1.3
1.3
Multifocal ERGs
Multifocal ERGs
The techniques for recording multifocal ERGs
were developed by Sutter and Tan in 1992 [1].
With this method, focal ERGs can be recorded
simultaneously from multiple retinal locations
during a single recording session using crosscorrelation techniques. Unlike conventional
focal macular ERGs, there are still questions
about how this method works and what it mea-
sures because the technique is relatively new.
Two techniques that have been used to understand multifocal ERGs were to (1) analyze the
waveforms and components of the multifocal
ERGs using pharmacological agents [2, 3] and
(2) compare conventional focal macular ERGs
and multifocal ERGs from patients with known
macular diseases [4].
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Principles and Methods
1.3.1
Principle
The stimulus matrix, the multifocal responses,
and a topographic plot of the amplitudes of the
standard multifocal ERGs are shown in Fig.
1.32. The retina was stimulated with an array of
hexagonal stimuli generated on a computer
monitor. The stimulus matrix consists of 103
hexagonal elements driven at a 75-Hz frame
rate. The sizes of the hexagons were scaled
with eccentricity to elicit approximately equalamplitude responses at all locations. Each
hexagon has a 50% chance of being light each
time the frame changes. The pattern appears to
flicker randomly, but each element follows a
fixed, predetermined m-sequence so the overall
luminance of the screen over time is relatively
stable. By correlating the continuous ERG
signal with the on and off phases of each stimulus element, the focal ERG signal associated
with a specific hexagonal element is recorded.
An array of the 103 focal responses of the
multifocal ERG and a topographic map of the
amplitudes of the ERGs at each locus are shown
for a normal subject.
Fig. 1.32. Stimulus matrix (top), multifocal ERG
responses (middle), and a topographic plot of the
amplitudes (bottom) of standard multifocal ERG
recordings from a normal subject.The array in the
middle shows a response from the area around
the optic disk
1.3
The multifocal ERG responses shown in Fig.
1.31 are the first-order kernels, and how the
first- and second-order kernels are derived (as
reported by Sutter et al [5]. and Hood [6]) is
shown in Fig. 1.33. The first-order kernel is
obtained by adding all the records following
presentation of a white hexagon and then subtracting all the records following a black
hexagon (Fig. 1.33A). The second-order kernel
is a measure of how the multifocal ERG
response is influenced by the adaptation to successive flashes. The first slice of the secondorder kernel is calculated by comparing the two
Multifocal ERGs
responses shown in Fig. 1.33B (arrows). The
upper large arrow points to the response to a
flash preceded by a flash; the lower large arrow
points to the response to a flash preceded by a
dark hexagon. If these two responses are not
identical, the first slice of the second-order
kernel appears; it is calculated by subtracting
one response from the other. The first slice of
the second-order kernel represents the effect of
an immediately preceding flash; the second
slice of the second-order is a measure of the
effect of the flash two frames earlier.
Fig. 1.33. Derivation of the first- and second-order
kernels of multifocal ERGs. White and black hexagons
indicate whether the hexagons are on or off during
that frame change. Hexagons with diagonal lines indicate a frame that could have been on or off. (From
Sutter et al. [5] and Hood [6])
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Principles and Methods
1.3.2
Origin of Components of
Multifocal ERGs
Whereas the origin of each component of the
full-field photopic ERGs elicited by short- and
long-duration stimuli is fairly well known, the
origin of the components of the multifocal ERG
elicited by binary m-sequence (pseudorandom)
stimuli has not been fully determined. A comparison of the waveforms of the first-order
kernel of the multifocal ERG to the full-field
photopic ERG elicited by short flashes, suggest-
ing that they originate from the same retinal
neurons [6]. It is generally accepted that little of
the multifocal ERG response is generated by the
cone receptors per se; rather, it is dominated by
the responses of the on and off bipolar cells [4,
6]. Pharmacological studies on rabbits [2] and
monkeys [3] showed that the second-order
kernel receives a strong contribution from cells
in the inner retinal layers [6].
1.3
1.3.3
Multifocal ERGs
Recording On and Off Responses
by Multifocal ERGs
The photopic ERGs elicited by long-duration
stimuli provide important information on
bipolar cell function because this allows an
independent evaluation of the on and off
responses in the cone visual pathway [7] (see
Fig. 1.9). However, standard multifocal ERG
procedures do not provide information that can
be used to evaluate these cells. By modifying the
multifocal stimulating conditions, we have successfully recorded the on and off responses of
the multifocal ERGs from the human retina and
have explored how each component (a-, b-, and
d-waves) changes at different retinal eccentricities [8, 9]. To do this, as shown in Fig. 1.34, each
hexagonal element was modulated between
stimulus A (eight consecutive dark frames
followed by eight consecutive light frames)
and stimulus B (16 consecutive dark frames)
according to a binary m-sequence. Under these
stimulus conditions, multifocal on and off
responses were recorded. Each focal response
was calculated as the difference between the
mean response to stimulus A and the mean
response to stimulus B. To minimize rod activity and the effect of scattered light, some background illumination was used for both the dark
frames and the periphery of the television
monitor.
An example of the 61 multifocal on and off
responses recorded from the left eye of a
normal subject is shown in Fig. 1.35. Each component of the focal photopic on responses (awaves and b-waves) and off responses (d-wave)
is identifiable. Representative focal responses
averaged from five stimuli with increasing
eccentricities are shown in Fig. 1.36. The scales
are varied to obtain approximately equal size
responses at the five loci. The a-wave and dwave become relatively larger with increasing
eccentricity when compared with the b-wave.
These changes were statistically significant for
five normal subjects. This differential distribution of the on and off components of the photopic ERG must be considered when a disease
is evaluated using this technique.
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Principles and Methods
Fig. 1.34. Top: Stimulus array of 61 hexagonal elements. Bottom: stimulus pattern for
recording multifocal on and off responses.
Each hexagon was modulated between stimulus A (8 consecutive white frames followed
by 8 consecutive dark frames) and stimulus B
(16 consecutive dark frames) according to a
binary m-sequence. Each focal ERG was calculated as the difference between the mean
response to stimuli A and B. (From Kondo
et al. [8, 9], with permission)
Fig. 1.35. Multifocal photopic on and off responses
in a normal subject. Arrow points to the response
from the area of the optic disk. (From Kondo and
Miyake [9], with permission)
Fig. 1.36. Changes in the waveform with retinal
eccentricity. Averaged ERG waveforms from five
eccentric annuli are shown for two normal
subjects (A.O. and M.K.). The waveforms were
normalized to produce approximately equal
b-wave amplitudes. (From Kondo and Miyake
[9], with permission)
1.3
1.3.4
Multifocal ERGs
Adaptational State
As described above, the amplitude of the photopic ERG increases during the course of light
adaptation when recorded after sufficient dark
adaptation (see Section 1.1.4.1). This phenomenon is important from two points of view
when recording multifocal ERGs: first, recordings should be made only after the changes in
the light-adapted responses have stabilized to
obtain valid responses during clinical tests; and
second, topographical variations in the neuronal makeup of the retina may alter the degree
of amplitude increase during the course of light
adaptation [8, 9].
An example of the increased amplitude of
the multifocal ERGs in a normal subject after 0,
4, and 16 min of light adaptation following 30
min of dark adaptation is shown in Fig. 1.37 [9].
There is an obvious increase in the amplitude
for the peripheral ERGs, whereas the increase
is not apparent in the central region. This difference was shown to be significant in five
normal subjects. These findings indicate that
the rod–cone interactions, the mechanism
for this phenomenon, are different in the
central and peripheral retina. This difference
in the topographical distribution of the rod–
cone interaction is most likely caused by the
higher concentration of rods in the peripheral
retina [8, 9].
Fig. 1.37. Relative amplitude of the positive components of multifocal ERG at various retinal eccentricities with time.The increase in amplitude is smallest in the central retina and becomes larger toward
the periphery. (From Kondo and Miyake [9], with permission)
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Principles and Methods
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