Schlemm’s canal imaging, pressure measurement, catheterization and substance delivery in live monkeys

Abstract

Purpose : 1) Schlemm’s canal pressure (SCP) is an important contributor to intraocular pressure (IOP). Developing an accurate, dynamic real time technique to estimate pressure in SC in non-human primates (NHP) may enhance understanding glaucoma pathophysiology and help evaluate potential therapeutic targets and treatments.
2) Advances have been made in gene therapy — an emerging treatment strategy for glaucoma. We describe a gene delivery technique allowing injection of smaller volumes and lower titers than other traditional delivery techniques directly into SC of live cynomolgus monkeys, likely preventing off-target transduction.

Methods : 1) A needle, connected to a pressure transducer and computer, is placed into the anterior chamber of live anesthetized monkeys to continuously record and control IOP. Concurrently, SC is imaged using an endoscope attached to a digital camera in turn connected to a computer. The images obtained are time synchronized with the collection of IOP data, so that the corresponding IOP is known for every frame of the video showing the canal’s configuration and coloration.
2) With gonioscopic/microscopic visualization of SC of live anesthetized monkeys, a microcatheter (outer diameter 125μm) is inserted into the canal circumferentially ab interno. The vector along with trypan blue dye is injected while withdrawing the catheter. An endoscope allows visualization of the vector in the SC over 360^o.

Results : 1) As IOP is lowered, SC fills with venous blood and is visible as a bright reddish-orange band. When IOP is raised, the canal narrows and blanches. The range of IOP over which these changes were noted was wider and higher than predicted (~5-22mmHg). Sausaging of blood column in SC was observed which may indicate segmental/regional differences.
2) 360° catheterization of SC was routinely executed. The vector was injected and visualized with an endoscope as a bright blue band within SC.

Conclusions : 1) Video recording canalicular morphology and digitally recording IOP, with synchronized time stamping, will provide a precise description of pressure-related canalicular dynamics in live NHP.
2) A microcatheter that can be placed directly into SC may reduce the complications of traditional intracameral gene delivery techniques, and facilitate development of gene therapies targeting all the structures of the conventional outflow pathway in live NHP.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.