The role of suppression in amblyopia.

Abstract

This study had three main goals: to assess the degree of suppression in patients with strabismic, anisometropic, and mixed amblyopia; to establish the relationship between suppression and the degree of amblyopia; and to compare the degree of suppression across the clinical subgroups within the sample.
Using both standard measures of suppression (Bagolini lenses and neutral density [ND] filters, Worth 4-Dot test) and a new approach involving the measurement of dichoptic motion thresholds under conditions of variable interocular contrast, the degree of suppression in 43 amblyopic patients with strabismus, anisometropia, or a combination of both was quantified.
There was good agreement between the quantitative measures of suppression made with the new dichoptic motion threshold technique and measurements made with standard clinical techniques (Bagolini lenses and ND filters, Worth 4-Dot test). The degree of suppression was found to correlate directly with the degree of amblyopia within our clinical sample, whereby stronger suppression was associated with a greater difference in interocular acuity and poorer stereoacuity. Suppression was not related to the type or angle of strabismus when this was present or the previous treatment history.
These results suggest that suppression may have a primary role in the amblyopia syndrome and therefore have implications for the treatment of amblyopia.

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The Role of Suppression in Amblyopia
Jingrong Li,1Benjamin Thompson,2Carly S. Y. Lam,3,4Daming Deng,1Lily Y. L. Chan,3,4
Goro Maehara,5George C. Woo,3Minbin Yu,1and Robert F. Hess5
PURPOSE. This study had three main goals: to assess the degree
of suppression in patients with strabismic, anisometropic, and
mixed amblyopia; to establish the relationship between sup-
pression and the degree of amblyopia; and to compare the
degree of suppression across the clinical subgroups within the
sample.
METHODS. Using both standard measures of suppression (Bago-
lini lenses and neutral density [ND] filters, Worth 4-Dot test)
and a new approach involving the measurement of dichoptic
motion thresholds under conditions of variable interocular
contrast, the degree of suppression in 43 amblyopic patients
with strabismus, anisometropia, or a combination of both was
quantified.
RESULTS. There was good agreement between the quantitative
measures of suppression made with the new dichoptic motion
threshold technique and measurements made with standard
clinical techniques (Bagolini lenses and ND filters, Worth 4-Dot
test). The degree of suppression was found to correlate directly
with the degree of amblyopia within our clinical sample,
whereby stronger suppression was associated with a greater
difference in interocular acuity and poorer stereoacuity. Sup-
pression was not related to the type or angle of strabismus
when this was present or the previous treatment history.
CONCLUSIONS. These results suggest that suppression may have
a primary role in the amblyopia syndrome and therefore have
implications for the treatment of amblyopia. (Invest Ophthal-
mol Vis Sci. 2011;52:4169–4176) DOI:10.1167/iovs.11-7233
S
by the pioneering work of Travers,1Jampolsky,2and later,
Pratt-Johnson and Wee,3,4who showed that its regional distri-
bution (visual field topography) depends on the type of stra-
bismus present. More recently, this approach has been carried
on by Joosse et al.5–7whose innovative work has highlighted
the different types of suppression that occur in strabismic
amblyopia and how it varies within any one strabismic subpop-
ulation.
Although we now have a better idea of the position and
shape of suppressed scotomata, we are still ignorant of their
role and importance in the amblyopia syndrome, a condition in
which there is loss of vision of a nonorganic nature, secondary
to strabismus, anisometropia or form deprivation. There are
some fundamental questions that remain unanswered, the
most important of which relates to whether suppression is of
primary or secondary importance to amblyopia. For example,
suppression could simply follow as a consequence of amblyo-
pia as a way of ensuring that the input from a weaker eye does
not disrupt binocular perception. This view is compatible with
current treatment approaches that focus on patching or penal-
ization as a first step without any regard for suppression, which
is often not quantified clinically and is rarely treated as a
separate entity. The idea that amblyopia and suppression are
separate entities gains some support from the suggestion that
there is a reciprocal relationship between the strength of
suppression and the degree of amblyopia; the greater the
amblyopia, the less suppression is needed to eliminate that
eye’s input from the binocular mix.8The opposite view, how-
ever, is that suppression causes the visual dysfunction in am-
blyopia. In this scenario, the suppression develops due to a
disruption of binocular function (strabismus or anisometropia),
and it is the chronic suppression itself that results in amblyo-
pia. This alternative view gains some support from the recent
finding that, even in adults using repetitive transcranial mag-
netic stimulation (rTMS), a noninvasive means of transiently
altering neural excitability in the human cortex, a 10-minute
application of TMS can temporarily improve contrast sensitiv-
ity in amblyopia,9suggesting that visual function is not lost but
suppressed. Further support comes from the finding that anti-
suppression therapy not only results in improved binocular
function but also in improved monocular functioning of the
adult amblyopic eye.10However, before one can accept that
suppression is of primary importance in the amblyopic syn-
drome, the issue of the relationship between the degree of
amblyopia and the strength of suppression should be re-
opened, for it is only if there is a direct relationship between
these two clinical features that it would be reasonable to
assume that suppression is of primary importance. The present
support for a reciprocal relationship rests on only a small
sample of patients with clinical suppression (n ? 10), only two
of whom had visual acuity worse than 20/30 in the amblyopic
eye.8
Recently a novel method of quantifying binocular combina-
tion in the normal visual system has been developed,11and we
uppression plays a key role in the amblyopic syndrome. Its
clinical importance was recognized more than 60 years ago
From the1State Key Laboratory of Ophthalmology, Zhongshan
Ophthalmic Center, Sun Yat-sen University, Guangzhou, People’s Re-
public of China; the2Department of Optometry and Vision Science,
Faculty of Science, The University of Auckland, Auckland, New Zea-
land; the3School of Optometry, and the4The Hong Kong Jockey Club
Sports Medicine and Health Sciences Centre, Faculty of Health and
Social Sciences, The Hong Kong Polytechnic University, Hong Kong
SAR, China; and the5Department of Ophthalmology, McGill Univer-
sity, Montreal, Quebec, Canada.
Supported by equipment/resources donated by The Hong Kong
Jockey Club Charities Trust, Hong Kong Polytechnic University Inter-
nal Competitive Research Grant CRG G-YH71 (CSYL), University of
Auckland Faculty Development Research Fund Award (BT), CIHR
Grants MOP 53346 and PPP93073 (RFH), the Fundamental Research
Funds of the State Key Lab of Ophthalmology, Sun Yat-sen University
(JL), a Thrasher Research Fund Early Career Award (JL), and the
Guangdong Province International
2010B050100014 (DD).
Submitted for publication January 15, 2011; revised February 27,
2011; accepted March 16, 2011.
Disclosure: J. Li, None; B. Thompson, None; C.S.Y. Lam, None;
D. Deng, None; L.Y.L. Chan, None; G. Maehara, None; G.C. Woo,
None; M. Yu, None; R.F. Hess, None
Corresponding author: Minbin Yu, Department of Glaucoma, De-
partment of Optometry and Vision Science, Zhongshan Ophthalmic
Center, Guangzhou 510060, People’s Republic of China;
max-yu@tom.com.
Collaboration Project Grant
Eye Movements, Strabismus, Amblyopia, and Neuro-Ophthalmology
Investigative Ophthalmology & Visual Science, June 2011, Vol. 52, No. 7
Copyright 2011 The Association for Research in Vision and Ophthalmology, Inc.
4169

Page 2

have applied it to quantifying the strength of suppression in
both strabismic and anisometropic amblyopes,12,13using a
global motion stimulus in which signal elements moving in a
coherent direction are seen by one eye and noise elements
moving in random directions are seen by the other eye. This
method is an accurate way, within the context of signal/noise
analysis, of measuring12,13and treating10suppression within
the central field. In this study we used this approach to assess
the strength of suppression in a group of anisometropic,
mixed, and strabismic amblyopes. The method provides a
more quantitative means (better resolution) of measuring the
degree of suppression compared with the Worth 4-Dot test or
the use of a red filter and neutral density wedge. We first
assessed the relationship between this new signal/noise
method that can precisely quantify suppression and more tra-
ditional, relatively coarse, measures of suppression (Worth
4-Dot test and modified Bagolini test). We then addressed the
following two questions: What is the relationship between
visual losses in amblyopia (acuity and stereo) and the degree of
suppression? How does suppression vary within the amblyopic
clinical population? The answers to these questions bear on the
issue of whether suppression plays a causal role in the visual
loss that characterizes amblyopia.
METHODS
Participants
A total of 43 amblyopic observers (23 females, 20 males), between the
ages of 9 and 56 years (mean age, 20.7 ? 11.9), and 10 normal
observers (4 females, 6 males), between the ages of 20 to 35 years
(mean age, 29.20 ? 5.39), who met the inclusion criteria were en-
rolled. Clinical details for the amblyopic observers are provided in
Table 1.
The normal observers acted as the control group and had equal
visual acuity in each eye of at least 20/20; absence of any ocular,
oculomotor, or binocular abnormalities; normal stereoacuity (?20
seconds of arc); and a spherical equivalent refractive error of between
?1.00 and ?3.00 D, with an unequal spherical equivalent of not more
than a 1-D difference between the eyes detected during a standard
ocular examination; and a cylindrical correction of less than 1 D. The
amblyopic group was defined according to the Preferred Practice
Protocol (PPP) of The American Academy of Ophthalmology14and
classified under one of the following clinical conditions: strabismic
amblyopia (with an angle of strabismus of less than 35?), anisome-
tropic amblyopia with a visual acuity loss in the worse eye of no worse
than 20/100, and mixed (those that met the criteria for both types of
amblyopia). Subjects with strabismus due to ocular albinism, diplopia,
anomalous correspondence, or a medical history of seizures were
excluded. All tests were conducted at a constant room luminance,
measured with a digital lux meter (TES Electronic Corp., Taipei, Tai-
wan). This study complied with the Declaration of Helsinki and was
approved by the Ethics Committee of Zhongshan Ophthalmic Center
and The Hong Kong Polytechnic University. Informed consent was
obtained from all participants before data collection. On the basis of
previous data from both amblyopic observers13and observers with
normal binocular vision (Thompson, unpublished data, 2010), we
estimated a difference in fellow fixing eye contrast at a balance point
of 70% contrast between controls and observers with amblyopia with
a maximum SD of 17%. To detect this difference at a significance level
of P ? 0.01 with a power of 0.99 would require three participants per
group. Our smallest subgroup contained 10 participants.
Stereo Acuity Test
Stereoacuity was assessed using the Randot stereo graded circle test
(Random Dot 2 Acuity Test, Vision Assessment Corp., Elk Grove Vil-
lage, IL). These values are reported in Table 1.
Suppression Measurement
The Worth-4-Dot Test. The Worth-4-Dot test was performed at
near (33 cm) and far (6 m) test distances. The filters were placed,
according to convention: red over the right eye and green over the left
eye. To ensure the visibility of each filter, the participants’ eyes were
covered alternately to ensure that each eye was visibly aware of the red
and green filters. When this testing was performed monocularly, all
participants reported seeing two red dots when the left eye was
occluded (right eye wearing the red filter) and three green dots when
the right eye was occluded (left eye wearing the green filter). Partici-
pants were asked to report the number and color of the dots they saw
under photopic (118 lux) followed by scotopic (?0.1 lux) conditions.
A scoring system was assigned to grade the depth and the size of the
suppression scotoma. For example, a four-dot response with the white
dot at the bottom was given a score of 0 (no suppression), while a two-
or three-dot response received a score of 2 (complete suppression). A
score of 1 (partial suppression) was assigned to observers who re-
ported that they saw four dots, with the color of the bottom white dot
being perceived as either green or red. The sum of near and far scores,
which could range from 0 to 4, was used to represent the overall level
of suppression as measured by this test, as we found no reliable
difference between the near and far measurements (sign test, P ? 1.0).
The Neutral-Density Filter with the Bagolini Striated
Lens Test. The relative depth of suppression in the amblyopic eye
was assessed by combining the Bagolini striated lenses test with neu-
tral-density (ND) filters.15Each observer viewed a light source (30
cd/m2) held at 33 cm while wearing Bagolini striated lenses under low
ambient room illumination (5 lux). Under normal viewing conditions,
participants with normal binocular function perceive an X, represent-
ing the combination of the / seen by one eye and the ? seen by the
other. However, for participants with suppression, only one line (/ or ?)
is perceived within the region affected by the suppression scotoma. To
measure the strength of this suppression, progressively stronger ND
filters can be placed over the fellow eye until the imbalance in lumi-
nance between the two eyes is sufficiently strong to overcome the
suppression and allow for the percept of the X. To achieve this, ND
filters (Wratten; Eastman Kodak Company, Rochester, NY), increasing
in 0.3-log-unit increments were mounted on a bar. The filters ranged
from 0.3 to 3 log units and had a transmittance ranging from 50% to
0.1%. The ND filter bar was held vertically in front of the fellow fixing
(fixating) eye and moved upward to increase the strength of the ND
filter. Participants were asked to report when they could perceive an
X. The end point of this test was defined as the ND filter strength at
which the intensity of the line seen by the amblyopic eye was per-
ceived as the same or slightly stronger than the line seen by the fellow
fixing (fixating) eye. To ensure the accuracy of this end point, the ND
filter strength was increased by an additional 0.6 log units below this
balance point, and the end point was measured again from seeing to
nonseeing until a balanced reversal point was achieved.
Dichoptic Motion Coherence
Threshold Measurements
The method we used for measuring interocular suppression using
random-dot kinematograms has been described in detail elsewhere.13
Briefly, stimuli were displayed using a video goggle apparatus (Z800 3D
Visor; eMagin Corp., Washington, DC) driven by a laptop computer
(MacBook Pro; Apple Computer, Cupertino, CA, running MatLab; The
MathWorks, Natick, MA) and the Psychophysics Toolbox, version
3.12,13,16This apparatus allowed for separate images to be presented to
each eye and for the images in each eye to be aligned by the partici-
pants, using routines within the stimulus presentation software. Stim-
uli were random-dot kinematograms, which consisted of a population
of signal dots, all moving in a common direction, and a population of
noise dots, that moved randomly. Dots were bright against a mean
luminance background (35 cd/m2). The luminance modulation (Mi-
chelson contrast) and hence the visibility of the dots could be varied by
4170Li et al.
IOVS, June 2011, Vol. 52, No. 7

Page 3

TABLE 1. Clinical Details for the Observers with Amblyopia
Observer Sex
Age
(y)Type
Cycloplegic
Refractive
Error (OD/OS)
LogMAR
Visual
Acuity (OD)
LogMAR
Visual Acuity
(OS)
Ocular Dev.
(Prism D) History
Stereopsis
(sec arc)
01F 17A
?3.35?0.50x145
?1.25?0.50x110
?2.00?0.25x161
?1.25?0.75x178
?0.75 DS
?3.25?0.50x076
?4.75 DS
?7.50?3.00x040
?2.75?0.50x170
?6.00?1.50x013
?2.50 DS
?4.50?2.50x095
Plano DS
?4.25?2.00x155
?0.50DS
?4.50DS
Plano DS
?2.50?3.50x175
?5.50?1.00x165
?1.00?0.75x175
?5.00?1.50x021
?6.75?1.75x170
?1.00DS
?2.25DS
Plano DS
?7.00?0.75x180
?1.00?0.50x180
?2.50?1.00x180
?1.00?3.50x165
Plano DS
?0.50?0.50x175
?7.50?1.25x75
?1.25?0.50x065
?3.50?1.25x175
?3.50 DS
Plano DS
?0.50 DS
?2.50 DS
?3.50?1.00x100
Plano DS
?1.25 DS
?4.50 DS
?5.00?0.50x130
?4.25?0.50x010
?6.50?1.50x177
?4.50?2.00x175
0.09
?0.084XPDiagnosed: 7 years old
(?) Patched: 4 years
Diagnosed: 8 years old
(?) Patched: 2 years
Diagnosed: 43 years old
No treatment
No detection
No treatment
No detection
No treatment
Diagnosed: 17 years old
No treatment
Diagnosed: 11 years old
No treatment
Diagnosed: 13 years old
No treatment
Diagnosed: 13 years old
No treatment
Diagnosed: 6 years old
(?) Patched: 6 years
Diagnosed: 6 years old
(?) Patched: 4 years
No detection
No treatment
No detection
No treatment
Diagnosed: 15 years old
No treatment
Diagnosed: 21 years old
No treatment
Diagnosed: 15 years old
No treatment
Diagnosed: 7 years old
(?) Patched: 4 years
No detection
No treatment
No detection
No treatment
No detection
No treatment
Diagnosed: 8 years old
(?) Patched: 2 years
No detection
No treatment
Diagnosed: 3 years old
(?) Patched: 2 years
(?) Surgery at 7 years old
Diagnosed: 6 years old
(?) Patched
(?) Surgery
Diagnosed: 6 years old
(?) Surgery at 5 years old
Diagnosed: 6 years old
(?) Patched
(?) Surgery at 7 years old
No detection
No treatment
No detection
No treatment
Diagnosed: 5 years old
(?) Patched
(?) Surgery
Diagnosed: 6 years old
(?) Patched
(?) Surgery
100
02F11A0.04
?0.184XP 50
03F 43A00.150 40
04F56A0 0.15070
05F 34A00.180 400
06 F17 A0 0.520Suppression
07F11 A0 0.400200
08F 13A
?0.180.700Suppression
09F13 A
?0.080.15 070
10F 32A 0.3000Suppression
11F 24A00.10070
12M43A0 0.400100
13 M 19A
?0.08 0.700 Suppression
14M 15A 0.1400 80
15M21A0.150.08 0100
16 M15 A
?0.180.700 Suppression
17M19A0 0.300 120
18M 21A0.15
?0.080100
19M40A00.10 0 100
20M37A 0.3000200
21 M10A00.700200
22 M18A00.10 0 200
23F10 AS 0.100 0*30
24F 48 AS
?5.00?0.50x130
?3.25?0.75x090
0.700 20ET, 35ET?
Suppression
25M10AS
?1.00?0.75x005
?2.75?1.75x170
?1.25 DS
?4.25?1.00x165
?0.080.050*20
26M17AS00.220*Suppression
27 M15AS
?1.25?1.00x175
?6.50?2.25x165
?5.25?2.00x165
Plano DS
?1.25 DS
?2.00?1.00x165
00.70 0, 20XT?
Suppression
28 M26AS0.52
?0.08 10XT, 15XT?
Suppression
29M29 AS
?0.180.05 15ET 70
30F10S
?7.00?2.25x010
?8.00?2.50x170
0 0.40*100
(continues)
IOVS, June 2011, Vol. 52, No. 7
The Role of Suppression in Amblyopia4171

Page 4

increasing the luminance of the dots, with respect to the background,
according to the following equation:
Dot luminance contrast (%) ? 100[(Ldots? Lbackground)/(Lbackground)]
where Ldotsand Lbackgroundare the dot and background luminance,
respectively. Signal dots were presented to one eye, and noise dots
were presented to the other eye. The task was to indicate the motion
direction of the signal dots. A staircase procedure controlled the
relative proportion of signal-to-noise dots in the stimulus to allow for
the measurement of a motion coherence threshold (the number of
signal dots required for 71% correct performance; see Black et al.13for
further details [their method 1] and illustrative figures of this tech-
nique). To measure suppression, the contrast of the dots presented to
the amblyopic eye was fixed at 100% whereas the contrast of the dots
presented to the fellow fixing eye was varied across five contrast levels
(100%, 80%, 50%, 25%, and 12.5% contrast, equivalent to dot lumi-
nances of 70, 63, 52.5, 43.8, and 39.4 cd/m2, respectively), using the
method of constant stimuli. Within a single measurement session, 10
randomly interleaved staircases were presented, five for each contrast
level with the signal dots shown to the amblyopic eye and five for the
signal dot presentation to the fellow fixing eye. Two measurement
sessions were conducted per patient separated by a 30-minute break.
The fellow fixing eye contrast at which the motion coherence thresh-
olds were the same irrespective of which eye saw the signal and which
saw the noise was calculated by fitting linear functions to the average
threshold data for each eye as a function of fellow fixing eye contrast
and calculating the intersection of these fits.13We refer to this dichop-
tic contrast offset as the “balance point,” as it represents the point at
which suppression has been overcome and information is being com-
bined between the two eyes in a normal fashion.12,13Therefore, the
balance point contrast can be considered as a parametric measurement
of suppression.12For the control group the nondominant eye, as
defined by the hole-in-the-card test, was designated as the amblyopic
eye for these measurements. The alignment of central nonius lines
(one to each eye) was used to ensure accurate alignment of the
stimulus fields seen by the right and left eyes. Subjects were asked to
attend to the central part of the stimulus field. The fact that for this
stimulus corresponding points are not stimulated (i.e., the signal and
noise dots do not overlap in space) allows fusion to occur on a more
global level, and we believe it is this that makes its use as a treatment
so effective. We view the point-wise suppression as more of V1 func-
tion and the global suppression more of extrastriate function.
RESULTS
A one-way ANOVA conducted on the balance point data re-
vealed a significant main effect of group (control versus stra-
bismic versus anisometropic versus mixed; F(3,49)? 12.18, P ?
0.0001. Post hoc Bonferroni tests (corrected for multiple com-
parison) revealed that the control group balance points were
significantly higher than those of each of the three amblyopic
groups (strabismic P ? 0.03; anisometropic P ? 0.001; mixed
P ? 0.001). The amblyopic groups did not differ significantly
from one another (P ? 0.05). The mean contrast presented to
the fellow fixing (or dominant) eye at the balance point and the
corresponding 95% confidence interval (CI) can be seen in
Figure 1. It is evident that amblyopic participants had a signif-
icantly larger imbalance between the eyes than the control
participants (i.e., lower fellow eye contrasts at balance point)
consistent with the presence of interocular suppression. The
fact that control participants did have a small contrast offset
TABLE 1 (continued). Clinical Details for the Observers with Amblyopia
Observer Sex
Age
(y)Type
Cycloplegic
Refractive
Error (OD/OS)
LogMAR
Visual Acuity
(OD)
LogMAR
Visual Acuity
(OS)
Ocular Dev.
(Prism D) History
Stereopsis
(sec arc)
31F 10S
?0.50?1.50x178
?0.50?0.50x178
0.14 0 15XT, 10XT?
(?) Surgery at 6 years old
(?) Patched
(?) Surgery
Detection N/A
(?) Vision training treatment
No detection
No treatment
Detection N/A
(?) Patched
(?) Surgery at 7 years
No detection
No treatment
Diagnosed: 8 years old
(?) Surgery at 10 years old
No detection
No treatment
No detection
No treatment
Diagnosed: 6 years old
No treatment
No detection
No treatment
Diagnosed: 4 years old
(?) Surgery at 6 years old
No detection
No treatment
No detection
No treatment
40
32F 26S
?1.75?1.00x032
?4.25?0.75x161
?2.00?1.50x010
?4.00?0.50x166
?1.25 DS
Plano DS
?.040.10 10XT, 15XT?
40
33F9S 0.16010ET, 15ET?
25
34F12S00.10 0, 10XT?
200
35F16 SPlano DS
Plano?0.50x175
?0.50 DS
?1.25?0.50x175
?1.00?0.50x030
?2.00?0.50x145
Plano DS
Plano DS
?0.75 DS
?0.75 DS
?1.00 DS
?0.25 DS
?0.25 DS
?0.50 DS
?0.50 DS
?0.75 DS
?4.00?2.75x002
?4.25?2.75x002
0.100 15XT, 10XT?
120
36F15S 0.160 20ET200
37F 15S00.22 35ET, 35ET?
400
38 F12S0 0.1525ET, 15ET?
80
39M14S00.15 30XT, 25XT?
100
40M 12S
?0.080.10 30XT, 25XT?
140
41M 12S
?0.080.1020ET, 15ET?
80
42M 32S00.1530ET, 35ET?
70
43F10S0.05 0.15 15XT, 10XT?
30
Ocular dev., ocular deviation; A, anisometropia; AS, mixed amblyopia with anisometropia and strabismus; S, strabismic amblyopia; plano, plain
lens; ET, esotropia; XP, exophoria; XT, exotropia; DS, diopter sphere.
* Strabismus that has been surgically corrected; (?), a positive therapeutic outcome. If the strabismus was different, at distance and near, both
deviations are supplied, the top one being distance.
4172Li et al.
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Page 5

reflects the sensitivity of this test to eye dominance.11,17The
mean coherence thresholds (i.e., the number of signal dots) at
the balance point (95% CI) were as follows: controls, 16 (14–
19); anisometropic, 10 (9–12); mixed, 11 (8–13); and strabis-
mic, 13 (11–15). These results demonstrate that once bal-
anced, the amblyopic participants performed no worse, in fact
a little better, than the control observers; however, thresholds
across the groups were generally comparable. The thresholds
of amblyopic participants were very similar to those in previ-
ous reports using related techniques in a group of observers
with amblyopia13and a group of observers with normal bin-
ocular vision who were shown stimuli of equal contrast to both
eyes.17The relatively elevated thresholds we found for the
control participants may reflect the fact that this technique is
designed to measure suppression, and the use of a large range
of contrasts may slightly bias motion coherence estimates
when suppression is not present.
As our group of observers with amblyopia included both
adult and juvenile (?17 years of age) patients, we conducted a
separate analysis to investigate the effect of age on the balance
point data and on motion coherence thresholds. We found no
difference between adults and juveniles for either the balance
point data (t(41)? 0.7, P ? 0.52; juvenile mean, 56.4 [SD 21.5];
adult mean, 52.7 [SD 15.3]) or the motion coherence threshold
data (t(41)? 0.53, P ? 0.60; juvenile mean, 11.5 [SD 3.8]; adult
mean, 11.0 [SD 3.1]). We also found no correlation between
age and either the balance point data (Spearman’s ? ? ?0.2,
P ? 0.22) or the motion coherence data (Spearman’s ? ? 0.07,
P ? 0.65). These analyses indicate that the patient’s age did not
systematically influence these variables. As such, the observers
with amblyopia were treated as a single group in subsequent
analyses.
To compare the balance point test with clinical tests of
suppression, we correlated the results of the Worth 4-Dot test
and the modified Bagolini striated lenses test with the balance
point contrast. The near and far results for the Worth 4-Dot test
were combined to give a score from 0 (no suppression for
either test) to 4 (full suppression on both tests). For both
suppression measures, there was a significant negative corre-
lation with the fellow fixing eye’s contrast at the balance point
(rank; Worth 4-Dot, ? ? ?0.57, P ? 0.0001; modified Bagolini,
? ? ?0.74, P ? 0.0001; Fig. 2). This finding demonstrates that
the larger the difference in contrast between the two eyes that
is necessary for normal binocular combination of motion sig-
nals (i.e., the lower the contrast in the fellow eye; recall that
the contrast to the amblyopic eye remains fixed at 100%), the
larger the amount of suppression measured using standard and
modified clinical tests.
The contrast at the balance point also correlated signifi-
cantly with both stereo sensitivity (? ? 0.47, P ? 0.002; the
greater the stereo sensitivity, the less the difference in contrast
between the eyes) and the acuity difference in log units be-
tween the eyes (? ? ?0.60, P ? 0.001; the greater the acuity
difference, the greater the contrast difference). These correla-
tions are shown in Figure 3. To assess whether the relationship
between these two variables and the contrast at balance point
differed among anisometropic, mixed, and strabismic amblyo-
pes, we performed a univariate general linear model analysis
on the contrast at balance point data with amblyopia type
(anisometropic versus mixed versus strabismic), acuity differ-
ence between the eyes, and stereo sensitivity as covariates. The
model revealed a significant interaction between amblyopia
type and acuity difference, F ? 10.02, P ? 0.003, demonstrat-
ing that the effect of visual acuity difference on balance point
contrast varied across the different amblyopia subtypes. There
was no significant interaction between amblyopia subtype and
stereo sensitivity, suggesting that the effect of stereo sensitivity
did not vary across the different amblyopia subtypes. To ex-
plore the interocular visual acuity difference and amblyopia
subtype interaction further, we correlated interocular visual
acuity difference with balance point contrast separately for
each amblyopia subtype. Both the strabismic and mixed am-
blyopes showed significant negative correlations (strabismic:
? ? ?0.62, P ? 0.018, mixed: ? ? ?0.82, P ? 0.023). The
anisometropic amblyopes also showed a negative correlation,
but it did not quite reach significance (? ? ?0.42, P ? 0.053),
suggesting that the presence of strabismus influenced the
FIGURE 1.
achieve balanced performance on the motion coherence task between
the two eyes (i.e., the same motion coherence threshold was achieved
regardless of which eye was presented with noise and which with
signal). Error bars, 95% CI of the mean. Controls, n ? 10, ani-
sometropes, n ? 22; mixed, n ? 7; and strabismics, n ? 14.
The contrast presented to the fellow (or dominant) eye to
FIGURE 2.
fellow fixing eye at the balance point and suppression on the Worth
4-Dot test (A) and the modified Bagolini striated lenses test (B). Higher
numbers on both the Worth and Bagolini tests (x-axis) are indicative of
greater suppression. Smaller contrast values for the balance point
(y-axis) are indicative of greater suppression, as a larger imbalance
between the eyes is required for binocular combination to occur. (A)
Interval data on the abscissa and ordinal data on the ordinate axis. The
statistical analysis for this comparison was nonparametric and con-
ducted on the ranked data using Spearman’s rho.
The relationship between the contrast presented to the
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The Role of Suppression in Amblyopia4173

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strength of the relationship between acuity difference and
balance point contrast.
We have shown that dichoptic motion coherence thresh-
olds can be used to assess sensory ocular dominance in observ-
ers with normal binocular vision.18Since the participants in
this previous study did not have any interocular suppression,
we did not vary contrast between the eyes but rather pre-
sented stimuli at 100% contrast to both eyes and calculated the
motion coherence threshold ratio for signal dots presented to
the left eye versus signal dots presented to the right eye. To
assess the relationship between this measure and the balance
point measure for amblyopic observers, for each participant,
we calculated the threshold ratio when stimuli were presented
at 100% contrast for both eyes and correlated the result with
the balance point measure. The threshold ratio was calculated
as amblyopic eye threshold/fellow eye threshold, and therefore
larger ratios indicate a greater degree of suppression of the
amblyopic eye. As shown in Figure 4 these two measures
correlated significantly (? ? ?0.77, P ? 0.001). This relation-
ship did not covary with amblyopia subtype (F(1,40)? 0.17,
P ? 0.69).
Next, we assessed whether the amount of suppression was
greater in participants who had never received treatment for
their amblyopia. Within our sample, 16 anisometropic and 7
strabismic amblyopes had never received treatment, 6 aniso-
metropic and 1 mixed amblyope had received patching only, 6
strabismic and 2 mixed amblyopes had received surgery only,
and 4 strabismic and 1 mixed amblyope had received both
patching and surgery. We found that the patients who had
received treatment showed no difference in any of our mea-
surements relative to the nontreated group (between-subjects
t-tests, P ? 0.05) and none of our outcome measures covaried
with treatment and amblyopia subtype (univariate ANOVA
with covariates of treatment type and amblyopia subtype).
Figure 5 shows the mean contrast for the fellow fixing eye at
balance point (Fig. 5A) and the mean interocular acuity differ-
ence (Fig. 5B) for each of the treatment groups (no treatment,
patching only, surgery only, and both surgery and patching.
Finally, we considered only the participants with strabismic
or mixed amblyopia who still had strabismus to assess whether
the extent of strabismus was related to the strength of suppres-
sion. The relationship between angle of deviation and suppres-
sion is shown in Fig. 6 for both the balance point measure (Fig.
6A) and the Bagolini measure (Fig. 6B) of suppression. Exo-
tropes and esotropes are identified in these plots by the use of
filled and hollow markers, respectively. There were no reliable
relationships between deviation angle and strength of suppres-
FIGURE 3.
eye at the balance point and stereo sensitivity (A) or acuity differ-
ence between the eyes (B). Dashed lines: the best linear fit to the
data. For stereo sensitivity (A) the negative correlation shows that
the lower the balance point contrast in the fellow fixing eye (i.e.,
the greater the difference between the eyes), the lower the stereo
sensitivity. The positive correlation for acuity difference (B) dem-
onstrates that the greater the difference between the eyes at bal-
ance point contrast, the larger the acuity difference.
The relationship between contrast in the fellow fixing
FIGURE 4.
point and the motion coherence threshold ratio between the eyes
when 100% contrast was shown to both eyes. Larger threshold ratios
and lower fellow eye contrasts indicate a greater deficit for the am-
blyopic eye under dichoptic viewing conditions.
The relationship between fellow eye contrast at balance
FIGURE 5.
cular acuity difference (B) for participants who had never received
treatment (n ? 23), received patching only (n ? 7), received surgery
only (n ? 8), or received both patching and surgery (n ? 5). Errors
bars, 95% CI.
Mean fellow eye contrast at balance point (A) and intero-
4174 Li et al.
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Page 7

sion; however, in the esotropes there was a trend toward
increasing suppression with increasing angle of deviation for
the balance point measure, which did not reach significance,
probably due to the small sample size of this group (n ? 5; ? ?
?0.7, P ? 0.2). In addition, we found no relationship between
angle of deviation and stereo acuity or interocular acuity dif-
ference (P ? 0.05 for both).
DISCUSSION
In this study, we set out to answer the three questions detailed
below.
How does the new balance point method compare with
the current clinical standards (Worth 4-Dot test and modified
Bagolini test) across a clinical population? Using a novel
approach involving the measurement of dichoptic motion
thresholds for stimuli of different interocular contrast, we
show that the degree of suppression is significant in strabis-
mus, anisometropia, and mixed amblyopia, but that there was
no significant difference across our clinical sample in the dif-
ferent subgroups (i.e., strabismics, anisometropes, and mixed).
We also demonstrate that this new quantitative approach to
the measurement of suppression correlates strongly with tra-
ditional, albeit qualitative, clinical measures. Finally, we show
a significant correlation between the balance point measure
and a more abbreviated measurement based on the same prin-
ciple previously used to quantify sensory dominance in the
normal population.17This conclusion is supported by data on
eye dominance within the normal population.18In all, these
results suggest that this new approach has promise for quan-
tifying suppression in binocular dysfunction and eye domi-
nance in both clinical and normal populations.12,13,17
What is the relationship between visual losses in amblyo-
pia (acuity and stereo) and the degree of suppression? We
determined the extent to which the contrast of the stimuli
(signal or noise) presented to the fellow fixing eye had to be
reduced in order for normal sensory binocular combination to
take place (the contrast of stimuli seen by the amblyopic eye
was fixed at 100%). As discussed above, this measure of sup-
pression is in close agreement with standard clinical measures.
We found that the degree of suppression measured using this
technique significantly correlated with the degree of amblyo-
pia and stereo loss. In other words, the greater the suppres-
sion, the greater the amblyopia. This result is contrary to
accepted wisdom8that stronger suppression is associated with
weaker amblyopia, but is consistent with previous reports
demonstrating stronger suppression with deeper amblyo-
pia.18–20It should be noted that our study differed from that of
Holopigian et al.8in several ways. Our sample was larger and
had a greater range of amblyopia severity than did the sample
reported by Holopigian et al., which mainly contained patients
with very mild amblyopia (visual acuity of 20/30?2or better in
the amblyopic eye). Also their sample contained a dispropor-
tionate number of patients with alternating strabismus (8 pa-
tients in a sample of 10), which may represent a special
category. A comparison of our findings with those of Holopi-
gian et al. therefore raises the possibility that the suppression
found in patients with amblyopia may differ from that in
patients with alternating strabismus without amblyopia or in
patients with very mild amblyopia. In addition, our primary
measure of suppression differed from that used by Holopigian
et al., who used monocular and dichoptic increment threshold
measurements for 3.3-cyc/deg sinusoidal gratings presented
foveally. Of note, their data show the same, albeit a weaker,
relationship between suppression and stereopsis that we re-
port wherein stronger suppression results in reduced stereop-
sis, as one would expect.
Our results, while being consistent with the idea that am-
blyopia results from suppression rather than the other way
around, do not in themselves prove a causal connection. It is
possible that they are positively correlated because both are
the result of another factor, as yet unknown. What we can say
is that if suppression were simply a mechanism to stop the
diplopic vision from an amblyopic eye from reaching percep-
tion, then a greater degree of suppression would be necessary
for mild compared with severe amblyopia. That is not what we
found.
How does suppression vary among the amblyopic clinical
population? Although it is commonly thought that the greatest
degree of suppression occurs in cases of strabismic amblyopia
and the least in cases of anisometropia, we did not find any
significant differences between the degree of suppression in
adults with strabismus, anisometropia, or mixed strabismus
and anisometropia using our balance point measurement. Fur-
thermore, we did not find that the degree of suppression
depended on the angle of the strabismus or the type of devia-
tion, in agreement with previous studies.8,21–26However our
sample size was necessarily small, and therefore these results
are not definitive. A caveat is needed here, because our method
averages sensitivity over the central 20° and can only provide
a global measure of suppression. Since there is evidence that
the size and extent of suppression scotomata depend on the
type and angle of squint,1–4,7a more localized measure is
needed to address this issue. We are currently investigating this
question.
FIGURE 6.
strength of suppression using the balance point measurement (A) and
the Bagolini method (B). The two larger circles indicate overlapping
esotrope and exotrope data points. Dashed lines: indicate linear fits to
the data.
The relationship between the angle of strabismus and
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The Role of Suppression in Amblyopia4175

Page 8

CONCLUSIONS
If it is indeed the case that suppression plays a causal role in
amblyopia, as our current data suggest, then there is an argu-
ment to be made for incorporating therapeutic approaches that
directly target amblyopic eye suppression into amblyopia treat-
ment regimens. We have recently shown that repeated expo-
sure to dichoptic motion coherence threshold stimuli can
effectively reduce suppression in adults with amblyopia, which
in turn can improve visual acuity and stereopsis.10,27These
findings add further weight to the hypothesis that suppression
plays a primary role in the amblyopia syndrome and the im-
portance of considering suppression when treating amblyopia.
These visual improvements are sustained and have so far been
demonstrated in adults well beyond the critical period of visual
development. We are presently developing a handheld, take
home device on which the balance point principles are imple-
mented in the form of a video game, suitable for the younger
age group.
References
1. Travers T. Suppression of vision in squint and its association with
retinal correspondence and amblyopia. Br J Ophthalmol. 1938;22:
577–604.
2. Jampolsky A. Characteristics of suppression in strabismus. Arch
Ophthalmol. 1955;54:683–696.
3. Pratt-Johnson J, Wee HS. Suppression associated with exotropia.
Can J Ophthalmol. 1969;4:136–144.
4. Pratt-Johnson JA, Wee HS, Ellis S. Suppression associated with
esotropia. Can J Ophthalmol. 1967;2:284–291.
5. Joosse MV, Simonsz HJ, Spekreijse H, Mulder PG, van MindeRhout
HM. The optimal stimulus to elicit suppression in small-angle
convergent strabismus. Strabismus. 2000;8:233–242.
6. Joosse MV, Simonsz HJ, van MindeRhout EM, Mulder PG, de Jong
PT. Quantitative visual fields under binocular viewing conditions
in primary and consecutive divergent strabismus. Graefes Arch
Clin Exp Ophthalmol. 1999;237:535–545.
7. Joosse MV, Simonsz HJ, van MindeRhout HM, de Jong PT, Noordzij
B, Mulder PG. Quantitative perimetry under binocular viewing
conditions in microstrabismus. Vision Res. 1997;37:2801–2812.
8. Holopigian K, Blake R, Greenwald MJ. Clinical suppression and
amblyopia. Invest Ophthalmol Vis Sci. 1988;29:444–451.
9. Thompson B, Mansouri B, Koski L, Hess RF. Brain plasticity in the
adult: modulation of function in amblyopia with rTMS. Curr Biol.
2008;18:1067–1071.
10. Hess RF, Mansouri B, Thompson B. A new binocular approach to
the treatment of amblyopia in adults well beyond the critical
period of visual development. Restor Neurol Neurosci. 2010;28:
793–802.
11. Hess RF, Hutchinson CV, Ledgeway T, Mansouri B. Binocular
influences on global motion processing in the human visual sys-
tem. Vision Res. 2007;47:1682–1692.
12. Mansouri B, Thompson B, Hess RF. Measurement of suprathresh-
old binocular interactions in amblyopia. Vision Res. 2008;48:
2775–2784.
13. Black JM, Thompson B, Maehara G, Hess RF. A compact clinical
instrument for quantifying suppression. Optom Vis Sci. 2011;88:
E334–E343.
14. American Academy of Ophthalmology. Preferred Practice Patterns.
Amblyopia PPP, September 2007. Available at http://www.aao.org/
ppp. Accessed April 23, 2009.
15. Steinman S, Steinman B, Garzia R. Foundations of Binocular
Vision: a Clinical Perspective. McGraw-Hill Companies. 2000;
145–147.
16. Brainard DH. The Psychophysics Toolbox. Spat Vis. 1997;10:433–
436.
17. Li J, Lam CS, Yu M, et al. Quantifying sensory eye dominance in the
normal visual system: a new technique and insights into variation
across traditional tests. Invest Ophthalmol Vis Sci. 2010;51:6875–
6881.
18. Sireteanu R. Binocular vision in strabismic humans with alternating
fixation. Vision Res. 1982;22:889–896.
19. Sireteanu R, Fronius M. Naso-temporal asymmetries in human
amblyopia consequence of long-term interocular suppression. Vi-
sion Res. 1981;21:1055–1063.
20. Wong AM, Burkhalter A, Tychsen L. Suppression of metabolic
activity caused by infantile strabismus and strabismic amblyopia in
striate visual cortex of macaque monkeys. J AAPOS. 2005;9:37–47.
21. Harrad R, Sengpiel F, Blakemore C. Physiology of suppression in
strabismic amblyopia. Br J Ophthalmol. 1996;80:373–377.
22. Hess RF. The site and nature of suppression in squint amblyopia.
Vision Res. 1991;31:111–117.
23. Hofeldt TS, Hofeldt AJ. Measuring colour rivalry suppression in
amblyopia. Br J Ophthalmol. 1999;83:1283–1286.
24. Joose MV, Simonsz HJ, de Jong PT. The visual field in strabismus:
a historical review of studies on amblyopia and suppression. Stra-
bismus. 2000;8:135–149.
25. Sengpiel F, Blakemore C. The neural basis of suppression and
amblyopia in strabismus. Eye (Lond). 1996;10:250–258.
26. Sireteanu R. Human amblyopia: consequence of chronic interocu-
lar suppression. Hum Neurobiol. 1982;1:31–33.
27. Hess RF, Mansouri B, Thompson B. A binocular approach to
treating amblyopia: antisuppression therapy. Optom Vis Sci. 2010;
87:697–704.
4176Li et al.
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