Ординатура / Офтальмология / Английские материалы / Electrodiagnosis of Retinal Disease_Miyake_2005
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1.1 Full-Field Electroretinograms 13
increased amplitude of the photopic ERG results from rod–cone interactions, the horizontal cells probably play a role; and we would expect the absence of horizontal cell function to result in disappearance of this phenomenon. However, even in the isolated photoreceptor potential (P111) of carp retina [42] and an eye with a central retinal arterial occlusion in humans, where the horizontal cells are not functional [44], this increase was observed to some degree. It is possible that alterations in the temporal response characteristics of the horizontal cells operate slowly via interplexiform feedback by means of dopamine and horizontal cells coupling; and in this case, the slow increase in the flicker response would parallel the changes in the temporal adaptation of the retina. It has also been reported that in the psy-
chophysical experiments paralleling the electrophysiological ones the subjective sensitivity did not increase; rather, it slightly decreased during the same time of the ERG increase, thereby demonstrating a difference between subjective-sensitivity and suprathreshold ERGs [38]. We assume, therefore, that although this phenomenon may ultimately have something to do with rod–cone interaction, and this kind of interaction may be different from the electrophysiological or psychophysical phenomena suggested by others [38, 39, 41, 44, 45]. One of the reasons we believe that it is worthwhile to investigate this phenomenon fully is that an exaggerated increase in 30-Hz flicker ERGs was observed only in the incomplete (not the complete) type of congenital stationary night blindness [44] (see Section 2.10.5.2).
Fig. 1.16. Changes in photopic ERGs during light adaptation in isolated carp retina after 60 min of dark adaptation (left) and after 60 min of dark adaptation followed by recording of photopic ERGs under light adaptation (right). (From Horiguchi et al. [42])
14 1 Principles and Methods
1.1.4.2Photopic Hill Phenomenon
The amplitude of the b-wave of the human photopic ERG elicited by short-flash increases with increasing stimulus intensities at lower intensities reaches a plateau and then decreases at higher stimulus intensities. Because a plot of the b-wave amplitude as a function of the stimulus intensity has an inverted U shape, this phenomenon has been termed the photopic hill phenomenon [45]. The photopic, short-flash ERGs elicited by increasing stimulus intensities in a normal subject are shown in Fig. 1.17. At the lower stimulus intensities, the amplitude of the b-wave increases with increasing stimulus intensities until it reaches a maximum at a stimulus intensity of 3.0logcd/m2. Further increases in the stimulus intensity result in a progressive decrease in the amplitude of the b- wave. This unusual property of the human photopic b-wave was first described by Peachey et al. [45] and has been confirmed by others [46, 47].
To confirm this phenomenon and compare it to the components of the photopic ERG, we studied photopic ERGs elicited by a short flash (5ms) and a long flash (250ms) of 2.7logcd/m2 under a constant background of 40cd/m2 (Fig. 1.17) [47]. In the short-flash recordings, the a- wave, b-wave, and i-wave were evaluated. The amplitudes of the short-flash b-wave and i-wave showed the photopic hill, decreasing at higher stimulus intensities; the a-wave amplitude did not show the photopic hill phenomenon and continued to increase with increasing stimulus intensity up to the maximum stimulus intensity. The implicit times of the b-wave remained unchanged but then increased at higher stimulus intensities, whereas those of the a-wave decreased with
increasing stimulus intensity up to the maximum stimulus intensity.
In the long-flash recordings, the b-wave did not decrease but plateaued. The d-wave (off response) decreased at higher stimulus levels, as did the short-flash elicited b-wave. The implicit times of the b-wave remained unchanged until 1.9logcd/m2 and then increased, confirming the results of earlier studies [45, 46]. The implicit time for the d- wave increased with increasing stimulus intensities at the higher stimulus levels, as did the b-wave implicit times elicited by short-flash stimuli. At the higher stimulus intensities the amplitude of the d-wave decreased, and another slow positive component (Fig. 1.17, asterisk) appeared and increased gradually in amplitude and timing; it dominated the off response. The long-flash a-wave showed a pattern similar to that of the short-flash ERG a-wave; that is, the amplitude continued to increase and the implicit time decreased for the entire range of stimuli.
Because the b-wave and the d (off)-wave interact to produce a single positive response with short flashes (see Fig. 1.10), the decrease in the b-wave amplitude at high stimulus intensities is caused by the decrease in the d-wave at the higher stimulus intensities. These observations can explain the major mechanism of the photopic hill in photopic ERGs elicited by short-flash stimuli. Our further study of this phenomenon using pharmacological agents in primate ERGs showed that the photopic hill results mainly from the reduction of the on component amplitude at higher intensities and the delay in the positive peak of the off component at higher intensities [48].
1.1 Full-Field Electroretinograms 15
Fig. 1.17. Left: Photopic short-flash ERGs elicited from a normal subject by various stimulus intensities. Stimulus duration is 5 ms and the constant background illumination is 40 cd/m2. Right: Photopic long-flash ERGs elicited by various stimulus intensities in the same normal subject. Vertical dashed line indicates 30 ms. At the higher stimulus intensities, the amplitude of the d-wave decreases, and another slow positive component (asterisk) dominates the off response. (From Kondo et al. [47], with permission)
16 1 Principles and Methods
1.1.4.3Rod–Cone Interactions in Full-Field ERGs
Little was known about whether the interaction could be evaluated by standard full-field ERGs. We have found that rod–cone interactions can be detected in the standard full-field ERG by carefully selecting suitable recording conditions. A rod–cone interaction can be seen in the full-field ERGs recorded with deep red stimuli (Kodak Wratten No. 29) in a normal subject (Fig. 1.18). The upper two recordings are the responses elicited by a stimulus intensity of 0.047cd/m2 ·s-1 (Fig. 1.18, stimulus A, left) and 0.1cd/m2 ·s-1 (Fig. 1.18, stimulus B, right) after 30min of dark adaptation. As can be seen in both responses, when the full-field ERG is elicited by a deep red stimulus in the dark, the earlier photopic component (Fig. 1.18, photopic b-wave, or BP) and the later scotopic component (Fig. 1.18, scotopic b-wave, or BS) are recorded separately to give a double peak response. The BP was first reported by Motokawa and Mita in 1947, and the initial
peak was called the X-wave [5]. ERGs were then recorded under six different white background illuminations (B.G.) ranging in intensity from 0.006 to 0.035cd/m2 (B.G. 0 indicates no background illumination). The changes in the cone (BP) and rod (BS) components were evaluated immediately after the onset of the B.G. illumination. Our results from 13 normal subjects indicated that the amplitude of BS decreased in accordance with the intensity of the background illumination for both stimuli. The amplitudes of BP for stimulus A increased slightly but not significantly, but those with stimulus B increased significantly at all background intensities (Fig. 1.19). In both stimuli, the amplitude of a-wave did not change significantly.
These results indicate that rod–cone interaction can be evaluated by standard full-field ERG technique with a proper combination of the stimulus light and background illumination.
1.1 Full-Field Electroretinograms 17
Fig. 1.18. Rod–cone interactions in full-field ERGs. Full-field ERGs recorded with a relatively weak red stimulus (A) and relatively intense red stimulus (B) in the dark after 30 min of dark adaptation (top) and under white background illumination (B.G.) with changing intensities. B.G. 0 and 6 indicate no background and maximum background illumination, respectively. BP, photopic b-wave; BS, scotopic b-wave
Fig. 1.19. Changes in the relative amplitude (% of maximum amplitude) of the scotopic b-wave (BS, top) and photopic a-wave and b-wave (BP, bottom) in 13 normal subjects recorded after stimulus A or stimulus B. Amplitude of BS gradually decreases as the intensity of the background illumination increases. The amplitude of BP significantly increases in B only when the background illumination is on
18 1 Principles and Methods
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1.1 Full-Field Electroretinograms 19
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20 1 Principles and Methods
1.2Focal Macular ERGs
The design and development of the instrument required for recording focal macular ERGs from normal subjects and patients with macular diseases have been major accomplishments in my life. I first took part in the study of focal macular ERGs in 1976 with Tatsuo Hirose in Boston [1] and have continued to refine the various aspects of this technique up to the present.
The principle of recording a focal macular ERG includes presenting a small stimulus to the macula and recording the response from the stimulated area. Many investigators have tried to obtain reliable responses from the human macula, but the results have not been satisfactory routine clinical examinations [2–6]. To eliminate contaminating stray light
responses, background illumination must be used to depress the sensitivity of the area surrounding the stimulus [7, 8]. By combining the focal stimulus with background illumination, focal responses can be recorded. It is also essential to monitor the location of the stimulus on the fundus during the recordings, particularly in eyes with a central scotoma, to be certain that only the fovea is stimulated [1, 9].
In 1981, we succeeded in building an instrument for recording focal macular ERGs [10, 11], and more than 3500 patients with various macular diseases have been examined to date [12]. The results have been informative, and valuable data have been obtained on the normal and abnormal physiology of the macular area of the retina.
1.2 Focal Macular ERGs 21
1.2.1The System
1.2.1.1Observation and Stimulation Systems
To develop an instrument to record focal macular ERGs with the capability of monitoring the location of the stimulus on the fundus, we modified an infrared television fundus camera (Canon CR-45NM).An overall view and diagram of the system are shown in Figs. 1.20 and 1.21, respectively. The light for viewing the fundus (2, in Fig. 1.21) passes through an infrared filter (4) before entering the eye (11). The fundus image is reflected into the television camera (22) and is viewed on a television screen with an overall field of view of 45° (24). The light for this viewing system is obtained from a tungsten light bulb (27), and the light beam passes through a fixation plate (26) with 16° of arc fixation target. By moving the fixation plate (26), the fixation point can be moved over 25° of the central fundus. Another target, attached to the side of the fundus camera, is used for fixation by the fellow eye when a large central scotoma is present in the eye being examined.
A 200-watt halogen lamp (33, in Fig. 1.21) is used as the source for the light stimulus. A rotating chopper blade (35) driven by pulses from an electronic stimulator (31) controls the frequency and duration of the light stimuli. The rise and decay time of the stimulus chopped by the shutter is 4.2ms. The stimulus light is carried to the fundus camera by a fiberoptic cable (36). The light is made homogeneous by
a diffuser (37), and the spot size is varied by adjusting the aperture (38) on a movable plate (39). By moving this plate (39), the stimulus spot can be moved over 25° of the central fundus, and its position can be monitored on the television screen. The intensity and color of the light stimulus can be changed by inserting neutral density and colored filters into the filter holder (40). Photographs of the stimulus spot on the fundus can be taken with a 35-mm camera (28) or a Polaroid camera (30).
The light source for the background illumination is another tungsten lamp (50, in Fig. 1.21). The light passes through a diffuser (48) to give homogeneous background illumination. The intensity of the background illumination is controlled by neutral density filters (49), and the light is transmitted into the eye at a visual angle of 45°. Additional background illumination is used for the peripheral retina outside the central 45°. A plastic hemisphere, 10cm in diameter, is attached to the top of the fundus camera (46). Miniature lamps (47) are installed on the inner wall of the hemisphere and are covered by a diffuser. The intensity of the peripheral background illumination is equalized subjectively to that obtained from the fundus camera. Thus, homogeneous background illumination of nearly the entire visual field is obtained.
22 1 Principles and Methods
Fig. 1.20. Overall view of the observation and stimulation systems for focal macular ERG and visually evoked response (VER) recordings. The examiner records the ERGs while monitoring the stimulus on the fundus by the infrared television fundus camera (A). A plastic hemisphere with miniature lamps is attached to the top of the camera to obtain background illumination for the peripheral retina (B). A Burian-Allen bipolar contact lens is used to record the ERGs (C). (From Miyake et al. [10])
Fig. 1.21. Optical components of the observation and stimulation systems. 1, reflector; 2, observation lamp; 3, condenser lens; 4, infrared filter; 5, flash tube; 6, condenser lens; 7, mirror; 8, annulus; 9, relay lens; 10, relay lens; 11, patient’s eye; 12, objective lens; 13, beam splitter; 14, mirror with an aperture; 15, focusing lens; 16, imaging lens; 17, beam splitter; 18, movable lens; 19, field lens; 20, beam splitter; 21, imaging lens; 22, infrared television camera; 23, cable; 24, television monitor; 25, relay lens; 26, fixation plate; 27, lamp; 28, 35mm film camera; 29, relay lens; 30, Polaroid camera; 31, controller; 32, reflector; 33, exciting light source; 34, motor; 35, chopper; 36, optic fiber; 37, diffuser; 38, aperture plate; 39, movable plate; 40, filter; 41, mirror; 42, mirror; 43, mirror; 44, projection lens; 45, reflector; 46, diffuser; 47, lamp; 48, diffuser; 49, filter; 50, lamp. (From Miyake et al. [10], with permission)