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  • 2020–2021 BCSC Basic and Clinical Science Course™

    Go to Academy Store Learn more and Purchase.

    12 Retina and Vitreous

    Part I: Fundamentals and Diagnostic Approaches

    Chapter 03: Retinal Physiology and Psychophysics

    Electroretinography

    The clinical electroretinogram (ERG) measures a massed electrical response from the retina, usually evoked by a brief flash of light. ERGs are usually recorded using active electrodes that contact the bulbar conjunctiva, with reference electrodes at the outer canthi. The active electrodes can be contact lens electrodes, although gold foil electrodes, H-K loop electrodes, and DTL fiber electrodes are also commonly used. The 3 main types of electroretinogram—the full-field (Ganzfeld) electroretinogram (ERG), the multifocal ERG (mfERG), and the pattern ERG (PERG)—are discussed in the following sections.

    Full-Field (Ganzfeld) ERG

    In full-field ERG, a Ganzfeld bowl uniformly illuminates the entire retina with a full-field luminance stimulus; the Ganzfeld also provides a uniform background for photopic adaptation and photopic ERG recording. Regular calibration of flash strength is required for clinical accuracy. Figure 3-1 shows typical ERG responses, but normal values vary with recording techniques, and each laboratory must establish its own normative data. Even with standardization, variations in the type of electrode and specific equipment will affect the test results.

    Most laboratories dark-adapt the patient while the pupils are dilating, position the corneal electrodes under dim red light, and then commence stimulation using an interstimulus interval sufficient to allow the retina to recover between flashes (from 2 seconds for low intensities up to 20 seconds for high intensities). Many laboratories record responses to a series of increasing stimulus strengths. The patient is then light-adapted (using standardized background intensity and adaptation time), and photopic testing is performed, in which the stimuli are delivered under rod-suppressing background illumination.

    The ISCEV standard full-field ERG consists of 6 different responses (see Fig 3-1). Nomenclature is based on the flash strength as measured in cd s/m2 (candela-seconds per square meter) and the adaptive state of the eye (ie, dark-adapted [DA] or light-adapted [LA]). Older terms are given in parentheses in the following list. Measurement of the ERG focuses on the size and timing of the major components, as indicated in Figure 3-1.

    1. DA 0.01 (rod-specific): In this response, a b-wave arises in the on-bipolar cells (BPCs) (inner nuclear layer) of the rod system. A reduction in this response identifies dysfunction within the rod system, but, as it arises at an inner retinal level, this response cannot differentiate between dysfunction at the level of the photoreceptor and inner retinal dysfunction. It therefore acts as a measure of rod system sensitivity.

      Figure 3-1 Basic electroretinogram (ERG) responses as defined by the International Society for Clinical Electrophysiology of Vision. The amplitude and peak times are typical, but normal values must be established for each laboratory using local techniques. a- = a-wave; b- = b-wave; DA = dark-adapted; LA = light-adapted; OPs = oscillatory potentials; numbers following abbreviations denote stimulus intensity (in candela-seconds per square meter).

      (Courtesy of Graham E. Holder, PhD.)

    2. DA 3.0 (mixed rod–cone): This response consists of an a-wave and a b-wave. The a-wave at this flash strength usually has 2 peaks between approximately 15 and 21 milliseconds (ms), either of which may be prominent. Because only approximately the first 8 ms of the DA a-wave reflects photoreceptor hyperpolarization, the ISCEV standard now includes additional brighter flash testing for better diagnostic specificity.

    3. DA 10.0/30.0: At either of these flash strengths, the a-wave has an easily measurable peak, and most of the a-wave reflects photoreceptor function. This response can therefore localize dysfunction either to a photoreceptor or inner-retinal level. Thus, a reduced DA 0.01 response accompanied by marked reduction in the a-wave of the DA 10.0/30.0 response indicates photoreceptor dysfunction; however, if the a-wave amplitude is normal or near-normal and the b-wave amplitude is lower than the a-wave (known as a negative or electronegative ERG waveform), then dysfunction occurs post-phototransduction, at an inner-retinal level.

    4. Oscillatory potentials: These small oscillations on the ascending limb of the b-wave probably arise largely in the amacrine cells and can be made more visible by filtering. They are reduced in retinal ischemic states and in most cases of congenital stationary night blindness but overall have limited diagnostic value.

    5. LA 3.0 (photopic single-flash): This ERG is obtained by stimulating with a flash superimposed upon a rod-suppressing background. The a-wave relates to function in the cone photoreceptors and off-BPCs. The b-wave arises as a synchronized component in on- and off-BPCs. This response thus enables some localization of cone-system dysfunction.

    6. LA 3.0 30 Hz (photopic flicker): The temporal resolution of the rod system is poor, and this response arises in the cone system. It is the more sensitive measure of cone-system dysfunction but allows no anatomical specificity. Both timing and amplitude are important parameters; delay in the flicker ERG response is a sensitive measure of generalized retinal cone system dysfunction, whereas reduced amplitude but normal peak time usually indicates restricted loss of function.

    A number of factors influence the size and timing of a normal ERG response, including pupil size; pupil diameter should always be measured. ERG amplitude declines with age, and age-related controls are needed. Newborns have small ERGs with simplified waveforms. The responses mature rapidly, reaching adult values in the first year of life. The ERG is relatively insensitive to refractive error; highly myopic eyes have lower amplitude ERGs but without the peak-time delay usually associated with inherited retinal degeneration.

    As a biological signal, ERGs have inherent noise. If amplitudes remain within the reference range (“normal range”) a reduction over time of more than 25% is usually considered significant. For peak-time measures, a change greater than 3 ms is regarded as significant for cone-derived response a- or b-waves and brighter-flash dark-adapted a-waves, and a change greater than 6 ms is significant for dark-adapted b-waves.

    In general, ERG peak-time shift suggests generalized dysfunction, whereas simple amplitude reduction suggests restricted loss of function such as may occur in a partial retinal detachment (loss of function in the detached area of retina but normal function in the attached retina), branch vascular occlusion, regional uveitic damage, or restricted (“sector”) forms of retinitis pigmentosa (RP). Timing is often best assessed using the 30-Hz flicker ERG peak time. Generalized inflammatory disease, such as posterior uveitis, may be associated with delay but preservation of amplitude. Indeed, marked 30 Hz flicker delay with a high amplitude almost always indicates an inflammatory etiology.

    Figure 3-2 presents examples of ERG patterns found in association with specific disorders. The full-field ERG is a mass response from the whole retina, and dysfunction confined to the macula is therefore accompanied by normal full-field ERG responses. Even though the central macula is cone-dense, the majority of retinal cones lie outside the macula; thus, the macula contributes little to a full-field ERG. Because abnormal photopic ERG responses indicate cone dysfunction outside the macula, ERG testing therefore helps the clinician distinguish between a macular dystrophy phenotype (normal ERG response) and a cone or cone–rod dystrophy phenotype (abnormal ERG response), which may have more serious visual implications for the patient. For example, ABCA4 retinopathy (eg, Stargardt disease; fundus flavimaculatus) can, in some patients, be associated with severe generalized cone and rod system dysfunction. If the full-field ERGs of the patient are normal at presentation, the dysfunction is confined to the macula and has prognostic value: 80% of such patients will still have normal full-field ERG responses at 10-year follow up.

    • Fujinami K, Lois N, Davidson AE, et al. A longitudinal study of Stargardt disease: clinical and electrophysiologic assessment, progression, and genotype correlations. Am J Ophthalmol. 2013; 155(6): 1075–1088.

    Excerpted from BCSC 2020-2021 series: Section 10 - Glaucoma. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.

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