Continuous Wireless Telemetric Measurement of Intraocular Pressure (IOP), Ocular Perfusion Pressure (OPP), and Cerebrospinal Fluid Pressure (CSFP) in Nonhuman Primates (NHPs).

Intraocular pressure (IOP) and cerebrospinal fluid pressure (CSFP) telemetry in large animal models can be used to determine the exact IOP, CSFP, translaminar pressure, and translaminar pressure gradient exposure that each normal and treated eye is subjected to relative to its fellow eye. In this way, it is possible to determine the independent contributions of each of these parameters (mean and/or transient fluctuations) to the risk of both the onset and rate of progression of glaucoma. Importantly, we have shown that IOP and CSFP fluctuate continuously by up to 100% over the course of the day, so snapshot cage-side IOP measurements are unable to adequately capture the pressure in the eye; CSFP is not measurable noninvasively at all.

Morphological and biomechanical analyses of the human healthy and glaucomatous aqueous outflow pathway: Imaging-to-modeling.

Background And Objective: Intraocular pressure (IOP) is maintained via a dynamic balance between the production of aqueous humor and its drainage through the trabecular meshwork (TM), juxtacanalicular connective tissue (JCT), and Schlemm's canal (SC) endothelium of the conventional outflow pathway. Primary open angle glaucoma (POAG) is often associated with IOP elevation that occurs due to an abnormally high outflow resistance across the outflow pathway. Outflow tissues are viscoelastic and actively interact with aqueous humor dynamics through a two-way fluid-structure interaction coupling.

Modeling the Endothelial Glycocalyx Layer in the Human Conventional Aqueous Outflow Pathway.

A layer of proteoglycans and glycoproteins known as glycocalyx covers the surface of the trabecular meshwork (TM), juxtacanalicular tissue (JCT), and Schlemm's canal (SC) inner wall of the conventional aqueous outflow pathway in the eye. This has been shown to play a role in the mechanotransduction of fluid shear stress and in the regulation of the outflow resistance. The outflow resistance in the conventional outflow pathway is the main determinant of the intraocular pressure (IOP) through an active, two-way, fluid-structure interaction coupling between the outflow tissues and aqueous humor.

The Effect of Intraocular Pressure Load Boundary on the Biomechanics of the Human Conventional Aqueous Outflow Pathway.

Background: Aqueous humor outflow resistance in the trabecular meshwork (TM), juxtacanalicular connective tissue (JCT), and Schlemm's canal (SC) endothelium of the conventional outflow pathway actively contribute to intraocular pressure (IOP) regulation. Outflow resistance is actively affected by the dynamic outflow pressure gradient across the TM, JCT, and SC inner wall tissues. The resistance effect implies the presence of a fluid-structure interaction (FSI) coupling between the outflow tissues and the aqueous humor.

Viscoelastic Biomechanical Properties of the Conventional Aqueous Outflow Pathway Tissues in Healthy and Glaucoma Human Eyes.

Background: Although the tissues comprising the ocular conventional outflow pathway have shown strong viscoelastic mechanical response to aqueous humor pressure dynamics, the viscoelastic mechanical properties of the trabecular meshwork (TM), juxtacanalicular connective tissue (JCT), and Schlemm's canal (SC) inner wall are largely unknown.

Methods: A quadrant of the anterior segment from two human donor eyes at low- and high-flow (LF and HF) outflow regions was pressurized and imaged using optical coherence tomography (OCT). A finite element (FE) model of the TM, the adjacent JCT, and the SC inner wall was constructed and viscoelastic beam elements were distributed in the extracellular matrix (ECM) of the TM and JCT to represent anisotropic collagen.

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.

Ocular Pulse Amplitude Correlates With Ocular Rigidity at Native IOP Despite the Variability in Intraocular Pulse Volume With Each Heartbeat.

Purpose: The purpose of this study was to assess ocular coat mechanical behavior using controlled ocular microvolumetric injections (MVI) of 15 µL of balanced salt solution (BSS) infused over 1 second into the anterior chamber (AC) via a syringe pump.

Methods: Intraocular pressure (IOP) was continuously recorded at 200 Hz with a validated implantable IOP telemetry system in 7 eyes of 7 male rhesus macaques (nonhuman primates [NHPs]) during 5 MVIs in a series at native (3 trials), 15 and 20 mm Hg baseline IOPs, repeated in 2 to 5 sessions at least 2 weeks apart. Ocular rigidity coefficients (K) and ocular pulse volume (PV) were calculated for each trial.

Biomechanics of human trabecular meshwork in healthy and glaucoma eyes via dynamic Schlemm's canal pressurization.

Background And Objective: The trabecular meshwork (TM) consists of extracellular matrix (ECM) with embedded collagen and elastin fibers providing its mechanical support. TM stiffness is considerably higher in glaucoma eyes. Emerging data indicates that the TM moves dynamically with transient intraocular pressure (IOP) fluctuations, implying the viscoelastic mechanical behavior of the TM.

Modeling the biomechanics of the conventional aqueous outflow pathway microstructure in the human eye.

Background And Objective: Intraocular pressure (IOP) is determined by aqueous humor outflow resistance, which is a function of the combined resistance of Schlemm's canal (SC) endothelium and the trabecular meshwork (TM) and their interactions in the juxtacanalicular connective tissue (JCT) region. Aqueous outflow in the conventional outflow pathway results in pressure gradient across the TM, JCT, and SC inner wall, and induces mechanical stresses and strains that influence the geometry and homeostasis of the outflow system. The outflow resistance is affected by alteration in tissues' geometry, so there is potential for active, two-way, fluid-structure interaction (FSI) coupling between the aqueous humor (fluid) and the TM, JCT, and SC inner wall (structure).

Ocular biomechanics during improvised explosive device blast: A computational study using eye-specific models.

Background: Eye injuries comprise 10-13% of civilian improvised explosive device (IED) injuries. The bomb blast wave induces a normal and shear forces on the tissues, causing a large acute IOP elevation. This study calculated the biomechanical stresses and strains in the eye due to IED explosion via eye-specific fluid-structure interaction (FSI) models.

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

Background And Objective: Accurate 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.

Ocular biomechanics due to ground blast reinforcement.

Background And Objective: Bomb blast injuries exerts a shearing force on the air-tissue interfaces, causing devastating ocular injury from the blast wave. Improvised explosive devices (IEDs) are usually placed at different heights from the ground to induce more severe injury through ground blast reinforcement (GBR). However, there is still a lack of knowledge of the role of GBR and IED height from the ground on ocular biomechanics, and how they can affect the intraocular pressure (IOP) in the eye.

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

Purpose: To 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.

Methods: The 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.

Modeling the biomechanics of the lamina cribrosa microstructure in the human eye.

Glaucoma is among the leading causes of blindness worldwide that is characterized by irreversible damage to the retinal ganglion cell axons in the lamina cribrosa (LC) region of the optic nerve head (ONH), most often associated with elevated intraocular pressure (IOP). The LC is a porous, connective tissue structure that provides mechanical support to the axons as they exit the eye and the biomechanics of the LC microstructure likely play a crucial role in protecting the axons passing through it. There is a limited knowledge of the IOP-driven biomechanics of the LC microstructure, primarily due to its small size and the difficulty with imaging the LC both in vitro and in vivo.

Histologic validation of optical coherence tomography-based three-dimensional morphometric measurements of the human optic nerve head: Methodology and preliminary results.

Purpose: To compare the three-dimensional (3D) morphology of the deep load-bearing structures of the human optic nerve head (ONH) as revealed in vivo by spectral domain optical coherence tomography (SDOCT) with ex vivo quantitative 3D histology.

Methods: SDOCT imaging of the ONH was performed in six eyes from three brain-dead organ donors on life-support equipment awaiting organ procurement (in vivo conditions). Following organ procurement (ex vivo conditions), the eyes were enucleated and underwent a pars plana vitrectomy followed by pressurization to physiologic IOP and immersion fixation.

Comparison of extraocular and intraocular pressure transducers for measurement of transient intraocular pressure fluctuations using continuous wireless telemetry.

The optimal approach for continuous measurement of intraocular pressure (IOP), including pressure transducer location and measurement frequency, is currently unknown. This study assessed the capability of extraocular (EO) and intraocular (IO) pressure transducers, using different IOP sampling rates and duty cycles, to characterize IOP dynamics. Transient IOP fluctuations were measured and quantified in 7 eyes of 4 male rhesus macaques (NHPs) using the Konigsberg EO system (continuous at 500 Hz), 12 eyes of 8 NHPs with the Stellar EO system and 16 eyes of 12 NHPs with the Stellar IO system (both measure at 200 Hz for 15 s of every 150 s period).

Quantification of Translaminar Pressure Gradient (TLPG) With Continuous Wireless Telemetry in Nonhuman Primates (NHPs).

Purpose: Recent retrospective clinical and animal studies suggest that cerebrospinal fluid pressure (CSFP) is important in glaucoma pathogenesis. Intraocular pressure (IOP) and CSFP are the driving components of translaminar pressure (TLP = IOP - CSFP), which acts across the lamina cribrosa (LC) thickness to create the translaminar pressure gradient (TLPG = TLP/LC thickness).

Methods: We developed an implantable wireless telemetry system based on a small piezoelectric sensor with low temporal drift.

Analysis of the effects of finite element type within a 3D biomechanical model of a human optic nerve head and posterior pole.

Background And Objective: Biomechanical stresses and strains can be simulated in the optic nerve head (ONH) using the finite element (FE) method, and various element types have been used. This study aims to investigate the effects of element type on the resulting ONH stresses and strains.

Methods: A single eye-specific model was constructed using 3D delineations of anatomic surfaces in a high-resolution, fluorescent, 3D reconstruction of a human posterior eye, then meshed using our simple meshing algorithm at various densities using 4- and 10-noded tetrahedral elements, as well as 8- and 20-noded hexahedral elements.

Effect of Body Position on Intraocular Pressure (IOP), Intracranial Pressure (ICP), and Translaminar Pressure (TLP) Via Continuous Wireless Telemetry in Nonhuman Primates (NHPs).

Purpose: Recent retrospective clinical studies and animal experiments have suggested that cerebrospinal fluid pressure (CSFP) is important in glaucoma, acting through the translaminar pressure (TLP = IOP - CSFP), which directly affects the optic nerve head. In this study, IOP and intracranial pressure (ICP; a surrogate of CSFP) were measured at various body positions to quantify the determinants of TLP.

Methods: We have developed an implantable wireless pressure telemetry system based on a small piezoelectric sensor with low temporal drift.

Intra-Subject Variability and Diurnal Cycle of Ocular Perfusion Pressure as Characterized by Continuous Telemetry in Nonhuman Primates.

Purpose: To characterize ocular perfusion pressure (OPP) fluctuations with continuous telemetry over 24-hour periods across multiple days in nonhuman primates (NHPs) to test the hypotheses that OPP differs among NHPs and that the diurnal cycle of OPP is characterized by low OPP during sleep.

Methods: We have developed and validated two implantable radiotelemetry systems that allow continuous measurement of intraocular pressure (IOP), arterial blood pressure (BP), and OPP up to 500 Hz. OPP was measured unilaterally in 12 male NHPs for periods of 38 to 412 days.

Diurnal Cycle of Translaminar Pressure in Nonhuman Primates Quantified With Continuous Wireless Telemetry.

Purpose: Recent retrospective clinical studies and animal experiments have suggested that cerebrospinal fluid pressure (CSFP) is important in glaucoma pathogenesis. Intraocular pressure (IOP) and CSFP are the driving components of the translaminar pressure (TLP), which directly effects the optic nerve head. This study measured the diurnal cycle of TLP using continuous wireless telemetry in nonhuman primates (NHPs), a common animal model of glaucoma.

A Mesh-Free Approach to Incorporate Complex Anisotropic and Heterogeneous Material Properties into Eye-Specific Finite Element Models.

Commercial finite element modeling packages do not have the tools necessary to effectively incorporate the complex anisotropic and heterogeneous material properties typical of the biological tissues of the eye. We propose a mesh-free approach to incorporate realistic material properties into finite element models of individual human eyes. The method is based on the idea that material parameters can be estimated or measured at so called control points, which are arbitrary and independent of the finite element mesh.

Acute Stress Increases Intraocular Pressure in Nonhuman Primates.

Purpose: To quantify intraocular pressure (IOP) change and time course during stressful activity.

Study Design: Experimental Study.

Subjects: Three nonhuman primates (NHPs).