Definition[edit | edit source]
The electroretinogram (ERG) is a diagnostic test that measures the electrical activity generated by neural and non-neuronal cells in the retina in response to a light stimulus. The electrical response is a result of a retinal potential generated by light-induced changes in the flux of transretinal ions, primarily sodium and potassium. Most often, ERGs are obtained using electrodes embedded in a corneal contact lens, which measure a summation of retinal electrical activity at the corneal surface. The International Society for Clinical Electrophysiology of Vision (ISCEV) introduced minimum standards for the ERG in 1989. The ERG can provide important diagnostic information on a variety of retinal disorders including, but not limited to congenital stationary night blindness, Leber congenital amaurosis, and cancer-associated retinopathy. Moreover, an ERG can also be used to monitor disease progression or evaluating for retinal toxicity with various drugs or from a retained intraocular foreign body.
History[edit | edit source]
The first known recording of an ERG was performed on an amphibian retina in 1865 by the Swedish physiologist Alarik Frithiof Holmgren. James Dewar of Scotland subsequently performed it in humans in 1877, however widespread clinical application did not occur until 1941, when American psychologist Lorin Riggs introduced the contact-lens electrode. In 1908, Einthoven and Jolly separated the ERG response into three components: a-wave, b-wave, and c-wave, which are further described below. Many of the observations and analyses that serve as the basis for understanding the ERG components today were conducted by Ragnar Granit for which he won the Nobel Prize for Physiology and Medicine in 1967. Granit’s studies were primarily conducted on dark-adapted, rod-dominated cat retina with which he was able to demonstrate the physiology of the receptor potential of each component of the ERG.
Components[edit | edit source]
a-wave: initial corneal-negative deflection, derived from the cones and rods of the outer photoreceptor layers
This wave reflects the hyperpolarization of the photoreceptors due to closure of sodium ion channels in the outer-segment membrane. Absorption of light triggers the rhodopsin to activate transducin, a G-protein. This leads to the activation of cyclic guanosine monophosphate phosphodiesterase (cGMP PDE) eventually leading to a reduction in the level of cGMP within the photoreceptor. This leads to closure of the sodium ion channels resulting in a decrease of inwardly directed sodium ions, or a hyperpolarization of the cell. The a-wave amplitude is measured from baseline to the trough of the a-wave.
b-wave: corneal-positive deflection; derived from the inner retina, predominantly Muller and ON-bipolar cells
The hyperpolarization of the photoreceptor cells results in a decrease in the amount of neurotransmitter released, which subsequently leads to a depolarization of the post-synaptic bipolar cells. The bipolar-cell depolarization increases the level of extracellular potassium, subsequently generating a transretinal current. It is this transretinal current that depolarizes the radially oriented Muller cells and generates the corneal-positive deflection. The b-wave amplitude is generally measured from the trough of the a-wave to the peak of the b-wave. This wave is the most common component of the ERG used in clinical and experimental analysis of human retinal function.
c-wave: derived from the retinal pigment epithelium and photoreceptors
The c-wave is a reflection of the resulting change in the transepithelial potential due to the hyperpolarization at the apical membrane of the RPE cells and the hyperpolarization of the distal portion of the Muller cells. The c-wave generally peaks within 2 to 10 seconds following a light stimulus, depending on flash intensity and duration. Due to the c-wave response developing over several seconds, it is susceptible to influences from electrode drift, eye movements, and blinks.
Latency of response refers to the onset of the stimulus to the beginning of the a-wave.
Implicit time is a measure of the time interval from onset of the stimulus to the peak of the b-wave.
Types of Recording Electrodes[edit | edit source]
Burian-Allen Electrode- (commonly used electrode for flash ERG) variable lens sizes consisting of an annular ring of stainless steel surrounding the central polymethylmethacrylate (PMMA) contact-lens core with a lid speculum
Dawson-Trick-Litzkow Electrode- low-mass conductive Mylar thread consisting of individual fibers impregnated with metallic silver
ERG-Jet Electrode- a disposable plastic lens with a gold-plated peripheral circumference
Mylar Electrode- aluminized or gold-coated Mylar
Skin Electrode- may be used as a replacement for corneal electrodes by placing an electrode on the skin over the infraorbital ridge near lower eyelid; due to decreased amplitudes and variable responses, the skin electrode is primarily used for screening purposes only
Cotton-Wick Electrode- Burian-Allen electrode shell fitted with a cotton wick which is useful for minimizing light-induced artifact
Hawlina-Konec Electrode- Teflon-insulated thin metal wire (silver, gold, platinum) with three central windows, 3 mm in length, molded to fit into the lower conjunctival sac
Normal ERG responses under scotopic and photopic conditions[edit | edit source]
The rod and cone photoreceptor function responses can be separated using a variety of ERG techniques. Scotopic (rod) responses are isolated by dark-adaptation for a minimum of 20 minutes per ISCEV standards followed by a short wavelength stimulus as a single flash or 10 Hz flicker. Although the resulting response has rod and cone components, the rod component is dominant and the primary contributor to the increased amplitude and increased implicit time.
Photopic (cone) responses can be obtained either before or after dark-adaptation. Since rods cannot follow a flicker stimulus greater than 20 Hz, cone photoreceptor function is primarily measured under light-adapted conditions for at least 10 minutes with either single flash (stimulus wavelength greater than 680 nm) or 30 Hz flicker stimulus. Photopic responses result in small b-wave amplitudes with a short latency (30-32 ms), whereas scotopic (rod) conditions produce much larger b-wave amplitudes with a longer latency (60 ms).
Oscillatory potentials (OP) are high-frequency, low-amplitude wavelets on the ascending limb of the b-wave with a frequency of about 100 to 160 Hz. Although it is not known for certain, it is suspected that OPs are generated from the amacrine cells located in the inner retina.
Factors affecting the ERG[edit | edit source]
Duration of stimulus
Size of retinal area illuminated
Interval between stimuli
Size of pupil
Systemic circulation and drugs
Development of Retina
Clarity of Ocular Media
Age, Sex, and Refractive Error
Types[edit | edit source]
The focal ERG (fERG; also known as the foveal ERG) is used primarily to measure the functional integrity of the fovea and is therefore useful in providing information in diseases limited to the macula. A variety of techniques have been described in the literature for recording fERGs. Differing field sizes varying from 3 degrees to 18 degrees and light stimulus frequencies have been used in the various methods, however each technique deals with the challenge of limiting amount of light scattered outside the focal test area. Focal ERG is useful for assessing macular function in conditions such as age-related macular degeneration, however requires good fixation from the subject. The full-field ERG (Ganzfeld; ffERG) measures the stimulation of the entire retina with a flashlight source under dark-adapted (scotopic) and light-adapted (photopic) types of retinal adaptation.This is useful in detecting disease with widespread generalized retinal dysfunction i.e. cancer associated retinopathy, toxic retinopathies, and cone-rod dysfunction. Due to the massed retinal electrical response, small retinal lesions may not be revealed in ffERG recordings.
The multifocal ERG (mfERG) simultaneously measures local retinal responses from up to 250 retinal locations within the central 30 degrees mapped topographically. This new technology was developed by Erich Sutter in the early 1990s and involves powerful computers and high –intensity display monitors. The light stimuli are presented on a video monitor in one of a large number of arrays consisting of hexagonal elements. The hexagonal elements in the array are distributed so that the focal retinal responses have an approximately equal signal-to-noise ratio. The central hexagons are smaller than those in the periphery. The elements are stimulated in a pseudo-random sequence of light and dark, called a maximum length sequence (or m-sequence). The resulting waveforms are similar to those of the ffERG: initial negative deflection (N1 or a-wave), followed by a positive deflection (P1 or b-wave), and a second negative deflection (N2 or c-wave). MfERGs are useful in detecting localized abnormalities within the retina in conditions such as retinitis pigmentosa, branch retinal artery occlusion, fundus flavimaculatus, and Stargardt’s disease. Degree of retinal toxicity related to certain drugs such as hydroxychloroquine or ethambutol is better detected using mfERG compared to ffERG. Early visual field defects due to glaucoma may also be detected sooner using mfERG compared to automated perimetry.
The pattern ERG (PERG) uses pattern-reversal stimuli similar to VEP testing and captures retinal ganglion cell activity predominantly in the N95 waveform component. The PERG is used to detect subtle optic neuropathies. In demyelinating optic neuropathy, the PERG is relatively normal, while it may be abnormal in ischemic optic neuropathies.
Abnormalities in various disease states[edit | edit source]
| Disease entity
|| full-field ERG findings
|| multifocal ERG findings|
| Multiple evanescent white dot syndrome (MEWDS)
|| initially depressed a- and b-wave responses with return to normal values
|| focal areas of retinal dysfunction|
| Vitamin A deficiency
|| marked rod dysfunction and elevated threshold of rods and cones on dark adaptation
|Cone dystrophy||markedly depressed photopic response and less affected scotopic response|
|Cancer associated retinopathy (CAR)||significantly reduced a-wave and b-wave amplitudes|
|Melanoma associated retinopathy (MAR)||
extinguished rod responses, normal a-wave, reduced b-wave (electronegative ERG)
|Retinitis pigmentosa||minimal or sub-normal a- and b-wave amplitudes (response primarily from cone system)|
|Congenital Achromatopsia (typical (rod) monochromat)||non-detectable cone response, normal or subnormal rod response|
|Congenital Achromatopsia (atypical (cone) monochromat)||normal ERG responses|
|Congenital Red-Green Color Deficiency||normal ERG responses|
|Congenital Hereditary Stationary Night Blindness (Schubert-Bornschein type)||normal scotopic a-wave with selectively reduced b-wave; implicit time of b-wave is approximately the same under scotopic and photopic conditions|
|Oguchi disease||normal photopic responses with predominantly reduced scotopic b-wave amplitudes|
|Fundus Albipunctatus||reduced scotopic amplitudes which improve to normal values after longer (variable) perior of dark adaptation|
|Fleck Retina of Kandori||reduced b-wave amplitudes relative to a-wave in scotopic and photopic conditions|
|Stargardt Macular Dystrophy (Fundus Flavimaculatus)||extent of reduced a- and b-wave amplitudes depends on extent of fundus pigmentary changes; longer duration of dark-adaptation may be necessary for scotopic amplitudes to reach normal values|
|Best Vitelliform Macular Dystrophy||normal ERG responses with an abnormal EOG|
|Pattern dystrophies||normal ERG responses|
|North Carolina Macular Dystrophy||normal ERG responses|
|Progressive Bifocal Chorioretinal Atrophy||subnormal 30-Hz flicker and single-flash scotopic responses|
|Fenestrated Sheen Macular Dystrophy||initially normal ERG responses with reduced scotopic and photopic responses in later stages|
|Familial Internal Limiting Membrane Dystrophy||reduced b-wave amplitudes|
|Gyrate Atrophy||significantly reduced or extinguished rod and cone responses|
|Choroideremia||reduced a- and b-wave amplitudes in both scotopic and photopic conditions; increased rod and cone b-wave implicit times|
|X-linked Juvenile Retinoschisis||reduced photopic and scotopic b-wave amplitudes|
|Goldmann-Favre Syndrome||non-detectable ERG response|
|Wagner Disease||normal or mild to moderately reduced photopic and scotopic responses (variable depending on extent of fundus involvement)|
|Autosomal Dominant Neovascular Inflammatory Vitreoretinopathy||selective reduction of b-wave amplitude|
|Autosomal Dominant Vitreoretinochoroidopathy||initially normal ERG with only mild to moderately reduced amplitudes in older patients|
|Familial Exudative Vitreoretinopathy||normal ERG responses (diminished oscillatory potentials may be observed)|
|Birdshot Retinochoroidopathy||selective reduction in b-wave amplitude more prominent in scotopic than photopic responses; delayed photopic and scotopic b-wave implicit times|
|Acute Zonal Occult Outer Retinopathy||ERG amplitudes vary from normal to subnormal with prolonged b-wave implicit times|
|Pseudo-Presumed Ocular Histoplasmosis Syndrome (Multifocal Choroiditis)||moderate to severely reduced rod and cone responses|
|Behcet Disease||initially loss of oscillatory potentials in flash ERG with subsequent reduction of b-wave amplitude|
|Sickle Cell Retinopathy||normal ERG in the absence of peripheral retinal neovascularization, reduced amplitudes of ERG components when peripheral retinal neovascularization is present|
|Takayasu Disease||initially decreased oscillatory potentials, later stages involve reduced a- and b-wave amplitudes|
|Carotid Artery Occlusion||reduced b-wave greater than a-wave amplitudes depending on extent and severity of occlusion|
|Central and Branch Artery and Vein Occlusions||reduced scotopic b-wave amplitudes in CRAO and CRVOs; slight b-wave reduction or normal ERG in branch retinal artery or vein occlusions|
|Hypertension and Arteriosclerosis||initially reduced oscillatory potentials followed by reduced a- and b-wave amplitudes|
|Chloroquine and Hydroxychloroquine toxicity||normal ERG responses unless presence of advanced retinopathy; cone function initially more affected than rod function|
|Thioridazine||decreased photopic and scotopic a- and b-wave responses depending on degree of fundus changes|
|Quinine||transiently decreased a- and b-wave amplitudes under both photopic and scotopic conditions with recovery after 24 hours|
|Methanol||reduced a- and b-wave amplitudes|
|Gentamicin||significantly reduced ERG amplitudes|
|Vitamin A deficiency||reduced ERG amplitudes particularly under scotopic conditions|
|Kearns-Sayre Syndrome||reduced ERG amplitudes|
|Siderosis||initially a transient supernormal response then negative pattern followed by non-detectable response in severe cases (rod function more affected than cones; reduction of b-wave amplitude more than a-wave)|
References[edit | edit source]
Bach, Michael, et al. “ISCEV standard for clinical pattern electroretinography (PERG): 2012 update.” Doc Ophthalmol 126 (2013): 1-7.
Berrow, Emma J., et al. “The electroretinogram: a useful tool for evaluating age-related macular disease?” Doc Ophthalmol. 121 (2010): 51-62.
Electrophysiologic Testing in Disorders of the Retina, Optic Nerve, and Visual Pathway (Pearls Series) by Gerald Allen Fishman M.D. Publication Date: January 2, 2001 | ISBN-10: 1560551984 | ISBN-13: 978-1560551980 | Edition: 2
Vincent, Ajoy, Anthony G. Robson, and Graham E. Holder. “Pathognomonic (Diagnostic) ERGs a Review and Update.” Retina, the Journal of Retinal and Vitreous Diseases. 33.1 (2013): 5-12.
Young, Blair, Eric Eggenberger, and David Kaufman. “Current electrophysiology in ophthalmology: a review.” Current Opinion Ophthalmology. 23 (2012): 497-505.