Michaël J. A. Girard

Shadow removal and contrast enhancement in optical coherence tomography images of the human optic nerve head.

PURPOSE To improve the quality of optical coherence tomography (OCT) images of the optic nerve head (ONH). METHODS Two algorithms were developed, one to compensate for light attenuation and the other to enhance contrast in OCT images. The former was borrowed from developments in ultrasound imaging and was proven suitable with either time- or spectral-domain OCT. The latter was based on direct application of pixel intensity exponentiation. The performances of these two algorithms were tested on spectral-domain OCT images of four adult ONHs. RESULTS Application of the compensation algorithm significantly reduced the intralayer contrast (from 0.74 ± 0.16 to 0.17 ± 0.12; P < 0.001), indicating successful blood vessel shadow removal. Furthermore, compensation dramatically improved the visibility of deeper ONH tissues, such as the peripapillary sclera and lamina cribrosa. Application of the contrast-enhancement algorithm significantly increased the interlayer contrast (from 0.48 ± 0.22 to a maximum of 0.89 ± 0.05; P < 0.001) and thus allowed a better differentiation of tissue boundaries. Contrast enhancement was robust only when compensation was considered. CONCLUSIONS The proposed algorithms are simple and can significantly improve the quality of ONH images clinically captured with OCT. This study has important implications, as it will help improve our ability to perform automated segmentation of the ONH; quantify the morphometry and biomechanics of ONH tissues in vivo; and identify potential risk indicators for glaucoma.

Scleral Biomechanics in the Aging Monkey Eye

PURPOSE To investigate the age-related differences in the inhomogeneous, anisotropic, nonlinear biomechanical properties of posterior sclera from old (22.9 +/- 5.3 years) and young (1.5 +/- 0.7 years) rhesus monkeys. METHODS The posterior scleral shell of each eye was mounted on a custom-built pressurization apparatus, then intraocular pressure (IOP) was elevated from 5 to 45 mm Hg while the 3D displacements of the scleral surface were measured with speckle interferometry. Each scleral shells geometry was digitally reconstructed from data generated by a 3-D digitizer (topography) and 20-MHz ultrasound (thickness). An inverse finite element (FE) method incorporating a fiber-reinforced constitutive model was used to extract a unique set of biomechanical properties for each eye. Displacements, thickness, stress, strain, tangent modulus, structural stiffness, and preferred collagen fiber orientation were mapped for each posterior sclera. RESULTS The model yielded 3-D deformations of posterior sclera that matched well with those observed experimentally. The posterior sclera exhibited inhomogeneous, anisotropic, nonlinear mechanical behavior. The sclera was significantly thinner (P = 0.038) and tangent modulus and structural stiffness were significantly higher in old monkeys (P < 0.0001). On average, scleral collagen fibers were circumferentially oriented around the optic nerve head (ONH). No difference was found in the preferred collagen fiber orientation and fiber concentration factor between age groups. CONCLUSIONS Posterior sclera of old monkeys is significantly stiffer than that of young monkeys and is therefore subject to higher stresses but lower strains at all levels of IOP. Age-related stiffening of the sclera may significantly influence ONH biomechanics and potentially contribute to age-related susceptibility to glaucomatous vision loss.

Enhancement of lamina cribrosa visibility in optical coherence tomography images using adaptive compensation.

PURPOSE We improved the visibility of the lamina cribrosa (LC), including its posterior boundary, in optical coherence tomography (OCT) images of the human optic nerve head (ONH). METHODS An adaptive compensation algorithm was developed to overcome a limitation of our standard compensation algorithm, that is the overamplification of noise at high depth. Such limitation currently hampers our ability to distinguish the posterior LC boundary. In adaptive compensation, standard compensation operations are performed until an energy threshold is reached, at which stage the compensation process is stopped to limit noise overamplification in the deeper portion of the OCT image. The performance of adaptive compensation was compared to that of standard compensation using OCT images of 5 human ONHs. RESULTS Adaptive compensation significantly reduced the intralayer contrast (a measure of pixel intensity uniformity) in the deeper portion of the OCT images (from 0.62 ± 0.11-0.30 ± 0.03, P < 0.001), indicating successful removal of noise overamplification. Furthermore, adaptive compensation significantly increased the interlayer contrast (a measure of boundary visibility) across the posterior LC boundary (from 0.29 ± 0.13-0.61 ± 0.21, P < 0.001), indicating improved posterior LC boundary visibility. CONCLUSIONS Adaptive compensation provided significant improvement compared to standard compensation by eliminating noise overamplification at high depth and improving the visibility of the posterior LC boundary. These improvements were performed while maintaining all other benefits of compensation, such as shadow removal and contrast enhancement. Adaptive compensation will help further our efforts to characterize in vivo ONH biomechanics for the diagnosis and monitoring of glaucoma.

Quantitative Mapping of Scleral Fiber Orientation in Normal Rat Eyes

PURPOSE Previous work has suggested a major role of scleral biomechanics in the pathogenesis of glaucoma. Since fiber orientation in connective tissues is a key determinant of tissue biomechanics, experimental characterization of scleral fiber orientation is needed to fully understand scleral biomechanics. This is a report of baseline experimental measurements of fiber orientation in whole normal rat scleras. METHODS Twenty ostensibly normal Norway brown rat eyes were fixed in 4% paraformaldehyde. The scleras were cleaned of intra- and extraorbital tissues and dissected into five patches, and each patch was glycerol treated to maximize its transparency. Fiber orientation was measured using small-angle light scattering (SALS). Scattering patterns were analyzed to extract two microstructural parameters at each measurement location-the preferred fiber orientation and the degree of alignment-yielding a fiber orientation map for each sclera. RESULTS Rat sclera is structurally anisotropic with several consistent features. At the limbus, fibers were highly aligned and organized primarily into a distinct ring surrounding the cornea. In the equatorial region, the fibers were primarily meridionally aligned. In the posterior and peripapillary region, the scleral fibers were mostly circumferential but less aligned than those in the anterior and equatorial regions. CONCLUSIONS Circumferential scleral fibers may act as reinforcing rings to limit corneal and optic nerve head deformations, whereas equatorial meridional fibers may either provide resistance against extraocular muscle forces or limit globe axial elongation.

Translating ocular biomechanics into clinical practice: Current state and future prospects

Abstract Biomechanics is the study of the relationship between forces and function in living organisms and is thought to play a critical role in a significant number of ophthalmic disorders. This is not surprising, as the eye is a pressure vessel that requires a delicate balance of forces to maintain its homeostasis. Over the past few decades, basic science research in ophthalmology mostly confirmed that ocular biomechanics could explain in part the mechanisms involved in almost all major ophthalmic disorders such as optic nerve head neuropathies, angle closure, ametropia, presbyopia, cataract, corneal pathologies, retinal detachment and macular degeneration. Translational biomechanics in ophthalmology, however, is still in its infancy. It is believed that its use could make significant advances in diagnosis and treatment. Several translational biomechanics strategies are already emerging, such as corneal stiffening for the treatment of keratoconus, and more are likely to follow. This review aims to cultivate the idea that biomechanics plays a major role in ophthalmology and that the clinical translation, lead by collaborative teams of clinicians and biomedical engineers, will benefit our patients. Specifically, recent advances and future prospects in corneal, iris, trabecular meshwork, crystalline lens, scleral and lamina cribrosa biomechanics are discussed.

Material properties of the posterior human sclera

To characterize the material properties of posterior and peripapillary sclera from human donors, and to investigate the macro- and micro-scale strains as potential control mechanisms governing mechanical homeostasis. Posterior scleral shells from 9 human donors aged 57-90 years were subjected to IOP elevations from 5 to 45mmHg and the resulting full-field displacements were recorded using laser speckle interferometry. Eye-specific finite element models were generated based on experimentally measured scleral shell surface geometry and thickness. Inverse numerical analyses were performed to identify material parameters for each eye by matching experimental deformation measurements to model predictions using a microstructure-based constitutive formulation that incorporates the crimp response and anisotropic architecture of scleral collagen fibrils. The material property fitting produced models that fit both the overall and local deformation responses of posterior scleral shells very well. The nonlinear stiffening of the sclera with increasing IOP was well reproduced by the uncrimping of scleral collagen fibrils, and a circumferentially aligned ring of collagen fibrils around the scleral canal was predicted in all eyes. Macroscopic in-plane strains were significantly higher in peripapillary region then in the mid-periphery. In contrast, the meso- and micro-scale strains at the collagen network and collagen fibril level were not significantly different between regions. The elastic response of the posterior human sclera can be characterized by the anisotropic architecture and crimp response of scleral collagen fibrils. The similar collagen fibril strains in the peripapillary and mid-peripheral regions support the notion that the scleral collagen architecture including the circumpapillary ring of collagen fibrils evolved to establish optimal load bearing conditions at the collagen fibril level.

Variation of the Axial Location of Bruch's Membrane Opening With Age, Choroidal Thickness, and Race

PURPOSE This study explores variation in the axial location of Bruchs membrane opening (BMO) to determine if this reference plane varies with age and race. METHODS There were 168 spectral-domain optical coherence tomography (SDOCT) optic nerve head volumes that were obtained from healthy subjects and manually delineated within 24 axial slices to develop point clouds for Bruchs membrane and anterior scleral surfaces. A BMO-independent reference plane was generated based on the peripapillary sclera to measure BMO position. General estimating equations were used to determine the relationship of the axial position of BMO (BMO height) with choroidal thickness, age, and race (African Descent [AD] versus European Descent [ED]) controlling for variations in axial length. RESULTS The peripapillary choroid was thinner with increasing axial length (-14.9 μm/mm, P = 0.0096), advancing age (-1.1 μm/y, P = 0.00091), and in the ED group (20.2 μm, P = 0.019) in a multivariable model. Choroidal thickness was also strongly related to BMO height (P < 0.00001) independent of all covariates. Bruchs membrane opening position was more posterior relative to the sclera in older subjects (1.3 μm/y, P = 0.00017), independent of axial length and race. However, when choroidal thickness was included in the model, this association was lost (P = 0.225). There was no significant difference in BMO height between racial groups after adjustment for age and axial length. CONCLUSIONS Bruchs membrane opening is more posteriorly located in older individuals. These differences are largely due to differences in choroidal thickness and suggest that BMO migrates posteriorly with age due to age-related choroidal thinning. However, additional studies in longitudinal datasets are needed to validate these findings.

Recent Structural Alteration of the Peripheral Lamina Cribrosa Near the Location of Disc Hemorrhage in Glaucoma

PURPOSE We investigated whether disc hemorrhage (DH) is associated with the recent structural alteration of the peripheral lamina cribrosa (LC) as assessed by enhanced depth imaging (EDI) spectral-domain optical coherence tomography (SD-OCT). METHODS Serial horizontal B-scan images were obtained by EDI SD-OCT from primary open-angle glaucoma (POAG) patients before and after the detection of DH (DH group, n = 45), and those who had no DH during the 1-year scan interval (non-DH group, n = 36). The images were processed using compensation and contrast enhancement. Then, 11 radial OCT images centered on the optic disc were generated from the 3-dimensionally reconstructed volume image. A recent structural alteration of the LC was defined when either the outward deformation of the anterior LC surface or radial disruption of the LC was identified in the temporal periphery. RESULTS A recent structural alteration of the LC was found in 40 (88.9%) eyes in the DH group versus 4 (11.1%) eyes in the non-DH group. The amount of maximum outward deformation (55.82 ± 34.60 vs. 20.15 ± 4.28 μm) and radial disruption (69.87 ± 46.74 vs. 18.31 ± 1.17 μm) was larger in the DH group than in the non-DH group. The maximum LC alteration was observed within 1 clock-hour distance from the location of DH in all 40 eyes. CONCLUSIONS The peripheral LC exhibited a recent alteration in eyes with DH. The alteration was correlated spatially with the location of the DH. These findings suggest that DH may result from microvascular damage incurred from alteration of the LC near its insertion.

Regional Variations in Mechanical Strain in the Posterior Human Sclera

PURPOSE The goal of this study was to establish sectorial and regional variability in the mechanical strain of peripapillary and mid-peripheral sclera in normal eyes from elderly human donors. METHODS Ten pairs of normal eyes from human donors aged 57 to 90 years old were mechanically inflation-tested within 48 hours post mortem. The intact posterior scleral shells were pressurized from 5 to 45 mm Hg while the full-field three-dimensional displacements of the scleral surface were measured using laser speckle interferometry. The displacement field was fit to continuous and differentiable analytical functions, from which the full strain tensor of the outer scleral surface was calculated. Mean maximum principal (tensile) strain was computed for eight circumferential sectors (45° wide) within the peripapillary and mid-peripheral regions surrounding the optic nerve head (ONH). RESULTS Overall, the peripapillary sclera exhibited significantly higher tensile strain (1.2%) than mid-peripheral sclera (0.95%) for a 40 mm Hg IOP elevation (P < 0.00001). In the peripapillary region, the inferotemporal sector exhibited the highest tensile strain (1.45%) while the superior sector had the lowest (1.19%; P < 0.00001). Mid-peripheral scleral strains were lower but exhibited a similar sectorial pattern. CONCLUSIONS Human posterior sclera exhibits complex regional mechanical behavior in response to acute IOP elevations from 5 to 45 mm Hg. Results indicate 1) the peripapillary sclera is subjected to significantly higher tensile strain than the adjacent mid-peripheral sclera, and 2) strains are significantly higher in the temporal and inferior quadrants of the peripapillary sclera, which may contribute to the increased prevalence of glaucomatous damage associated with these regions of the ONH.

Lamina cribrosa visibility using optical coherence tomography: comparison of devices and effects of image enhancement techniques.

PURPOSE To compare the visibility of the lamina cribrosa (LC) in optic disc images acquired from 60 glaucoma and 60 control subjects using three optical coherence tomography (OCT) devices, with and without enhanced depth imaging (EDI) and adaptive compensation (AC). METHODS A horizontal B-scan was acquired through the center of the disc using two spectral-domain (Spectralis and Cirrus; with and without EDI) and a swept-source (DRI) OCT. Adaptive compensation was applied post acquisition to improve image quality. To assess LC visibility, four masked observers graded the 1200 images in a randomized sequence. The anterior LC was graded from 0 to 4, the LC insertions from 0 to 2, and the posterior LC either 0 or 1. The effect of EDI, AC, glaucoma severity, and other clinical/demographic factors on LC visibility was assessed using generalized estimating equations. RESULTS The anterior LC was the most detectable feature, followed by the LC insertions. Adaptive compensation improved anterior LC visibility independent of EDI. Cirrus+EDI+AC generated the greatest anterior LC visibility grades (2.79/4). For LC insertions visibility, DRI+AC was the best method (1.10/2). Visibility of the posterior LC was consistently poor. Neither glaucoma severity nor clinical/demographic factors consistently affected LC visibility. CONCLUSIONS Adaptive compensation is superior to EDI in improving LC visibility. Visibility of the posterior LC remains poor suggesting impracticality in using LC thickness as a glaucoma biomarker.