Ординатура / Офтальмология / Английские материалы / Electrophysiology of Vision_Lam_2005

Figure 1.5 Examples of electrical noise and recording artifacts. The responses are from normal adults. The response with the 60-Hz noise and the response with the eye blink and movement are from the same individual; the response without the artifacts is shown for comparison. The responses of another normal adult, with and without eyelid spasm, are also shown.

Several commonly occurring ERG recording artifacts are recognized (Fig. 1.5). A voltage artifact spike coinciding with the flash stimulus is usually not significant in standard clinical recording because it is brief and does not affect the rest of

Reporting ERG Results and Establishing

Normative Data

The full-field ERG report, at the least, should display the recorded waveforms of all five recommended international standard responses along with the amplitudes and implicit times of the ERG components. Because ERG responses are variable among normal persons, a comparison of amplitudes and implicit times between the patient and a group of agematched normal subjects is required. Collection of normative ERG values by each facility is critical because of differences in recording equipment and technique (e.g., electrode type and position). The values from normal subjects are not distributed in a normal bell-shaped curve. Therefore, calculating the median and the 95% confidence limits are more appropriate than the mean and standard deviation. The normal lower and upper limits also aid interpretation. The effects of maturation and aging on the full-field ERG are discussed in Chapter 6. In addition to a comparison against normal values, an assessment of the interocular difference in ERG amplitudes and implicit times is also important to determine unilateral or asymmetric abnormality. The interocular percentage differences in ERG b-wave amplitude are usually 10% or less for most normal subjects with a difference of greater than 20% being highly unusual.

PHYSIOLOGIC ORIGIN OF THE

FULL-FIELD ERG

The ERG waveform represents a summation of the electrical activities of all cells of the retina. The physiologic origin of an ERG response is dependent on the adaptive state of the retina (scotopic vs. photopic), stimulus intensity and duration (flash vs. long-duration), stimulus type (flash vs. flicker), and stimulus color (white vs. chromatic). Knowledge of the physiologic origin of ERG components is derived primarily from animal studies by intraretinal microelectrode recordings and ERG changes in response to chemicals with known retinal cellular effects. This section discusses the physiologic origin of the

standard clinical ERG, assuming an understanding of basic retinal physiology detailed at the end of the chapter.

PI, PII, and PIII Potentials

Granit and Riddell (14) demonstrated that the ERG waveform is a summation of three processes or potentials called PI, PII, and PIII (Fig. 1.7). PI is a slow positive potential from the retinal pigment epithelium that contributes to the ERG c- wave which is not ordinarily measured in the clinic. PII is a positive inner retinal potential related mostly to bipolar cell activity and makes a major contribution to the ERG b-wave. PIII is a negative potential composed of two phases. The first phase called fast PIII is due to the closure of sodium ion channels of the photoreceptors and is responsible for the onset and

Figure 1.7 PI, PII, and PII potentials. The ERG waveform (a ¼ a- wave; b ¼ b-wave; c ¼ c-wave; d ¼ d-wave) is a summation of three potentials. PI is a slow positive potential from the retinal pigment epithelium that contributes primarily to the c-wave. PII is a positive inner retinal potential related mostly to bipolar cell activity and makes a major contribution to the ERG b-wave. PIII is composed of two phases. The first phase called ‘‘fast PIII’’ is related to photoreceptor activity and is responsible for the onset and descending phase of the a-wave. The second phase called ‘‘slow PIII’’ is related to Mu¨ ller cell activity. (From Ref. 93 with permission.)

descending phase of the a-wave, that is, the leading edge of a-wave. The second phase called slow PIII is due to hyperpolarization of the distal portion of the Mu¨ ller cells related to a decrease in extracellular potassium ions at the photoreceptor inner segments. The slow PIII contributes to the b- and c-waves.

Scotopic Rod Response—Physiologic Origin

The scotopic rod response has a prominent b-wave but no a-wave because the electrical activity of the rod photoreceptors to the dim stimulus is too small to be detected as an a- wave but this rod signal is amplified in the range of 100-fold by the rod-specific depolarizing ON-bipolar cells in the inner retina (15). In addition to this high retinal gain, the b-wave extracellular cellular current involves Mu¨ ller cells and is more extensive than the a-wave current of the rod photoreceptors (16).

Scotopic Combined Rod–Cone Response:

Physiologic Origin

The scotopic bright-flash combined rod–cone response has prominent a- and b-waves. The onset and descending phase of the a-wave are due to photoreceptor activity, that is, the fast PIII potential before PII arises (17,18). This leading edge of the a-wave, as shown by computational models, is directly related to the electrical activity generated by the phototransduction cascade (17,19). Therefore, the initial 14–20 msec of the response is essentially entirely due to photoreceptor activity with virtually no contribution from the inner retina (20). The shape and peak of the b-wave is determined by the interaction between the fast PIII potential of the photoreceptors and PII potential of the inner retina. The b-wave is primarily due to depolarizing ON-bipolar cell activity which produces a light-induced release of potassium that causes depolarization of the Mu¨ ller cells resulting in a corneal positive potential (21–24). Other cells of the inner retinal layers also contribute to the b-wave.

Photopic Single-Flash Cone Response:

Physiologic Origin

The photopic single-flash cone response has discernible a- and b-waves. The initial descending phase of the a-wave is due to the electrical activity generated by the phototransduction of the cones as demonstrated by computational models (25–28). However, the photopic a-wave receives a significant contribution from retinal activity postsynaptic to cone photoreceptors particularly for stimuli typically used for clinical standard ERG (29). The a-wave trough is influenced by inner retinal activity including those of hyperpolarizing OFF-bipolar cells. The photopic b-wave is not only due to the activity of depolarizing ON-bipolar cells affecting perhaps Mu¨ ller cells but is also shaped by the activities of hyperpolarizing OFF-bipolar cells and horizontal cells (30). The photopic b-wave can be explained by a push–pull model with the depolarizing ON-bipolar cells pulling the ascending phase of the b-wave up and the OFF-hyperpolarizing cells limiting b-wave amplitude by pulling the depolarization toward baseline (30).

Photopic 30-Hz Flicker Cone Response:

Physiologic Origin

The photopic 30-Hz flicker cone response consists of b-waves due to inner retinal post-photoreceptoral activity in response to cone activity but the direct contribution from cone photoreceptors is very small. The b-waves of flicker stimuli are made of ONand OFF-ERG components with large phase differences so that these components partially cancel each other (31,32).

Oscillatory Potentials: Physiologic Origin

The oscillatory potentials consist of about 4–6 wavelets during the ascending phase of the b-wave and have physiologic origin that differs from the a- and b-waves (33,34). The oscillatory potentials are due to both rodand cone-generated activities and can be recorded in scotopic as well as photopic conditions (35,36). Activity of inhibitory feedback circuits in

the inner plexiform layer as the origin of oscillatory potentials has been proposed, but the same retinal mechanisms may not apply to all oscillatory potentials. OP1 and OP2 appear to be more cone-mediated and OP3 and OP4 rodmediated, but this notion does not explain oscillatory potentials from all recorded conditions (37,38). The oscillatory potentials are likely generated by amacrine and bipolar cells, and the early wavelets are likely related to the ON-pathway while the later wavelets are related to the OFF-pathway (39).

ERG FLUCTUATION RELATED TO

CIRCADIAN RHYTHM

The outer segments of the photoreceptors are continuously regenerated, shed, and phagocytized by the retinal pigment epithelium. The greatest rate of shedding occurs diurnally when the photoreceptors are functionally less active—at about 1–3 hr following onset of daylight for rods and in the early darkness hours for cones. Small diurnal changes in ERG responses are found but are unlikely to be clinical significant (40–42). In one study of normal subjects, the scotopic a-wave showed no circadian rhythm, but the b-wave was greatest at noon and lowest at 6 AM in some subjects (43).

NEGATIVE ERG—SELECTIVE REDUCTION

OF b-WAVE

The negative ERG refers to selective reduction of the b-wave to the extent that the peak of the b-wave fails to reach baseline, and the b-wave to a-wave amplitude ratio is less than 1 (Fig. 1.8). In normal subjects, the peak of the b-wave is well above baseline, and the b-wave amplitude is at least nearly twice the a-wave amplitude. A selective reduction of the b-wave implies a selective dysfunction of the inner retina with a relative preservation of photoreceptor function. A number of conditions can cause a negative full-field ERG (Table 1.3). Although a selective impairment of both photopic and scotopic b-waves may occur, the selective b-wave

Figure 1.8 An example of ‘‘negative ERG’’ from a patient with retinal ischemia. The standard full-field ERG responses demonstrate reduced and prolonged rod and cone responses. Note the relatively selective reduction of b-wave on the scotopic combined rod–cone response such that the peak of the b-wave is below baseline and the b-wave amplitude is less than the a-wave amplitude. A selective b-wave reduction indicates greater inner retinal dysfunction. A number of conditions can cause a negative ERG (see Table 1.3).

reduction in the negative ERG is most notable for the scotopic combined rod–cone bright flash response.

ADVANCED CLINICAL FULL-FIELD ERG TOPICS

Chromatic Stimulus ERG—Isolated Rod, Cone,

and S-Cone Responses and x-Wave

The light-sensitive rod pigment rhodopsin has a spectral absorption peak at 496 nm, and each of the three types of color-sensitive cone pigments has peak sensitivity to longwavelength (558 nm), mid-wavelength (531 nm), or shortwavelength (419 nm) regions of the visible light spectrum.

Table 1.3 Disorders Associated with Selective b-Wave Reduction Large Enough to Produce a Negative b-Wave (Negative ERG)a

aTypically noted on the scotopic combined rod–cone response.

With selective color stimuli, more specific ERG responses of the rod or cone subtype are elicited.

An essentially pure rod response is elicited scotopically by a dim blue flash stimulus. The short-wavelength ( < 460 nm) characteristic of the blue flash minimizes stimulation of the long-wavelength and mid-wavelength sensitive cones while maximizing stimulation of the rods, and the short-wavelength sensitive cones are minimally active under this recording condition. For instance, a blue flash 1 log unit