A method for analyzing AFM force mapping data obtained from soft tissue cryosections.

Atomic force microscopy (AFM) is a valuable tool for assessing mechanical properties of biological samples, but interpretations of measurements on whole tissues can be difficult due to the tissue's highly heterogeneous nature. To overcome such difficulties and obtain more robust estimates of tissue mechanical properties, we describe an AFM force mapping and data analysis pipeline to characterize the mechanical properties of cryosectioned soft tissues. We assessed this approach on mouse optic nerve head and rat trabecular meshwork, cornea, and sclera. Our data show that the use of repeated measurements, outlier exclusion, and log-normal data transformation increases confidence in AFM mechanical measurements, and we propose that this methodology can be broadly applied to measuring soft tissue properties from cryosections.

Computational study on the effects of central retinal blood vessels with asymmetric geometries on optic nerve head biomechanics.

Optic nerve head (ONH) biomechanics are associated with glaucoma progression and have received considerable attention. Central retinal vessels (CRVs) oriented asymmetrically in the ONH are the single blood supply source to the retina and are believed to act as mechanically stable elements in the ONH in response to intraocular pressure (IOP). However, these mechanical effects are considered negligible in ONH biomechanical studies and received less attention. This study investigated the effects of CRVs on ONH biomechanics taking into consideration three-dimensional asymmetric CRV geometries. A CRV geometry was constructed based on CRV centerlines extracted from optical coherence tomography ONH images in eight healthy subjects and superimposed in the idealized ONH geometry established in previous studies. Mechanical analyses of the ONH in response to the IOP were conducted in the cases with and without CRVs for comparison. Obtained results demonstrated that the CRVs induced anisotropic ONH deformation, particularly in the lamina cribrosa and the associated upper neural tissues (prelamina) with wide ranges of spatial strain distributions. These results indicated that the CRVs result in anisotropic deformation with local strain concentration, rather than function to mechanically support in response to the IOP as in the conventional thinking in ophthalmology.

Fibrous finite element modeling of the optic nerve head region.

The optic nerve head (ONH) region at the posterior pole of the eye is supported by a fibrous structure of collagen fiber bundles. Discerning how the fibrous structure determines the region biomechanics is crucial to understand normal physiology, and the roles of biomechanics on vision loss. The fiber bundles within the ONH structure exhibit complex three-dimensional (3D) organization and continuity across the various tissue components. Computational models of the ONH, however, usually represent collagen fibers in a homogenized fashion without accounting for their continuity across tissues, fibers interacting with each other and other fiber-specific effects in a fibrous structure. We present a fibrous finite element (FFE) model of the ONH that incorporates discrete collagen fiber bundles and their histology-based 3D organization to study ONH biomechanics as a fibrous structure. The FFE model was constructed using polarized light microscopy data of porcine ONH cryosections, representing individual fiber bundles in the sclera, dura and pia maters with beam elements and canal tissues as continuum structures. The FFE model mimics the histological in-plane orientation and width distributions of collagen bundles as well as their continuity across different tissues. Modeling the fiber bundles as linear materials, the FFE model predicts the nonlinear ONH response observed in an inflation experiment from the literature. The model also captures important microstructural mechanisms including fiber interactions and long-range strain transmission among bundles that have not been considered before. The FFE model presented here advances our understanding of the role of fibrous collagen structure in the ONH biomechanics. STATEMENT OF SIGNIFICANCE: The microstructure and mechanics of the optic nerve head (ONH) are central to ocular physiology. Histologically, the ONH region exhibits a complex continuous fibrous structure of collagen bundles. Understanding the role of the fibrous collagen structure on ONH biomechanics requires high-fidelity computational models previously unavailable. We present a computational model of the ONH that incorporates histology-based fibrous collagen structure derived from polarized light microscopy images. The model predictions agree with experiments in the literature, and provide insight into important microstructural mechanisms of fibrous tissue biomechanics, such as long-range strain transmission along fiber bundles. Our model can be used to study the microstructural basis of biomechanical damage and the effects of collagen remodeling in glaucoma.

The role of intrapartum fetal head compression in neonatal retinal hemorrhage.

PURPOSE: Neonatal retinal hemorrhage is a common finding in newborns, but the underlying mechanisms are not fully understood. A computational simulation was designed to study the events taking place in the eye and orbit when the head is compressed as the neonate passes through the birth canal. METHODS: A finite element model of the eye, optic nerve sheath, and orbit was simulated and subjected to forces mimicking rises in intracranial pressure (ICP) associated with maternal contractions during normal vaginal delivery. Resulting changes in intraocular pressure (IOP), pressure in the optic nerve sheath, and stress within the sclera and retina were measured. RESULTS: During contractions, increased ICP was transmitted to the orbit, globe, and optic nerve sheath. IOP rose by 2.71 kPa near the posterior pole. Pressure at the center of the optic nerve sheath rose by 7.31 kPa and up to 9.30 kPa at its interface with the sclera. Stress in the retina was highest near the optic disk and reached 10.93, 10.99, and 13.28 kPa in the preretinal, intraretinal, and subretinal layers, respectively. Stress in the sclera peaked at 12.76 kPa. CONCLUSIONS: Increasing ICP associated with natural vaginal delivery increases intraorbital pressure, which applies stress to the retina. Associated retinal deformation may cause tearing of the retinal vasculature. Increased pressure within the optic nerve sheath may occlude the central retinal vein, resulting in outflow obstruction and subsequent rupture. Forces accumulated near the optic disk, likely accounting for the tendency of neonatal retinal hemorrhage to occur posteriorly.

Finite element modeling of effects of tissue property variation on human optic nerve tethering during adduction.

Tractional tethering by the optic nerve (ON) on the eye as it rotates towards the midline in adduction is a significant ocular mechanical load and has been suggested as a cause of ON damage induced by repetitive eye movements. We designed an ocular finite element model (FEM) simulating 6° incremental adduction beyond the initial configuration of 26° adduction that is the observed threshold for ON tethering. This FEM permitted sensitivity analysis of ON tethering using observed material property variations in measured hyperelasticity of the anterior, equatorial, posterior, and peripapillary sclera; and the ON and its sheath. The FEM predicted that adduction beyond the initiation of ON tethering concentrates stress and strain on the temporal side of the optic disc and peripapillary sclera, the ON sheath junction with the sclera, and retrolaminar ON neural tissue. However, some unfavorable combinations of tissue properties within the published ranges imposed higher stresses in these regions. With the least favorable combinations of tissue properties, adduction tethering was predicted to stress the ON junction and peripapillary sclera more than extreme conditions of intraocular and intracranial pressure. These simulations support the concept that ON tethering in adduction could induce mechanical stresses that might contribute to ON damage.

Relative Contributions of Intraocular and Cerebrospinal Fluid Pressures to the Biomechanics of the Lamina Cribrosa and Laminar Neural Tissues.

Purpose: The laminar region of the optic nerve head (ONH), thought to be the site of damage to the retinal ganglion cell axons in glaucoma, is continuously loaded on its anterior and posterior surfaces by dynamic intraocular pressure (IOP) and orbital cerebrospinal fluid pressure (CSFP), respectively. Thus, translaminar pressure (TLP; TLP = IOP-CSFP) has been proposed as a glaucoma risk factor. Methods: Three eye-specific finite element models of the posterior human eye were constructed, including full 3D microstructures of the load-bearing lamina cribrosa (LC) with interspersed laminar neural tissues (NTs), and heterogeneous, anisotropic, hyperelastic material formulations for the surrounding peripapillary sclera and adjacent pia. ONH biomechanical responses were simulated using three combinations of IOP and CSFP loadings consistent with posture change from sitting to supine. Results: Results show that tensile, compressive, and shear stresses and strains in the ONH were higher in the supine position compared to the sitting position (P < 0.05). In addition, LC beams bear three to five times more TLP-driven stress than interspersed laminar NT, whereas laminar NT exhibit three to five times greater strain than supporting LC (P < 0.05). Compared with CSFP, IOP drove approximately four times greater stress and strain in the LC, NT, and peripapillary sclera, normalized per mm Hg pressure change. In addition, IOP drove approximately three-fold greater scleral canal expansion and anterior-posterior laminar deformation than CSFP per mm Hg (P < 0.05). Conclusions: Whereas TLP has been hypothesized to play a prominent role in ONH biomechanics, the IOP and CSFP effects are not equivalent, as IOP-driven stress, strain, and deformation play a more dominant role than CSFP effects.

Elevated IOP Alters the Material Properties of Sclera and Lamina Cribrosa in Monkeys.

Objective: Elevated intraocular pressure (IOP) has significant impacts on different stages in the progression of chronic glaucoma. In this study, we investigated changes in the material properties of sclera and lamina cribrosa (LC) in a nonhuman primate model with elevated IOP. Methods: Normal adult Tibetan macaques were selected for the construction of elevated IOP model. After 40 days of stable maintenance on the ocular hypertension, the binocular eyeballs were obtained for the measurement of macroscopic parameters of the eyeballs. Posterior scleral tissue strips were obtained in circumferential and axial directions, and thickness was measured, respectively. Biomechanical parameters were obtained with stress relaxation, creep, and tensile test. The nanoindentation test was performed on the LC and scleral tissue around optic nerve head (ONH) to obtain compressive modulus. Results: In the presence of elevated IOP, variations of the axial diameter of the eyeball were greater than those of the transverse diameter, and the mean scleral thickness around ONH was smaller in the experimental group than control group. The elastic modulus and stress relaxation modulus of sclera were larger, and the creep rate was lower in the experimental group than control group. In the control group, the elastic modulus and stress relaxation modulus of the circumferential sclera were larger in the axial direction, and creep rate was smaller. In the experimental group, there was no significant difference in biomechanical characteristics between the two directions. Compared to the control group, the compression modulus of the LC was smaller, and the compression modulus of sclera around ONH was larger in the experimental group. Conclusion: Elevated IOP alters the viscoelasticity and anisotropy of sclera and LC. These may contribute to reduction of the organizational resistance to external forces and decline in the ability of self-recovery.

Highly accurate retinotopic maps of the physiological blind spot in human visual cortex.

The physiological blind spot is a naturally occurring scotoma corresponding with the optic disc in the retina of each eye. Even during monocular viewing, observers are usually oblivious to the scotoma, in part because the visual system extrapolates information from the surrounding area. Unfortunately, studying this visual field region with neuroimaging has proven difficult, as it occupies only a small part of retinotopic cortex. Here, we used functional magnetic resonance imaging and a novel data-driven method for mapping the retinotopic organization in and around the blind spot representation in V1. Our approach allowed for highly accurate reconstructions of the extent of an observer's blind spot, and out-performed conventional model-based analyses. This method opens exciting opportunities to study the plasticity of receptive fields after visual field loss, and our data add to evidence suggesting that the neural circuitry responsible for impressions of perceptual completion across the physiological blind spot most likely involves regions of extrastriate cortex-beyond V1.

Eye-specific 3D modeling of factors influencing oxygen concentration in the lamina cribrosa.

Our goal was to identify the factors with the strongest influence on the minimum lamina cribrosa (LC) oxygen concentration as potentially indicative of conditions increasing hypoxia risk. Because direct measurement of LC hemodynamics and oxygenation is not yet possible, we developed 3D eye-specific LC vasculature models. The vasculature of a normal monkey eye was perfusion-labeled post-mortem. Serial cryosections through the optic nerve head were imaged using fluorescence and polarized light microscopy to visualize the vasculature and collagen, respectively. The vasculature within a 450 µm-thick region containing the LC - identified from the collagen, was segmented, skeletonized, and meshed for simulations. Using Monte Carlo sampling, 200 vascular network models were generated with varying vessel diameter, neural tissue oxygen consumption rate, inflow hematocrit, and blood pressures (arteriole, venule, anterior boundary, and posterior boundary). Factors were varied over ranges of baseline ±20% with uniform probability. For each model we first obtained the blood flow, and from this the neural tissue oxygen concentration. ANOVA was used to identify the factors with the strongest influence on the minimum (10th percentile) oxygen concentration in the LC. The three most influential factors were, in ranked order, vessel diameter, neural tissue oxygen consumption rate, and arteriole pressure. There was a strong interaction between vessel diameter and arteriole pressure whereby the impact of one factor was larger when the other factor was small. Our results show that, for the eye analyzed, conditions that reduce vessel diameter, such as vessel compression due to elevated intraocular pressure or gaze-induced tissue deformation, may particularly contribute to decreased LC oxygen concentration. More eyes must be analyzed before generalizing.

Optic nerve-associated connective tissue structures revisited: A histological study using human fetuses and adult cadavers.

Unlike the usual peripheral nerve, the optic nerve accompanies a thick "dural sheath," a thin "sheath of pia mater" (SPM), and multiple "septa," which divides the nerve fibers into fascicles. We collected specimens from 25 adult cadavers and 15 fetuses and revisited the histological architecture of the optic and oculomotor nerves. In the optic chiasma, the meningeal layer of the dura joins the pia to form a thick SPM, and the periosteum of the sphenoid is continuous with the dural sheath at the orbital exit of the bony optic canal. The septa appeared as a cluster of irregularly arrayed fibrous plates in the intracranial course near the chiasma. Thus, the septa were not derived from either the SPM or the dural sheath. In the orbit, the central artery of the retina accompanies collagenous fibers from the dural sheath and the SPM to provide the vascular sheath in the optic nerve. These connective tissue configurations were the same between adult and fetal specimens. At the optic disk, the dural sheath and SPM merged with the sclera, whereas the septa appeared to end at the lamina cribrosa. However, in fetuses without lamina cribrosa, the septa extend into the nerve fiber layer of the retina. The SPM and septa showed strong elastin immunoreactivity, in contrast to the absence of reactivity in the sheaths of the oculomotor nerve. Each S100 protein-positive Schwann sheath of the oculomotor nerve was surrounded by collagenous endoneurium. Glial fibrillary acidic protein-positive astrocytes showed a linear arrangement along the septa.

A high-accuracy and high-efficiency digital volume correlation method to characterize in-vivo optic nerve head biomechanics from optical coherence tomography.

In-vivo optic nerve head (ONH) biomechanics characterization is emerging as a promising way to study eye physiology and pathology. We propose a high-accuracy and high-efficiency digital volume correlation (DVC) method to characterize the in-vivo ONH deformation from optical coherence tomography (OCT) volumes. Using a combination of synthetic tests and analysis of OCTs from monkey ONHs subjected to acutely elevated intraocular pressure, we demonstrate that our proposed methodology overcame several challenges for conventional DVC methods: First, a pre-registration technique was used to remove large ONH rigid body motion in OCT volumes which could lead to analysis failure; second, a modified 3D inverse-compositional Gaussian Newton method was used to ensure sub-voxel accuracy of displacement calculations despite high noise and low image contrast of some OCT volumes; third, a tricubic B-spline interpolation method was applied to improve computational efficiency; fourth, a confidence parameter was introduced to guide the searching path in the displacement calculation; fifth, a confidence-weighted strain calculation method was applied to further improve the accuracy. The proposed DVC method had displacement errors smaller than 0.037 and 0.028 voxels with Gaussian and speckle noises, respectively. The strain errors in the three directions were less than 0.0045 and 0.0018 with Gaussian and speckle noises, respectively. Compared with the conventional DVC method, the proposed method reduced the errors of displacement and strain calculations by up to 70% under large body motions, with 75% lower computation time, while saving about 30% memory. Our study demonstrates the potential of the proposed technique to investigate ONH biomechanics. STATEMENT OF SIGNIFICANCE: The biomechanics of the optic nerve head (ONH) in the posterior pole of the globe play a central role in eye physiology and pathology. The application of digital volume correlation (DVC) to the analysis of optical coherence tomography (OCT) images of the ONH has emerged as a promising way to quantify ONH biomechanics. Conventional DVC methods, however, face several important challenges when analyzing OCT images of the ONH. We introduce a high-accuracy and high-efficiency DVC method to characterize in vivo ONH deformations from OCT volumes. We demonstrate the new method using synthetic tests and actual OCT data from monkey ONHs. The new method also has the potential to be used to study other tissues, as OCT applications continue to expand.

Real-time imaging of optic nerve head collagen microstructure and biomechanics using instant polarized light microscopy.

Current tools lack the temporal or spatial resolution necessary to image many important aspects of the architecture and dynamics of the optic nerve head (ONH). We evaluated the potential of instant polarized light microscopy (IPOL) to overcome these limitations by leveraging the ability to capture collagen fiber orientation and density in a single image. Coronal sections through the ONH of fresh normal sheep eyes were imaged using IPOL while they were stretched using custom uniaxial or biaxial micro-stretch devices. IPOL allows identifying ONH collagen architectural details, such as fiber interweaving and crimp, and has high temporal resolution, limited only by the frame rate of the camera. Local collagen fiber orientations and deformations were quantified using color analysis and image tracking techniques. We quantified stretch-induced collagen uncrimping of lamina cribrosa (LC) and peripapillary sclera (PPS), and changes in LC pore size (area) and shape (convexity and aspect ratio). The simultaneous high spatial and temporal resolutions of IPOL revealed complex ONH biomechanics: i) stretch-induced local deformation of the PPS was nonlinear and nonaffine. ii) under load the crimped collagen fibers in the PPS and LC straightened, without torsion and with only small rotations. iii) stretch-induced LC pore deformation was anisotropic and heterogeneous among pores. Overall, with stretch the pores were became larger, more convex, and more circular. We have demonstrated that IPOL reveals details of collagen morphology and mechanics under dynamic loading previously out of reach. IPOL can detect stretch-induced collagen uncrimping and other elements of the tissue nonlinear mechanical behavior. IPOL showed changes in pore morphology and collagen architecture that will help improve understanding of how LC tissue responds to load.

Mechanical Deformation of Peripapillary Retina in Response to Acute Intraocular Pressure Elevation.

Elevated intraocular pressure (IOP) may cause mechanical injuries to the optic nerve head (ONH) and the peripapillary tissues in glaucoma. Previous studies have reported the mechanical deformation of the ONH and the peripapillary sclera (PPS) at elevated IOP. The deformation of the peripapillary retina (PPR) has not been well-characterized. Here we applied high-frequency ultrasound elastography to map and quantify PPR deformation, and compared PPR, PPS and ONH deformation in the same eye. Whole globe inflation was performed in ten human donor eyes. High-frequency ultrasound scans of the posterior eye were acquired while IOP was raised from 5 to 30 mmHg. A correlation-based ultrasound speckle tracking algorithm was used to compute pressure-induced displacements within the scanned tissue cross sections. Radial, tangential, and shear strains were calculated for the PPR, PPS, and ONH regions. In PPR, shear was significantly larger in magnitude than radial and tangential strains. Strain maps showed localized high shear and high tangential strains in PPR. In comparison to PPS and ONH, PPR had greater shear and a similar level of tangential strain. Surprisingly, PPR radial compression was minimal and significantly smaller than that in PPS. These results provide new insights into PPR deformation in response of IOP elevation, suggesting that shear rather than compression was likely the primary mode of IOP-induced mechanical insult in PPR. High shear, especially localized high shear, may contribute to the mechanical damage of this tissue in glaucoma.

VASCULAR PERFUSION DENSITY MAPPING USING OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY COMPARING NORMAL AND OPTIC DISK PIT EYES.

PURPOSE: Optic disk pits (ODPs) are typically detected incidentally as small, gray, unilateral, oval-shaped excavation in the temporal optic disk on routine fundus examination. In this cross-sectional retrospective case series, we report optical coherence tomography angiography findings in patients with unilateral ODPs and describe changes in vessel perfusion associated with ODP. METHODS: A total of eight eyes (four with ODP and four normal contralateral) were included in this study. Patients were excluded if any other optic disk abnormalities were present. Spectral-domain optical coherence tomography angiography (AngioVue; Optovue, Fremont, CA) imaging was conducted to map the vascularization of three layers in the optic nerve over a 4.5-mm × 4.5-mm region. The radial peripapillary capillaries, the nerve head capillaries, and the choriocapillaris were automatically segmented based on the OCT system software, and the capillary perfusion density (CPD) was quantified for each layer. Kruskal-Wallis one-way analysis of variance was used to compare CPD in normal and ODP eyes of four patients with monocular ODP. RESULTS: Overall, CPD was lower in eyes with ODP compared with the contralateral normal eye in the radial peripapillary capillary (0.4521 ± 0.08 vs. 0.5505 ± 0.03, P = 0.08) and nerve head capillary layers (0.5461 ± 0.08 vs. 0.5989 ± 0.01, P = 0.08). Significantly lower CPD values were associated with ODP eyes in the radial peripapillary capillary layer within the disk (P = 0.04), inferior nasal (P = 0.04), and temporal (P = 0.02) regions and in the nerve head vessel layer within the disk region (P = 0.04). Significantly higher CPD values were associated with ODP eyes in the choriocapillaris layer within the nasal (P = 0.02), superior temporal (P = 0.02), and inferior temporal (P = 0.02) regions. Visual acuity was also decreased in ODP eyes at 0.4 ± 0.3 logarithm of the minimum angle of resolution units (20/50) compared with normal eyes at 0.1 ± 0.1 logarithm of the minimum angle of resolution units (20/25) (P = 0.12). CONCLUSION: This study demonstrated that the presence of an ODP is associated with decreased vascular density in some regions of the optic disk and reduced visual acuity.

Method for the biomechanical analysis of aqueous veins and perilimbal sclera by three-dimensional photoacoustic imaging and strain field calculation.

A method motivated by the eye's aqueous veins is described for the imaging and strain calculation within soft biological tissues. A challenge to the investigation of the biomechanics of the aqueous vein-perilimbal sclera tissue complex is resolution of tissue deformations as a function of intraocular pressure and the subsequent calculation of strain (a normalized measure of deformation). The method involves perfusion of the eye with a contrast agent during conduction of non-invasive, optical resolution photoacoustic microscopy. This imaging technique permits three-dimensional displacement measurements of tracked points on the inner walls of the veins which are used in a finite element model to determine the corresponding strains. The methods are validated against two standard strain measurement methods. Representative porcine globe perfusion experiments are presented that demonstrate the power of the method to determine complex strain fields in the veins dependent on intraocular pressure as well as vein anatomy. In these cases, veins are observed to move radially outward during increases in intraocular pressure and to possess significant spatial strain variation, possibly influenced by their branching patterns. To the authors' knowledge, these are the only such quantitative, data driven, calculations of the aqueous vein strains available in the open literature.

Effect of axial length on peripapillary microvasculature: An optical coherence tomography angiography study.

OBJECTIVE: To investigate the effects of axial length (AL) on the peripapillary microvascular density acquired from optical coherence tomography angiography (OCTA). METHODS: Retrospective observational study. A total of 111 eyes from 111 normal healthy subjects were examined. The subjects were divided into three groups according to the AL: Group 1 (AL: < 24.0 mm; 35 eyes), Group 2 (AL: 24.0-25.99 mm; 37 eyes), and Group 3 (AL: ≥ 26 mm; 39 eyes). Peripapillary OCTA images were acquired using 6× 6 mm angiography scans, and vessel density (VD) and perfusion density (PD) of the superficial capillary plexus were calculated automatically. VD and PD were compared among the three groups according to the distance from the optic disc (inner and outer rings). Linear regression analyses were also performed to identify clinical factors associated with average VD. RESULTS: The average ALs of Groups 1-3 were 23.33± 0.57, 25.05± 0.60, and 27.42± 0.82, respectively. Average VD (P = 0.009) and PD (P = 0.029) in the inner ring increased with increasing AL. However, average VD (P < 0.001) and PD (P < 0.001) in the outer ring decreased with AL increased; the same trends were found for the full areas (VD, p<0.001; PD, p = 0.001). Average VDs in the inner and outer rings were not associated (P = 0.938). CONCLUSIONS: Peripapillary VD and PD were significantly associated with AL. Depending on the distance from the disc, peripapillary VDs and PDs of the inner and outer rings were differentially affected by AL. Physicians should therefore consider the effects of AL in the analyses of peripapillary microvasculature.

Material properties and effect of preconditioning of human sclera, optic nerve, and optic nerve sheath.

The optic nerve (ON) is a recently recognized tractional load on the eye during larger horizontal eye rotations. In order to understand the mechanical behavior of the eye during adduction, it is necessary to characterize material properties of the sclera, ON, and in particular its sheath. We performed tensile loading of specimens taken from fresh postmortem human eyes to characterize the range of variation in their biomechanical properties and determine the effect of preconditioning. We fitted reduced polynomial hyperelastic models to represent the nonlinear tensile behavior of the anterior, equatorial, posterior, and peripapillary sclera, as well as the ON and its sheath. For comparison, we analyzed tangent moduli in low and high strain regions to represent stiffness. Scleral stiffness generally decreased from anterior to posterior ocular regions. The ON had the lowest tangent modulus, but was surrounded by a much stiffer sheath. The low-strain hyperelastic behaviors of adjacent anatomical regions of the ON, ON sheath, and posterior sclera were similar as appropriate to avoid discontinuities at their boundaries. Regional stiffnesses within individual eyes were moderately correlated, implying that mechanical properties in one region of an eye do not reliably reflect properties of another region of that eye, and that potentially pathological combinations could occur in an eye if regional properties are discrepant. Preconditioning modestly stiffened ocular tissues, except peripapillary sclera that softened. The nonlinear mechanical behavior of posterior ocular tissues permits their stresses to match closely at low strains, although progressively increasing strain causes particularly great stress in the peripapillary region.

Risk factors and visual outcome of Non-Arteritic Ischemic Optic Neuropathy (NAION): Experience of a tertiary center in Kuwait.

BACKGROUND: Non-arteritic ischemic optic neuropathy (NAION) is the most common acute optic neuropathy over the age of 50 years. NAION is commonly associated with systemic vascular risk factors (diabetes, hypertension, hyperlipidemia) and small cup-to-disc-ratio. We have assessed the prevalence risk factors of NAION and the visual outcome in patients referred to a tertiary ophthalmology center in Kuwait. MATERIALS AND METHODS: A retrospective review of new cases of NAION presenting within 2 weeks of onset were included and baseline clinical and demographics characteristic were determined. The prevalence of risk factors and the visual outcome (change in logMAR visual acuity, mean deviation of visual field) was compared between young NAION patients (below 50 years of age) and older NAION patients (over 50 years of age). The odds ratio of a final favorable visual outcome (visual acuity 20/40 or better) by age category was determined. RESULTS: Seventy-eight eyes of 78 patients with recent onset NAION were included in the study. The most prevalent risk factors for NAION in our subjects were diabetes (64.1%), small cup-to-disc ratio (61.5%), hyperlipidemia (51.3%) and hypertension (38.5%). Young NAION patients had better final logMAR visual acuity (0.55 +- 0.57) then older NAION patients (0.9 +- 0.73), (p = 0.03). Furthermore, young NAION patients were 2.8 times more likely to have a final visual acuity of 20/40 or better than older NAION patients, odds ratio (OR), 2.87; 95% confidence interval (CI), 1.12-7.40, Chi-square p-value = 0.03). CONCLUSION: There is a high prevalence of systemic vascular risk factors and small cup-to-disc ratio in NAION patients referred to our center across different age groups (below and above 50 years). Patients below the age of 50 years with NAION are more likely to have a final visual acuity of 20/40 or better than NAION patients above the age of 50 years.

Ultrasonic elastography to assess biomechanical properties of the optic nerve head and peripapillary sclera of the eye.

PURPOSE: To quantitatively investigate both optic nerve head (ONH) and peripapillary sclera (PPS) biomechanical properties of porcine eyes through an ultrasonic elastography imaging system in response to both increasing and decreasing intraocular pressure (IOP). METHODS: The Young's modulus of the ONH and PPS were assessed using our high resolution ultrasonic imaging system which utilized a mechanical shaker to induce shear waves and an off-axis aligned 40 MHz needle transducer to track micron-level displacement along the direction of wave propagation. In this study, imaging on a total of 8 ex vivo porcine eyes preloaded with IOPs from 6 mmHg to 30 mmHg was performed. To have a better understanding of the effect of varying IOP on biomechanics, both increasing and decreasing IOPs were investigated. RESULTS: The increase of the Young's modulus of ONH (92.4 ± 13.9 kPa at 6 mmHg to 224.7 ± 71.1 kPa at 30 mmHg) and PPS (176.8 ± 14.3 kPa at 6 mmHg to 573.5 ± 64.4 kPa at 30 mmHg) following IOP elevation could be observed in the reconstructed Young's modulus of the shear wave elasticity (SWE) imaging while the B-mode structural images remained almost unchanged. In addition, for the same IOP level, both ONH and PPS have a tendency to be stiffer with decreasing IOP as compared to increasing IOP. CONCLUSIONS: Our results demonstrate the feasibility of using our ultrasonic elastography system to investigate the stiffness mapping of posterior eye with high resolution in both increasing and decreasing IOPs, making this technique potentially useful for glaucoma.

Role of radially aligned scleral collagen fibers in optic nerve head biomechanics.

Collagen fibers organized circumferentially around the canal in the peripapillary sclera are thought to provide biomechanical support to the sensitive tissues within the optic nerve head (ONH). Recent studies have demonstrated the existence of a family of fibers in the innermost sclera organized radially from the scleral canal. Our goal was to determine the role of these radial fibers in the sensitivity of scleral canal biomechanics to acute increases in intraocular pressure (IOP). Following the same general approach of previous parametric sensitivity studies, we created nonlinear generic finite element models of a posterior pole with various combinations of radial and circumferential fibers at an IOP of 0 mmHg. We then simulated the effects of normal and elevated IOP levels (15 and 30 mmHg). We monitored four IOP-induced geometric changes: peripapillary sclera stretch, scleral canal displacement, lamina cribrosa displacement, and scleral canal expansion. In addition, we examined the radial (maximum tension) and through-thickness (maximum compression) strains within the ONH tissues. Our models predicted that: 1) radial fibers reduced the posterior displacement of the lamina, especially at elevated IOP; 2) radial fibers reduced IOP-induced radial strain within the peripapillary sclera and retinal tissue; and 3) a combination of radial and circumferential fibers maintained strains within the ONH at a level similar to those conferred by circumferential fibers alone. In conclusion, radial fibers provide support for the posterior globe, additional to that provided by circumferential fibers. Most importantly, a combination of both fiber families can better protect ONH tissues from excessive IOP-induced deformation than either alone.