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Contents

Cisplatin . . . . 434

Indomethacin . . . . 435

16. Non-Organic Visual Loss and Other Ocular and

Systemic Disorders . . . . . . . . . . . . . . . . . . . . . . 449

Non-Organic Visual Loss . . . . 450

Ocular Disorders . . . . 452

Systemic Disorders . . . . 458

17. Optic Neuropathies and Central Nervous

System Disorders . . . . . . . . . . . . . . . . . . . . . . . . 473

Optic Neuropathies . . . . 474

Central Nervous System Disorders . . . . 487

Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 507

I. CLINICAL RECORDING TECHNIQUES

1

Full-Field Electroretinogram

The full-field electroretinogram (ERG) records the summed transient electrical responses from the entire retina elicited by a flash stimulus delivered in a full-field dome Fig. 1.1. The ERG was discovered in excised animal eyes in the middle 1800s, and ERG recording in humans was first reported in 1920s. The clinical use of full-field ERG began in the 1940s, and in 1989, standard for clinical full-field ERG was established by the International Society for Clinical Electrophysiology of Vision ISCEV (1). The ERG standard is reviewed every three years, and the most updated version is available on the ISCEV Internet site. No major revision of the standard has occurred over the years, and the standard is summarized in Table 1.1. This chapter discusses ERG assuming an understanding of basic retinal anatomy and physiology detailed at the end of the chapter.

CLINICAL USE OF FULL-FIELD ERG

The full-field ERG measures the overall rodand conegenerated retinal responses and is the only electrophysiologic

1

2

Chapter 1

Figure 1.1 Basic principles of full-field ERG. A summary of the international standard for clinical full-field ERG is provided in Table 1.1.

Full-Field Electroretinogram

3

Table 1.1 Summary of International Standard for Clinical FullField Electroretinography (ERG)

Clinical protocol

 

Preparation of patient

 

Pupillary dilation

Maximally dilated with eye drops

Pre-adaptation to light

20 min dark adaptation before

or darkness

recording rod responses

 

10 min light adaptation before

 

recording cone responses

Pre-exposure to light

Avoid fluorescein angiography or fundus

 

photography before ERG; 1 hr of

 

dark adaptation needed before ERG

 

after these procedures

Fixation

Fixation point incorporated into

 

stimulus dome

ERG measurement and

 

recording

 

Measurement of the

Amplitudes and implicit times

ERG

 

Averaging repetitive

Not ordinarily required, helpful to

responses

identify very weak responses; artifact

 

rejection must be a part of averaging

 

system

Normal values

Each laboratory establishes limits of

 

normal values for specific ERG

 

responses and provides median and

 

95% confidence limits from direct

 

tabulation of normal responses

Reporting of ERG

Display waveforms with amplitude and

 

timing with normal values and

 

variances; strength of stimulus and

 

level of light adaptation given in

 

absolute values

Pediatric ERG recording

 

Sedation or anesthesia

With or without anesthesia; full

 

anesthesia may modify responses, less

 

effect on ERG with sedation or brief,

 

very light anesthesia

Electrodes

Pediatric size electrodes

Normal values and

ERG responses mature during infancy,

measurement

interpret with caution; pediatric ERG

 

responses compared to normal

 

subjects of the same age

 

 

 

(Continued)

4

Chapter 1

Table 1.1 Summary of International Standard for Clinical FullField Electroretinography (ERG) (Continued )

Specific responses (Fig. 1.2)

1. Rod single-flash response after dark

 

adaptation with flash 2.5 log unit

 

dimmer than standard flash ( 2 sec

 

between flashes)

 

2. Maximal combined rod and cone

 

single-flash response after dark

 

adaptation ( 10 sec between flashes)

 

with standard flash

 

3. Oscillatory potentials with standard

 

flash (15 sec between scotopic flashes

 

or 1.5 sec between photopic flashes,

 

bandpass of amplifier changed to

 

75–300 Hz)

 

4. Cone single-flash response after light

 

adaptation with standard flash

 

( 0.5 sec between flashes)

 

5. Cone 30-Hz flicker response after

 

light adaptation with standard flash

Basic technology

 

Light diffusion

Full-field (‘‘ganzfeld’’) stimulation with

 

full-field dome

Electrode

 

Recording

Contact-lens type electrodes or

 

electrodes on cornea or nearby bulbar

 

conjunctiva, topical anesthesia needed

 

for contact-lens type electrodes

Reference

Incorporated into contact-lens electrode

 

or a separate reference skin electrode

 

placed temporally near orbital rim or

 

on forehead

Ground

Skin electrode connected to ground,

 

typically placed on forehead or ear

Skin electrode

Skin electrodes for reference or ground,

characteristics

5 KO impedance measured between

 

10 and 100 Hz

Stability

Stable baseline voltage in the absence of

 

light stimulation

Cleaning

Cleaned and sterilized after each use

Light sources

Flash with duration of 5 msec

Duration

Wavelength

Color temperature near 7000 K

 

used with dome or diffuser that

 

are visibly white

 

 

 

(Continued)

Full-Field Electroretinogram

5

Table 1.1 (Continued )

Strength

1.5–4.5 cd s m 2 at surface of ganzfeld

 

bowl, a flash of this strength is called a

 

standard flash (SF)

Background

For photopic recording, white

 

background with even and steady

 

luminance of 17–34 cd m 2

Light adjustment and

 

calibration

 

Adjustment of stimulus

System capable of attenuating flash

and background

strength from the SF over a range of

intensity

at least 3 log unit in steps of 0.3 log

 

unit without changing wavelength

 

composition

Stimulus and

Flash strength measured by an

background calibration

integrated photometer at location of

 

eye; separate calibrations for single

 

flash and repeated flashes.

 

Background luminance of Ganzfeld

 

bowl measured with photometer in

 

nonintegrating mode

Recalibration

Frequency of recalibration depending on

 

system used

Electronic recording

 

equipment

 

Amplification

Bandpass of amplifiers and

 

preamplifiers include range of 0.3–

 

300 Hz and adjustable for recording

 

oscillatory potentials: impedance of

 

preamplifiers 10 MO

Display of data and

Waveform displayed promptly; system

averaging

able to represent full amplifier

 

bandpass without attenuation

Patient isolation

Electrically isolated

 

 

test that assesses rod-generated activity. The full-field ERG is essential in the diagnosis of numerous disorders including cone dystrophy, retinoschisis, congenital stationary night blindness, Leber congenital amaurosis, rod monochromatism, and paraneoplastic retinopathies. The ERG should be used in conjunction with a thorough ocular examination and when necessary other tests such as visual field and fluorescein

6

Chapter 1

angiography. The full-field ERG provides no topographical information about localized defects, and an isolated macular lesion is unlikely to decrease the full-field ERG response substantially. In such cases, testing with focal or multifocal ERG is helpful.

RETINAL ELECTRICAL RESPONSES

The ERG response is produced by light-induced movements of ions in the retina. This activity is measured indirectly at the cornea with a recording electrode. The extracellular movement of predominantly positive potassium (Kþ) and sodium (Naþ) ions occurs as a result of opening (depolarization) and closure (hyperpolarization) of channels of the cellular membranes. The small size and short axons of the retinal cells are such that a change in ionic activity of one part of the cell is adequate to affect its synaptic activity. Both neuronal and non-neuronal retinal cells contribute to this light-evoked electrical current. The full-field ERG receives virtually no contributions from retinal ganglion cells that form the optic nerve. The ganglion cells utilize conventional all-or-none spike action potentials and are more response to the stimulus of the pattern ERG.

CLINICAL RECORDING OF FULL-FIELD ERG

Scotopic and Photopic Recordings

Dark-adapted or scotopic ERG responses are recorded after a period of at least 20 min of dark adaptation but a period of 30–40 min is preferable to allow more complete dark adaptation of the rods. Scotopic recordings are rod-driven although cones also contribute if bright stimuli are used. Light-adapted or photopic ERG responses are recorded with a lit white background after at least 10 min of light adaptation (2). Light adaptation is achieved with exposure to ambient room light or alternatively can be better standardized by exposing the patient to 10 min of the photopic background of the full-field dome. Photopic responses are cone-driven.

Full-Field Electroretinogram

7

Full-Field ERG Flash Stimulus

The white flash ERG stimulus is delivered in a white full-field dome. The maximal flash is called the standard flash with a recommended intensity of 1.5–4.5 cd s m 2. However, a brighter flash in the range of 10–12 cd s m 2 elicits a larger better-defined a-wave for assessing photoreceptor activity. The flash is brief lasting usually well under 1 msec. For scotopic rod responses, the flash is dimmed with built-in filters. During photopic cone response recordings, the background of the full-field dome is lit with an even and steady white luminance of 17–34 cd m 2 to maintain light adaptation and to suppress rod activity. A centrally located built-in small dim red light is typically used as a fixation target. Proper calibration and periodic re-calibration with a photometer ensure that appropriate light intensities are utilized and no substantial changes occur over time. International guidelines for calibration of stimulus are available on the ISCEV Internet site (3). Periodic calibration of the amplifier by passing a known square wave or sine wave signal through each recording channel ensures that the amplifiers are working accurately and the output of each channel is identical.

Although the flash ERG stimulus is defined by the luminance emitted from the reflecting surface of the full-field dome and the stimulus duration (candela-second per square meter, cd s m 2), a more precise measure of the effective light stimulus received by the retina is retinal illuminance expressed in troland. For clinical ERG, stimulus luminance is usually a more readily available measure than retinal illuminance, but some recording systems can automatically calculate retinal illuminance. The troland (td) is the stimulus luminance in cd m 2 multiplied by the pupillary area in mm2, and the retinal illuminance from a flash is expressed as troland multiplied by the stimulus duration (td s). Photopic troland differs from scotopic troland because the sensitivity of the eye to light wavelengths is different under light and dark adaptation, and the spectral distribution of the stimulus needs to be taken into account. The standard spectral sensitivity function of the eye under photopic condition (Vl) is a

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