(Investigative Ophthalmology and Visual Science. 1999;40:2633-2637.)
© 1999
by The Association for Research in Vision and Ophthalmology, Inc.
Amplitude Increase of the Multifocal Electroretinogram during Light Adaptation
Mineo Kondo,
Yozo Miyake,
Chang-Hua Piao,
Atsuhiro Tanikawa,
Masayuki Horiguchi and
Hiroko Terasaki
From the Department of Ophthalmology, Nagoya University School of Medicine, Nagoya, Japan.
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Abstract
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PURPOSE. To determine using the multifocal ERG technique whether there are any
regional differences in the increase in the amplitude of cone
electroretinograms (ERGs) during light adaptation.
METHODS. Multifocal ERGs were recorded with the Visual Evoked Response Imaging
System from five normal subjects. Thirty-seven hexagonal stimulus
elements and a recording time of 60 seconds were used. After 20 minutes
of dark adaptation, multifocal ERGs were repeatedly recorded every 2
minutes over a period of 16 minutes. The amplitudes of the multifocal
ERGs at different eccentricities were compared during the 16 minutes of
light adaptation.
RESULTS. During the 16 minutes of light adaptation, the summed responses of the
multifocal ERGs increased in amplitude an average of 36% and 47% for
the negative and positive components, respectively. The magnitude of
increase was minimal in the central retina at 22% and was
significantly larger in the peripheral retina at 58%. The implicit
time was slightly increased (<4%) with light adaptation, but there
were no regional differences.
CONCLUSIONS. The results demonstrated that there are topographic variations in the
amplitude increase of cone ERGs during light adaptation. This
topographic variation indicates that the mechanism for the increase
must be based on known regional differences in the
retina.
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Introduction
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If an eye is first dark adapted and then light adapted, the
amplitude of the electroretinograms (ERGs) elicited by photopic stimuli
increases progressively during the course of light adaptation,
stabilizing in approximately 15 to 20 minutes.1
2
3
4
5
6
7
8
9
10
11
12
The
mechanism for this unique phenomenon has not been fully determined,
although several explanations have been proposed—for example, a change
in the standing potential,3
interaction between rods and
cones,1
5
6
7
and a redepolarization of the cone
photoreceptors.8
Most of the investigators who have
studied this phenomenon used traditional full-field cone ERGs, and very
little is known about how different areas of the retina contribute to
this phenomenon. However, Weiner and Sandberg13
elicited
focal ERGs and reported that the foveal cone ERGs elicited by a 4°
fast-flickering stimulus also increase during light adaptation, as do
the full-field cone ERGs. Unfortunately, they did not compare the
magnitude of the increase at different retinal locations.
The multifocal ERG, recently developed by Sutter and
Tran14
and Bearse and Sutter,15
allows the
simultaneous recording of focal ERGs from multiple retinal locations in
a single recording session of several minutes. Because it has been
demonstrated that the multifocal ERG is a cone-mediated response and
that the negative and positive components of the multifocal ERG behave
as do the a- and positive peaks of the traditional full-field
photopic ERGs,16
17
it also could be expected that the
amplitude of the multifocal ERG increases during the course of light
adaptation. The multifocal technique is valuable, because it allows us
to explore regional variations.
In the present study, we first determined whether the multifocal ERGs
increase in amplitude during light adaptation as do the full-field cone
ERGs. We then explored whether there are any topographic variations in
this phenomenon across the human retina.
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Materials and Methods
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Subjects
Five normal subjects aged 26 to 35 years (mean age, 30.3 years)
participated. Except for refractive errors of -1.00 to -5.25 D, no
ophthalmologic or systemic abnormalities were present. Informed consent
was obtained after a full explanation of the procedures. All studies
were conducted in accordance with the principles embodied in the
Declaration of Helsinki.
Methods
The method for recording the multifocal ERG with the Visual Evoked
Response Imaging System (EDI, San Mateo, CA) has been described in
detail previously.14
15
In a clinical setting, 61 or 103
stimulus elements are widely used for eliciting the multifocal ERGs,
with a total recording time of 4 to 8 minutes.18
19
20
21
However, such a long recording period is not suitable for studying the
time course of this phenomenon, because it is known that the cone ERGs
increase rapidly in amplitude during the first several minutes of light
adaptation.6
8
9
10
11
Therefore, we used 37 stimulus elements
with a total recording time of 60 seconds.
The stimulus matrix consisted of 37 hexagonal elements that were
displayed on a color monitor (Model GDM 2038; Sony, Tokyo, Japan)
driven at a 75-Hz frame rate. These hexagons were scaled with
eccentricity to elicit approximately equal signal amplitudes at all
locations. At a viewing distance of 27 cm, the diameter of stimulus
array subtended approximately 60°. A small red fixation point was
placed at the center of the stimulus matrix. Each hexagon alternated
between white and black according to a pseudorandom binary m-sequence
at a rate of 75 times/sec. The luminance of the white frame and black
frame was 100.0 and 1.0 cd/m2, respectively,
resulting in a contrast of 98.0%. To suppress scattered light, the
periphery of the TV monitor, the diameter of which subtended 78°, was
set to a luminance of 50 cd/m2.
Recording and Data Analysis
The subject’s pupils were fully dilated with a combination of
0.5% tropicamide and 0.5% phenylephrine hydrochloride drops. After 20
minutes of dark adaptation, the Burian Allen bipolar contact lens
electrode was inserted under dim red illumination. A ground electrode
was attached to the ipsilateral earlobe. The opposite eye was occluded.
Optical lenses were used to correct the visual acuity that had been
determined before testing. After 5 additional minutes of readaptation
to darkness, multifocal ERGs were repeatedly recorded every 2 minutes
over a period of 16 minutes. Between each recording, the subjects were
asked to place their heads in a Ganzfeld dome with a constant
illumination of 50 cd/m2.
The signals were amplified by 100 K (Grass, Quincy, MA) with a
band-pass of 10 to 300 Hz. The data sampling rate was 1200 Hz. An
artifact-elimination technique was used once.14
The length
of the m-sequence used for the present study was
210 - 1, resulting in a total recording time of
approximately 60 seconds. Each local response (first-order kernel) was
calculated (VERIS Science 3.01 software, EDI). The array of local
responses was plotted in the same manner as the visual field.
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Results
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Time Course of Amplitude Increase
The amplitude of summed multifocal ERGs gradually increased with
time. Figure 1
shows the time course of the relative amplitudes for both the negative
and positive components of summed multifocal ERGs. The amplitude of the
initial negative component (N1) was measured from the baseline to
maximum initial negativity and the following positive component (P1)
was measured from the first trough to the positive peak. The means ± SEM of the relative amplitudes from the five subjects were plotted.
The negative component increased by approximately 36%, and the
positive component increased by approximately 47% during the 16
minutes of light adaptation. The increase of the positive component
tended to be larger than that of the negative component, although there
was no statistically significant difference between the two components.
This process was rapid for the first several minutes, then continued to
increase more slowly, and reached maximal values at approximately 16
minutes. The implicit times for the negative and positive components of
the summed multifocal ERG increased slightly by approximately 3% (0.5
msec) and 4% (0.8 msec), respectively, during the 16 minutes of light
adaptation. These findings were similar to those previously reported
for full-field cone ERGs.
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Figure 1. Relative amplitude of both the negative and positive components of the
summed multifocal ERGs during the course of light adaptation. The
means ± SEM of the relative amplitude obtained from five normal
subjects were plotted.
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Topographic Variations of the Amplitude Increase
We next explored the regional variations for this phenomenon.
Figure 2 shows representative multifocal ERGs at 0, 4, and 16 minutes after
light adaptation. There was an obvious increase in the amplitude for
peripheral ERGs, but the increase was not apparent in the central
regions. To quantify these changes, responses were grouped by retinal
eccentricity, as shown in the right half of Figure 3
, and the means ± SEM of the relative amplitudes of the positive
component at various retinal eccentricities were plotted and are shown
in the left half of Figure 3
. (See also Table 1
where both absolute and relative values at different retinal
eccentricities are shown.) The degree of amplitude increase in the
central retina was smallest at approximately 22%, at approximately
44% in the adjacent area, and at approximately 56% and 58% in the
third and fourth areas. This increase in the amplitude was
significantly larger with increasing retinal eccentricity (Spearman’s
rank correlation coefficient: rs =
0.68; P < 0.01).
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Figure 2. Multifocal ERGs recorded at different times after the onset of light
adaptation obtained from the left eye of a normal subject. Note that
the amplitude increase was more prominent in the peripheral retina than
in the central retina.
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Figure 3. The relative amplitude of the positive component of the multifocal ERG
at different retinal eccentricities with time. Means ± SEM of the
percentage amplitude for five normal subjects were plotted. The
magnitude of amplitude increase was smallest in the central retina and
became larger toward the peripheral retina.
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View this table:
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Table 1. Amplitudes for the Multifocal ERG Positive Component at Various Retinal
Eccentricities with Light Adaptation
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Table 2
shows the absolute and relative implicit times for the positive
component of the multifocal ERG at different eccentricities. Implicit
times were slightly increased (<4%) at all rings with adaptation, but
there were no statistically significant differences between different
retinal locations.
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Table 2. Implicit Time for the Multifocal ERG Positive Component at Various
Retinal Eccentricities with Light Adaptation
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To examine the influence of the stimulus configuration on our
results, we repeated the same experiment with 37 unscaled hexagonal
stimuli in one subject and confirmed that the magnitude of the increase
was consistently smallest in the central retina and became larger
toward the periphery (data not shown).
We also explored the amplitude increase of the second-order kernel
(representing the temporal interaction between two consecutive focal
flashes) and found that the time course, magnitude, and regional
variations of the amplitude increase were similar between first-order
and second-order kernels.
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Discussion
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Our results clearly demonstrate that the multifocal ERGs using
fast-flicker m-sequence stimulation increased in amplitude during light
adaptation. This phenomenon had been previously explored mainly with
full-field stimuli (30-Hz flicker, brief- or long-flash
stimuli).1
2
3
4
5
6
7
8
9
10
11
12
We found that both the negative and
positive components of the multifocal ERG increased during light
adaptation and that its time course was similar to that of conventional
full-field cone ERGs. These results, however, were not unexpected,
according to the results of two previous reports. First, Gouras and
MacKay8
reported that the traditional photopic ERG a-wave
and b-wave increase during light adaptation. Second, it was recently
shown that the negative and positive components of the multifocal ERG
have the same origins as the a- and positive peaks of the traditional
full-field photopic ERG.16
17
The mean of the multifocal ERG amplitude increase was 36% for
the negative component and 47% for the positive component. Both values
are smaller than the previously reported 60% to 75% increase with
full-field cone ERGs.6
8
The reason for the lower increase
in the multifocal ERGs can be explained partly by two differences in
the methods used. One difference is the longer recording time of the
multifocal ERG in our study (60 seconds) compared with those of
traditional full-field cone ERGs (less than 10 seconds). The amplitude
of the multifocal ERG in the first 60 seconds of recording just after
dark adaptation may increase considerably, even during the 60 seconds
of recording, because of the light-adapting effect of the stimulus.
Because the increase of the amplitude is calculated relative to this
first response, a larger initial response makes subsequent values
smaller. Another difference is the area of the retina stimulated. The
stimulus of the multifocal ERG falls within the central 60° of the
retina, whereas traditional full-field ERGs are elicited from the
entire retina. As noted in our results, the magnitude of amplitude
increase was smaller in the central retina and was larger toward the
peripheral retina, which may account for the smaller degree of increase
with multifocal ERGs than with full-field stimuli.
Our results showing that there are regional variations in the
amplitude increase across the retina are interesting in light of past
work. Weiner and Sandberg13
have also examined the
amplitude increase of foveal cone ERGs during light adaptation with a
4° flickering stimulus on the steady background illumination and
found that the foveal cone ERG amplitude increase was smaller (27%)
than that of reported full-field ERGs. Although they mentioned the
possibility of regional variation of this phenomenon, unfortunately,
they did not compare the magnitude of increase in different retinal
locations. Instead, they concluded that several differences in method
between foveal and full-field cone ERGs were the reasons for the
differences in the increase. Earlier, we showed that patients with the
incomplete type of congenital stationary night blindness had abnormally
large amplitude growth of the full-field 30-Hz flicker ERG during light
adaptation, but there was little amplitude growth of focal macular
30-Hz flicker ERGs.22
The exact mechanism for the amplitude increase of the cone ERGs
during light adaptation has not been determined. Armington and
Biersdorf3
previously suggested that the standing
potential of the eye may be involved. However, this possibility was
ruled out, because this phenomenon is observed even when the retina is
isolated from the retinal pigment epithelium, which is the origin of
the standing potentials. Gouras and MacKay8
proposed that
a redepolarization of the cone photoreceptors with light adaptation may
cause the cone ERG amplitude growth, because the a-wave also showed an
increase. Findings in studies of the cone membrane potential during
light adaptation are consistent with their
suggestion.23
24
If the increase originates from the
photoreceptors as they proposed, the present results would suggest that
there are regional variations in the magnitude of redepolarization of
the cone photoreceptors with light adaptation.
It has been also proposed that there may be factors other than the cone
photoreceptors contributing to the increase phenomenon. There is
evidence in the frog5
and carp7
retina that
not only cone but also rod light adaptation contributes to the
amplitude growth of the fast-flicker ERG during light adaptation. In
the dark-adapted condition, rods may normally inhibit cone response,
and in the light-adapted condition, this inhibition may be
released, resulting in the cone ERG growth. Although this idea still
remains controversial,10
our present results support this
hypothesis. It is well known that the activity of the rod system is
lowest in the central retina and increases toward the
periphery.25
This lower rod activity in the central retina
may result in the smaller amplitude increase at the center. It can be
expected that, if the amplitude increase is caused by suppression of
the rod system, the magnitude of increase would be maximal at a retinal
eccentricity of 15° to 25° where the rod density is maximal. We
could not confirm this point because of the limitation of the
equipment. Further, chromatic preadaptation periods5
may
provide a good test for the rod-suppression hypothesis.
Finally, it is important to emphasize that our results suggest that
considerable intra- and interindividual variations may result when
evaluating the multifocal ERG results in patients. We found that such
variations can be higher in the peripheral retina than in the central
retina. Therefore, to minimize variability, subjects should wait at
least 10 to 15 minutes under the light-adapted condition before the
test, if they have been tested previously in the dark.
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Footnotes
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Supported by Grant-in-Aid 08457462 from the Ministry of Education, Science, Sports and Culture, Japan.
Submitted for publication January 13, 1999; revised April 9, 1999; accepted May 20, 1999.
Commercial relationships policy: N.
Corresponding author: Mineo Kondo, W. K. Kellogg Eye Center, The
University of Michigan, 1000 Wall Street, Ann Arbor, MI
48105. E-mail: mkondo{at}umich.edu
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Abstract
Introduction
