3D gaze stability as a meausure for visual-vestibular function

Dizziness and instability are common symptoms. The primary cause is often
attributed to the vestibular system, which contributes to body balance by
generating muscle reflexes. Additionally, the vestibular system aids in gaze
stabilization through the vestibulo-ocular reflex (VOR). The VOR, along with
the optokinetic response (OKR), is responsible for generating eye movements
during head motions. Sudden loss of function in one vestibular organ, due to
illness or accident leads to dizziness, gait instability, and disorientation.
There are also complaints of visual disturbances during head movements, such as
visual lag and oscillopsia. Unilateral vestibular loss will be compensation by
the central nervous resulting in a reduction of symptoms. Complete compensation
can even lead to the resolution of symptoms. Examination of eye movements in
compensated cases reveals the disappearance of nystagmus and the development of
compensatory saccades. This compensation can occur spontaneously or be
facilitated by vestibular physiotherapy. A crucial prerequisite for complete
compensation is a well-functioning visual system, as it calibrates the
reflexes. Some patients with retinal abnormalities also experience dizziness
due to reduced motion detection. The retinal abnormality prevents the proper
use of visual signals for VOR adaptation. This condition affects patients with
stationary retinal dysfunction caused by an inherited gene defect, which can
cause night blindness or color blindness.

This study aims to measure both patient groups to comprehensively assess and
compare the eye movements under altered visual and vestibular input with those
of normal subjects. During the VOR test, a fixation point is presented, and the
subject's head is moved using a rotating chair. Compensatory eye movements,
generated by joint action of the vestibular system and the visual tracking
system, are measured using an eye movement tracking system. In the OKR test, a
moving visual stimulus is displayed on a screen while the subject's head
remains still. Once again, eye movements are measured using the eye movement
tracking system. Conventional clinical diagnostics typically tests the
vestibulo-ocular reflex (VOR) and the optokinetic reflex (OKR) separately,
using different stimuli. In the proposed experiment, the same stimuli are used
for both conditions, so the difference in gaze stability between the OKR and
compensatory eye movements is caused by the cooperation between OKR and VOR.
The aim is to determine how this cooperation affects gaze stability. The
hypothesis is that the ability of the vestibular system to improve the visual
response is an indicator of vestibular function.

An important clinical outcome measure of gaze stability is the combination of
gain and phase. Gain represents the ratio of head movements to eye movements
induced by a moving target in a stationary environment or the ratio of eye
movements to image movements with a stationary head. Phase refers to the
temporal difference between them. Both measures are relative indicators of gaze
stabilization. In this study, we will investigate retinal slip velocity as an
absolute measure of gaze stabilization accuracy. Typically, only horizontal and
vertical eye movements are measured, while torsion of the eyeball is a
component of nearly every eye movement. However, due to methodological
limitations in measuring torsion in patients, torsional movements are often
disregarded.

The aim of this observational and exploratory study is to describe the accuracy
of gaze stabilization in the presence of abnormal vestibular and visual
functions. Visually induced image movements are used as the basis for gaze
stability for each subject. Visuo-vestibular-induced eye movements generated by
similar stimuli are superimposed on these baseline movements. The interaction
between the visual tracking system and vestibular responses typically results
in improved gaze stability compared to the optokinetic response.

The study consists of 2 different experiments to answer the primary and
secondary research questions. During the first experiment, the participant
remains stationary behind a computer screen, and we measure the characteristics
and reflexes of eye movements while the head is still, inducing the OKR. During
the second experiment, we utilize the motion platform and measure the
characteristics and reflexes of eye movements during head movements, inducing
the VOR. To document hearing and vision, visual acuity is measured, and a tone
and speech audiogram is conducted. Two questionnaires, the Dizziness Handicap
Inventory (DHI) and a version of a questionnaire used in ERGO, are administered
to document the nature and severity of symptoms. Although some patients are
measured before and after treatment, this study does not evaluate the treatment
itself. Instead, it aims to determine whether the patient's perception (VAS
score) regarding the nature and severity of their symptoms aligns with the 3D
eye movements and questionnaires.

Experiment 1

During this experiment, the participant remains still in front of a monitor,
with the head supported by a chin rest to measure eye movements during image
motion. The visual tracking system and the balance system are thus decoupled.
We measure the participant's eye movements during:

Saccade test, examining the relationship between saccade duration, saccade
amplitude, and saccade velocity during shifts of a fixation target in
horizontal and vertical directions with various amplitudes. In the horizontal
direction, 10 amplitudes are tested 6 times, and in the vertical direction, 8
amplitudes are tested 6 times. A total of 108 trials (~7 min).
Smooth pursuit test in horizontal and vertical directions, where a fixation
target moves sinusoidally at a constant speed. Both horizontal and vertical
movements consist of 10 cycles at 3 different speeds. A total of 6 trials (~3
min).

Experiment 2

During this experiment, the participant sits on the motion platform and fixates
on a stationary visual target in space while being moved by the platform. The
platform's movements involve rotations around 5 different axes: roll, pitch,
yaw, LARP, and RALP. The visual and vestibular systems now work together
maximally for gaze stabilization. We measure the participant's eye movements
during 2 different motion stimuli:

Sinusoidal movements: The platform performs a sinusoidal motion around one of
the 5 main axes for 30 seconds. The sinusoidal movements are executed at 0.5 Hz
(with amplitudes of 2, 4, and 8 degrees) and at 1 Hz with a fixed amplitude of
2 degrees. A total of 20 trials (~12 min).
Impulse movements: Within 2 seconds, the platform rapidly rotates around one of
the 5 main axes to measure the vestibulo-ocular reflex in the first 100 ms of
the movement. The impulse is a maximum of 150 degrees/s^2, and each axis is
tested 3 times. A total of 15 trials (~5 min). Two different visual tasks are
used during this experiment.

Experiment 3
This is a repetition of experiment 1, but now the visual target is attached to
the platform, causing the target to move along with the platform. The
platform's movements are the same as those in experiment 1 (~5 min).

We measure eye movements using a video-oculography (VOG) headset. This VOG
headset measures horizontal, vertical, and rotational eye movements based on
pupil detection and iris features. The headset also includes an accelerometer
for precise measurement of the timing and magnitude of induced head rotations.
The VOG headset is described in Chapter 6 of this application: investigational
products and the IMDD. The use of the motion platform is described in Chapter 7
of this application and the corresponding IMDD. The total duration of the
experiments, including preparations, is approximately 45-60 minutes.

For the recording of horizontal, vertical, and rotational eye movements,
participants wear a video-oculography headset (see also the IMDD). This headset
has a tight fit but does not hinder the ability to make eye and head movements.
During Experiment 1, the participant sits in a chair in front of a computer
screen. During Experiments 2 and 3, the participant is seated in a rotating
chair setup. This setup is easily accessible for both young and elderly
participants, with a specially designed staircase. The participant is secured
"body-fixed" using a 5-point harness in a comfortable chair. The head is
immobilized using a headrest and a biteboard. This reduces comfort but is not
perceived as burdensome.