Ординатура / Офтальмология / Английские материалы / Electrophysiology of Vision_Lam_2005
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attached to a thin basement membrane forming the inner layer of Bruch’s membrane which separates the RPE from the choroid, and the RPE cell apical surface has multiple villous processes that adhere to the photoreceptor outer segments by a mucopolysaccharide matrix (Fig. 4.1). To maintain the RPE standing potential, the integrity of the RPE as well as the contact between the photoreceptors and the RPE must be intact. This explains why the EOG is decreased in retinal detachment as well as degenerative disorders involving the photoreceptors or the RPE or both. In those disorders due primarily to photoreceptor dysfunction, decreases in EOG generally parallel impaired ERG responses.
Figure 4.1 Schematic diagram of the physiologic origin of the clinical EOG. Light causes increase of a light-activated substance presumably produced by the photoreceptors, which binds to receptors at the RPE apical membrane surface. This activates an intracellular second messenger causing the basal surface of the RPE to depolarize with increased Cl conductance.
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The physiologic origin of EOG is not completely understood. Intraretinal microelectrode recordings in animals indicate that light adaptation causes increase of a biochemical agent, presumably produced by the photoreceptors, that bind to the membrane of the RPE apical surface (Fig. 4.1) (4–7). This causes an intracellular second messenger within the RPE to depolarize the basal surface of the RPE by increasing the conductance of negative chloride ions (Cl ). The result is a transepithelial potential of the RPE that produces, at the basal surface of the RPE, a negative charge which can be measured indirectly as a positive charge change at the cornea. This increase in the transepithelial potential of the RPE in response to light is referred to as the light-sensitive component of the EOG. A lower transepithelial RPE potential unrelated to light-induced photoreceptor activity exists in darkness and is the light-insensitive component of the EOG. Thus, the EOG is a measure of the function of the photoreceptors, subretinal space, and the RPE.
The resting potential of the retina is not a steady potential but a slow oscillating potential that continues to rise and fall even in a stable state of light adaptation. In a lightadapted retina, the rise reaches a higher peak amplitude than a dark-adapted retina in which the rise is minimal or absent. The EOG light rise reaches ‘‘light peak’’ in about 7–12 min from the onset of light adaptation and falls to a ‘‘dark trough’’ in about 12 min with dark adaptation. This ‘‘slow oscillation’’ is measured by the clinical EOG.
In reality, the slow oscillations of the EOG is not the only light-induced response of the RPE (Table 4.2) (4). Light absorption by the photoreceptors results in a decrease in extracellular potassium ions (Kþ) around its outer segments which causes a transient hyperpolarization at the apical RPE surface that is measured as part of the c-wave of the flash ERG occurring 2–5 sec after the light stimulus. Moreover, a transient rapid initial fall in the RPE standing potential over 60–75 sec follows the onset of light adaptation. This phenomenon is the ‘‘fast oscillation’’ and is produced by the hyperpolarization of the basal RPE membrane in response to the decrease in the extracellular Kþ of the photoreceptor
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Table 4.2 Light-Related Electrophysiologic Responses of the Retinal Pigment Epithelium
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Charge measured at |
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cornea, timing, and |
Clinical measure |
Origin |
Physiologic process |
characteristics |
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EOG slow oscillations |
RPE basal membrane |
Depolarization due to |
Positive standing potential |
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increased CI conductance |
peaking 7–12 min with light |
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adaptation |
EOG fast oscillations |
RPE basal membrane |
Hyperpolarization due to |
Standing potential |
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decreased extracellular Kþ |
decreasing rapidly during |
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from photoreceptor activity |
60–75 sec of light period and |
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increasing rapidly with |
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similar period of darkness |
ERG c-wave (positive |
RPE apical membrane |
Hyperpolarization due to |
contribution) |
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decreased extracellular Kþ |
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from photoreceptor activity |
Positive transient potential 2–5 sec after onset of flash stimulus
4 Chapter
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outer segments. The c-wave and the fast oscillations are not ordinarily recorded clinically. In contrast, the clinical EOG is a measure of the slow oscillations of the resting potential of the RPE which is not related to the decrease in Kþ at the subretinal space nor is it significantly affected by a brief light stimulus (8).
CLINICAL EOG RECORDING—PATIENT SET-UP
In clinical EOG recording, cutaneous electrodes made of sil- ver–silver chloride or gold are placed near the medial and lateral canthal regions of each eye, and the resting potential between the cornea and the retina is indirectly obtained by having the subject look back and forth repetitively at two fixation targets (Fig. 4.2). The fixation targets are located 15 from primary gaze horizontally to the right and the left of primary gaze. The fixation targets are typically red diodes that are built into the full-field stimulus dome of the full-field ERG or flash VEP (Fig. 4.3). To assist in the rapid saccadic eye movements, the fixation targets can be alternately lit and the subject is instructed to look at the lit target. The goal
Figure 4.2 Cutaneous electrodes for EOG recording placed near the medial and lateral canthi of each eye.
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Figure 4.3 Fixation targets for EOG recording. The targets are typically built into the full-field dome and consist of red diodes located 15 to the right and left of the primary gaze fixation target. The targets are alternately lit during EOG recording to assist the subject in making accurate saccades.
is to complete a cycle of right-to-left and left-to-right eye movements every 2–5 sec.
With the recording electrodes near the medial and lateral canthi, the relative position of each eyes with respect to the electrodes changes with the horizontal saccadic eye movements (Fig. 4.4). For instance, when the eyes are looking at the right fixation target, the cornea of the right eye is closer to the lateral canthus electrode and the retina is closer to the medial canthus electrode. The position of the right eye is reversed with fixation to the left target. Therefore, with the lateral canthus electrode serving as the recording electrode and the medical canthus electrode as the reference electrode, the change in the measured potential between right gaze and left gaze is the approximate potential difference between the cornea and the retina. The results of the EOG
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Figure 4.4 Clinical EOG recording. Note the change of the position of the eye relative to the electrodes with horizontal saccadic eye movements. The positive electrode at the lateral canthus of the right eye is closer to the cornea on right gaze and closer to the retina on left gaze. At the beginning of each minute of testing, at least 10 sets of back-and-forth horizontal saccades are obtained simultaneously from both eyes. The averaged amplitude of the saccades is the EOG amplitude for the given minute. The saccadic recording displayed by the recording system should be monitored for inaccurate eye movements such as saccadic overshoots that may adversely affect EOG result.
recording are a square-shaped waveform of the horizontal saccades with the height of the square waves corresponding to the EOG amplitude (Fig. 4.4). In short, the clinical EOG is an indirect measure of the resting potential of the retina by measuring the potential difference between the cornea and the retina. Aside from the transepithelial potential of the RPE, other ocular tissues also make small contributions to the measured EOG potential. Of interest, direct EOG
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recordings by the use of corneal electrode are possible with specialized technique; indirect and direct EOG recordings have comparable results (9,10).
At the beginning of each minute of EOG testing, at least 10 complete sets of horizontal saccades are obtained. The amplitudes of the 10 sets of saccades are averaged to provide the EOG amplitude for the given minute. The saccadic waveforms displayed by the recording system should be assessed to determine the stability and quality of the eye movements. Saccadic overshoots and imprecise saccades will produce inaccurate EOG amplitude (Fig. 4.4). Patients with eye movement disorders such as nystagmus and large angle strabismus may not be able to perform clinical EOG. Likewise, EOG testing may not be possible for those who are not cooperative enough to perform adequate saccades.
OBTAINING LIGHT PEAK AND DARK TROUGH EOG AMPLITUDES
The goal of EOG testing is to acquire the maximal lightadapted amplitude, the ‘‘light peak,’’ and the minimal dark-adapted amplitude, the ‘‘dark trough.’’ The light peak is influenced by the light intensity used for light adaptation (11–14). Therefore, whether the pupils should be dilated with eye drops is determined by the available background light intensity of the full-field dome. The international standard for clinical EOG recommends a luminance between 400 and 600 cd=m2 for undilated pupils and a luminance between 50 and 100 cd=m2 for dilated pupils. Further, the wavelength of the light stimulus may also influence the light peak, and white light is typically utilized. Periodic calibration of the recording system should be performed as recommended by the manufacturer and based on international calibration standard (15).
The EOG test session consists of three phases—preadap- tation, dark adaptation, and light adaptation (Fig. 4.5). During preadaptation, the patient is exposed to a recommended light level of 35–70 lux for at least 15 min. Dimmer
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Figure 4.5 Time vs. EOG saccadic amplitude plots. The plots of a normal EOG, reduced light-peak EOG, and no light-peak EOG are shown. The recordings were obtained from a normal subject and two patients with retinitis pigmentosa. The dark and light phases do not always have the same duration and are individualized depending on when dark trough and light peak occur.
preadaptation light levels may fail to suppress rod function and can diminish the size of the subsequent dark trough obtained during the second phase of testing. On the other hand, stronger light levels or sudden changes in illumination may produce excessive light stimulation and more difficulty in reaching a subsequent steady dark trough. Excessive light exposure such as ophthalmoscopy and fundus photography should be avoided prior to EOG testing. Although not required, commencing EOG recording during the preadaptation period has several advantages. First, it minimizes differences of light exposure among subjects by having all subjects exposed to a proper luminance level provided by the full-field dome. Second, it provides the patient with opportunities to practice performing EOG saccades, and it also allows the assessment of the quality of the saccadic recordings.
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The second phase of EOG is the dark adaptation phase |
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during |
which EOG amplitudes are recorded for about |
15 min in darkness. As the EOG amplitude gradual decreases, the dark trough is reached after about 11–12 min although it may be reached earlier or later. To ensure that the true minimal EOG amplitude has been reached, testing should continue until the EOG amplitudes have risen above the dark trough for at least 2 min.
The third phase of EOG is the light adaptation phase during which EOG amplitudes are recorded with the steady background light stimulus of the full-field dome. The light peak is usually reached after about 7–10 min, and testing is continued until the EOG amplitude has fallen below the light peak for at least 2 min. If no light peak can be identified, testing should be continued for a total of 20 min to exclude the presence of a late light peak.
The results of the EOG are typically plotted as a graph of time vs. saccadic amplitude by the recording system (Fig. 4.5). The dark trough and the light peak amplitudes are identified visually or mathematically by smoothing the plot. Unusually high or low points due to eye movement or blink artifacts should be excluded from analysis.
EOG AMPLITUDE RATIO—ARDEN RATIO
In 1962, Arden and Fojas (16) discovered that the ratio of the EOG light-peak to dark-trough amplitude ratio provides a more consistent measure and is clinically more useful than the actual value of the amplitudes which may vary widely among individuals. The large interindividual differences in EOG amplitudes are due not only to the normal physiologic variation of the resting retinal potential but also due to anatomical variation of the location of the globe to the canthi. For instance, persons with shallow orbits or proptosis have higher absolute EOG amplitude because the canthal electrodes are located more posteriorly to the globe during saccades (17). Differences in recording techniques also contribute to the interindividual differences in EOG amplitudes. In
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contrast, interocular amplitude differences in normal individual are usually small.
The light-peak to dark-trough amplitude ratio is commonly called the Arden ratio. The Arden ratio is typically 1.8 or greater in normal subjects, and is considered abnormal below 1.6. In rare cases, recorded EOG amplitudes may be so low that a minor upward drift of amplitude during the light adaptation phase could result in a falsely elevated Arden ratio. Re-test variability has less effect on the Arden ratio than on the actual EOG amplitudes. Collection of agematched normative data by each facility is recommended. The maturation and age-related changes of EOG are discussed in Chapter 6.
ALTERNATIVE EOG METHOD: LIGHT-PEAK TO DARK-ADAPTED BASELINE AMPLITUDE RATIO
As an alternative EOG measure to the light-peak to dark-trough amplitude ratio, the light-peak to dark-adapted baseline amplitude ratio can also be acquired. In this method, during the preadaptation phase, excessive light exposure should be similarly avoided but exposure to dimmer than recommended light levels has little effect on the ensuing extended dark adaptation phase. After at least 40 min of dark adaptation, the EOG is recorded for 5 min or longer until a stable baseline is reached. A light adaptation phase is then performed to establish the light peak, and the ratio of the light-peak to dark-adapted baseline amplitude is calculated.
REPORTING THE EOG RESULT
The EOG report should mention whether the procedure meets the international standard and whether the calculated lightpeak to darkness amplitude ratio is based on the dark-trough or the dark-adapted baseline. Amplitudes and latencies of the light peak and dark trough should be available, and the time vs. saccadic amplitude plot is helpful. An evaluation of the quality and accuracy of the saccades is also useful.
