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 cross- correlation 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 under- stand 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].
1.3 Multifocal ERGs
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 equal- amplitude 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 stim- ulus 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.
1.3.1 Principle
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
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 sub- tracting 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 suc- cessive flashes. The first slice of the second- order kernel is calculated by comparing the two
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 indi- cate a frame that could have been on or off. (From Sutter et al. [5] and Hood [6])
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 com- parison 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].
1.3.3 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 suc- cessfully 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 eccentric- ities [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 activ- ity and the effect of scattered light, some back- ground 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 com- ponent of the focal photopic on responses (a- waves 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 d- wave become relatively larger with increasing eccentricity when compared with the b-wave.
These changes were statistically significant for
five normal subjects. This differential distribu-
tion of the on and off components of the pho-
topic ERG must be considered when a disease
is evaluated using this technique.
Fig. 1.34. Top: Stimulus array of 61 hexago- nal elements. Bottom: stimulus pattern for recording multifocal on and off responses.
Each hexagon was modulated between stim- ulus 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 cal- culated 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)
As described above, the amplitude of the pho- topic ERG increases during the course of light adaptation when recorded after sufficient dark adaptation (see Section 1.1.4.1). This phenom- enon is important from two points of view when recording multifocal ERGs: first, record- ings 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 neu- ronal 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 dif- ference 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].
1.3.4 Adaptational State
Fig. 1.37. Relative amplitude of the positive components of multifocal ERG at various retinal eccen- tricities 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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