System for Rapid, Precise Modulation of Intraocular Pressure, toward Minimally-Invasive In Vivo Measurement of Intracranial Pressure

Abstract

Pathologic changes in intracranial pressure (ICP) are commonly observed in a variety of medical conditions, including traumatic brain injury, stroke, brain tumors, and glaucoma. However, current ICP measurement techniques are invasive, requiring a lumbar puncture or surgical insertion of a cannula into the cerebrospinal fluid (CSF)-filled ventricles of the brain. A potential alternative approach to ICP measurement leverages the unique anatomy of the central retinal vein, which is exposed to both intraocular pressure (IOP) and ICP as it travels inside the eye and through the optic nerve; manipulating IOP while observing changes in the natural pulsations of the central retinal vein could potentially provide an accurate, indirect measure of ICP. As a step toward implementing this technique, we describe the design, fabrication, and characterization of a system that is capable of manipulating IOP in vivo with <0.1 mmHg resolution and settling times less than 2 seconds. In vitro tests were carried out to characterize system performance. Then, as a proof of concept, we used the system to manipulate IOP in tree shrews (Tupaia belangeri) while video of the retinal vessels was recorded and the caliber of a selected vein was quantified. Modulating IOP using our system elicited a rapid change in the appearance of the retinal vein of interest: IOP was lowered from 10 to 3 mmHg, and retinal vein caliber sharply increased as IOP decreased from 7 to 5 mmHg. Another important feature of this technology is its capability to measure ocular compliance and outflow facility in vivo, as demonstrated in tree shrews. Collectively, these proof-of-concept demonstrations support the utility of this system to manipulate IOP for a variety of useful applications in ocular biomechanics, and provide a framework for further study of the mechanisms of retinal venous pulsation.

In vivo optic nerve head mechanical response to intraocular and cerebrospinal fluid pressure: imaging protocol and quantification method

“…In accordance with the approach used by Golzan et al . 12 , we estimated CSFP by measuring the IOP level at which spontaneous venous pulsation (SVP) 13 was unequivocally visible in both the infrared video image and the OCT live B-scan of the central ONH. At this point, SVP = 0 mmHg (SVP 0 ).…”

NLRP12 collaborates with NLRP3 and NLRC4 to promote pyroptosis inducing ganglion cell death of acute glaucoma

“…The corneas were subsequently treated with 1% tropicamide (Somno-Suite; Kent Scientific) to dilate the pupils. Cannulation of the right eye in the anterior chamber was achieved by inserting a 30-gauge needle (BD, Franklin Lakes, USA) attached to a normal saline reservoir to elevate and maintain an average IOP of 110 mmHg for 90 min, which was monitored by our modified system according to Stockslager MA's study [37]. The 30-gauge needle and attached normal saline reservoir were connected to a pressure transducer (Honeywell 142PC01G) attached to a three-way stopcock.…”

Development and Characterization of a Benchtop Corneal Puncture Injury Model

“…Next, the outflow rate when an enucleated porcine eye is connected, was measured by recording the pressure decay vs. time from 20 mmHg to 15 mmHg. Using a previously developed mathematical relationship 15 , outflow facility was determined to be approximately 0.71 µL/min/mmHg, differing slightly from previously reported outflow facility results of porcine tissue, which range from 0.24 to 0.61 µL/min/mmHg (Fig. 2C) [16][17][18] .…”

“…To characterize the fluidic system required for recording pressure, system compliance was measured and compared to ocular compliance. Compliance is a mechanical property defined as the change in volume for a given change in pressure 15 . System compliance was measured in a closed-system with the in-line pressure transducer and system fluidics isolated, and 20 µL being injected via syringe pump at 20 µL/s.…”

“…Next, outflow rate was determined based upon previously described methods 15 . Pressure was set at 20 mmHg by hydrostatic reservoir, the system was isolated from the reservoir, and pressure versus (vs.) time data were captured until pressure readings reached 15 mmHg.…”