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Evaluation of different recording parameters to establish a standard for flash electroretinography in rodents.

Different electrodes and stimulus protocols commonly used for electroretinography in rodent eyes were compared for convenience of use, degree of damage to corneal epithelium, and for magnitude of amplitude, reproducibility, left versus right eye accuracy, and reliability of recorded parameters of the flash electroretinogram (ERG). Adult C57BL/6 pigmented mice and albino Wistar rats were used to determine scotopic ERGs in response to Ganzfeld or strobe-light stimulation and light-adapted (photopic) ERGs recorded from both eyes at the same time. Test-retest data were used for statistical analyses to compare a monopolar gold-wire contact lens electrode (CLE), a cotton-wick silver-silver chloride electrode (CSCE), a DTL fiber electrode (DTLE), and a circular stainless steel wire electrode (SSE). Corneas were evaluated for abrasion after ERG recordings using fluorescein staining and also for the time taken, ease of insertion, and re-insertions required for the different electrodes. Compared to CSCE, DTLE, and SSE, the ERG potentials recorded by CLE had significantly larger scotopic amplitudes and oscillatory potentials under strobe or Ganzfeld stimulation and for light-adapted ERG b-wave amplitudes in both mice and rats. In analyzing test-retest data of scotopic ERG a-wave and b-wave amplitudes, the intraclass correlation coefficient showed the best agreement for the CLE (range 0.61-0.94) compared to the SSE (0.13-0.77), DTLE (0.02-0.69), and CSCE (0.12-0.51). In mice and rats, logistic regression analyses revealed significant correlations for amplitudes of most scotopic ERG parameters between contralateral eyes obtained with CLE and for some ERG components recorded by SSE. When comparing ERG amplitudes for stimulation by strobe or Ganzfeld, the difference was least with the CLE compared to DTLE, CSCE, or SSE. The time taken to insert the four different electrodes was greatest for the CLE in both mice and rats. The extent of corneal abrasion resulting from electrode use in mice was largest for the SSE followed by the CLE. However, in rats there was almost no corneal damage after ERG recordings with the CLE. Because of the stability of eye contact, the CLE allows ERGs to be determined over a longer recording session. Recording of scotopic and photopic (light-adapted) ERGs in rodents with monopolar gold-wire contact lens electrodes provides greater amplitudes and higher reproducibility when compared to other commonly used corneal electrodes. These electrodes are significantly better overall than others that were evaluated and should be considered for a standard protocol to monitor retinal function in rodent eyes.

Analysis of Variance↗

Short wavelength automated perimetry, frequency doubling technology perimetry, and pattern electroretinography for prediction of progressive glaucomatous standard visual field defects.

PURPOSE: To evaluate the clinical use of a test battery of short wavelength automated perimetry (SWAP), frequency doubling technology perimetry (FDT), and pattern electroretinography (PERG) in predicting progressive glaucomatous visual field defects on standard automated perimetry (SAP). STUDY DESIGN: A prospective, longitudinal, observational case series. PARTICIPANTS: One hundred and fifty-two patients with primary open-angle glaucoma (POAG) with bilateral glaucomatous visual field defects on SAP were followed at 6-month intervals over a period of 30 months. MAIN OUTCOME MEASURES: Short wavelength automated perimetry, FDT, and PERG results were compared between POAG eyes with and without progressive field loss on SAP. These two groups were used to evaluate whether PERG, SWAP, and/or FDT is predictive of future progression of field loss on SAP. RESULTS: Using the criteria of progressive field loss on SAP defined by the Collaborative Normal Tension Glaucoma Study, 54 eyes (study group) of 54 POAG patients showed progressive defects, whereas 84 eyes (control group) of 84 POAG patients showed no progression. Only 11.1% (6 of 54) of the eyes with a progression of field loss on SAP showed no increase of deficits on the three functional tests before progression. Short wavelength automated perimetry detected early progressive defects on SAP in 43 of the 54 eyes (79.6%). Of these 54 POAG eyes, FDT showed progressive deficits in 40 eyes (74.1%), whereas PERG amplitude P1N2 showed progressive deficits in 35 eyes (64.8%) before progression of field loss on SAP. A test battery consisting of SWAP and PERG P1N2-amplitude was able to detect 88.9% of eyes before a prediction of field loss on SAP. When comparing the results of the two functional tests, SWAP and FDT in the 84 eyes without progression of field loss on SAP between baseline and at 30 months, SWAP and FDT showed progressive deficits in 34.5% and 35.7%, respectively. CONCLUSIONS: All three tests (SWAP, FDT, and PERG) have been successful in detecting glaucoma eyes with a future progression of standard visual field defects. A test battery of SWAP and PERG P1N2-amplitude improved the power to predict these progressive defects on SAP. It remains to be seen whether the long-term follow-up in POAG eyes will improve the false-positive rate of SWAP and FDT.

Disease Progression↗

Detection of optic neuropathy in glaucomatous eyes with normal standard visual fields using a test battery of short-wavelength automated perimetry and pattern electroretinography.

PURPOSE: To evaluate the clinical use of a test battery of short-wavelength automated perimetry (SWAP), frequency-doubling technology (FDT) perimetry, and pattern-electroretinography (PERG) in patients with definite primary open-angle glaucoma (POAG) but normal results on standard automated perimetry (SAP). STUDY DESIGN: Prospective, comparative, observational case series. PARTICIPANTS: Thirty-six patients with POAG with standard visual field defects in one eye and normal standard visual fields in the contralateral eye and 36 normal controls were enrolled. MAIN OUTCOME MEASURES: SWAP, PERG, FDT, and SAP were performed in all eyes, and global indices and amplitudes were used for statistical analysis. RESULTS: When contralateral POAG eyes with asymmetric glaucomatous damage was compared, a paired t test showed significant differences in SAP mean deviation (MD) (P < 0.0001), SWAP-MD (P = 0.0003), FDT-MD (P = 0.0008), and PERG amplitudes (P < 0.0001). When comparing between POAG eyes with normal results on SAP and normal controls, Student's t test showed significant differences for SWAP-MD (P < 0.0001), FDT-MD (P = 0.0006), PERG N1P1-amplitude (P = 0.0486) and P1N2-amplitude (P < 0.0001); receiver operating characteristic analysis revealed promising accuracy for SWAP-MD of 73.6% (P < 0.0001). SWAP-MD (P < 0.0001) and FDT-MD (P < 0.0001) correlated significantly with SAP-MD and with each other (range, P < 0.0001 to P = 0.0020). Regression analysis revealed that PERG P1N2-amplitude could improve the power of SWAP-MD from 73.6% to detect early POAG in eyes with normal results on SAP to an accuracy of 81.9%. CONCLUSIONS: A test battery of SWAP-MD and PERG P1N2-amplitude could detect glaucomatous optic neuropathy in POAG eyes with normal standard visual fields, whereas FDT-MD and SWAP-MD significantly correlated with each other and with SAP-MD. All tests were able to detect the eye with the more severe glaucomatous optic neuropathy in patients with asymmetric POAG.

Electroretinography↗

Computer-assisted spectral electroretinography in vitrectomy patients.

Computer-assisted spectral electroretinography (CASE), using full field stimulation in the presence of a rod saturating background light, has been found to be a useful means of evaluating retinal function in patients with vitreal opacities. By this means, cone electroretinograms (ERGs) to white as well as spectrally selective stimuli could easily be detected in 22 of 24 eyes with vitreal opacities obscuring any view of the fundus and with minimal or no detectable ERGs to standard single flash stimuli. The responses to spectral stimuli in the presence of a rod saturating background light provides a means of estimating the optical density of the opacity. The results indicate that most patients undergoing vitrectomy for such opacities have considerable superimposed retinal damage and that the opacities themselves are seldom sufficiently dense to decrease the ERG to any great extent. Five eyes studied before and after vitrectomy indicate that successful vitrectomy has no effect on the ERG. The results suggest that CASE may be a useful substitute to the bright flash ERG for evaluating global retinal function behind an opaque media.

Adolescent↗

HPMPC therapy of MCMV-induced retinal disease in the SCID mouse measured by electroretinography, a non-invasive technique.

The purpose of these studies was to investigate the use of non-invasive electroretinography for the evaluation of retinal disease and its treatment in an ocular murine cytomegalovirus (MCMV) disease model. While under anesthesia, 10(2.6)plaque forming units (pfu) of salivary gland passaged, Smith strain MCMV was injected in the anterior chamber of 6- to 8-week-old severe combined immunodeficiency (SCID) mice. At various times post-inoculation, bright-flash scotopic electroretinogram, viral titer, and histology were obtained from the injected eye. Antiviral therapy was tested using 0.1 and 5mg/kg/day subcutaneous injections of HPMPC (Cidofovir) once daily for 5 consecutive days. In infected animals, the a- and b-waves of the electroretinographic (ERG) signal were significantly reduced as of 10 days post-inoculation when compared to control animals. Therapy with HPMPC 0.1mg/kg/day subcutaneously (s.c.) once daily for 5 consecutive days was able to delay the decrease in ERG wave amplitude and inhibit viral replication, whereas 5mg/kg/day s.c. significantly protected the ERG, completely inhibited viral replication, and maintained ocular viral titer below the limit of detection for up to 17 days post-infection. The reduction of ERG activity during progression of retinal disease correlated well with reduction of disease pathology. ERG recording represents a valuable non-invasive technique to measure the progression of the retinal disease induced by MCMV and the efficacy of antiviral treatment in the ocular MCMV disease model.

Animals↗

[Evaluation of trypan blue toxicity in idiopathic epiretinal membrane surgery with macular function test using multifocal electroretinography: seven prospective case studies].

INTRODUCTION: Idiopathic epiretinal membranes are considered the consequence of glial proliferation through a defect of the internal limiting membrane and can induce a functional macular syndrome associating mainly metamorphopsia and visual acuteness. Visual disturbance is not bound to the area and the degree of transparency of the membrane, but to distortion of external layers of the retina. Multifocal electroretinography (ERGm) can assess the macular area and retina extending 20 degrees. We used this tool to study macular function pre- and post-operatively with seven patients presenting idiopathic epiretinal membrane. PATIENT AND METHOD: All patients had successful vitrectomy, with 0.2 ml of 0.15% trypan blue (TB) staining to facilitate peeling. This stain is not toxic for the pigment epithelium but it becomes so for photoreceptors at doses exceeding 0.2%. We tried to estimate the echo of TB 0.15% on photoreceptors through this exam. An ERGm was done 1 week before the operation as well as 1 month and 4 months after on 14 eyes of seven patients with ERMs. RESULTS: Results show a pre-operative decrease in the electrical retinal response densities in the foveal, perifoveal and parafoveal areas. One month after operation, no significant difference was found compared to pre-operative results. However, at 4 months, an improvement of the retinal response density was observed. Retinal response densities in the macular area increased progressively after ERM surgery. CONCLUSION: The 0.15% TB facilitated ERM peeling and does not seem to present any retinal toxicity.

Electroretinography↗

Electroretinography in the evaluation of childhood myotonic dystrophy.

Electroretinography (ERG) may provide laboratory support for the diagnosis of childhood myotonic dystrophy. The sensitivity of ERG may exceed that of electromyography for early detection of the disease. The electroretinographic abnormalities are not specific for myotonic dystrophy.

Adolescent↗

Role of electroretinography in the assessment of retinal function as an indicator of vitamin A status.

Hypovitaminosis A is associated with exocrine pancreatic insufficiency in cystic fibrosis. Peripheral retinal dysfunction is an early finding of vitamin A deficiency. We evaluated serum retinol and zinc as well as visual adaptation in 41 patients with cystic fibrosis, receiving generous pancreatic enzyme and micronutrient supplementation. Forty-one normal individuals matched for age and sex served as controls. Peripheral retinal function was measured by clinical electroretinography using an Electrophysiologic Personal Interfaced Computer and applying a standard protocol. Serum retinol in cystic fibrosis was significantly lower than that of the control group (0.30+/-0.01 versus 0.39+/-0.02 mg/l, p<0.001). Serum zinc concentrations were normal in the cystic fibrosis group (1.21+/-0.03 mg/l) and significantly higher than that of the control group (1.02+/-0.01 mg/l, p<0.001). The overall visual adaptation, however, was found to be normal and comparable in the two groups. It is concluded that, in cystic fibrosis, despite appropriate vitamin A supplementation, retinol serum concentration may be low. As serum retinol does not reflect vitamin A status, evaluation of visual adaptation may be a more appropriate way to monitor for vitamin A deficiency in cystic fibrosis.

Adolescent↗

Effects of the beta1-selective adrenergic antagonist betaxolol on electroretinography in the perfused cat eye.

The effects of the beta1-selective adrenergic antagonist betaxolol on electroretinography (ERG) were studied in the isolated and arterially perfused cat eye. Betaxolol increased the perfusion flow rate, significantly at the administrations of more than 50 microM concentrations and induced a dose-related, reversible increase in the amplitudes of both the a-wave and b-wave of ERG. These results suggest that the calcium-channel blocking mechanism of betaxolol has a beneficial influence on ocular blood flow and retinal electrical activity in response to light. As it is known that ERG is a good indicator of the functional integrity of the retina, this indicates that betaxolol could be an ideal drug for treating glaucoma in which ischemia is involved to some extent.

Adrenergic beta-Antagonists↗

The changes of multifocal electroretinography in the early stage of photodynamic therapy for choroidal neovascularization.

To investigate short-term changes in the multifocal electroretinography (ERG) recordings after photodynamic therapy (PDT) for choroidal neovascularization (CNV), 16 patients (17 eyes) with classic CNV confirmed by fluorescein angiography (FA) and indocyanine green angiography (ICGA), including 11 cases (12 eyes) of exudative age-related macular degeneration (AMD), two cases (two eyes) of pathological myopia and three cases (three eyes) of idiopathic causes, were treated using PDT with verteporfin. The multifocal ERGs of these patients were tested with VERIS Science 4.0 imaging system. The latencies and average response densities of all six ring retinal regions were measured and compared before PDT and 3 or 7 days after PDT. The latencies and amplitude densities of the N1 and P1 waves in all six rings remained unchanged at 3 or 7 days post-treatment (p > 0.05). Therefore, there is no significant evidence to suggest an adverse effect from PDT for classic CNV on the outer retinal function in the early stage of treatment, with the aid of the multifocal ERG recordings.

Adult↗

Dystrophin expression in the human retina is required for normal function as defined by electroretinography.

We have studied retinal function by electroretinography in five Becker and six Duchenne muscular dystrophy patients. All had abnormal electroretinograms with a markedly reduced amplitude for the b-wave in the dark-adapted state. Using three antisera raised to different domains of dystrophin, we identified dystrophin in the outer plexiform layer of human retina. The retinal dystrophin is present in multiple isoforms as the result of alternative splicing. The localization of dystrophin to the outer plexiform layer coincident with the abnormal b-wave suggests that dystrophin is required for normal retinal electrophysiology.

Adolescent↗

The effect of light scattering on multifocal electroretinography.

PURPOSE: Unclear ocular media is a very common condition of older eyes characterized by significant light scattering and image degradation. The multifocal electroretinography (MERG) is a useful objective technique to measure retinal activity but its validity in the presence of cloudy ocular media remains unclear. We tested the MERG under controlled light scattering conditions using a liquid crystal diffuser (LCD) that simulated different degrees of image degradation. METHODS: The MERG were taken from 13 normal young subjects seated behind a LCD set under two conditions: scatter (visual acuity approximately 6/18) and non-scatter (visual acuity approximately6/6). The pupils had been dilated and the eyes were optically corrected for the working distance. The first-order kernel MERG response was analysed. Three subjects underwent MERG measurement with two additional intermediate light scattering levels (i.e. visual acuity approximately 6/9 and 6/12). RESULTS: The macular MERG response density was reduced (p < 0.001), but the peripheral MERG response densities were increased (p < 0.001) under the scattering condition. A similar trend was also observed with intermediate degrees of light scattering. Comparing the MERG waveforms without light scattering, a new retinal response was identified with a characteristic latency of about 60 ms (P60), but it was diminished in size under the scattering conditions. CONCLUSIONS: The veiling luminance might have caused the reduction in the macular MERG response and an elevation in the peripheral retina with light scatter. The functional suppression of P60 observed under the influence of light scatter may be related to retinal adaptation. Unclear optical media will affect the interpretation of MERG results.

Adolescent↗

Ocular optics, electroretinography and primary open angle glaucoma.

Advancing the knowledge of ocular image quality is important in the development of new tests for the earlier detection of primary open angle glaucoma (POAG). Loss of blue sensitivity is an important feature of POAG; however, it is difficult to separate this loss from the effects of wavelength related intraocular light scatter and media absorption. A technique for recording the S-cone electroretinogram is described which may solve these problems. The effect of scattered light is avoided by a Ganzfeld stimulus and the absorption of short wavelength light is compensated by a photometric balancing of blue and green stimuli using the M-cone response. The modulation transfer function of the eye has enabled the true spatial tuning function of the retina to be determined by pattern electroretinography (PERG). This has demonstrated the role of retinal ganglion cells in the generation of the PERG. These techniques are shown to be highly sensitive tests in the early stages of POAG.

Adult↗

[From the symptom to electroretinography diagnosis].

Retinal function can be documented noninvasively and objectively by electroretinography, complementing clinical examinations. Symptoms of nightblindness and of dayblindness with photoaversion, nystagmus, poor vision in infants or unclear visual field defects are meaningful indications for ERG testing. We use standardized (ISCEV) full-field single flash ERGs to evaluate the function of the rod- and of the cone-system. In infants, general anesthesia is useful to combine an abbreviated ERG protocol with ophthalmoscopy and fundus photography. ERG testing facilitates to distinguish between functional deficits in the rod- and cone-system, between congenital-stationary retinal dysfunction and progressive retinal heredo-degenerations. Frequently a functional deficit of the retina without ophthalmoscopic changes can be assessed. These entities include achromatopsia, congenital stationary night blindness, early stages of retinitis pigmentosa (RP) or progressive cone dystrophy, as well as toxic retinal changes. Congenital amaurosis Leber (LCA), infantile RP, Usher's syndrome and retinal involvement in other neuropediatric or metabolic syndromes can be diagnosed or excluded by ERG recording early-on. Synoptic evaluation of the full-field ERG, pattern-ERG and VEP completes neuro-ophthalmological screening.

Adult↗

[Objective assessment of visual field defects using multifocal electroretinography].

BACKGROUND: Multifocal electroretinography allows simultaneous recording of 61 focal electroretinographic signals from the retina of the posterior pole. The function of the outer retinal layers can be mapped for a visual field of 30.5 degrees radius. We herein describe the topography of such potentials in patients with hemianopic and concentric visual field defects. SUBJECTS AND METHODS: Six patients with visual field defects caused by chorioretinal and central visual pathways diseases were examined using multifocal ERG. RESULTS: In 30 normal volunteers in the entire 30 degrees visual field clear signals were obtained. In the patients with visual field defects caused by retinal diseases in areas with reduced light sensitivity diminished electroretinographical activity was found. In contrast, in patients with bitemporal hemianopsia due to a chiasmal lesion no correlation between visual field and magnitude of focal ERGs was seen. CONCLUSIONS: In retinal disorders defects in multifocal ERG presented the similar pattern as scotomata in perimetry. The patient with visual field defects due to disturbances in the chiasma exhibited a normal ERG-topography. In patients with visual field defects multifocal ERG supported differentiation of the location of the lesion.

Adult↗

[Multifocal electroretinography in acquired macular dysfunction].

BACKGROUND: Multifocal electroretinography allows physiological mapping of the central retina. The purpose of this study was to describe the spatial distribution of ERG-activity in patients with impairment of macular function which usually do not exhibit a pathologic Ganzfeld-ERG. SUBJECTS AND METHODS: 6 patients with macular lesions due to uveitis (4), retinitis centralis serosa (1), and contusio bulbi (1) were examined using the multifocal ERG technique. RESULTS: In normal volunteers the response density of the multifocal ERG decreased with eccentricity according to cone density distribution. In eyes with impaired central vision the foveal and macular responses were markedly diminished while surrounding signals were of normal or moderately decreased amplitudes. CONCLUSIONS: With the multifocal ERG disturbances of macular function due to oedema and secondary structural changes were detected in the presented cases and the extension of the central lesions was estimated.

Adolescent↗

[Photopsia: an often unrecognized symptom and sensitivity of electroretinography].

BACKGROUND: Photopsias are unformed luminous spontaneous visual hallucinations, often described as flickering or wiggling lights, sometimes like a glare. Phosphenes are more intense and of shorter duration whereas migraine fortifications have a specific time course and succession of events. Recognition of this symptom is often poor, hence patients are wrongly investigated. PURPOSE: To describe the clinical presentation and electroretinographic characteristics of patients with photopsias. METHODS: 4 patients were worked-up with clinical, psychophysical, angiographic and electroretinographic examinations. RESULTS: Despite normal fundus and angiographic examinations, full-field electroretinogram was diagnostic in all cases. Retinal dysfunction involved either inner or outer retina. Paraneoplastic, and probable autoimmune/inflammatory retinopathies were found in our cases. CONCLUSION: Photopsias are often secondary to sick retinal cells. In the presence of photopsias, investigations should be directed towards the retina and electroretinography is the gold standard. Recognition of the symptom should prevent useless and potentially harmful investigations for the patient.

Diagnosis, Differential↗

[Electroretinography changes in carriers of X-chromosomal retinitis pigmentosa].

Out of five families with pedigrees typical for X-linked retinitis pigmentosa (RP) the authors examined eight definite and eight possible female carriers. Subjective symptoms were mild and variable, consisting mainly of relative nyctalopia. Ophthalmoscopic examination revealed a normal fundus, or mild changes suggestive of RP, or even marked changes. Perimetry (Goldmann) revealed some narrowing of the outer isopter corresponding to a significant reduction in visual field area. In testing dark adaptation, the final rod threshold was slightly elevated in five out of 16 subjects. Ganzfeld-electroretinography using matched band filters in conditions of dark and light adaptation to selectively stimulate rod and cone signals revealed reduced b-wave amplitudes in most cases. White stimuli, applied in dark adaptation, generated ERGs with less abnormality than the selective rod and cone ERGs. Peak times of the cone b-waves were prolonged in most cases. The ERG abnormalities were more pronounced in definite carriers and in advanced age. In some cases remarkable differences were noted between the two eyes as regards fundus morphology and ERG responses. The authors conclude that the possibility of improved genetic and educational counseling in families afflicted by X-linked RP justifies the considerable diagnostic effort involved in such examinations.

Adolescent↗