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.     

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.     

Alteration of oscillatory potentials in diabetics induced by photocoagulation of the retina

Oscillatory potentials (OP) of the electroretinogram (ERG) were recorded and normalized with respect to the overall amplitude of the ERG in normal and diabetic subjects. Normalized OP decrease with increasing diabetic retinopathy, exhibiting a strict bilateral symmetry in normal individuals but an extremely wide scatter (of asymmetry between both eyes) in diabetics. It can be demonstrated that after successful (?) photocoagulation (partial or panretinal), the amplitude of the OP can sometimes increase, possibly indicating improved retinal function in the noncoagulated area.     

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.     

Electrophysiology in the investigation of acquired retinal disorders

Electrophysiological research on acquired retinal disorders, both common and rare, is reviewed. Age is a major factor influencing electroretinogram (ERG) and electro-oculogram (EOG) findings. Bipolar or Müller cell death in the aging retina could account for much of the amplitude decline that is observed with age. In diabetic retinopathy, the oscillatory potentials can monitor the progression of the disease and indicate neuronal alterations rather than diabetic angiopathy of the retina. Human ERG studies on glaucoma concentrated on ERG measures that are dominated by inner retinal contributions. It has been shown that the pattern ERG can serve as a predictor of ocular hypertension's progression to glaucoma. In retinal disorders caused by endogenous intoxication, such as hepatic retinopathy, or exogenous intoxication from chronic lead exposure, ERG changes give an objective measure of the damage and allow to study the pathophysiological mechanisms that are involved. Inflammations of the choroid and the retina affect the standard ERG when they are diffuse. In central serous chorioretinopathy, functional disturbances can be revealed not only in the photoreceptors but also in the middle and inner retinal layers with the use of focal stimuli. Choroidal melanoma leads to large reductions of the EOG light peak-to-dark trough ratio through its influence on the transepithelial potential of the retinal pigment epithelium (RPE). In cancer-associated retinopathy, both the rod and cone ERGs are reduced. However, selective cone dysfunction has been described. In melanoma-associated retinopathy, the long flash ERG may reveal a specific pathophysiological mechanism, namely the affection of the ON-pathway with preservation of the OFF-pathway. ERG measurements can reveal vitamin A deficiency and are altered in cases with a mutation in the gene for the retinol binding protein in which other organs are not affected. Photochemical damage to the retina from light emission by the operating microscope can be assessed by electrophysiological methods.     

Multifocal electroretinogram in diabetic subjects

PurposeTo identify local retinal abnormalities and evaluate the nature and extent of retinal dysfunction in diabetics using full field electroretinogram (ERG) and multifocal ERG (MF-ERG) and to determine the correlation between features of optical coherence tomography (OCT) and MF-ERG.MethodsTwenty-eight normal subjects (Control Group; 56 eyes) and 37 patients (72 eyes) with diabetes mellitus (DM Group) were evaluated. In the DM Group, 17 eyes had no retinopathy (grade 1), 18 eyes had early non proliferative diabetic retinopathy (NPDR) (grade 3), 16 eyes had late NPDR (grade 4), 21 eyes had proliferative diabetic retinopathy (PDR) (grade 5). Full field ERG and MF-ERG, were used to assess the effects of diabetic retinopathy on retinal function. OCT and fluorescein angiography were used to assess and compare morphological changes with functional changes in diabetes mellitus.ResultsIn diabetic patients without retinopathy (17 eyes), the amplitudes of the second order component of MF-ERG were reduced and implicit times were delayed, while only implicit times of first order component of MF-ERG were delayed but the amplitudes of first order component were normal. In diabetic patients with retinopathy (55 eyes), the overall amplitudes were reduced and peak implicit time increased in the first order component and second order component.OCT of the DM Group showed the fovea of eyes with edema were thicker than the Normal Group. The fovea of eyes with cystoid macular edema (CME) were significantly thicker than the fovea of eyes with diffuse swelling. The implicit times of MF-ERG were directly correlated with foveal thickness.ConclusionMF-ERG reveals local retinal dysfunction in diabetic patients. MF-ERG offers the advantage of topographic mapping of retinal dysfunction. The magnitude of delay of MF-ERG implicit time reflects the degree of local clinical abnormalities in eyes with retinopathy. Local response delays found in eyes without retinopathy detects subclinical local retinal dysfunction in diabetics. The combination of OCT and MF-ERG may provide objective criteria for evaluation and assessment of diabetic retinopathy.     

多焦视网膜电图检测糖尿病早期视功能的变化

目的：了解多焦视网膜电图（mfERG）在糖尿病患早期视功能的变化规律。方法：将所有被检分为正常对照组（33例）、糖尿病无视网膜病变组（63例）以及单纯期糖尿病视网膜病变组（43例）。采用mfERG对上述3组进行检测,比较3组mfERG一阶反应N1波与P1波的潜伏期与反应密度。结果：在糖尿病无视网膜病变组中,N1波与P1波反应密度低于正常对照组,异常范围位于环1一环3。其中P。波反应密度在单纯期糖尿病视网膜病变组中进一步降低。N1波与P1波的潜伏期在糖尿病无视网膜病变组中的变化无统计学意义,在糖尿病视网膜病变组中延长,异常范围扩大到环4与环5。结论：mfERG在糖尿病视网膜病变出现之前已发生异常变化,且能够定量地反映随着病情的进展,视功能的损害程度及范围。     

Selective reduction of the S cone electroretinogram in diabetes.

AIMS: To determine whether the short wavelength sensitive (S) cone electroretinogram (ERG) is selectively altered in diabetic patients with and without retinopathy. METHODS: Ganzfeld spectral flashes in the presence of bright white background illumination were used to elicit S cone ERGs is 15 non-retinopathic diabetics, 16 background retinopathic diabetics, and 16 age matched normal controls. RESULTS: The amplitude of the S cone ERG b-wave was significantly reduced in both non-retinopathic and retinopathic diabetics. An action spectrum based on equal response criteria revealed a selective loss of S cone sensitivity in diabetics. However, no significant difference was observed in the long and middle wavelength sensitive cone ERG. CONCLUSIONS: Diabetic patients showed selective reduction of the S cone ERG, which is thought to reflect changes in the outer retina.     

The nature and extent of retinal dysfunction associated with diabetic macular edema

PURPOSE: To evaluate the nature and extent of retinal dysfunction in the macular and surrounding areas that occurs in patients with diabetes with clinically significant macular edema (CSME). METHODS: Eleven patients were evaluated before focal laser treatment. Multifocal electroretinogram (ERG) and full-field ERG techniques were used to assess the effects of diabetic retinopathy and CSME on macular, paramacular, and peripheral retinal function. A modified visual field technique was used to obtain local threshold fields. The relationship between local sensitivity changes and local ERG changes was determined. RESULTS: Local ERG responses were significantly delayed and decreased in amplitude, and timing changes were observed in a larger area of the retina than amplitude changes. Visual field deficits were similarly widespread with marked sensitivity losses occurring in retinal areas with normal ERG amplitudes and in areas that appeared to be free of fundus abnormalities. Despite this similarity and the finding that retinal areas with elevated thresholds have timing delays, timing delays were not good predictors of the degree of threshold elevation. CONCLUSIONS: The results demonstrate the widespread nature of timing deficits and visual field deficits that are associated with CSME.     

NPDR患者黄斑区视网膜厚度、视网膜神经纤维层厚度与全视野闪光ERG的变化

目的探讨非增生性糖尿病视网膜病变(non-proliferative diabetic retinopathy,NPDR)患者黄斑区视网膜厚度(retinal thickness,RT)、视网膜神经纤维层(retinal nerve fiber layer,RNFL)厚度与全视野闪光视网膜电图(electroretinogram,ERG)的变化及相互关系。方法选择2010年2月至12月于我院就诊的2型糖尿病患者91例(168眼),依据糖尿病视网膜病变(diabetic retinopathy,DR)国际分期标准分为3组:无糖尿病视网膜病变(NDR)组39例(78眼),轻度NPDR组28例(52眼),中重度NPDR组24例(38眼)。另选择同龄正常人30例(60眼)作为正常对照组。通过光学相干断层扫描检测黄斑区中心RT及RN-FL厚度,全视野闪光ERG检测视网膜功能。结果 NDR组、轻度NPDR组、中重度NPDR组患者黄斑区RT分别为(198.01±22.51)μm、(218.00±28.15)μm、(239.90±65.04)μm,均较正常对照组(184.45±18.50)μm增厚,差异均有统计学意义(t=2.312、5.235、7.947,均为P<0.05);随着DR加重,糖尿病各组间黄斑区RT比较,差异均有显著统计学意义(t=3.305、6.300、3.069,均为P<0.01)。正常对照组与NDR组黄斑区RNFL厚度比较,差异无统计学意义(P>0.05);轻度NDPR组及中重度NPDR组与正常对照组相比,黄斑区RNFL厚度变薄,差异均有统计学意义(均为P<0.05)。与正常对照组比较,中重度NPDR组全视野闪光ERG暗适应0.01反应及明适应3.0反应b波潜伏期明显延长(均为P<0.05),暗适应0.01反应b波振幅和暗适应3.0反应a波振幅均下降(均为P<0.05)。结论随着NPDR病情加重,2型糖尿病患者黄斑区中心RT增加,RNFL厚度减小,视网膜功能受损。     

Retinal function in the von Hippel-Lindau disease

Purpose: To assess the retinal function in patients with von Hippel-Lindau disease (VHL). Patients: Studies were undertaken in 12 patients (17 eyes) with detected VHL gene mutation and 12 normal healthy controls (17 eyes). Methods: Pattern ERG (PERG), standard flash electroretinogram (ERG) recordings were performed in accordance with the International Society for Clinical Electrophysiology of Vision (ISCEV) standards. Results: In VHL patients, electrophysiological statistically significant changes were found. In PERG examination, increased latency of P50 was found in the total VHL group (p<0.02) and in the VHL subgroup with retinal angiomas (p<0.04). In ERG examination, photopic b-wave latency was increased in the total VHL group (p<0.03) and also in the VHL subgroup without retinal angiomas (p<0.05). In OPs, latency increase of OP2, OP3 waves and reduced amplitude of OP3 wave in the total VHL group (OP2 latency, p<0.05; OP3 latency, p<0.01; OP3 amplitude, p<0.03) and in the VHL subgroup with retinal angiomas (OP2 latency, p<0.02; OP3 latency, p<0.008; OP3 amplitude, p<0.02) were obtained. Conclusions: It can be hypothesized that dysfunction of the inner retinal layer is present in individuals with VHL disease even in patients without retinal angiomas.     

视网膜电图诊断早期糖尿病视网膜病变

视网膜电图是一项评价视网膜功能的客观检查,适用于评价多种眼科疾病的视网膜功能情况。近年研究发现,在早期糖尿病患者中,视网膜电图能够发现先于眼底视网膜形态学改变的功能变化,这一点为糖尿病视网膜病变的病理机制研究、早期诊断、以及预后评估提供了新思路,进而可能为治疗糖尿病视网膜病变提供新途径。我们就运用视网膜电图诊断早期糖尿病视网膜病变进行综述。     

眼底无可见视网膜病变的糖尿病患者多焦视网膜电图特征

目的 检测眼底无视网膜病变糖尿病患者的多焦视网膜电图(multifocol electmretinogram, mf-ERG),评价其在糖尿病患者早期视网膜功能改变中的作用.方法 应用mf-ERG检测30例(56只眼)正常对照组和32名(58只眼)无眼底镜下可查见的视网膜病变的糖尿病患者.对两组mf-ERG中a波和b波的潜伏期、振幅总和以及b波的振幅密度进行分析比较.结果 在糖尿病组,除0环和颞下象限之外.b波的潜伏期均明显延迟,而a波和b波振幅总和及b波的振幅密度减低主要集中在黄斑周围区域(0～1环)和颞上象限,差别有统计学意义(P<0.05).结论 mf-ERG能在DR出现之前客观定量地评定视网膜功能的变化程度和范围.     

PFCL and ILM peeling in macular hole with retinal detachment

To investigate the early changes of retinal function in diabetic patients detected by multifocal electroretinogram (mfERG). ·METHODS: The first-order kernel responses of mfERG were recorded fromeyes of 33 normal control subjects, 63 diabetic patients without retinopathy and 43 diabetic patients with background retinopathy. The response densities and implicit times of N₁ and P₁ were compared among the control, diabetic patients without retinopathy and diabetic patients with retinopathy. ·RESULTS: The response densities of N1 and P1 in central 3 rings were reduced significantly in diabetic eyes with and without retinopathy. And the implicit times of N₁ and P₁ were delayed significantly only in diabetic eyes with retinopathy. ·CONCLUSION: mfERG can detect the early changes of retinal function quantitatively in diabetic patients. Analysis of response densities and implicit times of N₁ and P₁ can reflect the progress of local retinal dysfunction in diabetes     

An electrophysiological study on panretinal photocoagulation in diabetic retinopathy

Twelve patients with proliferative diabetic retinopathy were treated with panretinal photocoagulation. EOG, ERG, and OPs were recorded before and after photocoagulation. It was found that EOG and ERG were reduced after photocoagulation. This may be explained by the fact that laser radiation is absorbed mainly in the pigment epithelium. As OPs amplitude improved after treatment, OP/ERG quotient may be said to reflect the new retinal situation and to represent a means of evaluating the course of retinopathy.     

Early changes of retinal function in diabetic patients detected by multifocal electroretinogram

To investigate the early changes of retinal function in diabetic patients detected by multifocal electroretinogram (mfERG). ·METHODS: The first-order kernel responses of mfERG were recorded fromeyes of 33 normal control subjects, 63 diabetic patients without retinopathy and 43 diabetic patients with background retinopathy. The response densities and implicit times of N₁ and P₁ were compared among the control, diabetic patients without retinopathy and diabetic patients with retinopathy. ·RESULTS: The response densities of N1 and P1 in central 3 rings were reduced significantly in diabetic eyes with and without retinopathy. And the implicit times of N₁ and P₁ were delayed significantly only in diabetic eyes with retinopathy. ·CONCLUSION: mfERG can detect the early changes of retinal function quantitatively in diabetic patients. Analysis of response densities and implicit times of N₁ and P₁ can reflect the progress of local retinal dysfunction in diabetes     

Multifocal electroretinogram delays reveal local retinal dysfunction in early diabetic retinopathy.

PURPOSE: To identify local retinal abnormalities in diabetic patients with and without retinopathy, by using the multifocal electroretinogram (M-ERG). METHODS: Electroretinograms were recorded at 103 discrete retinal locations in each eye of eight persons with nonproliferative diabetic retinopathy (NPDR) and eight diabetic persons without retinopathy, using VERIS (EDI, San Mateo, CA). The amplitude and implicit time of each local (first-order) retinal response were derived and compared with normal values obtained from 16 age-matched, nondiabetic subjects. Maps of local response amplitude and implicit time were compared with fundus photographs taken at the time of testing. RESULTS: In eyes with NPDR, the implicit times of responses from retinal sites manifesting clinical pathologic fundus lesions (e.g., microaneurysms and focal edema), were markedly delayed (e.g., up to 7 msec from normal). Responses from adjacent retinal sites that were more normal in clinical appearance were also delayed, but to a lesser extent (e.g., 2-5 msec). Smaller, yet significant local response delays were also found in eyes without retinopathy. By contrast, local response amplitudes bore no consistent relationship to fundus abnormalities in eyes with retinopathy, and amplitudes were typically normal in eyes without retinopathy. CONCLUSIONS: The M-ERG reveals local retinal dysfunction in diabetic eyes even before retinopathy. The magnitude of delay of local ERG implicit time reflects the degree of local clinical abnormality in eyes with retinopathy. Local response delays found in some eyes without retinopathy suggest that the M-ERG detects subclinical local retinal dysfunction in diabetes. Analysis of M-ERG implicit time, independent of amplitude, improves the sensitivity of detection of local retinal dysfunction in diabetes.     

Oscillatory potential changes related to stimulus intensity and light adaptation

The oscillatory potentials (OPs) are a series of subcomponents of the flash ERG which probably originate in the inner plexiform layer of the retina. Abnormal OPs in various forms of retinopathy include central retinal vein occlusion, congenital stationary night blindness, and diabetic retinopathy. We investigated the effects of stimulus intensity and light adaptation on the OP components identified in our laboratory. OPs were recorded from 20 adult eyes to full-field ganzfeld stimulation at four stimulus intensities from 12 to 62cd/m². Stimulus flashes were superimposed over a steady background luminance in the ganzfeld. Four background luminances were used over a 3-log unit range from mesopic to photopic levels. Peak-to-peak amplitude and peak implicit time measures of the OPs were obtained. Latency-intensity functions were derived for each of the four OP components at each light-adaptation level. These latency-intensity functions revealed similar curve fitting slopes for all OP subcomponents at lower light-adaptation levels. At higher levels of light adaptation the later subcomponents (OP3 and OP4) showed a flattening of the slope of the latency-intensity function. The investigator concludes that this saturation effect is related to an interaction of rod and cone contribution to the OP waveform.     

Colour Doppler imaging of the ocular circulation in diabetic retinopathy

PURPOSE: To measure blood flow velocity in the ophthalmic artery (OA) and central retinal artery (CRA) in patients with diabetic retinopathy. SUBJECTS AND METHODS: 62 age-matched subjects divided into 3 groups: nondiabetic controls (n=17); diabetics with no clinical retinopathy or background changes (n=24); diabetics with either pre-proliferative or proliferative retinopathy (n=21). Colour Doppler imaging was performed on supine patients by one masked observer using the Acuson 128 machine. RESULTS: There was a statistically significant (p<0.05) decrease in both the peak systolic velocity (PSV 0.073 m/s) and end diastolic velocity (EDV 0.014 m/s) of the central retinal artery in the pre-proliferative/proliferative group compared to the no retinopathy/background retinopathy group (PSV 0.096 m/s, EDV 0.024 m/s) and the control group (PSV 0.142 m/s, EDV 0.029 m/s). The resistance index of the ophthalmic artery was significantly increased in both the preproliferative/proliferative (0.81) and the no retinopathy/background group (0.81) compared to controls (0.72). CONCLUSION: Reduced blood flow velocity was found in the CRA of diabetic patients and appeared to become further reduced with the progression of retinopathy. This suggests that monitoring with Colour Doppler imaging may have predictive power in identifying those at greatest risk of developing sight threatening proliferative disease. The resistance index of the OA was increased in diabetics compared to controls.     

视网膜电图PhNR和OPs在非增生型DR中的变化特点

目的观察非增生型糖尿病视网膜病变（DR）中视网膜电图PhNR和OPs的变化特点,比较OPs、PhNR指标在早期诊断及评估视网膜功能的敏感性和特异性。方法选取经间接检眼镜、荧光素眼底血管造影（FFA）确诊的DR患者30例（30眼）,同时选取与其性别、年龄相匹配的正常对照25例（25眼）作为对照组。2组均进行视力、闪光视网膜电图（F-ERG）、FFA检查。比较2组PhNR振幅、OPs振幅及ERG其他参数指标,并探讨不同DR分级与PhNR振幅、OPs振幅的变化关系。结果在OPs指标中,DRⅠ~Ⅳ级OPs振幅与正常值比较差异均有统计学意义（P〈0.05）,PhNR指标显示,DRⅠ级PhNR振幅与正常值比较,差异无统计学意义（P〉0.05）,DRⅡ~Ⅳ级与正常组比较,差异均有统计学意义（P〈0.05）。在比较各参数ROC下面积（AUC）中,OPs指标的AUC最高,为0.866;其次是PhNR指标,AUC为0.754。OPs诊断NPDR的敏感性和特异性分别为63.6%和80%,而PhNR的敏感性和特异性分别为54.5%和73.3%。结论DR在病变初期即出现血液循环性改变、神经细胞功能障碍,表现为PhNR振幅和OPs振幅均明显降低。OPs指标在DR的早期诊断及评估视网膜功能方面敏感性和特异性更高。