Platform to investigate aqueous outflow system structure and pressure-dependent motion using high-resolution spectral domain optical coherence tomography

Abstract

Abstract. The aqueous outflow system (AOS) is responsible for maintaining normal intraocular pressure (IOP) in the eye. Structures of the AOS have an active role in regulating IOP in healthy eyes and these structures become abnormal in the eyes with glaucoma. We describe a newly developed system platform to obtain high-resolution images of the AOS structures. By incorporating spectral domain optical coherence tomography (SD-OCT), the platform allows us to systematically control, image, and quantitate the responses of AOS tissue to pressure with a millisecond resolution of pulsed flow. We use SD-OCT to image radial limbal segments from the surface of the trabecular meshwork (TM) with a spatial resolution of ∼5 μm in ex vivo nonhuman primate eyes. We carefully insert a cannula into Schlemm's canal (SC) to control both pressures and flow rates. The experimental results demonstrate the capability of the platform to visualize the unprecedented details of AOS tissue components comparable to that delivered by scanning electron microscopy, as well as to delineate the complex pressure-dependent relationships among the TM, structures within the SC, and collector channel ostia. The described technique provides a new means to characterize the anatomic and pressure-dependent relationships of SC structures, particularly the active motion of collagenous elements at collector channel ostia; such relationships have not previously been amenable to study. Experimental findings suggest that continuing improvements in the OCT imaging of the AOS may provide both insights into the glaucoma enigma and improvements in its management.

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

“…In this study, one end of SC in a quadrant of the anterior segment in LF and HF segmental regions of two human donors were cannulated, and pressures switched from 0 to 30 mmHg (Figures 123). Hariri using a precise perfusion pump measured the area in the SC as a function of the pressure, and reported the SC diameter of 124.66 ± 11.5 mmHg [80], that is in a very good agreement with our results (126 ± 5 µ m). This assures us the pressure of the SC in our FE simulations can be assumed to be ~30 mmHg.…”

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

“…In this study, one end of SC in a quadrant of the anterior segment in LF and HF segmental regions of two human donors were cannulated, and pressures switched from 0 to 30 mmHg (Figures 123). Hariri using a precise perfusion pump measured the area in the SC as a function of the pressure, and reported the SC diameter of 124.66 ± 11.5 mmHg [80], that is in a very good agreement with our results (126 ± 5 µ m). This assures us the pressure of the SC in our FE simulations can be assumed to be ~30 mmHg.…”

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

“…The SC opening at the cut end of the segment opposite the location of cannula entry was not occluded in our study. However, SC filled along its entire length in the steady-state 3D reconstructions in this study was consistent with prior studies in non-human primates (21) and humans (43,46).…”

“…Minimally invasive glaucoma surgeries can impact the distal outflow system in several ways. At the site of a MIGS stent insertion, our study demonstrated that the device compresses the TM and SC external wall as illustrated in Figure 2, consistent with previous reports (5,21,62). However, immediately distal to the ≈200 µm diameter MIGS-like device entry site region, the SC lumen is held open.…”

“…Non-human primate outflow studies identified similar structures, rapidity of motion, and associated changes in lumen size (21,60) that our current study identified in human tissue. The constellation of synchronous structural movement caused a rapid change in pathway lumen size.…”

OCT Study of Mechanical Properties Associated with Trabecular Meshwork and Collector Channel Motion in Human Eyes

“…The dimensions of SC, CCE and ISCC are small in relation to the fluid volume introduced into the lumen of SC in our technique. Findings from our study as well as the previous study in non-human primate eyes [ 29 ] suggest that pressure in the canal may remain relatively stable for two reasons. First, the canal is dilated not only in the proximal portion, but also distally far from the cannula tip.…”

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

“…In this study, one end of SC in a quadrant of the anterior segment in LF and HF segmental regions of two human donors were cannulated, and pressures switched from 0 to 30 mmHg (Figures 123). Hariri using a precise perfusion pump measured the area in the SC as a function of the pressure, and reported the SC diameter of 124.66 ± 11.5 mmHg [80], that is in a very good agreement with our results (126 ± 5 µ m). This assures us the pressure of the SC in our FE simulations can be assumed to be ~30 mmHg.…”

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

“…The SC opening at the cut end of the segment opposite the location of cannula entry was not occluded in our study. However, SC filled along its entire length in the steady-state 3D reconstructions in this study was consistent with prior studies in non-human primates (21) and humans (43,46).…”

“…Minimally invasive glaucoma surgeries can impact the distal outflow system in several ways. At the site of a MIGS stent insertion, our study demonstrated that the device compresses the TM and SC external wall as illustrated in Figure 2, consistent with previous reports (5,21,62). However, immediately distal to the ≈200 µm diameter MIGS-like device entry site region, the SC lumen is held open.…”

“…Non-human primate outflow studies identified similar structures, rapidity of motion, and associated changes in lumen size (21,60) that our current study identified in human tissue. The constellation of synchronous structural movement caused a rapid change in pathway lumen size.…”

OCT Study of Mechanical Properties Associated with Trabecular Meshwork and Collector Channel Motion in Human Eyes

“…The dimensions of SC, CCE and ISCC are small in relation to the fluid volume introduced into the lumen of SC in our technique. Findings from our study as well as the previous study in non-human primate eyes [ 29 ] suggest that pressure in the canal may remain relatively stable for two reasons. First, the canal is dilated not only in the proximal portion, but also distally far from the cannula tip.…”

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

“…In this study, one end of SC in a quadrant of the anterior segment in LF and HF segmental regions of two human donors were cannulated, and pressures switched from 0 to 30 mmHg (Figures 123). Hariri using a precise perfusion pump measured the area in the SC as a function of the pressure, and reported the SC diameter of 124.66 ± 11.5 mmHg [80], that is in a very good agreement with our results (126 ± 5 µ m). This assures us the pressure of the SC in our FE simulations can be assumed to be ~30 mmHg.…”

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

“…The SC opening at the cut end of the segment opposite the location of cannula entry was not occluded in our study. However, SC filled along its entire length in the steady-state 3D reconstructions in this study was consistent with prior studies in non-human primates (21) and humans (43,46).…”

“…Minimally invasive glaucoma surgeries can impact the distal outflow system in several ways. At the site of a MIGS stent insertion, our study demonstrated that the device compresses the TM and SC external wall as illustrated in Figure 2, consistent with previous reports (5,21,62). However, immediately distal to the ≈200 µm diameter MIGS-like device entry site region, the SC lumen is held open.…”

“…Non-human primate outflow studies identified similar structures, rapidity of motion, and associated changes in lumen size (21,60) that our current study identified in human tissue. The constellation of synchronous structural movement caused a rapid change in pathway lumen size.…”

OCT Study of Mechanical Properties Associated with Trabecular Meshwork and Collector Channel Motion in Human Eyes

“…The dimensions of SC, CCE and ISCC are small in relation to the fluid volume introduced into the lumen of SC in our technique. Findings from our study as well as the previous study in non-human primate eyes [ 29 ] suggest that pressure in the canal may remain relatively stable for two reasons. First, the canal is dilated not only in the proximal portion, but also distally far from the cannula tip.…”