Anthony J. Bellezza

Remodeling of the Connective Tissue Microarchitecture of the Lamina Cribrosa in Early Experimental Glaucoma

PURPOSE 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). METHODS 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. RESULTS 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). CONCLUSIONS 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.

Viscoelastic Characterization of Peripapillary Sclera: Material Properties by Quadrant in Rabbit and Monkey Eyes

In this report we characterize the viscoelastic material properties of peripapillary sclera from the four quadrants surrounding the optic nerve head in both rabbit and monkey eyes. Scleral tensile specimens harvested from each quadrant were subjected to uniaxial stress relaxation and tensile ramp to failure tests. Linear viscoelastic theory, coupled with a spectral reduced relaxation function, was employed to characterize the viscoelastic properties of the tissues. We detected no differences in the stress-strain curves of specimens from the four quadrants surrounding the optic nerve head (ONH) below a strain of 4 percent in either the rabbit or monkey. While the peripapillary sclera from monkey eyes is significantly stiffer (both instantaneously and in equilibrium) and relaxes more slowly than that from rabbits, we detected no differences in the viscoelastic material properties (tested at strains of 0-1 percent) of sclera from the four quadrants surrounding the ONH within either species group.

Correlation between Local Stress and Strain and Lamina Cribrosa Connective Tissue Volume Fraction in Normal Monkey Eyes

PURPOSE 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. METHODS 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. RESULTS 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. CONCLUSIONS 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.

Optic disc surface compliance testing using confocal scanning laser tomography in the normal monkey eye.

PurposeTo determine the effect of acute, experimentally increased intraocular pressure on deformation of the surface of the optic nerve head (optic nerve head surface compliance testing) in normal monkey eyes using confocal scanning laser tomography. MethodsA total of 156 compliance tests were performed on 48 normal eyes of 30 monkeys in three separate studies. Compliance testing involved obtaining confocal scanning laser tomographic images using a 10° and/or 15° and/or 20° scan angle at various times after intraocular pressure was raised from 10 to 30 or 45 mm Hg. At each point, six images were analyzed to provide a value for a parameter, called mean position of the disc, which was used to express the amount of deformation the surface of the optic nerve head had undergone at that point. Statistical analysis (ANOVA) was performed to evaluate differences in the amounts of deformation in individual eyes at different intraocular pressures and at different compliance testing sessions (studies 1 and 2) and in the two eyes of individual monkeys under the same conditions (study 3). ResultsThe majority of eyes showed posterior deformation of the surface of the optic nerve head ranging from 15 to 86 &mgr;m as early as 10 minutes after intraocular pressure was increased from 10 to 30 mm Hg. When pressure was increased from 30 to 45 mm Hg in a subset of these eyes, most showed additional deformation. Of the 12 eyes for which both 15° and 20° images were obtained at the same compliance test, 7 showed larger amounts of deformation in the 20° images. Of the 18 monkeys tested in both eyes, 12 showed some differences and 4 showed substantial differences between the two eyes. ConclusionsIn the normal monkey eye, the surface of the optic nerve head deforms rapidly (in as few as 10 minutes) in response to increased intraocular pressure. The amount of deformation varies between subjects and even within the two eyes of individual monkeys. Increasing the scan angle from 15° to 20° frequently increases the amount of deformation detected, suggesting that the peripapillary sclera and the optic nerve head may be involved in the deformation in some eyes.

Continuum-Level Finite Element Modeling of the Optic Nerve Head Using a Fabric Tensor Based Description of the Lamina Cribrosa

Glaucoma is a chronic disease of the eye that can progress to severe vision impairment or blindness if left untreated. The principal site of glaucomatous damage is believed to be within the optic nerve head (ONH) where the axons of the retinal ganglion cells pass through an opening in the back of the sclera (the eye wall) on their way to form the orbital optic nerve. This opening is spanned by the lamina cribrosa (LC), a fenestrated connective tissue structure which provides both a load bearing function for the eye as well as support (both structural and metabolic) for axonal bundles as they traverse the porous space of the LC.Copyright

Effects of ocular dimensions on IOP-related stress within the optic nerve head and posterior scleral shell

In glaucoma, retinal axons are damaged as they pass through the connective tissue beams (the lamina cribrosa) which span the scleral canal. We created a set of idealized finite element models (FEMs) of the posterior scleral shell of the human eye to study stresses within the lamina cribrosa and surrounding sclera. These models incorporate a range of human dimensions for scleral wall thickness (SWT), axial length (AL), and size and shape of the scleral canal. Stresses within the laminar tissues of circular canals ranged from 48/spl times/IOP (intraocular pressure) to 163/spl times/ IOP. In regions where laminar tissues inserted into the surrounding scleral shell, stresses were highest on the anterior (inner) side of the laminar beams. For elliptically shaped canals, the ratio of vertical to horizontal diameters had an effect on the maximum laminar stress and maximum stress at the insertion zones, and on the distance from the canal where the sclera withstands increased stresses. Decreasing SWT led to significant increases in laminar, insertion zone, and peripapillary scleral stress. Changes in AL of the hemisphere had little effect on stresses within the tissues.