Simplified electroretinography protocol and diagnosis of retinal dystrophies in children]

PURPOSE: To report results of a simplified electroretinogram in children. PATIENTS: 124 children under 6 years of age with nystagmus, blindness, neurological disease, cone rod dystrophy in the family, or abnormal fundus appearance were examined. METHOD: The electroretinogram was recorded by corneal electrodes in an awake state without sedation. A light-emitting orange diode stimulator was used. Stimulation was performed subsequently after 3 minutes of light adaptation and after 8 minutes of darkness. If the electroretinogram was abnormal, a second recording was done a few weeks later using the same method. In some cases, the children were re-examined, and a ganzfeld stimulation ERG was recorded. RESULTS AND DISCUSSION: This method allowed a reliable diagnosis of photoreceptor dystrophy: Leber's congenital amaurosis with or without rare metabolic diseases, X link pigmentary retinopathy or retinal dystrophy with general disease in children. It helped to differentiate isolated retinal pigment changes with normal electroretinogram from functional retinal impairment and rod-cone dystrophy from other retinal dystrophies.     

Double-flash electroretinography in human eyes

A tri-color Ganzfeld stimulator with light-emitting diodes as light sources is used to study the suppression of the second electroretinographic response in human eyes to double-flash stimulation. The mechanism suppressing the a- and b-waves of the response to the second (test) flash has a scotopic spectral sensitivity to the first (conditioning) flash. Responses to mild test stimuli are more sensitive to suppression by a conditioning flash than responses to strong test stimuli.Abbreviations ERG electroretinography/electroretinogram - LED light-emitting diode - phot.cd photopic candela - scot.cd scotopic candela     

Visual evoked potentials and electroretinography in brain-dead patients

Visual evoked potentials and electroretinograms were elicited by light-emitting diode stimulation and recorded simultaneously, with cephalic and noncephalic references, in 30 normal subjects and in 30 brain-dead patients. A characteristic pattern was found in the group of patients: when a cephalic reference was used for both visual evoked potentials and the electroretinogram, the a- and b-waves of the electroretinogram were recognized in all patients, and visual evoked responses consisted of waves with inverse polarity, similar morphologic characteristics, the same latency, and less amplitude than those of the electroretinogram. When a noncephalic derivation was chosen for the electroretinogram and visual evoked potentials, electroretinogram did not change in either morphologic features or latency, whereas the visual evoked potential channel showed no response. Only in two cases was it possible to record waves in the visual evoked potential lead with a noncephalic reference, showing a spread of the electroretinogram to the occipital area, with a considerably reduced amplitude. These results suggest that, although contamination of visual evoked potential records by the spread of the electroretinogram to the occipital area could occur, it is easy to confirm the absence of a true cortical visual response in brain-dead patients by means of a noncephalic reference. This pattern clearly confirms that in the visual pathways of brain-dead patients, electrical activity is confined to the retina.     

Spatial distribution of local flash electroretinogram by multi-input stimulation

A method was developed for recording the distribution of the local flash electroretinogram with multi-input stimulation. With the use of a long flash interval, such as 100 ms, the principle and the method are useful for clinicians who know the method for recording the conventional local flash electroretinogram with single-input stimulation. This method results in a long recording time, yet it presents real local flash electroretinogram waveforms at the output.     

A technique for in vivo measurement of photoreceptor orientation in the chicken retina.

The aim of the current study was to develop a method for simultaneously assessing central and peripheral photoreceptor alignment in vivo in animal models. The stimulus apparatus consisted of nine light-emitting diodes (LED) positioned 7.5 degrees apart around an arc. The stimulus was viewed through a pinhole imaged into the entrance pupil of the eye using a telecentric lens system. Photodiodes placed over an array of the VERIS imaging system stimulated the electroretinogram. Data were obtained by positioning the pinhole at 0.25-mm intervals across the pupil and recording (Volk Optical, Mentor, OH, USA) at each location. Orientation assessed in normal chickens demonstrates that photoreceptors orientate towards a locus near the centre of the pupil and that there is a systematic change in peak location with eccentricity. This technique provides a valuable method for determining photoreceptor orientation properties in vivo and can be applied to animal models of pathology.     

The pattern electroretinogram in retinal and optic nerve disease

A retrospective analysis was performed on the transient and steady-state pattern electroretinograms recorded from 42 patients with glaucoma, 13 patients with senile dementia of the Alzheimer's type, 58 patients with diabetes mellitus, and 92 control subjects to evaluate the pattern of electroretinographic changes associated with retinal and optic nerve disease. The amplitudes of both the initial positive component (N1 to P1) and the subsequent negative component (P1 to N2) of the transient (4 rps) responses were measured. From these measurements the (P1 to N2)/(N1 to P1) was derived. The N1 to P1 amplitude of the steady-state pattern electroretinogram also was measured. In the glaucoma patients all three amplitude measures, as well as the amplitude ratio of the components of the transient response, were reduced significantly compared with age-matched controls (p < 0.05). A similar pattern was detected in the patients with Alzheimer's disease, but in this case the only statistically significant amplitude reduction was in the steady-state pattern electroretinogram. A different pattern was observed among the diabetic patients (both with and without retinopathy). Only minor reductions in the amplitude of the transient pattern electroretinogram, which were not statistically significant, were noted. In addition, the ratio of the amplitudes of the components of the transient response did not differ from age-matched controls. The amplitude of the steady-state pattern electroretinogram was reduced in diabetics, but this was significant only for those patients with retinopathy (p < 0.01). These findings support the suggestion that an analysis of both the positive and negative components of the pattern electroretinogram may be useful for differentiating the contributions of retinal and optic nerve dysfunction to visual impairment. The results also indicate that in both retinal and optic nerve disease the steady-state pattern electroretinogram can be an earlier sign of dysfunction than the transient pattern electroretinogram.     

Pattern electroretinogram in glaucoma

PURPOSE OF REVIEW: Several studies have shown that the pattern electroretinogram, a direct, objective method of measuring retinal ganglion cell function, is altered early in ocular hypertension and glaucoma. Renewed interest in the pattern electroretinogram for early detection of pre-perimetric glaucoma has been sparked by noninvasive and reproducible methods of recording using skin electrodes. RECENT FINDINGS: With the noninvasive pattern electroretinogram, response abnormalities have been detected in up to 50% of glaucoma suspects with normal standard perimetry. In early glaucoma (with either normal or high intraocular pressure), a reduction of intraocular pressure has sometimes yielded improvement in pattern electroretinogram amplitude. A prolonged steady-state stimulus presentation reduces the pattern electroretinogram amplitude and increases optic nerve blood flow in normal subjects, suggesting that sustained activity of retinal ganglion cells is physiologically associated with autoregulatory changes of the neural-vascular system. It is unknown whether this autoregulation is altered in glaucoma. The multifocal pattern electroretinogram does not seem to have an advantage over the pattern electroretinogram in the early detection of glaucoma. The photopic negative response of the diffuse flash electroretinogram has shown changes in glaucoma, but may not be able to detect retinal dysfunction in normal tension glaucoma. SUMMARY: The pattern electroretinogram is a noninvasive, direct, objective method that may be useful to clinicians in detecting early retinal ganglion cell dysfunction in glaucoma suspects. The pattern electroretinogram may also optimize treatment strategies based on improvement of retinal ganglion cell function.     

Multifocal ERG in chloroquine retinopathy: regional variance of retinal dysfunction

· Background: A study was carried out to evaluate the regional variance of retinal dysfunction in chloroquine retinopathy. · Methods: In three patients with different stages of chloroquine retinopathy, ophthalmologic evaluations including recording of full-field electroretinogram (ISCEV standard) and multifocal electroretinogram were performed. · Results: In one patient with mild chloroquine retinopathy the visual acuity, visual fields and full-field electroretinogram were normal, but retinal dysfunction was indicated by color vision disturbances. The second patient had moderate chloroquine retinopathy with normal visual acuity, visual fields and dark-adapted full-field electroretinogram; light-adapted and flicker full-field electroretinogram responses were, however, borderline and color vision was abnormal. The third patient had severe chloroquine retinopathy with reduced visual acuity, visual field and color vision defects, and a reduced full-field electroretinogram. In the multifocal electroretinogram, recorded with 61 hexagons, amplitudes and implicit times were evaluated in rings surrounding the center. In all three patients severe dysfunction (either amplitudes or implicit times) was found in the parafoveal and perifoveal areas. In the fovea and towards the periphery the function was normal or only moderately reduced. · Conclusion: Chloroquine retinopathy of different severity presents with characteristic alterations in the multifocal electroretinogram. Regional distribution of cone dysfunction is in agreement with previously reported histologic findings. The multifocal electroretinogram can detect retinal dysfunction in chloroquine retinopathy even when the full-field electroretinogram is normal and retinal alterations are subtle. Received: 1 September 1998 Revised version reveived: 1 February 1999 Accepted: 10 February 1999     

The pattern electroretinogram in diabetes

In 27 normal subjects and 64 insulin-dependent diabetic patients, we evaluated the pattern electroretinogram, which may reflect the neural activity of the spatially sensitive retinal ganglion cells. The amplitude of the pattern electroretinogram was reduced in diabetic patients who had no observable retinal changes. The amplitude was further reduced with increasing retinopathy. The pattern electroretinogram amplitude change was a more sensitive indicator of retinal change among the diabetic subpopulations than the statistically significant changes in latency. A significant correlation between pattern electroretinogram amplitude and the duration of diabetes were found in diabetic patients with either no observable retinopathy or minimal background retinopathy. The pattern electroretinogram may be useful as a quantitative, dependent variable to establish and monitor short-term metabolic and physiologic changes in diabetic patients.     

Use of the multifocal electroretinogram in the evaluation of a patient with central areolar choroidal dystrophy

PURPOSE: To assess the multifocal electroretinogram and full-field electroretinogram findings in a patient with advanced central areolar choroidal dystrophy.DESIGN: Observational case report. METHODS: A 53-year-old man with central areolar choroidal dystrophy underwent multifocal electroretinogram and full-field electroretinogram testing. RESULTS: The multifocal electroretinogram demonstrated relative preservation of foveal function compared with the severely depressed retinal function of the perifoveal macula corresponding to the location of the retinal and retinal pigment epithelium atrophy. The full-field electroretinogram was normal for both photopic and scotopic responses. CONCLUSION: Despite a normal full-field electroretinogram, the multifocal electroretinogram demonstrated significant macular dysfunction with relative preservation of foveal function in a patient with central areolar choroidal dystrophy.     

The multifocal electroretinogram in retinal detachment

We evaluated the retinal electrophysiologic function in both the detached and attached areas of eyes with retinal detachment, and assessed the functional recovery of these areas after surgery by quantifying the results, obtained from multifocal electroretinograms. Multifocal electroretinographic recordings and central 0°, to 30°, visual field tests were performed preoperatively and 2 weeks 1, 3 and 6 months postoperatively in 12 patients with unilateral retinal detachment. Each patient's response to the multifocal electroretinogram and the visual field test was classified into two groups: group A, the response from the attached area; and group B, that from the detached retinal area. Individual mean deviation and percentage mean deviation were calculated for each group. All retinal detachments were successfully reattached by the conventional scleral buckling method. The retinal sensitivity in the visual field test of all the patients in group B greatly improved. However, the percentage mean deviation in the response density of the multifocal electroretinogram in group B was −81% preoperatively and −63% at 6 months postoperatively. Thus, the improvement was confined within narrow limits. The response density of the multifocal electroretinogram in group A was very low, and never improved beyond −50% of percentage mean deviation. In the eyes with retinal detachment, electroretinogram response in both the attached and detached areas was more disturbed, than predicted by means of the visual field test during the course of this study.     

Electroretinogram contact lens electrode with tri-color light-emitting diode

PURPOSE: This study was performed to evaluate a new electroretinogram (ERG) contact lens electrode containing four light-emitting diodes (LEDs) that are used for both stimulus and background light. METHODS: The luminance of each LED could be changed independently and used as stimulus light. Red, blue, bright white, and flickering ERGs were recorded in 12 normal subjects and two patients with progressive cone dystrophy. The long-duration light stimuli separated the on- and off-responses of the ERG. This equipment is not according to the ISCEV standard. RESULTS: The tri-color LED electrode contact lens can efficiently produce and record ERG responses. Off-responses were recordable separately from on-responses by lengthening the stimulus duration. CONCLUSION: This combined stimulus-electrode system is compact and portable. Combined with the portable amplifier and the recorder, the ERGs can be recorded easily in an operating room, at patients' bedside, and in remote locations away from clinics and hospitals.     

Acute effects of sildenafil on the electroretinogram and multifocal electroretinogram

PURPOSE: To evaluate the acute effects of sildenafil (Viagra; Pfizer, Inc, New York, New York) on the electroretinogram and multifocal electroretinogram. METHODS: Eighteen healthy individuals (ages 21-49 years) were studied; 14 were given 200 mg sildenafil orally and four were given only water. All subjects were tested before sildenafil and 1 hour after sildenafil (or water) with a desaturated Panel D-15 color test, a full-field standard electroretinogram, and a multifocal electroretinogram using the VERIS system; five subjects were also tested 5 hours after sildenafil. RESULTS: Responses from the subjects who received sildenafil were compared with those from the control subjects. At 1 hour after sildenafil, photopic single-flash waveforms were attenuated by 9% and scotopic maximal response amplitudes were increased slightly. Photopic and 30-Hz flicker electroretinogram responses were delayed; multifocal electroretinogram waveforms were delayed (5%-9%) and attenuated (14%-22%) across the posterior pole. These changes did not resolve by 5 hours. Nine of the subjects who had received sildenafil (64%) reported visual or systemic symptoms, including one who reported bluish vision. Ten of those subjects (71%) showed a slight increase in color test errors 1 hour after sildenafil. CONCLUSIONS: For at least 5 hours after taking 200 mg of sildenafil, cone function was slightly depressed in the macula and periphery, as measured by full-field electroretinogram and multifocal electroretinogram recordings. However, the affected electroretinogram and multifocal electroretinogram parameters still remained within normal limits.     

The c-wave of the direct-current-recorded electroretinogram and the standing potential of the albino rabbit eye in response to repeated series of light stimuli of different intensities

In 10 experiments on five albino rabbits, the direct-current electroretinogram and the standing potential of the eye were recorded in response to repeated light stimuli (duration, 10 s; interval, 70 s), presented in four series, each consisting of 25 light flashes. Light intensities were, in order of presentation to the eyes, 3, 2, 1 and 0 log rel units (series I, II, III and IV, respectively) below the maximum output of the system. Thirty minutes of dark adaptation preceded each series. At the end of series I, the mean amplitudes of the b- and c-waves were higher and that of the a-wave relatively unchanged compared with the corresponding initial amplitudes. During series II–IV, there was a marked decrease in mean a- and b-wave amplitudes between the first and the following electroretinogram responses, and at the end of the three series, the amplitudes were still significantly reduced compared with the corresponding initial values. The mean c-wave amplitude was also markedly decreased immediately after the first electroretinogram recording, but it later recovered to a large extent. A peak in the c-wave amplitude was discerned about 14–18 minutes after the start of the recordings. A standing potential minimum during the second light stimulus was followed by a peak after about 10–13 minutes. The partially parallel behavior of the c-wave and the standing potential suggests the operation of a pigment epithelial mechanism behind the recovery of the c-wave amplitude. The final amplitudes of the b- and c-waves, and to a large extent also of the a-wave, were about the same irrespective of stimulus intensity. The adaptational processes in the rabbit appear to be more complicated than was previously thought. When electroretinogram amplitudes and standing potential levels are discussed and when one experiment is compared with another one, it is important that adaptational and stimulus conditions, as well as time course, are well controlled and clearly specified.     

Cone dystrophies with negative photopic electroretinogram.

A scotopic electroretinogram with an a-wave amplitude larger than the b-wave amplitude traditionally is termed 'negative'. Six male patients with negative photopic electroretinograms were examined; three of them suffered from progressive cone dystrophy, in which negative electroretinograms are unusual. Another patient without symptoms was the brother of a patient with cone dystrophy. These patients are compared with others who characteristically have negative electroretinograms-one patient with incomplete congenital stationary night blindness and another with X linked congenital retinoschisis. Differential diagnosis between these unusual cases of cone dystrophies and X linked retinoschisis or congenital stationary night blindness was possible with funduscopy, adaptometry, and evaluation of progression, but not with the electroretinogram. Inner retinal defects may occur in cone dystrophies as indicated by the negative electroretinogram. The waveform variations between our patients may be due to different inner retinal defects. The findings in two brothers indicate that cone dystrophy and inner retinal defects may be inherited separately.     

Pattern electroretinogram and visual evoked potential amplitudes are influenced by different stimulus field sizes and scotomata

The pattern electroretinogram and the visual evoked potential were recorded simultaneously with various stimulus fields and artificial scotomata of increasing sizes. In contrast to an earlier study, a smaller check size (20) and two stimulus field sizes (20° × 20° and 10° × 10°) for the scotomata were used. With a concentric decreasing stimulus field, a reduction of both the pattern electroretinogram and visual evoked potential was found. Both showed a simultaneous reduction of amplitudes, but, compared with the amplitude in the full field, the reduction was more extensive for the pattern electroretinogram at each test field size. This implies a greater contribution to the pattern electroretinogram from more eccentric retinal parts. An artificial central scotoma of increasing size in the 20° × 20° field had less influence on the pattern electroretinogram than on the visual evoked potential. The percentage amplitude loss of the visual evoked potential was more pronounced. The visual evoked potential was eventually abolished by a scotoma size from 10° × 10° upward, while the pattern electroretinogram was still registrable. When scotomata of similar size were introduced in a smaller (10° × 10°) field, percentage pattern electroretinogram and visual evoked potential amplitude losses were less separated than in a larger (20° × 20°) test field.     

Screening for mouse retinal degenerations

Mice with hereditary retinal degeneration have provided excellent models for human disease of the biochemical and physiological events occuring in retinal degeneration. Since a number of mouse models are available for other human conditions, more mouse retinal degenerations would be expected to be known; however, finding new models has proved difficult since the search has usually involved laborious histologic screening.We applied the clinical technique of indirect ophthalmoscopy to screen mice for retinal degeneration and then used electroretinography and histology to determine whether true retinal degeneration was present.A Dawson-Trick-Litzkow microfiber corneal electrode was used to record the electroretinogram since the fiber does not occlude the pupil in these small eyes. Normal control values were developed. As an example of the success of the technique, one strain, lethal spot (ls) on indirect ophthalmoscopy appeared to have a retinal degeneration, but these mice had a normal electroretinogram indicating a primary optic atrophy. Likewise, one ls heterozygote that was tested as a control animal and was not suspected of having a retinal degeneration had an abnormal electroretinogram and peripheral retinal degeneration.     

Temperature effects on the electroretinogram of the isolated carp retina

The electroretinogram was recorded from the isolated retina of the carp while the temperature was varied systematically and while the preparation was under the influence of various pharmacological agents. In addition to the a-wave and the b-wave, the electroretinogram gave evidence of early and late oscillatory potentials. The procedures selectively modified the prominence of these and other less conspicuous components. A particularly significant finding was that some oscillatory potentials are largest at intermediate temperatures, but that they persist to very low ones. It is suggested that temperature control, variation of stimulus intensity, and the application of pharmacological agents may be combined to provide a useful method of separating retinal response components.     

Multifocal electroretinogram in multiple evanescent white dot syndrome

Electrophysiologic findings including multifocal electroretinogram and visual evoked cortical potentials were studied in a patient with multiple evanescent white dot syndrome. A 19-year-old woman was diagnosed as having multiple evanescent white dot syndrome because of decreased visual acuity, white dots on fundus examination and hyperfluorescence of the white dots in the right eye. The amplitude of the flicker electroretinogramwas reduced, but the single-flash electroretinogram was within the normal range. The P100 latency of the pattern visual evoked cortical potentials was slightly prolonged. The amplitudes of multifocal electroretinogram were, markedly reduced in the area corresponding to the scotoma and moderately reduced in other regions of the central field in the affected eye. The results suggest that the retinal dysfunction area is wider than that detected by subjective methods or conventional electrophysiological examinations. The delayed recovery of the visual evoked cortical potential latency suggests the involvement of the optic nerve in multiple evanescent white dot syndrome.