Clinical electrophysiology in veterinary ophthalmology – the past, present and future

The aim of this review is to introduce the reader to the world of clinical veterinary electroretinography. An important indication for ERG recordings in the dog is the early diagnosis of progressive retinal atrophy, an inherited form of photoreceptor degeneration, analogous to retinitis pigmentosa in humans. In most of the 20 canine breeds in which the disease has been studied electrophysiologically, changes in the ERG appear long before the appearance of clinical signs. This early diagnosis is a vital tool in efforts to eradicate the disease through preventive breeding. Pre-operative screening of canine cataract patients is another common indication for electroretinography in the dog. The ERG is also used to diagnose inherited and nutritional photoreceptor degenerations in the cat, and retinal disorders in a number of other animal species. The abundance of animal species (and breeds) seen by the veterinary ophthalmologist lends additional importance to the problem of a harmonized ERG recording protocol. The European College of Veterinary Ophthalmologists has set up a special committee to formulate guidelines for such a protocol. International meetings and wetlabs are also being organized as part of an effort to improve the quality of electrophysiological diagnosis that veterinary ophthalmologists provide their patients.     

Guidelines for clinical electroretinography in the dog: 2012 update

The full-field, flash electroretinogram (ERG) is now a widely used test of canine retinal function for the clinical diagnosis of hereditary retinal dystrophies and other causes of retinal degeneration, assessment of retinal function in patients with opaque media, ruling out of generalized retinal diseases in patients with sudden loss of vision and in ophthalmological research, as well as in pharmaceutical and toxicological screening for deleterious side effects of drugs and other chemical compounds. In 2002, the first guidelines for clinical ERGs in this species adopted by the European College of Veterinary Ophthalmologists were published. This work provides an update of these guidelines.     

Improved contact lens electrode for corneal ERG recordings in mice

The electroretinogram (ERG) is routinely used to study retinal physiology in the clinic and in research. Due to their outstanding properties, contact lens electrodes (CLEs) are widely used for ERG recordings. Though the procedures for ERG recordings in mice are similar to those used in humans and larger vertebrates, use of CLEs in the mouse has been limited because of difficulties involved with the manufacturing of small contact lenses. We describe a simple instrument and method for manufacturing contact lenses and CLEs for stable ERG recordings in mice. The instrument operates like a hole-punch and is based on slip joint pliers incorporating a ball bearing on one jaw and forming plate on the other. These CLEs are simple to manufacture, inexpensive and provide stable, long-term recordings of corneal ERGs in mice. With minor modifications, these CLEs could be made for other small animals such as rats or fish.     

Spectral sensitivity of the European ground squirrel (Citellus citellus L.)

The spectral sensitivity of the European ground squirrel was investigated by electroretinography (ERG) and visual-evoked cortical potentials. Using chromatic adaptation, two spectral systems were found, one peaking between 520 and 530 nm, the other at 465 nm. The blue system was characterized by a slower course of the potential, a lower threshold and the lack of a d wave in the ERG. However, its threshold is higher than the rod threshold and it was shown to be more resistant to adapting light stimuli than rod systems are. It is concluded that the second spectral system is a blue cone system which in its rod-like properties is comparable to the blue cones found in cat, monkey and man.     

Dissecting the dark-adapted electroretinogram

Although gross recordings of the ganzfeld flash-evoked electroretinogram (ERG) can potentially provide information about the activity of many, if not all, retinal cell types, it is necessary to dissect the ERG into its components to realize this potential fully. Here we describe various procedures that have been used in intact mammalian eyes to identify and characterize the contributions to the dark-adapted ERG of different cells in the retinal rod pathway. These include (1) examination of the very early part of the response to a flash (believed to reflect directly the photocurrent of rods), (2) application of high-energy probe flashes to provide information about the underlying rod photoreceptor response even when this component is obscured by the responses of other cells, (3) pharmacological suppression of responses of amacrine and ganglion cells to identify the contribution of these cells and to reveal the weaker responses of bipolar cells, (4) use of pharmacological agents that block transmission of signals from rods to more proximal neurons to separate responses of rods from those of later neurons, (5) examination of the ERG changes produced by ganglion-cell degeneration or pharmacological block of nerve-spike generation to identify the contribution of spiking neurons, (6) modeling measured amplitude-energy functions and timecourse of flash responses and (7) using steady backgrounds to obtain differential reductions in sensitivity of different cell types. While some of these procedures can be applied to humans, the results described here have all been obtained in studies of the ERG of anaesthetized cats, or macaque monkeys whose retinas are very similar to those of humans. This revised version was published online in July 2006 with corrections to the Cover Date.     

The effects of the phosphodiesterase type V inhibitor sildenafil on human and bovine retinal function in vitro

Background After the ingestion of sildenafil (Viagra), visual adverse events have been reported, possibly caused by an inhibition of the phototransduction cascade by sildenafil via phosphodiesterase (PDE 6). Therefore, we investigated the effects of sildenafil on photoreceptors and postsynaptic neurons of human and bovine retinas using the isolated superfused vertebrate retina technique. Methods Human and bovine retina preparations were perfused with an oxygen preequilibrated standard solution. The electroretinogram (ERG) was recorded using Ag/AgCl electrodes. After recording stable ERG amplitudes, sildenafil was added to the solution for 45 min. Thereupon, the preparations were reperfused with standard solution for 240 min. Results Following the application of sildenafil (3 μMol/l), the b-wave amplitude of bovine and human preparations was reduced continuously and disappeared completely. After reperfusion with the standard solution for 4 h, the b-wave amplitude did not recover completely. Using the same sildenafil concentration (3 μMol/l), the a-wave amplitude of the human retina was not totally abolished, but reduced to 21% of the initial amplitude and remained reduced at washout. For all retinal preparations, the implicit time of the ERG amplitudes remained significantly extended at the end of the washout. Conclusions Strong similarities were detected in the drug-induced changes of the ERG when comparing human and bovine retinas. The results suggest that sildenafil impairs retinal function at not only the level of the photoreceptors, but it also affects the neuronal network of the inner retina at concentrations of approximately 30-fold higher than at therapeutic plasma concentrations. Dedicated to the late Prof. Dr. Werner Sickel, who passed away on 18th December 2004.     

X-chromosomale Hemeralopie: Klinik und Elektrophysiologie einschließlich Gleichspannungs-ERG bei zwei Familien

Zusammenfassung Patienten aus zwei Familien mit x-chromosomal rezessiv vererbter Hemeralopie mit Myopie wurden klinischen (Visus, Gesichtsfeld, Farbsinn, Dunkeladaptation) und elektrophysiologischen Funktionsprüfungen (konventionelles ERG, EOG, Gleichspannungs-ERG) unterzogen. Das Gleichspannungs-ERG wurde am wachen Patienten gewonnen.In einem Fall standen Ergebnisse einer Untersuchung von 1967 zum Vergleich: für Progredienz ergab sich kein Hinweis. Anhand der elektrophysiologischen Befunde wird über Natur und Lokalisation des der Hemeralopie zugrundeliegenden Defektes diskutiert; er scheint nicht ausschließlich die inneren Netzhautschichten zu betreffen.

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X-linked night-blindness: Clinical and electrophysiological investigations including dc-ERG in two families

Summary Patients from two families with X-linked recessive nyctalopia and myopia were investigated. The functional tests included clinical examinations (visual acuity, color sense, visual fields, dark adaptation) and electrophysiological examinations (ac-coupled ERG, de-coupled ERG, EOG). The de-coupled ERG registrations were done without general anesthesia. In one case, a comparison with results obtained in 1967 was possible. There was no evidence of increase in functional impairment. On the basis of the electrophysiological results, the nature and localization of the defect causing nyctalopia are discussed. The postreceptoral retinal structures appear not to be involved exclusively.

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Mit Unterstützung der Deutschen Forschungsgemeinschaft

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Herrn Prof. Dr. H. Harms zum 70. Geburtstag gewidmet     

Congenital achromatopsia: electroretinogram in early diagnosis

PURPOSE: Achromatopsia is a hereditary disease responsible for congenital low vision. Patients present with nystagmus, abnormal visual behavior or photophobia. Only the electroretinogram (ERG) can confirm the diagnosis in infants. PATIENTS AND METHODS: Thirty children referred for nystagmus or low vision were included in this retrospective study. A complete ophthalmological examination, an ERG and when possible a color vision test (Ishihara, Farnsworth 15 Hue test) was done. A Ganzfeld ERG was performed in accordance with ISCEV standards in patients more than 6 years of age. In younger patients, a simplified method using electroluminescent diode stimulation was used and a comparative ERG in accordance with ISCEV standards was performed when the patients were old enough. RESULTS: The ERG response was identical in children and adults. It confirmed the diagnosis of achromatopsia: the scotopic components obtained in dark adapted conditions were normal, (scotopic a-wave, b2 wave). The photopic components, recorded in light-adapted conditions, in order to inhibit the scotopic response (photopic wave, b1 wave), were not recordable. The color vision tests confirmed color blindness; however, in some patients color denomination was correct. CONCLUSION: The simplified ERG procedures performed in our series were reliable in detecting achromatopsia. However, it may not be sufficient to discriminate complete from incomplete achromatopsia.     

The lens-coating agent and the electroretinogram

Purpose: To investigate the effects of 0.5, 1.0 and 2.5% methylcellulose coating agents on the ERG in normals. Methods: A total of 15 healthy volunteers underwent photopic ERG recordings in three experimental protocols comparing 0.5, 1.0 and 2.5% methylcellulose solutions. The conductivity of the solutions was measured. Results: The difference between 0.5 and 1.0% solutions showed significant changes (p<0.05) in ERG amplitudes. The 0.5% solution produced approximately 15% higher ERG amplitudes than the 1.0% solution. Comparison between 1.0 and 2.5% solutions did not show significant changes in ERG amplitudes. The conductivity was essentially the same for 0.5 and 1.0% solutions, but conductivity of the 2.5% solution was roughly half of that of the other two solutions. Conclusions: Although the 0.5% solution did yield significantly higher ERG values than the 1.0% and 2.5% solutions, the exact mechanism by which this occurs is not known. The source of these differences could arise from a combination of factors such as conductivity, viscosity, or other unknown components of the solutions. ERG laboratories should be consistent in the use of coating agents, and be aware that any change in solution might alter normative values by a modest percentage.     

ERG及VEP对白内障術後视力的预測

目的 探讨ERG及VEP对白内障术後视力的预测作用。方法 应用ERG及VEP对259只白内障眼进行检查并与术後视力进行分析。结果 259只眼中VEP表现为潜伏期延长66眼,P100及N75振幅降低73只眼,正常183只眼,ERC潜伏期延迟66眼,振幅降低67眼。结论 VEP及ERG潜伏期延迟,振幅降低,术後视力差,它们能较好的预测白内障的术後视力。     

ERGs in female carriers of incomplete Congenital Stationary Night Blindness (I-CSNB) A family report

ERG findings in five sisters are reported. By pedigree analysis, four of the five must be obligate carriers for I-CSNB since their sons were affected (impaired night vision, reduced visual acuity, variable ametropia, congenital nystagmus and ERG with both scotopic and photopic b-wave reduced amplitude). The fifth was childless at the time of examination and her ERG analysis was normal. Three of the four obligate carriers showed significant reduction in the sum of the OPs amplitude as previously reported as being an electrophysiological signs in female carriers: two without alteration in other ERG components and the third with association with a flicker ERG amplitude significantly increased. The fourth female carrier showed a normal sum of the OPs amplitude whereas the other b-wave ERG or flicker amplitudes were significantly decreased. These last two ERG results suggest a possible modifications of synaptic transmission at a post-receptoral site (outer plexiform layer or involvement of the bipolar pathways) in these two carriers.     

Kombination einer angeborenen Achromatopsie mit sektorenförmiger Degeneratio pigmentosa retinae

Zusammenfassung Seit der frühesten Jugend des 66jährigen Patienten besteht eine totale Farbenblindheit. Die Farbensinnprüfung mit den pseudoisochromatischen Tafeln nach Ishihara und der Farnsworth-Test ergeben eine Achromatopsie. Das Helligkeitsmaximum ist zum kurzwelligen Teil des Spektrums verschoben, was für angeborene Achromatopsie spricht. Im ERG ist keine x-Welle und keine photopische Flimmerantwort registrierbar.Seit dem 51. Lebensjahr des Patienten ist seine Pigmentdegeneration der Netzhaut bekannt. Die temporal oberen und ein Teil der nasal oberen Quadranten sind nahezu frei von pigmentierten Herden. Gesichtsfelder, Dunkeladaptation und ein kleines, aber deutlich registrierbares ERG sprechen für eine sektorenförmige Degeneratio pigmentosa retinae.Der Bruder des Patienten ist protanop.

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Summary A 66 year old man is presented, who is complaining of achromatopsia congenita. Colour tests with pseudoisochromatic tables and Farnsworth test show total colour blindness. The maximum brightness is shifted to the shortwave part of the spectrum. This indicates a hereditary achromatopsia. No x-wave and no photopic flicker ERG is recordable.When the patient was 51 years old, a pigmental degeneration of the retina was discovered. The upper temporal and a part of the upper nasal quadrants are almost free of pigmentary changes. Visual fields, dark adaption and a small, but clearly registrable ERG result in a sectoral retinopathia pigmentosa.The brother of the patient is protanope.

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Herrn Prof. Dr. J. Böck zum 70. Geburtstag gewidmet.     

Improving the diagnostic power of electroretinography by transient alteration of the ocular perfusion pressure.

In this report we present the results of a series of studies focusing on the effects of transient changes in the ocular perfusion pressure (OPP) on retinal function in normals as assessed by the flash electroretinogram (ERG). A transient increase or decrease in the OPP affected by body inversion and compression/suction ophthalmodynamometry (ODM), respectively, is shown to affect differentially the b-wave of scotopic and photopic ERG's. However, under dark-adapted conditions, the cone component of the red flash ERG b-wave exhibited a vulnerability to decreased OPP which approached that seen for the b-wave of the scotopic blue flash ERG b-wave. Similar test procedures used to investigate the functional response of the inner plexiform layer during altered OPP revealed component-specific changes in white flash scotopic oscillatory potentials (OP's). The results of these provocative tests of retinal function offer new insights into basic retinal physiology and encouraging prospects for practical clinical diagnostic procedures with enhanced sensitivity and specificity for subclinical retinal disorders.     

Über elektroretinographische verlaufs-kontrollen bei der pigmentdegeneration der Netzhaut

]Zusammenfassung In 25 Fällen von 147 Fällen von Retinitis pigmentosa (= 16,2%) war noch ein elektrisches Belichtungspotential auszulösen, das allerdings gegenüber dem ERG von Gesunden stets erniedrigte Werte aufwies. In der Regel konnten erst bei stark erhöhten Reizleuchtdichten kleine polyphasische Wellen als Antwort beobachtet werden.Bei 5 Patienten ließ sich innerhalb einer unterschiedlich langen Kontrollzeit ein Verlust der Potentialbildung unmittelbar verfolgen.Ein Vergleich der Funktionsausfälle (periphere Lichtsinnunterschiedsempfindlichkeit und ERG-Schwelle) zeigt: Die meisten Patienten mit erhaltenem ERG haben einen geringeren Gesichtsfeldverlust als diejenigen mit ausgelöschten Potentialen - eine Bestätigung der These (Armington, 1961), daß Amplitude und Schwelle des retinalen Summationspotentials (ERG) von der Größe intakter Netzhautbezirke abhängt.

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Summary Report of 47 cases of Retinitis pigmentosa with the following results: In 25 cases (16.2%) an electrical response to illumination of the retina could be produced, which however in comparison to the ERG of a normal control group showed lower values. Generally only small polyphase waves as response to very intense stimulating light could be observed. In 5 patients a further decrease of the ERG potential was observed during the following controls. The comparison of visual field and ERG demonstrates: Most of the patients with recordable ERG show less visual field defects than those with abolished potentials.

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Résumé Le rapport concerne 147 cas de Retinitis pigmentosa. Les résultats sont les suivants: Dans 25 cas (16,2%) il a été possible d'enregistrer un ERG dont l'amplitude a toujours été inférieure à l'amplitude normale. 5 patients soumis à un contrôle de plusieurs années montraient une dégradation du potential. Une comparaison des altérations fonctionnelles (champ visuel et ERG) montre que la plupart des patients dont on a pu obtenir des ERG ont un champ visuel plus étendu que les autres.

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Aus der Universitäts-Augenklinik Hamburg-Eppendorf (Direktor: Prof. Dr. H. Sautter).     

Clinical study of the pattern electroretinogram in patients with optic nerve damage

We have recorded both pattern and flash electroretinograms (ERG) in two patients with unilateral optic nerve damage due to optic canal fracture over one year. The pattern ERG from the affected eye was reduced in amplitude by approximately 40% in one patient, 60% in the other, compared with that from their other, normal eyes, while the flash ERG was normal in all eyes. Reduced pattern ERG responses may depend on retrograde degeneration following damage to the optic nerve. The pattern ERG, however, was not totally lost in the eyes with marked optic atrophy. There is a possibility that the pattern ERG contains both contrast and luminance components in various proportions.     

Indications for electrophysiologic studies of the eye

The phenomena of light-evoked electrical activity of the retinal pigment epithelium, retina, and visual cortex can be used for specific diagnostic testing. The EOG, with standing potential and light peak, reflects the functional state of the pigment epithelium; the ERG reflects the function of the photoreceptors (a-wave) and inner nuclear layer (b-wave), and the visual evoked response (VER) provides information on signal conduction along the entire visual pathway. The indications for electroretinography are discussed in detail, resulting in a broad spectrum including degenerative, metabolic, inflammatory and toxic changes of the retina. In addition, a condensed table of diagnoses that can hardly be established without ERG is proposed. The value of ERG recordings is extended by the possibility to document rate of progression and relative involvement of the rod- and/or the cone system of the retina. VER procedures are mainly directed towards demyelinating diseases of the CNS. We attempt to interpret results of electrophysiologic testing synoptically with subjective complaints and clinical observations.     

Detecting color vision in a malingerer

A patient describing himself as totally color blind was ordered by the judicial system to have his color vision investigated in order to establish his suitability for military service. Basic clinical (Farnsworth Panel D-15, Moreland and Rayleigh anomaloscope equations), electroretinographic (ERG) and psychophysical techniques (spectral sensitivities) were applied to determine the extent of his color discrimination performance and cone function. These standard procedures were complemented by a test for cone interaction (transient tritanopia) and by newly developed cone-isolating flicker large-field ERG recordings. The patient's data consistently indicate the function as well as the functional interaction of the middle-wavelength-sensitive (M-) and the short-wavelength-sensitive (S-) cones. But the function of the long-wavelength-sensitive (L-) cones was completely absent. Hence the patient was correctly demonstrated to be a protanope. This study establishes that standard classical procedures, in combination with newly developed and easy to apply psychophysical and ERG ones, which can be reliably used to assess true color discrimination performance, in difficult cases of malingering.     

The effects of various amino acids, dopamine and some convulsants on the electroretinogram of the rabbit.

The effects of various amino acids, dopamine and some convulsants on the rabbit's ERG were studied using an in situ eye-cup preparation. Allowing for the fact that ERG changes are open to different interpretations, taurine, glycine and β-alanine all appeared to depress the b wave and slow P 111 components, and may also have reduced the size of the a wave. Dopamine also exerted a depressant action on the ERG which was manifested as a diminution in the heights of both the a and b waves, but not slow P 111. On the other hand, GABA clearly potentiated both the b wave and slow P 111, but its action on the a wave was uncertain. Glutamate had little effect on the ERG. Strychnine and picrotoxin both seemed to cause an increase in the a wave and to attenuate slow P 111. Picrotoxin also decreased the size of the b wave, whereas strychnine did not. The action of strychnine, but not picrotoxin, was easily reversed by GABA. Also, GABA, but not glutamate, antagonized the actions of the glycine-like amino acids, but not that of dopamine. Bicuculline had no effect of its own on the ERG and was unable to modify the action of GABA.     

Dark-adapted red flash ERGs in healthy adults

Clinical electrophysiological testing of the visual system incorporates a range of noninvasive tests and provides an objective indication of function relating to different locations and cell types within the visual system. This document developed by the International Society for Clinical Electrophysiology of Vision provides an introduction to standard visual electrodiagnostic procedures in widespread use including the full-field electroretinogram (ERG), the pattern electroretinogram (pattern ERG or PERG), the multifocal electroretinogram (multifocal ERG or mfERG), the electrooculogram (EOG) and the cortical-derived visual evoked potential (VEP). The guideline outlines the basic principles of testing. Common clinical presentations and symptoms are described with illustrative examples and suggested investigation strategies.     

Electrophysiology in the investigation of acquired retinal disorders

Electrophysiological research on acquired retinal disorders, both common and rare, is reviewed. Age is a major factor influencing electroretinogram (ERG) and electro-oculogram (EOG) findings. Bipolar or Müller cell death in the aging retina could account for much of the amplitude decline that is observed with age. In diabetic retinopathy, the oscillatory potentials can monitor the progression of the disease and indicate neuronal alterations rather than diabetic angiopathy of the retina. Human ERG studies on glaucoma concentrated on ERG measures that are dominated by inner retinal contributions. It has been shown that the pattern ERG can serve as a predictor of ocular hypertension's progression to glaucoma. In retinal disorders caused by endogenous intoxication, such as hepatic retinopathy, or exogenous intoxication from chronic lead exposure, ERG changes give an objective measure of the damage and allow to study the pathophysiological mechanisms that are involved. Inflammations of the choroid and the retina affect the standard ERG when they are diffuse. In central serous chorioretinopathy, functional disturbances can be revealed not only in the photoreceptors but also in the middle and inner retinal layers with the use of focal stimuli. Choroidal melanoma leads to large reductions of the EOG light peak-to-dark trough ratio through its influence on the transepithelial potential of the retinal pigment epithelium (RPE). In cancer-associated retinopathy, both the rod and cone ERGs are reduced. However, selective cone dysfunction has been described. In melanoma-associated retinopathy, the long flash ERG may reveal a specific pathophysiological mechanism, namely the affection of the ON-pathway with preservation of the OFF-pathway. ERG measurements can reveal vitamin A deficiency and are altered in cases with a mutation in the gene for the retinol binding protein in which other organs are not affected. Photochemical damage to the retina from light emission by the operating microscope can be assessed by electrophysiological methods.