ABSTRACT: To investigate the biomechanical response to IOP elevation of normal monkey eyes using eye-specific, three-dimensional (3-D) finite element (FE) models of the ONH that incorporate lamina cribrosa (LC) microarchitectural information.
A serial sectioning and episcopic imaging technique was used to reconstruct the ONH and peripapillary sclera of four pairs of eyes fixed at 10 mm Hg. FE models were generated with local LC material properties representing the connective tissue volume fraction (CTVF) and predominant LC beam orientation and used to simulate an increase in IOP from 10 to 45 mm Hg. An LC material stiffness constant was varied to assess its influence on biomechanical response.
Strains and stresses within contralateral eyes were remarkably similar in both magnitude and distribution. Strain correlated inversely, and nonlinearly, with CTVF (median, r (2) = 0.73), with tensile strains largest in the temporal region. Stress correlated linearly with CTVF (median r(2) = 0.63), with the central and superior regions bearing the highest stresses. Net average LC displacement was either posterior or anterior, depending on whether the laminar material properties were compliant or stiff.
The results show that contralateral eyes exhibit similar mechanical behavior and suggest that local mechanical stress and strain within the LC are correlate highly with local laminar CTVF. These simulations emphasize the importance of developing both high-resolution imaging of the LC microarchitecture and next-generation, deep-scanning OCT techniques to clarify the relationships between IOP-related LC displacement and CTVF-related stress and strain in the LC. Such imaging may predict sites of IOP-related damage in glaucoma.
Investigative ophthalmology & visual science 09/2009; 51(1):295-307. · 3.43 Impact Factor
ABSTRACT: To characterize optic nerve head (ONH) connective tissue deformation after acute (15 or 30 minutes) intraocular pressure (IOP) elevation in six adult normal monkeys using three-dimensional (3-D) histomorphometry.
Trephined ONH and peripapillary sclera from both eyes of six monkeys, each perfusion fixed with one eye at IOP 10 mm Hg (IOP-10) and the other at IOP 30 or 45 mm Hg (IOP-30 or IOP-45, by anterior chamber manometer), were serially sectioned, 3-D reconstructed, 3-D delineated, and quantified according to standard parameters. For each monkey, intereye differences (high-IOP eye minus IOP-10) for each parameter were calculated and compared by ANOVA and EPIDmax both overall and regionally. EPIDmax deformations for each parameter were defined to be those statistically significant differences that exceeded the maximum physiologic intereye difference within six bilaterally normal monkeys in a previous report.
Regional EPIDmax laminar thinning, posterior bowing of the peripapillary sclera, and thinning and expansion of the scleral canal were present in most high-IOP eyes and were colocalized in those demonstrating the most deformation. Laminar deformation was minimal, not only posteriorly but in some cases anteriorly in the high-IOP eyes. No increase in deformation was seen in the IOP-45 versus the IOP-30 eyes.
ONH connective tissue alterations after acute IOP elevation involve regional thinning, stretching, and deformation of the lamina cribrosa and peripapillary sclera that are minimal to modest in magnitude. The time-dependent character of these alterations and their compressive, expansile, and shear effects on the axons, the astrocytes, and the laminar and posterior ciliary circulations remain to be determined.
Investigative ophthalmology & visual science 08/2009; 50(12):5785-99. · 3.43 Impact Factor
ABSTRACT: To characterize the trabeculated connective tissue microarchitecture of the lamina cribrosa (LC) in terms of total connective tissue volume (CTV), connective tissue volume fraction (CTVF), predominant beam orientation, and material anisotropy in monkeys with early experimental glaucoma (EG).
The optic nerve heads from three monkeys with unilateral EG and four bilaterally normal monkeys were three dimensionally reconstructed from tissues perfusion fixed at an intraocular pressure of 10 mm Hg. A three-dimensional segmentation algorithm was used to extract a binary, voxel-based representation of the porous LC connective tissue microstructure that was regionalized into 45 subvolumes, and the following quantities were calculated: total CTV within the LC, mean and regional CTVF, regional predominant beam orientation, and mean and regional material anisotropy.
Regional variation within the laminar microstructure was considerable within the normal eyes of all monkeys. The laminar connective tissue was generally most dense in the central and superior regions for the paired normal eyes, and laminar beams were radially oriented at the periphery for all eyes considered. CTV increased substantially in EG eyes compared with contralateral normal eyes (82%, 44%, 45% increases; P<0.05), but average CTVF changed little (-7%, 1%, and -2% in the EG eyes). There were more laminar beams through the thickness of the LC in the EG eyes than in the normal controls (46%, 18%, 17% increases).
The substantial increase in laminar CTV with little change in CTVF suggests that significant alterations in connective and nonconnective tissue components in the laminar region occur in the early stages of glaucomatous damage.
Investigative ophthalmology & visual science 09/2008; 50(2):681-90. · 3.43 Impact Factor