Laboratory of Ocular Biomechanics

Principal Investigator

Why biomechanics of the eye?

The eye is a remarkable structure, with biomechanics involved in many of its functions. The eye must be robust to last a lifetime, but also capable of growing with the rest of our body. For our eyes to be able to track moving objects, for example, requires a delicate balance of the forces exerted by several muscles. Forces are also responsible for deforming the lens and allow focusing. A slight imbalance between the forces and tissue properties may be enough to alter or even preclude vision.

The goal in the Laboratory of Ocular Biomechanics is to study the eye as a biomechanical structure. More specifically, we aim to understand the inter-relationship between healthy vision and ocular biomechanics, to identify the causes for ocular disease and find avenues for restoring lost vision.

Research Projects:

Tissue micro-architecture: We have developed techniques to determine in high resolution (down to millionths of a cm) the structure and organization of the collagen fibers that form the support tissues of the eye. This enables a detailed description of the architecture of the eye and allows an understanding of the fundamental processes guiding the development of disease.

Lamina micro architecture: In collaboration with Dr. Donald Brown from the University of California (Irvine), we have developed techniques based on second harmonic generated microscopy for measuring the architecture of the lamina cribrosa produced by changes in intraocular pressure. The lamina cribrosa is a region critical for the nerve fiber degeneration that causes vision loss in glaucoma. The figure shows a human lamina cribrosa colored by the thickness of the laminar beams. This image shows a human lamina cribrosa colored by the thickness of the beams.

Patient-specific numerical modeling: We have developed advanced patient-specific numerical models of the human optic nerve head. We use these models to understand the effects of elevated intraocular pressure on the tissues of the eye, and how it may be associated with glaucoma. Shown in the figure are cross sections through the model of a human eye. Through a collaboration with Dr. Ross Ethier (Georgia Tech) and Dr. John Flanagan (University of Toronto).

The eye as a living biomechanical system: Using experiments and numerical modeling we study the role of biomechanics on the development and aging of the eye, and in particular of the remodeling associated with disease. The image shows a proposed mechanism by which active remodeling can explain the development of glaucomatous cupping of the lamina cribrosa.

Why are there so many different eyes? We use numerical modeling to understand the wide variability in eyes, and what these tell us about how the eye achieves its remarkable robustness as well as when this fails and disease ensues.

 

Selected Publications

2013

H Ishikawa, CL Chen, G Wollstein, J Grimm, Y Ling, RA Bilonick, IA Sigal, L Kagemann and JS Schuman, “High Dynamic Range Imaging Concept-Based Signal Enhancement Method Reduced the Optical Coherence Tomography (OCT) Measurement Variability”, Invest Ophthalmol Vis Sci, 54(1):836-841, Jan 2013. PMID 23299477.

2012

IA Sigal, JG Flanagan, KL Lathrop, I Tertinegg and R Bilonick, “Human lamina cribrosa insertion and age”. Invest Ophthalmol Vis Sci, 53(11):6870-6879, Oct 2012. PMID 22956611.

AW Francis,  L Kagemann,  G Wollstein, H Ishikawa, S Folz, D Overby, IA Sigal, B Wang and JS Schuman, “Morphometric Analysis of Aqueous Humor Outflow Structures with Spectral Domain Optical Coherence Tomography”. Invest Ophthalmol Vis Sci, 53(9):5198-5207, Aug 2012, PMID 22499987.

L Kagemann, G Wollstein, H Ishikawa, Z Nadler, IA Sigal, LS Folio and JS Schuman, “Visualization of the Conventional Outflow Pathway in the Living Human Eye”. Ophthalmology, 119:8:1563-1568, Aug 2012. PMID 22683063.

IA Sigal and JL Grimm, “A few good responses. Which mechanical effects of IOP on the ONH to study?”, Invest Ophthalmol Vis Sci, 53(7):4270-4278, Jun 2012. PMID 22570343.

IA Sigal, RA Bilonick, L Kagemann, G Wollstein, H Ishikawa, J Schuman and JL Grimm, “The optic nerve head as a robust biomechanical system”. Invest Ophthalmol Vis Sci, 53(6):2658-2667, May 2012.  PMID 22427598.

R Grytz, IA Sigal, JW Ruberti, G Meschke and JC Downs, “Lamina cribrosa thickening in early glaucoma predicted by a microstructure motivated growth and remodeling approach”, Mechanics of Materials, Vol. 44:99-109, 2012. doi:10.1016/j.mechmat.2011.07.004.

2011

NG Strouthidis, B Fortune, H Yang, IA Sigal and CF Burgoyne, “The Effect of Acute Intraocular Pressure Elevation on the Monkey Optic Nerve Head As Detected by Spectral Domain Optical Coherence Tomography”. Invest Ophthalmol Vis Sci, 52(12):9431-37, Dec 2011. PMID 22058335.

IA Sigal, H Yang, MD Roberts, JL Grimm, CF Burgoyne, S Demirel and JC Downs, “IOP-induced lamina cribrosa displacement and scleral canal expansion. Are they independent or related?”. Invest Ophthalmol Vis Sci, 52(12):9023-32, Nov 2011. PMID 21989723.

L Kagemann, G Wollstein, H Ishikawa, IA Sigal, LS Folio, J Xu, H. Gong and JS Schuman, “3D visualization of aqueous outflow structures in-situ in humans”. Experimental Eye Research, 93(3): 308-315, Sep 2011. Camras Special Issue, PMID: 21514296.

H Yang, G Williams, JC Downs, IA Sigal, MD Roberts, H Thompson and CF Burgoyne. “Posterior (outward) migration of the lamina cribrosa and early cupping in monkey experimental glaucoma”. Invest Ophthalmol Vis Sci, 52(10):7109-21, Sep 2011. PMID 21715355.

JC Downs, MD Roberts and IA Sigal, “Glaucomatous cupping of the lamina cribrosa: a review of the evidence for active progressive remodeling as a mechanism”, Experimental Eye Research, 93(2):133-140, Aug 2011. PMID 20708001.

IA Sigal, “An applet to estimate the IOP-induced stress and strain within the optic nerve head”. Invest Ophthalmol Vis Sci. 52(8):5497-506, Jul 2011. PMID 21527378.

R Norman, JG Flanagan, IA Sigal, S Rausch, I Tertinegg and CR Ethier. “Finite element modeling of the human sclera: influence on optic nerve head biomechanics and connections with glaucoma”. Experimental Eye Research, 93(1):4-12, Jul 2011. PMID 20883693

IA Sigal, H Yang, MD Roberts, CF Burgoyne and JC Downs, “IOP-induced lamina cribrosa displacement and scleral canal expansion: an analysis of factor interactions using parameterized eye-specific models”, Invest Ophthalmol Vis Sci. 52(3):1896-1907, Mar 2011. PMID 20881292

NG Strouthidis, B Fortune, H Yang, IA Sigal and CF Burgoyne, “Longitudinal change detected by spectral domain optical coherence tomography in the glaucomatous optic nerve head and peripapillary retina”, Invest Ophthalmol Vis Sci. 52(3):1206-19, Mar 2011. PMID 21217108.

H Yang, H Thompson, MD Roberts, IA Sigal, JC Downs and CF Burgoyne. “Deformation of the early glaucomatous monkey optic nerve head connective tissue following acute IOP elevation within 3-D histomorphometric reconstructions”, Invest Ophthalmol Vis Sci, 52(1):345-63, Jan 2011. PMID 20702834.

2010

MD Roberts, IA Sigal, Y Liang, CF Burgoyne and JC Downs. “Changes in the biomechanical response of the optic nerve head in early experimental glaucoma”, Invest Ophthalmol Vis Sci. 51(11):5675-5684, Nov 2010. PMID 20538991.

PG Sanfilippo, A Cardini, IA Sigal, J Ruddle, BE Chua, AW Hewitt, and DA Mackey. “A geometric morphometric assessment of the optic cup in glaucoma”, Experimental Eye Research, 91(3): 405-414, Sep 2010. PMID 20599965.

R Norman, JG Flanagan, S Rausch, IA Sigal, I Tertinegg, A Eilaghi, S Portnoy, J Sled and CR Ethier. “Dimensions of the human sclera: thickness measurement and regional changes with axial length”, Experimental Eye Research, 90(2): 277-284, Feb 2010.

IA Sigal and CM Whyne. “Mesh morphing and response surface analysis: quantifying sensitivity of vertebral mechanical behaviour”, Annals of Biomedical Engineering, 38(1):41-56, Jan 2010.

IA Sigal, H Yang, MD Roberts and JC Downs. “Morphing methods to parameterize specimen-specific finite element model geometries”, Journal of Biomechanics, 43(2):254-262. 19, Jan 2010.

IA Sigal, JG Flanagan, I Tertinegg and CR Ethier, “3D morphometry of the human optic nerve head”, Experimental Eye Research, 90(1):70-80, Jan 2010.

MD Roberts, Yi Liang, IA Sigal, J Grimm, J Reynaud, A Bellezza, CF Burgoyne and JC Downs. “Correlation Between Local Stress and Strain and Lamina Cribrosa Connective Tissue Volume Fraction in Normal Monkey Eyes”, Invest Ophthalmol Vis Sci, 51(1):295-307, Jan 2010. PMID 19900442.

 

2009

H Yang, JC Downs, IA Sigal, M Roberts, H Thompson, CF Burgoyne. “Deformation of the normal monkey optic nerve head connective tissues following acute IOP elevation within 3-D histomorphometric reconstructions”, Invest Ophthalmol Vis Sci , 50(12): 5785-5789. Dec 2009. PMID 19628739.

IA Sigal. “Interactions between geometry and mechanical properties on the optic nerve head”, Invest Ophthalmol Vis Sci, 50(6): 2785-95. Jun 2009. PMID 19168906.

IA Sigal and CR Ethier. “Biomechanics of the optic nerve head”, Experimental Eye Research, 88(4):799-807, Apr 2009. PMID 19217902.

IA Sigal, JG Flanagan, I Tertinegg and CR Ethier. “Modeling individual-specific human optic nerve head biomechanics. Part II: Influence of material properties”, Biomech Model Mechanobiol, 8(2):99-109, Apr 2009. PMID 18301933.

IA Sigal, JG Flanagan, I Tertinegg and CR Ethier. “Modeling individual-specific human optic nerve head biomechanics. Part I: IOP-induced deformations and influence of geometry”, Biomech Model Mechanobiol, 8(2):85-98, Apr 2009. PMID 18309526.

2008 and earlier

IA Sigal, MR Hardisty and CM Whyne. “Mesh-morphing algorithms for specimen-specific finite element modeling”, J Biomech, 41(7):1381-1389, 2008. PMID 18397789.

IA Sigal, JG Flanagan, I Tertinegg and CR Ethier. “Predicted extension, compression and shearing of optic nerve head tissues”, Experimental Eye Research, 85(3):312-322, Sep 2007. PMID 17624325.

IA Sigal, JG Flanagan, I Tertinegg and CR Ethier, “Factors Influencing Human Optic Nerve Head Biomechanics”, Invest Ophthalmol Vis Sci, 46(11): 4189-4199, Nov 2005. PMID 16249498.

IA Sigal, JG Flanagan, I Tertinegg and CR Ethier. “Reconstruction of Human Optic Nerve Heads for Finite Element Modeling”, Technology and Health Care: Official Journal of the European Society for Engineering and Medicine, 13(4): 313-329, Aug 2005. PMID 16055979.

IA Sigal, JG Flanagan, I Tertinegg and CR Ethier. “Finite Element Modeling of Optic Nerve Head Biomechanics”, Invest Ophthalmol Vis Sci, 45(12): 4378-4387, Dec 2004. PMID 15557446.

IL Garzón, JA Reyes-Nava, JI Rodríguez-Hernández, I Sigal, MR Beltrán and K Michaelian. “Chirality in Bare and Passivated Gold Nanoclusters”, Phys. Rev. B 66(7), 073403, Aug 2002.