Purpose The purpose of this study was to establish in vivo data acquisition and processing protocols for repeatable measurements of heartbeat-induced corneal displacements and strains in human eyes, using a high-frequency ultrasound elastography method, termed ocular pulse elastography (OPE). Methods Twenty-four volunteers with no known ocular diseases were recruited for this study. Intraocular pressure (IOP) and ocular pulse amplitude (OPA) were measured using a PASCAL Dynamic Contour Tonometer (DCT). An in vivo OPE protocol was developed to measure heartbeat-induced corneal displacements. Videos of the central 5.7 mm of the cornea were acquired using a 50-MHz ultrasound probe at 128 frames per second. The radiofrequency data of 1000 frames were analyzed using an ultrasound speckle tracking algorithm to calculate corneal displacements and quantify spectral and temporal characteristics. The intrasession and intersession repeatability of OPE- and DCT-measured parameters were also analyzed. Results The in vivo OPE protocol and setup were successful in tracking heartbeat-induced corneal motion using high-frequency ultrasound. Corneal axial displacements showed a strong cardiac rhythm, with good intrasession and intersession repeatability, and high interocular symmetry. Corneal strain was calculated in two eyes of two subjects, showing substantially different responses. Conclusions We demonstrated the feasibility of high-frequency ultrasound elastography for noninvasive in vivo measurement of the cornea's biomechanical responses to the intrinsic ocular pulse. The high intrasession and intersession repeatability suggested a robust implementation of this technique to the in vivo setting. Translational Relevance OPE may offer a useful tool for clinical biomechanical evaluation of the cornea by quantifying its response to the intrinsic pulsation.

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The cornea’s mechanical response to intraocular pressure elevations may alter in ectatic diseases such as keratoconus. Regional variations of mechanical deformation in normal and keratoconus eyes during intraocular pressure elevation have not been well-characterized. We applied a high-frequency ultrasound elastography technique to characterize the regional deformation of normal and keratoconus human corneas through the full thickness of corneal stroma. A cross-section centered at the corneal apex in 11 normal and 2 keratoconus human donor eyes was imaged with high-frequency ultrasound during whole globe inflation from 5 to 30 mmHg. An ultrasound speckle tracking algorithm was used to compute local tissue displacements. Radial, tangential, and shear strains were mapped across the imaged cross-section. Strains in the central (1 mm surrounding apex) and paracentral (1 to 4 mm from apex) regions were analyzed in both normal and keratoconus eyes. Additional regional analysis was performed in the eye with severe keratoconus presenting significant thinning and scarring. Our results showed that in normal corneas, the central region had significantly smaller tangential stretch than the paracentral region, and that within the central region, the magnitudes of radial and shear strains were significantly larger than that of tangential strain. The eye with mild keratoconus had similar shear strain but substantially larger radial strains than normal corneas, while the eye with severe keratoconus had similar overall strains as in normal eyes but marked regional heterogeneity and large strains in the cone region. These findings suggested regional variation of mechanical responses to intraocular pressure elevation in both normal and keratoconus corneas, and keratoconus appeared to be associated with mechanical weakening in the cone region, especially in resisting radial compression. Comprehensive characterization of radial, tangential, and shear strains through corneal stroma may provide new insights to understand the biomechanical alterations in 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.