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 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     

Ocular haemodynamics and colour contrast sensitivity in patients with type 1 diabetes

BACKGROUND: There is evidence that altered ocular blood flow is involved in the development and progression of diabetic retinopathy. However, the nature of these perfusion abnormalities is still a matter of controversy. Ocular haemodynamics were characterised with two recently introduced methods. METHODS: The cross sectional study was performed in 59 patients with type 1 diabetes with a diabetes duration between 12 and 17 years and an age less than 32 years and a group of 25 age matched healthy controls. Scanning laser Doppler flowmetry and laser interferometric measurement of fundus pulsation amplitude were used to assess retinal and pulsatile choroidal blood flow, respectively. In addition, colour contrast sensitivity along the tritan axis was determined. RESULTS: Fundus pulsation amplitude, but not retinal blood flow, increased with the progression of diabetic retinopathy. Retinal blood flow was influenced by plasma glucose levels (r = 0.32), whereas fundus pulsation amplitude was associated with HbA(1c) (r = 0.30). In addition, a negative correlation between the colour contrast sensitivity along the tritan axis and retinal blood flow was observed. CONCLUSIONS: The present study indicates that pulsatile choroidal blood flow increases with the progression of diabetic retinopathy. Increased retinal blood flow appears to be related to loss of colour sensitivity in patents with type 1 diabetes.     

Tolerability of levocabastine eye drops

We used an oscillatory potential power method (a measure of the summed oscillatory potential activity) based on fast-Fourier transform analysis to study the oscillatory potentials in early diabetic retinopathy. The method was used in 29 diabetic patients with no ophthalmoscopically visible diabetic retinopathy, 29 diabetic patients with early signs only and 27 control subjects. The reduction in oscillatory potential power was compared with the reduction in the second and third oscillatory potential amplitudes and increase in implicit time in the diabetic patients. The amplitude of the second oscillatory potential was slightly more resistant to diabetic retinopathy than was the amplitude of the third oscillatory potential. Because the oscillatory potentials were detected by means of a high-resolution technique, their implicit times seem to be as discriminating as the oscillatory potential power in the detection of early 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.     

Choroidal blood flow in diabetic retinopathy

The ocular hemodynamics in diabetic patients with increasingly severe retinopathy have been evaluated using a non-invasive computerized methodology. In a group of 19 healthy volunteers the mean ophthalmic arterial pressure and the ocular pulsatile blood flow were 83 +/- 2.4 mmHg and 648 +/- 42 microliters min-1 respectively. Nine diabetics with no apparent retinopathy had ophthalmic pressures and pulsatile blood flows similar to those in the control subjects. In 11 diabetic patients with background retinopathy the mean pulsatile blood flow was 471 +/- 70 microliters min-1. Thirteen diabetics with proliferative retinopathy had a pulsatile blood flow of 210 +/- 37 microliters min-1 and abnormally low ophthalmic arterial pressures. The results provide evidence that the choroidal blood flow decreases with the severity of the retinopathy in diabetes due to increased vascular resistance and a decreased ocular perfusion pressure.     

Pattern electroretinograms become abnormal when background diabetic retinopathy deteriorates to a preproliferative stage: possible use as a screening test.

The pattern electroretinogram (PERG) and other tests were given to a selected group of patients with diabetes, ranging from those who had no retinopathy or funduscopic changes to those in the preproliferative state. None had visual symptoms. The PERG was found to be normal in patients with microaneurysms and a few blot haemorrhages. However, when cotton-wool spots and angiographic evidence of areas of capillary non-perfusion were present, the PERG was reduced below the normal value. Similar changes occurred with the oscillatory potentials of the ERG evoked by an intense flash, but the results were more variable. So in the individual patient the test is not a reliable indicator of the progress of the retinopathy. The value of the PERG in screening is discussed.     

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, macular recovery time, and diabetic retinopathy through 3 years of intensified insulin treatment

Forty-five diabetic patients, 18 to 45 years of age, with mild or no retinopathy, were randomly assigned to continuous subcutaneous insulin infusion (CSII), multiple injections (Mls), and conventional insulin treatment (CIT). The effects of near-normoglycemia (CSII and MI) on oscillatory potentials (electroretinography [ERG]) and macular recovery time (nyctometry) were studied prospectively for 41 months. Before randomization, the amplitudes of oscillatory potentials were negatively correlated to age (P = 0.002) and positively correlated to the diameter of retinal veins (P less than 0.05). Men had shorter macular recovery time than women (P = 0.03). Nyctometry and oscillatory potentials were not related to mean blood glucose values, glycosylated hemoglobin (HbA1), retinopathy, blood pressure levels, or duration of diabetes. Changes in metabolic control (MI and CSII; P less than 0.01) and in microaneurysms and hemorrhages (CSII and CIT) during the study did not affect oscillatory potentials or nyctometry. Soft exudates (15 patients) and proliferative retinopathy (1 patient) transiently developed with MI and CSII regimens. No changes in oscillatory potentials or nyctometry were observed and no pretreatment characteristics of these parameters predicted the occurrence of these ischemic lesions. At the stage of proliferation, however, lowered amplitudes of oscillatory potentials and lengthened macular recovery time were observed.     

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.     

视网膜激光光凝治疗糖尿疴陛视网膜病变的疗效分析

目的 观察糖尿病性视网膜病变（DR）眼行视网膜激光光凝前后视力、无灌注区、视网膜新生血管及闪光视网膜电图（f-ERG）的变化.方法 前瞻性病例对照研究.2009年1月至2010年7月在新疆维吾尔自治区人民医院眼科行视网膜激光光凝的增殖前期糖尿病性视网膜病变（PPDR）72眼和增殖性糖尿病性视网膜病变（PDR）48眼纳入研究.在光凝前1周及之后1个月行视力、荧光素眼底血管造影及f-ERG检查.对患眼视力、视网膜新生血管及无灌注区消退情况进行计数,记录光凝前后患跟视杆反应b波、混合反应b波、震荡电位、视锥反应b波及30 Hz振幅.治疗前后的数据采用配对t检验进行分析.结果 视网膜激光光凝后,PPDR组中48眼视力保持不变,24眼下降;54眼无灌注区全部消退,16眼部分消退,2眼未消退.PDR组中12眼视力提高,26眼保持不变,10眼下降;24眼新生血管全部消退,16眼部分消退,8眼未消退.光凝前后患眼视杆反应b波振幅分别为（186.7±34.1）μV和（106.7±24.8）μV;混合反应b波振幅分别为（381.2±60.4）μV和（273.2±47.8）μV;振荡电位振幅分别为（66.6±12.4）μV和（86.6±18.7）μV;视锥反应b波振幅分别为（97.4±13.5）μV和（67.2±9.4）μV;30 Hz振幅分别为（24.1±8.4）μV和（20.1±6.4）μV,差异均有统计学意义（t=5.672、5.343、3.427、3.578、2.979,P均＜0.01）.结论 视网膜激光光凝后,大部分DR眼的视力提高或保持稳定,无灌注区及新生血管消退,明显改善了视网膜的血液循环,是治疗糖尿病性视网膜病变的有效方法.     

Effect of isometric exercise on choroidal blood flow in type I diabetic patients

BACKGROUND: In healthy subjects, choroidal blood flow is regulated when the mean ocular perfusion pressure increases. Since capillary vascular beds are altered in diabetic patients, the regulation of choroidal blood flow could be affected by this pathology. PATIENTS AND METHODS: 10 type I diabetic patients without retinopathy (DNR group) and 7 type I diabetic patients with retinopathy (DR group) participated in the study. In NDR and DR groups, choroidal blood flow was measured while patients raised their mean arterial blood pressure by squatting. The results were compared to those of a previous study in normals. Pupillometry was performed at rest on the two diabetic groups and on seven normals during a modification of illumination (white/black screen transition). RESULTS: In the NDR and DR groups, mean ocular perfusion pressure raised by 61 and 50 % during squatting, respectively. Consecutively, choroidal blood flow did not change in NDR as in normals, but increased linearly in DR patients. The white/black screen transition produced an increase of the pupil diameter of 52 and 49 % in normals and NDR patients, respectively, while it increased by only 16 % in the DR patients. CONCLUSIONS: As already shown in healthy subjects, choroidal blood flow is regulated in NDR patients when the ocular perfusion pressure increases. In DR patients, the absence of this control could be due to a failure of the autonomic nervous system, as suggested by pupillometry results.     

Visual field constriction and electrophysiological changes associated with vigabatrin

Purpose: We investigated functional, morphological and electrophysiological changes in patients under anti-epileptic therapy with vigabatrin (VGB), a GABA aminotransferase inhibitor. Methods: 20 epileptic patients treated with vigabatrin (age range 25–66 years) were enrolled in this study. The referrals were made by the treating neurologist, based on suspected or known visual field changes in these patients. Two patients had vigabatrin monotherapy, 18 patients were treated with vigabatrin in combination with other antiepileptic drugs. None of the patients reported visual complaints. Patients were examined with psychophysical tests including colour vision (Farnsworth D15), dark adaptation threshold, Goldmann visual fields and Tuebingen Automated Perimetry (90°). A Ganzfeld ERG and an EOG following the ISCEV standard protocol were also obtained. Additionally, all patients were examined with the VERIS multifocal ERG including recordings of multifocal oscillatory potentials. Results: Visual acuity, anterior and posterior segments, colour vision and dark adaptation thresholds were normal in all patients. Of 20 patients, 18 presented visual field constriction. All patients with visual field defects revealed altered oscillatory potentials waveforms in the ERG, especially in those patients with marked visual field defects. Multifocal oscillatory potentials were also delayed in those patients. In some patients a delayed cone single flash response (6/20), a reduced mERG amplitude (12/20) and a reduced Arden ratio (9/20) were found. Conclusions: The present data indicate an effect of vigabatrin on the inner retinal layers. Since abnormalities of the oscillatory potentials were seen in all patients with visual field defects a dysfunction of GABA-ergic retinal cell transmission might be assumed.     

Early diagnosis of retinal changes in diabetes: a comparison between electroretinography and retinal biomicroscopy

The present study was undertaken in order to find out whether electroretinographic examinations could reveal signs of functional abnormalities before morphological changes are detected in the diabetic retina. Pattern-reversal and flash electroretinograms (ERG) and oscillatory potentials (OP) were recorded in 24 diabetics and 10 age-matched normal controls. The diabetic group consisted of 11 patients without retinopathy and 13 patients with background retinopathy. No significant changes in pattern-reversal or flash ERG or OP amplitudes were observed in the diabetic group with normal fundus or with background retinopathy. The findings imply that ERG examination with the described techniques does not reveal retinal dysfunction in diabetics before retinopathy can be detected by means of retinal biomicroscopy.     

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.     

Familial primary pulmonary hypertension and associated ocular findings

BACKGROUND: Familial primary pulmonary hypertension (PPH) is a rare, fatal, autosomal dominant disease that results in right heart failure from idiopathic obliteration of the pulmonary arteries. Patients develop stagnation of venous blood flow and elevated venous pressure. METHODS: The authors retrospectively reviewed the clinical records of three patients diagnosed with PPH that was confirmed on the basis of physical examination, chest X-ray, electrocardiogram, and echocardiogram. Cardiac catheterization excluded cardiac shunt and other secondary causes of pulmonary hypertension. RESULTS: Two patients presented with a clinical picture resembling venous stasis retinopathy, and one with bilateral choroidal detachments. Two patients had delayed choroidal filling on fluorescein angiography, which was confirmed in one patient with indocyanine green videoangiography. CONCLUSIONS: Elevated venous pressure found in PPH is responsible for the delayed choroidal perfusion and the reduced venous blood outflow. This explains the clinical findings of venous stasis retinopathy and choroidal detachments seen in these patients.     

脉络膜厚度对糖尿病患者视网膜病变病情影响的研究

目的研究脉络膜厚度对糖尿病患者视网膜病变病情的影响。方法选取于我院2013年1月至2015年12月收治的90例糖尿病患者作为治疗对象,早期糖尿病视网膜病变(DR)治疗研究(ETDRS)标准规定DR可分为5类:无DR无糖尿病黄斑水肿(DR-/DME-)组17例(17只眼);非增生型糖尿病视网膜病变(NPDR)无糖尿病黄斑水肿(NPDR+/DME-)组23例(23只眼);增生型糖尿病视网膜病变(PDR)无糖尿病黄斑水肿(PDR+/DME-)组10例(10只眼);NPDR伴糖尿病黄斑水肿(NPDR+/DME+)组34例(34只眼);PDR伴糖尿病黄斑水肿(PDR+/DME+)组6例(6只眼)。对照组选取同期在我院体检中心进行体检的90例健康体检者。全部研究对象进行增强深部成像相干光断层扫描(EDI-OCT)。对中心凹下脉络膜厚度(SFCT)进行比较,判断其在不同阶段DR中存在的差异,分析脉络膜厚度对DR病情的影响。结果对照组、无DR无糖尿病黄斑水肿组、NPDR无糖尿病黄斑水肿组、PDR无糖尿病黄斑水肿组、NPDR伴糖尿病黄斑水肿组、PDR伴糖尿病黄斑水肿的SFCT平均值分别为(273士24)、(272±23)、(260±26)、(244士25)、(227±27)、(214±30);对照组各组SFCT均大于观察组,差异具有统计学意义(P<0.05),其中PDR无糖尿病黄斑水肿(PDR+/DME-)组SFCT值小于无DR无糖尿病黄斑水肿(DR-/DME-)组,差异具有统计学意义(P<0.05),NPDR伴糖尿病黄斑水肿(NPDR+/DME+)组SFCT值小于PDR无糖尿病黄斑水肿(PDR+/DME-)组,差异具有统计学意义(P<0.05)。结论脉络膜厚度的变化与DR之间存在联系,二者相互影响,使病情加重,对患者脉络膜厚度进行监测,将有助于综合分析糖尿病患者的视网膜病变情况。     

芪明颗粒对糖尿病患者脉络膜循环的影响

目的:探讨芪明颗粒对糖尿病患者眼部特别是视网膜及脉络膜血液循环的影响.方法:根据眼底造影结果将所有患者分为两组:无糖尿病视网膜病变组(no diabetic retinopathy,NDR)和非增殖型糖尿病视网膜病变组(nonproliferative diabetic retinopathy,NPDR),运用眼底血管造影检查评价糖尿病患者视网膜及脉络膜的血液循环状态及造影特征,重点观察服药前和服用芪明颗粒后的视网膜及脉络膜动脉的充盈时间,利用精确数据评价芪明颗粒对糖尿病患者眼部血液循环的影响.结果:在服用芪明颗粒3mo后NDR和NPDR两组糖尿病患者视网膜及脉络膜动脉充盈时间均加快,充盈倒置及脉络膜晚期斑点状强荧光的发生率明显下降.结论:芪明颗粒可以使视网膜及脉络膜的血流加快,改善糖尿病患者眼部血液循环状态,延缓糖尿病视网膜病变的发生和发展.     

糖尿病视网膜病变临床前期的视功能变化分析

目的:观察糖尿病视网膜病变临床前期患者的图形视觉诱发电位、视网膜振荡电位以及视神经纤维层厚度的变化,评估糖尿病视网膜病变临床前期视功能的变化.方法:收集糖尿病视网膜病变临床前期的2型糖尿病患者89例,以及健康志愿者80例.均采用罗兰电生理检查系统检测图形诱发电位(P-VEP)的P100潜伏期和振幅、视网膜振荡电位(Ops)总振幅和各子波振幅,以及RTVueOCT检测视神经纤维层厚度(RNFL),对检测结果进行比较分析.结果:糖尿病组患者的P100潜伏期比正常对照组的P100潜伏期明显延长,差异有统计学意义(t=-10.633,P=0.000).糖尿病组患者的P100振幅比正常对照组的P100振幅明显降低,差异具有统计学意义(t=3.610,P=0.000).糖尿病组患者OPS总振幅及各子波振幅均比正常对照组OPS总振幅及各子波振幅明显降低,差异具有统计学意义(t=17.320,P=0.000;t=3.239,P=0.000;t=4.144,P=0.000;t=7.666,P=0.000;t=5.319,P=0.000).与正常对照组相比,糖尿病组患者的平均RNFL厚度及鼻侧、下方及颞侧RNFL厚度均无明显改变,差异无统计学意义(t=1.730,P=0.085;t=0.664,P=0.547;t=1.923,P=0.063;t=1.814,P=0.072).而上方RNFL厚度明显变薄,与正常对照组相比差异显著(t=7.989,P=0.000).结论:在糖尿病视网膜病变临床前期的患者,视乳头及黄斑区均出现了视功能改变.