Electroretinographic oscillatory potentials in diabetic retinopathy

The oscillatory potentials of the electroretinogram in dark and light adaptation were evaluated by Fourier transform in 87 diabetics and 74 age-matched controls. The study consisted of four groups: normal control, no observable diabetic retinopathy, background diabetic retinopathy and proliferative diabetic retinopathy. A reduction in the amplitude of each oscillatory potential, the summed amplitudes, the area and the total power of the oscillatory potentials as well as delayed implicit time of each oscillatory potential peak in dark and light adaptation could be found in patients with background diabetic retinopathy and proliferative diabetic retinopathy. The amplitude of oscillatory potential 4 in dark adaptation and the total power of the oscillatory potentials in light adaptation seemed to be affected in patients with no observable diabetic retinopathy. The implicit time of oscillatory potential 2 in dark adaptation was valuable to distinguish between patients with no observable diabetic retinopathy and background diabetic retinopathy.Abbreviations NC normal control - NDR no observable diabetic retinopathy - BDR background diabetic retinopathy - PDR proliferative diabetic retinopathy     

Methodologic dependence of electroretinogram oscillatory potential amplitudes

The International Society for Clinical Electrophysiology of Vision (ISCEV) protocol for eliciting oscillatory potentials uses a considerably lower flash intensity and a different preconditioning stimulus than the only oscillatory potential protocol used to predict progression of diabetic retinopathy. To determine if the ISCEV protocol will be useful in predicting progression of diabetic retinopathy, summed oscillatory potential amplitudes were measured by both protocols in a population of diabetics. Summed oscillatory potential amplitudes measured by the ISCEV protocol, although smaller, are highly correlated with the summed oscillatory potential amplitudes measured with the higher-intensity flash. Thus, summed oscillatory potential amplitudes measured with the ISCEV protocol should be useful in predicting outcome in diabetic retinopathy. Different signal processing filters used to extract oscillatory potentials from the electroretinogram waveform have a small, but significant, effect on summed oscillatory potential amplitude. Use of the caliper-square method or the summed peak-to-trough method for measuring oscillatory potential heights had an insignificant effect on measured oscillatory potential amplitude.Abbreviation FIR finite impulse response     

Changes in the oscillatory potentials in the electroretinogram during the evolution of diabetic retinopathy

Oscillatory potentials where intensely studied in diabetic patients with various degrees of retinopathy. Classical reports pointed out the early reduction of their amplitude, as well as of their latency, while a and b waves remained still normal. A prognostic value was attached to these modifications, the reduction of oscillatory potentials being correlated with a ten time higher probability of developing a high risk retinopathy. 27 diabetic patients where investigated electroretinographically by us. No significant variation of the amplitude of oscillatory potentials was observed during the progression of diabetic retinopathy.     

Oscillatory potentials in early diabetic retinopathy

To study the oscillatory potentials in early diabetic retinopathy the authors developed a new power measurement based on the fast Fourier transform. Three groups totalling 46 patients were examined, varying from nonvisible to preproliferative diabetic retinopathy. The oscillatory potentials expressed in microwatts were measured under scotopic and photopic conditions. The data of the three groups are compared with those of a group of 22 normal individuals. The oscillatory potential power measurement appears to be a reliable method in detecting diabetic retinopathy at an early stage.     

Measuring oscillatory potentials: Fourier analysis

Studying the oscillatory potentials in diabetic retinopathy, the authors experienced several problems interpreting results of digital filtering. The main problem was the separation of the first potential from the a-wave, since their frequencies are within the same range. To improve the procedure of measuring implicit times and of calculating amplitudes, the filtering was started with a finite impulse response filter and followed by a fast Fourier transform. The power of the oscillatory potential was calculated by determining the dominant frequency in the Fourier transformed response and expressed in microwatts. A group of normal subjects was compared with a group of early diabetic retinopathy patients. It appears that even in pathological circumstances a quantitative expression of the oscillatory potential is possible.     

Electroretinographic evaluation in adult diabetics

In cross-sectional fashion, we recorded the maximal combined response and 30-Hz flicker responses in 178 adult diabetics and 40 normal controls according to the recommendations of the International Society of Clinical Electrophysiology of Vision. The oscillatory potentials were extracted from the maximal combined response by high-pass filtering. The clear media and attached retina were criteria for inclusion in this study. The data were statistically analyzed with the expectation that this procedure may provide a new feature that could have some clinical significance. Timing delays occurred more frequently than amplitude reductions in the maximal combined response and flicker responses, while amplitude reductions were more common in the first and second oscillatory potentials. The hypernormal b-wave amplitude was rare. The summed amplitude of the oscillatory potentials was highly correlated with the total power of the oscillatory potentials (the frequency domain). A reduction of the second oscillatory potential amplitude was more common than a reduction of the summed amplitude or total power. The electroretinographic component that demonstrates retinal dysfunction in the earlier stage may be a valuable indicator. In the early stage, a delay in the a-wave time and a reduction in the second oscillatory potential amplitude were the most frequent abnormalities: analysis of variance demonstrated that the summed amplitude of the oscillatory potentials and second oscillatory potential amplitude and time were the most sensitive measures of the diabetic retina. Hence, the second oscillatory potential amplitude may be the most sensitive and valuable indicator representing a quantitative measure of overall retinal dysfunction.     

糖尿病视网膜病变的视网膜振荡电位

目的 研究振荡电位（ＯＰｓ）在糖尿病视网膜病变（ＤＲ）不同阶段的表现,探讨ＤＲ早期诊断的敏感性指标,并为ＤＲ国内分期提供功能学信息。方法 选择８３名糖尿病患者、１５５眼,进行眼底检查、眼底摄像;按国内ＤＲ分期将患眼分成眼底无改变、１期、２期、３期、４期但无玻璃体出血等５组,对所有患眼按国际标准化方法进行ＯＰｓ检测。选择４３只正常眼作对照。结果 ＯＰｓ总和振幅、ＯＰ２振幅在眼底无改变时下降,在１期时进一步下降;ＯＰ３振幅在１期时较对照下降,ＯＰ１振幅在２期对较对照和无改变组下降,ＯＰ４在３期时较对照下降,４期的ＯＰ２振幅以及３期和４期的ＯＰｓ总振幅分别与０期、１期和对照组的相应指标有差异。结论 ＯＰｓ和ＯＰ２振幅在ＤＲ临床前期下降,是ＤＲ早期诊断的敏感与客观性指标;ＯＰｓ及其子波振幅在ＤＲ早期和病变分期呈负相关,     

Variability in clinically measured photopic oscillatory potentials

Oscillatory potentials found on the ascending phase of the electroretinogram b-wave probably originate in some element(s) of the inner plexiform layer. As oscillatory potentials are particularly sensitive to changes in retinal, and possibly choroidal, blood flow, they have been used extensively to provide clinical measures of the degree of retinal ischemia during the progression of diabetic retinopathy. Recent studies in our laboratories have disclosed previously unreported significant variability in the photopic oscillatory potentials on repeated measures even in tightly controlled conditions. The amplitude of five recordable light-adapted wavelets exhibited considerable intra- and inter-subject variability. Until further investigation can determine factors affecting standardization of testing, it appears that changes in oscillatory potential implicit times rather than in amplitudes are a better measurement in clinical neurophysiology.     

Oscillatory potentials. History,techniques and potential use in the evaluation of disturbances of retinal circulation

The oscillatory potentials seem to reflect severe disturbances in the retinal (and perhaps choroidal) circulation. In some cases of diabetic retinopathy with severe microangiopathy, the oscillatory potentials may be selectively reduced or extinguished while the amplitude of the a- and b-waves of the ERG remains normal. A correlation appears to exist between severely reduced oscillatory potentials and a circulatory deficiency in the retina. This selective reduction of the oscillatory potentials during advancing retinopathy is considered to be indirect evidence that they are generated independently from the mechanism producing the primary components (the a- and b-waves). The usefulness of the oscillatory potentials in the prognosis of retinal disease, particularly in diabetic retinopathy, is reviewed. The historical background, the techniques and instrumentation necessary to produce and record them, the experimental data available on the site of their origin, the clinical significance to data and the experimental efforts in our laboratory are summarized.     

Electroretinographic evaluation of diabetic retinopathy: sensitivity of amplitude and time of response

Amplitude and delay of oscillatory potentials were studied in the electroretinograms (ERGs) of patients with diabetes to see which was the more sensitive for evaluating diabetic retinopathy. Loss of amplitude was more sensitive in identifying eyes with early stages of retinopathy, in which funduscopic evidence of retinopathy was still absent, whereas delay of response was more sensitive in grading eyes with later stages. With cases classified according to stage of retinopathy, loss of amplitude and delay of response, a theoretic curve of the electrophysiologic time-course of diabetic retinopathy was drawn. The curve showed that amplitude can distinguish normal from preretinopathic eyes, that with a loss of amplitude of less than 50% no retinopathy will be found ophthalmoscopically, and that with a delay of response greater than 8% the delay will correlate well with the stage of retinopathy.     

A comparison of oscillatory potential and pattern electroretinogram measures in diabetic retinopathy

Both basic and clinical electrophysiological investigations have established that the oscillatory potentials (OP) and pattern electroretinogram (PERG) appear to originate from retinal sites that are in proximity. The OPs, subcomponents of the flash ERG, have been shown to reflect disturbances in retinal circulation, and OP amplitude attenuation or loss may be a distinctive feature of diabetic retinopathy. The PERG has been shown to be abnormal in diseases of the optic nerve and ganglion cell body. Thus its relative sensitivity for detection of electroretinal abnormalities in diabetic retinopathy is in question. This study assessed the sensitivity of ERG and OP measures in their detection of abnormalities of electroretinal function in diabetic patients referred to our laboratory. Thirty-five adult Type I patients were studied: 21 with background retinopathy (BR group), 14 with no evidence of background retinopathy (No BR group), and 25 normal control subjects.Monocular OPs were recorded to full-field ganzfeld stimulation at four stimulus intensities. PERGs were obtained from checkerboard pattern reversal stimulation (checksize = 30 arc). Peak-to-peak amplitude and peak implicit time measures of PERGs and OPs were obtained. Subsequent multivariate analysis demonstrated significant differences between normals and diabetic patients, including diabetics with no clinical evidence of retinopathy. In addition, the OP and PERG implicit times appear to be unaffected while OP and PERG amplitudes were diminished in patients with background retinopathy. Only OP amplitudes were found to be significantly diminished in diabetic patients with no photographic evidence of background retinopathy. The PERGs were normal in these patients. Overall, the OP amplitude measures were more sensitive than PERG measures in detecting abnormalities in patients with no retinal photographic evidence of background retinopathy.     

视网膜振荡电位和视觉诱发电位检测在糖尿病视网膜病变前期诊断中应用

目的:观察尚未发生眼底病变的糖尿病确诊患者在不同病程时期视网膜振荡电位(OPs)和视觉诱发电位(VEP)的变化情况。方法:采用国际标准法对35例70眼正常人进行OPs和VEP的检测,对94例188眼未发生眼底病变糖尿病确诊患者按病程长短分为3组,分别进行OPs和VEP的检测。结果:各实验组与对照组相比表现为OPs幅值的降低和VEP峰值降低,潜时值延长,P<0.01,有显著统计学差异。各实验组之间相比表现为病程越长OPs幅值越低和VEP峰值越低,潜时值越长,P<0.01,有显著统计学差异。结论:糖尿病患者在眼底尚无病变前,其OPs和VEP已经出现异常,并且随着糖尿病病程的延长,各项指标的变化更加明显。因此,采用OPs和VEP的联合检测可以为糖尿病视网膜病的早期诊断提供依据。     

Changes of Oscillatory Potentials and Photopic Negative Response in Patients with Early Diabetic Retinopathy

Purpose

To investigate the clinical significance of the oscillatory potentials (OPs) and photopic negative response (PhNR) of the electroretinogram (ERG) in patients with early diabetic retinopathy.

Methods

One hundred two diabetic patients with diabetic retinopathy at different stages were examined. Thirty-two age-matched normal controls were also studied. Full-field maximal and photopic cone ERGs were recorded. The amplitudes and implicit times of the OPs, cone b wave, and PhNR were compared at the different stages of diabetic retinopathy.

Results

The a and b wave amplitudes of the maximal scotopic ERGs remained unchanged despite advancing stages of retinopathy, but the OP amplitudes were significantly attenuated even at an early stage of diabetic retinopathy. The amplitudes of both the PhNR and cone b wave were reduced at an early stage of diabetic retinopathy. Analysis of the receiver operating characteristic curves demonstrated that the amplitudes and implicit times of the OPs were more sensitive and specific than those of the PhNR in detecting changes of retinal function in the early stages of diabetic retinopathy.

Conclusions

The amplitudes of the OPs and PhNR progressively decrease with the progression of diabetic retinopathy. The PhNR amplitudes were reduced along with the cone b wave, indicating that earlier change of the PhNR in diabetic patients reflects reduced input to the retinal ganglion cell from the distal retina. The amplitudes and implicit times of the OPs are better indicators than those of the PhNR in detecting functional decreases in patients with early diabetic retinopathy.?Jpn J Ophthalmol 2006;50:367–373 © Japanese Ophthalmological Society 2006     

A comparison of photopic and scotopic electroretinographic changes in early diabetic retinopathy.

Previous studies of early diabetic retinopathy have shown that oscillatory potential (OP) amplitudes are reduced in many diabetic patients. OP amplitude is believed to be a more sensitive indicator of the development of future retinopathy than b-wave amplitude of the scotopic electroretinogram (ERG). Because OPs measured to a bright white flash reflect both rod and cone system activity, it is important to compare OP amplitudes to photopic ERG measures as well as scotopic measures in early diabetic retinopathy. In this study, OPs and ERG responses were measured under photopic and scotopic conditions in a group of diabetic patients. Although OPs were reduced in amplitude in the diabetic group, several other parameters of the scotopic and photopic b-waves were impaired. The results indicate that b-wave activity may indicate retinal changes in early diabetic retinopathy in the same manner as the OPs.     

Frequency spectrum and amplitude analysis of dark- and light-adapted oscillatory potentials in albino mouse,rat and rabbit

We studied frequency spectrum, implicit time and amplitude of oscillatory potentials (OPs) in albino mice, rats, and rabbits. Oscillatory potentials were extracted digitally from dark- and light-adapted electroretinograms (ERGs) recorded with a protocol commonly used in our laboratory. The frequency spectra of OPs were analyzed by using Fast Fourier Transform (FFT). Oscillatory potential amplitudes were calculated via numerically integrating the power spectrum. Oscillatory potential frequency spectra vary among species and are light-intensity dependent. In dark-adapted ERG, mouse and rat OPs have one major component with a frequency peak at approximately 100 Hz. Rabbits show multiple frequency peaks with a low frequency peak around 75 Hz. In all the three species, the implicit time of light-adapted OP is longer than that of the dark-adapted OPs. At a given intensity, mice have the highest OP responses. Our data suggest that the commonly used bandpass of 75 Hz (or even 100 Hz) to 300 Hz for OP extraction is insufficient in these animals. In order to acquire the complete OP responses from the ERG signals, it is necessary to determine the OP frequency spectrum. In this study, the lower end cutoff frequency was set at 40 Hz in mice, 65 Hz in rats and rabbits.     

Light adaptation of the human photopic oscillatory potentials: Influence of the length of the dark adaptation period

Photopic electroretinograms recorded immediately after a period of dark adaptation show a regular increase in amplitude with time spent in light. The retinal mechanisms at the origin of this light adaptation effect remain obscure. The purpose of this study was to investigate the duration of the dark adaptation period needed to produce an optimal light adaptation effect as demonstrated by photopic oscillatory potential recordings. Our results indicate that the light adaptation effect can be separated into two distinct processes. The first one, activated early in the dark adaptation process, reduces the amplitude of the fourth oscillatory potential to 32% of control after less than 5 min of dark adaptation, while the second process, activated after more than 10 min of dark adaptation, appears to impact solely the amplitude of the earlier oscillatory potentials 2 and 3. Our results suggest that the light adaptation effect is mediated by two distinct retinal pathways or mechanisms.Abbreviations DA dark adaptation - LAE light adaptation effect     

Lobular delayed choroidal perfusion as an early angiographic sign of diabetic retinopathy: a preliminary report

Between January 1982 and December 1983 stereo colour photography covering 10 standard fields of 30 degrees and fluorescein angiography were performed in 64 consecutive patients with diabetes mellitus who had no clinical evidence of diabetic retinopathy. Fifty-two patients were excluded on the basis of the slightest photographic or angiographic evidence of retinopathy or any other ocular disease. Electroretinogram oscillatory potentials were recorded in the remaining 12 patients. Four of the 12 had normal oscillatory potentials, colour photographs and angiograms, while 8 had angiographic evidence of lobular delayed choroidal perfusion and abnormal oscillatory potentials. Although only a small number of patients in the preclinical stages of diabetic retinopathy were studied, the results warrant that further attention be given to lobular delayed choroidal perfusion, which may represent early evidence of choroidal involvement in diabetic retinopathy.     

Measurement of the oscillatory potentials of the electroretinogram in the domains of frequency and time

The dark-adapted and light-adaped electroretinograms of 13 subjects with 23 normal eyes were analyzed by means of Fourier spectrum. The oscillatory potentials in the time domain were filtered out from the electroretinogram after a corresponding bandpass was given in the frequency domain. The coefficient of variation of total power, dominant power and dominant frequency of the isolated oscillatory potentials in the frequency domain, summed amplitudes and area of the isolated oscillatory potentials, each amplitude and implicit time of the first four major oscillatory potential wavelets in the time domain were compared. The implicit time showed the smallest coefficient of variation; summed amplitudes of OP1 to OP4 showed smaller coefficients of variation than those of the area, the amplitude of each oscillatory potential wavelet, dominant frequency and dominant and total power. The coefficient of variation of these measurement parameters in light-adapted electroretinograms was smaller than those in dark-adapted electroretinograms.Abbreviations CV coefficient of variation - OP oscillatory potential     

Physiological development of the kitten's retina: an ERG study

The physiological development of the retina was followed by recording ERGs and OPs from kittens of different ages. We found that different properties of the retina attain adult values at different ages: the b-wave elicited by higher stimulus intensities became adultlike by five to seven weeks while the b-waves elicited by lower stimulus intensities required another 3-5 weeks; the implicit time for the b-waves elicited by the full intensity stimulus attained adult values by 10 weeks of age; and the oscillatory potentials did not become adultlike until 18 weeks of age. The physiological development of the ERG was related to the development of the photoreceptors and the ganglion cells as well as to the morphological development of the second order neurons. It was concluded that the physiological development, as the morphological development, proceeds in three stages: an initial slow phase during which the late receptor potential and the b-waves are first recorded; a second rapid phase, during which the amplitude of the b-waves and OPs increase rapidly; and a third slow differentiation phase during which the final development of the properties of the retina are attained.     

Oscillatory potentials in electroretinographic evaluation of retinal function in insulin-dependent diabetics without retinopathy

PURPOSE: Can oscillatory potentials be a useful method for detection of retinal dysfunction in insulin-dependent diabetics without retinopathy? MATERIAL AND METHODS: In this study scotopic oscillatory potentials (OPs) were obtained in 35 subjects (70 eyes) with insulin-dependent diabetes without retinopathy (mean disease duration--5 years) and in 15 healthy subjects (30 eyes). This examination was performed according to the recommendations of the International Society of Clinical Electrophysiology of Vision (ISCEV). The oscillatory potentials were extracted from the maximal combined response by high-pass filtering. We analysed amplitude and peak-latencies of the first three electroretinographic oscillatory potentials O1, O2, O3, index of wavelets [sum of amplitudes (O1 + O2 + O3)] and compared with the results of the control group. RESULTS: In group of patients with insulin-dependent diabetes without retinopathy, we received statistically significant reduction of amplitude O1 (p < 0.003) and index of wavelets (p < 0.04). Reduced amplitude O1 was obtained in 10%, index of wavelets in 31.4% of analysed eyes. We didn't observe statistically significant changes in amplitudes O2, O3 and latencies O1, O2, O3. CONCLUSIONS: Our results suggest that retinal dysfunction is present in insulin-dependent diabetics without retinopathy 5 years after onset of the disease. The sum of amplitudes (O1 + O2 + O3) was the most sensitive parameter of retinal abnormalities. It seems reasonable to have more frequent ophthalmological examination of the diabetics with abnormal oscillatory potentials.