Color vision and neuroretinal function in diabetes.

PURPOSE: We investigate how type 2 diabetes (T2DM) and diabetic retinopathy (DR) affect color vision (CV) and mfERG implicit time (IT), whether CV and IT are correlated, and whether CV and IT abnormality classifications agree. METHODS: Adams desaturated D-15 color test, mfERG, and fundus photographs were examined in 37 controls, 22 T2DM patients without DR (NoRet group), and 25 T2DM patients with DR (Ret group). Color confusion score (CCS) was calculated. ITs were averaged within the central 7 hexagons (central IT; ≤4.5°) and outside this area (peripheral IT; ≥4.5°). DR was within (DRIN) or outside (DROUT) of the central 7 hexagons. Group differences, percentages of abnormalities, correlations, and agreement were determined. RESULTS: CCS was greater in the NoRet (P = 0.002) and Ret (P < 0.0001) groups than in control group. CCS was abnormal in 3, 41, and 48 % of eyes in the control, NoRet, and Ret groups, respectively. Ret group CV abnormalities were more frequent in DRIN than in DROUT subgroups (71 vs. 18 %, respectively; P < 0.0001). CCS and IT were correlated only in the Ret group, in both retinal zones (P ≤ 0.028). Only in the Ret group did CCS and peripheral IT abnormality classifications agree (72 %; P < 0.05). CONCLUSION: CV is affected in patients with T2DM, even without DR. Central DR increases the likelihood of a CV deficit compared with non-central DR. mfERG IT averaged across central or peripheral retinal locations is less frequently abnormal than CV in the absence of DR, and these two measures are correlated only when DR is present.

Towards optimal filtering of "standard" multifocal electroretinogram (mfERG) recordings: findings in normal and diabetic subjects.

AIMS: To study the effects of two commonly used pre-amplifier filtering bandwidths on normal multifocal electroretinogram (mfERG) responses and their comparative abilities to detect retinal disease. METHODS: 103 standard mfERGs were recorded simultaneously in two channels with different pre-amplifier settings (10-100 Hz and 10-300 Hz) from one eye of each of 20 normal subjects, 17 diabetics with non-proliferative diabetic retinopathy (NPDR), and 12 diabetics without retinopathy. Signal to noise ratios (SNR) of the normal subjects' first order mfERGs were compared between channels. All subjects' amplitudes and implicit times were derived using a "template stretching" method. For comparison, implicit time was also measured using a "template sliding" method. mfERG amplitudes and implicit times were compared between the channels and among subject groups. RESULTS: Normal mean amplitudes and implicit times were similar for the two channels. However, normal 10-100 Hz recordings had significantly higher SNR and lower intersubject variability than 10-300 Hz recordings. In NPDR, the 10-100 Hz channel identified significantly more implicit time and amplitude abnormalities. In the diabetics without retinopathy, 10-100 Hz filtering identified significantly more implicit time abnormalities than 10-300 Hz filtering. For both filter settings, diabetic implicit times were more often abnormal than amplitudes. The 10-100 Hz channel was superior for both implicit time measurements. CONCLUSION: Standard mfERGs recorded from normal eyes and filtered 10-100 Hz contain less noise, higher SNR, and less intersubject variability than those filtered at 10-300 Hz. This underlies the finding that the 10-100 Hz filter setting identifies more retinal dysfunction than the 10-300 Hz setting.

The optic nerve head component of the monkey's (Macaca mulatta) multifocal electroretinogram (mERG).

To search for an optic nerve head component (ONHC) in the monkey's (Macaca mulatta) multifocal electroretinogram (mERG), mERGs from three animals were recorded with different electrode configurations. A component with a latency that varied with distance from the optic nerve head was easily identified by eye in recordings from the speculum of a Burian-Allen electrode referenced to a DTL on the unstimulated eye. This component was reasonably well isolated by subtracting a weighted version of a Burian-Allen bipolar recording or by employing the extraction algorithm of Sutter and Bearse (1999, Vision Research, 39, 419-436). The waveform of this component resembles the ONHC reported for the human mERG.

Assessment of early retinal changes in diabetes using a new multifocal ERG protocol.

AIMS: To assess early functional retinal changes in diabetics without retinopathy, a new multifocal stimulus paradigm was used that emphasises fast adaptive response contributions. METHODS: 25 normal control subjects (25 eyes) and 11 diabetics without retinopathy (22 eyes) served as subjects. Stimulation and analysis were performed with Veris Science 4.0. A stimulation protocol was used that combines regular multifocal flicker stimulation with a periodic "global" flash inserted between the multifocal stimuli. The multifocal stimuli were presented four video frames apart. The global flash covered the entire screen in the third frame of the four frame interval. The remaining two frames were dark. The periodic global flashes could only contribute to the focal responses if they were affected by the multifocal stimulation. A non-linear component induced by the interaction of the focal and global flashes was observed. The differences between control subjects and diabetics were assessed in both the multifocal responses and their induced effect on the following global flashes. RESULTS: The responses to focal flashes were reduced significantly in diabetics matched in age to the control subjects. The induced components showed large intersubject variability in controls and patients, and did not differ significantly between the two groups. CONCLUSION: The periodic global flashes produce a greater multifocal response reduction in diabetics than in normals, indicating impairment in the rate or magnitude of recovery from the bright preceding stimulus. The new stimulation protocol reveals early changes in retinal function of diabetics.

Distribution of oscillatory components in the central retina.

This study examines the characteristics and the naso-temporal asymmetries of the higher-order oscillatory components of the multifocal electroretinogram (mERG). The magnitude of the mERG asymmetry and the mechanisms which produce it have not been studied previously. We recorded the mERG from seven normal observers using slow multifocal flicker and response filtering of 10-300 Hz. This permitted, without additional filtering, examination of the dominant first order component and the oscillation-rich components in the first and second order kernels. The oscillatory components in the two kernels had multiple peaks separated by about 6.8 ms, similar to those of conventional oscillatory potentials. Naso-temporal asymmetry of the three response components was analyzed in three groups (concentric rings around the fovea) spanning 1.5-10 deg of retinal eccentricity. The oscillation-rich components were, on average, approximately 14% larger in amplitude in the temporal retina than in corresponding nasal locations (p < 0.05) while the dominant first order component was not asymmetrically distributed. We tested the hypothesis that the asymmetry could be modeled as a combination of a retinal component (RC) and an optic nerve head component (ONHC) which varies in latency as a function of distance from the optic disc. We found that both oscillatory components and the dominant first order response could be decomposed into RCs and ONHCs that are symmetrically distributed. Thus, it appears that the naso-temporal asymmetries of the oscillation-rich components are produced primarily by the relative alignment and enhancement of RC and ONHC wavelets in the temporal retina, and misalignment and partial cancellation in the nasal retina.

Das multifokale elektroretinogramm in der diagnostik und verlaufskontrolle lokalisierter Netzhautfunktionsstörungen: fallbericht eines patienten mit chorioretinopathia centralis serosa.

The role of multifocal electroretinography (MF-ERG) in the diagnosis and follow-up of localized areas of retinal dysfunction is discussed. A 42-year-old male with the preliminary diagnosis of optic neuritis in his left eye was referred for evaluation with the MF-ERG. Simultaneous cone ERGs were obtained from 103 locations within the central 50 degrees of the retina. During an 8-month follow-up four MF-ERGs were obtained. Bilaterally reduced paracentral response amplitudes contradicted the preliminary diagnosis. Subsequently central serous chorioretinopathy was diagnosed. Follow-up showed normalization of the MF-ERG responses in the left eye while retinal function in the right eye showed initial worsening. The noninvasive MF-ERG lends itself to follow-up in patients with central serous chorioretinopathy.

Topography of cone electrophysiology in the enhanced S cone syndrome.

PURPOSE: To investigate the topography of cone electroretinographic (ERG) responses in the enhanced S cone syndrome (ESCS). METHODS: A 19-year-old female with ESCS who was one of the original cases defining the syndrome was studied. Full-field, focal (Maculoscope) and multifocal (VERIS) ERGs were performed using white light. Multifocal ERG responses were also generated with red and blue stimuli and with a slow m-sequence to elicit off-responses. Results were analyzed by averaging data in rings at increasing eccentricity from the fovea and compared to data recorded identically from a normal subject. RESULTS: The full-field ERG from this patient showed typ ical large slow photopic waveforms and was unchanged from recordings made 9 years earlier. The focal ERG showed signals of borderline low amplitude from the fovea with the multifocal ERG, the ESCS responses from the central macula had a relatively normal waveform, and those 9 degrees to 20 degrees from fixation showed the prolonged wave-form that characterizes the full-field ERG. Responses were larger to blue light than red light in ESCS in both center and periphery. The central ESCS responses were relatively normal in timing to both red and blue light, whereas the peripheral ESCS responses were markedly delayed to both. Off-responses were seen in ESCS only near the foveal center. CONCLUSIONS: The marked differences between central and peripheral ERG responses in ESCS suggest that there are different distributions of S, L, and M cones in these regions and that S cones may feed into different neural pathways in the center and periphery. It was postulated that in ESCS, S cones may partially replace L and M cones centrally and feed into the usual S cone pathways. In the periphery, however, there is little L and M cone b-wave activity in ESCS, and S cones may usurp both the space and neural pathways of the rods.

[Multifocal electroretinogram (MF-ERG) in diagnosis of macular changes. Example: senile macular degeneration]. / Multifokales Elekroretinogramm (MF-ERG) in der Diagnostik von Makulaveränderungen. Beispiel: Altersabhängige Makuladegeneration (AMD).

PURPOSE: Small areas of retinal pathology may pose diagnostic difficulties. The noninvasive multifocal electroretinogram (MF-ERG) provides a topographical mapping of retinal function. Its role in the diagnosis of macular diseases is examined in age-related macular degeneration (AMD). AMD is a main cause of central visual loss in the elderly population, affecting the second eye in 75%. METHODS: MF-ERG recordings of three patients with AMD were compared to the findings of fundus photography and fluorescein angiography. During the MF-ERG recordings the central 50 degrees of the retina was stimulated. The visual stimulus consisted of 241 hexagons that alternated, independently and pseudorandomly, between black and white according to a special predetermined binary sequence. Local retinal response components were extracted using the Fast m-Transform Algorithm. RESULTS: Three of six eyes had undergone cataract surgery with implantation of a posterior chamber lens (PCL). In accordance with an increase in light transmission through PCLs, these eyes showed an increase in the MF-ERG responses. MF-ERG allowed accurate topographic mapping of focal areas of retinal dysfunction in all patients tested. There was good correspondence to anatomical changes detected by fluorescein angiography. CONCLUSION: The high resolution of the MF-ERG enables detection of small areas of retinal pathology. It thus presents a clinically useful, noninvasive method in the early diagnosis and follow-up of macular disease.

The optic nerve head component of the human ERG.

The local responses of the multifocal ERG reveal continuous changes in the second order waveforms from the nasal to the temporal retina. Scrutiny of these changes suggests the presence of an additive component whose latency increases with the distance of the stimulus from the optic nerve head. This observation led to the hypothesis of a contributing source in the vicinity of the optic nerve head whose signal is delayed in proportion to the fiber length from the stimulated retinal patch to the nerve head. The hypothesis was tested with two independent methods. In Method 1, a set of different local response waveforms was approximated by two fixed components whose relative latency was allowed to vary and the fit of this two component model was evaluated. In Method 2, two signals were derived simultaneously using different placements for the reference electrode. The placements were selected to produce a different ratio of the signal contributions from the retina and the nerve head in the two recording channels. The signals were then combined at a ratio that canceled the retinal component. Method 1 yielded an excellent fit of the two component model. Waveforms and latencies of the hypothetical optic nerve head component derived from the two methods agree well with each other. The local latencies also agree with the propagation delays measured in the nerve fiber layer of the monkey retina. In combination, these findings provide strong evidence for a signal source near the optic nerve head.

Mapping of retinal function in diabetic retinopathy using the multifocal electroretinogram.

PURPOSE: To investigate focal abnormalities in the electroretinogram (ERG) signal in diabetic patients, with and without retinopathy, using a multifocal ERG. METHODS: Sixteen patients with diabetes mellitus, 8 of whom had diabetic retinopathy (mean duration of diabetes: 18.5 years) and 19 approximately age-matched healthy volunteers underwent multifocal ERG testing. One hundred three retinal locations within the central 50 degrees were stimulated concurrently, according to a pseudorandom m-sequence. Response components were extracted for each stimulated retinal location. RESULTS: In diabetic patients with retinopathy, the overall amplitudes were reduced (P < 0.01), and peak implicit times were increased (P < 0.01) in the first-order component (mean flash response) and in the first slice of the second-order component (local two flash interaction). In addition, local reductions of amplitude could be seen in the first- and second-order components. In patients without retinopathy, only amplitudes of the second-order component were reduced (P < 0.01). Another salient difference was observed in a special feature of the second-order component that was reduced in diabetic patients, with and without retinopathy (P < 0.05). CONCLUSIONS: Second-order components depend on nonlinear dynamics. Thus our findings indicate changes in the nonlinear dynamics of a fast-gain control in diabetic patients, presumably located in the inner retina. This suggests that early functional changes of the inner retina are evident in diabetic patients before impairment of the outer retina is observed. Multifocal nonlinear analysis permits the detection of subclinical diabetic retinopathy and offers the advantage of topographic mapping of retinal dysfunction.

Imaging localized retinal dysfunction with the multifocal electroretinogram.

Conventional electroretinographic techniques do not permit efficient mapping of retinal responsiveness for the detection of small dysfunctional areas. This study explores the application of a new technique that makes such mapping possible. It utilizes a multifocal electroretinogram technique based on binary m sequences that simultaneously tests a large number of small retinal areas by multiplexing their responses onto a single signal derived from the human cornea. The focal responses are subsequently extracted for the derivation of high-resolution maps that characterize retinal responsiveness. The required recording times are short enough to make such testing feasible in the clinic. In this study we demonstrate the high sensitivity of the technique by mapping a small area that has been partially bleached by a strobe flash in a normal retina and by mapping dysfunctional areas in three patients with different, well-documented retinal pathologies. The results suggest that the multifocal electroretinogram has the potential to become a valuable clinical tool.

Contrast coding by cells in the cat's striate cortex: monocular vs. binocular detection.

Many psychophysical studies of various visual tasks show that performance is generally better for binocular than for monocular observation. To investigate the physiological basis of this binocular advantage, we have recorded, under monocular and binocular stimulation, contrast response functions for single cells in the striate cortex of anesthetized and paralyzed cats. We applied receiver operating characteristic analysis to our data to obtain monocular and binocular neurometric functions for each cell. A contrast threshold and a slope were extracted from each neurometric function and were compared for monocular and binocular stimulation. We found that contrast thresholds and slopes varied from cell to cell but, in general, binocular contrast thresholds were lower, and binocular slopes were steeper, than their monocular counterparts. The binocular advantage ratio, the ratio of monocular to binocular thresholds for individual cells, was, on average, slightly higher than the typical ratios reported in human psychophysics. No single rule appeared to account for the various degrees of binocular summation seen in individual cells. We also found that the proportion of cells likely to contribute to contrast detection increased with stimulus contrast. Less contrast was required under binocular than under monocular stimulation to obtain the same proportion of cells that contribute to contrast detection. Based on these results, we suggest that behavioral contrast detection is carried out by a small proportion of cells that are relatively sensitive to near-threshold contrasts. Contrast sensitivity functions (CSFs) for the cell population, estimated from this hypothesis, agree well with behavioral data in both the shape of the CSF and the ratio of binocular to monocular sensitivities. We conclude that binocular summation in behavioral contrast detection may be attributed to the binocular superiority in contrast sensitivity of a small proportion of cells which are responsible for threshold contrast detection.

Binocular summation in orientation discrimination depends on stimulus contrast and duration.

Binocular summation, an improvement in visual performance with binocular viewing compared to monocular viewing, has been studied extensively in detection tasks. Monocular detection thresholds for stationary stimuli are typically about 40% higher than binocular thresholds. Binocular summation in discrimination tasks, however, is often lower and less consistent. A possible explanation for this difference is that saturation of responses limits the extent of binocular summation in discrimination tasks. To investigate this possibility, we used an orientation discrimination task and varied stimulus contrast and exposure duration. Monocular and binocular orientation discrimination thresholds were obtained using one-dimensional difference-of-Gaussian stimuli. For briefly exposed stimuli, binocular summation is greatest at low contrasts (e.g. 66% at 8% contrast) and is reduced systematically at higher contrasts so that monocular and binocular thresholds are approximately equal at contrasts above 15%. Binocular summation for low-contrast stimuli is greatest at a brief exposure duration (50 msec), is reduced at longer durations, and is not significant at durations of 100 msec or longer. Thus, binocular summation in orientation discrimination is greatest for relatively low-energy stimuli. These results are consistent with models of binocular energy summation and the hypothesis that saturation of responses after binocular combination can limit binocular summation in discrimination tasks.

Spatial linearity of the pattern electroretinogram.

We modeled the spatial-frequency sensitivity of the human pattern-reversal electroretinogram (PERG) with the linear, two-parameter, spatially bandpass model of Kelly [J. Opt. Soc. Am. A 2, 810 (1985)]. In the model temporal linearity or linearity with luminance is not assumed, but linearity with contrast is assumed. Measurements relating PERG amplitudes to stimulus element size were taken from 13 earlier reports. Stimuli were two-dimensional Fourier analyzed. The bandpass model fitted well and thus supported linearity (spatial superposition) and suggested that large PERG's to large checks (low-pass data) reflect mainly responses to higher-spatial-frequency stimulus components.