mfERG Amplitudes Research Articles

A comparison of pattern and multifocal electroretinography in the evaluation of age-related macular degeneration and its treatment with photodynamic therapy

This study compares pattern electroretinography (PERG) and multifocal electroretinography (mfERG) measures in 13 patients with predominantly classic choroidal neovascularisation (CNV) associated with age-related macular degeneration (ARMD, 9/13 unilateral, 4/13 bilateral), assesses the usefulness of each test in monitoring disease progression, and identifies electrophysiological predictors of outcome following treatment with photodynamic therapy (PDT). PERG and mfERGs were recorded at presentation, 2 weeks post-treatment, and at 3 monthly intervals for 2 years. The PERG was detectable in 8/13 patients with unilateral disease; the mfERG was detectable in 12/13 patients. P50 and N95 amplitudes increased in 6/8 patients and mfERG p1 increased in 7/13 patients at 2 years. PERG amplitudes correlated strongly with mfERG amplitudes in patients with unilateral disease. PERG P50 and mfERG p1 amplitude correlated with visual acuity at 2 years (R = 0.68, R = 0.82, respectively). The largest PERG P50 and mfERG p1 amplitude difference between treated and fellow eyes of all the groups on initial visit was associated with a poor visual outcome (P50 64% difference; p1 29% difference) whereas those with the smallest P50 and p1 amplitude difference was associated with improved vision at 2 years (P50 30% difference; p1 21% difference). The PERG and mfERG provide an objective measure of central retinal function in the progression of ARMD. A detectable PERG on presentation was the single best indicator of improved function and visual acuity at 2 years. The mfERG demonstrated disease progression from central retina into the paramacular regions over 2 years. Patients with poor visual outcomes had the largest inter-ocular amplitude difference on presentation, suggesting that such patients may have a worse prognosis following treatment.

Effects of unsteady fixation on multifocal electroretinogram (mfERG)

To investigate the effect of unsteady fixation on the multifocal electroretinogram (mfERG) measurement in normal subjects. The mfERGs of 20 subjects with normal vision (mean age=23.5 years) were recorded with different levels of voluntary eye movements made to mimic unsteady fixation. Subjects were required to move their fixation regularly every 2 s between the center and the ends of a fixation cross, so that 51.2% of the time fixation was at the center and 12.2% of the time it was at each end of the fixation cross. Four different conditions were performed: central fixation (without voluntary eye movements) and with 2 degrees, 4 degrees and 6 degrees magnitude of unsteady fixation. First-order kernel mfERG findings are presented. Analysis of the ring responses indicated that the central mfERG amplitude was most affected by unsteady fixation. There was significantly reduced amplitude for 4 degrees unsteady fixation and as expected, this reduction became larger with 6 degrees unstable fixation. However, there was no significant effect on the center hexagon amplitude for 2 degrees unsteady fixation. The amplitudes of the ring-2 responses were only affected in the 6 degrees unsteady fixation condition. No significant change in implicit time was found for any level of unsteady fixation. These results suggest that mfERG amplitude is not substantially affected if fixation is maintained within the central stimulus hexagon. We conclude that, for patients with poor fixation, the accuracy of mfERG results may be difficult to interpret and the use of a fixation-monitoring system is desirable for ideal measurement. The depth of depression at the blind spot area may be another useful parameter to interpret the accuracy of mfERG results in patients with poor fixation.

Multifocal Electroretinogram in Adults and Children With Myopia

To determine the correlation between multifocal electroretinogram (mfERG) parameters and the severity of myopia in adults and children. Observational study. Multifocal electroretinograms were recorded using the VERIS system from randomly selected eyes of 104 children and 31 adults with various degrees of myopia. Dawson, Trick, and Litzkow fiber electrodes were used and the pupil was dilated with 1% tropicamide. Subjective refraction was performed under cycloplegia and axial length measurement was determined by A-scan ultrasonography. The N1 (first negative trough), P1 (first positive peak), and N2 (second negative trough) components of the first-order kernel response of the mfERG were measured and correlated with the refractive data. First-order kernel mfERG responses. The N1, P1, and N2 amplitudes were significantly correlated with the severity of myopia in adult subjects (N1, r = 0.591, P = .001; P1, r = 0.682, P<.001; N2, r = 0.732, P<.001). The response amplitudes of N1, P1, and N2 decreased as the dioptric power of myopia increased. However, there were no significant correlations found between N1 (r = 0.073, P = .30), P1 (r = 0.071, P = .31), and N2 (r = 0.052, P = .46) amplitudes and the severity of myopia in children. The severity of myopia was also significantly correlated with N1 (r = -0.750, P<.001), P1 (r = -0.769, P<.001), and N2 (r = -0.664, P<.001) implicit times in adults with myopia, however, only the P1 (r = -0.166, P = .02) implicit time was significantly correlated with children with myopia. There is a significant correlation between the refractive error and mfERG amplitude in adults with myopia; however, such a relationship is absent in children with myopia. These findings suggest that the severity of myopia has little influence on the ERG amplitude, at least in children.

Ocular Changes after Photodynamic Therapy

The aim of this study was to identify the changes in the primate visual system after a single session of photodynamic therapy (PDT) in an intact nonhuman primate retina. As part of a larger study, PDT (wavelength 689 nm, 50 J/cm2, 600 mW/cm2, 83 seconds, 4-mm spot size) with verteporfin (6 mg/m2 intravenous infusion) was performed in one eye each of two cynomolgus monkeys. Fundus photography, fluorescein angiography (FA), indocyanine green angiography (ICG), optical coherence tomography (OCT), and multifocal electroretinography (mfERG) were performed at baseline and 12 time points (1-283 days) after PDT. In addition, retinal histopathologic findings were evaluated at 9 months. Various morphologic changes, including whitening of the treated area, RPE proliferation, closure of the choroidal vasculature, and subretinal edema (followed by foveolar thinning) were observed. Most of the changes persisted and were detectable in histopathologic evaluation at 9 months. Reductions of the mfERG amplitude, followed by varying degrees of recovery from the treated and the border regions, were observed. This was accompanied by progressive delay of P1 peak time up to 3 months after treatment, followed by complete recovery at 9 months. In addition, the nontreated area showed amplitude and timing mfERG deficits, which underwent gradual (but not complete) recovery. In a primate model, under standard clinical parameters, a single PDT treatment resulted in various dynamic morphologic and functional retinal changes detectable for up to 9 months after treatment. The significance of the observed changes and possible ways of pharmacologic interference with PDT adverse effects are discussed.

Multifocal visual evoked potentials to cone specific stimuli in patients with retinitis pigmentosa

Our aim was to determine whether patients with retinitis pigmentosa show differences in L- and M-cone multifocal visual evoked potential (mfVEP) responses that are eccentricity dependent, as has been shown for control subjects. Second, we compared the losses for mfVEPs to losses on achromatic visual field and multifocal electroretinogram (mfERG) measures in the patients. Monocular mfVEPs were recorded to a pattern reversing display that modulated only the L- or M-cones. Also, standard automated achromatic visual fields and mfERGs were obtained. For the control subjects, the ratio of L-cone to M-cone mfVEP amplitudes increased as a function of retinal eccentricity. For the patients, the ratio did not vary with eccentricity. For all measures, responses were least affected for the first ring (central 2.4°) and most affected for the third ring (11.6°–44.4°). For the first ring, mfERG amplitudes were more impaired than were the mfVEPs or the visual field thresholds. For most of the patients, there was local response correspondence among our measures of visual function.

Visual function in Vogt-Koyanagi-Harada patients

Vogt-Koyanagi-Harada (VKH) disease presents with anterior segment inflammation, choroiditis and exudative retinal detachment. Following resolution of the inflammation, VKH patients have been noted to complain of visual disturbances despite good visual acuity. We therefore investigated the visual function deficits of convalescent VKH patients. A cross-sectional observational nonrandomized controlled study of convalescent VKH patients from the Uveitis Service of the Singapore National Eye Centre, and normal subjects was performed. The best-corrected visual acuities (BCVA) and multifocal electroretinograms (mfERGs) of VKH patients with and without peripapillary atrophy (PPA) were compared with those of the normal eyes. The mfERG results were subdivided into those obtained from the peripapillary area and those from the rest of the macular. Eleven VKH eyes with large PPA to disc ratios (PPA/D ratio >2), 15 VKH eyes with PPA/D ratios<1 and 6 normal eyes were included in the study. Five eyes (54.5%) of VKH patients with PPA/D>2 had a BCVA of less than 20/40. All the other eyes had 20/20 vision. Nine of the 11 VKH eyes with PPA/D>2 also had large areas of chorioretinal atrophy. The mfERG responses of VKH eyes with PPA/D ratio >2 were markedly reduced in amplitude (p<0.001) and delayed in implicit time (p<0.001) throughout the entire macular area. VKH patients with PPA/D ratio<1 had significantly reduced mfERG amplitudes throughout the entire macular area, as well as delayed implicit times at the peripapillary region (p=0.026). Sub-division of VKH eyes with PPA/D<1 into eyes with no PPA and eyes with a small PPA, showed that both groups had a similar reduction in response amplitude over the entire macular region. However, the implicit time was significantly delayed in eyes with small PPA when compared to those without PPA (p<0.03). VKH patients with large PPA have clinically significant visual dysfunction. VKH patients without PPA also have subclinical retinal dysfunction. The mfERG may be a useful adjunct in the management of VKH by detecting early retinal damage.

Assessing Responses of the Macula in Patients with Macular Holes using a New System Measuring Localized Visual Acuity and the mfERG

To evaluate acuity and multifocal electroretinogram (mfERG) responses from the macula in affected and unaffected fellow eyes of patients with macular holes. We tested 10 eyes with macular hole and 10 fellow eyes from 11 patients. We measured local visual acuity thresholds at 27 discrete locations within 21 degrees diameter using the Functional Fundus Imaging System (FFIS), a psychophysical system that measures visual acuity as a function of visual field location, and local ERG responses within 45 degrees diameter using the mfERG. In the affected eyes, the mean FFIS visual acuity thresholds were significantly elevated within the central 21 degrees diameter area, compared to a group of control eyes. No significant differences were found between the acuities of the fellow eyes compared to those of the control group. The amplitudes of the first positive peak of the mfERG were reduced in the central 7.8 degrees in affected eyes. In the central 2 degrees , 4 out of 10 affected eyes showed non-measurable ERG signals. The remaining six eyes showed significantly reduced mean amplitudes, but not delayed implicit times, when compared to the control group. For the fellow eyes, the mean amplitudes of the mfERG and implicit times did not differ from the means of the control eyes. Both local psychophysical and electrophysiological testing demonstrated retinal dysfunction extending beyond the site of the macular holes in some patients (three of the patients had central mfERG amplitudes falling within the normal range).

Test?retest reliability of the multifocal electroretinogram and Humphrey visual fields in patients with retinitis pigmentosa

We examined the reliability of Humphrey visual field thresholds and multifocal electroretinogram (mfERG) amplitudes and timing in a group of patients with Retinitis Pigmentosa (RP). Eight patients with RP and seven control subjects were tested five times: at baseline (visit #0), at three weekly follow-up visits (visits #1 - #3), and at three months (visit #4). For the Humphrey thresholds, differences between dB values on repeat visits were obtained. Differences between log values on repeat visits were calculated for mfERG amplitude and implicit time. We used the standard deviations of these difference scores as a measure of reliability and the means of the difference scores as a measure of progression. We found that the majority of the patients' repeat data were more variable than that of the control subjects for both the Humphrey and mfERG. We found no single factor that predicted the magnitude, or the variance, of the SD of differences scores for the patients. We recommend that each patient's reliability be assessed individually. Ultimately, the choice of an outcome measure must be guided by its reliability, as well as its ability to assess the visual function of interest.

Multifocal Electroretinographic Evaluation of Long-term HydroxychloroquineUsers

To observe the long-term effects of hydroxychloroquine sulfate on retinal electrical activity by multifocal electroretinography (mfERG) and to evaluate the regional variation of retinal dysfunction in subjects with hydroxychloroquine retinopathy. Multifocal ERG with 103-hexagon stimulation was performed on 19 patients (36 eyes) treated with hydroxychloroquine for systemic lupus erythematosus, rheumatoid arthritis, or localized atypical scleroderma. Visual acuity testing, Amsler grid testing, and Ishihara color vision testing were also performed. In 2 of the patients, hydroxychloroquine was discontinued due to concerns about toxicity. Both of these patients had additional mfERG performed after discontinuation of medication. Twelve patients (19 eyes) had a normal response density in one or both eyes, including 6 patients (12 eyes) with a low lifetime dose (< or =438 g) of hydroxychloroquine who had normal response densities in both eyes. Eleven patients (17 eyes) had abnormal response densities in one or both eyes, and 2 of these patients (4 eyes) had significant attenuation of response densities in almost the whole tested field; 4 patients had a normal mfERG result for one eye but had a slight decrease of response densities for the other eye. There were 4 patterns of abnormal mfERG amplitude change observed: (1) paracentral loss, (2) foveal loss, (3) peripheral loss, and (4) generalized loss. Implicit times were abnormal for pericentral responses in 3 patients. The results of color vision and Amsler grid testing were normal, except for one patient with a generalized loss pattern. In 2 subjects in whom hydroxychloroquine toxicity was suspected, response densities improved after termination of hydroxychloroquine. Long-term hydroxychloroquine use may be associated with mfERG abnormalities. The mfERG appears to detect retinal physiological change earlier than visual acuity testing, color vision testing, or Amsler grid testing can. The greatest value of the mfERG is in differentiating a retinal cause and, hence, providing important evidence for hydroxychloroquine toxicity, for whatever visual field loss is apparent on perimetry.

Multifocal electroretinogram delays predict sites of subsequent diabetic retinopathy.

To examine the potential of abnormal mfERGs to predict the development of diabetic retinopathy at corresponding retinal locations 1 year later. One eye of 11 diabetic patients with nonproliferative diabetic retinopathy (NPDR) and 11 diabetic patients without retinopathy were retested 12 months after initial testing. At each time, mfERGs were recorded from 103 retinal locations, and fundus photographs were taken within 1 month of each recording. Local mfERG implicit times were measured and their z-scores were calculated based on results obtained from 20 age-matched control subjects. mfERG abnormalities were defined as z-scores of 2 or more for implicit time and z-scores of -2 or less for amplitude (P < or = 0.023). mfERG z-scores were mapped onto fundus photographs, and the relationship between baseline abnormal z-scores and new retinopathy at follow-up was examined. New retinopathy developed in 7 of the eyes with NPDR after 1 year. In these eyes, 70% of the mfERGs in areas of new retinopathy had abnormal implicit times at baseline. In contrast, only 24% of the responses in regions that remained retinopathy free were abnormal at baseline. Relative risk of development of new retinopathy over 1 year in the areas with abnormal baseline mfERG implicit times was approximately 21 times greater than that in the areas with normal baseline mfERGs (odds ratio = 31.4; P < 0.001). Eyes without initial retinopathy did not develop new retinopathy within the study period, although 4 of these 11 eyes had abnormal implicit times at baseline. mfERG implicit times tended to be more delayed at follow-up than at baseline in NPDR eyes, but not in eyes without retinopathy and control eyes. mfERG amplitudes had no predictive power. Localized functional abnormalities of the retina reflected by mfERG delays often precede the onset of new structural signs of diabetic retinopathy. Those functional abnormalities predict the local sites of new retinopathy observed 1 year later.

Localized retinal dysfunction in central serous chorioretinopathy as measured using the multifocal electroretinogram

Purpose To determine the extent of electrophysiologic dysfunction in patients with central serous chorioretinopathy (CSC). Design Prospective observational case series. Participants Six patients with unilateral CSC (mean age, 40 years) were recruited into the study. Methods Six patients with CSC underwent multifocal electroretinogram (mfERG) testing on both their clinically affected and opposite uninvolved eyes using the VERIS System, with a stimulus array of 103 scaled hexagons. The first positive peak responses were analyzed within six concentric ring annuli centered on the fovea. Amplitudes and implicit times were compared with those of an age-similar control group. Main outcome measures Local electroretinographic response amplitudes and implicit times within the central 40° with the mfERG. Results All the clinically uninvolved eyes showed mfERG amplitudes and implicit times within the normal range throughout the central 40° of the retina. All six eyes with CSC showed reduced amplitudes and/or delayed implicit times that were limited to the regions of the macula in which clinical changes associated with CSC were apparent. Conclusions We observed electroretinographic changes only in the clinically affected eyes, and these were limited to regions with ophthalmoscopically apparent fundus changes. Our findings do not support the conclusion that functional impairment, as measured by the mfERG, in eyes with CSC extends beyond clinically observed fundus changes. We did not observe abnormal mfERG responses in the clinically normal eyes of such patients.

Mapping of retinal function in Best macular dystrophy using multifocal electroretinography

In order to evaluate the function of the retina in Best macular dystrophy (BMD) 18 patients were examined by means of the multifocal electroretinogram (mfERG). The mfERG peak amplitudes of the central and pericentral responses were significantly reduced in the BMD patients ( p<0.001). The ERG amplitude decrease of the central response was significantly correlated with visual acuity loss and with the funduscopic staging. The implicit times in more eccentric groups were slightly but significantly increased. The markedly reduced mfERG amplitudes with only slightly increased implicit times may indicate cone photoreceptor cell loss or damage to the cone outer segments.

Detection using the multifocal electroretinogram of mosaic retinal dysfunction in carriers of X-linked retinitis pigmentosa

PurposeTo examine whether a mosaic pattern of retinal dysfunction in obligate carriers of X-linked retinitis pigmentosa (XLRP) could be observed in local electroretinographic responses obtained with the multifocal electroretinogram (mfERG). DesignProspective observational case series. ParticipantsFive obligate carriers of XLRP (mean age, 53.2 years) were recruited into the study. MethodsExamination of each subject included a complete ocular examination, Humphrey visual field, standard full-field electroretinogram (ERG), and mfERG testing. For the mfERG, we used a 103-scaled hexagonal stimulus array that subtended a retinal area of approximately 40° in diameter. The amplitudes and implicit times in each location for the mfERG was compared with the corresponding value determined for a group of normally sighted, age-corrected control subjects. Main outcome measuresMapping of 103 local electroretinographic response amplitudes and implicit times within the central 40° with the multifocal electroretinogram. ResultsLocalized regions of reduced mfERG amplitudes and/or delayed implicit times were found in four of five carriers. In one of these four carriers, a mosaic pattern of mfERG dysfunction was present even in the absence of any clinically apparent retinal changes, retinal sensitivity losses on Humphrey field testing, or abnormal full-field cone ERG responses. However, one carrier with a typical tapetal-like reflex demonstrated no deficit on any functional tests. ConclusionsThe mfERG demonstrated patchy areas of retinal dysfunction in some carriers of XLRP. This mosaic pattern of dysfunction may be observed in some patients with a normal-appearing fundus, normal psychophysical thresholds, and normal amplitude and implicit time full-field ERG cone responses.

A method for comparing psychophysical and multifocal electroretinographic increment thresholds

The multifocal electroretinogram (mfERG) has been commonly used as a method for obtaining objective visual fields. Although qualitative comparisons have been good, quantitative comparisons between the results from mfERG and the results from Humphrey Visual Field Analyser (HVFA) have found variable degrees of agreement depending upon the mfERG response parameter examined and/or the disease studied. Lack of agreement may be due to differences in methodology, differences in the sites of response generation, and/or differences derived from comparing suprathreshold versus threshold responses. In addition, the two procedures are performed at different levels of adaptation. We developed an approach for matching stimulus parameters and compared mfERG and psychophysical thresholds to assess the effects of technique and level of adaptation on the two responses. Psychophysical and mfERG thresholds were obtained as a function of the adaptation level (1.5–4.0 log td) and retinal location. The derived increment threshold-versus-intensity functions for both measures were fitted using the equation log T=log T 0+log(( A+ A 0)/ A 0) n . We found that the values of A 0 for the mfERG data were one log unit higher than those for the psychophysical data. In addition, the value of the slope ( n) for the mfERG data was shallower (0.8) than that of the psychophysical data (1.0). Predictions were made about comparisons of HVFA threshold and mfERG amplitude data in patients with retinal disease based upon a two-site model of adaptation. The data for some groups of patients could be best-fitted with a model of a disease acting at a site distal to all gain changes, whereas data from other patients were best fitted with a model of a disease acting at a site proximal to all retinal gain. The relationship between the Humphrey visual field threshold losses and mfERG amplitude reductions depends upon the site and mechanism of a particular disease process and the model of retinal gain assumed. In no case is a one-to-one relationship between the losses in the two measures predicted.