Function Of Intraocular Pressure Research Articles

Optical coherence elastography measures the biomechanical properties of the ex vivo porcine cornea after LASIK.

The biomechanical impact of refractive surgery has long been an area of investigation. Changes to the cornea structure cause alterations to its mechanical integrity, but few studies have examined its specific mechanical impact. To quantify how the biomechanical properties of the cornea are altered by laser assisted in situ keratomileusis (LASIK) using optical coherence elastography (OCE) in ex vivo porcine corneas. Three OCE techniques, wave-based air-coupled ultrasound (ACUS) OCE, heartbeat (Hb) OCE, and compression OCE were used to measure the mechanical properties of paired porcine corneas, where one eye of the pair was left untreated, and the fellow eye underwent LASIK. Changes in stiffness as a function of intraocular pressure (IOP) before and after LASIK were measured using each technique. ACUS-OCE showed that corneal stiffness changed as a function of IOP for both the untreated and the treated groups. The elastic wave speed after LASIK was lower than before LASIK. Hb-OCE and compression OCE showed regional changes in corneal strain after LASIK, where the absolute strain difference between the cornea anterior and posterior increased after LASIK. The results of this study suggest that LASIK may soften the cornea and that these changes are largely localized to the region where the surgery was performed.

Multiple Optical Elastography Techniques Reveal the Regulation of Corneal Stiffness by Collagen XII.

Collagen XII plays a role in regulating the structure and mechanical properties of the cornea. In this work, several optical elastography techniques were used to investigate the effect of collagen XII deficiency on the stiffness of the murine cornea. A three-prong optical elastography approach was used to investigate the mechanical properties of the cornea. Brillouin microscopy, air-coupled ultrasonic optical coherence elastography (OCE) and heartbeat OCE were used to assess the mechanical properties of wild type (WT) and collagen XII-deficient (Col12a1-/-) murine corneas. The Brillouin frequency shift, elastic wave speed, and compressive strain were all measured as a function of intraocular pressure (IOP). All three optical elastography modalities measured a significantly decreased stiffness in the Col12a1-/- compared to the WT (P < 0.01 for all three modalities). The optical coherence elastography techniques showed that mean stiffness increased as a function of IOP; however, Brillouin microscopy showed no discernable trend in Brillouin frequency shift as a function of IOP. Our approach suggests that the absence of collagen XII significantly softens the cornea. Although both optical coherence elastography techniques showed an expected increase in corneal stiffness as a function of IOP, Brillouin microscopy did not show such a relationship, suggesting that the Brillouin longitudinal modulus may not be affected by changes in IOP. Future work will focus on multimodal biomechanical models, evaluating the effects of other collagen types on corneal stiffness, and in vivo measurements.

Torsional wave elastography to assess the mechanical properties of the cornea

Corneal mechanical changes are believed to occur before any visible structural alterations observed during routine clinical evaluation. This study proposed developing an elastography technique based on torsional waves (TWE) adapted to the specificities of the cornea. By measuring the displacements in the propagation plane perpendicular to the axis of the emitter, the effect of guided waves in plate-like media was proven negligible. Ex vivo experiments were carried out on porcine corneal samples considering a group of control and one group of alkali burn treatment (hbox {NH}_text {4}OH) that modified the mechanical properties. Phase speed was recovered as a function of intraocular pressure (IOP), and a Kelvin-Voigt rheological model was fitted to the dispersion curves to estimate viscoelastic parameters. A comparison with uniaxial tensile testing with thin-walled assumptions was also performed. Both shear elasticity and viscosity correlated positively with IOP, being the elasticity lower and the viscosity higher for the treated group. The viscoelastic parameters ranged from 21.33 to 63.17 kPa, and from 2.82 to 5.30 Pa s, for shear elasticity and viscosity, respectively. As far as the authors know, no other investigations have studied this mechanical plane under low strain ratios, typical of dynamic elastography in corneal tissue. TWE reflected mechanical properties changes after treatment, showing a high potential for clinical diagnosis due to its rapid performance time and paving the way for future in vivo studies.

Analysis of vitreous opacities in chronic glaucoma by vitreo‐optical coherence tomography imaging

AbstractPurposeTo analyze the vitreous opacities of rat eyes by optical coherence tomography (OCT) in two models of chronic glaucoma. Hyperreflective opacities at the vitreoretinal interface, their dynamics over time (changes in number, size, intensity, eccentricity, and orientation) and as a function of intraocular pressure were analyzed in two different glaucoma models and compared to healthy controls.MethodsImages of the vitreoretinal interface were obtained by OCT and exported as videos (composed of cross‐sectional images acquired by means of 61 b‐scans measuring around 3 mm in length and centred on the optic nerve). These videos were analysed using a custom program implemented in Matlab. The vitreous opacities, closely related to the immune cells, were analysed.ResultsHyperreflective opacities, extrapolated as soma areas, were classified according to their size: isolated cells (&lt;10 μm2), non‐activated cells (10–50 μm2), activated cells (50–250 μm2) and cell complexes (&gt;250 μm2). In glaucoma models, right eyes showed significant increase of total area compared with left non‐induced eyes, and left eyes showed significant increase compared to healthy controls. The physiological number of opacities was 10–20. Glaucoma‐induced right eyes showed a mean of 70 opacities, a specular response between activated cells and non‐activated cells, and a greater variation in intensity in the smallest cells, that showed an early change in orientation compared with physiological eyes.ConclusionsOur method of analyzing vitreous opacities by OCT could serve as a reliable neuroimaging biomarker to detect disease onset and early progression applicable to glaucoma and potentially other neurodegenerative diseases impacting the retina and optic nerve.

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.

Nearly-incompressible transverse isotropy (NITI) of cornea elasticity: model\xa0and experiments with acoustic micro-tapping OCE

The cornea provides the largest refractive power for the human visual system. Its stiffness, along with intraocular pressure (IOP), are linked to several pathologies, including keratoconus and glaucoma. Although mechanical tests can quantify corneal elasticity ex vivo, they cannot be used clinically. Dynamic optical coherence elastography (OCE), which launches and tracks shear waves to estimate stiffness, provides an attractive non-contact probe of corneal elasticity. To date, however, OCE studies report corneal moduli around tens of kPa, orders-of-magnitude less than those (few MPa) obtained by tensile/inflation testing. This large discrepancy impedes OCE’s clinical adoption. Based on corneal microstructure, we introduce and fully characterize a nearly-incompressible transversely isotropic (NITI) model depicting corneal biomechanics. We show that the cornea must be described by at least two shear moduli, contrary to current single-modulus models, decoupling tensile and shear responses. We measure both as a function of IOP in ex vivo porcine cornea, obtaining values consistent with both tensile and shear tests. At pressures above 30 mmHg, the model begins to fail, consistent with non-linear changes in cornea at high IOP.

Conceptual design considerations for a wireless intraocular pressure sensor system for effective glaucoma management

As a leading form of preventable visual impairment, it is imperative to assess glaucoma treatment as a function of intraocular pressure (IOP). IOP can spike throughout the day. This necessitates a device that can (1) monitor IOP outside of clinical visits by providing a memory when IOP exceeds a set threshold indicating the possibility for glaucomatous damage to occur; and (2) accurately assess IOP. Both requirements point ultimately towards the development of an implantable device. The Wireless Intraocular Pressure Sensor System (WIPSS) devised by our team uses optical technologies and may assist an overseeing clinician with assessing glaucoma treatment efficacy and avoiding irreversible glaucomatous visual field loss downstream.

Dynamic optical coherence elastography: Emerging tool for noninvasive quantification of mechanical properties of ocular tissues

Optical coherence elastography (OCE) is an emerging method for noninvasive quantification of tissue viscoelastic properties. The underlying technology is based on Optical Coherence Tomography (OCT) imaging and analysis of external (or internal) force-induced mechanical waves propagating through the tissue. In this presentation, I will overview recent progress made in my lab on quantification of mechanical properties of ocular tissues (such as cornea and the lens of the eye) using OCE and their alternations during diseases progression. In particular, I will demonstrate that it is possible to quantify mechanical properties of the cornea and lens as a function of Intra-Ocular Pressure (IOP) and during controlled tissue modifications and treatments, such as corneal cross-linking. These results indicate that OCE is a powerful new technology that can be utilized for the nondestructive biomechanical characterization of ocular tissues in normal and pathological states and could not only assist in basic biomechanical studies but also lead to a new class of optical sensors for diagnosis of diseases. [Work supported, in part, by the U.S. National Institutes of Health (NIH) under Grant Nos. 2R01EY022362 and 1R01HL120140 and U.S. Department of Defense (DOD) Congressionally Directed Medical Research Programs (CDMRP) under Grant No. PR150338.]

Measuring the elastic wave velocity in the lens of the eye as a function of intraocular pressure using optical coherent elastography

The dependence of the elastic properties of the eye lens on the intraocular pressure is investigated in porcine eyes ex vivo. To measure the stiffness of the lens, the method of dynamic optical coherent elastography is used, in which the propagation velocity of surface elastic waves in the lens is measured using phase-sensitive optical coherent tomography. Measurement data show an increase in Young’s modulus of the lens by ∼30% with an increase in intraocular pressure from 10 to 40 mm Hg. This result allows us to conclude that the effect of intraocular pressure on the rigidity of the lens is less significant than on the rigidity of other eye tissues, such as the cornea and sclera. The method of optical coherent elastography makes it possible to measure the elastic properties of the lens without removing it from the eyeball and has considerable potential for clinical use.

Assessing the biomechanical properties of the porcine crystalline lens as a function of intraocular pressure with optical coherence elastography.

In this study, we investigated the relationship between the biomechanical properties of the crystalline lens and intraocular pressure (IOP) using a confocal acoustic radiation force (ARF) and phase-sensitive optical coherence elastography (OCE) system. ARF induced a small displacement at the apex of porcine lenses in situ at various artificially controlled IOPs. Maximum displacement, relaxation rate, and Young's modulus were utilized to assess the stiffness of the crystalline lens. The results showed that the stiffness of the crystalline increased as IOP increased, but the lens stiffening was not as significant as the stiffening of other ocular tissues such as the cornea and the sclera. A mechanical hysteresis in the lens was also observed while cycling IOP, indicating that the viscoelastic response of the lens is crucial to fully understanding its biomechanical properties.

Optical coherence elastography assessment of corneal viscoelasticity with a modified Rayleigh-Lamb wave model

The biomechanical properties of the cornea play a critical role in forming vision. Diseases such as keratoconus can structurally degenerate the cornea causing a pathological loss in visual acuity. UV-A/riboflavin corneal collagen crosslinking (CXL) is a clinically available treatment to stiffen the cornea and restore its healthy shape and function. However, current CXL techniques do not account for pre-existing biomechanical properties of the cornea nor the effects of the CXL treatment itself. In addition to the inherent corneal structure, the intraocular pressure (IOP) can also dramatically affect the measured biomechanical properties of the cornea. In this work, we present the details and development of a modified Rayleigh-Lamb frequency equation model for quantifying corneal biomechanical properties. After comparison with finite element modeling, the model was utilized to quantify the viscoelasticity of in situ porcine corneas in the whole eye-globe configuration before and after CXL based on noncontact optical coherence elastography measurements. Moreover, the viscoelasticity of the untreated and CXL-treated eyes was quantified at various IOPs. The results showed that the stiffness of the cornea increased after CXL and that corneal stiffness is close to linear as a function of IOP. These results show that the modified Rayleigh-Lamb wave model can provide an accurate assessment of corneal viscoelasticity, which could be used for customized CXL therapies.

Investigating Elastic Anisotropy of the Porcine Cornea as a Function of Intraocular Pressure With Optical Coherence Elastography

To evaluate the elastic anisotropy of porcine corneas at different intraocular pressures (IOPs) using a noncontact optical coherence elastography (OCE) technique. A focused air-pulse induced low amplitude (≤ 10 µm) elastic waves in fresh porcine corneas (n = 7) in situ in the whole eye globe configuration. A home-built phase-stabilized swept source optical coherence elastography (PhS-SSOCE) system imaged the elastic wave propagation at different stepped radial directions. A closed-loop feedback system was used to artificially control the IOP and the OCE measurements were repeated as the IOP was incrementally increased from 15 to 30 mm Hg in 5-mm Hg increments. The OCE measurements demonstrated that the stiffness of the cornea increased as a function of IOP and elastic anisotropy of the cornea became more pronounced at higher IOPs. The standard deviation of the modified planar anisotropy coefficient increased from 0.72 ± 0.42 at an IOP of 15 mm Hg to 1.58 ± 0.40 at 30 mm Hg. The presented noncontact OCE method was capable of detecting and assessing the corneal elastic anisotropy as a function of IOP. Due to the noninvasive nature and small amplitude of the elastic wave, this method may be able to provide further information about corneal health and integrity in vivo. [J Refract Surg. 2016;32(8):562-567.].

Importance of accurately assessing biomechanics of the cornea.

This article summarizes the state-of-the-art in clinical corneal biomechanics, including procedures in which biomechanics play a role, and the clinical consequences in terms of error in estimating intraocular pressure (IOP). Corneal biomechanical response to refractive surgery can be categorized into either stable alteration of surface shape and thus visual outcome, or unstable biomechanical decompensation. The stable response is characterized by central flattening and peripheral steepening that is potentiated in a stiffer cornea. Two clinical devices for assessing corneal biomechanics do not yet measure classic biomechanical properties, but rather provide assessment of corneal deformation response. Biomechanical parameters are a function of IOP, and both the cornea and sclera become stiffer as IOP increases. Any assessment of biomechanical parameters must include IOP, and one value of stiffness does not adequately characterize a cornea. Corneal biomechanics plays a role in the outcomes of any procedure in which lamellae are transected. Once the corneal structure has been altered in a manner that includes central thinning, IOP measurements with applanation tonometry are likely not valid, and other technologies should be used.

Manometric measurement of the outflow facility in the living human eye and its dependence on intraocular pressure.

The intraocular pressure (IOP) is determined by a dynamic equilibrium between the production and outflow of the aqueous humour. The relationship between IOP and the outflow rate through the conventional and unconventional pathway is quantified by the outflow facility coefficient (C). The purpose of this study is to employ a direct (manometric) tonographic technique and determine C as well as its inverse, resistance (R), as a function of IOP in the living human eye. Nineteen cataract patients were enrolled in the study. An intraoperative manometric device was used to measure IOP. After cannulation of the anterior chamber, the IOP was increased by infusion of controlled amounts of saline solution. At 40 mmHg, the infusion stopped, and a pressure sensor recorded the IOP. The measured pressure-volume relationship was considered in order to convert pressure changes to corresponding ocular volume changes. An appropriate mathematical model was applied to calculate C and (its inverse), R. The average C was 0.0672 ± 0.0296 μl/min/mmHg at 40 mmHg and 0.2652 ± 0.1164 μl/min/mmHg at 20 mmHg. There was a strong dependence of coefficient C on IOP in all subjects (p < 0.001). The corresponding values for R were 17.9 ± 11.17 min mmHg/μl at 40 mmHg and 4.51 ± 2.69 min mmHg/μl at 20 mmHg. This study provides measurement of outflow facility and its dependence with pressure in healthy living human eyes. This relation is shown to be non-linear, using a direct manometric method.

Analysis of the viscoelastic properties of the human cornea using Scheimpflug imaging in inflation experiment of eye globes.

PurposeTo demonstrate a Scheimpflug-based imaging procedure for investigating the depth- and time-dependent strain response of the human cornea to inflation testing of whole eye globes.MethodsSix specimens, three of which with intact corneal epithelium, were mounted in a customized apparatus within a humidity and temperature-monitored wet chamber. Each specimen was subjected to two mechanical tests in order to measure corneal strain resulting from application of cyclic (cyclic regimen) and constant (creep regimen) stress by changing the intra-ocular pressure (IOP) within physiological ranges (18–42 mmHg). Corneal shape changes were analyzed as a function of IOP and both corneal stress-strain curves and creep curves were generated.ResultsThe procedure was highly accurate and repeatable. Upon cyclic stress application, a biomechanical corneal elasticity gradient was found in the front-back direction. The average Young's modulus of the anterior cornea ranged between 2.28±0.87 MPa and 3.30±0.90 MPa in specimens with and without intact epithelium (P = 0.05) respectively. The Young's modulus of the posterior cornea was on average 0.21±0.09 MPa and 0.17±0.06 MPa (P>0.05) respectively. The time-dependent strain response of the cornea to creep testing was quantified by fitting data to a modified Zener model for extracting both the relaxation time and compliance function.ConclusionCyclic and creep mechanical tests are valuable for investigating the strain response of the intact human cornea within physiological IOP ranges, providing meaningful results that can be translated to clinic. The presence of epithelium influences the results of anterior corneal shape changes when monitoring deformation via Scheimpflug imaging in inflation experiments of whole eye globes.

Biomechanical changes in the human cornea after transepithelial corneal crosslinking using iontophoresis.

To evaluate the corneal response to variable intraocular pressure (IOP) in human eye globes after ultraviolet-A (UVA) transepithelial corneal crosslinking using iontophoresis. Fondazione G.B. Bietti IRCCS, Rome, Italy. Experimental study. Four human donor eye globes were treated with transepithelial crosslinking using iontophoresis and rapid UVA corneal irradiation, and 4 globes had standard crosslinking. Inflation experiments were performed on the globes before and after crosslinking. Topographic maps of the anterior and posterior cornea were acquired using Scheimpflug topography. Images were obtained using a mechanical regimen to analyze corneal strain in response to cyclic stress. Corneal shape changes were analyzed as a function of IOP, and corneal stress-strain curves were generated. Before crosslinking, instillation of hypotonic riboflavin-5-phosphate sodium 0.1% solution using iontophoresis increased corneal thickness by 5% and instillation of dextran-enriched riboflavin 0.1% solution decreased corneal thickness by 13%. Five minutes after treatment, both crosslinking procedures reduced corneal thickness by 2%. Young's modulus (E) of the anterior cornea increased by a mean of 1.8 times (from 1.6 to 2.9 MPa) and 1.9 times (from 1.3 to 2.5 MPa) after transepithelial crosslinking using iontophoresis and standard crosslinking, respectively. The E value of the posterior cornea also increased after both procedures (mean 1.7 times versus 3.1 times). Transepithelial crosslinking using iontophoresis increased the biomechanical strength of human corneal tissue in inflation testing of donor eye globes. The effect on corneal stiffness was almost comparable to that of standard crosslinking. No author has a financial or proprietary interest in any material or method mentioned.

Corneal Biomechanics as a Function of Intraocular Pressure and Pachymetry by Dynamic Infrared Signal and Scheimpflug Imaging Analysis in Normal Eyes

To evaluate corneal biomechanical deformation response using Ocular Response Analyzer (ORA) and Corvis ST data. Prospective observational case-control study. A total of 1262 eyes of 795 patients were enrolled. Three groups were established, according to the corneal compensated intraocular pressure (IOPcc): Group I (10-13 mm Hg), Group II (14-17 mm Hg), and Group III (18-21 mm Hg). Each group included 3 subgroups, based on central corneal thickness (CCT): Subgroups 1 (465-510 μm), 2 (510-555 μm), and 3 (555-600 μm). In addition, similar groups of CCT were divided into subgroups of IOPcc. Corneal hysteresis (CH) and corneal resistance factor (CRF) were derived from ORA. The parameters of highest concavity with the parameters of first and second applanation were recorded from Corvis ST. CH and CRF, applanation 1 time, and radius of curvature at highest concavity showed significant differences between CCT subgroups for each IOPcc group (P < .0001). CH, applanation 1 and 2 time, and applanation 2 velocity, as well as deformation amplitude (DA), showed significant differences by IOP subgroups for all CCT groups. IOPcc is correlated negatively with CH (r = -0.38, P < .0001). There are positive correlations of IOPcc with applanation 1 time, applanation 2 velocity, and radius and negative correlations with applanation 2 time (r = -0.54, P < .0001), applanation 1 velocity (r = -0.118, P < .0001), and DA (r = -0.362, P < .0001). ORA and Corvis ST parameters are informative in the evaluation of corneal biomechanics. IOP is important in deformation response evaluation and must be taken into consideration.

Effect of Hydration State and Storage Media on Corneal Biomechanical Response From In Vitro Inflation Tests

To evaluate corneal deformation with varying intraocular pressure and the dependency of the biomechanical response on the corneal hydration state, modulated by the storage solutions or postmortem period. Thirty fresh enucleated porcine eyes were used for in vitro whole eye globe inflation experiments. The eyes were separated into five groups and treated with different solutions: 20% dextran, 8% dextran, 0.125% riboflavin-20% dextran, Optisol-GS (Bausch & Lomb, Rochester, NY), and one control group of virgin (untreated) eyes. Intraocular pressure was increased (from 15 to 55 mm Hg) and decreased (to 15 mm Hg) in 5-mm Hg steps and Scheimpflug images were taken at each step. Measurements were repeated after 24 hours. Thickness and curvature changes were analyzed as a function of intraocular pressure. Corneal deformation differed across conditions and hydration states. Dehydration by any dextran solution increased the hysteresis after the inflation/deflation cycle (14.29 vs 22.07 to 41.75 μm), whereas overnight hydration did not lead to a significant difference. Compared to control corneas, corneas treated with Optisol-GS showed the most similar behavior. Corneas treated with 0.125% riboflavin-20% dextran deformed most (Δthickness(max) = 38.27 μm), indicating a softening of the corneal tissue compared to control corneas (23.18 μm) and corneas treated with 8% dextran (21.01 μm) and 20% dextran (29.07 μm). Dextran instillation decreased corneal thickness on average to 56.5% at 0 hours and 72.7% at 24 hours. Corneal hydration and tissue preservation changed corneal biomechanics, in particular its relaxation over a period of 24 hours.

A Minimally Invasive Implantable Wireless Pressure Sensor for Continuous IOP Monitoring

This paper presents a minimally invasive implantable pressure sensing transponder for continuous wireless monitoring of intraocular pressure (IOP). The transponder is designed to make the implantation surgery simple while still measuring the true IOP through direct hydraulic contact with the intraocular space. Furthermore, when IOP monitoring is complete, the design allows physicians to easily retrieve the transponder. The device consists of three main components: 1) a hypodermic needle (30 gauge) that penetrates the sclera through pars plana and establishes direct access to the vitreous space of the eye; 2) a micromachined capacitive pressure sensor connected to the needle back-end; and 3) a flexible polyimide coil connected to the capacitor forming a parallel LC circuit whose resonant frequency is a function of IOP. Most parts of the sensor sit externally on the sclera and only the needle penetrates inside the vitreous space. In vitro tests show a sensitivity of 15 kHz/mmHg with approximately 1-mmHg resolution. One month in vivo implants in rabbits confirm biocompatibility and functionality of the device.

Metabolic Vulnerability Disposes Retinal Ganglion Cell Axons to Dysfunction in a Model of Glaucomatous Degeneration

We tested the hypothesis that glaucoma disrupts electrophysiological conduction properties and axon function in optic nerve as a function of intraocular pressure (IOP) levels and age in the DBA/2J mouse model of glaucoma. The amplitude and the integral of electrical signals evoked along the axons decreased considerably by 6 months of age as a function of increasing IOP levels. At young ages, raised IOP was directly associated with increased vulnerability to metabolic challenge. Changes in the physiological function of the optic nerves were accentuated with aging, leading to loss of compound action potential in an entire population of fibers: small, slow conducting axons. This loss was accompanied with loss of small fiber axon counts and declining metabolic reserve by demonstrating IOP-dependent ATP decrease in mouse optic nerves. These data shed light on a novel potential mechanism of glaucoma pathology whereby increased IOP and declining metabolic capacity lead to axon liability and eventually dysfunction and loss.