The clinical utility of the foveal electroretinogram: A review

The historical development of the foveal electroretinogram is reviewed. The factors required to obtain a local cone electroretinogram with a small focal source of illumination against a lighted background are discussed. From these considerations and various studies of macular degeneration, the optimal size of the foveal source is found to be 5° diameter or less. Applications of the foveal electroretinogram in various diseases are summarized. The foveal electroretinogram is abnormal with reduced acuity in age-related macular degeneration, juvenile macular degeneration (Stargardt's disease), retinitis pigmentosa, and diabetic retinopathy. Normal foveal electroretinograms are found in optic atrophy, amblyopia, and optic neuritis. Foveal electroretinograms are normal or abnormal in Best's disease, central serous retinopathy, and several other diseases discussed.     

Variability of the pattern electroretinogram

Conflicting results have been obtained concerning the parametric properties of the pattern electroretinogram. These discrepancies may be due to the large amount of variability inherent in recording amplitudes. We have found the variability within a single stimulus condition to be so large (ranging from 30% to 67% of the mean value) that it could mask any underlying spatial frequency tuning. Changing the stimulus conditions failed to significantly reduce the observed variability, although changing recording conditions produced some reduction. The use of a narrower rejection band, a greater number of sweeps, and placement of the reference electrode on the ipsilateral ear (as opposed to the ipsilateral temple) combined to decrease variability of the pattern electroretinogram within a single recording session; however, intersession variability remained high. Therefore one must be careful in evaluating data from this technique, and caution is advised in its clinical use.     

Multifocal pattern electroretinogram: cellular origins and clinical implications.

PURPOSES: The purposes of this article are to gain insight into the cellular origins of the multifocal pattern electroretinogram (mPERG) and evaluate its potential for clinical use. METHODS: mPERGs were recorded from four anesthetized monkeys before and after pharmacologic blockade of light-driven activity of inner-retinal neurons and from 55 normal human subjects (19-91 years) and six patients with glaucoma (43-77 years of age). Stimuli consisted of counterphase-modulated black and white triangles organized in 61-scaled hexagons with mean luminance 100 cd/m2 and 100% contrast. The stimulus array subtended 31 degrees vertically and 37 degrees horizontally at 48 cm. The amplifier cutoff frequencies were 3 and 100 Hz. Responses were grouped as quadrants and the first slice of the second-order kernel was analyzed. RESULTS: The mPERG responses of monkeys and humans were similar. In the monkey responses, there was an early positive potential (P1) around 25 ms and a later positive potential (P2) found selectively in the nasal field quadrants around 31 ms. These responses were seen around 22 and 36 ms in the human responses. After blockade of inner-retinal activity in monkeys, P1 amplitude was greatly reduced at all retinal locations and P2 was eliminated. P1 and P2 amplitudes were significantly reduced in the glaucomatous eyes relative to amplitudes of age-matched controls. Reductions in the amplitudes of P1 and P2 could easily discriminate between glaucomatous visual field quadrants with and without behavioral sensitivity losses. However, these alterations are likely to reflect diffuse losses. CONCLUSIONS: mPERG responses contain prominent contributions from inner-retinal neurons that can be reduced in glaucomatous eyes. These findings raise the possibility that the mPERG could be potentially useful in the objective estimation of neural damage in glaucoma. However, further refinement of recording techniques will be required if the mPERG is to be used to detect focal damage.     

The mouse pattern electroretinogram

Mouse models of optic nerve disease such as glaucoma, optic neuritis, ischemic optic neuropathy, and mitochondrial optic neuropathy are being developed at increasing rate to investigate specific pathophysiological mechanisms and the effect of neuroprotective treatments. The use of these models may be greatly enhanced by the availability of non-invasive methods able to monitor retinal ganglion cell (RGC) function longitudinally such as the Pattern Electroretinogram (PERG). While the use of the PERG as a tool to probe inner retina function in mammals is known since 25 years, relatively less information is available for the mouse. Here, the PERG technique and the main applications in the mouse are reviewed.     

The wide-angle pattern electroretinogram

Pattern electroretinograms (PERGs) were recorded from two normal human subjects in response to various spatial frequencies and stimulus areas. The maximum stimulus area was 75° × 86° which was achieved by using a standard TV monitor and a reduced viewing distance. The amplitude of the PERG increased with area in an approximately logarithmic fashion over the range investigated. The explanation relates to non-linearities of the stimulus, the retinal image and neural processing. The wide-angle PERG may be useful in the assessment of retinal diseases affecting the mid-peripheral inner retina, such as diabetic retinopathy.     

A spatial frequency-doubling illusion-based pattern electroretinogram for glaucoma

PURPOSE: A pattern electroretinogram (PERG) in which stimuli displaying the frequency-doubling (FD) illusion are presented simultaneously to multiple parts of the visual field was evaluated for its ability to diagnose glaucoma. This multiregion FD PERG is referred to in the current study as the MFP. METHODS: The nine stimulus regions were temporally modulated at incommensurate frequencies typically producing an FD percept. Two other spatial scales of the stimuli were also investigated. The sensitivity and specificity of MFP were examined using linear and quadratic discriminant methods. RESULTS: Even with the simpler linear discriminant classification, sensitivities and specificities of 100% were obtained in eyes with moderate to severe glaucoma. Of eyes with glaucoma strongly suspected, 67% were classified as being glaucomatous. Stimulus patterns having differing spatial scales produced different PERG visual field dependencies. CONCLUSIONS: The differing results for the 16-fold change in spatial scale may reflect the accessing of different mechanisms. The MFP method appears to have significant value for the diagnosis of glaucoma.     

Contrast sensitivity of the human pattern electroretinogram

Contrast thresholds for the pattern electroretinogram (PERG) were measured using lock-in amplifier retrieval of the retinal signal and a swept contrast display. Contrast sensitivity functions (CSF) developed from these PERG contrast thresholds were compared with those established psychophysically under identical stimulus conditions. Whereas the PERG CSF showed a band-pass characteristic across temporal frequency, the psychophysical CSF (and a temporal CSF developed from visual evoked potential contrast thresholds) had a low-pass pattern. Across spatial frequency, the PERG and psychophysical CSFs had similar shapes, although the PERG CSF peaked at a lower spatial frequency than the psychophysical CSF.     

The pattern electroretinogram in diabetes

In 27 normal subjects and 64 insulin-dependent diabetic patients, we evaluated the pattern electroretinogram, which may reflect the neural activity of the spatially sensitive retinal ganglion cells. The amplitude of the pattern electroretinogram was reduced in diabetic patients who had no observable retinal changes. The amplitude was further reduced with increasing retinopathy. The pattern electroretinogram amplitude change was a more sensitive indicator of retinal change among the diabetic subpopulations than the statistically significant changes in latency. A significant correlation between pattern electroretinogram amplitude and the duration of diabetes were found in diabetic patients with either no observable retinopathy or minimal background retinopathy. The pattern electroretinogram may be useful as a quantitative, dependent variable to establish and monitor short-term metabolic and physiologic changes in diabetic patients.     

Spatial selectivity of pattern electroretinogram components

Pattern electroretinograms were recorded to checkerboard stimuli of various check size to both onset-offset pattern and pattern reversal under most similar conditions of contrast and luminance. With onset-offset pattern the amplitude of the p-q and q-r components of the onset response showed a peak for checks of about 20 min of arc (spatial tuning), whereas the offset response was spatially nonselective at high contrast regardless of the luminance level. With pattern reversal the potentials were similar to those after algebraic summation of onset and offset responses both in waveform and check size of peak amplitude at 50 min of arc. From this we conclude that summation of contrast (onset) and luminance (offset) components is responsible for the shift from 20 min of arc (onset tuning) to 50 min of arc (reversal tuning). The study recommends the application of pattern stimuli in an onset-offset mode for studying antagonistic receptive field properties in the human electroretinogram.     

Spatial-temporal interactions in the steady-state pattern electroretinogram

It is currently assumed that steady-state pattern electroretinograms can be obtained only at high rates of pattern reversal. However, steady-state responses can also be obtained at very low temporal frequencies (less than 1 Hz), provided that the reversal is sinusoidal. In five healthy volunteers, we studied the frequency characteristics of the pattern-reversal electroretinogram in response to sinusoidal gratings of 0.4 and 4 c/deg, reversed sinusoidally in contrast at frequencies ranging from 1 to 27 Hz. Steady-state responses dominated by the second harmonic component were obtained at all temporal frequencies tested; the amplitude of the second harmonic changed with stimulus temporal frequency. In the low-temporal-frequency range, stimuli of high spatial frequency appear to elicit larger contribution of generators with sustained or tonic characteristics compared with stimuli of low spatial frequency.     

Computation of the luminance and pattern components of the bar pattern electroretinogram

Pattern onset electroretinograms (PERGs) were recorded from four normal subjects. Square-wave gratings of 75% contrast were presented in three approximately contiguous, concentric zones of outer angular radius, 5.1°, 12.6°, and 23.6°. The zones were calculated to give equal numbers of ganglion cell receptive fields. The recorded PERGs were considered to include luminance and pattern components which have low and bandpass spatial tuning functions respectively. These components combine in the PERG to produce a broad spatial tuning characteristic. The amplitude of PERGs in response to low spatial frequency stimuli is widely reported to be linearly related to contrast. The retinal illuminance response at every spatial frequency was computed from the eye's modulation transfer function. This function characterizes the reduction in contrast that occurs because of optical degradation. The computed retinal illuminance response was subtracted from the PERG waveform and a pattern-specific response was revealed. The latter had a highly tuned bandpass function which peaked at higher spatial frequencies than the PERG at corresponding peripheral angles.     

小鼠图形视网膜电图记录方法探讨

背景 由于小鼠与人类基因的高度同源性和眼病的高度相似性,小鼠已更多地用于人的眼病模型,视网膜电图(ERG)作为无创性检查手段,是评价小鼠眼病模型视功能不可替代的手段,但目前实验中多采用闪光ERG(FERG)进行检查,只能评价视网膜外层的功能,采用图形ERG(PERG)评价小鼠视网膜内层功能的研究较少. 目的 探讨小鼠PERG的记录方法、波形特点及影响因素,为视觉电生理在小鼠眼模型研究中的应用提供依据. 方法 6周龄清洁级雄性C57BL/6N小鼠30只,采用德国RETLport视觉生理检测系统进行PERG检测,记录电极为自制针灸针电极,置于角膜缘,参考电极和地电极分别置于颊部和尾部皮下,明适应状态下记录小鼠不同时间频率(0.5、1.0、2.0、4.0 Hz)、不同空间频率(0.05、0.10、0.20 cpd)下的PERG,分析同一时间频率和空间频率组合下不同对比度(95％和99％)、不同通频带(1～ 100 Hz、5～ 30 Hz)设置对小鼠PERG的影响,探讨PERG不同的参数设置对小鼠PERG记录结果的影响. 结果 正常成年小鼠PERG波形趋势较为明显,N1波约出现在37 ms,P波约出现于86 ms,N1-P波振幅值为2～6 μV.不同的空间频率、时间频率及对比度的设置均影响小鼠电生理的幅值,其中时间频率分别为0.5、1.0、2.0、4.0Hz时,所测得的N1-P波的振幅均值分别为(3.40±0.71)、(5.08±0.88)、(3.21±1.54)、(3.85±1.96) μV,差异有统计学意义(F=7.43,P=0.00).在电磁波干扰明显时,通频带设置在5～ 30 Hz时可以得到质量较好的波形,并不影响其记录的振幅值.刺激屏对比度设置为99％、叠加次数为200次时可记录到明显而稳定的波形. 结论 成年小鼠PERG波形以及变化趋势与人类较为相似,PERG可以作为在体评价小鼠视网膜内层功能的指标用于眼科的实验室研究,合理的参数设置和标准化记录条件可提高记录结果的可比性和可靠性.     

Pharmacological dissociation of the b-wave and pattern electroretinogram

Electroretinographic responses to modulation of either luminance (focal ERG) or spatial contrast (pattern ERG) were recorded from the pigeon eye before and after intravitreal injection of glutamate analogues DL amino adipic acid (DL AA) and 2-amino-4 phosphonobutyric acid (APB). Both toxins reversibly abolished the b-wave. The pattern ERG was still present, however, when the b-wave had been abolished by the toxins. This result demonstrates that the b-wave and the pattern ERG can be pharmacologically dissociated and suggests the possibility that in pigeons the b-wave and pattern ERG reflect the activity of different generators.     

正常人多焦图形视网膜电图的特征

目的　检测正常人多焦图形视网膜电图 (m PERG)特征。方法　 2 0只正常眼 ,罗兰视觉电生理仪行m PERG检查 ,重复测试 5次。记录波形成分并进行统计学处理。结果　P1、N1波 :第 1至 5环间的振幅密度值逐渐下降(P <0 0 1) ,差异无显著性 (P >0 0 5 ) ,颞侧视网膜的峰时较鼻侧延长峰时差异无显著性 (P >0 0 5 ) ,4个象限间的振幅密度值差异有极显著性 (P <0 0 1) ,上下半部视网膜的振幅密度值和峰时差异均无显著性 (P >0 0 5 )。N1波峰时 :颞上较鼻上、鼻下象限 ,颞下较鼻上、鼻下象限延长 (P <0 0 1)。结论　多焦视网膜电图能定位、定量地反映视网膜神经节细胞功能 ,为临床提供正常参考值