Collagen microstructural factors influencing optic nerve head biomechanics.
OBJECTIVE
Previous studies have suggested that the lamina cribrosa (LC) and its surrounding sclera are biomechanically important in the pathogenesis of glaucoma, but many were limited by assumptions of tissue isotropy and homogeneity. Here, we used an improved biomechanical model driven by experimental measurements of scleral and LC collagen fiber organization to more accurately evaluate optic nerve head (ONH) biomechanics.


METHODS
Collagen fiber organization was quantitatively mapped across human ONH cryosections (three normal and three glaucomatous) using small-angle light scattering (SALS) and fed into two-dimensional finite element models loaded under biaxial stress to simulate raised intraocular pressure. Effects of artificial variations in collagen fiber microstructure and stiffness on LC and scleral strains were also investigated.


RESULTS
Scleral collagen fibers were circumferential and exhibited the highest alignment in a region not immediately adjacent to, but at a distance (400-500 μm) away from, the LC. In models, such a fiber arrangement yielded rings of low strain (second principal and effective) in the scleral region immediately adjacent to the LC. Further sensitivity analyses showed that scleral fiber alignment was crucial in determining LC strain levels. Moderate scleral anisotropy (as observed physiologically) was more effective than isotropy or high anisotropy in limiting LC and scleral strain magnitude.


CONCLUSIONS
The presence of a heterogeneous collagen fiber organization in the peripapillary sclera appears effective in limiting LC strain and is able to reduce strain levels at the scleral canal boundary: a transition zone prone to LC disinsertion, focal lamina cribrosa defects, and optic disc hemorrhages in glaucoma.
NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore In vivo Biomechanics Laboratory, Department of Biomedical Engineering, National University of Singapore, Singapore.
Liang
L
Zhang
Optic Nerve Head Group, School of Optometry and Vision Sciences, Cardiff Centre for Vision Sciences, Cardiff University, Cardiff, United Kingdom.
Julie
J
Albon
Optic Nerve Head Group, School of Optometry and Vision Sciences, Cardiff Centre for Vision Sciences, Cardiff University, Cardiff, United Kingdom.
Hannah
H
Jones
LadHyX, Department of Mechanics, École Polytechnique, CNRS UMR7646, Palaiseau, France.
Cecile L M
CL
Gouget
Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia, United States.
C Ross
CR
Ethier
Tissue Repair Laboratory, Department of Biomedical Engineering, National University of Singapore, Singapore.
James C H
JC
Goh
In vivo Biomechanics Laboratory, Department of Biomedical Engineering, National University of Singapore, Singapore Singapore Eye Research Institute, Singapore National Eye Centre, Singapore.
Michaël J A
MJ
Girard
D000368:Aged; D000369:Aged, 80 and over; D001696:Biomechanical Phenomena; D002102:Cadaver; D005260:Female; D024022:Fibrillar Collagens / Q000648:ultrastructure*; D020342:Finite Element Analysis; D005901:Glaucoma / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008954:Models, Biological; D008962:Models, Theoretical; D009898:Optic Disk / Q000502:physiology / Q000503:physiopathology; D009901:Optic Nerve Diseases / Q000503:physiopathology*; D012590:Sclera / Q000033:anatomy & histology / Q000502:physiology
D024022:Fibrillar Collagens
collagen microstructure; finite element modeling; glaucoma; ocular biomechanics; optic nerve head biomechanics