Visual evoked potentials in macular hole

Pattern reversal visual evoked potentials (VEPs) with checks of 50 and 12 were recorded in 15 patients with idiopathic unilateral macular hole. VEPs from the affected eyes were reduced in amplitude compared with those from the fellow eyes, especially with checks of 12 (percentage of the amplitude in the affected eye to that in the fellow eye was 86% ± 19% with checks of 50 and 61% ± 35% with checks of 12). The latencies showed no statistically significant difference between the affected and the fellow eyes, although a marked interocular delay was found in a few patients. The degree of amplitude reduction and interocular delay had no relation to the size of the macular hole or visual acuity. The effects of experimental scotomata of various sizes on the VEPs, which were evaluated in nine normal subjects, were also variable among the subjects. We conclude that although the macula predominantly participates in the pattern VEP, an estimation of the extent of macular pathology from the VEP changes may be difficult because the VEP changes induced by a macular hole have wide individual variation and have no relation to the size of the hole.     

A study of the effects of contrast change on pattern VEPs, and the transition between onset, reversal and offset modes of stimulation

We studied the relationship between the visual evoked potential (VEP) components by tracing the transition from onset/offset mode of stimulation to the reversal mode by a series of contrast change steps. VEPs on the ipsilateral and contralateral side of the scalp with respect to the left half-field checkerboard stimulus (checksizes: 12, 50 and 80) were recorded in 15 subjects. Eight contrast steps for each checksize were recorded. Each test step consisted of the alternation of a constant high contrast checkerboard (A), with a second checkerboard (B) in which the contrast was changed. Checkerboard B was initially of identical spatial phase to A, but contrast was reduced systematically until B was a uniform grey field (i.e. onset/offset). In subsequent steps checkerboard B was of opposite spatial phase and contrast was increased until the final step when B was of equal high contrast (i.e. full reversal). All ipsilateral and contralateral onset components, ipsilateral offset components, and the reversal P100 component significantly enlarged with increasing contrast. The extent of amplitude change with contrast was greatest for offset, followed by onset and then reversal. A clear association could be discerned between all offset and reversal components. Onset CI and CII appeared to be related to the reversal P100 and N145, respectively. When small 12 checks were used, onset Co appeared to have common features with the reversal N80. The contralateral onset P105 component did not have a comparable component in the reversal mode.     

Visual evoked potentials to flash and pattern reversal stimulation after administration of systemic or topical scopolamine

It has previously been shown that 0.6 mg of scopolamine produces a delay in the flash visual evoked potential of young normal volunteers, while the pattern-reversal response does not change in latency. Recent work has shown that this drug differentially affects parvocellular and magnocellular systems. To investigate this effect, two studies were performed. In the first study, 0.4 mg of scopolamine was injected intramuscularly into 11 young, healthy male volunteers who had fasted overnight. The visual evoked potential was recorded to both binocular flash stimulation and monocular pattern-reversal stimulation by means of a checkerboard consisting of 56 checks in a 28° field. Responses were recorded before administration of the drug and then 1, 2, 4 and 6 hours after administration. The scopolamine produced a slowing of the flash P2 latency of approximately 6 ms (p < 0.05) two hours after drug administration. There was no effect on the latency of the flash N2 or pattern-reversal N75 or P100. There was an increase in amplitude of the flash N2-P2 component 6 hours after drug administration and an increase in the amplitude of the N75 and P100 2, 4 and 6 hours after the drug. Further subjects were investigated with the use of topical administration of 0.125% scopolamine applied monocularly. In all studies the other eye acted as a control. The subjects were again young healthy volunteers. The visual evoked potential was recorded to both flash and pattern-reversal stimulation with a checkerboard consisting of 60 checks counterphasing at 2 Hz within a 5° field. Results suggest that systemic scopolamine affects the tectal pathway but has no peripheral effect.     

Influence of simultaneous pattern-reversal electroretinogram recording on visual evoked potentials

Little is known about the influence of the presence of a gold-foil electrode on pattern-reversal visual evoked potential recording, although simultaneous pattern-reversal electroretinography has been applied in several clinical investigations. We compared the results of pattern-reversal visual evoked potentials simultaneously recorded with pattern-reversal electroretinograms with those obtained during separate pattern-reversal visual evoked potential recording in 10 normal subjects. Transient response (reversal rate, 1 Hz; check size, 30) and steady-state response (reversal rate, 5 Hz; check size, 120, 60, 30, 15 and 7.5) were analyzed under the stimulus contrast condition of 90%. Neither P100 latency in transient responses nor amplitudes in steady-state responses exhibited significant change at any check size when they were recorded separately or simultaneously with pattern-reversal electroretinograms. The results suggest that the gold-foil electrode exerts no significant influence on pattern-reversal visual evoked potentials. Simultaneous pattern-reversal electroretinogram and visual evoked potential recording is therefore confirmed to be a clinically useful method. This procedure makes the synchronous recording of both responses possible under the identical stimulus conditions.     

The effect of motion on pattern-onset visual evoked potentials in adults and children

Visual evoked potentials can be elicited by a variety of visual stimuli, including pattern-onset and motion-onset. It may be desirable to combine pattern-onset with motion-onset stimuli, for example, to make a direct comparison between optokinetic nystagmus and visual evoked potential acuity thresholds. Both procedures employ grating stimuli; however, the gratings must be moving to produce optokinetic nystagmus. We compared pattern-onset visual evoked potentials with both a static and a moving pattern to investigate the effect of motion on the pattern-onset visual evoked potential waveform. Visual evoked potential recordings were made from 10 adults (aged 20–37 years) and 10 children (aged 5–7 years) with the active electrode at O_z. Stimuli consisted of onset of high-contrast vertical bars of three sizes (12, 30 and 60) both with and without motion (3 cycles/s). In a subgroup of subjects, visual evoked potentials were recorded to motion onset of constantly present gratings. Motion of the pattern had no significant effect on any of the latency components of the visual evoked potential waveform in adults or children. The amplitude of the C2–C3 component was significantly increased (p < 0.001) in adults. The motion appears to add a late negative component to the visual evoked potential similar to that produced by the motion-only stimulus. The latency of the early components of the pattern-onset visual evoked potential was unaffected by the presence of motion. Therefore, pattern-onset visual evoked potentials with moving gratings could be used to estimate visual acuity, and direct comparisons could be made between visual evoked potential and optokinetic nystagmus acuity thresholds with the use of the same stimulus parameters.Abbreviations ANOVA analysis of variance - OKN optokinetic nystagmus - ON-M onset with motion - ON onset without motion     

Effect of stimulus check size on multifocal visual evoked potentials

In this study we examined the effects of varying stimulus check size on multifocal visual evoked potential (VEP). We also evaluated the currently used cortical scaling of stimulus segments. The ObjectiVision^TM multifocal objective perimeter stimulates the eye with random check patterns at 56 cortically scaled segments within the visual field extending to a radius of 26°. All cortically scaled segments have equal number of checks, which gradually increase in size from the center to the periphery, proportional to the size of the segment. Stimuli with 9, 16, 25, 36 and 49 checks/segment were tested on 10 eyes belonging to 10 normal subjects. The check size varied inversely with number of checks per segment. VEP was recorded using bipolar occipital cross electrodes (7min/eye), the amplitude and latency of responses obtained were compared with the check size at different eccentricities. Our findings suggest that the existing setting with 16 checks/segment subtending 26 to 140 from center to periphery, is the most effective amongst all the check sizes. Decreasing the check size prolongs the latency in the central field only. Cortical scaling of segments generates responses of the same order of magnitude throughout the field, but could be improved slightly to enhance the signal from the outer two rings.     

Effect of α2-macroglobulin on retinal glial cell proliferation

Background Activation of the receptor for 2-macroglobulin (2M), the low-density lipoprotein-related protein (LRP1; CD91), has been suggested to represent a possible strategy for the inhibition of uncontrolled retinal cell proliferation via stimulation of the clearance of 2M-bound growth factors and proteinases from the extracellular space. In order to prove this assumption, we investigated the effect of 2M on the proliferation of Müller glial cells in vitro.Methods Proliferation assays using bromodeoxyuridine were carried out on cultured Müller glial cells of the guinea pig in the absence and presence of 2M.Results Activated 2M evoked a slight increase of the cell proliferation at control conditions. Addition of 2M to the culture medium inhibited the proliferation evoked by agonists of G-protein-coupled receptors [adenosine 5-triphosphate (ATP), neuropeptide Y]. However, 2M did not diminish the proliferation evoked by agonists of receptor tyrosine kinases (epidermal and platelet-derived growth factors) and by serum, respectively. Inhibition of LRP1 by a neutralizing antibody did not alter the ATP-evoked proliferation while it increased the proliferation in the presence of 2M.Conclusion It is concluded that 2M inhibits the proliferation evoked by agonists of G-protein-coupled receptors, possibly via enhanced growth factor clearance by LRP.     

Evoked responses in patients with macular holes

Thirty-two eyes with idiopathic macular holes and one eye with a traumatic macular hole were assessed by pattern-reversal electroretinography, ganzfeld electroretinography and pattern-reversal visual evoked potentials. Results were inspected for qualitative abnormalities and then measured in comparison with fellow eyes and 41 control eyes of similar age. Qualitative abnormalities occurred in some eyes with macular holes, most commonly a reduction in pattern-reversal electroretinogram or pattern-reversal visual evoked potential amplitude; 15 check amplitudes were significantly lower in eyes with macular holes than in control eyes, but no significant difference in latency was found. Control pattern-reversal electroretinogram and pattern-reversal visual evoked potential amplitudes were noted to decline with age, and paired t-tests on an age-matched subgroup of eyes with macular holes and control eyes showed appreciable differences only in the pattern-reversal electroretinogram q-r (N95) amplitude.     

Steady-state visual evoked cortical potentials from stimulation of visual field quadrants

The effects of check size and stimulus size were investigated to optimize the steady-state visual evoked cortical potentials from pattern-reversal stimulation of the visual field quadrants. Check sizes of 15, 30, 60, 90, 120 and 180 were investigated at a pattern reversal rate of 11.6 per second for field sizes varying from 2° × 2° to 24° × 24°. The visual evoked cortical potentials were recorded from mid occipital, right occipital and left occipital positions. In the inferonasal quadrant, the largest amplitudes were obtained with 30 and 60 check sizes; however, for these check sizes, the visual evoked cortical potential yielded limited additional information for field sizes greater than 4° × 4° and 6° × 6°, respectively. When a field size of 12° × 12° was investigated, a 90 check size was optimal. The results indicated hat, with the above recording positions and check sizes of 15 to 120, there is an optimal number of pattern elements, 40 to 100, for stimulation of the inferonasal quadrant. This should be taken into account when a check size is selected to investigate a field quadrant of a particular size. Digital signal processing techniques were applied to analyze the visual evoked cortical potential, and the system shows promise for objective examination of the visual field.     

The effect of contrast reduction on pattern-reversal VEPs in suspected multiple sclerosis and optic neuritis

A retrospective study was conducted to investigate whether the use of low-contrast stimuli in addition to the standard high-contrast stimuli would increase the sensitivity of the pattern-reversal P100 when testing for multiple sclerosis (MS) and optic neuritis (ON). We found that there was a statistically significant increase in the number of abnormal results when using 25 checks, but not for 50 checks. Examination of patient records showed that VEP abnormalities to low-contrast stimuli only was not prognostic for subsequent development of multiple sclerosis.     

The topographic distribution of the magnetic P100M to full- and half-field stimulation

Visual evoked magnetic responses were recorded to full-field and left and right half-field stimulation with three check sizes (70, 34 and 22) in five normal subjects. Recordings were made sequentially on a 20-position grid (4 × 5) based on the inion, by means of a single-channel direct current-Superconducting Quantum Interference Device second-order gradiometer. The topographic maps were consistent on the same subjects recorded 2 months apart. The half-field responses produced the strongest signals in the contralateral hemisphere and were consistent with the cruciform model of the calcarine fissure. Right half fields produced upper-left-quadrant outgoing fields and lower-left-quadrant ingoing fields, while the left half field produced the opposite response. The topographic maps also varied with check size, with the larger checks producing positive or negative maximum position more anteriorly than small checks. In addition, with large checks the full-field responses could be explained as the summation of the two half fields, whereas full-field responses to smaller checks were more unpredictable and may be due to sources located at the occipital pole or lateral surface. In addition, dipole sources were located as appropriate with the use of inverse problem solutions. Topographic data will be vital to the clinical use of the visual evoked field but, in addition, provides complementary information to visual evoked potentials, allowing detailed studies of the visual cortex.     

Dynamic topography of pattern visual evoked potentials (PVEP) in psychogenic visual loss patients

We investigated to measure the objective visual acuity using pattern visual evoked potentials (PVEP) to help the diagnosis with psychogenic visual loss (PVL) who ranged in age from 7 to 14 years old. Pattern stimuli consisted of black and white checkerboard patterns (39, 26, 15 and 9) with a visual angle of 8 degrees and a contrast level of 15%. The pattern reversal frequency was 0.7 Hz. This resulted in an average of 100 PVEP per session. Visual acuity of 0.1 was consistent with the 39 pattern, 0.2 with the 26 pattern, 0.5 with the 15 pattern, and 1.0 with the 9 pattern. As the results, five PVL patients could measure visual acuity with this method in the present study. The PVEP is useful in evaluating the visual acuity and helped to diagnose the PVL patients. In addition we used the dynamic topography to study the difference in the results of the PVEP. The dynamic topography obtained from the results of the PVEP was analyzed. The flow type of the P100 component diverged into three types (separated type, hollow type and localized type) in the PVL patients and the normal children. The localized type was observed in 59.1% of normal children and in 56.3% of PVL patients. While the separated type was shown in 6.8% of normal children and in 8.3% of PVL patients. There were not significant differences between the PVL patients and the normal children in each type.     

Late components of lambda responses in cognitive tasks

The effects of stimulus probability were investigated on the late components of saccade-related brain potentials (lambda responses) in two paradigms, counting and guessing. Subjects performed saccadic eye movements from a middle light to the target area where one of three kinds of target light stimuli appeared in a randomized sequence, each with a different probability (0.17, 0.33, and 0.50). Brain activity was recorded from six scalp areas. In the counting task subjects were instructed to count the prespecified low-probability stimuli. In the guessing experiment they had to make a guess before each trial as to which kind of target stimulus would appear. In both experiments the late positive components showed significantly greater amplitude in the lambda responses associated with infrequent stimuli than in those elicited by frequent stimuli. Principal component-Varimax analysis of the lambda responses revealed factors corresponding to the P300 and the slow wave components of traditional evoked potential studies.     

Electrophysiological evidence that early glaucoma affects foveal vision

The pattern electroretinogram (PERG) and visual evoked potential (PVEP) were recorded simultaneously using a 1.1 cpd pattern which was counterphase modulated at 1 Hz. The responses of ocular hypertensive (OHT) eyes (with normal visual fields) and eyes with early glaucoma (with early visual field defects and/or early cupping of the optic nervehead) were compared to age-matched normal observers. All patients (26 eyes) and normal observers (14 eyes) had normal transient flash electroretinograms. Delays were seen in mean PERG latency in both OHT and early glaucoma eyes, while mean PERG amplitude was significantly reduced only in the early glaucoma eyes. The PVEP responses were unmeasurable in 11/26 patient eyes because the waveforms were grossly abnormal in shape, making it impossible to identify the N- and P-components. The data were categorized in this manner: a patient response was considered abnormal if latency or amplitude exceeded normal limits (PERG or PVEP) or if the waveform was unmeasurable due to its shape (PVEP only). Of the 26 patient eyes, we found that 8 eyes had normal PERG and PVEP, 11 eyes had abnormal PERG and PVEP, one eye had an abnormal PERG and a normal PVEP, and 6 eyes (3 patients) had a normal PERG and an abnormal PVEP. These data support the proposition that foveal vision (as assessed by the PVEP) may be affected by early glaucomatous damage. The relationship between the PERG and PVEP also was evaluated using a new measurement which we call the latency window. Using this measurement, 15/26 patient eyes were abnormal - 9 of these had unmeasurable PVEPs. This measurement could be useful in classifying W-shaped PVEPs as normal or abnormal.This study was supported in part by Grants EY01708 and EY01867 from the National Eye Institute, Bethesda, MD, by Fight For Sight Grant-in-Aid G-274, and by an unrestricted grant from Research to Prevent Blindness, Inc., New York, NY.     

The pattern visual evoked potential

The peak latency of the pattern-reversal visual evoked potential is a sensitive measure of conduction delay in the optic nerve caused by demyelination. Despite its clinical utility, the pattern-reversal visual evoked potential has not previously been used in multicenter clinical trials, presumably because of difficulty in standardizing conditions between centers. To establish whether the pattern-reversal visual evoked potential could be adequately standardized for use as a measure in multicenter therapeutic trials for optic neuropathy or multiple sclerosis, stimulus and recording variables were equated at four centers and pattern-reversal visual evoked potentials were recorded from 64 normal subjects and 15 patients with resolved optic neuritis. Results showed equivalent latency and amplitude data from all centers, suggesting that stimulus and recording variables can be satisfactorily standardized for multicenter clinical trials. N70 and P100 peak latencies and N70-P100 interocular amplitude difference were sensitive measures of resolved optic neuritis.Abbreviations ANOVA analysis of variance - ON optic neuritis     

Pattern VEP is a useful technique in monitoring the effectiveness of occlusion therapy in amblyopic eyes under occlusion therapy

Purpose To evaluate the effectiveness and clinical significance of pattern visual evoked potential (P-VEP) parameters on visual acuity in amblyopic patients under occlusion therapy.Methods A total of 34 consecutive children with anisometropic amblyopia were included in this study. All patients underwent a full initial ophthalmologic and orthoptic evaluation. P-VEP test was performed in all cases and binocular vision was tested and recorded with Worths four-dot test and Bagolini striated glasses at each visit. Part-time occlusion therapy was performed by using adhesive patches.Results The mean (±SEM) cycloplegic refractive error was +5.6± 0.6 diopters (D) in the amblyopic eyes and +1.8±0.2 D in the normal eye. The mean levels of best-corrected visual acuity were statistically differed between each measurement for occlusion therapy (for each, p<0.05). The ratio of the patients with binocular vision increased after 6months occlusion therapy and the difference was statistically significant (p<0.05). In addition, P100 amplitude improved at each visit and the difference was significant when compared with baseline values (for each,p<0.05).Conclusions P100 amplitude of the P-VEP test parallels the improvement in subjective visual acuity in amblyopic eyes under occlusion therapy. Therefore, this test may be useful in monitoring the visual acuity in the preverbal or non-verbal patched patients.     

Distortion of spatial selectivity by pattern onset stimulation

Spatial selectivity of pattern evoked potentials has been thought to provide evidence of lateral inhibition. However, spatial tuning functions may be distorted by pattern onset stimulation that is applied repeatedly to the same area of retina so an after-image is formed. This only applies at low spatial frequencies because of the randomizing effects of eye movements. Low-frequency attenuation may therefore be exaggerated. Pattern reversal stimulation has the opposite effect and this is reflected in the literature by fewer reports of bandpass functions. A new method has therefore been devised to provide the true spatial response function. The spatial phase is reversed after every two consecutive presentations. By combining this paradigm with a correction for the optical transfer function of the eye, the true neural response function is obtained.Ten subjects participated in this study to evaluate the distortion of spatial selectivity in the pattern electroretinogram. The new stimulus paradigm reduced the low spatial frequency attenuation to a barely significant level giving an almost flat amplitude response for the + ve and - ve transients of the pattern electroretinogram for check sizes from 222 to 7 angular subtense. However, correction for optical degradation produces bandpass curves, which closely correspond to those predicted from recent data on receptive fields of primate retinal ganglion cells.     

Determining abnormal interocular latencies of multifocal visual evoked potentials

Purpose: To describe methods for measuring interocular latency differences of multifocal visual evoked potentials (mfVEP) and for determining regions with abnormal interocular latencies in patients. Methods: The mfVEPs from 100 individuals with normal visual fields and normal fundus examinations were analyzed. Individuals ranged in age from 21.6 to 92.4 years. The stimulus was a 60 sector, pattern-reversing dartboard display. Each sector had 16 checks, 8 white (200 cd/m²) and 8 black (<1 cd/m²). Interocular latency was measured as the temporal shift producing the best cross-correlation value between the corresponding responses of each eye. The corrected interocular latency was defined as the difference between this shift and the mean interocular latency (shift) for a particular sector and recording channel. Results: The variability of the corrected interocular latency decreased as the signal-to-noise ratio (SNR) of the mfVEP responses increased. For example, the 95% confidence intervals decreased from over 16 ms to under 4 ms as SNR increased. Grouping and summing the responses also lead to an increase in SNR and a decrease in the confidence interval. The results of various cluster criteria were also derived. A cluster criterion (e.g. two or more contiguous points within a hemisphere exceeding a given confidence interval), can serve to increase the specificity for detection of eyes or individuals with abnormal interocular latencies. For example, while 21% of the eyes had 3 or more points exceeding the 5% confidence interval, only 1.8% of the eyes had a cluster of 3 or more of these points. Finally, interocular latency was only weakly correlated with age (r=0.26). Conclusion: In testing for abnormalities in interocular latencies, the confidence interval should be based upon the SNR of the response. Grouping and summing responses to increase SNR or employing a cluster test may also prove useful.     

Neural conduction in the visual pathways in ocular hypertension and glaucoma

Background: The aim of our work was to evaluate neural conduction in visual pathways in subjects with ocular hypertension and glaucoma. Methods: We assessed simultaneous recordings of pattern electroretinograms (PERG) and visual evoked potentials (VEP) in 16 subjects with ocular hypertension (OHT), in 16 subjects with primary open-angle glaucoma (POAG) and in 15 age-matched controls. The visual stimuli were checkerboard patterns (the check edges subtend 15 min of visual arc; contrast 70%) reversed at the rate of 2 reversals/s. Results: In OHT and POAG patients we found PERG and VEP latencies signficantly longer than in controls. The P50-N95 PERG amplitudes were significantly reduced in OHT and POAG eyes. VEP amplitudes were significantly reduced in POAG eyes, while in OHT they were similar to controls. The retinocortical time (RCT; difference between VEP P100 latency and PERG P50 latency) was longer in POAG patients than in controls; no differences between patients with OHT and controls were observed. Moreover, we observed that in POAG the longer RCT was inversely related to the PERG amplitude. Conclusion: Our results suggest that involvement of the innermost retinal layers in POAG is accompanied by slowed neural conduction in the visual pathways.Presented in part at the Annual Meeting of the Association for Research in Vision and Ophthalmology, Fort Lauderdale, Florida, May 1995     

Visual evoked cortical potential can be used to differentiate between uncorrected refractive error and macular disorders

The visual evoked cortical potential (VECP) is widely used to verify complaints of reduced visual performance and to identify the site of the disorder. In this study, we investigated the correlation between reduced visual acuity and VECP in volunteers with normal corrected visual acuity and in patients suffering from inherited macular degeneration or from age related macular degeneration (ARMD). Flash evoked VECP was not affected by the visual acuity in the cases of refractive error and in ARMD patients but was reduced in amplitude and delayed in implicit time in the patients suffering from inherited macular degeneration. The VECP elicited by pattern reversal checkerboard (PVECP) was not affected by the quality of the visual image in volunteers with uncorrected refractive error when checks of 60 or larger were used but were considerably reduced in size and prolonged in implicit time for checks smaller than 15. In both groups of patients suffering from macular dysfunction, pattern reversal VECP was very subnormal and was characterized by prolonged implicit time compared to values expected from their visual acuity. These findings indicate that the PVECP does not directly correlate with visual acuity but rather with foveal function. Therefore, we suggest that recordings of PVECP can be used to differentiate between refractive error and macular disorders as causing reduction in visual acuity when other clinical signs are missing or not available.