Ординатура / Офтальмология / Английские материалы / Electrodiagnosis of Retinal Disease_Miyake_2005

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].

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.

The multifocal ERG responses shown in Fig. 1.31 are the first-order kernels, and how the firstand 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

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.

Whereas the origin of each component of the full-field photopic ERGs elicited by shortand 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].

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 (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 distribution of the on and off components of the photopic ERG must be considered when a disease is evaluated using this technique.

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 16min 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].

References

1.Sutter EE, Tan D (1992) The field topography of ERG components in man. 1. The photopic luminance response. Vis Res 32:433–446

2.Horiguchi M, Suzuki S, Kondo M, Tanikawa A, Miyake Y (1998) Effect of glutamate analogues and inhibitory neurotransmitters on the electroretinograms elicited by random sequence stimuli in rabbits. Invest Ophthalmol Vis Sci 39:2171–2176

3.Hood DC, Frishman LJ, Sazik S, Viswanathan S, Robson JG,Ahmed J (1999) Evidence for a ganglion cell contribution to the primate electroretinogram (ERG): effects of TTX on the multifocal ERG in macaque. Vis Neurosci 16:411–416

4.Kondo M, Miyake Y, Horiguchi M, Suzuki S, Tanikawa A (1995) Clinical evaluation of multifocal electroretinogram. Invest Ophthalmol Vis Sci 36:2146–2150

5.Sutter EE, Shimada Y, Li Y, Bearse MA (1999) Mapping inner retinal function through enhance-

ment of adaptive components in the m-ERG. In: Vision science and its applications. OSA Technical Digest Series. Optical Society of America,Washington, DC, pp 52–55

6.Hood DC (2000) Assessing retinal function with the multifocal technique. Prog Retinal Eye Res 19:607– 646

7.Sieving PA, Murayama K, Naarendorp F (1994) Push-pull model of the primate photopic electroretinogram: a role for hyperpolarizing neurons in shaping the b-wave. Vis Neurosci 11:519–532

8.Kondo M, Miyake Y, Horiguchi M, Suzuki S, Tanikawa A (1998) Recording multifocal electroretinogram on and off responses in humans. Invest Ophthalmol Vis Sci 39:574–580

9.Kondo M,Miyake Y (2000) Assessment of local cone onand off-pathway function using multifocal ERG technique. Doc Ophthalmol 100:139–154

In 1948 Du Bois Reymond reported that in the normal eye there is a flow of electrical current that is oriented so the cornea is relatively more positive than the posterior pole of the eye. This potential difference is referred to as the standing potential or resting potential of the eye. The electrooculogram (EOG) is an indirect measure of the amplitude of the standing potential, which changes during dark and light adaptation. To obtain an EOG, electrodes are placed at the inner and outer canthi of the eyes, and the patient is asked to look back and forth between a pair of fixation lights.When the cornea moves closer to one of the electrodes, it becomes more positive and the other electrode becomes more negative. The opposite happens when the eyes move to the other side.

The changes in the amplitude of the EOG in the dark-adapted and light-adapted state of a normal subject are shown in Fig. 1.38. The smaller amplitudes are recorded when the eyes make the saccadic eye movements in the dark; this is called the “dark trough.” The peak amplitude is recorded against a steady light background, which is called the “light peak.” The light peak/dark trough (L/D) ratio is an index (Arden index) used to assess retinal function [1]. A ratio of 1.80 is the lower limit of normal in our clinic.

The origin of the retinal standing potential is thought to be in the retinal pigment epithelium (RPE). However, the light rise is generated by light stimulation of the photoreceptor–RPE complex; and it is detected only if certain structures in the middle retinal layer are normal.

Optical coherence tomography (OCT) is a relatively new diagnostic imaging technique that can be used to obtain cross-sectional or tomographic images of biological tissues with micron resolution. By comparing the focal macular ERGs or multifocal ERGs with the OCT

images, a layer-by-layer correlation can be obtained on the physiology and morphology of the macular area for various macular diseases [1]. The most recent model of the OCT (OCT3) can obtain images in which the retinal layers are clearly identifiable (Fig. 1.39).

Fig. 1.39. Optical coherence tomography images of the macula in a normal subject showing the layered structure of the retina. RNFL, retinal nerve fiber layer; GCL, ganglion cell layer; RPE, retinal pigment epithelium, PR/IS, photoreceptor inner segment; PR/OS, photoreceptor outer segment/ INL, inner nuclear layer; ONL, outer nuclear layer; OPL, outer plexiform layer; IPL, inner plexiform layer; ELM, external limiting membrane