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

Abstract

We report the use of a high-resolution optical coherence tomography (OCT) imaging platform to identify and quantify pressure-dependent aqueous outflow system (AOS) tissue relationships and to infer mechanical stiffness through examination of tissue properties in ex vivo human eyes. Five enucleated human eyes are included in this study, with each eye prepared with four equal-sized quadrants, each encompassing 90 degrees of the limbal circumference. In radial limbal segments perfusion pressure within Schlemm’s canal (SC) is controlled by means of a perfusion cannula inserted into the canal lumen, while the other end of the cannula leads to a reservoir at a height that can control the pressure in the cannula. The OCT system images the sample with a spatial resolution of about 5 μm from the trabecular meshwork (TM) surface. Geometric parameters are quantified from the 2D OCT images acquired from the sample subjected to controlled changes in perfusion pressures; parameters include area and height of the lumen of SC, collector channel entrances (CCE) and intrascleral collector channels (ISCC). We show that 3D OCT imaging permits the identification of 3-D relationships of the SC, CCE and ISCC lumen dimensions. Collagen flaps or leaflets are found at CCE that are attached or hinged at only one end, whilst the flaps are connected to the TM by cylindrical structures spanning SC. Increasing static SC pressures resulted in SC lumen enlargement with corresponding enlargement of the CCE and ISCC lumen. Pressure-dependent SC lumen area and height changes are significant at the 0.01 levels for ANOVA, and at the 0.05 for both polynomial curves and Tukey paired comparisons. Dynamic measurements demonstrate a synchronous increase in SC, CCE and ISCC lumen height in response to pressure changes from 0 to 10, 30 or 50 mm Hg, respectively, and the response time is within the 50-millisecond range. From the measured SC volume and corresponding IOP values, we demonstrate that an elastance curve can be developed to infer the mechanical stiffness of the TM by means of quantifying pressure-dependent SC volume changes over a 2 mm radial region of SC. Our study finds pressure-dependent motion of the TM that corresponds to collagen leaflet configuration motion at CCE; the synchronous tissue motion also corresponds with synchrony of SC and CCE lumen dimension changes.

Impaired angiopoietin/Tie2 signaling compromises Schlemm’s canal integrity and induces glaucoma

“…We note that a more than 50% reduction in SC area and a marked reduction in transcytotic activity in SC ECs are prerequisites for the significant elevation of IOP, retinal neuronal damage, and impairment of retinal ganglion cell function. This phenomenon could be explainable based on a previous report (48) showing SC elasticity in tolerating increased resistance to AHOc to a certain degree. In fact, patients with POAG have markedly reduced SC dimensions, which are correlated with increased outflow resistance (49-52), emphasizing a significance IOP and recovers SC regression in double Angpt1/Angpt2-deleted mice.…”

Aqueous outflow - A continuum from trabecular meshwork to episcleral veins

“…Such resistance changes can occur, since the trabecular tissue distends into SC to occlude SC lumen (Grierson and Lee, 1975b; Johnstone and Grant, 1973a; Johnstone and Grant, 1973b), distends into the collector channels (Lee and Grierson, 1974), compresses SC structures, and reconfigures the CCE at SC external wall through their connections (Johnstone, 2016; Rohen and Rentsch, 1968; Xin et al, 2016a). …”

“…The hinged arrangement provides a mechanism by which the thin septa can actively move and alter the dimensions of the lumen of the ISCC. Recently, both the CCE and ISCC dynamic dimension changes were demonstrated using OCT (Hariri et al, 2014; Xin et al, 2016a). …”

“…Such movement is particularly likely given recent evidence that the CCE and ISCC geometry and constituent properties permit free movement in response to pressure changes (de Kater et al, 1992; de Kater et al, 1990; Hariri et al, 2014; Xin et al, 2016a; Xin et al, 2016b). …”

Structure-Function Changes of the Distal Outflow Tract in Response to Nitric Oxide

“…A single vessel of this diameter could carry the entire flow, 5 a principle applied to ab interno micro gel stents to allow for a slow and safe aqueous humor drainage from the anterior chamber to the subconjunctival space. 15 CC diameter changes from IOP variations 16 and with the cardiac pulse wave 17 do not explain the remaining distal outflow resistance, nor do valves at the orifices of collector channels 18 as their removal by deep sclerotomy fails to reduce IOP further. 19,20 In this study, we hypothesized that NO, an established hypotensive agent, can increase the facility in a TM-independent manner by dilating outflow tract vessels.…”