A method for non-invasive intracranial pressure measurement in glaucoma

Glaucoma is a chronic, progressive disease of the optic nerve in which there
are detrimental effects on field of vision and visual acuity. The relationship
between intraocular pressure (IOP) and intracranial pressure (ICP) is a crucial
aspect of the pathology of Glaucoma. At the back of the eye is a mesh-like
structure called the lamina cribrosa (LC) that contains pores through which the
optic nerve fibers run. Alterations in IOP, ICP, or both can lead to a change
in the pressure gradient across the LC and cause it to bulge and damage the
nerve fibers. If left untreated, this can eventually lead to blindness.

Currently the only clinically reliable methods of measuring ICP are by lumbar
puncture and intraventricular catheter, two extremely invasive techniques. It
is therefore necessary to establish an accurate non-invasive measurement of ICP
for evaluating the cause and progression of Glaucoma. Distortion product
otoacoustic emissions (DPOAEs) may be one such method.

DPOAEs are sounds emitted by the inner ear in response to tones at specified
levels and frequencies that are presented by a microphone placed in the ear.
These emissions are thought to represent ICP because there is a connection
between the cranium and perilymphatic fluid via the cochlear aqueduct.
Previous research has shown that DPOAEs can accurately represent changes in ICP.

The proposed study investigates the utility of DPOAEs to represent changes in
ICP in healthy controls and in 3 patient populations. The first patient group
will have diagnosed glaucoma and raised IOP and the second will have diagnosed
glaucoma but normal IOP (this is called normal tension glaucoma, or NTG).
Finally, there is patient population that has raised IOP, but does not have any
signs of glaucoma. It is suspected that these patients enjoy a compensatory
rise in ICP that protects the LC. This will be our third patient group.

To the best of our knowledge, this technique has never been utilized to measure
ICP in glaucoma patients. It has been shown with invasive techniques that
patients with glaucoma have a lower ICP than the healthy population and that
those with NTG have the lowest. We aim to reproduce these findings with a
noninvasive measurement.

Primary Objective:
The primary objective is to evaluate the use of DPOAEs as a representation of
ICP in Glaucoma patients by investigating changes in DPOAE amplitudes and phase
angles with changes in posture in subgroups of glaucoma patients and in healthy
controls. Blood pressure, corneal thickness, and systemic medication will be
recorded as well, being possible confounders.

Hypothesis 1:
The changes in DPOAEs from upright to 30 degrees HDT will be greatest for
subjects who are expected to have the lowest ICP (primarily NTG subjects).
Alternatively, the least amount of change in DPOAEs will occur in subjects who
are expected to have the highest ICP (primarily the high IOP, non glaucomatous
subjects).

Hypothesis 2:
Those with the greatest difference between IOP and ICP will have the most
severe disease progression.

Cross-sectional, observational study

Patients and healthy subjects will have one visit to the ENT and ophthalmology
departments to perform the screening tests and if selected, the experiment.
Healthy subjects will undergo a routine screening test in the ophthalmology
department to rule out the presence of glaucoma. Screening in the ENT
department will take place for patients and healthy subjects and will include
tympanometry to assess any middle ear problems, audiograms to determine hearing
threshold, and a test to detect the presence or absence of DPOAEs. If abnormal
eye screening results are obtained for healthy subjects, they will be referred
to their GP, as will be the case for ear abnormalities in all participants.
Detection of signs of an eye or ear condition may cause psychological stress,
however, an early diagnosis will allow treatments to be initiated and therefore
more preservation of visual or hearing functioning. Glaucoma patients will not
perform any ophthalmological screening tests; therefore there is no risk of
identifying any other eye conditions. Subjects who meet the selection criteria
will then undergo the DPOAE testing. The test is non-invasive but they will be
tilted on a table, which may cause minimal discomfort. Patients will spend 1
hour for reception, additional questions, and screening and, if they meet the
selection criteria, 40 minutes for the experiment. The total time will
therefore be about 1 hour and 40 minutes. Healthy subjects will require 30
extra minutes for the eye screening, which will make their total participation
time 2 hours and 10 minutes.