Purpose:In vivo biomechanical characterization of the cornea remains a challenge. We have developed a high-resolution ultrasound elastography technique, termed ocular pulse elastography (OPE), to measure corneal deformation in response to the intraocular pressure (IOP) pulsation at each heartbeat. In this study, we aimed to compare corneal axial strains (CASs) between patients with keratoconus and normal subjects and evaluate the spatial mapping of CAS in high grade keratoconus. Methods:Forty patients with keratoconus (63 eyes) and 40 normal controls (80 eyes) were enrolled in this study. Each eye underwent 4 ultrasound measurements using the Vevo2100 high-frequency ultrasound system. Each measurement acquired 1000 continuous B-mode scans in 8 seconds. Corneal axial displacements and strains were quantified using an ultrasound speckle tracking algorithm. Results:CAS magnitude was significantly higher in keratoconus than normal corneas (-0.13% ± 0.09% vs. -0.06% ± 0.04%, P < 0.001) with an increasing trend in higher grades (P < 0.001). CAS in keratoconus corneas had a greater spatial variance as higher strains were observed in the cone center than its surrounding regions in grade 3 and 4 keratoconus corneas. Conclusions:Our results showed that high-frequency ultrasound elastography was able to detect and quantify the larger deformation of keratoconus corneas than normal corneas in response to the natural fluctuations of IOP at each heartbeat, and it also detected the spatial variance showing greater deformation in the cone region. Translational Relevance:High-resolution ultrasound may provide a sensitive tool for quick, spatially resolved characterization of corneal biomechanics to aid keratoconus detection and diagnosis.

The anisotropic mechanical properties of fiber-embedded biological tissues are essential for understanding their development, aging, disease progression, and response to therapy. However, accurate and fast assessment of mechanical anisotropy in vivo using elastography remains challenging. To address the dilemma of achieving both accuracy and efficiency in this inverse problem involving complex wave equations, we propose a computational framework that utilizes the traveling wave expansion model. This framework leverages the unique wave characteristics of transversely isotropic material and physically meaningful operator combinations. The analytical solutions for inversion are derived and engineering optimization is made to adapt to actual scenarios. Measurement results using simulations, ex vivo muscle tissue, and in vivo human white matter validate the framework in determining in vivo anisotropic biomechanical properties, highlighting its potential for measurement of a variety of fiber-embedded biological tissues.

Computational models predicted that peripapillary sclera (PPS) stiffening may reduce intraocular pressure (IOP) induced stresses and strains at the optic nerve head (ONH). Experimental studies in animal models of glaucoma however did not confirm such benefit. In this study, we used high-resolution ultrasound elastography to quantify PPS and ONH strains to evaluate biomechanical changes associated with PPS stiffening. Sixteen pairs of porcine globes were used. One globe in each pair was randomly assigned to the stiffening or the control group. Inflation tests were performed before and after treatment with 1.25 % glutaraldehyde (stiffening group) or saline (control group). IOP was raised from 5 to 30 mmHg while 2D cross-sectional images of the PPS and ONH were obtained using a 50 MHz ultrasound probe. PPS and ONH displacements and strains were calculated using a validated ultrasound speckle tracking algorithm. In the stiffening group, there was an increase in ONH shear strain (by 11.8 %, P = 0.025) and an increase in the posterior displacement of the ONH relative to PPS (P < 0.001). In contrast, ONH shear strain decreased (by 8.1%, P=0.006) and the relative ONH posterior displacement did not change in the control group. ONH tangential strains were reduced in both groups, but more so in the stiffening group. These results suggest that the biomechanical effects of PPS stiffening are complex. While a reduction of ONH tangential strain could be protective, the concomitant increase in ONH shear strain and ONH posterior displacement could be detrimental. Future studies are needed to optimize PPS biomechanical properties for neuroprotection.

PURPOSE . A thin cornea is a potent risk factor for glaucoma. The underlying mechanisms remain unexplained. It has been postulated that central corneal thickness (CCT) may be a surrogate for biomechanical parameters of the posterior eye. In this study, we aimed to explore correlations of biomechanical responses between the cornea and the optic nerve head (ONH) and the peripapillary sclera (PPS) to elevated intraocular pressure (IOP), the primary risk factor of glaucoma. METHODS . Inflation tests were performed in nine pairs of human donor globes. One eye of each pair was randomly assigned for cornea or posterior eye inflation. IOP was raised from 5 to 30 millimeters of mercury (mmHg) at 0.5 mmHg steps in the whole globe and the cornea or the ONH/PPS was imaged using a 50 MHz ultrasound probe. Correlationbased ultrasound speckle tracking was used to calculate tissue displacements and strains. Associations of radial, tangential, and shear strains at 30 mmHg between the cornea and the ONH or PPS were evaluated. RESULTS . Corneal shear strain was significantly correlated with ONH shear strain ( R = 0.857, P = 0.003) and PPS shear strain ( R = 0.724, P = 0.028). CCT was not correlated with any strains in the cornea, ONH, or PPS. CONCLUSIONS . Our results suggested that an eye that experiences a larger shear strain in the cornea would likely experience a larger shear strain in its ONH and PPS at IOP elevations. The strong correlation between the cornea's and the ONH's shear response to IOP provides new insights and suggests a plausible explanation of the cornea's connection to glaucoma risk.

The ocular lens is the primary organ within the eye responsible for accommodation. During accommodation, the lens is subject to biomechanical forces. We previously demonstrated that stretching the porcine lens can increase lens epithelial cell proliferation. Although murine lenses are commonly employed in lens research, murine lens stretching has remained unexplored. Murine lens stretching thus represents a novel source of potential discovery in lens research. In the present study, we describe a method for stretching the murine lens by compressing the murine globe embedded in a hydrogel. We hypothesized that, as the eye is compressed along the optic axis, the lens would stretch through zonular tension due to the equatorial region of the eye bulging outward. Our results showed that this led to a compression-dependent increase in murine lens epithelial cell proliferation, suggesting that compression of the embedded murine globe is a viable technique for studying the mechanobiology of the lens epithelium.

PURPOSE. High-frequency ultrasound elastography offers a tool to resolve the complex and heterogeneous deformation through the full thickness of the optic nerve head (ONH) and peripapillary sclera (PPS). Using this tool, we quantified the three-dimensional deforma-tion of the ONH and PPS in human donor eyes and evaluated age-associated changes.METHODS. The ONH and PPS in 15 human donor globes were imaged with a 50-MHz ultrasound probe while increasing intraocular pressure (IOP) from 15 to 30 mm Hg. Tissue displacements were obtained using correlation-based ultrasound speckle tracking. Three-dimensional spherical strains (radial, circumferential, meridional, and respective shear strains) were calculated for the ONH and PPS volumes segmented from three-dimensional ultrasound images. Age-related trends of different strains in each region of interest were explored.RESULTS. The dominant form of IOP-induced deformation in the ONH and PPS was radial compression. High-magnitude localized out-of-plane shear strains were also observed in both regions. Most strains were concentrated in the anterior one-half of the ONH and PPS. The magnitude of radial and volumetric strains increased with age in the anterior ONH and anterior PPS, indicating greater radial compression and volume loss during IOP elevation in older age.CONCLUSIONS. The age-associated increase of radial compression, the predominant form of IOP-induced deformation in anterior ONH and PPS, may underlie age-associated glau-coma risk. High-frequency ultrasound elastography offers a useful tool to quantify all types of deformation comprehensively in all regions of ONH and PPS, which may improve our understanding of the biomechanical factors contributing to glaucoma risk.

In vivo biomechanical characterization of the cornea remains a challenge. We have developed a high-frequency ultrasound elastography method, the ocular pulse elastography (OPE), to measure corneal axial displacement (CAD) induced by the ocular pulse. Here we compared CAD and a stiffness index derived from CAD between keratoconus patients and normal controls. We also explored the trend of these parameters with keratoconus grade. Twenty normal subjects and twenty keratoconus patients were recruited in this study. Corneal topography, tomography, intraocular pressure (IOP) and ocular pulse amplitude (OPA) were obtained in each measured eye. The cornea’s heartbeat-induced cyclic axial displacements were measured by high-frequency (50 MHz) ultrasound. A corneal stiffness index (CSI) was derived from CAD normalized against OPA. CAD and CSI were compared between normal and keratoconus groups, and across keratoconus grades. Keratoconus corneas had significantly greater CAD and lower CSI than normal controls (p’s<0.01). Both parameters correlated strongly with grade, in which CAD increased significantly (p = 0.002) and CSI decreased significantly (p = 0.011) with grade. These results suggested a biomechanical weakening in keratoconus which worsens at higher disease severity. This study also demonstrated the ability of high-frequency ultrasound elastography to provide a safe, quick, and accurate evaluation of the cornea’s biomechanical condition in vivo. The OPE-measured biomechanical metrics, when integrated with existing diagnostic criteria, may aid the decision-making in the early and definitive diagnosis and staging of keratoconus.

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.

PURPOSE To establish a method to determine central corneal thickness (CCT) and anterior chamber depth (ACD) of an air-puff-deformed cornea at the highest concavity (HC) state. METHODS The Fink method for refractive correction of Scheimpflug images of a convex pre-deformed (PRE) cornea was implemented for 155 eyes of 155 participants imaged with the Corvis ST (Oculus Optikgeräte GmbH). This method was subsequently modified for the HC state of deformation. The tracked edges of each participant's cornea were exported at the PRE and HC states. Ten participants who had a visible crystalline lens in the image were selected to determine ACD in both states. The center points on the corneal tracked edges and lens were used to determine uncorrected CCT and ACD, respectively. RESULTS Average undeformed CCTPRE was significantly lower than deformed CCTHC (584 ± 31 and 626 ± 34 µm, respectively) (P < .0001). No significant difference was found for the corrected ACD between the two states. Corrected CCT and ACD were significantly greater than the corresponding uncorrected values for both deformation states (P < .0001). Percent change in CCT was found to be correlated to change in arc length at HC (P < .0001). CONCLUSIONS Distortion in Corvis ST images at the HC state can be corrected using a modified Fink method. CCT was found to increase in the HC state, compared to the PRE state. The CCT change during deformation may be important in the study of the compressive response of the cornea. [J Refract Surg. 2021;37(6):422-428.].

Pressure overload (PO) and volume overload (VO) of the heart result in distinctive changes to geometry, due to compensatory structural remodeling. This remodeling potentially leads to changes in tissue mechanical properties. Understanding such changes is important, as tissue modulus has an impact on cardiac performance, disease progression, and influences on cell phenotype. Pressure-volume (PV) loop analysis, a clinically relevant method for measuring left ventricular (LV) chamber stiffness, was performed in vivo on control rat hearts and rats subjected to either chronic PO through Angiotensin-II infusion (4-weeks) or VO (8-weeks). Immediately following PV loops, biaxial testing was performed on LV free wall tissue to directly measure tissue mechanical properties. The beta coefficient, an index of chamber stiffness calculated from the PV loop analysis, increased 98% in PO (n = 4) and decreased 38% in VO (n = 5) compared to control (n = 6). Material constants of LV walls obtained from ex vivo biaxial testing (n = 9-10) were not changed in Angiotensin-II induced PO and decreased by about half in VO compared to control (47% in the circumferential and 57% the longitudinal direction). PV loop analysis showed the expected increase in chamber stiffness of PO and expected decrease in chamber stiffness of VO. Biaxial testing showed a decreased modulus of the myocardium of the VO model, but no changes in the PO model, this suggests the increased chamber stiffness in PO, as shown in the PV loop analysis, may be secondary to changes in tissue mass and/or geometry but not an increase in passive tissue mechanical properties.