Case of adult-onset neuronal intranuclear hyaline inclusion disease with negative electroretinogram

Purpose

To report the findings in a 72-year-old man with neuronal intranuclear hyaline inclusion disease (NIHID) with the negative-type electroretinogram (ERG) and without night blindness.

Methods

Standard ophthalmological examinations including the medical history, measurements of the best-corrected visual acuity and intraocular pressures, slit-lamp biomicroscopy, ophthalmoscopy, spectral-domain optical coherence tomography, fundus autofluorescence, and perimetry were performed. In addition, neurological and electrophysiological examinations were performed.

Results

NIHID was confirmed by skin biopsy. The ophthalmologic examinations revealed sluggish pupillary reflexes without visual disturbances and retinal abnormalities. The amplitudes of the dark-adapted 0.01 ERG was absent, and light-adapted 3 ERG and light-adapted 30 Hz flicker ERG were reduced in amplitude and delayed in implicit time. The rod system was more severely affected than the cone system, indicating that NIHID is classified as one of rod-cone dysfunction syndrome. The dark-adapted 3 ERG consisted of a markedly reduced b-wave with larger a-wave (negative ERG), but the amplitude of a-wave was smaller than normal.

Conclusions

Since the ophthalmoscopical findings and the subjective visual functions may be essentially normal, the characteristic ERG abnormalities can be an important findings in adult-onset NIHID without night blindness.

     

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.     

Two neuronal retinal components of the electroretinogram c-wave

Although the rising phase of the b-wave seems to be generated mainly in the rod bipolar cells and the cone on-bipolar cells, the slow component of the electroretinogram, the c-wave, evidently originates in the Müller cells and the pigment epithelium. The c-wave has three components. One cornea-positive component derives from the pigment epithelium, while a distal cornea-negative component (slow PIII) and a proximal slow component originate in the Müller cells. This third proximal component of the c-wave differs between mammalian species: it is negative in the rat retina, positive in the rabbit and human retina and may be lacking in the cat retina.     

Values of electroretinogram responses according to axial length

Accurate interpretation of electroretinograms (ERGs) requires knowledge of effects of axial myopia on ERG responses. Our purpose was to derive expected changes of ERG responses according to axial length, to stimulus conditions that conform to the International Society for Clinical Electrophysiology of Vision (ISCEV) Standard for Electroretinography. ERGs from 60 subjects were recorded. The subjects were assigned to one of three groups according to the level of myopia. Thirty-three subjects had high myopia (–6.00 D to –14.50 D; mean age, 31 years), eight had mild myopia (–3.00 D to –5.00; mean age, 28 years), and 19 had a small refractive error (+0.75 D to –2.75 D; mean age, 27 years). No subjects had myopic retinopathy. Stimulus-response curves were fitted to dark-adapted b-wave amplitudes and maximum amplitude and semi-saturation constants derived. Axial lengths, measured with A scan ultrasound, ranged from 22.2 mm to 30.0 mm. Analysis of variance and post hoc t-tests revealed significant difference between subjects with high myopia and subjects with small refractive error for ERG amplitude data. There were no significant differences between the three groups for implicit times, the ratio of b- to a-wave and semi-saturation constant. There is linear reduction in the logarithmic transform of ERG amplitude with increasing axial length, related more to axial length than refractive error. We provide relative slope and intercept values, allowing labs to derive expected ERG amplitudes according to axial length. These derivations are valid for persons with no retinopathy.     

Neural retinal contribution to the slow negative potential of the canine electroretinogram

To establish the normal waveform of the electrical responses from canine eyes, electroretinograms and the light peak were recorded in hybrid and beagle dogs under general anesthesia and artificial ventilation. The neural retinal and retinal pigment epithelial components were pharmacologically isolated by intravitreal glutamate injection and systemic sodium iodate administration, respectively. The a- and b-waves elicited by either flash or rectangular stimuli, the oscillatory potentials elicited by flash stimuli and the light peak elicited either by a single maintained illumination or by repetitive stimuli were almost identical with those of other vertebrates thus far studied. In contrast, in response to rectangular (several-second duration) stimuli, the c-wave was usually absent and was replaced by a slow cornea-negative potential that had a time course similar to that of the c-wave in other species. This slow negative potential was elicited at such low stimulus intensities that the a-wave was absent, was deepened by an intravenous administration of sodium iodate, was not affected by an intravitreal injection of sodium glutamate and was shallowed during the light peak. These results suggest that the slow negative potential that replaces the c-wave consists of large slow PIII, small retinal pigment epithelial c-wave and negligible contribution from the late photoreceptor potential and the dc component of the PII.     

视网膜电图明视负向反应研究进展

视网膜电图（ERG）的明视负向反应（PhNR）是在明适应条件下用亮光刺激时在正向b波后记录到的一负向电位。灵长类动物实验研究及临床研究证实,PhNR的产生与视网膜神经节细胞（RGCs）及其轴突有关,而研究啮齿类动物发现,PhNR起源于无长突细胞的电活动。就灵长类动物PhNR记录条件的改进、不同记录条件下其波形特点、啮齿类动物PhNR的记录条件及特点,以及局部视网膜PhNR在临床应用中的新进展进行综述。     

Luminance-contrast evoked responses and color-contrast evoked responses in the human electroretinogram

Pattern electroretinograms to onset-offset stimuli were studied in response to luminance-contrast (e.g. red-black or green-black) and color-contrast (e.g. red-green) stripe patterns of equal luminance. Onset responses to color-contrast patterns show no spatial selectivity and a constant peak latency at all spatial frequencies, a behavior different from that of luminance-contrast evoked responses (spatial selectivity and increasing peak latency with spatial frequency). These results are tentatively related to the physiology of tonic and phasic primate retinal ganglion cells and to the spatially selective and non-selective human contrast sensitivity to respectively luminance-contrast and color-contrast gratings.     

视网膜电图明视负波反应在检测原发性开角型青光眼中的应用

目的 探讨视网膜电图( Electroretinogram,ERG)明视负波反应(Photopic Negative Response,PhNR)在检测原发性开角型青光眼(Primary Open angle Glaucoma,POAG)中的应用.方法 应用德国罗兰视觉电生理仪测量52例(67只眼)正常人及137例(173只眼)POAG患者的a波振幅、b波振幅、PhNR振幅和潜时.全视野刺激器由LED光源发光,选用白色背景光和白色刺激光.采用HumphreyC24-2程序检查患者视野的平均缺失(Mean Deviation,MD)和(Pattern Standard Deviation,PSD),并根据视野检查结果将POAG患者分为早期组55例(62只眼),进展期组40例(60只眼)和晚期组42例(51只眼).应用频域OCT (Cirrus OCT)检测全部POAG患者的平均视网膜神经纤维层(mean retinal nerve fiber layer,mRNFL)厚度.结果 四组中a波振幅、b波振幅、PhNR潜时、PhNR振幅的差异均具有统计学意义(P＜0.05).a波振幅、b波振幅、PhNR潜时的变异程度较大.MD、mRNFL与PhNR振幅均呈正的直线关系(P=0.000),相关系数分别为0.59、0.45.PSD与PhNR振幅呈负的直线关系(P =0.016)相关系数为-0.37.a波、b波振幅、PhNR振幅的ROC曲线下面积分别为0.853、0.830和0.918.其中,PhNR振幅的诊断价值较高.在设定特异性≥95％的情况下,其敏感性分别为60.4％、54.2％和85.4％.结论 POAG组PhNR振幅和潜时较正常对照组明显降低和延迟;PhNR振幅降低与青光眼病变的严重程度相关;PhNR振幅在POAG早期诊断方面具有较高的敏感性,因此PhNR可以作为一个评价POAG视功能的有用指标.     

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。     

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。     

正常人视网膜电图明视负波反应的研究

目的 建立国人正常人视网膜电图明视负波反应(Photopic negative response,PhNR)的振幅和潜伏期的正常值,探讨其PhNR振幅和潜伏期的变异程度和与年龄、性别、眼别的关系.方法 应用ROLAND生产的视觉电生理仪测量正常人150名(150只眼)在蓝-红和白-白两种刺激下的PhNR潜伏期和振幅.分别按间断年龄20岁进行分组和性别统计其正常值范围并进行比较,用Spss17.0对数据进行统计学处理.结果 蓝-红和白-白PhNR潜伏期在四个年龄组之间差异无统计学意义(P=0.348);而蓝-红PhNR振幅在四个年龄组之间差异有显著性(P =0.007),但白-白PhNR振幅在四个年龄组之间差异无统计学意义(P =0.077).在各年龄组PhNR潜伏期和振幅的变异系数中,＜20岁的PhNR潜伏期和振幅变异系数最小,20～ 40岁的PhNR潜伏期和振幅变异系数最大.在两种刺激下,PhNR潜伏期与年龄无直线相关关系(P =0.210,0.646);而PhNR振幅与年龄呈负的直线相关关系(P =0.007,0.006).PhNR潜伏期和振幅在左右眼之间的差异无统计学意义(P＞0.05),其在男女之间的差异也无显著性(P＞0.05).结论 在蓝-红和白-白两种刺激下PhNR潜伏期和振幅不受性别和眼别的影响;但PhNR振幅受年龄的影响,随着年龄的增长而下降.在进行PhNR检查时,应综合考虑上述因素的影响.     

The photopic negative response of the flash electroretinogram in retinal vein occlusion

The photopic negative response (PhNR) has recently been shown to be severely affected in central retinal artery occlusion (CRAO), despite relative preservation of the cone b-wave compared to that in the healthy unaffected fellow eye. The aim of this study was to test how the PhNR of the flash electroretinogram (ERG) is affected in human retinal vein occlusion. PhNR was elicited with red stimuli (1 cd s/m², 5 cd s/m², and 7 cd s/m² with 4 ms duration) and blue background (10 cd/m²). Standard Ganzfeld flash ERG was produced according to the ISCEV standard for the clinical electroretinogram (2004). Sixteen patients with central retinal vein occlusion (CRVO), 14 patients with branch retinal vein occlusion (BRVO), and 16 controls were analyzed. The amplitude of the PhNRs was significantly smaller in the CRVO and BRVO eyes than those in the unaffected fellow or control eyes (p = 0.000). There was a significantly greater reduction of PhNR amplitudes than that of other waves including the OPs, rod b-wave, combined a-wave and b-wave, cone a-wave and b-wave, and 30 Hz flicker ERG. Thus, PhNR amplitude in retinal vein occlusion is severely affected. There is a potential role for PhNR in assessing inner retinal damage and evaluating the effect of treatment.     

Time courses for maturation of electroretinogram responses from infancy to adulthood

The purpose of this study was to determine how responses in the normal human electroretinogram (ERG) change with subject age. We studied 62 children, 10 days to 15 years old, and 30 subjects 15–37 years old, using the standard protocol established by the International Society for Clinical Electrophysiology of Vision, with Burian-Allen bipolar contact-lens electrodes. We measured rod response, maximal response, oscillatory potentials (OPs), cone response, flicker response, and b-wave amplitude/log intensity (V/log I) curve. A logistic growth curve was used to describe the developmental changes. Dark- and light-adapted ERG a- and b-wave amplitudes reached adult levels by three to five years of age, although b-wave amplitudes of scotopic rod-mediated responses were slower to reach maturity than mixed rod-cone mediated responses. In early infancy OPs were the most immature of the ERG responses, although the rate of development thereafter exceeded that of the other responses such that OP amplitudes were within adult levels by two years of age. Amplitudes of the ERG responses in 21 children sedated with chloral hydrate did not differ significantly from 21 who had not been sedated. ERG responses developed at varying rates, reflecting different developmental stages in photoreceptors, middle retinal layers and more proximal retina. This revised version was published online in July 2006 with corrections to the Cover Date.     

The effect of postnatal exposure to lead on the electroretinogram in young rats

The morphological and electrophysiological effects on the retina resulting from lead exposure were assessed in neonatal rats. The electroretinogram (ERG), light and electron microscopy and morphometry of the retina were evaluated at 9, 11 and 13 days of age. The lead concentration in the blood was on average between 276 and 311 micrograms/100 ml in the different age groups. The brain concentration of lead varied on average between 102 and 104 micrograms/100 g. A reduction in amplitude, a prolonged latency and an elevated threshold sensitivity of the a-wave was observed in the 11 days old lead-exposed pups. The 13 days old lead-fed rats showed depressed amplitudes and delayed peak times of both the a- and b-waves. The latency of the a-wave was also longer in the lead-treated 13 days old animals. No ERG was recorded at the age of 9 days in neither the lead-exposed or control animals. No significant change in the morphology of the retina was found. We propose that lead exposure seem to induce a change primarily in the electrophysiological function of the photoreceptors. There was no evidence for a direct retardation of the development of the retina by the administration of lead.     

Effects of sodium iodate on the electroretinogram c-wave in the cat.

The c-wave of the vitreal electroretinogram decreased in amplitude and was replaced by a slow, polarity reversed potential following an i.v. infusion of sodium iodate, as first described by Noell. Intraretinal recordings showed that the negative-going c-wave, induced by iodate (30 mg/kg), was composed of reduced slow pIII and trans-epithelial c-wave. The effects of iodate on these components may originate from direct effects on the retinal pigment epithelial cells, namely, a large decrease in the trans-epithelial resistance. Other factors could have contributed to the change in the c-wave amplitude.     

Spinocerebellar degeneration with negative electroretinogram: dysfunction of the bipolar cells

We report the characteristics of three patients with spinocerebellar degeneration (SCD) with negative-type electroretinograms (ERGs). None of the patients showed retinal degeneration, but all had severe cerebellar ataxia, and brain MRIs showed cerebellar atrophy. Negative-type ERGs have been implicated in the selective functional impairment of the inner retinal layer, but few studies have reported dysfunction of the inner nuclear layer in SCD patients. Our subjects may be the first reported SCD cases with negative-type ERGs. Our results suggest that an etiologic relationship exists between cerebellar ataxia and negative-type ERGs. Further investigation of ERGs in patients with SCD could potentially lead to the identification of an increased number of SCD patients with negative-type ERGs and retinal pathogenesis.     

Studies on developmental alterations in the electroretinogram in rats after post-natal exposure to lead

The effects of post-natal exposure to lead on the development of the electroretinogram in rats were studied. Newborn rats were fed with lead acetate by gastric intubation and weight and age-matched control rats were given sodium acetate in a similar way. At 15 and 26 days of age the lead concentrations in blood were on average 298 micrograms/100 ml and 80 micrograms/100 ml, respectively. The brain concentrations of lead were on average 248 micrograms/100 mg in the 15-day-old lead-fed animals and 244 micrograms/100 mg in the 26-day-old ones. Lead produced a transient depression of the post-natal development of the electroretinogram. A decrease in the amplitudes of the a- and b-waves, as well as an increase in the peak times of these potentials were found in the 15-day-old animals. The ERGs of the 26-day-old animals did not differ from controls. There were no morphological changes of the retina.