Ординатура / Офтальмология / Английские материалы / Electrophysiology of Vision_Lam_2005

used. Aside from stimulator-ophthalmoscope devices, fullfield domes or fundus cameras may also be modified for focal ERG recording.

Foveal cone responses obtained from focal ERG are mini cone flicker responses that resemble the photopic full-field ERG cone flicker response. Collecting a group of age-related normal values is critical in the clinical inter pretation of focal foveal ERG as response amplitudes and timings are related not only to age but also to the stimulus diameter, flickering rate, and retinal illuminance (7). Because of the numerous focal ERG methodologies, international standard or guidelines have not been established. Focal ERG responses are particularly unreliable in patients with poor fixation or media opacity, which may result in falsely impaired foveal responses.

Focal rod ERG responses from a relatively large test spot of 30 –40 may be recorded with specialized techniques but are not commonly performed in the clinic (8,9). To maintain dark adaptation, a concentric annulus ring of steady background light cannot be used. Without the suppressive effect of the surrounding light ring, the scattered light from the test stimulus that falls outside of the test area will result in unwanted response from the surrounding retina. The effect of this stray-light response can be reduced by subtracting response from a dimmer rod-matched full-field flash (8).

MULTIFOCAL ELECTRORETINOGRAM

The multifocal ERG is a technique developed by Sutter and Tran (10) to provide topographical retinal function by simultaneously recording and calculating ERG signals from multiple retinal areas (Fig. 2.2). This technique evolved because sequential recordings from multiple retinal areas using traditional focal ERG are too time-consuming to be practical. The multifocal ERG has emerged as a valuable clinical tool to assess topographical photopic retinal function (11). Experience with quality full-field ERG recordings is beneficial

Figure 2.2 Schematic diagram showing the basic principles of multifocal ERG.

in dealing with similar recording issues in multifocal ERG. Like all diagnostic tests, the multifocal ERG is not a test without limitations. For instance, the multifocal ERG cannot easily assess scotopic retinal function, and a quality recording may be difficult to obtain from a patient with poor visual acuity due to inadequate steady fixation. Therefore, the multifocal ERG is not a replacement for the full-field ERG but

may be considered as a different test that provides important topographical retinal information. Guidelines for basic multifocal ERG have been established by the International Society for Clinical Electrophysiology of Vision (ISCEV) and are available on the ISCEV Internet site (1).

MULTIFOCAL ERG RECORDING

ENVIRONMENT AND PATIENT SET-UP

The recording environment and patient set-up for multifocal ERG are similar to those of full-field ERG (see Chapter 1). First, the pupils are dilated fully with eye drops. Several types of recording electrodes may be used. Contact-lens electrodes such as the Burian–Allen electrodes provide stable recordings with less blink artifacts, and the newer version provides clearer view of the stimulus. Contact-lens electrodes are less comfortable than non-contact-lens electrodes; among which the DTL electrode is the most commonly used. As with full-field ERG, some differences in recording results exist when different types of electrodes are employed (12).

Similar to the focal ERG, multifocal ERG is used to assess light-adapted retinal activity generated by the cone photoreceptors. Although multifocal ERG recording of rod function is possible, maintaining dark adaptation during testing is difficult, and the effect of light scatter is greater under dark adaptation. Taken together, these factors make recording multifocal rod ERG responses challenging in clinical settings. Therefore, clinical multifocal ERG recordings are performed under light-adapted condition. Because photopic ERG responses are known to stabilize after 15 min of light adaptation, the patient should have been exposed to ordinary ambient room light for at least 15 min before multifocal ERG testing (13). To maintain full-field light adaptation, the room lights should produce illumination close to that of the stimulus screen during testing. Multifocal ERG recording may follow standard photopic full-field ERG as long as the exposure to the full-field flash stimulus is not excessive.

MULTIFOCAL ERG STIMULUS

The multifocal ERG stimulus is displayed on a video monitor and typically has a diameter of about 50 subtending about 25 radially from fixation. Therefore, the multifocal ERG tests the activity generated by only about 25% of cone photoreceptor cells. The stimulus consists of a pattern of hexagons such that the size of each hexagon is scaled to produce approximately equal ERG responses from the normal retina (Fig. 2.3). For example, in a 103-hexagon display, each central hexagon is about 3 wide while each outermost hexagon is more than 7 wide. During recording, each hexagon reverses from white- to-black or white-to-black in a predetermined fixed pseudo-ran- dom maximum-length sequence called the ‘‘m-sequence’’ and has a probability of 0.5 of reversing on any frame change. The sequence is the same for each hexagon but the starting point is different for each hexagon. To maintain overall isoluminance and thus the same level of retinal light adaptation through the test, approximately half of the total hexagons are white and half are black. The area of the display outside of the hexagons should have a luminance equal to the mean luminance of the stimulus array. For example, the luminance of a hexagon when it is white could be 100 cd=m2 compared to 2 cd=m2 when it is dark with a brightness of 50 cd=m2 for the part of display outside of the stimulus. The rate of frame change is rapid in the order of 75 Hz with a frame change occurring every 13.3 msec. The number of hexagons for the multifocal stimulus array ranges from 61 to 241, and tradeoffs are made when choosing the number of hexagons. A lower number of hexagons requires shorter recording time, produces larger responses and lower noise-to-signal ratio but decreases spatial resolution. Conversely, a higher number of hexagons requires longer recording time, produces smaller responses and higher noise-to-signal ratio but increases resolution. An array of 103 hexagons is commonly used.

RECORDING MULTIFOCAL ERG

Stable central fixation during multifocal ERG recording is critical to ensure accuracy of the topographical ERG

Figure 2.3 Multifocal ERG stimulus. The hexagons of the multifocal ERG stimulus are smaller centrally and larger peripherally and are scaled to produce approximately equal ERG response for each hexagon from the normal retina. The 103-hexagon and 241hexagon stimuli are shown with concentric circles indicating the distance from the fovea in 5 steps. The stimulus typically subtends approximately 25 radially from the fovea. The number of hexagons usually ranges from 61 to 241. A high number of hexagons increases topographical resolution of the calculated responses but produces smaller responses with higher noise-to-signal ratio and requires longer recording time.

information (14). Poor fixation will lead to falsely impaired responses and erroneous clinical interpretation. A central fixation target such as a dot, ‘‘X’’, or cross is provided by the system, and the target size should be increased accordingly

based on reduced visual acuity. Fixation can be monitored during testing with simultaneous viewing of the test eye by using an infrared external video camera or a fundus video camera. Because a steady fixation does not necessary imply an accurate fixation, the use of a fundus video camera helps to monitor the location of the stimulus array on the retina and thus the accuracy of the fixation (15).

Sequential monocular recordings are usually performed. During monocular recording, the fellow eye is occluded with a patch or the patient may feel more comfortable holding the eyelid closed with his hand. Sufficient period of light adaptation should be allowed before the testing of the second eye. Binocular recording is possible but simultaneous monitoring of decentration of the stimulus in each eye is required.

Best-corrected vision is recommended for recording especially for persons with high refractive errors. Corrective lens may be placed in front of the eye but an adjustment of the viewing distance to account for change in magnification of the stimulus is needed based on the manufacturer’s recommendations (16). This problem is reduced in newer recording systems with a compact stimulus display mounted on a swingarm so that the display is brought close in front of the eye being tested. A built-in focusing knob on the display allows the patient to self-adjust the focus for optimal viewing clarity without the use of corrective lens. Regardless of the system used, periodic calibration of the system should be performed as recommended by the manufacturer and based on international calibration standard (17).

Multifocal ERG may be recorded in a single continuous recording lasting several minutes or in a series of shorter recording runs lasting less than 1 min. Recording in segments reduces patient fatigue and allows discarding and repeating low quality recording segments without re-running the entire test. Regardless, the sequence of white-to-black or black-to- white reversal of each hexagon follows a fixed m-sequence predetermined by the computer. Programs are available to remove recording artifacts from blinks and eye movements and should not be applied multiple times.

Similar to other electrophysiologic tests, multifocal ERG results vary depending on the protocol and the recording system (16,18,19). Therefore, collection of age-matched normative data by each facility is recommended. Age-related changes of multifocal ERG are discussed in Chapter 6. For each ERG parameter, the median normal value along with 5% and 95% percentile normal values should be reported and used for interpretation.

FIRST-ORDER ‘‘RESPONSE’’ OF

MULTIFOCAL ERG

In multifocal ERG, local retinal signals are calculated by correlating the continuous recorded ERG signal with the on–off phases of each hexagon. Multifocal waveforms are not true direct, recorded responses but mathematical calculations (20). The first-order ‘‘response,’’ known as first-order kernel (K1), of each hexagon is calculated by adding all ERG recordings following a white frame and then subtracting all ERG recordings following a black frame (Figs. 2.4 and 2.5). In this way, the response of the hexagon is summed and isolated while the responses from other hexagons are eliminated. The calculated first-order response lasts much longer than the duration of one frame (13.3 msec at 75 Hz).

The calculated first-order response consists of an initial negative component (N1) followed by a positive component (P1) and then a second negative component (N2) (Fig. 2.4). The N1 amplitude is measured from baseline to the N1 trough, and the P1 amplitude is measured from the N1 trough to the P1 peak. The implicit time of N1 is measured from the onset of the stimulus to the N1 trough, and the implicit time of P1 is measured from stimulus onset to the P1 peak. Programs to reduce background electrical noise and to smooth waveforms are available. These programs average the response from each hexagon with a percentage of the signals from adjacent hexagons and should be used with caution such that no more 50% of the waveform are contributed from neighbor hexagons.

Figure 2.4 First-order calculated responses of the multifocal ERG. A normal trace array and a proposed model of cellular origin of the first-order waveform are shown. (From Ref. 22 with permission of Investigative Ophthalmology and Visual Science.)

The clinical utility of the first-order response in evaluating topographical retinal function is well established (Fig. 2.6). The calculated N1 and P1 components of the multifocal ERG correlate with but are not exact equivalents of the a- and b-waves of the recorded responses of the photopic full-field ERG (21). Not all aspects of cellular activity contribution to the multifocal ERG are understood. A detailed

Figure 2.5 Schematic representation of how the first-order response (first-order kernel, K1) of the multifocal ERG is calculated for a specific hexagon. The first-order response is calculated by adding all of the calculated records following the stimulus, a white frame, and subtracting all calculated records following no stimulus, a black frame. Note that whether the preceding frame is white or black influences the calculation. The calculated first-order response lasts much longer than the duration of one frame (13.3 msec at 75 Hz).

review of retinal physiology is provided in the full-field ERG chapter (Chapter 1). Similar to the full-field ERG, multifocal ERG components are influenced mostly by bipolar cell activity with contributions from photoreceptors and other cells of the