Abstract
purpose. The aim of this study was to define the nature of functional visual
loss in amblyopia and to identify those subjects whose amblyopia is
chiefly due to one or more of the following deficits: abnormal contour
interaction, abnormal eye movements, abnormal contrast perception, or
positional uncertainty.
methods. Fifty amblyopic children with a mean age of 5.6 ± 1.3 years were
referred from diverse sources. In addition to routine orthoptic and
optometric evaluation the principal visual deficits in the amblyopic
eye of each subject were identified using the following measures of
visual acuity: high contrast linear, single optotype, repeat letter and
low contrast linear, plus Vernier and displacement thresholds. These
measures were repeated as the children underwent a prescribed occlusion
therapy regime, after parental consent.
results. All amblyopic subjects demonstrated a functional loss in each of the
tests used, and occlusion therapy appeared to improve all aspects of
the amblyopia. High contrast visual acuity was not always the primary
deficit in visual function, and when amblyopic subjects were divided
according to their primary visual loss, this visual function was found
to show the greatest improvement with treatment.
conclusions. These results suggest that to successfully identify the primary visual
deficit and monitor the success of occlusion therapy it is necessary to
assess other aspects of visual function in
amblyopia.
Previous investigations into amblyopia treatment often contain
methodological difficulties, such as small subject numbers or
inadequate measurement of sensory function and motor
function,
1 2 3 4 5 which prevents accurate conclusions being
drawn. Although there have been extensive psychophysical and
electrophysical investigations (see Ciuffreda et al.
1991)
6 into both human and animal models of amblyopia,
there is still no conclusive evidence as to why some amblyopic subjects
respond to treatment and others do not.
1 2 3 4 5
The associated conditions thought to be responsible for the amblyopia
(anisometropia, strabismus, refractive error, or deprivation) are
normally used to classify the condition. The use of the apparent causal
agent in classifying amblyopia is convenient and leads to immediate
corrective action but may not be of value in assessing the multifaceted
loss in visual function. The current underlying hypothesis in the
treatment of amblyopia is that therapy treats the whole condition,
assuming all aspects of visual function are equally reduced, and that
the success of amblyopia therapy is most often defined in terms of
improvement in high contrast visual acuity, which only measures one
aspect of visual function.
7 8 Active therapies for
amblyopia treatment, have been used over the years by clinicians and
are designed to stimulate a specific visual function, either
accommodation, eye movements and fixation pattern, or form recognition
in an attempt to eliminate what is thought to be the underlying cause
of reduced vision.
9 A full review of these training
procedures is not in the scope of this article; for more detailed
treatment of this area other sources should be
consulted.
6 10
If the success of amblyopia therapy is to be evaluated it is essential
to quantify and monitor the loss in visual function with a range of
sensory tests and not by the use of high contrast visual acuity alone.
The purpose of this study was to try and define the nature of
functional visual loss in amblyopia and to identify those children
whose amblyopia is chiefly due to one or more of the following
deficits: abnormal contour interaction,
11 12 13 which can be
assessed using the difference between linear and single optotype
acuity
14 15 16 ; abnormal contrast
perception,
12 17 which can be assessed using the
difference between a high and low contrast linear acuity
measure
14 15 16 ; abnormal eye movements,
18 19 which can be assessed using the difference between a high contrast and
repeat letter format acuity measure
14 15 16 ; and positional
uncertainty,
20 21 which is assessed by hyperacuity
measurements.
Amblyopic subjects can be assigned to these groups using a battery of
simple clinical and psychophysical tests of visual
function,
14 15 16 the following tests were included in the
study: LogMAR Crowded Acuity Test (CAT), Single Letter Acuity Cards
(SLA), Low Contrast Glasgow Acuity Cards (LC), Regan Repeat Letter
Acuity Cards (RRL), and Alignment and Displacement Thresholds (AT,
OMDT).
These tests will divide the amblyopic subjects into the four
functionally based categories outlined above and quantify the different
aspects of functional visual loss in the major amblyopic groupings.
The aims of these investigations were as follows: to determine the
functional characteristics of amblyopia, to ascertain the pattern of
recovery of each characteristic during therapy, and to relate each
characteristic and its recovery pattern to the classic diagnostic
categories.
In addition to routine orthoptic and optometric evaluation, the
tests outlined above were performed to identify the principal visual
deficit/s in the amblyopic eye of each subject. For a full description
of these tests, see Simmers and Gray 1999.
16
All letter charts were based on a six-alternative forced choice
procedure. The logarithmic scale used in all charts provides a constant
change in resolution between each acuity level of 0.1 log units. In
addition the use of a logarithmic scale allows the facility to extend
the scale in either direction, by increasing or reducing the distance.
A modified logMAR scoring system
22 was used, with four
letters presented at each acuity level. The system designates 6/6 a
score of 1 and 6/60 a score of 0 with visual acuities of less than 6/60
carrying a negative sign (1 − logMAR). Because the angular size
of the letters changed by a factor of 0.1 log unit, and because all the
letters were equally legible, each letter was scored individually
(0.025 log units). The end point was defined when no letters could be
identified at a particular acuity level, with the subject being
encouraged to guess until this point was reached. This equated the
scoring systems between all acuity cards.
The order of presentation of the test charts and hyperacuity measures
was assigned randomly, and all acuity tests were externally illuminated
to 300 lux. The same test room was used for each visit. Younger
children performed the acuity tests as letter matching tests using an
appropriate key card, in older children verbal responses were pursued.
Test session duration was approximately 40 minutes.
From the results of these investigations and after a full refraction,
each subject was prescribed occlusion therapy based on the management
plan outlined below.
Type of Amblyopia Present.
Ametropic and meridional amblyopias are usually bilateral, therefore
early and accurate correction of refractive error is very important.
Alternate occlusion was prescribed if residual amblyopia was present.
Strabismic or anisometropic amblyopia, correction of any refractive
error, and then occlusion prescribed according to degree of amblyopia
and state of binocular single vision (BSV).
Degree of Amblyopia.
Presence of BSV.
If BSV was constant or intermittent then occlusion was always
part-time. If microtropia was present then part-time occlusion was also
deemed necessary.
Baseline data collection were taken with the subjects wearing their
full correction but before any occlusion therapy was prescribed. Each
subject then received a full orthoptic examination, including all five
acuity tests, once a month during the course of treatment prescribed.
Measurement of compliance with the occlusion regime prescribed was
undertaken using a diary system, in which the parents logged the number
of hours’ occlusion achieved each day and the visual tasks undertaken.
So that the relative improvements in visual acuity thresholds and
hyperacuities could be compared, the absolute change in score (in log
units) relative to the initial pretherapy value was calculated for each
visit.
Due to cancellations and non-attendance, not every child was seen at
identical intervals, therefore visits were categorized with visit 1
representing baseline measurements; visit 2, 4 to 8 weeks after initial
visit; visit 3, 10 to 12 weeks; and so on.
The mean posttherapy visual acuity and hyperacuity scores for the
amblyopic subjects with respect to the primary visual deficit are
summarized in
Table 4 .
When the amblyopic subjects are grouped according to primary visual
loss, it is this visual function that shows the greatest improvement in
response to treatment. It is interesting then to compare the mean
changes posttherapy in those groups with a specific visual deficit. For
instance, group D demonstrated increased fixation instability. The mean
difference in scores posttherapy reduced to 0.060 log units (2 or 3
letters better with RRL) due to an increase in high contrast linear
acuity (CAT), a mean difference now within the previously set 95%
confidence limits (±0.175 log units) for normality.
14 15
Group E demonstrated increased levels of contour interaction. The mean
difference in scores posttherapy reduced to 0.136 log units (1.5 lines
better with SLA), a mean difference now within the previously set 95%
confidence limits (±0.150 log units) for normality.
14 The
mean crowding ratio also reduced to 1.2, a value now within previously
set 95% confidence limits for normality.
14 15
Group B demonstrated significantly reduced low contrast acuity
pretherapy; although this visual function improved, the changes were
concurrent with high contrast acuity. Therefore, the mean difference in
scores posttherapy remained unchanged (0.385 log units), a value still
outside previously set 95% confidence limits (±0.175 log units) for
normality.
14 15
Figure 2 shows the cumulative improvement for all subjects
(absolute change in log units) during the course of therapy. Occlusion
therapy appeared to improve all aspects of visual function, with these
results demonstrating concurrent changes in both the acuity card
measurements and hyperacuities. High and low contrast linear acuity
appeared to have the greatest overall relative improvement in
performance. The greatest improvement in visual function appeared to
occur with the first 4 to 6 visits, although in the cumulative data
high contrast acuity appeared to suddenly surge after visit 6.
Figure 3 illustrates the relative improvement in performance in all measurements
during the course of occlusion therapy individually in anisometropic
(Fig. 3A) , strabismic
(Fig. 3B) , and anisometropic + strabismic
amblyopes
(Fig. 3C) . Again all measurements show improvement.
In the anisometropic subject group, high and low contrast linear acuity
showed a significant improvement (0.300–0.350 log units). In this
subject group both high and low contrast acuity showed improvements as
late as visits 7 and 9. Hyperacuity thresholds demonstrated the
smallest degree of improvement.
In the strabismic subject group all visual functions show a steady and
significant improvement, with low contrast linear acuity showing the
greatest degree of improvement (just under 0.300 log units). Again, the
majority of visual function improvement levels off after visit 4 to 6.
Compared with the anisometropes, AT and OMDT improved to a greater
extent in strabismic amblyopes.
In the anisometropic + strabismic subject group all visual functions
showed a steady and significant improvement, with high contrast linear
acuity showing the greatest degree of improvement (around 0.250 log
units). The majority of visual function improvement levels off after
visit 4 to 6. Again, interestingly, compared with the pure
anisometropes, AT and OMDT improved to a greater extent in this group.
Figure 4 indicates the rate of improvement with occlusion therapy in relation to
the primary functional visual deficit in the amblyopic subjects, as
described in
Table 4 . In all cases the primary visual deficit
demonstrated the most prominent rate of improvement in performance.
Figure 4A shows that the primary visual deficit in this group was
revealed by a significantly reduced CAT score; with occlusion therapy
it was this deficit (high contrast linear acuity) that showed the
greatest degree of improvement (nearly 0.300 log units).
The primary visual deficit in the group illustrated in
Figure 4B was
revealed by a significantly reduced LC score; with occlusion therapy it
was this deficit (low contrast linear acuity) that showed the greatest
degree of improvement (0.300 log units). However because of the
concurrent changes in high contrast acuity, to a similar extent this
group maintained a low contrast deficit (mean difference 0.387 log
units), a value still outside previously set 95% confidence limits
(±0.175 log units) for normality.
14
The primary visual deficit shown in
Figure 4C was revealed by
significantly reduced hyperacuity thresholds; and with occlusion
therapy, it was this deficit that showed the greatest degree of
improvement (0.150–0.300 log units). RRL and SLA failed to demonstrate
a substantial improvement (<0.100 log units). Again, the majority of
visual function improvement levels off after visit 4 to 6, with the
exception of the hyperacuity measures in a single amblyopic subject
(which continue to show improvement up to visit 9).
The group shown in
Figure 4D demonstrated an increased fixation
instability (revealed by a higher score with RRL than in CAT). The mean
difference in scores reduced from 0.212 log units pretherapy to 0.060
log units posttherapy, with a significant increase in CAT score
demonstrated (0.275 log units). Interestingly, this group of amblyopic
subjects also demonstrated a deficit with hyperacuity measures which
also improved significantly posttherapy. Again, it was the primary
visual deficit in this group which showed the greatest degree of
improvement.
Group E shown in
Figure 4E demonstrated increased levels of contour
interaction (revealed by a higher score with SLA than with CAT). The
mean difference in scores reduced from 0.300 log units pretherapy to
0.136 log units posttherapy, with a significant increase in CAT score
demonstrated (0.443 log units). The mean crowding ratio also reduced
from 2.3 to 1.2. However, CAT and SLA visual thresholds are still below
previously set 95% confidence limits for normality.
14 Visual function improvement is very slow for most visual functions;
however, in this subject group high contrast acuity surges ahead at
about visit 7 to 9, which is very similar to the plot for anisometropic
amblyopes in
Figure 3 (anisometropia was present in 72% of the
amblyopic subjects in group E).
Linear regression analysis revealed a significant correlation between
the initial pretherapy score and the absolute change in visual function
with acuity card measures, the lower the initial value the greater the
improvement (
Fig. 5 A;
P < 0.01); however, no correlation was evident with
either hyperacuity measure (
Fig. 5B ;
P > 0.05).
Linear regression analysis revealed no significant correlation between
the absolute change in visual function during the course of occlusion
therapy and the age of the amblyopic subject at the beginning of
treatment with either acuity card measures (
Fig. 6 A;
P > 0.05) or hyperacuity measures (
Fig. 6B ;
P > 0.05).
Demonstrable binocular vision was evident in 34 children, with 28 of
these children achieving stereopsis. The mean stereoacuity values were
654.6 ± 853.4 seconds of arc with the TNO stereotest and
338.7 ± 351.02 seconds of arc with the Frisby stereotest; these
values improved to 501.8 ± 740.4 seconds of arc (TNO) and
195.5 ± 158.8 seconds of arc (Frisby) during occlusion therapy. A
significant difference between thresholds obtained using TNO and Frisby
was evident pretherapy (P = 0.001) and posttherapy
(P = 0.03); the higher values with the TNO test may be
due to its more dissociative design. No amblyopic subjects regained
binocularity through the course of occlusion therapy.
Treatment diaries were completed and returned in 35 cases. Part-time
occlusion hours appeared easily administrated, although those children
who required full-time occlusion often divided the prescribed time
during the course of the day. As may be expected, there was a
significant difference (P = 0.001) between part-time
hours (mean, 3.8 ± 0.5 hours) administered and full-time hours
(mean, 7.9 ± 1.3 hours) of occlusion administered. The most
common activities while wearing the patch were school, computer games,
and television. In children who wore the patch at school (part-time or
full-time) the vision tended to improve quicker, consequently producing
a shorter duration of therapy.
No significant relationship could be found between the absolute
improvement in visual function and the amount of occlusion therapy
administered in either visual acuity thresholds (
Fig. 7 A;
P > 0.05) or hyperacuity measures (
Fig. 7B P > 0.05).
In this study we have examined periodically various parameters of
visual function in a group of young amblyopic subjects throughout the
course of occlusion therapy.
The results of this study suggest strongly that other aspects of visual
function should be monitored during occlusion therapy. We provide
evidence that many aspects of visual function are adversely affected by
the presence of amblyopia; all the subjects in this study demonstrated
a functional loss in each of the tests used. Initial pretherapy values
can be used to identify the visual deficit that is most impaired.
Interestingly, when the amblyopic subjects were divided according to
this primary visual loss, it was this visual function that was found to
have the greatest improvement during occlusion therapy
(Fig. 4) . Thus,
an amblyopic patient could show little or no improvement on a
traditional Snellen visual acuity test, although changes are occurring
in other aspects of visual function (e.g., low contrast perception,
fixation steadiness, motion detection). Often these visual functions
are not affected equally, that is, a reduction in low contrast may be
greater than the deficit with traditional high contrast letter charts.
Our results also reveal a significant correlation between the initial
pretherapy scores and the absolute improvement in visual function, with
the greater deficit leading to the more substantial degree of
improvement
(Fig. 6) .
There is no consensus in the literature as to the correct treatment or
the factors influencing the treatment of
amblyopia.
6 23 24 25 We could find no relationship between
the hours of occlusion prescribed (part-time or full-time) and the
absolute improvement in visual function
(Fig. 7) , in those children who
completed the treatment diaries. Our results show that it is the time
course of treatment and not necessarily the duration (hours per day) of
occlusion that is a key factor.
The greatest improvement in visual function(s) occurred within
the first 4 to 5 visits (16–24 weeks), although certain subjects did
show changes over a longer time interval. In clinical practice,
occlusion therapy is often prescribed over many months and sometimes
years; the results of our study question the need to continue occlusion
beyond this time scale.
In practice, many clinicians feel that treatment after 6 to 8 years of
age is ineffective, and in many cases treatment would remain
uninitiated. Nevertheless, several reports in the literature now exist
that detail the successful treatment of amblyopia in older children and
adults.
5 16 26 27 28 In the present study we could find no
relationship between age and degree of visual function improvement
(Fig. 6) , compliance with treatment rather than the patient’s age
appears to be a key factor. The clinical pertinence of the treatment of
older subjects has been questioned, however,
29 with
amblyopic subjects reportedly still maintaining fixation with the
dominant eye and eventually demonstrating a regression of visual
function. The risk of insuperable diplopia in strabismic amblyopia is
also a factor that deters treatment in an older age-group. If
suppression is overcome, subjects may find it impossible to resuppress
or learn to ignore the diplopia at this age, and if fusion is absent it
will be impossible to re-join the diplopia
The results of this study provide further evidence for the multifarious
reduction in visual performance that occurs in amblyopia. Success must
be assessed not simply by a change in high contrast visual acuity but
by examining a number of parameters that relate to an individual’s
visual capacity.
Occlusion therapy appeared to improve all aspects of the amblyopia,
with a significant difference between pre- and posttherapy results
(Table 5) . However, to establish the most effective form of treatment in
amblyopia, it would be interesting to compare in isolation and in
combination the effects of occlusion therapy and specific active
therapies targeted at an individual’s primary functional visual
deficit. If individual therapies for the different functional
subcategories could be found, then these individuals could be
identified and subsequently targeted with a specific therapy.
It is, therefore, important to appreciate this diverse reduction in
visual performance that occurs in amblyopic eyes and the need to
monitor other aspects of visual function during occlusion therapy to
allow for the optimum management of the patient.
Supported by a Vision Research Training Fellowship from the Wellcome Trust (PVM).
Submitted for publication January 22, 1999; revised June 17, 1999; accepted July 12, 1999.
Commercial relationships policy: N.
Corresponding author: Anita J. Simmers, Visual Perception Unit,
Department of Psychology, University of Essex, Wivenhoe Park,
Colchester, UK. E-mail:
[email protected]
Table 1. Clinical Details of All Subjects
Table 2. Mean Pretherapy Visual Acuity Thresholds
Table 2. Mean Pretherapy Visual Acuity Thresholds
Acuity Card | Anisometropic Amblyopes (n = 20) | Strabismic Amblyopes (n = 16) | Anisometropic, and Strabismic Amblyopes (n = 14) | All Amblyopes (n = 50) |
CAT | 0.485 ± 0.2 | 0.511 ± 0.2 | 0.487 ± 0.2 | 0.499 ± 0.2 |
SLA | 0.708 ± 0.3 | 0.679 ± 0.3 | 0.692 ± 0.1 | 0.663 ± 0.2 |
LC | 0.428 ± 0.2 | 0.386 ± 0.2 | 0.350 ± 0.2 | 0.322 ± 0.2 |
RRL | 0.603 ± 0.3 | 0.557 ± 0.2 | 0.575 ± 0.3 | 0.567 ± 0.3 |
Table 3. Identification of the Amblyopes with Primary Functional Visual Deficit
as Determined by the Tests Outlined
Table 3. Identification of the Amblyopes with Primary Functional Visual Deficit
as Determined by the Tests Outlined
Primary Visual Deficit | Determined by | Number of Amblyopic Subjects |
Group A | CAT | 12 |
Reduced High Contrast Visual Acuity | | (4 A, 5 S, 3 S+ A) |
Group B | LC | 10 |
Reduced Low Contrast Visual Acuity | | (4 A, 2 S, 4 S+ A) |
Group C | OMDT | 13 |
Reduced Hyperacuity Thresholds | AT | (6 A, 4 S, 3 S+ A) |
Group D | RRL > CAT | 8 |
Increased Fixation Instability | | (3 A, 3 S, 2 S+ A) |
Group E | SLA–CAT | 7 |
Increased Contour Interaction | | (3 A, 2 S, 2 S+ A) |
Table 4. Mean Visual Function Thresholds Pretherapy and Posttherapy (Final
Visit) + Standard Deviation (Modified LogMAR) and Hyperacuity
Thresholds + Standard Deviation (Seconds of Arc), for All
Amblyopic Subjects Grouped with Respect to the Primary Visual Deficit
(see
Table 3 )
Table 4. Mean Visual Function Thresholds Pretherapy and Posttherapy (Final
Visit) + Standard Deviation (Modified LogMAR) and Hyperacuity
Thresholds + Standard Deviation (Seconds of Arc), for All
Amblyopic Subjects Grouped with Respect to the Primary Visual Deficit
(see
Table 3 )
Test of Visual Function | Primary Visual Deficit | | | | |
| A (n = 12) | B (n = 10) | C(n = 13) | D(n = 8) | E(n = 7) |
CAT | 0.522 ± 0.193 | 0.490 ± 0.096 | 0.648 ± 0.138 | 0.447 ± 0.119 | 0.232 ± 0.079 |
0.89± 0.07 | 0.782 ± 0.169 | 0.783 ± 0.137 | 0.835 ± 0.113 | 0.731 ± 0.116 | 0.675 ± 0.102 |
SLA | 0.710 ± 0.201 | 0.518 ± 0.093 | 0.777 ± 0.162 | 0.703 ± 0.099 | 0.532 ± 0.168 |
1.02± 0.08 | 0.873 ± 0.137 | 0.830 ± 0.122 | 0.873 ± 0.125 | 0.891 ± 1.120 | 0.811 ± 0.117 |
LC | 0.408 ± 0.175 | 0.096 ± 0.158 | 0.369 ± 0.139 | 0.412 ± 0.171 | 0.153 ± 0.123 |
0.62± 0.09 | 0.562 ± 0.134 | 0.397 ± 0.098 | 0.625 ± 0.091 | 0.575 ± 0.127 | 0.479 ± 0.094 |
RRL | 0.619 ± 0.216 | 0.400 ± 0.234 | 0.719 ± 0.150 | 0.659 ± 0.180 | 0.329 ± 0.074 |
0.96± 0.07 | 0.829 ± 0.173 | 0.792 ± 0.147 | 0.814 ± 0.117 | 0.791 ± 0.125 | 0.714 ± 0.117 |
OMDT | 100.63 ± 21.60 | 102.12 ± 44.01 | 124.14 ± 25.33 | 97.32 ± 21.19 | 86.29 ± 22.19 |
59.69± 8.59 | 64.72 ± 21.31 | 72.01 ± 48.42 | 67.59 ± 25.33 | 61.78 ± 18.15 | 74.25 ± 25.59 |
AT | 211.85 ± 78.44 | 241.26 ± 70.84 | 268.92 ± 95.73 | 226.68 ± 45.08 | 236.09 ± 94.77 |
69.18± 19.38 | 137.08 ± 73.15 | 176.09 ± 68.48 | 183.55 ± 46.73 | 116.12 ± 51.75 | 180.14 ± 95.61 |
Table 5. Comparison of Pre- and Posttherapy findings
Table 5. Comparison of Pre- and Posttherapy findings
Test | Pretherapy | Posttherapy | P |
CAT | 0.499 ± 0.193 | 0.736 ± 0.140 | 0.0001 |
SLA | 0.663 ± 0.182 | 0.873 ± 0.124 | 0.0001 |
LC | 0.322 ± 0.206 | 0.564 ± 0.120 | 0.0001 |
RRL | 0.567 ± 0.231 | 0.795 ± 0.140 | 0.0001 |
OMDT | 100.62 ± 26.44 | 69.79 ± 14.72 | 0.0001 |
AT | 234.37 ± 83.92 | 166.54 ± 28.69 | 0.0001 |
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