Browsing by Subject "Intraocular pressure regulation"

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    Aqueous outflow regulation – 21st century concepts
    (Elsevier, 2021-07) Johnstone, Murray; Xin, Chen; Tan, James; Martin, Elizabeth; Wen, Joanne; Wang, Ruikang K.; Ophthalmology, School of Medicine
    We propose an integrated model of aqueous outflow control that employs a pump-conduit system in this article. Our model exploits accepted physiologic regulatory mechanisms such as those of the arterial, venous, and lymphatic systems. Here, we also provide a framework for developing novel diagnostic and therapeutic strategies to improve glaucoma patient care. In the model, the trabecular meshwork distends and recoils in response to continuous physiologic IOP transients like the ocular pulse, blinking, and eye movement. The elasticity of the trabecular meshwork determines cyclic volume changes in Schlemm's canal (SC). Tube-like SC inlet valves provide aqueous entry into the canal, and outlet valve leaflets at collector channels control aqueous exit from SC. Connections between the pressure-sensing trabecular meshwork and the outlet valve leaflets dynamically control flow from SC. Normal function requires regulation of the trabecular meshwork properties that determine distention and recoil. The aqueous pump-conduit provides short-term pressure control by varying stroke volume in response to pressure changes. Modulating TM constituents that regulate stroke volume provides long-term control. The aqueous outflow pump fails in glaucoma due to the loss of trabecular tissue elastance, as well as alterations in ciliary body tension. These processes lead to SC wall apposition and loss of motion. Visible evidence of pump failure includes a lack of pulsatile aqueous discharge into aqueous veins and reduced ability to reflux blood into SC. These alterations in the functional properties are challenging to monitor clinically. Phase-sensitive OCT now permits noninvasive, quantitative measurement of pulse-dependent TM motion in humans. This proposed conceptual model and related techniques offer a novel framework for understanding mechanisms, improving management, and development of therapeutic options for glaucoma.
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    Trabecular Meshwork Movement Controls Distal Valves and Chambers: New Glaucoma Medical and Surgical Targets
    (MDPI, 2023-10-18) Johnstone, Murray; Xin, Chen; Martin, Elizabeth; Wang, Ruikang; Ophthalmology, School of Medicine
    Herein, we provide evidence that human regulation of aqueous outflow is by a pump-conduit system similar to that of the lymphatics. Direct observation documents pulsatile aqueous flow into Schlemm's canal and from the canal into collector channels, intrascleral channels, aqueous veins, and episcleral veins. Pulsatile flow in vessels requires a driving force, a chamber with mobile walls and valves. We demonstrate that the trabecular meshwork acts as a deformable, mobile wall of a chamber: Schlemm's canal. A tight linkage between the driving force of intraocular pressure and meshwork deformation causes tissue responses in milliseconds. The link provides a sensory-motor baroreceptor-like function, providing maintenance of a homeostatic setpoint. The ocular pulse causes meshwork motion oscillations around the setpoint. We document valves entering and exiting the canal using real-time direct observation with a microscope and multiple additional modalities. Our laboratory-based high-resolution SD-OCT platform quantifies valve lumen opening and closing within milliseconds synchronously with meshwork motion; meshwork tissue stiffens, and movement slows in glaucoma tissue. Our novel PhS-OCT system measures nanometer-level motion synchronous with the ocular pulse in human subjects. Movement decreases in glaucoma patients. Our model is robust because it anchors laboratory studies to direct observation of physical reality in humans with glaucoma.
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    Valve-Like Outflow System Behavior With Motion Slowing in Glaucoma Eyes: Findings Using a Minimally Invasive Glaucoma Surgery–MIGS-Like Platform and Optical Coherence Tomography Imaging
    (Frontiers Media, 2022-04-29) Johnstone, Murray; Xin, Chen; Acott, Ted; Vranka, Janice; Wen, Joanne; Martin, Elizabeth; Wang, Ruikang K.; Ophthalmology, School of Medicine
    Purpose: This study aimed to investigate anatomic relationships and biomechanics of pressure-dependent trabecular meshwork and distal valve-like structure deformation in normal and glaucoma eyes using high-resolution optical coherence tomography (HR-OCT). Methods: We controlled Schlemm's canal (SC) pressure during imaging with HR-OCT in segments of three normal (NL) and five glaucomatous (GL) ex vivo eyes. The dissected limbal wedges were studied from 15 locations (5 NL and 10 GL). A minimally invasive glaucoma surgery (MIGS)-like cannula was inserted into the SC lumen, whereas the other end was attached to a switch between two reservoirs, one at 0, the other at 30 mm Hg. A steady-state pressure of 30 mm Hg was maintained to dilate SC and collector channels (CC) during 3D volume imaging. The resulting 3D lumen surface relationships were correlated with internal structural features using an image mask that excluded tissues surrounding SC and CC. While imaging with HR-OCT, real-time motion responses in SC and CC areas were captured by switching pressure from 0 to 30 or 30 to 0 mm Hg. NL vs. GL motion differences were compared. Results: Lumen surface and internal relationships were successfully imaged. We identified SC inlet and outlet valve-like structures. In NL and GL, the mean SC areas measured at the steady-state of 0 and 30 mm Hg were each significantly different (p < 0.0001). Synchronous changes in SC and CC lumen areas occurred in <200 ms. Measured SC area differences at the steady-state 0 and 30 mmHg, respectively, were larger in NL than GL eyes (p < 0.0001). The SC motion curves rose significantly more slowly in GL than NL (p < 0.001). Pressure waves traveled from the cannula end along the SC lumen to CC and deep intrascleral channels. Conclusion: HR-OCT provided simultaneous measurements of outflow pathway lumen surfaces, internal structures, and biomechanics of real-time pressure-dependent dimension changes. We identified SC inlet and outlet valve-like structures. GL tissues underwent less motion and responded more slowly than NL, consistent with increased tissue stiffness. A MIGS-like shunt to SC permitted pulse waves to travel distally along SC lumen and into CC.