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Chapter 107 – Electrophysiology

Chapter 107 – Electrophysiology

 

ELIAS REICHEL

 

 

 

 

 

DEFINITIONS

• The electroretinogram records the electrical response evoked from the entire retina by a brief flash of light and consists of an “A” wave, a photoreceptor response, and a “B” wave that emanates from the Müller and bipolar cells.

• The electro-oculogram records the standing electrical potential generated by the retinal pigment epithelium.

• The focal electroretinogram records the central retinal function and represents an isolated foveal cone response.

 

 

 

INTRODUCTION

Electrophysiology encompasses several tests that measure the function of the various components of the retina. In this section, the focus is on full-field electroretinography (ERG), because this is the most useful of these techniques in the assessment of retinal function to help establish retinal diagnoses.[1] Full-field ERG is useful, particularly, in the determination of the abnormal nature of what appears to be a retina of “normal” appearance. It is useful, also, to determine the existence of retinal degeneration that may arise from hereditary, toxic, metabolic, retinal vascular, or inflammatory causes. Only in conjunction with careful history, ophthalmic examination, and laboratory testing can exact diagnoses be made. Therefore, ERG is useful as an adjunct in establishing loss of function; diagnoses should be made only in conjunction with a complete medical and ophthalmic evaluation. Electro-oculography (EOG) and focal ERG are discussed briefly.

HISTORICAL REVIEW

As early as 1865, Holmgren showed that an alteration in electrical potential occurred when light fell on the retina. In 1877, Dewar recorded a light-evoked electrical response, ERG, from humans for the first time. In 1941, Riggs introduced a contact lens electrode for human use. Modern adaptations to ERG testing included Ganzfeld or full-field diffuse illumination to elicit a response from the entire retina. More recently, computer averaging and narrow bandpass filters have enabled the detection of ERG responses below 1?mV.

It was Holmgren, again in 1865, who identified a constant standing or resting potential between the cornea and the back of the eye that was altered by changes in retinal illumination. Marg,[2] in 1951, coined the term electro-oculogram for the measurement of this potential.

PURPOSE OF THE TEST

Full-field ERG measures a mass response generated by cells from the entire retina. Under dark-adapted conditions, a single flash

 

 

Figure 107-1 Full-field electroretinograms, normal individual. Dark adaptation is elicited by a single flash of bright white light after 30 minutes. This stimulus elicits both cone-mediated and rod-mediated responses. The green arrow denotes the “A” wave and the red arrows the “B” wave. The small wavelets on the ascending limb of the “B” wave are oscillatory potentials. Normal response to a 30?Hz red flicker stimulus after testing with the bright white flash. This represents a pure cone response.

of light results in a response that is both rod and cone mediated. Of this response, 80% is attributable to rods and the remainder results from cones. The photoreceptors generate the initial cornea-negative component, or “A” wave, in the ERG, whereas Müller cells and bipolar cells are responsible for the later, cornea-positive, “B” wave ( Fig. 107-1 ). The full-field ERG is useful for establishing generalized loss of rod or cone function, or both. Patients who have focal macular disorders do not have abnormalities of full-field ERG amplitude, nor do patients who have optic nerve or cortical conditions.

Mild reductions in cone amplitudes can be observed when macular scarring covers four or more disc areas. In contrast, individuals who have early retinitis pigmentosa typically display delayed cone “B” wave implicit times; amplitudes are subnormal, although they may not be reduced markedly during the early stages of the disease.

The full-field ERG can be affected by a variety of pathological states unrelated to the function of the retina.[1] [3] [4] It is important to be aware of these conditions in which the normalcy or abnormalcy of the test is established. Media opacities, which include cataract, vitreous hemorrhage, and vitreous debris, may cause a reduction in ERG amplitude and lengthen the implicit time. Age and myopia also affect the ERG amplitude, but implicit time appears to be unaffected. Pupil size also can affect the amplitude of the ERG, which may account for the decline in ERG amplitude associated with age.

 

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UTILITY OF THE TEST

ERG establishes the loss of retinal function. Specific patient complaints that may warrant the use of ERG include loss of peripheral vision and night blindness. Determination of retinal function when the media is obscured is another important use of full-field ERG. Not only is ERG useful for establishing pathological conditions, it also provides solace to the patient and reassurance to the physician when normalcy of retinal function is established. For situations in which the retina is deemed to be normal, the optic nerve and central nervous system must be evaluated.

Many conditions display loss of retinal function and, therefore, a careful history and ophthalmoscopic examination are necessary to establish a diagnosis. Further, laboratory tests often are necessary to confirm metabolic conditions or rule out the possibility of cancer-associated retinopathy. A test of retinal function is important for the diagnosis of retinal degeneration and allied conditions (including metabolic disorders), unexplained loss of vision, siderosis, cancer-associated retinopathy, stationary forms of night blindness, vitamin A deficiency, and drug toxicities (including chloroquine, hydroxychloroquine, chlorpromazine, thioridazine, and quinine). When the test is performed on individuals who are considered to have retinal degeneration, the ERG can differentiate between an isolated cone abnormality and a condition that involves both the cones and the rods. In addition, the test can differentiate between stationary forms of night blindness and progressive degenerations. Also, ERG can play a role in the evaluation of retinal ischemia, specifically with respect to central retinal vein obstruction and diabetic retinopathy. Therefore, ERG may help in the decision as to which patients are amenable to laser treatment to prevent retinal neovascularization.

PROCEDURE

Standards have been established for the performance of basic clinical ERG. Patients who are to be tested undergo dark adaptation for approximately 30 minutes. Multiple adhesive patches are placed over both eyes to allow for total occlusion of light. After a topical anesthetic has been placed in the eye, a contact-lens electrode is inserted underneath the lids. The Burian–Allen contact lens electrode is used widely[5] ; alternative electrode materials include ERG-jet and Mylar electrodes. A ground electrode is placed on the patient’s earlobe using electrode paste. A reference, or “inactive,” electrode is placed centrally on the patient’s forehead. The Grass xenon-arc photostimulator, with flash duration of 10 microseconds, commonly is used to obtain electroretinograms over a range of stimulus intensities. A Ganzfeld stimulus is necessary to standardize the flash stimulus.

The corneal contact lens serves as the active electrode and connects to a junction box along with the ground and reference electrodes. The difference in voltage between the active corneal electrode and the reference electrode is recorded by a differential amplifier.

A series of electroretinograms are obtained using different light intensities. Typically, a white or red 30?Hz flicker is obtained to isolate a cone response.

COMPLICATIONS

Difficulty in placement of the contact lens electrode may result in mild corneal abrasions. In individuals who have small palpebral fissures, a pediatric contact lens may be used to avoid this complication.

INTERPRETATION OF RESULTS

When evaluating patients who have retinal degeneration, it is important to quantify the function of both the rod and cone systems. The rod-isolated response is achieved by dark adaptation of the patient’s eye and a dim white or blue flash, below cone threshold, is used to stimulate the retina. A waveform results

 

 

Figure 107-2 Full-field electroretinograms, retinitis pigmentosa. Response to a single flash of bright white light is diminished markedly, consistent with the diagnosis of a retinal degeneration. The cone response to 30?Hz red flicker is not recordable.

that has almost no detectable “A” wave but a large “B” wave. A bright, white flash used in the dark-adapted state causes maximal stimulation of both rods and cones and results in large “A” and “B” waves, with oscillatory potentials in the ascending “B” wave (see Fig. 107-1 ). Oscillatory potentials are believed to be the result of inhibitory influences from amacrine cell input. Oscillatory potentials are diminished when retinal ischemia is present. Cone responses are obtained when the eye is in a light-adapted state (i.e., after a white flash), and the signal is evoked using a red light flash. Cone responses also can be elicited using a flickering stimulus light at 30–40?Hz (see Fig. 107-1 ). Markedly reduced rod and cone responses to a bright flash and markedly reduced cone responses to a 30?Hz flicker are typical of a patient who has retinitis pigmentosa ( Fig. 107-2 ).

Normal values for ERG results depend upon stimulus conditions and patient variables and must be considered when normalcy is established. As a rough approximation, a bright, white flash intensity results in a dark-adapted “B” wave amplitude of at least 350?mV in individuals less than 50 years of age. The normal value of the 30?Hz flicker stimulus is an amplitude of at least 50?mV.

ALTERNATIVE TESTS

EOG has been used to evaluate a variety of retinal diseases. It appears to be useful in the evaluation of Best’s macular dystrophy and pattern dystrophies. It appears to have little value in the assessment of patients who have retinal photoreceptor degenerations or stationary night blindness.

Focal foveal cone ERG may be used to measure the electrical response of the most central cone photoreceptors.[6] Full-field ERG represents a mass response of the entire retina and, therefore, focal ERG may have practical diagnostic value in the evaluation of patients who have localized macular disease and in patients who have loss of vision and otherwise normal full-field electroretinograms and normal ophthalmic examination findings.

Multifocal ERG (MFERG) is a relatively recent development in recording the ERG and variable evoked potential response and is gaining acceptance as a useful tool for retinal disease evaluation. This technique relies on obtaining multiple samples of ERG responses from different parts of the retina. Fourier transform analysis results in topographical localization of the ERG

 

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responses. Therefore, a response can be obtained that encompasses 1 to 5 degrees of the retina, dependent upon photoreceptor density. Localized structural abnormalities can be identified using this functional assessment tool.[7]

 

REFERENCES

 

1. Berson EL. Electrical phenomena in the retina. In: Moses RA, Hart WM, eds. Adler’s physiology of the eye: clinical application. St Louis: CV Mosby; 1987:506–67.

 

2. Marg E. Development of electro-oculography. Arch Ophthalmol. 1951;45:169–85.

 

3. Marmor MF, Arden GB, Nilsson SE, et al. Standard for clinical electroretinography. Arch Ophthalmol. 1989;107:816–9.

 

4. Carr RE, Siegel IM. Electrodiagnostic testing of the visual system: a clinical guide. Philadelphia: FA Davis; 1990.

 

5. Burian HM, Allen L. A speculum contact lens electrode for electroretinography. Electroencephalogr Clin Neurophysiol. 1954;6:509–11.

 

6. Sandberg MA, Ariel M. A hand-held two channel stimulator ophthalmoscope. Arch Ophthalmol. 1977;95:1881–2.

 

7. OM, Miyake Y, Horiguchi M, et al. Clinical evaluation of the multifocal electroretinogram. Invest Ophthalmol Vis Sci. 1955;36:2146–50.

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