- Pittsburgh, Pennsylvania, United States
Richard Bilonick
University of Pittsburgh, Ophthalmology and Bioengineering, Faculty Member
Research Interests: Materials Science, Ophthalmology, Optical coherence tomography, Medicine, Biological Sciences, and 15 moreHumans, Glaucoma, Intraocular Pressure, Three Dimensional Imaging, Eye, Aged, In Vivo, Adult, Vision Disorders, Retinal Ganglion Cells, Optic Disk, Visual Fields, Lamina, Medical and Health Sciences, and Nerve fibers
PURPOSE. To test the hypothesis that in healthy human eyes the lamina cribrosa (LC) insertion into the pia mater increases with age. METHODS. The optic nerve heads (ONHs) of donor eyes fixed at either 5 or 50 mm Hg of IOP were sectioned,... more
PURPOSE. To test the hypothesis that in healthy human eyes the lamina cribrosa (LC) insertion into the pia mater increases with age. METHODS. The optic nerve heads (ONHs) of donor eyes fixed at either 5 or 50 mm Hg of IOP were sectioned, stained, and imaged under bright- and dark-field conditions. A 3-dimensional (3D) model of each ONH was reconstructed. From the 3D models we measured the area of LC insertion into the peripapillary scleral flange and into the pia, and computed the total area of insertion and fraction of LC inserting into the pia. Linear mixed effect models were used to determine if the measurements were associated with age or IOP. RESULTS. We analyzed 21 eyes from 11 individuals between 47 and 91 years old. The LC inserted into the pia in all eyes. The fraction of LC inserting into the pia (2.2%–29.6%) had a
The lamina cribrosa is a primary site of damage in glaucoma. While mechanical distortion is hypothesized to cause reduction of axoplasmic flow, little is known about how the pores, which contains the retinal ganglion cell axons, traverse... more
The lamina cribrosa is a primary site of damage in glaucoma. While mechanical distortion is hypothesized to cause reduction of axoplasmic flow, little is known about how the pores, which contains the retinal ganglion cell axons, traverse the lamina cribrosa. We investigated lamina cribrosa pore paths in vivo to quantify differences in tortuosity of pore paths between healthy and glaucomatous eyes. We imaged 16 healthy, 23 glaucoma suspect and 48 glaucomatous eyes from 70 subjects using a swept source optical coherence tomography system. The lamina cribrosa pores were automatically segmented using a previously described segmentation algorithm. Individual pore paths were automatically tracked through the depth of the lamina cribrosa using custom software. Pore path convergence to the optic nerve center and tortuosity was quantified for each eye. We found that lamina cribrosa pore pathways traverse the lamina cribrosa closer to the optic nerve center along the depth of the lamina cribr...
To introduce an experimental approach for direct comparison of the primate optic nerve head (ONH) before and after death by exsanguination. The ONHs of four eyes from three monkeys were imaged with spectral-domain optical coherence... more
To introduce an experimental approach for direct comparison of the primate optic nerve head (ONH) before and after death by exsanguination. The ONHs of four eyes from three monkeys were imaged with spectral-domain optical coherence tomography (OCT) before and after exsanguination under controlled IOP. ONH structures, including the Bruch membrane (BM), BM opening, inner limiting membrane (ILM), and anterior lamina cribrosa (ALC) were delineated on 18 virtual radial sections per OCT scan. Thirteen parameters were analyzed: scleral canal at BM opening (area, planarity, and aspect ratio), ILM depth, BM depth; ALC (depth, shape index, and curvedness), and ALC visibility (globally, superior, inferior, nasal, and temporal quadrants). All four ALC quadrants had a statistically significant improvement in visibility after exsanguination (overall P < 0.001). ALC visibility increased by 35% globally and by 36%, 37%, 14%, and 4% in the superior, inferior, nasal, and temporal quadrants, respec...
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Although collagen microstructural crimp is a major determinant of ocular biomechanics, no direct measurements of optic nerve head (ONH) crimp have been reported. Our goal was to characterize the crimp period of the lamina cribrosa (LC)... more
Although collagen microstructural crimp is a major determinant of ocular biomechanics, no direct measurements of optic nerve head (ONH) crimp have been reported. Our goal was to characterize the crimp period of the lamina cribrosa (LC) and peripapillary sclera (PPS) at low and normal IOPs. ONHs from 11 sheep eyes were fixed at 10-, 5-, or 0-mm Hg IOP and crimp periods measured manually from coronal cryosections imaged with polarized light microscopy (PLM). Using linear mixed-effect models, we characterized the LC and PPS periods, and how they varied with distance from the scleral canal edge. A total of 17,374 manual collagen crimp period measurements were obtained with high repeatability (1.9 μm) and reproducibility (4.7 μm). The periods were smaller (P < 0.001) and less variable in the LC than in the PPS: average (SD) of 13.8 (3.1) μm in the LC, and 31.0 (10.4) μm in the PPS. LC crimp period did not vary with distance from the scleral canal wall (P > 0.1). PPS period increase...
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The purpose of this study was to determine how the architecture of the lamina cribrosa (LC) microstructure, including the shape and size of the lamina pores, influences the IOP-induced deformation of the neural tissues within the LC pores... more
The purpose of this study was to determine how the architecture of the lamina cribrosa (LC) microstructure, including the shape and size of the lamina pores, influences the IOP-induced deformation of the neural tissues within the LC pores using computational modeling. We built seven specimen-specific finite element models of LC microstructure with distinct nonlinear anisotropic properties for LC beams and neural tissues based on histological sections from three sheep eyes. Changes in shape (aspect ratio and convexity) and size (area and perimeter length) due to IOP-induced hoop stress were calculated for 128 LC pores. Multivariate linear regression was used to determine if pore shape and size were correlated with the strain in the pores. We also compared the microstructure models to a homogenized model built following previous approaches. The LC microstructure resulted in focal tensile, compressive, and shear strains in the neural tissues of the LC that were not predicted by homogen...
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There is increasing clinical evidence that the eye is not only affected by intraocular pressure (IOP), but also by intracranial pressure (ICP). Both pressures meet at the optic nerve head of the eye, specifically the lamina cribrosa (LC).... more
There is increasing clinical evidence that the eye is not only affected by intraocular pressure (IOP), but also by intracranial pressure (ICP). Both pressures meet at the optic nerve head of the eye, specifically the lamina cribrosa (LC). The LC is a collagenous meshwork through which all retinal ganglion cell axons pass on their way to the brain. Distortion of the LC causes a biological cascade leading to neuropathy and impaired vision in situations such as glaucoma and idiopathic intracranial hypertension. While the effect of IOP on the LC has been studied extensively, the coupled effects of IOP and ICP on the LC remain poorly understood. We investigated in-vivo the effects of IOP and ICP, controlled via cannulation of the eye and lateral ventricle in the brain, on the LC microstructure of anesthetized rhesus monkeys eyes using the Bioptigen spectral-domain optical coherence tomography (OCT) device (Research Triangle, NC). The animals were imaged with their head upright and the re...
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Glaucoma is a leading cause of blindness that leads to characteristic changes in the optic nerve head (ONH) region, such as nasalization of vessels. It is unknown whether the spatial location of this vessel shift inside the ONH occurs... more
Glaucoma is a leading cause of blindness that leads to characteristic changes in the optic nerve head (ONH) region, such as nasalization of vessels. It is unknown whether the spatial location of this vessel shift inside the ONH occurs within the lamina cribrosa (LC) or the prelaminar tissue. The purpose of this study was to compare the location of the central retinal vessel trunk (CRVT) in the LC and prelaminar tissue in living healthy and glaucomatous eyes. We acquired 3-dimensional ONH scans from 119 eyes (40 healthy, 29 glaucoma suspect, and 50 glaucoma) using optical coherence tomography (OCT). The CRVT location was manually delineated in separate projection images of the LC and prelamina. We found that the CRVT in glaucoma suspect and glaucomatous eyes was located significantly more nasally compared to healthy eyes at the level of the prelamina. There was no detectable difference found in the location of the CRVT at the level of the LC between diagnostic groups. While the nasal...
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To assess the effect of the previously reported optical coherence tomography (OCT) signal normalization method on reducing the discrepancies in image appearance among spectral-domain OCT (SD-OCT) devices. Healthy eyes and eyes with... more
To assess the effect of the previously reported optical coherence tomography (OCT) signal normalization method on reducing the discrepancies in image appearance among spectral-domain OCT (SD-OCT) devices. Healthy eyes and eyes with various retinal pathologies were scanned at the macular region using similar volumetric scan patterns with at least two out of three SD-OCT devices at the same visit (Cirrus HD-OCT, Zeiss, Dublin, CA; RTVue, Optovue, Fremont, CA; and Spectralis, Heidelberg Engineering, Heidelberg, Germany). All the images were processed with the signal normalization. A set of images formed a questionnaire with 24 pairs of cross-sectional images from each eye with any combination of the three SD-OCT devices either both pre- or postsignal normalization. Observers were asked to evaluate the similarity of the two displayed images based on the image appearance. The effects on reducing the differences in image appearance before and after processing were analyzed. Twenty-nine re...
Evaluation of the effect of prelaminar tissue thickness on visualization of the lamina cribrosa (LC) using optical coherence tomography (OCT). The optic nerve head (ONH) region was scanned using OCT. The quality of visible LC... more
Evaluation of the effect of prelaminar tissue thickness on visualization of the lamina cribrosa (LC) using optical coherence tomography (OCT). The optic nerve head (ONH) region was scanned using OCT. The quality of visible LC microstructure was assessed subjectively using a grading system and objectively by analyzing the signal intensity of each scan's superpixel components. Manual delineations were made separately and in 3-dimensions quantifying prelaminar tissue thickness, analyzable regions of LC microstructure, and regions with a visible anterior LC (ALC) boundary. A linear mixed effect model quantified the association between tissue thickness and LC visualization. A total of 17 healthy, 27 glaucoma suspect, and 47 glaucomatous eyes were included. Scans with thicker average prelaminar tissue measurements received worse grading scores (P = 0.007), and superpixels with low signal intensity were associated significantly with regions beneath thick prelaminar tissue (P < 0.05)...
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To investigate how the lamina cribrosa (LC) microstructure changes with distance from the central retinal vessel trunk (CRVT), and to determine how this change differs in glaucoma. One hundred nineteen eyes (40 healthy, 29 glaucoma... more
To investigate how the lamina cribrosa (LC) microstructure changes with distance from the central retinal vessel trunk (CRVT), and to determine how this change differs in glaucoma. One hundred nineteen eyes (40 healthy, 29 glaucoma suspect, and 50 glaucoma) of 105 subjects were imaged using swept-source optical coherence tomography (OCT). The CRVT was manually delineated at the level of the anterior LC surface. A line was fit to the distribution of LC microstructural parameters and distance from CRVT to measure the gradient (change in LC microstructure per distance from the CRVT) and intercept (LC microstructure near the CRVT). A linear mixed-effects model was used to determine the effect of diagnosis on the gradient and intercept of the LC microstructure with distance from the CRVT. A Kolmogorov-Smirnov test was applied to determine the difference in distribution between the diagnostic categories. The percent of visible LC in all scans was 26 ± 7%. Beam thickness and pore diameter ...
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Developing a novel image enhancement method so that nonframe-averaged optical coherence tomography (OCT) images become comparable to active eye-tracking frame-averaged OCT images. Twenty-one eyes of 21 healthy volunteers were scanned with... more
Developing a novel image enhancement method so that nonframe-averaged optical coherence tomography (OCT) images become comparable to active eye-tracking frame-averaged OCT images. Twenty-one eyes of 21 healthy volunteers were scanned with noneye-tracking nonframe-averaged OCT device and active eye-tracking frame-averaged OCT device. Virtual averaging was applied to nonframe-averaged images with voxel resampling and adding amplitude deviation with 15-time repetitions. Signal-to-noise (SNR), contrast-to-noise ratios (CNR), and the distance between the end of visible nasal retinal nerve fiber layer (RNFL) and the foveola were assessed to evaluate the image enhancement effect and retinal layer visibility. Retinal thicknesses before and after processing were also measured. All virtual-averaged nonframe-averaged images showed notable improvement and clear resemblance to active eye-tracking frame-averaged images. Signal-to-noise and CNR were significantly improved (SNR: 30.5 vs. 47.6 dB, C...
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Excitotoxicity has been linked to the pathogenesis of ocular diseases and injuries and may involve early degeneration of both anterior and posterior visual pathways. However, their spatiotemporal relationships remain unclear. We... more
Excitotoxicity has been linked to the pathogenesis of ocular diseases and injuries and may involve early degeneration of both anterior and posterior visual pathways. However, their spatiotemporal relationships remain unclear. We hypothesized that the effects of excitotoxic retinal injury (ERI) on the visual system can be revealed in vivo by diffusion tensor magnetic resonance imagining (DTI), manganese-enhanced magnetic resonance imagining (MRI), and optical coherence tomography (OCT). Diffusion tensor MRI was performed at 9.4 Tesla to monitor white matter integrity changes after unilateral N-methyl-D-aspartate (NMDA)-induced ERI in six Sprague-Dawley rats and six C57BL/6J mice. Additionally, four rats and four mice were intravitreally injected with saline to compare with NMDA-injected animals. Optical coherence tomography of the retina and manganese-enhanced MRI of anterograde transport were evaluated and correlated with DTI parameters. In the rat optic nerve, the largest axial dif...
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We developed a method to normalize optical coherence tomography (OCT) signal profiles from two spectral-domain (SD) OCT devices so that the comparability between devices increases. We scanned 21 eyes from 14 healthy and 7 glaucoma... more
We developed a method to normalize optical coherence tomography (OCT) signal profiles from two spectral-domain (SD) OCT devices so that the comparability between devices increases. We scanned 21 eyes from 14 healthy and 7 glaucoma subjects with two SD-OCT devices on the same day, with equivalent cube scan patterns centered on the fovea (Cirrus HD-OCT and RTVue). Foveola positions were selected manually and used as the center for registration of the corresponding images. A-scan signals were sampled 1.8 mm from the foveola in the temporal, superior, nasal, and inferior quadrants. After oversampling and rescaling RTVue data along the Z-axis to match the corresponding Cirrus data format, speckle noise reduction and amplitude normalization were applied. For comparison between normalized A-scan profiles, mean absolute difference in amplitude in percentage was measured at each sampling point. As a reference, the mean absolute difference between two Cirrus scans on the same eye also was mea...
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To test the effect of a novel signal normalization method for reducing systematic optical coherence tomography (OCT) measurement differences among multiple spectral-domain (SD) OCT devices. A total of 109 eyes from 59 subjects were... more
To test the effect of a novel signal normalization method for reducing systematic optical coherence tomography (OCT) measurement differences among multiple spectral-domain (SD) OCT devices. A total of 109 eyes from 59 subjects were scanned with two SD-OCT devices (Cirrus and RTVue) at the same visit. Optical coherence tomography image data were normalized to match their signal characteristics between the devices. To compensate signal strength differences, custom high dynamic range (HDR) processing was also applied only to images with substantially lower signal strength. Global mean peripapillary retinal nerve fiber layer (RNFL) thicknesses were then measured automatically from all images using custom segmentation software and were compared to the original device outputs. Structural equation models were used to analyze the absolute RNFL thickness difference between original device outputs and our software outputs after signal normalization. The device-measured RNFL thickness showed a...
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Research Interests: British, Optical coherence tomography, Medicine, Prospective studies, Humans, and 15 moreFemale, Male, Intraocular Pressure, Clinical Sciences, Aged, Middle Aged, Optometry and Ophthalmology, Image Enhancement, Adult, Public health systems and services research, Retinal Ganglion Cells, Reproducibility of Results, Optic Disk, Visual Fields, and Angle
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Research Interests: Ophthalmology, British, Optical coherence tomography, Medicine, Image Quality, and 15 moreHumans, Glaucoma, Female, Male, Regression Analysis, Clinical Sciences, Aged, Middle Aged, Optometry and Ophthalmology, Adult, Public health systems and services research, Angle, Logistic Regression Model, Ophthalmoscopy, and Signal strength
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Research Interests: Optical coherence tomography, Confocal Microscopy, Medicine, Prospective studies, Humans, and 15 moreGlaucoma, Female, Male, Intraocular Pressure, Middle Aged, Optometry and Ophthalmology, Odds ratio, Vision Disorders, Retrospective Studies, Retinal Ganglion Cells, Optic Disk, Disease Progression, Ambulatory Care, Ocular Hypertension, and Ophthalmoscopy
The first edition of this book was devised as an adequate but simplified condensation of Dr. Pierre Gy&#x27;s work, suitable as a manual for the teaching of a short course. Despite a few minor mistakes and typos, the first edition was... more
The first edition of this book was devised as an adequate but simplified condensation of Dr. Pierre Gy&#x27;s work, suitable as a manual for the teaching of a short course. Despite a few minor mistakes and typos, the first edition was an overwhelming success and well-...
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ABSTRACT
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To determine the retinal nerve fiber layer (RNFL) thickness profile in the peripapillary region of healthy eyes. Three-dimensional, Fourier/spectral domain optical coherence tomography (OCT) data were obtained as raster scan data (512 x... more
To determine the retinal nerve fiber layer (RNFL) thickness profile in the peripapillary region of healthy eyes. Three-dimensional, Fourier/spectral domain optical coherence tomography (OCT) data were obtained as raster scan data (512 x 180 axial scans in a 6 x 6-mm region centered on the optic nerve head [ONH]) with high-speed, ultrahigh-resolution OCT (hsUHR-OCT) from 12 healthy subjects. RNFL thickness was measured on this three-dimensional data set with an in-house software program. The disc margin was defined subjectively in each image and RNFL thickness profiles relative to distance from the disc center were computed for quadrants and clock hours. A mixed-effects model was used to characterize the slope of the profiles. Thickness profiles in the superior, inferior, and temporal quadrants showed an initial increase in RNFL thickness, an area of peak thickness, and a linear decrease as radial distance from the disc center increased. The nasal quadrant showed a constant linear decay without the initial RNFL thickening. A mixed-effects model showed that the slopes of the inferior, superior, and nasal quadrants differed significantly from the temporal slope (P = 0.0012, P = 0.0003, and P = 0.0004, respectively). RNFL thickness is generally inversely related to the distance from the ONH center in the peripapillary region of healthy subjects, as determined by hsUHR-OCT. However, several areas showed an initial increase in RNFL, followed by a peak and a gradual decrease.