Continuous Telemetric Measurement and Chronic Control of Cerebrospinal Fluid Pressure
The pressure inside the eye, or intraocular pressure (IOP), has long been thought to play a dominant role in glaucoma, but recent work suggests that pressure from cerebrospinal fluid surrounding the optic nerve exiting the eye is also involved. These pressures are not easy to measure, so there has been no good way to determine if the pressure around the nerve where it exits the eye is truly important. We have developed a new system to wirelessly measure and record the IOP continuously in research subjects, and we now want to extend that system to measure the pressure around the nerve exiting the eye. Using this system, we can definitively determine if the pressure around the nerve is important in glaucoma, which could lead to new treatment approaches for this blinding disease.
The pressure inside the eye, known as intraocular pressure (IOP) has long been thought to play a dominant role in glaucoma, but recent work suggests that fluid pressure from cerebrospinal fluid surrounding the nerve exiting the eye is also involved. IOP and cerebrospinal fluid pressure (CSFP) counteract each other at the optic nerve head (ONH), which is generally accepted as the site of damage in glaucoma. These pressures are difficult to measure and so there has been no good way to determine if the pressure around the nerve is truly important in glaucoma pathogenesis or progression. We have developed a new system to wirelessly measure and record the pressure in the eye continuously in research subjects, and we now want to extend that system to measure CSFP as well. Using this system, we can definitively determine if CSFP is important in glaucoma, which could lead to new treatment approaches for this blinding disease.
In Aim 1, we propose to develop, implant and validate an implantable CSFP transducer for addition to our existing wireless IOP telemetry system, and to quantify the translaminar pressure difference (IOP-CSFP) with body position and normal activity. To accomplish this, we will develop a CSFP telemetry sensor, implant the wireless system (including unilateral IOP) in four research animals, and test transducer performance via bi-weekly calibration against a gold standard clinical monitor. Once validated, we will measure and quantify baseline CSFP and unilateral IOP near-continuously (200Hz for 12 seconds every 2 minutes, 24 hours per day) for 2 months, and characterize the translaminar pressure difference (IOP - CSFP) in various body positions.
In Aim 2, we propose to lower CSFP to one-third of normal levels for 9 months using an implanted CSF shunt and determine if a CSFP-driven increase in the translaminar pressure difference (IOP-CSFP) induces a glaucoma-like optic neuropathy. Once CSFP is lowered and stable, we will perform bi-weekly imaging of the ONH at a manometer-controlled IOP of 10 mmHg to assess longitudinal change in ONH morphology and retinal nerve fiber layer (RNFL) thickness compared to baseline measurements taken before CSFP lowering. Differences in optic disk appearance, ONH structure, and/or decreases in RNFL thickness will indicate that CSFP is potentially an important contributor to glaucoma or a related optic neuropathy.
The ultimate outcome of this research line, wherein we are monitoring bilateral IOP, CSFP, and ocular blood perfusion pressure (OPP) via radiotelemetry and using experimental interventions to chronically alter CSFP and IOP, is to elucidate the contributions of each of these variables to glaucoma pathogenesis and progression. We know IOP is involved in the disease, and the only clinical treatments for glaucoma are based upon IOP lowering. Many patients continue to progress following maximum IOP lowering and new treatment modalities are desperately needed. Furthermore, the validation of CSFP and/or OPP as proven risk factors would give treating physicians another piece of data upon which to base clinical management decisions. If we can show that low CSFP and/or OPP independently contribute to glaucoma, then we can design therapies to alter these variables as new glaucoma treatments.