Optic Nerve Head Deformations Research Articles

Optic Nerve Tortuosity and Globe Proptosis in Normal and Glaucoma Subjects.

The purpose of this study was to assess the difference in optic nerve tortuosity during eye movements and globe proptosis between primary open angle glaucoma and normal subjects using orbital magnetic resonance imaging (MRI). Ten Chinese subjects matched for ethnicity and refractive errors were recruited, including 5 normal controls and 5 patients with primary open angle glaucoma. All subjects underwent MRI to assess their optic nerves and globes for 3 eye positions: primary gaze, adduction, and abduction. Optic nerve tortuosity (optic nerve length divided by the distance between 2 ends) and globe proptosis (maximum distance between the cornea and interzygomatic line) were measured from MRI images. In adduction, the tortuosity of normal eyes was significantly larger than that of the glaucomatous eyes. Optic nerve tortuosity in adduction in the control and glaucoma groups were 1.004±0.003 (mean±SD) and 1.001±0.001, respectively (P=0.037). Globe proptosis (primary gaze) in glaucoma subjects (19.14±2.11 mm) was significantly higher than that in control subjects (15.32±2.79 mm; P=0.046). In this sample, subjects with glaucoma exhibited tauter optic nerves and more protruding eye globes compared with normal eyes. This may impact optic nerve head deformations in anatomically predisposed patients.

Myopic optic disc changes and its role in glaucoma.

Optic nerve head (ONH) changes such as tilt and torsion are associated with the progression of myopia, and may in turn predispose toward glaucoma. At the same time, these ONH deformations also make the structural assessment for glaucoma difficult. Here, we review the mechanisms and changes to the myopic optic disc, and the advances in structural imaging to better evaluate the ONH in myopia. The distance, depth, and angle between the optic disc and the deepest point of the elongated eyeball may be related to the degree and direction of optic disc tilt and torsion. It is hypothesized that as the eyeball grows axially, the disc is pulled toward its most protruded point. These ONH deformations in myopia are thought to induce strain on the lamina cribrosa and the axons passing through it. Recent studies have shown unique characteristics of the lamina cribrosa in myopia that may account for susceptibility toward glaucoma. New developments in imaging the ONH in myopia, including the use of optical coherence tomography-angiography may also further our understanding of the relationship between myopia and glaucoma. Optic disc changes in myopia are secondary to the configuration of the posterior globe. These ONH deformations may predispose toward glaucoma, although the causative relationship between myopia and glaucoma remains to be further clarified.

Pulling and Tugging on the Retina: Mechanical Impact of Glaucoma Beyond the Optic Nerve Head.

Several retinal conditions have been recently revealed by optical coherence tomography (OCT) to occur more frequently in glaucoma than in healthy eyes: paravascular defects, peripapillary retinoschisis, and pseudo-cysts of the inner nuclear layer (INL). Here the clinical OCT findings described in these reports are reviewed and a framework that could explain why they are related and occur more frequently in glaucoma is proposed. Evidence suggests that these conditions all share in common a strong tendency to develop in association with severe and/or rapidly progressing disease and a likelihood of involving biomechanical forces and differential tissue deformation. Müller glia are mechanosensitive and known to react to shear and axial strain, and to participate in homeostasis of water and ion flux through the retina, and to provide spring-like capability to buffer of mechanical forces. Thus, Müller cell integrity is also likely to be involved in the development and/or response to such events. OCT has also revealed that Müller cell optical properties (scatter and attenuation) appear to be altered in at least two of these retinal conditions: peripapillary retinoschisis and pseudo-cysts of the INL. Future studies applying 3D strain mapping techniques might reveal structural changes over time (either acute or longer-term deformations) that predict the onset and location of these retinal defects and their relationship to progressive optic nerve head deformation, retinal nerve fiber layer, and retinal ganglion cell loss in glaucoma.

Finite Element Modelling Predicts Large Accommodation Induced Optic Nerve Head Deformations

Finite Element Modelling Predicts Large Accommodation Induced Optic Nerve Head Deformations

The relationship between optic nerve head deformation and visual field defects in myopic eyes with primary open-angle glaucoma.

PurposeTo investigate the relationship between the morphologic features of myopic optic nerve head (ONH) and visual field (VF) defects in myopic subjects with primary open-angle glaucoma (POAG) by intraindividual comparison.MethodsMyopic POAG subjects with unilateral glaucomatous VF defect were recruited. The morphologic features of myopic ONH, including optic disc tilt, optic disc rotation, and β-zone parapapillary atrophy (PPA) were measured from color fundus photographs. The comparisons were performed between the eyes with VF defects and the contralateral eyes without VF defects. Logistic regression analysis was performed to investigate the relationship between various ocular parameters and the presence of VF defects.ResultsWe retrospectively included 100 eyes of 50 myopic POAG subjects. (Mean age: 50.1 ± 10.0 years). The tilt ratio was similar between the paired eyes. The degree of optic disc rotation (12.96 ± 7.21°) in eyes with VF defects were statistically greater than the contralateral eyes (6.86 ± 4.30°; P < 0.001) without VF defect. The β-zone PPA-to-disc area ratio was significantly greater in eyes with VF defects than the contralateral eyes (P = 0.024) without VF defect. In multivariate logistic regression analysis, the greater degree of optic disc rotation was significantly associated with the presence of VF defects (P < 0.001). However, tilt ratio, β-zone PPA-to-disc area ratio, refractive error, and axial length were not associated with the presence of VF defects.ConclusionsAmong the morphologic features of myopic ONH, only the greater degree of the optic disc rotation was associated with the presence of VF defects in myopic subjects with POAG.

EFFECT OF GEOMETRICAL PARAMETERS ON THE DEFORMATIONS OF THE HUMAN OPTIC NERVE HEAD BASED ON INDIVIDUAL-SPECIFIC MODELS

The elevated intraocular pressure (IOP) is one of the important risk factors of glaucomatous optic nerve damage. The deformations of glaucomatous optic nerve head (ONH) due to the elevated IOP might lead to further damage to the optic nerve. The ONH deformations due to the elevated IOP depend on their geometry. Therefore, it is meaningful to investigate the relationship between geometrical parameters and the deformation of ONH. Firstly, the geometrical parameters of ONH were obtained by in vivo using spectral domain optical coherence tomography. Then, individual-specific three-dimensional (3D) models of ONH for glaucoma and normal subjects were established and the deformations of ONH were acquired by using finite element method. Furthermore, the thickness changes of retina and lamina cribrosa were calculated under different IOPs. Finally, correlations between geometrical parameters and the relative deformations of the human ONH were researched by using Spearman correlation. It was found that the relative thickness change of patient’s retina was larger than that of normal subjects under the same condition. The correlation of several parameters, including cup area, and lamina cribrosa depth, with relative deformations of ONH had statistical significance.

The Impact of Choroidal Swelling on Optic Nerve Head Deformation.

Choroid geometry and swelling have been proposed to contribute to ocular pathologies. Thus, it is important to understand how the choroid may impact the optic nerve head (ONH) biomechanical environment. We developed a finite element model to study how acute choroidal swelling and choroid geometry affect ONH deformation. We developed two geometric models of the ONH: one with a "blunt" choroidal insertion and another with a "tapered" choroid insertion. We examined how choroidal volume changes (2.1-14.2 μL, estimated to occur during the ocular pulse) impact biomechanical strain in three tissue regions: the prelaminar neural tissue, lamina cribrosa, and retrolaminar neural tissue. Then, we performed a sensitivity analysis to understand how variation in ONH pressures, tissue material properties, and choroidal swelling influenced the peak tissue strains. Choroidal swelling in the blunt choroid geometry had a large impact on the strains in the prelaminar neural tissue, with magnitudes comparable to those expected to occur due to an IOP of 30 mm Hg. Choroidal swelling in the tapered choroid geometry also affected strains but to a lesser extent compared to the blunt geometry. A sensitivity analysis confirmed that choroidal swelling was more influential on prelaminar neural tissue strains in the blunt choroid geometry. Choroid anatomy and swelling can interact to play an important role in prelaminar neural tissue deformation. These findings suggest that the choroid may play an important, and previously unappreciated, role in ONH biomechanics, and motivate additional research to better define the in vivo effects of choroidal volume change.

Modeling the Origin of the Ocular Pulse and Its Impact on the Optic Nerve Head.

To use finite element (FE) analysis to understand the origin of the ocular pulse and predict its biomechanical impact on the optic nerve head (ONH). An FE model of a healthy eye was reconstructed. The choroid was biphasic and consisted of a solid phase (connective tissues) and a fluid phase (blood). We applied arterial blood pressure at 18 entry sites (posterior ciliary arteries) and venous blood pressure at 4 exit sites (vortex veins). For one cardiac cycle, we reported the resulting pulse volume, the ocular pulse amplitude (OPA), and diastole-to-systole ONH deformations. We also studied the effect of a change in scleral stiffness, in arterial pressure, and in baseline IOP. During the cardiac cycle, a change in arterial pressure resulted in choroidal expansion, which in turn induced a change in IOP (the OPA) and ONH deformations. From diastole to systole, we found that choroidal expansion made the peripapillary retina move anteriorly, but both choroidal expansion and the OPA made the prelamina and LC move posteriorly. The net result was shearing of neural tissues in the neuroretinal rim. Both a stiffer sclera and a higher IOP resulted in a higher OPA, smaller pulse volume, larger diastole-to-systole ONH strains, and neural tissue shear in the neuroretinal rim. Increasing the arterial pressure had the same effect, except that it increased the pulse volume. Our models indicate that, during the cardiac cycle, the OPA and choroidal expansion can deform the ONH with a net shearing of neural tissues within the neuroretinal rim.

Regional Deformation of the Optic Nerve Head and Peripapillary Sclera During IOP Elevation.

PurposeTo measure the deformation of the porcine optic nerve head (ONH) and peripapillary sclera (PPS) in response to intraocular pressure (IOP) elevation.MethodsHigh-frequency ultrasound was used to image the ONH and PPS of 12 porcine eyes during ex vivo inflation testing from 5 to 30 mm Hg. A speckle tracking algorithm was used to compute tissue displacements in the anterior-posterior direction and expansion of the scleral canal. Through-thickness, in-plane, and shear strains were calculated within the ONH. Regional displacements and strains were analyzed and compared.ResultsThe ONH and PPS showed overall posterior displacement in response to IOP elevation. Posterior displacement of the ONH was larger than and strongly correlated with the posterior displacement of the PPS throughout inflation testing. Scleral canal expansion was much smaller and leveled off quicker than ONH posterior displacement as IOP increased. Through-thickness compression was concentrated in the anterior ONH, which also experienced larger in-plane and shear strains than the posterior ONH. Within the anterior ONH, all three strains were significantly higher in the periphery compared with the center, with the shear strain exhibiting the greatest difference between the two regions.ConclusionsHigh-resolution ultrasound speckle tracking revealed the full-thickness mechanical response of the posterior eye to IOP elevation. A mismatch in posterior displacement was found between the ONH and PPS, and regional analyses showed a concentration of strains within the periphery of the anterior porcine ONH. These deformation patterns may help in understanding IOP-associated optic nerve damage and glaucoma susceptibility.

Association Between Optic Nerve Head Deformation and Retinal Microvasculature in High Myopia

To evaluate the retinal microvasculature of peripapillary and macular regions in highly myopic eyes and investigate the association between the vascular parameters and optic nerve head (ONH) deformation. Cross-sectional study. Seventy-one subjects with highly myopic eyes and 26 subjects with emmetropic eyes were included. Horizontal B-scan images of the ONH were obtained using optical coherence tomography (OCT) and horizontal tilt angles were measured. Integrated automated algorithms in the Avanti OCT angiography were used to quantify the peripapillary vessel density and area of the foveal avascular zone (FAZ) at the level of superficial and deep vascular networks. Association between horizontal disc tilt and the vascular parameters was evaluated. The mean axial length and horizontal tilt angle were 26.73 ± 0.63mm and 9.77 ± 3.00 degrees in the highly myopic group and 23.46 ± 0.55mm and 5.95 ± 3.48 degrees in the emmetropic group, respectively. Highly myopic eyes exhibited significantly lower average peripapillary vessel density (P= .010) and larger superficial and deep FAZs (P= .001 and P < .001, respectively) compared with emmetropic eyes. Linear regression analyses showed that horizontal tilt angle significantly correlated the average peripapillary vessel density (P= .037) and the areas of superficial (P<.001) and deep (P < .001) FAZs. The retinal microvasculature was significantly different in highly myopic eyes according to the degree of horizontal optic disc tilt. In addition to peripapillary vessel density, FAZ can be affected by the degree of optic disc tilt.

Development of a Platform for Studying 3D Astrocyte Mechanobiology: Compression of Astrocytes in Collagen Gels.

Glaucoma is a common optic neuropathy characterized by retinal ganglion cell death. Elevated intraocular pressure (IOP), a key risk factor for glaucoma, leads to significant biomechanical deformation of optic nerve head (ONH) cells and tissues. ONH astrocytes respond to this deformation by transforming to a reactive, proliferative phenotype, which has been implicated in the progression of glaucomatous vision loss. However, little is known about the mechanisms of this transformation. In this study, we developed a 3D collagen gel culture system to mimic features of ONH deformation due to elevated IOP. Compressive loading of astrocyte-seeded collagen gels led to cell alignment perpendicular to the direction of strain, and increased astrocyte activation, as assayed by GFAP, vimentin, and s100β levels, as well as MMP activity. This proof-of-concept study shows that this system has potential for studying mechanisms of astrocyte mechanobiology as related to the pathogenesis of glaucoma. Further work is needed to establish the possible interplay of mechanical stimulation, matrix properties, and hypoxia on the observed response of astrocytes.

Verification of a virtual fields method to extract the mechanical properties of human optic nerve head tissues in vivo.

We aimed to verify a custom virtual fields method (VFM) to estimate the patient-specific biomechanical properties of human optic nerve head (ONH) tissues, given their full-field deformations induced by intraocular pressure (IOP). To verify the accuracy of VFM, we first generated 'artificial' ONH displacements from predetermined (known) ONH tissue biomechanical properties using finite element analysis. Using such deformations, if we are able to match back the known biomechanical properties, it would indicate that our VFM technique is accurate. The peripapillary sclera was assumed anisotropic hyperelastic, while all other ONH tissues were considered isotropic. The simulated ONH displacements were fed into the VFM algorithm to extract back the biomechanical properties. The robustness of VFM was also tested against rigid body motions and noise added to the simulated displacements. Then, the computational speed of VFM was compared to that of a gold-standard stiffness measurement method (inverse finite element method or IFEM). Finally, as proof of principle, VFM was applied to IOP-induced ONH deformation data (obtained from one subject's eye imaged with OCT), and the biomechanical properties of the prelamina and lamina cribrosa (LC) were extracted. From given ONH displacements, VFM successfully matched back the biomechanical properties of ONH tissues with high accuracy and efficiency. For all parameters, the percentage errors were less than 0.05%. Our method was insensitive to rigid body motions and was also able to recover the material parameters in the presence of noise. VFM was also found 125 times faster than the gold-standard IFEM. Finally, the estimated shear modulus for the prelamina and the LC of the studied subject's eye were 33.7 and 63.5 kPa, respectively. VFM may be capable of measuring the biomechanical properties of ONH tissues with high speed and accuracy. It has potential in identifying patient-specific ONH biomechanical properties in the clinic if combined with optical coherence tomography.

In Vivo 3-Dimensional Strain Mapping Confirms Large Optic Nerve Head Deformations Following Horizontal Eye Movements.

To measure lamina cribrosa (LC) strains (deformations) following abduction and adduction in healthy subjects and to compare them with those resulting from a relatively high acute intraocular pressure (IOP) elevation. A total of 16 eyes from 8 healthy subjects were included. Among the 16 eyes, 11 had peripapillary atrophy (PPA). For each subject, both optic nerve heads (ONHs) were imaged using optical coherence tomography (OCT) at baseline (twice), in different gaze positions (adduction and abduction of 20°) and following an acute IOP elevation of approximately 20 mm Hg from baseline (via ophthalmodynamometry). Strains of LC for all loading scenarios were mapped using a three-dimensional tracking algorithm. In all 16 eyes, LC strains induced by adduction and abduction were 5.83% ± 3.78% and 3.93% ± 2.57%, respectively, and both significantly higher than the control strains measured from the repeated baseline acquisitions (P < 0.01). Strains of LC in adduction were on average higher than those in abduction, but the difference was not statistically significant (P = 0.07). Strains of LC induced by IOP elevations (on average 21.13 ± 7.61 mm Hg) were 6.41% ± 3.21% and significantly higher than the control strains (P < 0.0005). Gaze-induced LC strains in the PPA group were on average larger than those in the non-PPA group; however, the relationship was not statistically significant. Our results confirm that horizontal eye movements generate significant ONH strains, which is consistent with our previous estimations using finite element analysis. Further studies are needed to explore a possible link between ONH strains induced by eye movements and axonal loss in optic neuropathies.

Deformation of Optic Nerve Head and Peripapillary Tissues by Horizontal Duction

To ascertain deformation of the optic nerve head (ONH) and peripapillary tissues caused by horizontal duction. Prospective, experimental study. Optical coherence tomography of the ONH region was performed in 23 eyes of 12 normal volunteers in central gaze and increasing (10, 20, and 30 degrees) adduction and abduction. Main outcome measures were changes from central gaze in the configuration of the ONH and peripapillary tissues in eccentric gazes. Adduction but not abduction was associated with significant, progressive relative posterior displacement of the temporal peripapillary retinal pigment epithelium (tRPE) from its position in central gaze reaching 49 ± 10μm in 30-degree adduction (standard error of mean, P < .0001). Absolute (anterior or posterior) optic cup displacement (OCD) averaged 41 ± 7μm in 30-degree adduction. Linear regression showed significant effect of adduction on absolute OCD (slope 1.09 ± 0.36 μm/degree, P= .0037). In 20-degree and 30-degree adduction, all eyes exhibited significant progressive temporal ONH tilting reaching 3.1 ± 0.4 degrees in 30-degree adduction (P < .0001). Abduction was not associated with significant peripapillary RPE displacement, OCD, or ONH tilt. Both nasal and temporal peripapillary choroid averaged 9-19μm thinner in adduction and abduction than in central gaze (P < .02). Adduction temporally tilts and displaces the prelaminar ONH and peripapillary tissues. Both adduction and abduction compress the peripapillary choroid. These effects support magnetic resonance imaging and biomechanical evidence that adduction imposes strain on the ONH and peripapillary tissues. Repetitive strain from eye movements over decades might in susceptible individuals lead to optic neuropathies such as normal tension glaucoma.

Optic Nerve Head Deformation in Glaucoma: The Temporal Relationship between Optic Nerve Head Surface Depression and Retinal Nerve Fiber Layer Thinning

To investigate the temporal relationship between optic nerve head (ONH) surface depression and retinal nerve fiber layer (RNFL) thinning measured by confocal scanning laser ophthalmoscopy (CSLO) and spectral-domain optical coherence tomography (SD-OCT), respectively, during the course of glaucoma progression. Prospective, longitudinal study. A total of 146 eyes of 90 patients with glaucoma and 70 normal eyes of 35 healthy individuals followed for an average of 5.4 years (range, 48.0-76.6 months). Eyes were imaged by CSLO (Heidelberg Retinal Tomograph [HRT]; Heidelberg Engineering, GmbH, Dossenheim, Germany) and SD-OCT (Cirrus HD-OCT; Carl Zeiss Meditec AG, Dublin, CA) at approximately 4-month intervals for measurement of ONH surface topography and RNFL thickness, respectively. Significant ONH surface depression and RNFL thinning were defined with reference to Topographic Change Analysis (TCA) with HRT and Guided Progression Analysis (GPA) with Cirrus HD-OCT, respectively. The survival probabilities were compared with a Cox proportional hazards model. Number of eyes with progressive ONH and RNFL changes and the sequence of changes. A total of 3238 OCT and 3238 CSLO images obtained in the same follow-up visits were analyzed. At a specificity of 94.3% (4 eyes showed ONH surface depression and 4 eyes showed RNFL thinning in the normal group), 57 eyes (39.0%) had ONH surface depression, 46 eyes (31.5%) had RNFL thinning, and 23 eyes (15.8%) had evidence of both in the glaucoma group. Among these 23 eyes, 19 (82.6%) had ONH surface depression detected before RNFL thinning, with a median lag time of 15.8 months (range, 4.0-40.8 months). Although only 7.0% of eyes (4/57) had RNFL thinning at the onset of ONH surface depression, 45.7% (21/46) had ONH surface depression at the onset of RNFL thinning. The survival probability of eyes with ONH surface depression was significantly worse than eyes with RNFL thinning (P = 0.002). With reference to the HRT TCA and OCT GPA, ONH surface depression occurred before RNFL thinning in a significant proportion of patients with glaucoma. A time window for therapeutic intervention may exist on detection of ONH surface depression before there is observable RNFL thinning in glaucoma.

A Method to Estimate Biomechanics and Mechanical Properties of Optic Nerve Head Tissues From Parameters Measurable Using Optical Coherence Tomography

Optic nerve head (ONH) tissue properties and biomechanics remain mostly unmeasurable in the experiment. We hypothesized that these can be estimated numerically from ocular parameters measurable in vivo with optical coherence tomography (OCT). Using parametric models representing human ONHs we simulated acute intraocular pressure (IOP) increases (10 mmHg). Statistical models were fit to predict, from OCT-measurable parameters, 15 outputs, including ONH tissue properties, stresses, and deformations. The calculations were repeated adding parameters that have recently been proposed as potentially measurable with OCT. We evaluated the sensitivity of the predictions to variations in the experimental parameters. Excellent fits were obtained to predict all outputs from the experimental parameters, with cross-validated R2s between 0.957 and 0.998. Incorporating the potentially measurable parameters improved fits significantly. Predictions of tissue stiffness were accurate to within 0.66 MPa for the sclera and 0.24 MPa for the lamina cribrosa. Predictions of strains and stresses were accurate to within 0.62% and 4.9 kPa, respectively. Estimates of ONH biomechanics and tissue properties can be obtained quickly from OCT measurements using an applet that we make freely available. These estimates may improve understanding of the eye sensitivity to IOP and assessment of patient risk for development or progression of glaucoma.

Sequential-Digital Image Correlation for Mapping Human Posterior Sclera and Optic Nerve Head Deformation

Optic nerve head (ONH) deformations may be involved in the onset or further development of glaucoma, including in patients with relatively normal intraocular pressures (IOPs). Characterizing posterior scleral deformations over physiological pressures may provide a better understanding of how changes in IOP lead to changes in the mechanical environment of the ONH and possibly retinal ganglion cell death. Pressure inflation measurement test protocols are commonly used to measure deformation of the peripapillary sclera with full-field noncontact optical methods. The purpose of this work was to develop and validate a new sequential 3D digital image correlation (S-DIC) approach for quantification of posterior scleral pressure induced deformation that improves z (in-depth) resolution of the DIC measurement without losing in-plane sensitivity, while also being able to contour and map deformations of the complex-shaped ONH. Our approach combines two orthogonal axes of parallax with standard 3D DIC methods using a single high-resolution camera. The enhanced capabilities of S-DIC with respect to standard 3D DIC has been demonstrated by carrying out a complete benchmark for shape, deformation, and strain measurement on an object of known complex geometry. Our S-DIC method provided a reconstruction accuracy of 0.17% and an uncertainty in z-position measurement of 8 μm. The developed methodology has also been applied to a human posterior scleral shell, including the full peripapillary sclera and optic nerve. The relatively inexpensive S-DIC approach may provide new information on the biomechanical deformations of the optic nerve head and, thus, the death of retinal ganglion cells in primary open angle glaucoma.

Scleral anisotropy and its effects on the mechanical response of the optic nerve head.

This paper presents a computational modeling study of the effects of the collagen fiber structure on the mechanical response of the sclera and the adjacent optic nerve head (ONH). A specimen-specific inverse finite element method was developed to determine the material properties of two human sclera subjected to full-field inflation experiments. A distributed fiber model was applied to describe the anisotropic elastic behavior of the sclera. The model directly incorporated wide-angle X-ray scattering measurements of the anisotropic collagen structure. The converged solution of the inverse method was used in micromechanical studies of the mechanical anisotropy of the sclera at different scales. The effects of the scleral collagen fiber structure on the ONH deformation were evaluated by progressively filtering out local anisotropic features. It was found that the majority of the midposterior sclera could be described as isotropic without significantly affecting the mechanical response of the tissues of the ONH. In contrast, removing local anisotropic features in the peripapillary sclera produced significant changes in scleral canal expansion and lamina cribrosa deformation. Local variations in the collagen structure of the peripapillary sclera significantly influenced the mechanical response of the ONH.

Quantitative Mapping of Scleral Fiber Orientation in Normal Rat Eyes

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. 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. 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. 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.

Study of regional deformation of the optic nerve head using scanning laser tomography

PURPOSE. Previous studies have suggested that IOP-induced deformation of the optic nerve head (ONH) at the level of the lamina cribrosa may contribute to axonal damage in glaucomatous optic neuropathy. Our purpose was to introduce a novel enucleated eye model for characterizing acute IOP-induced changes in ONH topography, and to develop improved analytical methods for detection of regional topographic change in the ONH. METHODS. Using a specially designed experimental apparatus, enucleated human eyes were progressively pressurized to 5, 15, 30, and 50 mmHg. Seven topographic images of the optic disc were taken at each pressure by a scanning laser tomographer (Heidelberg Retina Tomograph–HRT). The dependence of ONH topography on IOP was quantified for the entire nerve using standard HRT indices of ONH topographic change. The supero-inferior and nasal-temporal hemifields were also analyzed. A new method of analysis was developed which computes the location of the point of maximum slope within a 10° sector of the ONH, as well as the magnitude of this slope. This method, termed "Inflection Point Analysis," was designed to be robust to the potential artefacts of image translation, reference plane location, and the subjective determination of ONH limits. RESULTS. The results of three eyes are presented to illustrate the techniques. In our enucleated eye model, average ONH depth progressively increased with IOP, showing a maximum average posterior displacement of 36 µm as IOP was changed from 5 to 50 mmHg. Significant regional variability in ONH displacement was observed, which both Inflection Point Analysis and standard HRT parameters were able to detect. Inflection point analysis showed several advantages over standard HRT parameters: it was insensitive to artefacts due to tilt, was able to objectively delineate the boundary between the optic cup and neuroretinal rim, and was able to sensitively track changes in the location of this margin. CONCLUSIONS. Scanning laser tomography is capable of detecting regional variation in the deformation of the ONH in response to acute changes in IOP. Our enucleated eye model and Inflection Point Analysis are promising tools for basic studies of ONH deformation in response to IOP. More extensive studies of both enucleated and in vivo eyes are required to determine the potential of Inflection Point Analysis for studying and tracking the progression of glaucomatous optic neuropathy.