Electroretinography

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Electroretinography
Maximal Response ERG.png
Maximal response ERG waveform from a dark adapted eye.
ICD-9-CM 95.21
MeSH D004596
Schematic Electroretinography waves of healthy people. GraphAB ERG Electroretinography.jpg
Schematic Electroretinography waves of healthy people.

Electroretinography measures the electrical responses of various cell types in the retina, including the photoreceptors (rods and cones), inner retinal cells (bipolar and amacrine cells), and the ganglion cells. Electrodes are placed on the surface of the cornea (DTL silver/nylon fiber string or ERG Jet) or on the skin beneath the eye (Sensor Strips) to measure retinal responses. Retinal pigment epithelium (RPE) responses are measured with an EOG test with skin-contact electrodes placed near the canthi. During a recording, the patient's eyes are exposed to standardized stimuli and the resulting signal is displayed showing the time course of the signal's amplitude (voltage). Signals are very small, and typically are measured in microvolts or nanovolts. The ERG is composed of electrical potentials contributed by different cell types within the retina, and the stimulus conditions (flash or pattern stimulus, whether a background light is present, and the colors of the stimulus and background) can elicit stronger response from certain components.[ citation needed ]

Contents

If a dim flash ERG is performed on a dark-adapted eye, the response is primarily from the rod system. Flash ERGs performed on a light adapted eye will reflect the activity of the cone system. Sufficiently bright flashes will elicit ERGs containing an a-wave (initial negative deflection) followed by a b-wave (positive deflection). The leading edge of the a-wave is produced by the photoreceptors, while the remainder of the wave is produced by a mixture of cells including photoreceptors, bipolar, amacrine, and Müller cells or Müller glia. [1] The pattern ERG (PERG), evoked by an alternating checkerboard stimulus, primarily reflects activity of retinal ganglion cells.

Diagnostics

An electroretinogram (ERG) test performed in 2014. 2014 ERG test.jpg
An electroretinogram (ERG) test performed in 2014.
A historical photo of a patient undergoing an electroretinogram. Electroretinogram.jpg
A historical photo of a patient undergoing an electroretinogram.

Clinically used mainly by ophthalmologists and optometrists, the electroretinogram (ERG) is used for the diagnosis of various retinal diseases. [2]

Inherited retinal degenerations in which the ERG can be useful include:[ citation needed ]

Other ocular disorders in which the standard ERG provides useful information include:

The ERG is also used extensively in eye research, as it provides information about the function of the retina that is not otherwise available.

Other ERG tests, such as the photopic negative response (PhNR) and pattern ERG (PERG) may be useful in assessing retinal ganglion cell function in diseases like glaucoma.

The multifocal ERG is used to record separate responses for different retinal locations.

The international body concerned with the clinical use and standardization of the ERG, EOG, and VEP is the International Society for the Clinical Electrophysiology of Vision (ISCEV). [7]

Other uses

In addition to its clinical diagnostic purpose, the ERG can be used during the course of drug development and in clinical trials for testing ocular safety and efficacy of new or existing drugs and treatment modalities. [8]

A 2013 study [9] by Nasser et al. found that the retinal dopaminergic response to eating a brownie is equivalent in magnitude to the response to a 20 mg dose of methylphenidate, which implies that the activity of dopamine neurons in the retina reflects brain dopaminergic activity. The study concludes that, if verified by further research, "ERG could provide the neurotransmitter specificity of PET at a much lower cost".

The ERG has been shown to differ in people with schizophrenia [10] and may be useful in helping to differentiate schizophrenia and bipolar disorder. [11]

History

ERG was one of the earliest recorded biological potential. The first known ERG was recorded by the Swedish physiologist Alarik Frithiof Holmgren, who recorded it in 1865 on an amphibian retina. [12] However, he failed to understand his findings accurately. He thought the responses he recorded were from the optic nerve instead of the retina. [13] The first human ERG was recorded in 1877 by Scottish chemist and physicist Sir James Dewar. [12] James Dewar and John Gray McKendrick independently suggested that the biological potential was from retina. [13] In 1908, Einthoven and Jolly divided the ERG response into three components: A-wave, B-wave, and C-wave. [12] In 1941, American psychologist Lorraine Riggs introduced a contact lens electrode for ERG recording. [12] Many of Ragnar Granit's observations became the basis of ERG understanding, for which he was awarded the 1967 Nobel Prize in Physiology and Medicine. [12]

See also

Related Research Articles

Retina Part of the eye

The retina is the innermost, light-sensitive layer of tissue of the eye of most vertebrates and some molluscs. The optics of the eye create a focused two-dimensional image of the visual world on the retina, which then processes that image within the retina and sends nerve impulses along the optic nerve to the visual cortex to create visual perception. The retina serves a function which is in many ways analogous to that of the film or image sensor in a camera.

Retinitis pigmentosa Gradual retinal degeneration leading to progressive sight loss

Retinitis pigmentosa (RP) is a genetic disorder of the eyes that causes loss of vision. Symptoms include trouble seeing at night and decreasing peripheral vision. As peripheral vision worsens, people may experience "tunnel vision". Complete blindness is uncommon. Onset of symptoms is generally gradual and often begins in childhood.

Photoreceptor cell Type of neuroepithelial cell

A photoreceptor cell is a specialized type of neuroepithelial cell found in the retina that is capable of visual phototransduction. The great biological importance of photoreceptors is that they convert light into signals that can stimulate biological processes. To be more specific, photoreceptor proteins in the cell absorb photons, triggering a change in the cell's membrane potential.

The National Eye Institute (NEI) was established in 1968. It is located in Bethesda, Maryland. The NEI is one of 27 institutes and centers of the US National Institutes of Health (NIH), an agency of the US Department of Health and Human Services. The mission of NEI is to prolong and protect the vision of the American people. The NEI conducts and performs research into treating and preventing diseases affecting the eye or vision.

Retinal ganglion cell Type of cell within the eye

A retinal ganglion cell (RGC) is a type of neuron located near the inner surface of the retina of the eye. It receives visual information from photoreceptors via two intermediate neuron types: bipolar cells and retina amacrine cells. Retina amacrine cells, particularly narrow field cells, are important for creating functional subunits within the ganglion cell layer and making it so that ganglion cells can observe a small dot moving a small distance. Retinal ganglion cells collectively transmit image-forming and non-image forming visual information from the retina in the form of action potential to several regions in the thalamus, hypothalamus, and mesencephalon, or midbrain.

Sensory neuron Nerve cell that converts environmental stimuli into corresponding internal stimuli

Sensory neurons, also known as afferent neurons, are neurons in the nervous system, that convert a specific type of stimulus, via their receptors, into action potentials or graded potentials. This process is called sensory transduction. The cell bodies of the sensory neurons are located in the dorsal ganglia of the spinal cord.

Retina bipolar cell Type of neuron

As a part of the retina, bipolar cells exist between photoreceptors and ganglion cells. They act, directly or indirectly, to transmit signals from the photoreceptors to the ganglion cells.

Melanopsin Mammalian protein found in Homo sapiens

Melanopsin is a type of photopigment belonging to a larger family of light-sensitive retinal proteins called opsins and encoded by the gene Opn4. In the mammalian retina, there are two additional categories of opsins, both involved in the formation of visual images: rhodopsin and photopsin in the rod and cone photoreceptor cells, respectively.

Amacrine cell

Amacrine cells are interneurons in the retina. They are named from the Greek roots a– ("non"), makr– ("long") and in– ("fiber"), because of their short neuronal processes. Amacrine cells are inhibitory neurons, and they project their dendritic arbors onto the inner plexiform layer (IPL), they interact with retinal ganglion cells and/or bipolar cells.

Retina horizontal cell

Horizontal cells are the laterally interconnecting neurons having cell bodies in the inner nuclear layer of the retina of vertebrate eyes. They help integrate and regulate the input from multiple photoreceptor cells. Among their functions, horizontal cells are believed to be responsible for increasing contrast via lateral inhibition and adapting both to bright and dim light conditions. Horizontal cells provide inhibitory feedback to rod and cone photoreceptors. They are thought to be important for the antagonistic center-surround property of the receptive fields of many types of retinal ganglion cells.

Intrinsically photosensitive retinal ganglion cells (ipRGCs), also called photosensitive retinal ganglion cells (pRGC), or melanopsin-containing retinal ganglion cells (mRGCs), are a type of neuron in the retina of the mammalian eye. The presence of ipRGCs was first suspected in 1927 when rodless, coneless mice still responded to a light stimulus through pupil constriction, This implied that rods and cones are not the only light-sensitive neurons in the retina. Yet research on these cells did not advance until the 1980s. Recent research has shown that these retinal ganglion cells, unlike other retinal ganglion cells, are intrinsically photosensitive due to the presence of melanopsin, a light-sensitive protein. Therefore they constitute a third class of photoreceptors, in addition to rod and cone cells.

Retinal implant

Retinal prostheses for restoration of sight to patients blinded by retinal degeneration are being developed by a number of private companies and research institutions worldwide. The system is meant to partially restore useful vision to people who have lost their photoreceptors due to retinal diseases such as retinitis pigmentosa (RP) or age-related macular degeneration (AMD). Three types of retinal implants are currently in clinical trials: epiretinal, subretinal, and suprachoroidal. Retinal implants introduce visual information into the retina by electrically stimulating the surviving retinal neurons. So far, elicited percepts had rather low resolution, and may be suitable for light perception and recognition of simple objects.

Progressive retinal atrophy (PRA) is a group of genetic diseases seen in certain breeds of dogs and, more rarely, cats. Similar to retinitis pigmentosa in humans, it is characterized by the bilateral degeneration of the retina, causing progressive vision loss culminating in blindness. The condition in nearly all breeds is inherited as an autosomal recessive trait, with the exception of the Siberian Husky and the Bullmastiff. There is no treatment.

Retinal degeneration (rhodopsin mutation) Retinopathy

Retinal degeneration is a retinopathy which consists in the deterioration of the retina caused by the progressive death of its cells. There are several reasons for retinal degeneration, including artery or vein occlusion, diabetic retinopathy, R.L.F./R.O.P., or disease. These may present in many different ways such as impaired vision, night blindness, retinal detachment, light sensitivity, tunnel vision, and loss of peripheral vision to total loss of vision. Of the retinal degenerative diseases retinitis pigmentosa (RP) is a very important example.

Retinal gene therapy holds a promise in treating different forms of non-inherited and inherited blindness.

Autoimmune retinopathy (AIR) is a rare disease in which the patient's immune system attacks proteins in the retina, leading to loss of eyesight. The disease is poorly understood, but may be the result of cancer or cancer chemotherapy. The disease is an autoimmune condition characterized by vision loss, blind spots, and visual field abnormalities. It can be divided into cancer-associated retinopathy (CAR) and melanoma-associated retinopathy (MAR). The condition is associated with retinal degeneration caused by autoimmune antibodies recognizing retinal proteins as antigens and targeting them. AIR's prevalence is extremely rare, with CAR being more common than MAR. It is more commonly diagnosed in females in the age range of 50–60.

Emixustat

Emixustat is a small molecule notable for its establishment of a new class of compounds known as visual cycle modulators (VCMs). Formulated as the hydrochloride salt, emixustat hydrochloride, it is the first synthetic medicinal compound shown to affect retinal disease processes when taken by mouth. Emixustat was invented by the British-American chemist, Ian L. Scott, and is currently in Phase 3 trials for dry, age-related macular degeneration (AMD).

AII amacrine cells are a subtype of amacrine cells present in the retina of mammals. AII amacrine cell serve the critical role of transferring light signals from rod photoreceptors to the retinal ganglion cells

Occult macular dystrophy (OMD) is a rare inherited degradation of the retina, characterized by progressive loss of function in the most sensitive part of the central retina (macula), the location of the highest concentration of light-sensitive cells (photoreceptors) but presenting no visible abnormality. "Occult" refers to the degradation in the fundus being difficult to discern. The disorder is called "dystrophy" instead of "degradation" to distinguish its genetic origin from other causes, such as age. OMD was first reported by Y. Miyake et al. in 1989.

Sickle cell retinopathy can be defined as retinal changes due to blood vessel damage in the eye of a person with a background of sickle cell disease. It can likely progress to loss of vision in late stages due to vitreous hemorrhage or retinal detachment. Sickle cell disease is a structural red blood cell disorder leading to consequences in multiple systems. It is characterized by chronic red blood cell destruction, vascular injury, and tissue ischemia causing damage to the brain, eyes, heart, lungs, kidneys, spleen, and musculoskeletal system.

References

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  2. Electroretinography, U.S. National Library of Medicine, 11 April 2005 (accessed 19 January 2007)
  3. Maa; et al. (2015). "A novel device for accurate and efficient testing for vision-threatening diabetic retinopathy". Journal of Diabetes and Its Complications. 30 (3): 524–32. doi:10.1016/j.jdiacomp.2015.12.005. PMC   4853922 . PMID   26803474.
  4. Zeng, Yunkao; Cao, Dan; Yang, Dawei; Zhuang, Xuenan; Yu, Honghua; Hu, Yunyan; Zhang, Yan; Yang, Cheng; He, Miao; Zhang, Liang (2019-11-12). "Screening for diabetic retinopathy in diabetic patients with a mydriasis-free, full-field flicker electroretinogram recording device". Documenta Ophthalmologica. doi:10.1007/s10633-019-09734-2. ISSN   1573-2622. PMID   31720980.
  5. Brigell, Mitchell G.; Chiang, Bryce; Maa, April Yauguang; Davis, C. Quentin (3 August 2020). "Enhancing Risk Assessment in Patients with Diabetic Retinopathy by Combining Measures of Retinal Function and Structure". Translational Vision Science & Technology. 9 (9): 40–40. doi: 10.1167/tvst.9.9.40 . PMC   7453041 .
  6. Miyata, Ryohei; Kondo, Mineo; Kato, Kumiko; Sugimoto, Masahiko; Matsubara, Hisashi; Ikesugi, Kengo; Ueno, Shinji; Yasuda, Shunsuke; Terasaki, Hiroko (2018-12-14). "Supernormal Flicker ERGs in Eyes With Central Retinal Vein Occlusion: Clinical Characteristics, Prognosis, and Effects of Anti-VEGF Agent". Investigative Ophthalmology & Visual Science. 59 (15): 5854–5861. doi: 10.1167/iovs.18-25087 . ISSN   1552-5783. PMID   30550616.
  7. ISCEV Website
  8. Brigell; et al. (2005). "An overview of drug development with special emphasis on the role of visual electrophysiological testing". Doc. Ophthalmol. 110 (1): 3–13. doi:10.1007/s10633-005-7338-9. PMID   16249953.
  9. Nasser, J.a.; Parigi, A. Del; Merhige, K.; Wolper, C.; Geliebter, A.; Hashim, S.a. (2013-05-01). "Electroretinographic detection of human brain dopamine response to oral food stimulation". Obesity. 21 (5): 976–980. doi:10.1002/oby.20101. ISSN   1930-739X. PMC   4964968 . PMID   23784899.
  10. Demmin, Docia L.; Davis, Quentin; Roché, Matthew; Silverstein, Steven M. (2018). "Electroretinographic anomalies in schizophrenia". Journal of Abnormal Psychology. 127 (4): 417–428. doi:10.1037/abn0000347. ISSN   1939-1846.
  11. Hébert, Marc; Mérette, Chantal; Gagné, Anne-Marie; Paccalet, Thomas; Moreau, Isabel; Lavoie, Joëlle; Maziade, Michel (2020-02-01). "The Electroretinogram May Differentiate Schizophrenia From Bipolar Disorder". Biological Psychiatry. 87 (3): 263–270. doi:10.1016/j.biopsych.2019.06.014. ISSN   0006-3223. PMID   31443935.
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