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.     

正常成年家猫不同明适应条件下闪光视网膜电图的变化

目的:探讨正常成年家猫不同明适应条件下闪光视网膜电图(flash electtoretinogram,F-ERG)最大反应的变化并建立正常值范围,为相关研究提供一种创伤较小且实用可行的实验方法和相关依据.方法:成年家猫37只,全麻状态下暗适应20min后开启背景光计时,在明适应5,15,30,60s;3,5,10,20,30min用相同强度的光刺激、采集并记录分析不同明适应时间点F-ERG的a,b波的峰潜时及振幅并描出a,b波的振幅变化曲线图.结果:在不同明适应时间成功记录到典型且重复性好的F-ERG波形.经过分析观察到在不同的明适应时间,a,b波的潜伏期均无明显差异,b波的振幅变化较为明显,明适应5min后记录到的F-ERG,b波振幅值达高峰.结论:本法为成年家猫明适应F-ERG的检测提供了一种创伤小且具有较好重复性的实验方法和实验参考依据.     

The diagnostic use of the second oscillatory potential in clinical electroretinography

Of all the electroretinogram (ERG) components (a-wave, b-wave, and oscillatory potentials) only one oscillatory potential, OP₂, was found to be significantly correlated with the absolute intensity of the flash stimulus (i.e., the intensity of the stimulus irrespective of the state of retinal adaptation). Our finding was further confirmed in single cell recordings of lateral geniculate unit activity in rabbits in which peak time of OP₂ was found to correlate better with the geniculate activity. For these reasons we have identified OP₂ as the intensity coding oscillatory potential of the ERG. In order to investigate if this new feature could have some clinical significance, we examined photopic ERGs recorded from patients affected with various retinopathies. In most instances the peak time of OP₂ paralleled that of the b-wave, that is, in the ERG with delayed b-wave the peak time of OP₂ was also delayed, while in ERGs with normal b-wave peak time the peak time of OP₂ was also normal. However, in some conditions (especially in cone-rod diseases) a delayed OP₂ was found in ERGs with normal b-wave peak times.     

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。     

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.     

Clinical Application of Photopic Negative Response of the Flash Electroretinogram in Primary Open-angle Glaucoma

 PURPOSE: To evaluate the diagnostic performance of the photopic negative response (PhNR) for the detection of primary open-angle glaucoma (POAG). METHODS: Fifty-two normal subjects (52 eyes) and 173 POAG patients (173 eyes) were studied. The PhNR was elicited using a white stimuli on a white background. The mean deviation (MD) and pattern standard deviation (PSD) of the visual field were measured using standard automated perimetry (SAP). Spectral domain optical coherence tomography (SD-OCT) was used to measure the mean thickness of the retinal nerve fiber layer (RNFL). RESULTS: In the glaucoma group, as compared to the normal group, the amplitudes of a-waves, b-waves and PhNR were significantly smaller (P<0.001), and the PhNR implicit time was significantly longer (P=0.004). The MD, PSD and mean thickness of the RNFL were significantly correlated with the amplitude of the PhNR (P<0.001). The area under the receiver operating characteristic curve (AUCs) for the amplitudes of a-waves, b-waves and PhNR were 0.853, 0.830 and 0.918, respectively. When the specificity was ≥95%, the sensitivities were 60.4%, 54.2% and 85.4% respectively. CONCLUSION：The PhNR amplitude was reduced even when the loss in visual field sensitivity was mild, which suggests that PhNR might be a useful indicator of early glaucoma disease.       

Oscillatory potentials as predictors to amplitude and peak time of the photopic b-wave of the human electroretinogram

The oscillatory potentials are viewed by many as small oscillations of a highfrequency domain that ride on the b-wave of the electroretinogram. A study of electroretinograms and oscillatory potentials performed in 25 normal subjects was undertaken to substantiate my claim that oscillatory potentials are fast retinal potentials that are integrated to form the b-wave. The prominence of the OPs on the ascending limb of the b-wave was found to be only weakly correlated (r = –0.37) to the amplitude of the oscillatory potentials (measured in the 100–1000 Hz recordings). There was, however, a high correlation (r = 0.78) between the prominence of the oscillatory potentials and their frequency domain as determined by the peak-to-peak timing. Furthermore, the peak-to-peak timing of the oscillatory potentials was highly correlated with the b-wave peak time (r = 0.86) as well as with the a-wave trough to b-wave peak time (r = 0.90), while the amplitude of the oscillatory potentials was correlated to the amplitude of the b-wave (r = 0.78). Interestingly, when combining the amplitude of the oscillatory potentials with the time interval between oscillatory potentials 2 and 3 and 3 and 4, a higher correlation (r = 0.88) was found with the b-wave amplitude. The latter finding would support my claim that the b-wave represents an integration (amplitude as a function of time) of the oscillatory potentials.     

The photopic hill: A new phenomenon of the light adapted electroretinogram

Utilizing a high intensity photographic flash unit, electroretinograms were recorded from normal adults under fully light adapted conditions over a 5 log unit range of stimulus luminance (-1.35 to 3.34 log cd-s/m²). At lower luminance levels b-wave amplitude increased with increased luminance until it reached a maximum (V_max of the Naka-Rushton equation) in agreement with previous work. At higher luminance levels, the b-wave amplitude decreased to 33% of V_max and then plateaued. This previously unreported phenomenon has been named the photopic hill. There was no appreciable change in b-wave amplitude with increased interstimulus intervals from 15 sec to 5 min and luminance-response functions serially recorded for increasing and for decreasing stimulus luminance were very similar. These latter results indicate that the photopic hill is not due to light adaptation. The reason for the photopic hill and possible clinical implications are discussed.Abbreviations ISI interstimulus interval - L-R function luminance-response function - ND neutral density     

电生理测试作为早期青光眼诊断指标的横断面研究

明视负向反应(PhNR)和图形视网膜电图(PERG)的结果作为评估青光眼的诊断指标.10例对照组和15例早期青光眼患者接受了完整的眼科检查,包括视力测量,眼压(IOP)测量,眼底检查和视野检查.同时进行图形视网膜电图和全视野视网膜点图纪录.青光眼组的平均偏差和图形平均标准偏差显著较低(P＜0.001,P＜0.01).PERGN95,PhNR,b波以及PhNR/b波的幅值显著较低(P＜0.001).眼压升高降低了PERG与PhNR的振幅.     

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。     

The electroretinogram recorded at the onset of dark-adaptation: understanding the origin of the scotopic oscillatory potentials

The purpose of this study was to examine the origin of the oscillatory potentials (OPs) recorded at the onset of dark-adaptation. Our results show that following pre-exposure of the retina to progressively brighter photopic backgrounds there is a complete abolition of OP₄ and approximately 50% of OP₃, while OP₂ is not affected in responses evoked to dim flashes of white light and recorded at the onset of dark-adaptation. These results bring further support to the claim that the short latency OP₂ is cone-mediated while the OP₃ and OP₄ would have a significant rod contribution. However, a more complex picture of OP genesis arises when flicker and response to brighter white light flashes, also obtained within the first minute of dark-adaptation are considered. The latter would suggest that our understanding of the origin of the OPs cannot be exclusively based on which of the two class of photoreceptors is preferentially stimulated at the time the response is recorded. This revised version was published online in July 2006 with corrections to the Cover Date.     

The relation of apparent brightness to contrast threshold on a photopic background :Dependence on retinal position and target size

The luminance necessary for constant apparent brightness was measured as a function of retinal eccentricity at several photopic brightness levels and compared with the corresponding increment threshold functions. Thresholds rose substantially from the fovea to the periphery, but the contrast required for constant brightness showed little change as a function of eccentricity. A change of target size had relatively little effect on the shapes of the equal brightness curves. Two contributing factors to the difference between the threshold and equal brightness curves are systematic changes in

(1) the apparent brightness at threshold

(2) the exponent of the brightness power function. A neural mechanism is proposed which accounts for the results. A comparison with known retinal ganglion cell properties leads to the conclusion that this mechanism must be located proximally to the retina.

A physiological basis for definition of the ISCEV ERG standard flash (SF) based on the photopic hill

The ISCEV Standard for Clinical Electrophysiology indicates that the ERG standard flash should be defined within a very narrow range of intensities. Yet no information is provided as to how this intensity range was identified. We present evidence that would support a redefinition of the SF based on known photopic ERG properties.     

显性遗传先天性静止性夜盲全视野明视ERG的分析

对同一家系11名显性遗传CSNB 患者进行全视野明视ERG 分析,发现8名患者出现异常,表现为:1.明视白光刺激的b 波峰时延长或振幅降低;2.白光刺激出现负电反应;3.对闪烁光刺激的反应振幅降低甚至无波。认为CSNB 的主要病损在视网膜杆体系统,但锥体系统也受到不同程度的损害。提出根据电生理和心理物理检查可将本病分为仅累及杆体系统的单纯型和杆体、锥体均受到损害的混合型。临床上这两种不同的亚型是CSNB 基因不同表现度的反映。     

Scotopic versus photopic pattern onset-offset electroretinograms

We investigated the contribution of rods and cones to the human pattern electroretinogram to onset and offset checkerboards of different spatial frequency and wavelength in a 39° × 39° field. Under strictly scotopic conditions, there was a negative potential at onset and a positive potential at offset, whereas under photopic conditions, there was a positive potential at onset and a negative/positive potential at offset. Thus, the waveform to pattern onset (offset) was that of the luminance electroretinogram to decreasing (increasing) luminances. For pattern onset, the sensitivity difference 486–601 nm under scotopic and photopic conditions closely followed the luminosity function of rods and cones. The amplitude of the scotopic onset response increased with check size up to 3°30 and that of the photopic onset response, up to 30. With larger checks, the scotopic and photopic onset response markedly decreased. This indicates antagonistic center-surround organization of the receptive fields under both scotopic and photopic conditions. By contrast, the offset response monotonically increased with check size under scotopic and photopic conditions, which suggests a luminance component in the pattern electroretinogram. Consequently, the pattern electroretinogram to reversing checker-boards has to be regarded as a mixture of both pattern- (contrast) and luminance-specific components.     

Photopic negative response in diagnosis of glaucoma:an experimental study in glaucomatous rabbit model

AIM:To determine whether the photopic negative response (PhNR) elicited by transient white flash on white background is characterizing for glaucoma model in rabbits.METHODS:Glaucoma was induced in twelve rabbits by subconjunctival injection of 0.05 mL of betamethasone in right eyes (each 1 mL contain betamethasone dipropionate 5 mg and betamethasone sodium phosphate 2 mg).The intraocular pressure (IOP) , electroretinogram (ERG) and visual evoked potential (VEP) were measured successively prior and on the 3, 7d, two weeks and four weeks postglaucoma induction. After four weeks, the animals were sacrificed and the globes were histopathologically examined.RESULTS:The IOP increased significantly after one week (P=0.0001), then it gradually returned to the control level . In ERG examination, the means of a and b wave amplitude and latency were not affected significantly. PhNR amplitude decreased significantly within one week (P=0.0001), but its latency was not affected significantly (P=0.132). The means of VEP latency and amplitude were significantly affected after two weeks and four weeks of glaucoma induction (P=0.0001 and 0.02, respectively). The histopathologic examination of the globes showed reduced number of cells in the retinal ganglion cell layer with multiple vacuoles in the retinal nerve fibre layer.There was significant positive correlation between ganglion cell layer cells and PhNR amplitude (r=0.8, P=0.002).CONCLUSION:The rise in IOP resulted in irreversible changes or incomplete recovery of VEP and PhNR amplitude. Both PhNR and VEP represented good additional tools in early diagnosis of glaucoma.     

One year follow‐up of contrast sensitivity following conventional laser in situ keratomileusis and laser epithelial keratomileusis

Purpose: To determine the effect of conventional laser in situ keratomileusis (LASIK) and laser epithelial keratomileusis (LASEK) for myopia on contrast sensitivity (CS) using the Pelli‐Robson and Vector Vision CSV‐1000E CS tests. Methods: A prospective, comparative study was conducted on 36 eyes of 36 patients with myopia undergoing LASIK (18 eyes) and LASEK (18 eyes). Surgery was performed using the Technolas 217z laser (Bausch & Lomb). CS was recorded preoperatively and at 3, 6 and 12 months postoperatively. Results: No statistically significant difference was found in LogMAR uncorrected visual acuity post‐LASIK (?0.02 ± 0.16) and LASEK (?0.04 ± 0.14). Using the Pelli‐Robson, CS was significantly lower in the LASIK group 3 and 6 months postoperatively. No significant postoperative reduction in CS was observed in either treatment group. Using the CSV‐1000E test, CS was significantly reduced post‐LASIK at 3 (p = 0.05) and 6 (p = 0.05) cycles/degree under photopic conditions. No significant postoperative change occurred in the LASEK group under photopic or scotopic conditions. There was no significant difference in postoperative CS between the LASIK and LASEK groups at 3, 6, 12 or 18 cycles/degree using the CSV‐1000E test. Conclusion: One year postoperatively, there was no difference in CS between both treatment groups using the Pelli‐Robson and CSV‐1000E tests. CS was reduced postoperatively in the LASIK group at the lower spatial frequencies under photopic conditions. No postoperative change was detected in CS following LASIK or LASEK using the Pelli‐Robson test.     

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。     

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...     

Ambient Light Regulates Retinal Dopamine Signaling and Myopia Susceptibility

PurposeExposure to high-intensity or outdoor lighting has been shown to decrease the severity of myopia in both human epidemiological studies and animal models. Currently, it is not fully understood how light interacts with visual signaling to impact myopia. Previous work performed in the mouse retina has demonstrated that functional rod photoreceptors are needed to develop experimentally-induced myopia, alluding to an essential role for rod signaling in refractive development.MethodsTo determine whether dim rod-dominated illuminance levels influence myopia susceptibility, we housed male C57BL/6J mice under 12:12 light/dark cycles with scotopic (1.6 × 10⁻³ candela/m²), mesopic (1.6 × 10¹ cd/m²), or photopic (4.7 × 10³ cd/m²) lighting from post-natal day 23 (P23) to P38. Half the mice received monocular exposure to −10 diopter (D) lens defocus from P28–38. Molecular assays to measure expression and content of DA-related genes and protein were conducted to determine how illuminance and lens defocus alter dopamine (DA) synthesis, storage, uptake, and degradation and affect myopia susceptibility in mice.ResultsWe found that mice exposed to either scotopic or photopic lighting developed significantly less severe myopic refractive shifts (lens treated eye minus contralateral eye; –1.62 ± 0.37D and −1.74 ± 0.44D, respectively) than mice exposed to mesopic lighting (–3.61 ± 0.50D; P < 0.005). The 3,4-dihydroxyphenylacetic acid /DA ratio, indicating DA activity, was highest under photopic light regardless of lens defocus treatment (controls: 0.09 ± 0.011 pg/mg, lens defocus: 0.08 ± 0.008 pg/mg).ConclusionsLens defocus interacted with ambient conditions to differentially alter myopia susceptibility and DA-related genes and proteins. Collectively, these results show that scotopic and photopic lighting protect against lens-induced myopia, potentially indicating that a broad range of light levels are important in refractive development.