Neurology Department, Zurich University Hospital, CH-8091 Zurich, Switzerland
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ABSTRACT |
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Kori, A. A., A. Schmid-Priscoveanu, and D. Straumann. Vertical Divergence and Counterroll Eye Movements Evoked by Whole-Body Position Steps About the Roll Axis of the Head in Humans. J. Neurophysiol. 85: 671-678, 2001. In healthy human subjects, a head tilt about its roll axis evokes a dynamic counterroll that is mediated by both semicircular canal and otolith stimulation, and a static counterroll that is mediated by otolith stimulation only. The vertical ocular divergence associated with the static counterroll too is otolith-mediated. A previous study has shown that, in humans, there is also a vertical divergence during dynamic head roll, but this report was not conclusive on whether this response was mediated by the semicircular canals only or whether the otoliths made a significant contribution. To clarify this issue, we applied torsional whole-body position steps (amplitude 10°, peak acceleration of 90°/s2, duration 650 ms) about the earth-vertical (supine body position) and earth-horizontal (upright body position) axis to healthy human subjects who were monocularly fixating a straight-ahead target. Eye movements were recorded binocularly with dual search coils in three dimensions. The dynamic parameters were determined 120 ms after the beginning of the turntable movement, i.e., before the first fast phase of nystagmus. The static parameters were measured 4 s after the beginning of the turntable movement. The dynamic gain of the counterroll was larger in upright (average gain: 0.48 ± 0.10 SD) than in supine (0.36 ± 0.10) position. The static gain of the counterroll in the upright position (0.21 ± 0.06) was smaller than the dynamic gain. Divergent eye movements (intorting eye hypertropic) evoked during the dynamic phase were not significantly different between supine (average vergence velocity: 0.87 ± 0.51°/s) and upright (0.84 ± 0.64°/s) positions. The static vertical divergence in upright position was 0.32 ± 0.14°. The results indicate that the dynamic vertical divergence in contrast to the dynamic ocular counterroll is not enhanced by otolith input. These results can be explained through the different patterns of connectivity between semicircular canals and utricles to the eye muscles. Alternatively, we hypothesize that the small dynamic vertical divergence represents the remaining vertical error necessary to drive an adaptive control mechanism that normally maintains a vertical eye alignment.
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INTRODUCTION |
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Divergent vertical ocular
deviation, i.e., skew deviation, combined with conjugate ocular
counterroll (lower eye extorted) is an important neurological sign that
may be present as a consequence of labyrinthine (Halmagyi et al.
1979; Wolfe et al. 1993
), brain stem
(Brandt and Dieterich 1994
), or cerebellar
(Mossman and Halmagyi 1997
) lesions. If, in addition,
the head tilts toward the lower eye and in the same direction as the
ocular counterroll, the syndrome is called ocular tilt
reaction (Brandt and Dieterich 1987
;
Westheimer and Blair 1975
). It has been proposed that
this ocular tilt reaction may reflect an asymmetric input of ascending
afferents carrying otolith (Dieterich et al.
1989
; Halmagyi et al. 1979
; Wolfe
et al. 1993
) or a combination of otolith and semicircular canal
signals (Brandt and Dieterich 1993
; Dieterich and
Brandt 1992
; Lopez et al. 1992
). To date, it is
unclear whether a skew deviation is just an exaggerated physiological
reflex (vestibular-ocular reflex) due to asymmetric vestibular signals
or to a breakdown of mechanisms that normally maintain vertical eye
alignment. To understand the pathophysiology of the ocular tilt
reaction better, it is important to find out whether ocular counterroll
in healthy subjects is already associated with a small vertical
divergence and, if so, whether these vestibularly evoked divergent
vertical eye movements are due to otolith and/or semicircular canal inputs.
In human subjects, head roll evokes counterrotations of both eyes
about head-fixed axis that are oriented approximately parallel to the
stimulus axis. This vestibuloocular response is called ocular
counterroll and is conjugate (Collewijn et al.
1985; Diamond and Markham 1983
). A
dynamic and a static counterroll can be
distinguished. The dynamic counterroll is mediated by both otolith and
semicircular canal stimulation because the gain of the torsional eye
movement response is higher in upright than in supine position
(Groen et al. 1999
; Morrow and Sharpe
1993
; Schmid-Priscoveanu et al. 2000
). The
static counterroll, observed after positioning the head in a roll tilt
position, is mainly due to otolith stimulation, but somatosensory
inputs might also play a small role (Krejcova et al.
1971
).
Less is known of the vertical eye movements associated with dynamic and
static counterroll. Betts et al. (1995) reported a vertical ocular divergence with the hypertropic eye on the side of the
lower ear, when subjects were laying in a side position. They measured
subjectively this vertical divergence with a Hess screen.1 Clearly,
this static vertical divergent response is otolith-mediated. Using
video-oculography, Jáuregui-Renaud et al. (1998)
measured the eye movements of three healthy subjects during
oscillations around the naso-occipital axis in upright and supine
positions at 0.1 and 0.4 Hz. In the dark at 0.4 Hz, two of the subjects showed a significant increase of vertical divergent movements. The
torsional gain, however, increased significantly in only one of the
subjects in the upright position.
Taken together, the data on vertical divergent movements do not yet
allow a conclusion on a probable common mechanism for the vertical
divergent and counterroll responses. The reports are conflicting and,
hence, the role of the otoliths during the dynamic phase of the
responses remains unclear. We attempted to clarify this issue by
strictly controlling eye position during vestibular stimulation. This
was achieved by letting the subjects monocularly fixate a visual target
straight ahead. By covering the other eye, the vertical fusional reflex
was not activated and, at the same time, the direction of the
line-of-sight was restricted. This tight control of gaze during head
roll stimulation was crucial, because a change of the line-of-sight
tilts the eye rotation axis away from the stimulus axis
(Misslisch et al. 1994). Since the pursuit system is not
effective in the torsional direction, fixating a light dot straight
ahead on an unstructured background or in complete darkness has only a
small effect on the gain of the torsional vestibulo-ocular reflex
(Leigh et al. 1989
). In healthy human subjects, we
applied whole-body position steps about the roll axis of the head in
the upright and supine positions and measured the torsional, vertical,
and horizontal movements of both eyes with dual search coils. By
comparing the evoked eye movements between the two stimulation
conditions, we quantified the contribution of the otoliths to the
dynamic component of both the vertical vergence and counterroll
responses. Specifically, we asked whether vertical vergence and
counterroll were directly linked to each other, both statically and
dynamically, as part of a fixed ocular movement pattern. Alternatively,
the relative contribution of the otoliths and semicircular canals to
the static and the dynamic components of vertical vergence and
counterroll could differ. The results from all six subjects in this
study supported the latter hypothesis.
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METHODS |
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Subjects
Six healthy human subjects (3 males and 3 females, between 25 and 56 years old) participated in this study. Subjects were informed of the experimental procedures. The protocol was approved by a local committee and was in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki.
Experimental setup
Subjects were seated on a turntable with three servo-controlled
motor driven axes (prototype built by Acutronic, Jona,
Switzerland). The head was restrained with an individually
molded three-point-mask (Sinmed BV, Reeuwijk, The Netherlands).
The subject was positioned so that the center of the interaural line
was at the intersection of the three axes of the turntable. Movements
of the body were minimized by evacuation pillows and safety belts. The
head was surrounded by an aluminum coil frame (side length 0.4 m)
through which three orthogonal magnetic fields with frequencies of
55.5, 83.3, 41.6 kHz were produced. The synchronous detection of the amplitude-modulated signals yielded instantaneous voltages induced by
the three magnetic fields (Lasker 1995). With a
bandwidth filtering of 0-90 Hz, the peak-to-peak noise was 0.2° in
the torsional and 0.1° in the horizontal and vertical directions.
Eye movement recordings
Three-dimensional eye movements were recorded binocularly with
dual scleral search coils (Skalar Instruments, Delft, The Netherlands) (Collewijn et al. 1985; Robinson 1963
).
For calibration, the voltage offsets of the system were zeroed by
placing the search coils in the center of a metal tube to shield them
from the magnetic field. Then the relative gains of the three magnetic
fields were determined with the search coils mounted on a gimbal system
that was placed in the center of the coil frame. Details of the
calibration procedure can be found in detail elsewhere
(Straumann and Zee 1995
). After local anesthesia of the
conjunctiva and cornea with oxybuprocaine 0.4%, the search coil annuli
were placed around the cornea of both eyes. Eye and chair movements
were digitized at a frequency of 1000 Hz with 16-bit resolution and
stored on a computer hard disk for off-line processing.
Experimental protocol
On the three-dimensional turntable, subjects were moved in the upright or supine position. Then the turntable axis that was oriented parallel to the x-axis of the coil frame (torsional axis) rotated the whole body of the subject clockwise or counterclockwise by 10° with a bell-shaped velocity profile and a peak acceleration of 90°/s2. The duration of the step was 650 ms. Ten position steps were applied to each side in both supine and upright body positions.
During the position steps about the roll axis of the head, the right eye was covered to avoid vertical fusion that might minimize the skew deviation; the left eye was fixing a laser target (diameter 0.1°) projected straight ahead unto an unstructured background to keep the gaze direction of this eye constant during the vestibular stimulation. The distance of the target was 1.52 m in upright and 1.76 m in supine position. Experiments were performed in dim light.
Data analysis
The data analysis was performed with an interactive program
written in MATLAB Version 11. The three-dimensional eye position was
expressed in rotation vectors. A rotation vector r = (rx, ry,
rz) describes the instantaneous
orientation of a body as a single rotation from the reference position;
the vector is oriented parallel to the axis of this rotation and its
length is defined by tan (/2), where
is the rotation angle. The
coordinate system of rotation vectors was defined by the three
head-fixed orthogonal axes of the coil frame with the x-axis pointing
forward, the y-axis leftward, and the z-axis upward. The signs of
rotations about these cardinal axes were determined by the right-hand
rule, i.e., clockwise, leftward, and downward rotations, as seen by the
subject, were positive.
From the rotation vectors, three-dimensional angular velocity vectors
were computed, using the formula (Hepp 1990
)
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RESULTS |
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In all subjects, whole-body steps about the roll axis of the head in upright and supine position evoked an ocular counterroll. A typical example is shown in Fig. 1, where the thick solid line represents the median torsional eye position of 10 trials (thin lines) at each moment in time. In upright position, both dynamic and static torsional eye responses were elicited (Fig. 1A). In supine position, quick phases of nystagmus shortly after the beginning of the turntable rotation moved the eye back or even beyond the zero torsional baseline (Fig. 1B).
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The vertical and horizontal components of evoked eye movements were processed in the same way, i.e., by computing the median trace of the 10 responses. Vergence eye movements were analyzed by subtracting the median traces of the right eye from the median traces of the left eye. The analysis of static responses was based on rotation vectors, and the analysis of dynamic responses on angular velocity vectors. The eye movements evoked by turntable steps about the roll axis of the head to the right and left were symmetric. In the following, we only report on eye movements elicited by stimulation to the left.
Figure 2 summarizes the torsional,
vertical, and horizontal movements of both eyes during torsional
position steps in upright and supine position in a typical subject
(subject 2). In upright position (Fig. 2,
A-C), the ocular counterroll evoked by whole-body steps was
conjugate (Fig. 2A). Vertical eye movements, however, were
clearly disconjugate both in the dynamic and the static phase of the
response (Fig. 2B). The phenomenon that the viewing eye was
the one moving was probably due to the fact that the fovea usually is
not exactly aligned with the optical axis (Carpenter 1988; Howard and Rogers 1995
) and the fact that
the torsional rotation axis of the turntable was head-centered, not
eye-centered. Both these effects, however, could not have influenced
the consistent vertical vergence response, because the horizontal
movements of both eyes were found to be approximately conjugate (Fig.
2C). No consistent pattern of horizontal eye movements was
found during the dynamic phase. During the static phase, however, both
eyes shifted horizontally to the side with the higher ear (in this case
the right side).
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Vestibular stimuli about the naso-occipital axis in the supine position (Fig. 2, D-F) evoked only a small torsional conjugate eye movement response during the dynamic phase, and no static counterroll (Fig. 2D). Vertical eye movements showed variable amounts of divergence during the dynamic phase, but conjugacy during the static phase (Fig. 2E). The horizontal movement components were conjugate at the beginning of the vestibular stimulation, but then the eyes diverged somewhat (Fig. 2F).
Two moments in time after the beginning of the turntable movement were defined to quantify the dynamic and static behavior of eye movements evoked by the vestibular stimulus in the roll axis of the head in supine and upright body position: 1) at 120 ms the dynamic parameters and 2) at 4 s the static parameters. For the torsional component, we computed the dynamic torsional gain by dividing the torsional eye velocity by the torsional chair velocity. For the horizontal and vertical components, it was not possible to compute a gain; hence, we took the velocity values of the eye for further data analysis. As static parameters, 4 s after the beginning of the turntable movement, we determined the three-dimensional position of both eyes. For the torsional component a static gain was computed by dividing the torsional eye position by the turntable position in the roll axis.
For all six subjects, Fig. 3 shows the dynamic and static torsional gains in upright and supine positions during the turntable step in the roll axis of the head. In both body positions, the torsional dynamic gains were significantly above zero; the average dynamic gain was 0.48 in upright position and 0.36 in supine position (Fig. 3A). This difference was significant. The static torsional gains in upright position (Fig. 3B) had an average of 0.21 and therefore were smaller than the corresponding dynamic gains, but still significantly different from zero. Obviously, there was no static counterroll in supine position. Averages and standard deviations are given in Table 1.
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To compare the torsional eye movements with the vertical and horizontal
ones better, Fig. 4 and Table 1 summarize
the torsional, vertical, and horizontal velocities (dynamic responses)
and positions (static responses) of the covered right eye of all
six subjects in supine and upright body positions. The dynamic
torsional velocities were significantly larger in upright than in
supine position (Fig. 4A). The average velocity of the
dynamic torsional component was 3.6°/s in upright position and
2.6°/s in supine position. There was also a significant difference in
the static torsional eye position between upright and supine, with the
torsional position in upright significantly different from zero (Fig.
4B). The average position of the static torsional component
was 2.09° in upright position and 0.13° in supine position. The
dynamic vertical velocities showed no differences between upright and
supine positions (Fig. 4C). During static roll stimulation,
there was a significant difference of vertical eye position between
supine and upright (Fig. 4D); in upright position the
covered right eye (on the side of the upper ear) was significantly
lower (positive according to right-hand rule) than in the supine
position. The average static vertical eye position was 0.2° in
upright and 0.01° in supine position. During the dynamic phase, the
median horizontal velocities were unchanged between upright and supine
positions (Fig. 4E). In the static phase, however, there was
a significant horizontal displacement of the covered eye to the side
with the higher ear in the upright position (Fig. 4F).
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A summary of the torsional, vertical, and horizontal vergence responses
to the whole-body step movements about the roll axis of the head in
both supine and upright positions is given in Fig. 5 and Table
2. Torsional eye movements were conjugate
in the upright and supine positions during both the dynamic (Fig.
5A) and static (Fig. 5B) phases of vestibular
stimulation. During the dynamic phase, the vertical divergence in
upright and supine positions were significantly different from zero,
but there was no difference between the two body positions (Fig.
5C). The average dynamic vertical divergence was 0.84°/s
in upright position and 0.87°/s in supine position. During the static
phase, the average vertical divergence was 0.32° in upright position
and 0.05° in supine position. Thus the results show a significant
vertical divergence during the static phase in upright position (Fig.
5D). There was no difference between the horizontal vergence
elicited in upright and supine positions during both the dynamic (Fig. 5E) and static (Fig. 5F) phases.
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DISCUSSION |
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The present study investigated the contribution of the otoliths to the counterroll and skew deviation observed in healthy human subjects during a head tilt about the roll axis. To eliminate possible contributions of the cervico-ocular reflex, whole-body step movements were applied. This stimulus evoked 1) a dynamic counterroll that was larger in upright than in supine position; 2) a dynamic vertical divergence (intorting eye hypertropic) that was not affected by body position; and 3) a static counterroll and vertical divergence (intorting eye hypertropic) in upright position.
Earlier studies using sinusoidal oscillations in the roll plane have
demonstrated dynamic counterroll in healthy subjects (Averbuch-Heller et al. 1997; Collewijn et al.
1985
; Diamond and Markham 1983
; Peterka
1992
). Recently, we showed that the gains of dynamic
counterroll were significantly smaller in the supine position than in
the upright position (Schmid-Priscoveanu et al. 2000
),
confirming the contribution of both the semicircular canals and the
otoliths to the dynamic counterroll. In the present study, in which
subjects were not oscillated but stimulated with impulses of velocity,
the dynamic gain of ocular torsion was again significantly increased by
the otoliths (~40%). One study, however, reported unchanged
torsional gains in the upright and supine positions during passive roll
tilt (Tweed et al. 1994
). These results could be due to
a different analytical method for computing gain. The authors
determined the three-dimensional VOR-gain matrices by pooling the data
from rotations about horizontal, vertical, and torsional axes and
assuming vectorial summation of gains in three dimensions, which is
only an approximation to the actual VOR behavior.
It is well known that ocular counterroll can be also evoked by static
head roll (Diamond and Markham 1983), but the gain is considerably smaller than during dynamic counterroll
(Averbuch-Heller et al. 1997
; Collewijn et al.
1985
; Diamond and Markham 1983
). In our study,
the gain of the static counterroll was less than half of the dynamic
counterroll in upright position (~45%).
Betts et al. (1995) described a vertical divergence
during static roll tilt in healthy subjects using the Hess screen
(hypertropic eye ipsilateral to the head tilt). We were able to
replicate this finding of a static vertical divergence; the average
static vertical divergence was 0.32° when the head was rolled 20°
from the upright position.
Jáuregui-Renaud et al. (1998) reported that
a vertical divergence can be also evoked by oscillatory dynamic roll
tilt. Whether additional otolith input in upright position could
enhance this response remained unclear, since the coordinate system of
three-dimensional eye velocity was not specified and, hence, the effect
of eye position could not be derived from the published data. The
authors reported that two of the three subjects showed a significant
increase of vertical divergence velocity in the upright position
compared with the supine position. Our results, which are based on
position steps and the precise control of eye position by monocular
fixation, show that there is no significant increase of vertical
divergence velocity by otolith input. A limitation of the dynamic data
in our study, however, has to be taken into account; because of
intervening quick phases, which appeared very shortly after the
beginning of the turntable movement, dynamic vertical divergence was
determined after 120 ms. We therefore do not know whether, in the
absence of quick phases, a larger dynamic vertical divergence would
have developed a few milliseconds later.
A model of the vestibular system that includes dynamic counterroll and
dynamic vertical divergence must solve the following problem that is
posed by the experimental results described: Dynamic counterroll has a
higher gain with additional otolith contribution, but dynamic vertical
divergence does not. On the other hand, both static counterroll and
static vertical divergence are evoked by otolith input. This can be
explained through the different contribution of the otoliths and
semicircular canals during head roll. Unilateral utricular stimulation
in cats (Suzuki et al. 1969) induced mainly a
contraction of the oblique muscles and, to a lesser extent, a
contraction of the recti muscles. The stimulation of the semicircular canals, on the other hand, led to a stronger contraction of the recti
muscles than of the oblique muscles. This could explain why only during
the static phase of the response in upright position, when just the
otoliths are stimulated, a small vertical divergence is elicited.
During the dynamic phase, however, when both otolith and semicircular
canal are stimulated, due to the main contribution of the semicircular
canals to vertical divergence, no significant difference can be
appreciated between the upright and supine positions. Recently,
Cremer et al. (2000)
reported a single case of a patient with an isolated posterior semicircular canal fistula in whom ear
pressure led to a conjugate vertical-torsional nystagmus but no skew
deviation. Stimulation of the posterior semicircular canal leads to an
activation of the ipsilateral superior oblique and contralateral
inferior rectus, both of which are eye depressors. Thus vertical
conjugate eye movements are expected. Similarly, stimulation of the
anterior semicircular canal leads to an excitation of the ipsilateral
superior rectus and contralateral inferior oblique, also with conjugate
vertical eye movements since both muscles are elevators. However, a
simultaneous stimulation of both semicircular canals (as it happens
during head roll) might result in a vertical divergence; the primary
action of the superior rectus is that of elevation and would prevail
over the depression of the ipsilateral superior oblique since this is
only its secondary action. In the other eye, a depression which is the
primary action of the inferior rectus would prevail over the elevation
of the inferior oblique because this is its secondary action.
An alternative explanation is also purely hypothetical: Vertical
divergence might inherently be a part of the torsional vestibulo-ocular reflex in that the intorting eye is driven upward by activation of the
superior rectus muscle, while the extorting eye is driven downward by
activation of the inferior rectus muscle, because, as we mentioned
before, the vertical action of the recti muscles exceeds the antagonist
vertical action of the oblique muscles. During binocular vision, the
static vertical divergence can easily be overcome by the vertical
fusional reflex. This reflex, however, is too slow to suppress the
dynamic vertical divergence (latency ~160 ms). For the prevention of
dynamic vertical diplopia during torsional vestibular stimulation, only
an adaptive control mechanism, e.g., via the cerebellum (Leigh
and Zee 1999; Raymond et al. 1996
) is realistic.
The remaining dynamic vertical divergence, which is unchanged with or
without otolith stimulation, might simply reflect the minimal dynamic
error necessary to drive this adaptive control mechanism to maintain
vertical alignment. In pathologic circumstances the vertical
misalignment becomes manifest because the otolith (Dieterich et
al. 1989
; Halmagyi et al. 1979
;
Wolfe et al. 1993
) and, sometimes in addition,
semicircular canal (Brandt and Dieterich 1993
;
Dieterich and Brandt 1992
; Lopez et al.
1992
) signals are so asymmetric that the hypothetical adaptive
control mechanism breaks down.
To confirm our hypothesis of an active suppression mechanism of
vertical divergence by the CNS, it will be necessary to record binocular three-dimensional eye movements during torsional vestibular stimulation in patients or animals with specific lesions. If for instance, the cerebellar flocculus would be the main structure that
adaptively suppresses the dynamic vertical divergence during head roll,
we expect that patients with floccular lesions (e.g., cerebellar
atrophy) would show an increase in the velocity of the vertical
divergence during the torsional position step. It is known that
cerebellar disease often leads to an eye-position-dependent, vertical
ocular misalignment (Versino et al. 1996). It would be of no surprise if in these patients large vertical divergence movements
during vestibular stimulation could be observed. So far we only know
that specific cerebellar lesions including the nodulus and uvula may
cause a static vertical divergence in the context of an ocular tilt
reaction (Mossman and Halmagyi 1997
).
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ACKNOWLEDGMENTS |
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We are grateful to A. Züger for technical assistance.
This work was supported by the Swiss National Science Foundation (3231-051938.97 and 3200-052187.97) and the Betty and David Koetser Foundation for Brain Research.
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FOOTNOTES |
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Address for reprint requests: A. A. Kori (E-mail: adriana.kori{at}nos.usz.ch).
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1
The Hess screen test measures the horizontal and
vertical deviation between both eyes in the absence of fusional
constraints (Hess 1916).
Received 6 June 2000; accepted in final form 10 October 2000.
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REFERENCES |
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