et al.  High-Resolution Quantitative Imaging of Cornea Elasticity Using Supersonic Shear Imaging , 2009, IEEE Transactions on Medical Imaging.

[84]  J. Sugar,et al.  Proteoglycan molecules in keratoconus corneas. , 1991, Investigative Ophthalmology and Visual Science.

[85]  M. Doughty,et al.  Keratocytes: no more the quiet cells. , 1998, Journal of the American Optometric Association.

[86]  Konstantin Kotliar,et al.  Air-pulse corneal applanation signal curve parameters for the characterisation of keratoconus , 2011, British Journal of Ophthalmology.

[87]  I. Cunliffe,et al.  Assessment of the biomechanical properties of the cornea with the ocular response analyzer in normal and keratoconic eyes. , 2007, Investigative ophthalmology & visual science.

[88]  Y. Mandel,et al.  Clinical and Corneal Biomechanical Changes After Collagen Cross-Linking With Riboflavin and UV Irradiation in Patients With Progressive Keratoconus: Results After 2 Years of Follow-up , 2012, Cornea.

[89]  Farhad Hafezi,et al.  Intra- and postoperative variation in ocular response analyzer parameters in keratoconic eyes after corneal cross-linking. , 2010, Journal of refractive surgery.

[90]  E. Spoerl,et al.  Induction of cross-links in corneal tissue. , 1998, Experimental eye research.

[91]  G. Labiris,et al.  Evaluation of corneal hysteresis and corneal resistance factor after corneal cross-linking for keratoconus , 2012, Graefe's Archive for Clinical and Experimental Ophthalmology.

[92]  C. Foster,et al.  Collagen crosslinking in keratoconus. , 1978, Investigative ophthalmology & visual science.

[93]  H. Radhakrishnan,et al.  Biomechanical properties of corneal tissue after ultraviolet-A-riboflavin crosslinking. , 2013, Journal of cataract and refractive surgery.

[94]  Michael Lawless FeRACO,et al.  Keratoconus: diagnosis and management. , 1989, Australian and New Zealand journal of ophthalmology.

[95]  D M Meisler,et al.  Keratocyte apoptosis associated with keratoconus. , 1999, Experimental eye research.

[96]  C. Edmund,et al.  Corneal elasticity and ocular rigidity in normal and keratoconic eyes , 1988, Acta ophthalmologica.

[97]  J. Sugar,et al.  Three-dimensional scanning electron microscopic study of keratoconus corneas. , 1998, Archives of ophthalmology.