Adaptational changes in cone electroretinograms in man

Changes of amplitude and implicit time of human cone electroretinogram (ERG) were studied during dark adaptation and succeeding light adaptation. Dark-adapted cone ERG was isolated by subtracting scotopic blue response from matched scotopic red response. The former represented the rod-mediated b-wave, while the latter consisted of both rod-mediated b-wave and cone-mediated b-wave or x-wave. The b-wave amplitude of dark-adapted cone ERG remained unchanged during dark adaptation, while the implicit time increased systematically, reaching a plateau. Light-adapted cone ERG was obtained by red stimulus lights under a bright background light. The amplitude of light-adapted cone ERG was markedly suppressed through dark adaptation but it recovered gradually during light adaptation, reaching the base line level. The implicit time was unchanged during light adaptation.     

The effect of stimulus intensity and background luminance on the b-wave implicit time of photopic electroretinogram in normal human eyes]

The authors studied the effect of stimulus intensity and background luminance on the b-wave implicit time of photopic electroretinogram in normal human eyes. Photopic electroretinograms were recorded at various stimulus intensities and background luminances in the range of 2.5 log scale using an integrating sphere of 30 cm diameter in the first experiment. The results from two normal eyes showed that with increasing stimulus intensity or with decreasing background luminance the b-wave implicit time of photopic electroretinogram prolonged and one or three wavelets superimposed on the ascending limb of the b-wave. The second experiment was performed using a half dome sphere of 60 cm diameter to study the b-wave implicit time at three different stimulus intensities. The results from 30 normal eyes disclosed a statistically significantly longer implicit time at the greater stimulus intensities. These results suggest that b-wave implicit time in photopic electroretinogram becomes delayed with increasing stimulus intensity and becomes shorter with brighter background luminance.     

Effects of IBMX on the rod ERG of the isolated perfused cat eye: antagonism with light, calcium or L-cis-diltiazem.

Full-field electroretinograms (ERGs) were recorded from isolated cat eyes perfused through the ophthalmociliary artery with the cGMP-PDE inhibitor, 3-isobutylmethylxanthine (IBMX). Under dark-adapted conditions perfusion with IBMX resulted in reduced ERG b-wave amplitudes at low stimulus luminances and supernormal b-wave amplitudes at high stimulus luminances with reduced b-wave sensitivity; b-wave implicit times were more delayed at low than at high stimulus luminances. Presentation of a steady white background or high calcium fully reversed the supernormal amplitudes and partially reversed the delayed implicit times produced by IBMX. Rod ERG b-wave sensitivity, reduced with IBMX alone, was partially reversed with calcium but further reduced with background light. Perfusion with the cation channel blocker, L-cis-diltiazem, also reversed the supernormal amplitudes produced by IBMX but had no effect on implicit times or b-wave sensitivity. Possible mechanisms of action of these antagonists and clinical implications of these findings are considered.     

Electroretinogram b-wave implicit time and b/a wave ratio as a function of intensity in central retinal vein occlusion.

The ability of electroretinogram (ERG) b-wave implicit time and b/a wave ratio to predict iris neovascular response was analyzed as a function of stimulus intensity over a 3.6 log unit intensity range in 39 patients with central retinal vein occlusion (CRVO). Predictive power for CRVO patients was evaluated using ROC area at intensities of 1.23, 1.83, 2.43, and 3.03 effective log quanta/rod, where reliable data for both parameters were obtainable from most patients. The relative predictive power of b-wave implicit time and b/a wave ratio were shown to vary with stimulus intensity. The predictive power of b-wave implicit time, as measured by ROC area, declined to below significance at high intensity (above 1.83 log quanta/rod), while b/a wave ratio performed best at middle intensities (1.83 and 2.43 log quanta/rod) and not as well at high and low intensities. Further analysis of statistical behavior of both ERG parameters was obtained from the t statistic. Insight into the mechanism influencing predictive power of b-wave implicit time was derived from measurements on normal adults and CRVO patients with response data taken at high intensities. These results suggest that an optimal stimulus intensity range can be found for these ERG parameters in the evaluation of CRVO.     

Dark-adapted luminance-response functions with skin and corneal electrodes

Normative dark-adapted electroretinograms were recorded simultaneously with a skin electrode and corneal electrode for varying stimulus intensities. The electroretinogram b-wave amplitudes for each electrode were fitted by the Naka-Rushton equation, and the parameters Vmax, K and n were evaluated. A comparison of parameters between the two electrodes showed a significant difference for Vmax and K but not for n. Vmax was approximately eight times smaller and K was 0.3 log unit smaller for the skin electrode than for the corneal electrode. B-wave amplitude and implicit time were also compared between the two electrodes. The b-wave amplitude ratio of the corneal electrode to that of the skin electrode increased with luminance and ranged from 1.83 to 7.68. Overall, b-wave implicit time for the skin electrode was approximately 10 ms shorter than that of the corneal electrode.Abbreviations CV coefficient of variation - L-R function luminance-response function - ND neutral density     

On-response deficit in the electroretinogram of the cone system in X-linked retinoschisis

PURPOSE: The purpose of this study was to evaluate the hypothesis that the reduced b-wave to a-wave ratio of the brief-flash electroretinogram (ERG) of the cone system typically observed in X-linked retinoschisis (XLRS) represents a relatively greater deficit in the ON response (response to light onset) than the OFF response (response to light offset). A second purpose was to investigate the use of sawtooth flicker as a stimulus for eliciting ERG ON and OFF responses. METHODS: Light-adapted, full-field ERGs were recorded in six patients with XLRS and six age-similar control subjects in response to 8-Hz rapid-on and rapid-off sawtooth flicker to emphasize ON and OFF responses, respectively. ERG responses were analyzed in terms of the amplitudes and implicit times of the a-wave, b-wave, and d-wave components. RESULTS: There was no significant difference between the patients with XLRS and the control subjects for either the amplitude of the a-wave of the ON response or the amplitude of the d-wave of the OFF response. However, the amplitude of the b-wave of the ON response was reduced significantly in the patients with XLRS, resulting in a significantly reduced b-wave to d-wave ratio. The patients' implicit times were increased significantly for all waveform components. CONCLUSIONS: The reduced b-wave to d-wave ratio of the ERG of the cone system in these patients with XLRS is consistent with a relative dysfunction of the cone ON bipolar cell pathway in this disorder. The results show further that sawtooth flicker is a promising stimulus for eliciting well-defined ERG waveforms that can provide a quantitative assessment of the properties of ON and OFF responses in retinal disease.     

Cone dystrophy and supernormal dark-adapted b-waves in the electroretinogram

A male patient suffering from cone dystrophy was followed over 9 years. In addition to the typical clinical and electrophysiologic signs, supernormal b-waves were found in the dark-adapated electroretinogram. Our case is compared with 12 similar patients described in the literature. Our patient differed from the other patients in the following aspects: he was male and had a congenital stationary disease with a small pigment epithelial scar in the left eye only and no other fundus changes up to the age of 22 years. He did not complain of night blindness. The dark-adapted electroretinogram of our patient showed a normal b-wave threshold with increased b-wave amplitudes and markedly prolonged b-wave latencies and implicit times. This combination of signs has not been reported to date in any other patient and points towards a postreceptoral defect of the interneuronal connection.     

Cone dystrophy and supernormal dark-adapted b-waves in the electroretinogram

A male patient suffering from cone dystrophy was followed over 9 years. In addition to the typical clinical and electrophysiologic signs, supernormal b-waves were found in the dark-adapted electroretinogram. Our case is compared with 12 similar patients described in the literature. Our patient differed from the other patients in the following aspects: he was male and had a congenital stationary disease with a small pigment epithelial scar in the left eye only and no other fundus changes up to the age of 22 years. He did not complain of night blindness. The dark-adapted electroretinogram of our patient showed a normal b-wave threshold with increased b-wave amplitudes and markedly prolonged b-wave latencies and implicit times. This combination of signs has not been reported to date in any other patient and points towards a postreceptoral defect of the interneuronal connection.     

Cone positive off-response in normal and dystrophic cats

Light-adapted cone ERG in response to white stimuli with long duration (200 ms) was studied in seven normal cats and six cats with early to moderate, inherited retinal dystrophy. The stimuli typically elicited an ERG consisting of an a- and b-wave in response to light onset, whereas light-offset was followed by a cornea-positive d-wave and subsequent negative dip and occasionally a second positive peak in both normal and dystrophic cats, although b- and d- waves had less distinct peaks in cats with moderately advanced retinal dystrophy. Linear regression models indicated a positive correlation between d-wave amplitude and stimulus luminance, whereas a negative correlation was found between amplitude and background light luminance in normal cats. The d-wave implicit time was independent of both stimulus and background light luminance in normal cats. The d-wave amplitude was not significantly different in dystrophic cats, whereas the implicit time was increased when affected cats were compared to normal cats. The significant increase in implicit time in dystrophic cats could not be explained with a reduced sensitivity of the off-pathway to background or stimulus light. This is supported by the finding that d-wave amplitude was not significantly altered in early to moderately advanced dystrophic cats. This revised version was published online in July 2006 with corrections to the Cover Date.     

Cone electroretinogram amplitude growth with light adaptation in patients with retinitis pigmentosa

PURPOSE: It has been hypothesized that the increase in the b-wave during light adaptation is directly related to the level of cone malfunction in patients with retinitis pigmentosa (RP). Because this hypothesis has important bearing on the mechanism for the increase in the electroretinogram (ERG), we examined the increase in the amplitude of the cone ERG during light adaptation in patients with typical RP. METHODS: Cone ERGs were recorded to Ganzfeld white flash stimuli in the presence of white background illumination in 51 RP patients and in 27 normal subjects. RESULTS: In the normals, the increase in the b-wave amplitude during light adaptation ranged from 14-92% of the dark-adapted amplitude. All RP patients showed an amplitude increase that ranged from 5 to 100% of the baseline amplitude. This increase was not significantly different from that of the normals (p = 0.71, unpaired t-test). The baseline amplitudes and the increase in the relative amplitude were weakly correlated in the RP patients (r = 0.31; p = 0.029). No significant difference was observed in the amplitude increase between patients with near normal b-wave implicit times and those with delayed times (p = 0.17, unpaired t-test). Changes of the b-wave implicit time were not significantly different from those in the controls. CONCLUSION: These findings that the changes in the cone ERG with light adaptation in the RP patients were very similar to those in normal subjects do not support the proposed hypothesis that the increase in the b-wave amplitude during light adaptation was directly related to the level of cone malfunction.     

Rod and cone dysfunction in carriers of X-linked retinitis pigmentosa

Carriers of X-linked retinitis pigmentosa were studied using electroretinographic and psychophysical procedures. Under both dark- and light-adapted (cone-isolated) conditions, electroretinogram (ERG) a-waves of carriers were reduced in amplitude but normal in implicit time, whereas b-waves were reduced in amplitude and delayed in implicit time. Reductions in b-wave amplitudes of the carriers as a group were equivalent for the rod and cone systems. Luminance-response functions for both dark-adapted and cone-isolated b-waves were fit by the Naka-Rushton equation and demonstrated a selective reduction of Rmax; the semi-saturation constant (K) and the slope parameter (n) were normal. Electroretinograms recorded using the brightest stimulus flashes were most effective at distinguishing carriers from normals. Absolute thresholds of the carriers were elevated significantly across the central 40 degrees of the visual field. As a group, the threshold elevations of the carriers were approximately equal for the rod and cone systems.     

Amplitude decrease of photopic ERG b-wave at higher stimulus intensities in humans

PURPOSE: The b-wave of the human photopic electroretinogram (ERG) elicited by a short-flash increases in amplitude with increasing stimulus intensities at lower stimulus levels, but then decreases at higher stimulus intensities. The purpose of the present study was to explore this phenomenon in more detail, using short- and long-flash stimuli. METHODS: The intensity-response functions of the b-wave elicited by short- and long-flashes were compared from threshold to higher stimulus intensities in 5 normal subjects. Short- and long-flash ERGs were elicited under rod-saturating background levels using white light-emitting diodes built into a contact lens electrode. RESULTS: Whereas the amplitude of the short-flash b-wave decreased at higher intensities, the amplitude of the long-flash ERG b-wave did not decrease but plateaued. The long-flash ERG d-wave or OFF-response decreased at higher stimulus levels as did the short-flash elicited b-wave. CONCLUSIONS: Because it is widely accepted that the b-wave and the OFF-response d-wave interact to produce a single positive response, our results suggest that the decrease in the b-wave amplitude at high stimulus intensity is caused by the decrease of the d-wave at the higher stimulus intensities.     

Color electroretinography

Electroretinograms to white and color stimuli were recorded in four normal subjects and nine subjects with different cone dysfunctions, including protanopia, cone dystrophy, cone dystrophy with supernormal b-waves at dark adaptation, cone dystrophy with missing b-waves during light adaptation and rod-cone dystrophy with blue cone hypersensitivity. Color stimuli were obtained with Kodak Wratten filters in blue, blue-green, green, yellow and red. Electroretinograms to all stimuli were recorded during dark and light adaptation with different stimulus intensities and to 30-Hz flicker stimulation. In protanopia, responses to red during light adaptation and flicker stimulation were reduced. All cone dystrophies showed reduced amplitudes and prolonged implicit times to red when dark adapted. The light-adapted responses were equally reduced to all color stimuli in cone dystrophy and cone dystrophy with supernormal b-waves. Contrary to other cone dystrophies, in cone dystrophy with missing b-waves, responses to red were severely reduced and responses to green were preserved, indicating a predominantly red cone dysfunction. Blue cone hypersensitivity was clearly distinct from other dystrophies in having large responses to blue and blue-green and much smaller responses to all other colors in all stimulus conditions. The electroretinogram with color stimuli allowed separation of different cone dysfunctions and identification of new retinal dysfunction syndromes.     

Is optical coherence tomography really a new biomarker candidate in multiple sclerosis?--A structural and functional evaluation

PURPOSE: To assess the structural and functional status of patients with multiple sclerosis (MS) without a history of optic neuritis. METHODS: Thirty-nine patients with MS who had reported no visual symptoms before and after the time of MS diagnosis were included. Thirty-eight healthy subjects were included as a control group. Retinal nerve fiber layer (RNFL) thickness was determined by optical coherence tomography. Pattern visual evoked potentials (PVEP), full-field electroretinogram (ERG), and multifocal electroretinogram (mfERG) were performed. RESULTS: There was a significant reduction (P = 0.011) only in temporal RNFL thickness in patients with MS. P(100) latency was significantly delayed with both 60-min arc checks (P < 0.001) and 15-min arc checks (P < 0.001); however, P(100) amplitude was significantly reduced only in 60-min arc checks (P = 0.026). Rod response b-wave implicit time and standard combined response a- and b-wave implicit times were significantly delayed in patients with MS. Patients with MS with a delayed P(100) latency (21/39; 53.8%) had significantly reduced cone response b-wave amplitude and significantly delayed cone response a- and b-wave implicit times in ERG. mfERG results did not differ between MS and control subjects and between patients with a delayed and a normal P(100) latency. Pearson correlations between RNFL thickness and P(100) amplitude and latency in patients with MS were not significant (P > 0.05). CONCLUSIONS: There is no correlation between RNFL thickness and P(100) response in patients with MS. PVEP seems to be a more reliable biomarker in determining visual pathway involvement in patients with no history of optic neuritis.     

The short wavelength-sensitive cone electroretinogram in diabetes: relationship to systemic factors

The short wavelength-sensitive (S-) cone electroretinogram (ERG) is selectively reduced in diabetic patients both with and without retinopathy, but the exact machanism of the vulnerability of the S-cone system is still unclear. This study examined relationships of the S-cone ERG to systemic factors in diabetes. Cone ERGs to different color flash stimuli were examined in the presence of bright white background illumination in 17 diabetic patients without retinopathy and in 17 diabetics with background retinopathy. Relationships of the amplitude and implicit time of the S-cone ERG to the following systemic factors were statistically analyzed: patients' age, hemoglobin A₁ level, method of diabetic control, presence of retinopathy, and presence of nephropathy. The amplitude of the S-cone ERG b-wave was significantly reduced in diabetics treated with insulin and in those associated with nephropathy. No significant correlation was found between the S-cone ERG and patient's age, hemoglobin A₁ level and presence or absence of retinopathy. A selective reduction of the S-cone ERG is observed in patients whose metabolic control has been poor for a longer period, suggesting that microvascular changes may play a role in the S-cone ERG impairment.     

Rod electroretinograms in an elevated cyclic guanosine monophosphate-type human retinal degeneration. Comparison with retinitis pigmentosa.

Unusual rod electroretinogram (ERG) intensity-response functions were recorded from three female patients with retinal degeneration who had visual acuities of 20/200, retinal arteriolar narrowing, and diffuse granularity of the retinal pigment epithelium. All three patients had rod b-waves that were profoundly subnormal in amplitude and markedly delayed in implicit time to bright stimuli. Rod a-wave slopes were reduced 50% below normal, indicating photoreceptor involvement. These unusual rod ERG intensity-response functions are similar to those previously reported for the isolated cat eye with elevated retinal cyclic guanosine monophosphate (cGMP) after perfusion with isobutylmethylxanthine. This finding supports the idea that these three patients may have an elevation of retinal cGMP. Their rod ERG intensity-response functions are contrasted with those recorded from some patients with retinitis pigmentosa.     

Attenuating effects of diazepam on the electroretinogram of normal humans

Response/log I curves were obtained under conditions of dark-and light-adaptation in seven normal male volunteers. For each subject, a baseline electroretinogram (ERG) was recorded. In the same afternoon, a second ERG was obtained after 0.05 mg/kg diazepam, and a third ERG was recorded following 0.10 mg/kg diazepam. Under conditions of dark-adaptation, the following dose-dependent changes were identified: 1) Diazepam attenuated the rod b-wave peak amplitude and increased its implicit time; 2) The dark-adapted longer wavelength cone a-wave and 'blue cone' b-wave showed an increased implicit time; 3) All oscillatory potentials showed an increased implicit time. Under conditions of light-adaptation, dose-dependent decreases in peak amplitude and delays in implicit time were observed for the a- and b-waves. The effects of diazepam on the human ERG were more profound under conditions of light- than dark-adaptation.     

Association of electroretinogram and morphological findings in branch retinal vein occlusion with macular edema

The objective of this study is to evaluate the relations among electroretinogram parameters (cone a-wave, cone b-wave, and 30-Hz flicker), retinal thickness, and retinal volume in patients with branch retinal vein occlusion (BRVO) and macular edema. We prospectively examined 33 patients (33 eyes) with BRVO and macular edema. The amplitude and implicit time of the a-wave cone, b-wave cone, and 30-Hz flicker were calculated automatically from the ERG. Retinal thickness and volume were measured by optical coherence tomography (OCT) in nine macular subfields. Then, correlations between the ERG parameters and morphological parameters were analyzed. The 30-Hz flicker amplitude was significantly smaller in the eyes with BRVO and macular edema than in the unaffected contralateral eyes. Thirty-hertz flicker and cone b-wave implicit times were significantly longer in the eyes with macular edema than in the unaffected eyes. The implicit time of the cone b-wave was correlated with both retinal thickness and retinal volume in the temporal subfields. Thirty-hertz flicker amplitude was correlated with both retinal thickness and volume in the temporal and superior outer (site of occlusion) subfields, while 30-Hz flicker implicit time was correlated with retinal thickness and volume in the outer temporal subfield. Multiple regression analysis demonstrated that the retinal thickness and volume of the temporal subfields were significant “determinants” of the implicit time for the cone b-wave and 30-Hz flicker, as well as the 30-Hz flicker amplitude. These findings suggest that OCT parameters of the temporal region may reflect postreceptoral cone pathway function in BRVO patients with macular edema.     

The human focal electroretinogram as a function of stimulus area

Focal electroretinograms to on-off luminance modulation (2.7 Hz) of uniform fields with a different area (144-2.25 deg²) centered on the fovea were recorded in two young normal subjects. The electroretinogram responses typically consisted of an a-wave, a b-wave, a PIII component and a d-wave. The concentric reduction of the test field size caused progressive amplitude decrement of all components, while their response density increased. The spatial summation properties of the b-wave differed from those of the a-wave, PIII component and d-wave so that the relative contribution of the b-wave to the electroretinogram waveform depended on the stimulus area. For a critically small field size, the electroretinogram was dominated by the PIII and d-wave components. Only these two electroretinogram components displayed a density profile that could be compared with that of cone distribution.     

Supernormal scotopic ERG in cone dystrophy.

Three patients with a bull's-eye macular lesion and other signs characteristic of cone dystrophy gave an unusual ERG finding. In response to a white flash of moderate intensity the scotopic b-wave amplitude was considerably larger than normal. One patient had elevated rod thresholds and nyctalopia, while the other 2 had normal rod sensitivity associated with the supernormal scotopic b-wave amplitude. In the latter 2 patients the abnormal ERG pattern was unchanged for 4 years and 7 years respectively. This atypical finding, of a supernormal scotopic b-wave amplitude in response to light of moderate intensity, appears to characterise a subgroup of patients with cone dystrophy, probably of autosomal recessive inheritance. The pathogenesis of the abnormal ERG remains uncertain.