Finite element modeling of the human sclera: influence on optic nerve head biomechanics and connections with glaucoma.

Scleral thickness, especially near the optic nerve head (ONH), is a potential factor of interest in the development of glaucomatous optic neuropathy. Large differences in the dimensions of the sclera, the principal load-bearing tissue of the eye, have been observed between individuals. This study aimed to characterize the effects of these differences on ONH biomechanics. Eleven enucleated human globes (7 normal and 4 ostensibly glaucomatous) were imaged using high-field microMRI and segmented to produce 3-D individual-specific corneoscleral shells. An identical, idealized ONH geometry was inserted into each shell. Finite element modeling predicted the effects of pressurizing the eyes to an IOP of 30 mmHg, with the results used to characterize the effect of inter-individual differences in scleral dimensions on the biomechanics of the ONH. Measurements of the individual-specific corneoscleral shells were used to construct a 2-D axisymmetric idealized model of the corneoscleral shell and ONH. A sensitivity analysis based on this model quantified the relative importance of different geometrical characteristics of the scleral shell on the biomechanics of the ONH. Significant variations were observed in various measures of strain in the idealized lamina cribrosa (LC) across the seven normal corneoscleral shells, implying large differences in individual biomechanics due to scleral anatomy variations alone. The sensitivity analysis revealed that scleral thickness adjacent to the ONH was responsible for the vast majority of variation. Remarkably, varying peripapilary scleral thickness over the physiologically measured range changed the peak (95th percentile) first principal strain in the LC and radial displacement of the ONH canal by an amount that was equivalent to a change in IOP of 15 mmHg. Inter-individual variations in scleral thickness, particularly peripapillary scleral thickness, can result in vastly different biomechanical responses to IOP. These differences may be significant for understanding the interactions between IOP and scleral biomechanics in the pathogenesis of glaucomatous optic neuropathy. The relationship between scleral thickness and material properties needs to be studied in human eyes.

[1]  S Tane,et al.  [The study on the microscopic biometry of the thickness of the human retina, choroid and sclera by ultrasound]. , 1984, Nippon Ganka Gakkai zasshi.

[2]  Eric R. Ziegel,et al.  Engineering Statistics , 2004, Technometrics.

[3]  Andreas G Boehm,et al.  The influence of various substances on the biomechanical behavior of lamina cribrosa and peripapillary sclera. , 2005, Investigative ophthalmology & visual science.

[4]  S. Margulies,et al.  A proposed tolerance criterion for diffuse axonal injury in man. , 1992, Journal of biomechanics.

[5]  Theodore T. Allen,et al.  Introduction to Engineering Statistics and Lean Sigma , 2010 .

[6]  Ian A Sigal,et al.  Deformation of the normal monkey optic nerve head connective tissue after acute IOP elevation within 3-D histomorphometric reconstructions. , 2009, Investigative ophthalmology & visual science.

[7]  Ian A Sigal,et al.  Predicted extension, compression and shearing of optic nerve head tissues. , 2007, Experimental eye research.

[8]  Ian A Sigal,et al.  Biomechanics of the optic nerve head. , 2009, Experimental eye research.

[9]  Ian A Sigal,et al.  Interactions between geometry and mechanical properties on the optic nerve head. , 2009, Investigative ophthalmology & visual science.

[10]  R. T. Hart,et al.  Multiscale finite element modeling of the lamina cribrosa microarchitecture in the eye , 2009, 2009 Annual International Conference of the IEEE Engineering in Medicine and Biology Society.

[11]  R. Massof,et al.  Morphologic changes in the lamina cribrosa correlated with neural loss in open-angle glaucoma. , 1983, American journal of ophthalmology.

[12]  R. T. Hart,et al.  A cellular solid model of the lamina cribrosa: mechanical dependence on morphology. , 2004, Journal of biomechanical engineering.

[13]  Michaël J A Girard,et al.  Peripapillary and posterior scleral mechanics--part II: experimental and inverse finite element characterization. , 2009, Journal of biomechanical engineering.

[14]  G. B. Sinclair,et al.  On the Three-Dimensional Finite Element Analysis of Dovetail Attachments , 2003 .

[15]  H W Thompson,et al.  Corneal thickness measurements with the Orbscan Topography System and ultrasonic pachymetry , 1997, Journal of cataract and refractive surgery.

[16]  Ian A Sigal,et al.  Dimensions of the human sclera: Thickness measurement and regional changes with axial length. , 2009, Experimental eye research.

[17]  W. Green,et al.  Optic nerve damage in human glaucoma. II. The site of injury and susceptibility to damage. , 1981, Archives of ophthalmology.

[18]  Ian A Sigal,et al.  Modeling individual-specific human optic nerve head biomechanics. Part II: influence of material properties , 2009, Biomechanics and modeling in mechanobiology.

[19]  Zhengyou Zhang,et al.  Iterative point matching for registration of free-form curves and surfaces , 1994, International Journal of Computer Vision.

[20]  S. Tane,et al.  The microscopic biometry of the thickness of human retina, choroid and sclera by ultrasound , 1987 .

[21]  J. Downs,et al.  Peripapillary and posterior scleral mechanics--part I: development of an anisotropic hyperelastic constitutive model. , 2009, Journal of biomechanical engineering.

[22]  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.

[23]  A. Sommer,et al.  Relationship between intraocular pressure and primary open angle glaucoma among white and black Americans. The Baltimore Eye Survey. , 1991, Archives of ophthalmology.

[24]  H. Dongqi,et al.  A biomathematical model for pressure-dependent lamina cribrosa behavior. , 1999, Journal of biomechanics.

[25]  C Ross Ethier,et al.  Scleral biomechanics and glaucoma--a connection? , 2006, Canadian journal of ophthalmology. Journal canadien d'ophtalmologie.

[26]  C. R. Ethier,et al.  Finite element modeling of optic nerve head biomechanics. , 2004, Investigative ophthalmology & visual science.

[27]  E. Bartov,et al.  Axial length and scleral thickness effect on susceptibility to glaucomatous damage: a theoretical model implementing Laplace's law. , 1992, Ophthalmic research.

[28]  A. Hofman,et al.  Distribution of central corneal thickness and its association with intraocular pressure: The Rotterdam Study. , 1997, American journal of ophthalmology.

[29]  R W Flower,et al.  The mechanism of optic nerve damage in experimental acute intraocular pressure elevation. , 1980, Investigative ophthalmology & visual science.

[30]  C. Núñez‐Álvarez,et al.  Experimental Eye Research , 2019, Nature.

[31]  Ian A Sigal,et al.  Correlation between local stress and strain and lamina cribrosa connective tissue volume fraction in normal monkey eyes. , 2010, Investigative ophthalmology & visual science.

[32]  J. Jonas,et al.  Lamina cribrosa and peripapillary sclera histomorphometry in normal and advanced glaucomatous Chinese eyes with various axial length. , 2009, Investigative ophthalmology & visual science.

[33]  R. T. Hart,et al.  Posterior scleral thickness in perfusion-fixed normal and early-glaucoma monkey eyes. , 2001, Investigative ophthalmology & visual science.

[34]  C. R. Ethier,et al.  Factors influencing optic nerve head biomechanics. , 2005, Investigative ophthalmology & visual science.

[35]  Ian A Sigal,et al.  Modeling individual-specific human optic nerve head biomechanics. Part I: IOP-induced deformations and influence of geometry , 2009, Biomechanics and modeling in mechanobiology.

[36]  T. Good,et al.  Use of a mathematical model to estimate stress and strain during elevated pressure induced lamina cribrosa deformation , 2001, Current eye research.

[37]  H F Edelhauser,et al.  Human sclera: thickness and surface area. , 1998, American journal of ophthalmology.

[38]  Ian A Sigal,et al.  3D morphometry of the human optic nerve head. , 2010, Experimental eye research.

[39]  R. T. Hart,et al.  The optic nerve head as a biomechanical structure: initial finite element modeling. , 2000, Investigative ophthalmology & visual science.