Ever since Dewar [1] first recorded electrical potentials from the human eye in 1877, electroretinography (ERG) has held promise as an objective measure of retinal function. Over the intervening years, it has become possible to relate the components of full-field, focal, multifocal, and pattern ERGs to their cellular origins within the retina. Thus, each of these tests can provide specific information about retinal disease.

Infants and children typically are referred for ERG to help distinguish retinal from postretinal disease or because of early symptoms or signs suggestive of known retinal disease. Alternately, electrodiagnostic testing may be important to confirm a diagnosis, to objectively assess visual function, and/or to evaluate a possible retinal basis for unexplained visual loss. ERG testing is often useful for ruling out retinal disease in patients involved with medicolegal issues and patients with defects associated with psychiatric disturbances. Occasionally, ERG may be required for monitoring the health of a patient taking medications or exposed to environmental agents with possible retinal toxicity. More specialized ERG services may provide early detection of children affected by disease or those, particularly women, showing the carrier state of a genetic retinal degeneration. Similarly, clinics may be requested to provide quantitative assessment of the progress of a retinal disease. Finally,

D.G. Birch (*) and E.E. Birch

Retina Foundation of the Southwest, Dallas, TX 75231, USA and Department of Ophthalmology, UT Southwestern Medical Center, Dallas, TX, USA

e-mail: dbirch@retinafoundation.org

R. Spencer

Retina Foundation of the Southwest, Dallas, TX 75231, USA and Texas Retina Associates, Dallas, TX, USA

ERGs may be requested for the assessment of retinal function following trauma.

ERG in infants and children requires a friendly environment, specialized techniques, and modified protocols and interpretation. It is known that the retina is immature at birth and that ERG responses in young infants are smaller than those in adults. This chapter will describe the protocols suitable for testing infants and children, summarize the time course of maturation, and provide examples of representative responses from patients.

3.1  Full-Field ERG

The full-field ERG represents the summed activity of the retina in response to a light flash. A typical response to white light contains an early, corneal-negative component (a-wave) and a slower, corneal-positive component (b-wave). Based on the pioneering work of Granit [2] in 1933, the cellular origin of these waves has been determined by applying toxic agents [3] and by recording with microelectrodes at different depths within the retina [4–6]. The a-wave is known to be generated within the photoreceptor layer and directly reflects photoreceptor activity. The b-wave is generated at the level of the inner nuclear layer (INL) and indirectly reflects bipolar cell activity.

There are approximately 120 million rods and 9 million cones in a single healthy retina. Since the proportion of rods to cones is roughly 13:1, the ERG to single flashes of white light is dominated by responses emanating from the rod pathway. Special techniques are needed to separate cone-mediated from rod-mediated responses. Furthermore, about 90% of cones are outside the macula despite the maximum concentration in the fovea. Thus, the full-field ERG is dominated by extramacular rods and cones and is most useful in patients

suspected of having widespread retinal disease. In the early days of ERG, responses were elicited with a bright light source, such as a flash unit or photostimulator, placed before the patient. Even when close to the eye, illumination from these light sources is not evenly spread across the retina. The central retina is stimulated by intense direct illumination, while the periphery is stimulated by less intense stray light. The resulting ERG is a sum of activity from unevenly illuminated retinal areas. Therefore, caution is necessary in interpreting the older literature and careful attention to the type of stimuli is needed while interpreting published findings.

This problem of light scatter has been largely eliminated by the widespread adoption of full-field (or ganzfeld) stimulators. Full-field stimulators typically use a Grass photostimulator or equivalent as the light source. The advantage of this Xenon gas-discharge source is that each flash lasts only 10–20 ms and can be repeatedly flashed to produce a flicker response. Generally, brief flashes are preferable to longer flashes because they do not light-adapt the retina. However, longer duration stimuli may be used in specialized protocols, when, for example, it is desirable to separate on and off retinal responses.

Full-field ERGs are typically measured with a contact lens electrode. The most reliable and widely used lens is the Burian–Allen bipolar contact lens electrode. The lens is available in several sizes to fit very low-birth weight infants through adults. Although each lens is expensive, it can be reused indefinitely with occasional restoration by the manufacturer. In light of present concern about the transmission of viruses, especially HIV by tears, we have adopted the recommendations of the American Academy of Ophthalmology for sterilizing lenses. Immediately after the recording session, the lens is placed in an ultrasound unit for 2 min and then left to soak for 15 min in a 1% sodium hypochlorite solution. This solution is made by diluting one part liquid bleach with five parts water. After careful rinsing, we allow the lens to air dry. An alternative to the Burian–Allen lens is a disposable monopolar lens. These lenses are inexpensive and readily available. Their disadvantages are that they are not as comfortable for the patient and are not as reliable. They also tend to be more susceptible to contamination from 60 Hz (line) noise than the bipolar lenses. Skin electrodes also tend to be unreliable and are not recommended for the ERG.

Contact lens electrodes are well tolerated by infants through the age of 6 months. ERGs in toddlers from

6 months to 5 years of age present the greatest challenge and are typically obtained under sedation. Chloral hydrate is commonly used at a dose of 25–80 mg/kg (maximum dosage 1 g). Examinations under anesthesia may be required for particularly challenging cases. However, some anesthetic drugs selectively affect components of the ERG. The rod b-wave is particularly susceptible, with reductions in amplitude of up to 50%, while the rod a-wave and cone b-wave appear less affected. Pupils should be maximally dilated for ERG recording to minimize variations in retinal illuminance. For older children, we use a combination of 1% cyclopentolate hydrochloride and 10% phenylephrine hydrochloride, although 1% tropicamide can be substituted in light-pigmented patients who often remain dilated for more than a day. Lower concentrations in special dispensers are available for infants and are also used for retinopathy of prematurity exams. To minimize lens-wearing time, infants are typically placed in the dark with a parent for at least 30 min prior to inserting the lens. During this time, the parent can nurse the baby and encourage a nap. For older children, a combination of opaque black patches and gauze occluders can be used for dark adaptation. Infants are tested in the supine position with a dome that lowers over the head (Fig. 3.1). For infants up to 6 months, tight swaddling in blankets is usually sufficient for restraint. A peep hole in the dome is useful for monitoring the position of the pupil during testing. Two drops of

Fig. 3.1  Full-field ERG testing. The infant is swaddled tightly in a bassinette with a contact lens electrode in the eye. The fullfield dome is lowered over the head and contains a peep hole for monitoring the position of the pupil. Since the testing is conducted in the dark, there is a tendency for the infant to fall asleep. Constant monitoring is necessary to ensure that the appropriate flash energy is reaching the retina

topical anesthesia (proparacaine hydrochloride) are applied. A silver-chloride disc electrode filled with electrode cream serves as a ground on the forehead. The contact lens electrode is inserted in the eye in dim red illumination provided by a head-mounted flashlight. The use of red illumination avoids light adapting the rods, which are relatively insensitive to long-wave- length light.

3.1.1  ISCEV Standard Full-Field

ERG Protocol

The International Society for Clinical Electrophysiology of Vision (ISCEV) recommends a basic protocol as a minimum requirement for providing comparable recordings for all patients worldwide [7, 8]. The “standard flash” is defined as a stimulus strength at the surface of the ganzfeld bowl of 1.5–3.0 cd-s/m2 (1.9–2.2 log trolands). The five responses that comprise the standard protocol are shown in Fig. 3.2.

3.1.1.1  Rod Response

The first response that should be recorded following at least 30 min of dark adaptation is a rod response. The preferred procedure for obtaining this response is to attenuate the Standard Flash with a 2.5 log unit neutral density filter. Such a stimulus is below cone threshold and produces a “pure” rod ERG. The waveform of the rod ERG is simple. Frequently, there is no a-wave even in normal subjects, but when it is present, as in the example in Fig. 3.2, it is generally less than 5 mV in adults and has an implicit time of approximately 40 ms. The b-wave is generally slow and smooth, without subcomponents or oscillations, and peaks in adults at approximately 85 ms.

3.1.1.2  Standard Combined Response

This response is also elicited following at least 30 min of dark adaptation. In the standard protocol, it is obtained immediately after the rod response by removing the 2.5 log unit filter. Because the flash is intense, at least 5 s should be allowed between stimuli for the retina to recover. The response is complex in shape and contains both rod and cone components in the normal eye.

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Fig. 3.2  Representative ERGs from a normal infant tested under ISCEV standard conditions