Trabecular Meshwork Response to Pressure Elevation in the Living Human Eye

Abstract

The mechanical characteristics of the trabecular meshwork (TM) are linked to outflow resistance and intraocular pressure (IOP) regulation. The rationale behind this technique is the direct observation of the mechanical response of the TM to acute IOP elevation. Prior to scanning, IOP is measured at baseline and during IOP elevation. The limbus is scanned by spectral-domain optical coherence tomography at baseline and during IOP elevation (ophthalmodynamometer (ODM) applied at 30 g force). Scans are processed to enhance visualization of the aqueous humor outflow pathway using ImageJ. Vascular landmarks are used to identify corresponding locations in baseline and IOP elevation scan volumes. Schlemm canal (SC) cross-sectional area (SC-CSA) and SC length from anterior to posterior along its long axis are measured manually at 10 locations within a 1 mm segment of SC. Mean inner to outer wall distance (short axis length) is calculated as the area of SC divided by its long axis length. To examine the contribution of adjacent tissues to the effect IOP elevations, measurements are repeated without and with smooth muscle relaxation with instillation of tropicamide. TM migration into SC is resisted by TM stiffness, but is enhanced by the support of its attachment to adjacent smooth muscle within the ciliary body. This technique is the first to measure the living human TM response to pressure elevation in situ under physiological conditions within the human eye. Video LinkThe video component of this article can be found at

Visualization of conventional outflow tissue responses to netarsudil in living mouse eyes

“…For example, behavior of TM/SC can be monitored at different IOP levels (Li et al, 2014a; Li et al, 2014b) and at different disease stages (Li et al, 2014b). Similar to healthy human volunteers (Kagemann et al, 2015), we observed that mouse SC dimensions are reduced in a pressure-dependent manner that is quickly reversible (Li et al, 2014a; Li et al, 2014b). The mouse eyes also respond to topical cholinergic treatment similarly to that of human eyes (Flocks and Zweng, 1957; Li et al, 2014a; Lutjen-Drecoll, 1973), with the ciliary muscle contracting to maintain a patent conventional outflow tract (Li et al, 2014a).…”

“…Major advancements in OCT technology for the anterior eye have resulted in increased reproducibility and accuracy in the assessment of progressive tissue damage (Kagemann et al, 2015; Li et al, 2007) and enhanced penetration of the OCT signal into ocular tissues, including conventional outflow structures (Francis et al, 2012; Kagemann et al, 2014a; Kagemann et al, 2010). Interest in imaging the trabecular meshwork/Schlemm’s canal (TM/SC) has increased in recent years since reduced aqueous humor drainage through these tissues is the root cause of ocular hypertension in glaucoma.…”

“…For example, OCT was used to monitor mechanical responses of the TM to acute intraocular pressure (IOP) elevation in living human eyes. Elevated IOP reduced SC cross-sectional area (Kagemann et al, 2015; Kagemann et al, 2014b), which was enhanced in the presence tropicamide, a drug that disables the ciliary muscle (Kagemann et al, 2015). …”

Schlemm’s Canal and Trabecular Meshwork in Eyes with Primary Open Angle Glaucoma: A Comparative Study Using High-Frequency Ultrasound Biomicroscopy

“…The dysregulation of the extracellular matrix caused fibrosis and increased stiffness of the TM. TM stiffness that could influence the extent of deformation of TM and the inner wall of SC [ 45 – 47 ]. Using atomic force microscopy, Last et al [ 48 ] found that the elastic modulus of the TM was higher in eyes with glaucoma than in normal eyes, suggesting an increased TM stiffness in eyes with glaucoma.…”

Disease-related and age-related changes of anterior chamber angle structures in patients with primary congenital glaucoma: An in vivo high-frequency ultrasound biomicroscopy-based study

“…When the investigators disagreed on the delineation of SC, a mutual conclusion was reached after discussion. These parameters were then measured by a masked, experienced investigator (YS) using ImageJ software (version 1.47, National Institutes of Health, Bethesda, Maryland, USA) transformed from pixel to anatomic values as previously described [16]. SS was defined as the end point of the curved interface between the ciliary body and the sclera/ TM based on previous studies [17].…”