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J Crawford Downs

Publications and source records attributed to J Crawford Downs.

10 recordsLinked to original sources

Segmentation of trabeculated structures using an anisotropic Markov random field: application to the study of the optic nerve head in glaucoma.

The study of the architecture of the optic nerve head (ONH) may provide valuable information about the development and progression of glaucoma. To this end, we have generated three-dimensional datasets from monkey eyes under controlled intraocular pressure (IOP). Segmentation of the connective tissues in this area is crucial to obtain an accurate measurement of geometrical parameters and to build mechanical models. However, this segmentation is made difficult by the complicated geometry and the artifacts introduced in the dataset building process. We present a novel segmentation algorithm, based on expectation-maximization, which incorporates an anisotropic Markov random field (MRF) to introduce prior knowledge about the geometry of the structure. The structure tensor is used to characterize the predominant structure direction and the spatial coherence at each point. The algorithm, which has been validated on an artificial validation dataset that mimics our ONH datasets, shows significant improvement over an isotropic MRF. Results on the real datasets demonstrate the ability of the new algorithm to obtain accurate, spatially consistent segmentations of this structure.

Algorithms↗

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.

We propose here a conceptual framework for understanding the optic nerve head (ONH) as a biomechanical structure. Basic principles of biomechanical engineering are used to propose a central role for intraocular pressure (IOP)-related stress and strain in the physiology of ONH aging and the pathophysiology of glaucomatous damage. Our paradigm suggests that IOP-related stress and strain (1) are substantial within the load-bearing connective tissues of the ONH even at low levels of IOP and (2) underlie both ONH aging and the two central pathophysiologies of glaucomatous damage--mechanical failure of the connective tissues of the lamina cribrosa, scleral canal wall, and peripapillary sclera, and axonal compromise within the lamina cribrosa by a variety of mechanisms. Modeling the ONH as a biomechanical structure generates a group of testable hypotheses regarding the central mechanisms of glaucomatous damage and provides a logic for classifying the principal components of the susceptibility of an individual ONH to a given level of IOP.

Animals↗

Viscoelastic material properties of the peripapillary sclera in normal and early-glaucoma monkey eyes.

PURPOSE: To test the hypothesis that changes in the viscoelastic material properties of peripapillary sclera are present within monkey eyes at the onset of early experimental glaucoma detected by confocal scanning laser tomography (CSLT). METHODS: Short-term (3-9 weeks), moderate (< or =44 mm Hg) intraocular pressure (IOP) elevation was induced in one eye of each of eight male monkeys by lasering the trabecular meshwork. This procedure generated early experimental glaucoma, defined as the onset of CSLT-detected optic nerve head (ONH) surface change, in the treated eye. Scleral tensile specimens from the superior and inferior quadrants of the eight early-glaucoma eyes were subjected to uniaxial stress relaxation and tensile tests to failure and the results compared with similar data obtained in a previous study of 12 normal (nonglaucomatous) eyes. Linear viscoelastic theory was used to characterize viscoelastic material property parameters for each specimen. Differences in each parameter due to quadrant and treatment were assessed by analysis of variance (ANOVA). RESULTS: Peripapillary sclera from the early-glaucoma eyes exhibited an equilibrium modulus (7.46 +/- 1.58 MPa) that was significantly greater than that measured in normal eyes (4.94 +/- 1.22 MPa; mean +/- 95% confidence interval, P < 0.01, ANOVA). Quadrant differences were not significant for the viscoelastic parameters within each treatment group. CONCLUSIONS: The long-term viscoelastic material properties of monkey peripapillary sclera are altered by exposure to moderate, short-term, chronic IOP elevations and these alterations are present at the onset of CSLT-detected glaucomatous damage to the ONH. Damage to and/or remodeling of the extracellular matrix of these tissues may underlie these changes in scleral material properties.

Animals↗

Time scale for periosteal readhesion after brow lift.

OBJECTIVES/HYPOTHESIS: The objective was to determine the time interval after brow lift required to achieve periosteal readhesion to the skull with preoperative strength [corrected]. STUDY DESIGN: Randomized prospective analysis of variance with repeated measures. METHODS: Twenty-one New Zealand white rabbits, each serving as its own control, underwent subperiosteal elevation on one side of the skull. The elevated periosteum was lifted and fixed to a resorbable screw, and the contralateral periosteum was left untouched. Adhesion characteristics were subsequently examined at postoperative days 5, 6, 7, 8, 10, 12, and 17. Seven subjects were assessed histologically to determine attachment of periosteum to underlying bone. Fourteen subjects underwent biomechanical analysis of the bone-periosteum interface using the following three measures of periosteal readhesion strength: ultimate shear strength, shear stiffness, and shear energy [corrected]. RESULTS: Blinded histological analysis showed a qualitative increase in the number of markers of periosteal healing on days 8 to 12 for the operated sides. Analysis of ultimate shear strength and shear stiffness demonstrated a significant relationship to postoperative day (P <.001). The ultimate shear strength and shear stiffness of the operated side approached that of the nonoperated side by postoperative days 12 and 8, respectively. Shear energy was significantly lower for all time points on the operated side as compared with the control (P <.02). CONCLUSION: Periosteal readhesion after surgical elevation approaches preoperative strength by the twelfth postoperative day.

Absorbable Implants↗

Tethered protein/peptide-surface-modified hydrogels.

We investigated a wet chemistry method to covalently bond polyethylene glycol (PEG)-tethered extracellular matrix (ECM) proteins (laminin and fibronectin) or peptide (fibronectin-adhesion-peptide sequence) onto the surface of a poly(2-hydroxylethyl methacrylate-co-methylacrylic acid) (PHEMA/MAA) hydrogel that could potentially be used as a replacement for corneal tissue in the eye. An essential requirement for the success of such a surface in the biological environment is its ability to support the growth and attachment of corneal epithelial cells; ECM proteins are known to promote cellular attachment and growth. We hypothesized that the use of tethers or long hydrophilic chains would allow the attached ECM protein/peptide molecules to move two-dimensionally in space, thereby increasing their ability to bind with epithelial cell membranes. Additionally, the tethers would prevent the specifically added growth-enhancing factors from being obscured by any non-specific protein binding occurring on the hydrogel surface. In this surface-modification study, carbodiimidazole (CDI) was used to activate the carboxylic groups (-COOH) on the hydrogel surface in anhydrous dimethylsulfoxide (DMSO) before addition of the PEGylated proteins/peptide. The resulting tethered protein/peptide surface-modified hydrogels were analyzed in terms of percent grafting efficiency, biological activity and mechanical properties. X-ray photoelectron spectroscopy (XPS) and 125I radioactive labeling demonstrated the successful covalent bonding between the moieties and the hydrogel surface. Radiolabeling and enzyme-linked immunosorbent assay (ELISA) studies indicated that the tethered proteins attached to the hydrogel surface at a concentration of approx. 0.1 microg/cm2. ELISA testing further showed that tethered proteins remained biologically active. However, mechanical tensile testing indicated that the mechanical properties of these chemically modified hydrogels were somewhat altered in comparison with the unmodified hydrogel. Future studies will evaluate the cellular response to these surface-modified materials in vitro and in vivo.

Biocompatible Materials↗

Three-dimensional reconstruction of normal and early glaucoma monkey optic nerve head connective tissues.

PURPOSE: To introduce high-resolution, digital three-dimensional (3-D) reconstruction of the connective tissues of the optic nerve head (ONH). METHODS: Trephinated ONH and peripapillary sclera from both eyes of three monkeys with early glaucoma (EG; one eye normal, one eye given laser-induced EG) were embedded in paraffin and serial sectioned at 3-mum thickness from the vitreous surface through the orbital optic nerve, with the embedded tissue block face stained and imaged after each cut. Each image was aligned, and then the scleral canal wall, sclera, border tissue of Elschnig, Bruch's membrane, lamina cribrosa, optic nerve septa, pial sheath, and vasculature were delineated as unique objects. Delineated images were stacked, color mapped, and volume rendered and then serial sagittal and transverse digital sections of the resultant voxel geometries were viewed and measured. RESULTS: Substantial differences in the 3-D architecture of the peripapillary sclera, scleral canal wall, and lamina cribrosa were present among the three normal eyes. All three EG eyes displayed permanent posterior deformation of the central lamina cribrosa, as well as expansion of the anterior and posterior neural canal openings in comparison with their respective contralateral normal control eyes. Peripherally, whereas laminar deformation was greatest inferiorly or superiorly in all three EG eyes, statistically significant deformation was present in all four quadrants of all three eyes. CONCLUSIONS: High-resolution, digital 3-D reconstructions of the load-bearing connective tissues of the monkey ONH confirm that the ONH connective tissues are profoundly altered at the onset of detectable ONH surface change in experimental glaucoma.

Animals↗

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.

Animals↗

Deformation of the lamina cribrosa and anterior scleral canal wall in early experimental glaucoma.

PURPOSE: To test the hypothesis that pathophysiologic deformation of the lamina cribrosa and anterior scleral canal wall underlies the onset of confocal scanning laser tomography (CSLT)-detected optic nerve head (ONH) surface change in early experimental glaucoma. METHODS: Both eyes of four normal (two normal eyes) monkeys and four with early glaucoma (one eye with laser-induced IOP elevation, observed until the onset of CSLT-detected ONH surface change) were enucleated immediately after death and immersion fixed at IOP 0 mm Hg. In an additional four normal monkeys and five with early glaucoma, both eyes were cannulated, and IOP set to 10 mm Hg in one normal eye and either 30 or 45 mm Hg in the other (normal or early-glaucoma) eye. After 15 to 80 minutes of acute IOP elevation, these nine monkeys were perfusion-fixed. Within images of serial sagittal sections of the ONH tissues in all 17 monkeys, anterior lamina cribrosa position, laminar thickness, and scleral canal diameter were measured. For each parameter, differences between the two eyes of each monkey and between treatment groups were assessed by ANOVA. RESULTS: Within the eyes of the eight monkeys with IOP 0 mm Hg, the lamina cribrosa was posteriorly displaced and thicker and the scleral canal was enlarged at Bruch's membrane and at the anterior laminar insertion in the early-glaucoma eyes compared with the contralateral normal eyes (plastic deformation). Within the high-IOP normal eyes, the lamina cribrosa was posteriorly displaced compared with that in the low-IOP normal eyes, but there were no significant differences in laminar thickness or scleral canal diameter (normal compliance). Within the high-IOP early-glaucoma eyes, the lamina cribrosa was posteriorly displaced and thicker and the scleral canal enlarged, compared with both low-IOP normal eyes and high-IOP normal eyes (hypercompliant deformation). Differences in laminar position between the high-IOP early-glaucoma eyes and the contralateral low-IOP normal eyes (hypercompliant plus plastic deformation) were more than eight times greater than the differences between the high-IOP normal eyes and the contralateral low-IOP normal eyes (normal compliance). CONCLUSIONS: Both plastic (permanent) and hypercompliant deformation of the lamina cribrosa and anterior scleral canal wall are present in young adult monkey eyes with early experimental glaucoma. These findings suggest that damage to the ONH connective tissues occurs early in the monkey model of experimental glaucoma.

Animals↗

Peripapillary scleral thickness in perfusion-fixed normal monkey eyes.

PURPOSE: To characterize the thickness of the peripapillary sclera in perfusion-fixed normal monkey eyes so as to build accurate computational models of intraocular pressure (IOP)-related stress and strain within these tissues. METHODS: Nine rhesus monkeys were perfusion fixed, each with one normal eye set to an IOP of 10 mm Hg by manometer. A 6-mm-diameter specimen containing the optic nerve head and peripapillary sclera was trephined from each scleral shell and cut into 4-microm serial sagittal sections across the scleral canal opening, either horizontally (four eyes) or vertically (five eyes). The thickness of the peripapillary sclera was measured on every 24th section at 100-microm intervals from the posterior scleral canal opening (PSCO) to the peripheral edge of the specimen. The data were pooled by quadrant (superior, inferior, nasal, and temporal), regions within each quadrant, and distance from the PSCO, overall and for individual eyes, and subjected to analysis of variance. RESULTS: In terms of distance from the PSCO, the peripapillary sclera was thinnest nearest the PSCO (201 microm, nasal; 201 microm, temporal; 240 microm, inferior; 249 microm, superior), thickened progressively to a maximum in the midperiphery approximately 600 to 1000 microm from the PSCO (326 microm, nasal; 415 microm, superior; 420 microm, temporal; 422 microm, inferior), and thinned again peripherally in all quadrants. The peripapillary sclera was thinner in the nasal quadrant when compared with the other quadrants superiorly, inferiorly, and temporally (central region means of 291 microm, nasal; 369 microm, superior; 372 microm, inferior; and 369 microm, temporal; P < 0.0001). CONCLUSIONS: In the normal monkey eye, peripapillary scleral thickness varies significantly with distance from the posterior scleral canal opening and is thinner in the nasal quadrant than in the other quadrants. These differences are substantial and are likely to affect the magnitude of IOP-related stress and strain within these tissues for a given level of IOP.

Animals↗

Periosteal readhesion after brow-lift in New Zealand white rabbits.

OBJECTIVES: To define the postoperative time interval required for elevated periosteum to readhere to the skull and regain its preoperative strength, and to evaluate whether fixation of the periosteum affects this interval or the strength of postoperative readhesion. DESIGN: Prospective analysis of variance and covariance with repeated measures. SUBJECTS: Thirty-six New Zealand white rabbits, each serving as its own control. INTERVENTIONS: Subperiosteal elevation was performed on one side of the skull, leaving the contralateral periosteum untouched. The periosteum in half of the subjects was lifted and fixed to a resorbable screw, with the comparison group undergoing subperiosteal elevation only, without lifting and fixation. Several adhesion characteristics were subsequently examined at postoperative weeks 1, 3, 5, 7, 8, 9, 10, 11, and 12. Half of the subjects were assessed histologically to determine attachment of periosteum onto underlying bone. The other half underwent analysis of periosteal readhesion strength. RESULTS: The 3 independent measures of periosteal adherence to the skull all lacked significant differences between sides after the first postoperative week. Blinded histologic analysis showed no evidence of ongoing periosteal healing and demonstrated no difference between operated-on and nonoperated-on sides. Analysis of periosteal stiffness (P =.76) and energy density (P =.74) also demonstrated no significant differences between sides. CONCLUSIONS: Periosteal readhesion after surgical elevation is virtually complete by the seventh postoperative day. In addition, tension secondary to periosteal elevation with suspension has no influence on postoperative healing. These findings will contribute to the debate regarding the most appropriate brow-lift fixation technique.

Absorbable Implants↗