Focal macular photopic negative response in patients with optic neuritis

Purpose

To investigate, by focal macular electroretinography (ERG), the change of photopic negative response (PhNR) in the recovery of visual function in patients with optic neuritis.

Methods

Focal macular ERG was recorded from nine patients with acute optic neuritis (38.6±10.2 years). The photostimulator device projected 15° visual angle spotlight onto the macula. Focal macular ERG recording was performed at the onset and at 1 month and 6 months after the onset of optic neuritis. The results were compared between each recording for seven of the patients.

Results

All patients decreased in the vision below 20/100 and had central scotoma. Vision improved more than 20/20 within 1 month and full-visual field recovered within 6 months after the onset in all patients. The amplitude of the a-wave, b-wave, and PhNR of focal macular ERG at the onset was significantly attenuated in eyes with optic neuritis (66.8±15.5, 65.8±17.7, and 65.2±14.4% of normal control, respectively). The amplitude of the a-wave and b-wave increased gradually after steroid pulse therapy. The increase in a-wave amplitude was significant at 6 months (P=0.046), whereas the PhNR amplitude did not show any significant change over 6 months after the onset of optic neuritis.

Conclusions

Our results suggest that inflammation at the onset of optic neuritis leads to functional deficits that extend to at least the inner nuclear layers of the retina, and that all but the ganglion cell layers of retina recover.     

Comparison of photopic negative responses elicited by red and white xenon flashes in monkeys

PURPOSE: The photopic negative response (PhNR) is a negative component of the photopic electroretinogram (ERG), and is believed to originate mainly from the retinal ganglion cells. The PhNR is commonly elicited by red light-emitting diodes. The purpose of this study was to compare the amplitude of the PhNR elicited in monkeys by red stimuli and white stimuli obtained from a xenon light source. METHODS: The PhNRs were elicited from six rhesus monkeys by photopically matched red and white xenon flashes (peak output, 600 nm) on a rod-saturating blue background. The amplitudes of the PhNR elicited by white flashes were compared with those elicited by the red flashes before and after the intravitreal injection of tetrodotoxin (TTX). RESULTS: The differences in PhNR amplitudes between the red and white stimuli, and the changes in the PhNR amplitudes after the injection of TTX, were not statistically significant. CONCLUSION: These results suggest that red and white xenon flashes are of approximately equal value for assessing inner retinal function using the PhNR under our recording conditions.     

阿柏西普治疗糖尿病性黄斑水肿患者多焦视网膜电图明视负反应变化

目的:观察糖尿病性黄斑水肿(DME)患者接受阿柏西普治疗前后多焦视网膜电图(mf-ERG)明视负反应(PhNR)的变化。方法:回顾性队列研究。收集2019-05/2022-06在武汉大学附属爱尔眼科医院(武汉爱尔眼科医院)就诊的DME患者37例37眼,每月注射阿柏西普0.05mL,连续注射3mo。并选取排除相关眼部疾病的体检正常者20例20眼作为对照组。比较两组参与研究者治疗前后mf-ERG的PhNR振幅,最佳矫正视力(BCVA)(LogMAR)、中央视网膜厚度(CRT)、黄斑区毛细血管丛血管密度(CPVD)。结果:治疗前DME患者mf-ERG PhNR振幅(201.69±80.92nV)明显低于正常对照组(398.87±77.92nV)(P<0.01)。治疗后6mo DME患者mf-ERG的PhNR平均振幅与治疗前明显升高(P=0.036),但在治疗后6mo时仍明显低于正常对照组(P=0.031)。治疗后6mo DME患者BCVA(LogMAR)从0.64±1.33提高到0.37±1.39(P=0.021),CPVD较治疗前明显增加(P=0.029)。治疗后6mo DME患者m...     

正常眼视网膜电图明视负向反应研究

目的研究不同性别、年龄正常眼的视网膜电图（electroretinogram，ERG）中明视负向反应（photopic negative response，PhNR）的潜伏期和振幅，并分析性别、年龄对PhNR的影响。方法选取正常健康者和单眼外伤者共54例（60眼），进行ERG检查，记录其视网膜电图PhNR的潜伏期和振幅，分别按年龄（〈20岁组，20-40岁组，〉140岁组）和性别统计其正常值范围并进行比较。结果PhNR潜伏期女性较男性略短，PhNR振幅女性较男性略低，但差异无显著性（P〉0.05）。随年龄增大，PhNR的潜伏期延长，各组间差异均有显著性（P〈0．01）；随年龄增大，PhNR的振幅下降，差异出现在40岁以上组与其他两组之间（P=0．02）。结论与其他ERG成分类似，PhNR的潜伏期和振幅亦受年龄和性别的影响，故在进行视网膜电图PhNR分析时应综合考虑性别、年龄等因素。     

视网膜电图明视负向反应对外伤性视神经萎缩的诊断意义

目的研究外伤性视神经萎缩的视网膜电图（ERG）各成分及其明视负向反应（PhNR）的变化特点，并进行PhNR与视网膜神经纤维层厚度（RNFLT）、视野平均缺损值（MD），以及杯盘比（C／D）的相关性研究，探索在外伤性视神经萎缩中PhNR的变化规律。方法选取外伤性视神经萎缩的患者21例（25眼）和与其性别年龄相匹配的正常人25例（25眼）。分别对两组进行ERG、视野、眼底照相和光学相干断层扫描（OCT）检查，比较两组视网膜电图，并将外伤性视神经萎缩组的PhNR振幅分别与MD、C／D和RNFLT进行相关性分析。结果外伤性视神经萎缩组的PhNR振幅比对照组明显下降（P〈0．01），而外伤性视神经萎缩组和对照组的ERG中暗视反应、最大反应、30Hz震荡电位的振幅差异无统计学意义，视神经萎缩组明视反应a波和b波振幅差异也无统计学意义。PhNR的振幅与视神经损伤情况如RNFLT（r=0．665）、MD（r=0．564）、杯盘比（r=0．686）等相关，且相关关系有统计学意义（P〈0．01）。结论视网膜电图PhNR振幅在外伤性视神经萎缩眼明显地下降甚至消失，PhNR可作为外伤性视神经萎缩的诊断和神经节细胞及其轴突功能评价的良好指标。     

原发性视神经萎缩患者视网膜电图明视负向反应振幅异常

目的研究视网膜电图(ERG)明视负向反应(PhNR)在原发性视神经萎缩进展中的变化特点以及与视网膜神经纤维层厚度(RNFLT)的关系。设计前瞻性、对照性研究。研究对象正常健康者18例(18眼)和原发性视神经萎缩稳定期患者15例(18眼)及7例(7眼)视神经挫伤导致视神经萎缩的患者。方法对正常健康者和原发性视神经萎缩者进行ERG和相干光断层扫描(OCT)检查,比较两组PhNR振幅,并将原发性视神经萎缩者的PhNR振幅与RNFLT进行相关分析;另对视神经挫伤导致视神经萎缩者随访半年,研究其PhNR振幅与RNFLT变化规律。主要指标PhNR振幅与RNFLT。结果稳定期原发性视神经萎缩组和对照组的ERG中暗视反应、最大反应、30Hz震荡电位的振幅及明视反应a波和b波振幅差异均无显著性意义,但原发性视神经萎缩组的PhNR振幅比对照组明显下降(P<0.01),而且PhNR的振幅与RNFLT显著相关(r=0.688,P<0.01)。视神经挫伤导致视神经萎缩的患者随访第1~3个月,PhNR振幅下降先于RNFLT的变薄。结论原发性视神经萎缩眼ERGPhNR振幅明显下降甚至消失,且PhNR振幅下降早于RNFLT变薄。     

用DTL电极测量我国正常人视网膜电图的明视负波反应

目的用DTL电极测量我国正常人视网膜电图的明视负波反应(PhNR)的正常值,探讨正常人PhNR的特征。方法应用美国ESPION视觉电生理仪及一次性使用的DTL电极测量我国正常人65例(112眼)的PhNR。全视野刺激器由LED发出光源,选用蓝色背景光(亮度为10cd/m2),刺激光为红色(刺激光强度分别为1、5cd.s/m2和7cd.s/m2)。按10岁一年龄组分组统计PhNR的振幅和潜伏期。结果经统计学分析,将年龄组间无显著统计学差异的组作合并后,分成<50岁和≥50岁两个年龄组。这两组的正常振幅值在1、5cd.s/m2和7cd.s/m2时分别为(-38.94±10.21)μV和(-32.41±7.76)μV,(-38.51±10.97)μV和(-34.52±8.90)μV,(-38.62±9.98)μV和(-33.96±9.81)μV,正常潜伏值分别为(65.83±4.06)ms和(69.86±5.68)ms,(66.17±6.48)ms和(71.33±4.90)ms,(65.81±6.71)ms和(70.40±4.61)ms,表明两个年龄组的振幅和潜伏值均有显著统计学差异。结论一次性DTL电极可防止交叉感染。研究确定了按相关年龄分组的我国正常人PhNR的正常值。     

Inter-ocular and inter-session reliability of the electroretinogram photopic negative response (PhNR) in non-human primates

PURPOSE: To assess the inter-ocular and inter-session reliability for a range of parameters derived from the photopic electroretinogram (ERG) in a group of normal non-human primates. METHODS: Inter-ocular differences for photopic ERGs were assessed in a group of normal anesthetized adult rhesus monkeys (Macaca mulatta, n=29); inter-session reliability was assessed for 23 eyes of 23 animals tested 3 months later. Signals were acquired using Burian-Allen contact lens electrodes, whereby the contralateral cornea served as a reference. Photopic ERGs were elicited using red Ganzfeld flashes (-0.5-0.67 log photopic cd.sm(-2)) on a rod suppressing blue-background (30 scotopic cdm(-2)). Measurement reliability was established for a-wave, b-wave, photopic negative response (PhNR) and oscillatory potential (OP) amplitudes, as well as for their implicit times, by calculation of the 95% limits-of-agreement (LOA) and the coefficient-of-variation (COV) for each parameter. RESULTS: OP and a-wave amplitudes increased with intensity up to 0.67 log photopic cd.sm(-2), following a typical saturating function, whereas b-wave and PhNR amplitudes both declined above 0.42 log photopic cd.sm(-2). Inter-session variability was greater than inter-ocular variability. The inter-session COVs for PhNR amplitude (10-20%) were similar to the other photopic ERG components (a-wave: 12-17%, b-wave: 12-17%, OPs: 13-19%). Inter-session LOAs were also similar across components, but on average, were smallest for responses to moderate intensities (0.0-0.42 log photopic cd.sm(-2)). CONCLUSION: In non-human primates, the 95% LOA for inter-session measurements of the photopic ERG a-wave, b-wave, OPs and PhNR are all similar. Inner-retinal damage may best be measured using the PhNR amplitude for moderately bright stimulus intensities. B-wave and PhNR amplitudes for brighter flashes are smaller and more variable. The ratio of PhNR:b-wave amplitudes manifests smaller variability and may therefore be useful for detection of selective PhNR loss.     

The negative response of the flash electroretinogram in glaucoma

The existence of a negative ERG component following the b-wave has been known for a long time. Recently, in unilateral macaque experimental glaucoma, a negative response in flash electroretinograms under scotopic as well as photopic conditions has been shown to be greatly reduced or absent compared to the healthy fellow eye. The aim of this pilot study was to test whether a late negative electroretinogram component is reduced also in human glaucoma patients under different stimulus conditions. Dark-adapted ganzfeld flash electroretinograms were recorded after 30 min of dark using two test conditions, obtained as optimal in pilot studies on controls. Under the scotopic condition I white Xenon-flashes of intensity 0.53 Log photopic Td s were presented on a low white background of 1.38 Log scotopic Td. Under the more photopic condition II orange flashes of intensity –0.37 Log photopic Td s were presented on a blue-adapting background of 2.5 Log scotopic Td. Nine controls and 18 patients with advanced glaucoma were analyzed. The amplitude of the negative response was not significantly reduced in glaucoma patients (condition I: –28.5±23.7 V; condition II: –25.2±19.7 V) compared to controls (condition I: –41.4±36.6 V; condition II: –31.3±26.2 V). The peak latency of the responses under condition I and II did not differ significantly between patients and controls. Thus, the late negative electroretinogram component in ganzfeld flash electroretinograms obtained under scotopic and more photopic conditions does not seem to distinguish as easy between human controls and glaucoma patients as animal experiments suggest.     

视网膜电图明视负波反应在开角型青光眼中的临床应用价值

目的评价视网膜电图(electroretinogram,ERG)的明视负波反应(photopic negative response,PhNR)在开角型青光眼患者中的临床应用价值。方法应用美国ESPION视觉电生理仪及一次性使用的DTL微纤维电极测量67例(67眼)正常人(年龄为21~76岁)、41例(62眼)开角型青光眼患者(年龄为21~77岁)的PhNR。全视野刺激器由LED光源发光,选用蓝色背景光(亮度为10 cd/m2),刺激光为红色光(刺激光强度分别为1 cd.s/m2、5 cd.s/m2和7 cd.s/m2)。采用Humphrey C30-2程序检查患者的视野,根据视野检查结果将青光眼患者分为早期组12例(21眼),进展期组13例(17眼)和晚期组16例(24眼)。在记录视网膜电图时,患者的眼压控制在正常范围内。检查患者的眼底并测量视盘的杯盘比。结果正常人的明视ERG都有伴随b波的缓慢的负向电位,即PhNR,其振幅随年龄的增大而降低。青光眼患者的a波及b波的振幅和潜伏期与年龄匹配的正常值对照差异无显著性,但是PhNR振幅较正常值明显降低,甚至在视野敏感度轻度缺失的早期组患者就出现PhNR的振幅下降,并且随视野敏感度缺失的增加,进展期和晚期组患者PhNR的振幅下降更加明显。在全部青光眼患者中,PhNR的振幅与视野的平均偏差(mean deviation,MD)、模式标准差(pattern stan-dard deviation,PSD)和垂直方向的杯盘比(C/D)存在明显的相关性(P<0.01)。结论开角型青光眼患者的PhNR的振幅比正常对照组低,PhNR振幅降低与青光眼病情的严重程度相关,早期青光眼患者的PhNR振幅就出现下降,并随视野敏感度缺失的增加下降更加明显。PhNR振幅降低对青光眼有较高的敏感性和特异性。PhNR可以作为开角型青光眼的早期检测及其青光眼损伤进展的一个视功能评价指标。     

眼部缺血综合征患者视网膜电图明视负向反应和震荡电位的变化特点

目的观察眼部缺血综合征(ocular ischemic syndrome,OIS)患者视网膜电图(electroretinogram,ERG)明视负向反应(PhNR)和震荡电位(oscillatory potentials,OPs)的变化特点。方法选取2009年6月至2010年2月在我院就诊的OIS患者12例15眼行常规闪光ERG检查,同时选取正常对照眼15人15眼,视网膜中央静脉阻塞(central retinal vein occlusion,CRVO)患者15例15眼行闪光ERG检查。比较OIS患眼与正常对照眼、CRVO患眼的PhNR和OPs,及其余各项ERG指标的振幅变化差异。采用Stata11统计学软件分析受试者工作曲线下面积(AUC),并进行数据分析,比较OPs及PhNR区分正常眼及OIS眼的敏感度及特异性。结果 PhNR振幅在OIS组为(49.36±12.20)μV、CRVO组为(25.62±6.72)μV、正常组为(59.79±11.83)μV。三组之间两两比较,差异有显著统计学意义(F=41.287,P<0.01)。OPs振幅在OIS组为(128.44±23.86)μV、CRVO组为(102.69±10.55)μV、正常组为(154.01±15.08)μV。三组之间两两比较,差异也有显著统计学意义(F=78.098,P<0.01)。PhNR指标的AUC为0.7240±0.0945,95%的可信区间为(0.53871,0.90925),其敏感度为73.3%,特异性为86.7%。OPs指标的AUC为0.8170±0.0810,95%的可信区间为(0.65814,0.97579),其敏感度为86.7%,特异性为80.0%。结论 OIS患者PhNR、OPs振幅较正常对照组明显降低,但较CRVO患者降低程度轻,表明OIS患者视网膜组织存在缺血的现象,但其缺血程度较CRVO患者轻。OPs在评估OIS患者内层视网膜的血液循环功能方面比PhNR更好。     

弱视眼视网膜电图明视负波反应的研究

目的 通过对正常人与弱视患者视网膜电图明视负波(PhNR)对比分析,探讨PhNR在弱视患者中的临床应用价值.方法 正常人30名60只眼(年龄5～35岁),弱视48例60只眼(5～35岁),选择蓝色背景光(亮度为25 cd/m2),刺激光为红色光(亮度2 cds/m2)下进行明视负波检查,再根据视觉发育敏感期分为＜12岁和≥12岁两个年龄组,记录各种检查结果并分析.结果 (1)弱视组PhNR反应振幅均值均较正常组降低,其差异有统计学意义.(2)弱视组PhNR潜伏期和正常组相 似,其差异不具有统计学意义.(3)正常人≥12岁年龄组PhNR反应振幅均值较＜12岁年龄组降低,潜伏期延迟,其差异具有统计学意义.结论 (1)弱视患者PhNR反应振幅降低,与正常组差异显著有统计学意义,提示PhNR可以作为弱视患者的一个视功能评价指标,弱视患者视网膜神经节细胞功能存在一定程度的抑制.(2)≥12岁PhNR的反应振幅较＜12岁降低,潜伏期延迟,提示PhNR反应与年龄有关联.     

Early macular dysfunction detected by focal electroretinographic recording in non-insulin-dependent diabetics without retinopathy

The focal electroretinogram, which measures the functional integrity of the distal retina of the macula, was recorded with a hand-held stimulator-ophthalmoscope in 26 eyes from patients with non-insulin-dependent diabetes mellitus with normal fundus photography, and in 52 control eyes of similar age range. Implicit time and amplitude of the responses were studied as a function of the age, glycemic control through glycosylated hemoglobin measurement and duration of diabetes. Implicit time and amplitude were significantly delayed (F=5.05, p=0.028) and reduced (F=11.26, p=0.013) in diabetic patients without diabetic retinopathy compared to control subjects. Moreover, there was a significant relationship between the implicit time (r=0.57, p=0.002) and amplitude (r=−0.65, p=0.0004) with the duration of diabetes but not with hemoglobin Alc. These results strongly suggest an early macular dysfunction in noninsulin-dependent diabetes mellitus before the appearance of diabetic retinopathy.     

明视负波反应在青光眼早期诊断中的临床意义

视网膜电图的明视负波反应(PhNR)是在明适应条件下,用亮光刺激时,在正向b波后记录到缓慢的负向电位,但当用色光作背景和色光作为刺激光时,PhNR反应明显增大。动物实验证实PhNR产生于视网膜神经节细胞及其轴突,在实验性青光眼的视野轻度缺失时出现PhNR振幅下降。PhNR可以在开角型青光眼患者中呈特征性的振幅降低,并在可疑开角型青光眼中表现PhNR振幅降低。提示PhNR可以作为早期开角型青光眼损伤或者其青光眼损伤进展的一个视功能评价指标。     

非动脉炎性前部缺血性视神经病变患者的明适应负向波变化特点分析

目的　探讨非动脉炎性前部缺血性视神经病变（non-arterial anterior ischemic optic neuropathy,NAION）患者随病程变化的明适应负向波（photopic negative response,PhNR）变化特点。方法　选取2018年6月至12月就诊于我院的NAION患者18例作为NAION组,另选取正常16人作为正常对照组。根据NAION患者不同视盘水肿状态盘周视网膜神经纤维层（retinal nerve fiber layer,RNFL）厚度的差别,将NAION组进一步分为视盘水肿时的盘周RNFL厚度增加组（以下简称“增加组”）和视盘水肿消退后的盘周RNFL厚度正常及减少组（以下简称“正常及减少组”）。所有受检者均进行PhNR和光学相干断层扫描（optical coherence tomography,OCT）的盘周RNFL厚度检查。结果　NAION组与正常对照组相比,PhNR幅值［分别为（28.23±14.62）μV、（46.24±16.04）μV］显著降低,差异有统计学意义（P=0.00）。增加组、正常及减少组与正常对照组相比,PhNR幅值［（28.77±11.87）μV、（27.96±16.32）μV、（46.24±16.04）μV］均显著降低,差异均有统计学意义（P=0.03、0.00）,但增加组和正常及减少组相比,PhNR幅值差异无统计学意义（P=0.92）。增加组PhNR幅值与RNFL厚度呈负相关性（r=-0.86,P=0.03）,正常及减少组PhNR幅值与RNFL厚度呈正相关性（r=0.96,P=0.00）。结论　NAION患者发病初期PhNR幅值即显著降低,随着病程进展,PhNR幅值未发生显著变化。NAION视盘水肿时盘周RNFL厚度越大,PhNR幅值越低;视盘水肿消退后盘周RNFL厚度越小,PhNR幅值越低。     

The effect of broadband and monochromatic stimuli on the photopic negative response of the electroretinogram in normal subjects and in open-angle glaucoma patients

The aim was to investigate the effects of monochromatic and broadband stimuli on the amplitude of the photopic negative response (PhNR) and to compare the sensitivities of these stimuli for the detection of ganglion cell damage in glaucoma patients. Forty-one healthy subjects were studied, along with 16 patients with open-angle glaucoma. Photopic electroretinograms (ERGs) were elicited with monochromatic red, amber, green, and broadband white stimuli of progressively brighter intensities in a blue background. Pattern ERGs were also recorded using a 0.8° checkerboard pattern on a 21.6° × 27.8° screen. In the photopic ERGs of the control subjects, the PhNR amplitude was significantly higher (P < 0.01) to red than to monochromatic amber, green, and broadband white stimuli of the same intensity. In glaucoma patients, the percentage of amplitude reduction was greater for the PhNR to red (68%, P < 0.001) than to the broadband stimulus (38%, P = 0.001). The PhNR to red monochromatic stimulus appeared to be a more sensitive parameter, with a larger area enclosed by the receiver-operating characteristic curve (0.97) than for the PhNR to broadband stimulus (0.76). Also, the PhNR to red stimulus showed a more significant correlation with the pattern ERG and the visual field defects (P < 0.05) than the PhNR elicited with broadband stimulus. These findings suggest that ganglion cell activity can be more efficiently evaluated with the PhNR elicited with a red than with a broadband stimulus. The PhNR thus appears to be a promising test for the diagnostics of the ganglion cell dysfunction.     

Inner-retinal contributions to the photopic sinusoidal flicker electroretinogram of macaques. Macaque photopic sinusoidal flicker ERG

The purpose of this study was to examine inner-retinal contributions to the photopic sinusoidal flicker ERG. ERGs were recorded from 5 anesthetized monkeys to sinusoidally modulated (100%, 0.5–120 Hz) red full field flicker at L_mean of 3.2 log phot td on a rod saturating blue background (3.7 log scot td; 3.0 log phot td) before and after intravitreal injections of tetrodotoxin (TTX) to block Na⁺-dependent spikes of retinal ganglion and amacrine cells, followed by N-methyl-D-aspartate (NMDLA) to suppress all activity of these cells. Recordings also were made after blocking bipolar (and horizontal) cell responses with L-2-amino-4-phosphonobutyric acid (APB) and 2-cis-piperidine-2,3-dicarboxylic acid (PDA) or 6-cyano-nitroquinoxaline-2,3-dione (CNQX). Control fundamental (F1) and second harmonic (F2) amplitudes were large and variable at temporal frequencies up to 2 Hz. At higher frequencies, F1 amplitude was minimal with a phase step at a frequency between 13 and 19 Hz and maximal at 27–33 Hz. F2 was minimal at 2–3 Hz and maximal at 6–8 Hz, again with a phase step near the minimum. TTX, or NMDLA, produced small changes in F1 that shifted the amplitude minimum to a lower and the maximum to a higher frequency. In contrast, F2 was more strongly affected; both the amplitude minimum (and phase step) and maximum were greatly attenuated, leaving a moderate response from 0.5 to 8 Hz, which then declined as frequency was increased to 30 HZ. After APB and PDA or CNQX, F1 decreased continuously with increasing frequency and F2 was generally much smaller. The nearly linear F1 phase plot was consistent with the presence of a single mechanism (i.e. photoreceptors). Inner-retinal neurons contribute to the photopic sinusoidal flicker ERG. Whereas for F1, inner-retinal contributions are small relative to those from bipolar cells; for F2, they are equal or greater between 2 and 16 Hz.