Full-field ERG Research Articles

Multifocal, pattern and full field electroretinograms in cats with unilateral optic nerve section.

To look for a subcomponent of the mFERG generated at the optic nerve head and increasing in latency with distance from it. To compare multifocal electroretinogram (mFERG, mPERG) changes to those in full field ERGs and transient and steady state pattern and focal ERGs (PERGs, FERGs) in cats with total unilateral optic nerve section. We recorded multifocal flash ERGs (mFERGs) at three levels of intensity and multifocal pattern ERGs (mPERGs) within 61 equal areas after total unilateral optic nerve section in five long term (> 18 month) survival cats, as part of a long term serial study of full field flash and pattern ERG changes to many stimuli, in a larger population. Cats were anaesthetised with Ketamine/Xylazine and wore Henkes electrodes with 6mm artificial pupils. Intact retinal circulation was verified by fluorescein angiography and optic nerve section by retinal photography and histology. We compared the mean and mean summed multifocal responses, from the normal and denervated eyes. We also compared the mean interocular difference around the area centralis and as a function of distance from the optic nerve head, across the horizontal meridian for the mFERG to the most intense stimulus. The degree of change was compared to that in other types of ERG, in the larger set of cats. mFERGs were similar across cats. Response density was flat with no prominence at the area centralis. Average summed mFERGs were similar in the normal and denervated eye. In the interocular differences a component near OP2 was reduced in the first kernel to the most intense stimulus, near OP1 and OP3 in the second kernel and locally, there was a hint of a component near OP2, which varied in latency in a ring around the disk and at the area centralis. Nevertheless, no component could be seen, varying in latency with distance from the optic nerve head, across the horizontal meridian. No mPERG was recordable in these conditions. Full field PERGs and FERGs were very reduced. Full field flash ERG amplitude changes were small (4-20%) and slower to appear than PERG changes. Degree of ERG reduction and correlation with PERG losses was greatest for the mesopic OPs, low for the scotopic tests (STR, ERG and OPs) and near zero for the mesopic ERG. The mFERG and mesopic ERG both lost OPs without overall amplitudes. The cat mFERG does not have a component, varying in latency with distance from the optic nerve head. The only change was qualitiatively similar to that in the light adapted ERG. With intense stimuli there were local changes around the time of OP2 near the area centralis which might be explained by local variations in ganglion cell density.

Clinical applications of multifocal electroretinography.

The multifocal ERG using the m-sequence stimulation technique allows the derivation of 61 - 241 local ERG signals in a central visual field of about 60 degree diameter in a short time between 4 and 16 min. A recording in a light adapted state offers local information comparable to cone responses in the full-field ERG. Retinal functional losses due to regional disorders in outer retinal layers can be described in detail with this technique. In maculopathies decreased or absent central ERGs are found surrounded by normal ERG. The extent of the central lesion can be estimated. In diseases of the outer retina the pattern of distribution of multifocal ERG activity is similar to the the pattern of the visual field defect. In addition to decreased ERG amplitudes a delay of implicit time may be an important sign of pathology, i.e. the pronounced delay of implicit times in the periphery in retinitis pigmentosa and the implicit time delays in regions associated with retinal edema like CRVO and cystoid macula edema in intermediate uveitis. No simple correlation of the first order kernel multifocal ERG and field defects could be found in disorders of the ganglion cell layer. The multifocal ERG is therefore useful in the differential diagnosis of retinal and optic nerve diseases.

Visual phenotype in patients with Arg41Gln and Ala196+1bp mutations in the CRX gene

Our aim was to describe the visual function characteristics of affected members from two unrelated families with different dominant mutations in the CRX gene. Standard full-field ERGs and high-intensity a-wave series were obtained. In addition, in most subjects, dark-adapted (DA) thresholds, color vision function (arrangement tests), and static perimetry were assessed. A point mutation in codon 41 of the CRX gene (Arg41Gln) was identified in family members from the RFS087 family who were tested on several occasions since 1983. Depending on age, affected members showed varying degrees of acuity loss, normal or slightly elevated DA thresholds, reduced cone a- and b-wave amplitudes, normal or minimally delayed cone b-wave implicit times, and normal rod and cone phototransduction gain parameters. An insertion mutation (Ala196+1bp) was found in two members of another family (RFS014). Affected members showed reduced visual acuity, normal or slightly elevated DA thresholds, relatively preserved rod ERG and substantially reduced or undetectable cone ERG, and normal rod phototransduction gain parameters. The Arg41Gln was associated with a late-onset, slowly progressing mild form of cone-rod dystrophy with cone loss but preserved rod and cone sensitivity until later in life. The Ala196+1bp mutation was associated with an early-onset, severe form of cone-rod dystrophy similar to that described in the original CORD2 family (Evans et al., Arch Ophthalmol 1995;113:195-201).

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.

Central serous chorioretinopathy: bilateral multifocal electroretinographic abnormalities.

To assess retinal function topographically in the posterior pole of affected and fellow eyes with central serous chorioretinopathy. Multifocal electroretinograms (MERGs) were recorded from 6 patient with active central serous chorioretinopathy and 5 normal control subjects. Two patients also had full-field conventional ERGs. The MERG responses were averaged in rings radiating out from the foveal center. All of the patients had central macular detachments in the affected eyes, while the fellow eyes were normal except for a few small retinal pigment epithelial abnormalities. The MERG was not only depressed in areas of detachment as expected, but was also reduced beyond the area of detachment in affected eyes and throughout the posterior pole of the fellow eyes. Full-field ERGs were normal. The MERG findings show that there is broad retinal functional disturbance in central serous chorioretinopathy involving both eyes and areas beyond the zone of detachment. These data strongly suggest that diffuse and possibly systemic pathologic conditions underlie this disease and that the leak itself may be a somewhat incidental event. The MERG may prove useful as a clinical marker for susceptibility to serous detachment.

Assessment of local retinal function in patients with retinitis pigmentosa using the multi-focal ERG technique.

To assess local retinal function in patients with retinitis pigmentosa (RP), multi-focal ERGs and local thresholds (static visual fields) were obtained on eight RP patients with visual acuities of 20/25 or better. All eight patients showed multi-focal responses with normal timing within the central 5 deg. However, there were few responses with normal timing in the areas outside the central 7.5 deg, except in the case of the only patient with a 30 Hz full-field response with normal timing. Since full-field ERGs are dominated by responses from the periphery, this finding supplies a foundation for the commonly observed delays in the full-field cone ERGs of patients with RP. With respect to amplitude, only two patients showed multi-focal responses with near normal amplitudes anywhere in the field. The loss of amplitude at any point was not a good predictor of visual sensitivity in the Humphrey visual field. On the other hand, all areas with normal timing had near normal sensitivity. Timing changes appear to be an early indication of local retinal damage to the cone system. Nearly all areas with sensitivity losses greater than 0.5 log unit, and some areas with near normal sensitivity, showed significantly delayed multi-focal ERGs. Finally areas with extreme sensitivity loss show multi-focal responses with a wide range of amplitudes and implicit times across patients, suggesting different mechanisms of disease action in different patients.

Visual electrodiagnostic findings in mild traumatic brain injury

Patients with traumatic brain injury TBI frequently exhibit varied forms of visual system dysfunction including: binocular, oculomotor, accommodative, refractive error shift, visual field loss, and visual perceptual deficits. A 5-year collaborative study between optometry and ophthalmology was initiated to follow documented mild TBI patients utilizing diagnostic methods to assess the quantity and quality of visual system deficits and recovery. A group of patients with mild TBI receiving optometric rehabilitation were compared with a group of age-matched, gender-matched, and headsize-matched TBI patients not receiving such treatment. Eighteen patients diagnosed with mild TBI underwent a treatment regimen of optometric rehabilitation group I ; 32 patients diagnosed with mild TBI did not receive optometric rehabilitation group II. Pattern visually evoked cortical potential VECP testing and electroretinography ERG evaluation were utilized initially, repeated 6-12 months later and then 12-18 months after baseline. All TBI patients' VECP and ERG results were compared to agematched, headsize-matched controls. Once the ERG had been used to exclude retinal involvement, identification of visual pathway dysfunction was possible with the VECP. Full-field ERG results in all groups were not remarkable and not sensitive for patients with mild TBI. Initial testing results revealed that 72 of those TBI patients in group I demonstrated VECP waveform abnormalities and 81 of those patients in group II showed waveform dysfunction. In the testing performed 12-18 months later, 38 of group I TBI patients, after receiving a treatment regimen of optometric rehabilitation, showed VECP waveform abnormalities; 78 of group II TBI patients demonstrated waveform abnormalities. VECP evaluation in patients with mild TBI can provide a useful and reliable tool for objective assessment of visual system deficit and recovery. Significant differences in visual system recovery were shown when comparing group I and group II.

Full‐field electroretinogram in a patient with cutaneous melanoma‐associated retinopathy

A patient operated for malignant melanoma developed night blindness and a sensation of shimmering light, strong enough to make him unable to work. Shortly afterwards, melanoma metastases became apparent. A full-field ERG examination showed absence of rod responses but normal cone amplitudes, suggesting a malfunctioning rod system in the retina. The patient was not on chemotherapy. A few similar cases have previously been reported. The disease appears to differ from the cancer-associated retinopathy (CAR) syndrome, which affects mainly the photoreceptor cells.

Electroretinograms in patients with achromatopsia

Eleven patients with X-linked and 9 patients with autosomal recessive achromatopsia were examined with full-field electroretinograms. In the standard full-field ERG's, normal rod responses were obtained, but the amplitude of the cone b-waves was not detectable. With computer averaging and narrow bandpass filtering, residual cone b-wave responses could be detected in 10 of the 20 patients. The residual cone b-wave amplitudes were markedly different in the 3 families with X-linked achromatopsia. In two of them, residual cone b-wave responses were seen in all patients examined. In contrast, such responses were seen only in 2 of 7 patients in the third family. There were also differences in other clinical observations (mainly in the visual acuity and refractive error) and we therefore suggest that there are at least two forms of X-linked achromatopsia. The ratios of the cone response amplitudes to 30 Hz flickering orange and blue-green light suggested that the defect in the X-linked achromatopsia patients was of the protanope type, whereas in the autosomal patients, both the protanope and the deutanope type was seen. In conclusion, measurements of the residual cone b-wave amplitude responses are of diagnostic and may possibly be of prognostic value when examining children and other members of families with achromatopsia.

Local ERG for clinical examination of eye diseases

We used a suction electrode with a frosted front window to record a full-field (general) ERG, and a suction electrode with a short-focus lens and a red-green light diode to record a local ERG. As the suction electrode moved with the eye, the stimulus struck the macula in all positions of gaze. Our data showed that only mildly intense stimuli with an angular size of 10 to 15 degrees induced a retinal response, with a macular contribution of 70%. Patients with various dystrophic changes of the retina, such as Stargardt's dystrophy, vitelliform dystrophy of the Best type, X-linked juvenile retinoschisis, and age-related macular dystrophy of different stages, were examined. In patients with retinitis pigmentosa, the cones were involved in the pathologic process to varying degrees; the behavior of the local ERGs helped determine the final visual acuity. We also observed a reduction in the local ERG in patients with Stargardt's dystrophy that disappeared as the disease progressed. In age-related macular dystrophy, a disturbance of the electrogenesis mainly occurred in the central retina in advanced stages of the disease.

Electroretinographic diagnosis in families with X‐linked retinitis pigmentosa

Four families with X-chromosome linked retinitis pigmentosa (14 patients, 14 carriers and 11 normal relatives) were investigated with full-field ERG with computer averaging and an electronic narrow bandpass filter. Reliable ERGs were obtained with 30 Hz flickering white light from 13 out of 14 patients with the disease, all severely affected. Further, B-wave implicit times were found to be more informative than B-wave amplitudes for identifying carriers of the disease. Full-field ERG appears to be a valuable tool for studying X-chromosome linked retinitis pigmentosa families, when necessary supported with computer averaging and a narrow bandpass filter.

Foveal cone optical density in retinitis pigmentosa

We have used a color matching technique to estimate the optical density of the foveal cone photopigments in a group of patients with retinitis pigmentosa. We find that foveal cone optical density is reduced in patients with retinitis pigmentosa. This reduction of density can occur early in the disease process and is found in patients with minimal visual field loss or 20/20 visual acuity. Foveal cone optical density is highly correlated with visual acuity and correlated with visual field area. Full-field ERG measurements are severely reduced early in the disease before significant foveal changes occur.