Effect of alcohol and light on the retinal pigment epithelium of normal subjects and patients with retinal dystrophies

BACKGROUND: Light absorbed by photoreceptors causes oscillations in the voltage across the retinal pigment epithelium (RPE). This is the basis of the clinical test, electro-oculography (EOG). We have previously shown that alcohol causes a sequence of voltage changes which are so precisely the same as those caused by light that they must be produced by the same RPE machinery. There is good evidence that alcohol produces its effect by a direct action on the RPE. Consequently, in diseases associated with loss of photoreceptors, alcohol should continue to produce the voltage changes of the EOG unless secondary changes have occurred in the RPE. METHODS: The alcohol response in patients with retinitis pigmentosa (RP) was investigated using EOG. RESULTS: In no patient with RP was there any alcohol rise. CONCLUSION: In patients with RP secondary abnormalities of function of the RPE must occur.     

Light rise of the human electroretinogram is normal in retinitis pigmentosa

Aim: To determine if the electroretinogram (ERG) light rise is reduced below normal in patients with retinitis pigmentosa (RP) and whether it is greater in patients with smaller ERG. Methods: Both eyes of 31 normal subjects and 59 subjects with RP had photopic ERGs on ISCEV standard and brighter backgrounds, before and after dark adaptation. Recordings <2.5 µV were excluded. Results: Ratios of amplitudes before and after dark adaptation varied little. The b‐wave averaged 1.88 (SD 0.41) in normal subjects and 1.66 (SD 0.62) in RP subjects, and a‐waves averaged 1.44 (SD 0.42) and 1.31 (SD 0.73), respectively. None of eight t?tests were significant (<2.4). There was a positive (not negative) correlation between RP subjects’ initial b‐wave amplitude and light rise but not for a‐waves. A‐wave light rises were smaller. Conclusion: Retinitis pigmentosa does not reduce the light rise of recordable ERG. The light rise of the ERG is larger in those RP subjects with larger initial b‐waves. This confirms previous findings. The difference between a‐ and b‐waves in RP suggests post‐receptoral processes are involved.     

The human electro-oculogram: interaction of light and alcohol

PURPOSE: To investigate the production of the voltage changes evoked in the retinal pigment epithelium (RPE) by light and alcohol and the interaction of these agents. METHODS: The eye movement potential in humans was intermittently recorded to standard horizontal excursions for long periods during which either retinal illumination was altered or ethyl alcohol was administered by the oral, intragastric, or intravenous route. In other experiments, both light and alcohol were administered. RESULTS: Alcohol and light produced near identical corneofundal voltage changes (positive and then negative) over more than 40 minutes. Differences in timing between alcohol and light increases are explicable by the delays in alcohol absorption. Weak background light suppressed the effect of light steps, and low levels of background alcohol suppressed the response to subsequent doses. Backgrounds of one agent did not affect the voltage changes caused by the other. Minimal alcohol effects were seen after administration of 1 g orally or 270 mg intravenously--that is, doses that produced undetectable changes in breath alcohol. The semisaturating oral dose was approximately 20 mg/kg. CONCLUSIONS: Alcohol and light act through separate pathways to form a final common pathway inside the RPE cell that is responsible for triggering the timing of the slow oscillatory changes of EOG voltage. The sensitivity and duration with which alcohol affects the RPE are comparable with the effect of melatonin or dopamine, although only the former interacts with light similarly to alcohol. Transient modulation of the acetylcholine (Ach) neuronal receptor occurs at similar sensitivity, but all other known actions of alcohol require higher concentrations than this RPE action.     

視網膜色素變性(RP)患者的EOG异常改變

目的探討RP患者眼電圖(EOG)的特徵以及EOG作為評估RP手術療效的客觀指標的可能性.方法采用MVT-3型視覺電生理儀的EOG采集和分析軟件,對正常對照組和RP患者組在術前與術後進行檢測.結果(1)105名RP患者的EOG曲綫大體可分為兩種類型,即彎曲型與平坦型.彎曲型EOG各項參數較接近正常組EOG,該組絕大部分患者的視野為斑駁狀;而平坦型EOG的一些主要參數(如Arden比和G比值等),明顯地低于正常組,該組患者的視野多為管狀視野或視野完全缺損.(2)在進行手術後半年以上復查EOG,則一些主要參數數值增加,有的患者(34.5%)的EOG由平坦型轉變為彎曲型.結倫RP患者的EOG具有為該病所特有的特徵,術後隨主觀癥狀的改善,EOG异常也恢復或部分恢復,這些都可作為該病診斷以及術後療效評估的客觀指標之一.     

视网膜色素变性患者手术治疗45名

目的:评估视网膜色素变性患者的手术疗效。方法:对45名视网膜色素变性患者90眼进行手术治疗,术前和术后分别对这些患者进行了视锐度、自动视野计和三种视觉电生理指标(F-ERG、EOG和P-VEP)的检测。结果:术后3～22月,患者的视锐度得到了明显的改善,视野显著扩大,视野缺损减低。术前在90眼中有73眼(81.1%)的暗视F-ERG为熄灭型,在术后3～22月期间进行复查时,有些曾消失的F-ERG波复现,暗视F-ERG为熄灭型的眼下降至66(73.3%)只(P <0.05, t检验),一些原来残存的F-ERG波的波幅增加,峰潜伏期也缩短。EOG曲线变得更为弯曲,某些EOG的参数(如Arden比和G比值)也明显的增加(P <0.05, t检验)。用棋盘格翻转刺激中央6о视野时能够记录到P-VEP的患者数目,在45例中由术前的22例在术后增加到31例。这45例的残存P100波的平均振幅由术前的1.007μV增加到术后的2.236μV,有显著的统计学差异(P<0.005, t检验)。结论:手术治疗RP是有效和安全的,并能改善患者的视觉和阻止RP病程的发展。     

Differential effects of light and alcohol on the electro-oculographic responses of patients with age-related macular disease

PURPOSE: Alcohol (EtOH) affects the electro-oculogram (EOG) in ways very similar to light, although the two agents act on the RPE through different routes. Are the EOGs to light and to alcohol affected similarly in age-related macular degeneration (AMD) and age-related maculopathy (ARM)? METHODS: Standard eye movements and recording of EOGs were used. After 26 minutes of baseline recording in darkness, subjects were either exposed to 30 cd/m(2) light or drank 226 mg/kg alcohol (7.1% vol/vol) in water. RESULTS: In 17 patients with ARM and AMD (aged 67-86 years; mean, 77), the light-EOG was slowed in comparison to normal, and the voltage changes were somewhat reduced. The mean reduction in the alcohol-EOG (EtOH-EOG) was much greater. The reduction was equal in the two eyes, regardless of uniocular foveal impairment. Some EtOH-EOG loss occurred in patients with minor fundus changes and no loss of acuity, but the loss was greater in patients with "wet" or "dry" ARM and AMD. Grading of RPE changes correlated with the decrease in EtOH-EOG responsiveness, but not with light-EOG responsiveness. CONCLUSIONS: EtOH- and light-EOGs are affected differentially. In ARM, even with minor fundus changes, patients appear to have a general abnormality in the RPE. The alcohol response abnormality is correlated to the fundus appearance, but not with age. These results provide further evidence that EtOH acts by a pathway different from that governing the action of light. These results support histologic and other evidence that in ARM there is a functional barrier between the choroid and the RPE-retina.     

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.     

Electrooculographic study in the chicken after treatment with neurotoxin 6-hydroxydopamine

The implication of dopamine in the modulation of the standing potential of the eye was tested in the chicken by an indirect electrooculogram (EOG) method. After a single rapid systemic injection of dopamine, a transient dose-dependent increase in the EOG voltage was observed. EOG recordings during light and dark adaptation were performed after retinal dopamine depletion was induced by intraocular injections of the neurotoxin 6-hydroxydopamine (6-OHDA). The eyes were injected on two successive days with a mixture of 6-OHDA (50 g), pargyline (a monoamine oxidase inhibitor), and ascorbate added as an antioxidant. Following this treatment EOG recordings were performed 1, 4, and 8 days after the second injection. The electrophysiological changes appeared most spectacular on the fourth day: an important increase in the EOG basal values as well as of the amplitude of the light peak and of the dark trough were observed. Substantial reduction in retinal concentration of dopamine was found in treated retinas. These unexpected electrophysiological data offer additional evidence for the involvement of a catecholamine in the generation of the light peak and the dark trough of the EOG.     

Alcohol- and Light-induced Electro-oculographic Responses: Variability and Clinical Utility

The alcohol-induced electro-oculographic (EOG) response has been proposed by Arden as an indicator of retinal pigment epithelial (RPE) integrity. We have evaluated the consistency of the alcohol-EOG with respect to clinical applicability and compared this response to the ISCEV-standard EOG. We recorded, in a group of normal subjects (n=29, 14 men with mean age 42±11 years and 15 women with mean age 36±13 years), the alcohol response to a single oral dose of ethanol at 160 mg/kg (as 40 proof vodka, drunk in 15 s after 12 h of fasting), followed by an ISCEV-standard EOG 90 min after alcohol administration. Blood alcohol levels were monitored at regular intervals with a breath analyzer. We found a wide range of amplitudes in both light and alcohol responses among participants, from minimal to large values. Subjects had a wide range of blood alcohol concentrations from 0.02 to 0.10%; near the time of the response peak, but there was no relationship between alcohol levels and peak/baseline ratios. In addition, there was no relationship between alcohol peak/baseline ratio and the Arden ratio. Neither the alcohol nor the light response parameters showed any relationship with age or gender. Some of the inter-individual variability in the EOG response to alcohol may reflect variable absorption of oral alcohol. The alcohol-induced EOG has too broad a range of responses to be useful clinically for the one-time evaluation of individual patients. We have similar concerns regarding clinical applications of the standard light-induced EOG.     

Detecting chloroquine retinopathy: electro-oculogram versus colour vision

AIM: To investigate the relative sensitivity and specificity of two tests of retinal function (the electro-oculogram (EOG) and a computerised colour vision test) in screening for ocular toxicity caused by chloroquine and hydroxychloroquine. METHODS: 93 patients with rheumatic diseases receiving long term chloroquine and hydroxychloroquine therapy were followed for an average of 2.6 years. Clinical examination, an EOG, and a quantitative test of colour vision were carried out every 6 months. RESULTS: Mild fundus changes were observed in 38 patients. Four patients developed typical bull's eye maculopathy, three of whom had received 250, 365, and 550 g total dose of chloroquine, and one 1500 g of hydroxychloroquine. Statistical analysis of all patients showed that for those with no fundus changes or stippled pigmentation a number showed elevation of tritan threshold, so that if macular stippling is a sign of mild retinopathy the test on tritan changes has a 64% sensitivity and 63% specificity for an upper threshold value of 7%. All four patients with bull's eye lesions showed a marked disturbance of tritan colour vision, with a threshold of 14.8%, a sensitivity of 75%, and a specificity of 94%. For protan colour vision a threshold of 10% gives 75% sensitivity and 91% specificity. By contrast, neither an absolute nor a relative EOG reduction was a valid criterion for early or late chloroquine retinopathy. In advanced retinopathy an Arden coefficient (AQ) <180% yields 50% sensitivity and 54% specificity. When AQ <160% is the threshold, sensitivity does not increase but specificity rises to 82%. Occurrence of marked corneal deposits on clinical examination yields 50% sensitivity and 90% specificity in this situation. CONCLUSION: Screening for chloroquine retinopathy can be improved by using a sensitive colour test. Disturbance of the tritan axis appears to occur first. A normal test result on computerised colour testing virtually excludes any retinopathy by antimalarials. The EOG is of little diagnostic value.     

视网膜色素变性97例的眼电图研究(英文)

目的 研究视网膜色素变性的超微结构及病理性改变与眼电图之间的关系 方法 采用视觉电生理技术,对97例视网膜色素变性患者进行眼电图(EOG)检测,观察光峰电位等十项指标、并与47名健康者进行比较 结果 视网膜色素变性患者的色素上皮层功能明显损害,97例视网膜色素变性患者的眼电图检测表现为三种类型:①光波明显降低(低波型)54例,占55.67％;②光峰暗谷消失(无波型)14例,占14.43％;③暗谷光峰倒转(倒置型)29例,占29.90％。低波型者提示色素上皮功能轻度损害;无波型者提示色素上皮严重受损,倒置波提示锥体细胞受损较杆细胞为重,明适应阶段锥体细胞反应低下。结论 眼电图的检测有助于视网膜色素变性患者的诊断及判断病程进展情况     

視網膜色素變性97例的眼電圖研究

目的研究視網膜色素變性的超微結構及病理性改變與眼電圖之間的關系.方法采用視覺電生理技術,封97例視網膜色素變性患者進行眼電圖(EOG)檢測,觀察光峰電位等十項指標,并與47名健康者進行比較.結果視網膜色素變性患者的色素上皮層功能明顯損害,97例視網膜色素變性患者的眼電圖檢測表现爲三種類型(①光波明顯降低(低波型)54例,占55.67%;(②光峰暗谷消失(無波型)14例,占14.43%;③暗谷光峰倒轉(倒置型)29例,占29.90%.低波型者提示色素上皮功能輕度損害;無波型者提示色素上皮嚴重受損,倒置波提示錐髓细胞受損較杆细胞爲重,明通應階段锥髓细胞反應低下.結論眼電圖的檢測有助于視網膜色素變性患者的診斷及判斷病程進展情况.     

Effects of ethyl alcohol on the electrooculogram and color vision

Color vision tests and electrooculography (EOG) were performed in 6 male and 2 female healthy young trichromatic volunteers between 60 and 130 min after finishing consumption of ethyl alcohol leading to blood levels of approximately 0.07% to 0.16%. The average number of errors in the desaturated Panel D-15 arrangement test rose from 0.86 to 2.0; the average error score in the Farnsworth-Munsell 100-Hue test rose from 26 to 79. The axis of errors in both tests was clearly tritanopic and tetartanopic, pointing to a specific effect of ethyl alcohol on the function of blue-sensitive cones and/or their interaction with longer wavelength-sensitive cones.Ethyl alcohol decreased the size of the light-peak, apparently in a dose-dependent fashion, in each of the 16 eyes by values between 3% and 79%. The effect of alcohol on the EOG light peak was stronger between 30 and 95 min (23% decrease in average) than between 95 and 130 min (14% decrease) after the finish of alcohol administration.     

Autosomal dominant vitreoretinochoroidopathy with normal electrooculogram in a German family

• Background: Autosomal dominant vitreoretinochoroidopathy (ADVIRC) is a rare disorder previously described in four families residing in the USA and one family residing in Germany. We report the clinical and unexpected electrophysiological findings in a sixth family, residing in Germany. • Methods: An affected 23-year-old man, his 52-year-old affected mother and his 55-year-old unaffected father were examined by testing visual acuity, fluorescein angiography, visual fields, dark adaptation, electrooculography (EOG) and electroretinography (ERG). • Results: The 23-year-old man showed a circumferential retinochoroidal dystrophy extending from the mid-periphery to the ora serrata. There was a sharp demarcation between affected and nonaffected retina. Peripheral to the damarcation, bone spicules and yellow-white deposits were present, and the retinal vessels were severely attenuated. In addition, vitreous opacities were present. The EOG light rise was normal. The ERG amplitudes were reduced to 35% of the normal in all recording conditions. The 52-year-old mother showed marked peripheral pigmentation, but no bone spicules, deposits or vitreous opacities. Her EOG and ERG recordings were normal. • Conclusions: Expression of ADVIRC can be very variable within the same family. A reduced EOG light rise, previously suggested as a characteristic sign for ADVIRC, is not a typical sign for all affected patients. Received: 8 January 1997 Revised version received: 26 February 1997 Accepted:17 April 1997     

The Effects of Darkness on Retrobulbar Hemodynamics in Patients with Early Stages Retinitis Pigmentosa

PURPOSE: To investigate the retrobulbar hemodynamic changes occurring in light and darkness in patients with early stages retinitis pigmentosa (RP). METHODS: Eleven early stages RP patients were enrolled in the study. The peak systolic velocity (PSV), end-diastolic velocity (EDV), pulsatility index (PI) and resistivity index (RI) of the ophthalmic artery (OA) and central retinal artery (CRA) were measured by color Doppler imaging in light and darkness. The results were compared with that of 10 age-matched normal subjects. RESULTS: PSV and EDV of the OA did not show significant differences in both groups. However, PSV and EDV of the CRA in RP patients decreased significantly in darkness (p = 0.001, p < 0.001, respectively). In addition, we found a significant increase in RI of the CRA in RP patients in darkness (p = 0.003). On the contrary, PSV and EDV of the CRA in control subjects showed a significant increase (p = 0.002, p < 0.001, respectively) and RI showed a significant decrease in darkness (p = 0.004). CONCLUSIONS: Darkness causes a decreased blood flow in the CRA in early stages of RP.     

Acute zonal occult outer retinopathy: towards a set of diagnostic criteria

BACKGROUND: Individuals with acute zonal occult outer retinopathy (AZOOR) present with initially progressive scotomata and photopsia. Characteristically, the extent of the visual field defect is unexplained by fundal examination, but there is marked retinal dysfunction evident electrophysiologically. It is the authors' experience that a group of patients exhibit characteristic clinical and electrophysiological abnormalities, which serve as criteria for a working diagnosis. METHODS: A retrospective observational case series of 28 patients were identified with the clinical diagnosis of AZOOR who shared similar abnormal electrophysiology. Details of the history and ophthalmic findings were obtained from the case notes. RESULTS: Electrophysiology demonstrated a consistent pattern of dysfunction both at the photoreceptor/retinal pigment epithelial complex but also at inner retinal levels, essentially comprising a delayed 30 Hz flicker ERG and a reduction in the EOG light rise. CONCLUSION: This study determines diagnostic criteria applicable to a group of patients with AZOOR, typically those with classic symptomatology. Electrophysiological testing can help avoid lengthy, costly, and potentially invasive investigations, and the unnecessary use of immunosuppressive therapy.     

Visual sensitivity at an edge

The threshold for a small spot of light rises as it approaches the edge of an illuminated area and gradually falls in the dark. The threshold rise on the illuminated side of the edge was found to be dependent on the intensity of the illuminated field, absent at low in tensity. Short duration flashes of both edge and test spot abolished the threshold elevation on the illuminated side of the edge regardless of field intensity. While the threshold rise may be associated with lateral inhibitory effects, the fall in the dark was shown to be due to stray light in the eye.     

The standing potential of the eye in retinal detachments

To investigate the standing potential and its light rise in retinal detachments, a group of 33 patients was examined preoperatively. The group was divided into 3 subgroups according to the extent of the detachment. Apart from practical interest, this investigation was carried out to answer the question whether contact between the pigment epithelium and the receptor layer is necessary for the generation of the standing potential. This appeared not to be the case, on the contrary the standing potential was often higher.The EOG light rise, on the other hand, was more disturbed in comparison with the extent of the detachment. Various features of the EOG may be explained, if we assume an inhibitory action of the retina on the generator of the standing potential under normal conditions.     

Vigabatrin: longterm follow-up of electrophysiology and visual field examinations

BACKGROUND: To report the results of repeated electrophysiological and visual field examinations in patients with vigabatrin-associated visual field loss (VGB-VFL) and the relationship between these electrophysiological findings, the cumulative dose of vigabatrin and the extent of visual field loss. METHODS: Twenty-two eyes of 11 patients with VGB-VFL were studied. All patients underwent surgery for therapy-resistant epilepsy. Repeated electro-oculograms (EOGs) and flash electroretinograms (ERGs) were made and the cumulative dose of vigabatrin and the visual field loss were recorded after a period of 37-47 months. RESULTS: The visual field loss was stable in patients who had stopped vigabatrin at the time of the first examination. There was a slight increase in VFL in patients who continued vigabatrin. During the second EOG and ERG, abnormalities in scotopic and photopic a-wave latencies and in scotopic b-wave amplitude were found in more than 50% of patients. Only b-wave latency became normal, while EOG, a-wave latency, a-wave amplitude and b-wave amplitude stayed abnormal. The amount of VFL and the cumulative dose of vigabatrin were statistically correlated with the b-wave amplitude, mainly photopic, found during the first and second examinations. CONCLUSION: After 4 years, EOG, flash ERG and visual field loss had not improved in patients with VGB-VFL. The statistically significant correlation found during the first examination between the amount of VFL and the cumulative dose of vigabatrin with the (mainly photopic) b-wave amplitude remained constant.     

55th Annual Symposium of the International Society for Clinical Electrophysiology of Vision (ISCEV 2017)

The clinical electro-oculogram (EOG) is an electrophysiological test of the outer retina and retinal pigment epithelium (RPE) in which changes in the electrical potential across the RPE are recorded during successive periods of dark and light adaptation. This document presents the 2017 EOG Standard from the International Society for Clinical Electrophysiology of Vision (ISCEV: www.iscev.org). This standard has been reorganized and updated to include an explanation of the mechanism of the EOG, but without substantive changes to the testing protocol from the previous version published in 2011. It describes methods for recording the EOG in clinical applications and gives detailed guidance on technical requirements, practical issues and reporting of results with the main clinical measure (the Arden ratio) now termed the light peak:dark trough ratio. The standard is intended to promote consistent quality of testing and reporting within and between clinical centers.