Optic Nerve Head Deformations Research Articles

Optic Nerve Head in Case of Increased Intraocular Pressure, High Intracranial Pressure and Increased Intracranial Pressure with Simultaneous Intraocular Pressure

The optic nerve, as part of the central nervous system, is surrounded by meninges and cerebrospinal fluid (CSF). This review discusses the effects of increased intraocular pressure (IOP), elevated intracranial pressure (ICP), and the simultaneous rise in both pressures on the optic nerve head (ONH). Increased IOP, caused by the balance of aqueous humor production and drainage, can lead to glaucomatous optic neuropathy, particularly through mechanical and ischemic damage to the lamina cribrosa. Elevated ICP, characterized by increased CSF pressure, can result in optic nerve edema, impairing axonal transport and blood flow. The complex interactions between IOP and ICP are critical for understanding their combined impact on ONH deformation and glaucomatous damage. It is essential to consider both pressures in clinical evaluations and treatment strategies for optic nerve-related diseases. Recent studies suggest that both IOP and ICP influence the optic nerve head morphology and pathology, highlighting the importance of comprehensive management approaches. Further research is needed to elucidate the intricate dynamics of IOP and ICP in the pathogenesis of optic nerve diseases.

Effect of Eye Globe and Optic Nerve Morphologies on Gaze-Induced Optic Nerve Head Deformations.

The purpose of this study was to investigate the effect of globe and optic nerve (ON) morphologies and tissue stiffnesses on gaze-induced optic nerve head deformations using parametric finite element modeling and a design of experiment (DOE) approach. A custom software was developed to generate finite element models of the eye using 10 morphological parameters: dural radius, scleral, choroidal, retinal, pial and peripapillary border tissue thicknesses, prelaminar tissue depth, lamina cribrosa (LC) depth, ON radius, and ON tortuosity. A central composite face-centered design (1045 models) was used to predict the effects of each morphological factor and their interactions on LC strains induced by 13 degrees of adduction. Subsequently, a further DOE analysis (1045 models) was conducted to study the effects and potential interactions between the top five morphological parameters identified from the initial DOE study and five critical tissue stiffnesses. In the DOE analysis of 10 morphological parameters, the 5 most significant factors were ON tortuosity, dural radius, ON radius, scleral thickness, and LC depth. Further DOE analysis incorporating biomechanical parameters highlighted the importance of dural and LC stiffness. A larger dural radius and stiffer dura increased LC strains but the other main factors had the opposite effects. Notably, the significant interactions were found between dural radius with dural stiffness, ON radius, and ON tortuosity. This study highlights the significant impact of morphological factors on LC deformations during eye movements, with key morphological effects being more pronounced than tissue stiffnesses.

Optic Nerve Head Pulsatile Displacement in Open-Angle Glaucoma after Intraocular Pressure Reduction Measured by Optical Coherence Tomography: A Pilot Study.

This study investigated the effect of intraocular pressure (IOP) reduction on pulsatile displacement within the optic nerve head (ONH) in primary open-angle glaucoma (POAG) patients with and without axial myopia. Forty-one POAG patients (19 without myopia, 9 with axial myopia and 13 glaucoma with no intervention) participated. Swept-source optical coherence tomography (OCT) videos of the ONH were obtained before and after IOP-lowering treatment (medical or surgical) achieving a minimum IOP drop of 3 mmHg. A demons registration-based algorithm measured local pulsatile displacement maps within the ONH. Results demonstrated a significant 14% decrease in pulsatile tissue displacement in the non-myopic glaucoma cohort after intervention (p = 0.03). However, glaucoma patients with axial myopia exhibited no statistically significant change. There were no significant changes in the pulsatile ONH deformation in the control group. These findings suggest a potential link between IOP reduction and reduced pulsatile displacement within the ONH in POAG patients without myopia, offering new insights into the disease's pathophysiology and warranting further investigation into underlying mechanisms and clinical implications.

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.

Deep Optic Nerve Head Morphology in Tilted Disc Syndrome and Its Clinical Implication on Visual Damage.

To study deep optic nerve head (ONH) morphology in tilted disc syndrome (TDS) and identify factors associated with retinal nerve fiber layer (RNFL) defect. In patients with TDS, we evaluated the optic disc shape using the Bruch's membrane opening (BMO)-anterior scleral canal opening (ASCO) offset and measured the border tissue (BT) length, depth, and angle in the direction of the tilt, using radial ONH optical coherence tomography (OCT). We compared the parameters between the TDS groups with and without RNFL defects. Twenty-one eyes had no glaucomatous RNFL defect, and 38 eyes had a glaucomatous RNFL defect. The group with RNFL defects had a higher baseline IOP, larger tilt axis of BMO-ASCO optic disc margin (76.4° ± 14.5° vs. 87.9° ± 15.4°, P = 0.012), larger BMO-lamina cribrosa insertion (LCI) angle (25.6° ± 9.3° vs. 43.6° ± 15.2°, P < 0.001), and more lamina cribrosa (LC) defects (4.3% vs. 30.6%, P = 0.028) than without RNFL defects. The tilt axis and BMO-LCI angle were significant factors after adjusting for baseline IOP and LC defect. The BMO-LCI angle had excellent diagnostic power for glaucomatous RNFL defect in TDS, similar to the visual field mean deviation. OCT-based large deep ONH BT angle and tilt axis were factors associated with the presence of RNFL defects in TDS. The results suggest a mechanism of RNFL defect associated with structural ONH deformation. Further investigations are warranted to understand the role of ONH structures in a general population with and without optic disc tilt.

Dense optic nerve head deformation estimated using CNN as a structural biomarker of glaucoma progression.

To present a new structural biomarker for detecting glaucoma progression based on structural transformation of the optic nerve head (ONH) region over time. Dense ONH deformation was estimated using deep learning methods namely DDCNet-Multires, FlowNet2, and FlowNetCorrelation, and legacy computational methods namely the topographic change analysis (TCA) and proper orthogonal decomposition (POD) methods. A candidate biomarker was estimated as the average magnitude of deformation of the ONH and evaluated using longitudinal confocal scans of 12 laser treated and 12 contralateral normal eyes of 12 primates from the LSU Experimental Glaucoma Study (LEGS); and 36 progressing eyes and 21 longitudinal normal eyes from the UCSD Diagnostic Innovations in Glaucoma Study (DIGS). Area under the ROC curve (AUC) was used to assess the diagnostic accuracy of the biomarker. AUROC (95% CI) for LEGS were: 0.83 (0.79, 0.88) for DDCNet-Multires; 0.83 (0.78, 0.88) for FlowNet2; 0.83 (0.78, 0.88) for FlowNet-Correlation; 0.94 (0.91, 0.97) for POD; and 0.86 (0.82, 0.91) for TCA methods. For DIGS: 0.89 (0.80, 0.97) for DDCNet-Multires; 0.82 (0.71, 0.93) for FlowNet2; 0.93 (0.86, 0.99) for FlowNet-Correlation; 0.86 (0.76, 0.96) for POD; and 0.86 (0.77, 0.95) for TCA methods. Lower diagnostic accuracy of the learning-based methods for LEG study eyes were due to image alignment errors in confocal sequences. Deep learning methods trained to estimate generic deformation were able to estimate ONH deformation from image sequences and provided a higher diagnostic accuracy. Our validation of the biomarker using ONH sequences from controlled experimental conditions confirms the diagnostic accuracy of the biomarkers observed in the clinical population. Performance can be further improved by fine-tuning these networks using ONH sequences.

Peripapillary Retinoschisis in a Patient with Severe Primary Open Angle Glaucoma

Peripapillary retinoschisis is a rare finding that may be associated with the progression of primary open angle glaucoma (POAG). Potential pathophysiological mechanisms have been proposed to explain this association, such as acute and chronic increase in intraocular pressure, vitreopapillary traction, and Müller cell dysfunction from optic nerve head deformation. OCT imaging has revealed hyper-reflective strut-like pillars within the schisis cavity described as “bridging structures.” While peripapillary retinoschisis may spontaneously resolve, other strategies may include lowering intraocular pressure, intraocular injections, or pars plana vitrectomy.present a patient with peripapillary retinoschisis incidentally found during a workup for primary open angle glaucoma.

Adduction induces large optic nerve head deformations in subjects with normal-tension glaucoma

PurposeTo assess intraocular pressure (IOP)-induced and gaze-induced optic nerve head (ONH) strains in subjects with high-tension glaucoma (HTG) and normal-tension glaucoma (NTG).DesignClinic-based cross-sectional study.MethodsThe ONH from one eye of 228...

Distribution of the Retinal Microcirculation Based on the Morphology of the Optic Nerve Head in High Myopia

ABSTRACT Purpose To explore the retinal microvasculature of the optic nerve head and macula and their associations with the optic nerve head deformation in high myopia. Methods One hundred sixty-seven eyes from patients with high myopia (HM) were enrolled in a cross-sectional study. We have evaluated and measured characteristics like the tilt ratio of the optic disc, interpupillary vascular density (IVD), peripapillary vascular density (PVD), macular vascular density (MVD), subfoveal choroidal thickness (SFCT) and foveal avascular zone (FAZ). The subjects were classified as a non-tilt group (control group) and a tilt group based on the tilt index. The above parameters were utilized to compare the two groups. In addition, we collected the data from the subjects’ right eyes to analyze variance, the Kruskal-Wallis test, and the least significant difference. Results The patients were divided into the non-tilt group of ninety-one eyes and the tilt group of seventy-six eyes. We found that the IVD in the tilt group was more significant than in the non-tilt group (t = −2.794, P = .006). On the other hand, the PVD was less in the tilt group than in the non-tilt, especially in the NS, NI and IN directions (tNS = 3.782; tNI = 3.07; tIN = 2.086; P < .05). Interestingly, the values of PVD were the highest in temporal, second in superior and inferior and lowest in nasal. Concerning the fovea-DMVD (including fovea, parafovea and perifovea), we characterized them as more minor in the tilt group when compared to those in the non-tilt group (P < .05). Conclusion Herein, we discovered that the retinal microvasculature differed significantly in patients with HM according to the ONH morphology. In this population, lower PVD and thinner SFCT were associated with higher odds of the tilted optic disc. In addition, the other two characteristics, the IVD and DMVD, were affected by the ONH deformation. Finally, we showed that PVD demonstrated better predictability of rapid myopic progression than MVD.

A Potential Role of Acute Choroidal Expansion in Nonarteritic Anterior Ischemic Optic Neuropathy.

PurposeNonarteritic anterior ischemic optic neuropathy (NAION) has been associated with a thickened choroid at the optic nerve head (ONH). Here, we use computational modeling to better understand how choroidal expansion and choroidal geometry influence tissue deformation within the ONH relative to intraocular pressure (IOP) and intracranial pressure (ICP) effects.MethodsUsing a model of the posterior eye that included the sclera, peripapillary sclera, annular ring, pia mater, dura mater, neural tissues, Bruch's membrane, choroid, and lamina cribrosa, we examined how varying material properties of ocular tissues influenced ONH deformations under physiological and supra-physiological, or “pathological,” conditions. We considered choroidal expansion (c. 35 µL of expansion), elevated IOP (30 mm Hg), and elevated ICP (20 mm Hg), and calculated peak strains in the ONH relative to a baseline condition representing an individual in the upright position.ResultsSupra-physiological choroidal expansion had the largest impact on strains in the prelaminar neural tissue. In addition, compared to a tapered choroid, a “blunt” choroid insertion at the ONH resulted in higher strains. Elevated IOP and ICP caused the highest strains within the lamina cribrosa and retrolaminar neural tissue, respectively.ConclusionsAcute choroidal expansion caused large deformations of the ONH and these deformations were impacted by choroid geometry. These results are consistent with the concept that compartment syndrome due to the choroid geometry and/or expansion at the ONH contributes to NAION. Prolonged deformations due to supra-physiological loading may induce a mechanobiological response or ischemia, highlighting the potential impact of choroidal expansion on biomechanical strains in the ONH.

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 significanceThe 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.

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.

Finite element modeling of the complex anisotropic mechanical behavior of the human sclera and pia mater

Background and objectiveAccurate finite element (FE) simulation of the optic nerve head (ONH) depends on accurate mechanical properties of the load-bearing tissues. The peripapillary sclera in the ONH exhibits a depth-dependent, anisotropic, heterogeneous collagen fiber distribution. This study proposes a novel cable-in-solid modeling approach that mimics heterogeneous anisotropic collagen fiber distribution, validates the approach against published experimental biaxial tensile tests of scleral patches, and demonstrates its effectiveness in a complex model of the posterior human eye and ONH. MethodsA computational pipeline was developed that defines control points in the sclera and pia mater, distributes the depth-dependent circumferential, radial, and isotropic cable elements in the sclera and pia in a pattern that mimics collagen fiber orientation, and couples the cable elements and solid matrix using a mesh-free penalty-based cable-in-solid algorithm. A parameter study was performed on a model of a human scleral patch subjected to biaxial deformation, and computational results were matched to published experimental data. The new approach was incorporated into a previously published eye-specific model to test the method; results were then interpreted in relation to the collagen fibers’ (cable elements) role in the resultant ONH deformations, stresses, and strains. ResultsResults show that the cable-in-solid approach can mimic the full range of scleral mechanical behavior measured experimentally. Disregarding the collagen fibers/cable elements in the posterior eye model resulted in ∼20–60% greater tensile and shear stresses and strains, and ∼30% larger posterior deformations in the lamina cribrosa and peripapillary sclera. ConclusionsThe cable-in-solid approach can easily be implemented into commercial FE packages to simulate the heterogeneous and anisotropic mechanical properties of collagenous biological tissues.

Strain by virtual extensometers and video-imaging optical coherence tomography as a repeatable metric for IOP-Induced optic nerve head deformations

PurposeTo determine if in vivo strain response of the Optic Nerve Head (ONH) to IOP elevation visualized using Optical Coherence Tomography (OCT) video imaging and quantified using novel virtual extensometers was able to be provided repeatable measurements of tissue specific deformations. MethodsThe ONHs of 5 eyes from 5 non-human primates (NHPs) were imaged by Spectralis OCT. A vertical and a horizontal B-scan of the ONH were continuously recorded for 60 s at 6 Hz (video imaging mode) during IOP elevation from 10 to 30 mmHg. Imaging was repeated over three imaging sessions. The 2D normal strain was computed by template-matching digital image correlation using virtual extensometers. ANOVA F-test (F) was used to compare inter-eye, inter-session, and inter-tissue variability for the prelaminar, Bruch's membrane opening (BMO), lamina cribrosa (LC) and choroidal regions (against variance the error term). F-test of the ratio between inter-eye to inter-session variability was used to test for strain repeatability across imaging sessions (FIS). ResultsVariability of strain across imaging session (F = 0.7263, p = 0.4855) and scan orientation was not significant (F = 1.053, p = 0.3066). Inter session variability of strain was significantly lower than inter-eye variability (FIS = 22.63, p = 0.0428) and inter-tissue variability (FIS = 99.33 p = 0.00998). After IOP elevation, strain was highest in the choroid (−18.11%, p < 0.001), followed by prelaminar tissue (−11.0%, p < 0.001), LC (−3.79%, p < 0.001), and relative change in BMO diameter (−0.57%, p = 0.704). ConclusionsVirtual extensometers applied to video-OCT were sensitive to the eye-specific and tissue-specific mechanical response of the ONH to IOP and were repeatable across imaging sessions.

Gaze-evoked deformations of the optic nerve head in thyroid eye disease

PurposeTo assess gaze evoked deformations of the optic nerve head (ONH) in thyroid eye disease (TED), using computational modelling and optical coherence tomography (OCT).MethodsMultiple finite element models were constructed: one...

Age-dependent changes in visual sensitivity induced by moving fixation points in adduction and abduction using imo perimetry

Visual field (VF) testing has usually been performed with the central gaze as a fixed point. Recent publications indicated optic nerve head deformations induced by optic nerve traction force can promote the progression of optic neuropathies, including glaucoma. We generated a new static test protocol that adds 6° adduction and abduction to gaze position (fixation points) movement. The aim of this study was to investigate both whether quantifying VF sensitivities at lateral horizontal gaze positions is feasible and whether horizontal gaze positions change sensitivities differently in subjects of different ages. Healthy adult eyes from 29 younger (≤ 45 years) and 28 elderly (> 45 years) eyes were examined in this cross-sectional study. After VF testing with central gaze as a fixation point using 24 plus (1) imo static perimetry, subjects underwent VF testing with 6° adduction and 6° abduction as fixation points. The average mean sensitivities with central gaze, adduction, and abduction were 29.9 ± 1.0, 29.9 ± 1.3, and 30.0 ± 1.2 decibels (dB) in younger subjects and 27.7 ± 1.2, 27.5 ± 1.7, and 28.1 ± 1.3 dB in elderly subjects, respectively. Visual sensitivity in young healthy subjects was similar among the three fixation points, whereas visual sensitivity in elderly healthy subjects was significantly better with abduction as a fixation point than with central gaze and adduction (both p < 0.05). We expect this test protocol to contribute to our understanding of visual function during horizontal eye gaze movement in various eye diseases.

Retinal and Optic Nerve Deformations Due to Orbital Versus Intracranial Venous Hypertension.

Abnormal forces around the optic nerve head (ONH) due to orbital diseases, intracranial hypertension (IH), glaucoma, and space travel, are associated with alterations of the ONH shape. Elevated cerebral and ophthalmic venous pressure can contribute to stress and strain on the ONH and peripapillary retina. We hypothesize that IH and elevated ophthalmic venous pressure without IH cause different ONH and retinal changes. We compared MRI and spectral domain optical coherence tomography (SDOCT) findings in patients with cavernous sinus arteriovenous shunts (CSAVSs), where orbital venous pressure is known to be elevated, with patients with intracranial dural venous sinus thrombosis and secondary IH. We also compared the results to those obtained in the Idiopathic IH (IIH) Treatment Trial. Among 18 patients with dural venous sinus thrombosis, the MRI/magnetic resonance venography displayed partial empty sella (61%) and optic nerve sheath distension (67%). None exhibited ophthalmic vein dilation or signs of orbital congestion. SDOCT of these eyes and IIH eyes showed a similar frequency of abnormal thickening of the mean retinal nerve fiber layer, anterior displacement of the basement membrane opening, peripapillary wrinkles, retinal folds (RF), and choroidal folds (CF). Among 21 patients with CSAVSs, MRI showed ipsilateral dilated superior ophthalmic vein (76%) and orbital congestion (52%) without distension of the optic nerve sheath or globe distortion. SDOCT showed CF (19%), one with overlying RF, and no ONH deformations. SDOCT findings for dural venous sinus thrombosis are similar to those seen with IIH but distinct from changes due to local ophthalmic venous hypertension. These data support the concept that IH even if due to a vascular cause and local orbital venous hypertension cause different stresses and strains on the ONH.

Effect of Changing Heart Rate on the Ocular Pulse and Dynamic Biomechanical Behavior of the Optic Nerve Head.

PurposeTo study the effect of changing heart rate on the ocular pulse and the dynamic biomechanical behavior of the optic nerve head (ONH) using a comprehensive mathematical model.MethodsIn a finite element model of a healthy eye, a biphasic choroid consisted of a solid phase with connective tissues and a fluid phase with blood, and the lamina cribrosa (LC) was viscoelastic as characterized by a stress-relaxation test. We applied arterial pressures at 18 ocular entry sites (posterior ciliary arteries), and venous pressures at four exit sites (vortex veins). In the model, the heart rate was varied from 60 to 120 bpm (increment: 20 bpm). We assessed the ocular pulse amplitude (OPA), pulse volume, ONH deformations, and the dynamic modulus of the LC at different heart rates.ResultsWith an increasing heart rate, the OPA decreased by 0.04 mm Hg for every 10 bpm increase in heart rate. The ocular pulse volume decreased linearly by 0.13 µL for every 10 bpm increase in heart rate. The storage modulus and the loss modulus of the LC increased by 0.014 and 0.04 MPa, respectively, for every 10 bpm increase in heart rate.ConclusionsIn our model, the OPA, pulse volume, and ONH deformations decreased with an increasing heart rate, whereas the LC became stiffer. The effects of blood pressure/heart rate changes on ONH stiffening may be of interest for glaucoma pathology.

Three-Dimensional Inflation Response of Porcine Optic Nerve Head Using High-Frequency Ultrasound Elastography.

Characterization of the biomechanical behavior of the optic nerve head (ONH) in response to intraocular pressure (IOP) elevation is important for understanding glaucoma susceptibility. In this study, we aimed to develop and validate a three-dimensional (3D) ultrasound elastographic technique to obtain mapping and visualization of the 3D distributive displacements and strains of the ONH and surrounding peripapillary tissue (PPT) during whole globe inflation from 15 to 30 mmHg. 3D scans of the posterior eye around the ONH were acquired through full tissue thickness with a high-frequency ultrasound system (50 MHz). A 3D cross-correlation-based speckle-tracking algorithm was used to compute tissue displacements at ∼30,000 kernels distributed within the region of interest (ROI), and the components of the strain tensors were calculated at each kernel by using least square estimation of the displacement gradients. The accuracy of displacement calculation was evaluated using simulated rigid-body translation on ultrasound radiofrequency (RF) data obtained from a porcine posterior eye. The accuracy of strain calculation was evaluated using finite element (FE) models. Three porcine eyes were tested showing that ONH deformation was heterogeneous with localized high strains. Substantial radial (i.e., through-thickness) compression was observed in the anterior ONH and out-of-plane (i.e., perpendicular to the surface of the shell) shear was shown to concentrate in the vicinity of ONH/PPT border. These preliminary results demonstrated the feasibility of this technique to achieve comprehensive 3D evaluation of the mechanical responses of the posterior eye, which may provide mechanistic insights into the regional susceptibility in glaucoma.

PRELIMINARY STUDY ON THE BLOCKADE OF AXONAL TRANSPORT BY ACTIVATED ASTROCYTES IN OPTIC NERVE HEAD UNDER CHRONIC OCULAR HYPERTENSION

Glaucoma is considered a group of neurodegenerative diseases that damage the optic disc and result in a reduction of the field of vision. High intraocular pressure-induced deformation of optic nerve head (ONH) may compress the optic nerve and affect axonal transport. This study aims to show experimental observations: the activated astrocytes under high intraocular pressure play an important role in compression of optic nerve and block of axonal transport. Four-week duration of ocular hypertension (more than 20[Formula: see text]mm Hg) rats induced by cauterizing of three episcleral vessels and administering a fluorouracil subconjunctival injection in the right eye were enrolled and the left eyes of all the rats were used as a self-control. The axonal transport of the optic nerve was examined by a confocal laser scanning microscope after intravitreally injecting rhodamine-[Formula: see text]-isothiocyanate. The morphology of the optic nerve head was examined by hematoxylin–eosin (HE) staining, immunofluorescence staining and transmission electron microscopy (TEM). The results showed transport of rhodamine-[Formula: see text]-isothiocyanate was blocked in the experimental group, and fluorescent dye accumulated around the ONH. The nucleus counts of the coronal section kidney-shaped area showed that the number of cell nucleus in experimental eye was more than that of the control according to the results of HE staining. The increased collagen fibers in ONH were observed. The density of the glial fibrillary acidic protein in experimental eyes was a little bit higher than that in the control group by quantify analysis of the expression. The obvious changes of microstructure of the ONH also were found according to the images of TEM. It can be concluded that the activated astrocytes might squeeze the optic nerve, likely leading to optic nerve distortion and axonal flow blockage.