Persistent functional and structural retinal anomalies in newborn rats exposed to hyperoxia.

Previous studies have shown that newborn rats exposed postnatally to hyperoxia will develop a permanent impairment of the retinal function as determined with the electroretinogram (ERG). The purpose of our study was to examine whether postnatal hyperoxia equally alters the light- and dark-adapted ERGs and oscillatory potentials (OPs) as well as leads to permanent structural modification of the retina. During the first 14 days of life, cohorts of Sprague-Dawley rats were exposed to a hyperoxic environment, and ERGs were recorded at mean ages of approximately 25 and 55 days. Our results indicate that both light- and dark-adapted ERGs and OPs are already significantly altered within a few days following exposure to hyperoxia. None of the ERG and (or) OP parameters, with the exception of the a-wave, returned to normal values by 55 days of age. In fact some dark-adapted OPs were completely abolished following postnatal O2 exposure. Histological analysis revealed that the retina of rats exposed to hyperoxia failed to develop an outer plexiform layer and had a reduced count of horizontal cells, consistent with the permanent postreceptoral anomalies seen in the ERG responses. Our results suggest that postnatal hyperoxia causes a generalized retinal disorder leading to permanent structural modifications of the retinal cytoarchitecture and lasting anomalies of the rod and cone functions.     

正常成年猫多导程视觉诱发电位研究

用平面均匀闪光和棋盘格图形翻转刺激,研究了１７只正常猫的多导程视觉诱发电位（ＶＥＰｓ）,主要结果为：１．图形刺激引起的Ｐ－ＶＥＰ波形为两个正相成份（Ｐ１和Ｐ２）夹着一个负相成份（Ｎ１）组成“Ｗ”型的波复合;而平面均匀闪光引起的Ｆ－ＶＥＰ则为两个负相成分（Ｎ１和Ｎ１）成分夹着一个正相成分（Ｐ１）构成“Ｍ”型的波复合。这两种ＶＥＰ均表现出明显的双眼总和现象,而且Ｐ－ＶＥＰ的总和率大于Ｆ－ＶＥＰ的。２．     

Intraoperative Electroretinograms before and after Core Vitrectomy

Purpose

To evaluate retinal function by intraoperative electroretinograms (ERGs) before and after core vitrectomy.

Design

Retrospective consecutive case series.

Method

Full-field photopic ERGs were recorded prior to the beginning and just after core vitrectomy using a sterilized contact lens electrode in 20 eyes that underwent non-complicated vitreous surgery. A light-emitted diode was embedded into the contact lens, and a stimulus of 150 ms on and 350 ms off at 2 Hz was delivered. The amplitudes and latencies of the a-, b-, and d-waves, photopic negative response (PhNR), and oscillatory potentials (OPs) were analyzed. The intraocular temperature at the mid-vitreous was measured at the beginning and just after the surgery with a thermoprobe.

Results

The intraocular temperature was 33.2 ± 1.3°C before and 29.4 ± 1.7°C after the vitrectomy. The amplitudes of the PhNR and OPs were significantly smaller after surgery, and the latencies of all components were prolonged after the surgery. These changes were not significantly correlated with the changes of the temperature.

Conclusion

Retinal function is reduced just after core vitrectomy in conjunction with significant temperature reduction. The differences in the degree of alterations of each ERG component suggests different sensitivity of each type of retinal neuron.     

Effects of age and sex on pattern electroretinograms and visual evoked potentials

Pattern-electroretinograms (P-ERGs) and visual evoked potentials (VEPs) were simulataneously recorded in 112 normal individuals aged 20–75. Two sized checks subtending 15′ and 31′ were used as stimuli. A weighted regression analysis was used to determine which of the variables, sex or age, was significant. The latency of the a and b wave of the P-ERGs showed a progressive increase with age but no difference between sexes. The effect was statistically significant for both 15′ and 31′ checks. There was no statistically significant aging effects for VEPs elicited by 31′ checks. Aging, however, affected N70, P100, and the interpeak interval between b wave to N70 and b wave to P100 for responses to 15′ checks. Shorter VEP latencies were noted in females for both 15′ and 31′ checks.The simultaneous recording of P-ERGs and VEPs has demonstrated that aging is a major variable at the retinal level. The effects on the a and b waves are mostly due to optic changes with aging and only partially to aging changes in the neuronal retinal circuitry. The effect of aging on VEPs is different for different size stimuli. The cause is a random neuronal cell loss in the visual pathways from the optic nerve to the visual cortex as the individual ages.The difference in VEP data between sexes may be related to anatomical size and hormonal influences.     

幼猫单眼视剥夺和反缝过程中显示的双眼竞争机制

本研究以光栅为刺激所同时产生的图形视觉诱发电位和图形视网膜电图为指标,测定了单眼视剥夺和缝的新生幼猫个体在发育不同阶段的空间频率调谐曲线,并与同龃正常猫,成年正常猫进行了比较研究。结果显示,在０．１２－１．５ｃ／ｄ空间频率范围内,正常幼猫单独刺激其左眼和右眼所驱动的Ｐ－ＶＥＰ振幅相近,但都明显地比双眼驱动的为小。在单眼剥夺的幼猫,由剥夺眼所驱动的Ｐ－ＶＥＰ振幅大幅度下降,健康眼所驱动的Ｐ－ＶＥＰ则     

Effect of spatial frequency on simultaneous recorded steady-state pattern electroretinograms and visual evoked potentials

Pattern electroretinograms (P-ERGs) and visual evoked potentials (VEPs) to 4 Hz alternating square-wave gratings were simultaneously recorded in 23 subjects. Responses were Fourier analyzed and amplitude and phase of the 2nd and 4th temporal harmonics were measured.The spatial frequency-amplitude function of the P-ERG 2nd harmonic component displayed either a bandpass tuning behavior, or a low-pass behavior. The peak amplitude for subjects with bandpass tuning was at 1.5 c/deg. The phase of the P-ERG 2nd harmonic decreased monotonically as spatial frequency increased. The VEP 2nd harmonic had a bimodal spatial frequency function with a peak at 3 c/deg and a second increase at spatial frequencies below 1 c/deg, regardless of the P-ERG characteristics. The phase of VEP 2nd and 4th harmonic had an inverted U-shaped function with peak at 3 c/deg and 1.5 c/deg respectively.Comparison of simultaneously recorded P-ERG and VEP spatial frequency functions demonstrated different tuning behavior for cortical and retinal responses. It is concluded that the proposed technique permits the separate analysis of retinal and cortical processing of visual information. The 2nd and 4th harmonic components of VEP behave independently of each other suggesting they may be generated by different subsystems.     

Preservation of neural function in the perinate by high PGE(2) levels acting via EP(2) receptors.

Despite increasingly frequent and longer lasting hypoxic episodes during progressive labor, the neonate is alert and vigorous at birth. We investigated whether high levels of PGs during the perinatal period assist in preserving neural function after such "stressful" hypoxic events. Visual evoked potentials (VEPs) and electroretinograms (ERGs) were recorded before and 45 min after mild moderate asphyxic hypoxia (two 4-min asphyxic-hypoxic periods induced by interrupting ventilation at 8-min intervals) in newborn piglets <12 h old treated or not treated with inhibitors of PG synthase (ibuprofen or diclofenac) with or without PG analogs. At 45 min after the hypoxic episode, P2 and b-wave amplitudes were slightly decreased and latencies were delayed. These changes in the VEP and ERG returned to near normal by 120 min. Ibuprofen and diclofenac decreased brain and retinal PG levels and markedly intensified 45 min after hypoxia-induced changes in VEP and ERG, but cerebral and retinal blood flows improved. Combined treatment with PG synthase inhibitor in combination with 16,16-dimethyl-PGE(2) (a PGE(2) analog), but not with PGI(2) and PGF(2alpha) analogs, and in combination with the EP(2) receptor agonist butaprost (but not EP(1) or EP(3) agonists), prevented ibuprofen- and diclofenac-aggravated postasphyxia electrophysiological changes. In conclusion, high levels of PGE(2) in nervous tissue, via actions on EP(2) receptors, seem to contribute to preservation of neural function in the perinate subjected to frequent hypoxic events.     

Recognition of joy, anger, and fear by face expression in humans

Behavioral and neurophysiological characteristics of a visual recognition of emotions of joy, anger, and fear were studied in 9 young healthy men and 10 women. It was shown that these emotions were identified by subjects with different rate and accuracy; significant gender differences in recognition of anger and fear were found. Recording of visual evoked potentials (VEP) from the occipital (O1/2), medial temporal (T3/4), inferior temporal (T5/6), and frontal (F3/4) areas revealed differences (related with the type of emotion) in the latencies of P150, N180, P250, and N350 waves and in the amplitude of VEP components with the latencies longer than 250 ms. These differences were maximally expressed in T3/4 derivation. The subjects could be divided in two groups. The first group was characterized by increased VEP latencies and higher amplitudes of VEP components later than 250 ms in response to anger (in comparison with other types of emotions). These phenomena were observed in all the derivations but were most pronounced in T3/4. In the second group, only late P250 and N350 components had shorter latencies during recognition of fear. VEP amplitude variations related with the type of emotions were insignificant and were recorded in the occipital and frontal areas. The two groups of subjects also differed in psychoemotional personality characteristics. It is suggested that primary recognition of facial expression takes place in the temporal cortical areas. A possible correlation of electrophysiological indices of emotion recognition with personality traits is discussed.     

Effects of 3,4-methylenedioxymethamphetamine administration on retinal physiology in the rat

3,4-Methylenedioxymethamphetamine (MDMA; ecstasy) is known to produce euphoric states, but may also cause adverse consequences in humans, such as hyperthermia and neurocognitive deficits. Although MDMA consumption has been associated with visual problems, the effects of this recreational drug in retinal physiology have not been addressed hitherto. In this work, we evaluated the effect of a single MDMA administration in the rat electroretinogram (ERG). Wistar rats were administered MDMA (15 mg/kg) or saline and ERGs were recorded before (Baseline ERG), and 3 h, 24 h, and 7 days after treatment. A high temperature (HT) saline-treated control group was also included. Overall, significantly augmented and shorter latency ERG responses were found in MDMA and HT groups 3 h after treatment when compared to Baseline. Twenty-four hours after treatment some of the alterations found at 3 h, mainly characterized by shorter latency, tended to return to Baseline values. However, MDMA-treated animals still presented increased scotopic a-wave and b-wave amplitudes compared to Baseline ERGs, which were independent of temperature elevation though the latter might underlie the acute ERG alterations observed 3 h after MDMA administration. Seven days after MDMA administration recovery from these effects had occurred. The effects seem to stem from specific changes observed at the a-wave level, which indicates that MDMA affects subacutely (at 24 h) retinal physiology at the outer retinal (photoreceptor/bipolar) layers. In conclusion, we have found direct evidence that MDMA causes subacute enhancement of the outer retinal responses (most prominent in the a-wave), though ERG alterations resume within one week. These changes in photoreceptor/bipolar cell physiology may have implications for the understanding of the subacute visual manifestations induced by MDMA in humans.     

Comparison of the mechanisms of latency shift in pattern reversal visual evoked potential induced by blurring and contrast reduction

Reduction of visual acuity or of the contrast of the stimulus induces a prolongation of the pattern reversal visual evoked potential (PR-VEP) latencies, perhaps because these conditions cause deterioration of the visual capacity to recognize objects and may preferentially activate the slower central retina channel. The PR-VEP was obtained with a video stimulator and 3 kinds of stimuli: total video field, video with a central scotoma and a restricted central stimulus. The subjects were tested under conditions of normal (20/20) and reduced visual acuity (20/200) with 14′ and 56′ checks and 60% contrast, and under conditions of normal visual acuity (20/20) with 14′ checks and with stimulus contrast of 60% and 25%. Blurring increased latencies and decreased amplitudes only with the 14′ checks stimulus but no with 56′ checks, and the amplitudes obtained with the central stimulus became greater than those obtained with a central scotoma. Reducing contrast increased only latency, and there was not difference between amplitudes obtained with a central stimulus or a central scotoma. We conclude that blurring small checks induces a preferential stimulation of receptors in the central retina, but the same effect was not observed when stimulus contrast was reduced.     

Interocular interaction assessed by VEPs to pattern-onset, -reversal,and -offset in normally sighted and amblyopic subjects

The extent of interocular interaction reflected in sequentially averaged VEPs to checkerboard onset, reversal and offset stimulation was investigated to assess the relative efficacy of the three modes of pattern stimulation. Thirty-one controls and 18 amblyopic children were studied. Components on the side of the scalp ipsilateral and contralateral to the stimulated left half-field were measured for checksizes 12′, 20′, 50′ and 80′. Binocular:monocular amplitude ratios for normals were compared with `binocular:good eye' amplitude ratios for amblyopes. The reversal P100 ratio was found to differ significantly between normals and amblyopes for 12′, 20′ and 50′ checks. Ipsilateral (CII) and contralateral (P105) onset components also differed significantly but for the smallest 12′ checks only. In controls, onset components (P105 and CIII) and, reversal components (N80 and P100) showed significantly shorter binocular as compared with monocular latencies. These latency differences were not found in amblyopes. Our results show that interocular interaction in normals is best shown by potentials which predominantly reflect macular pathway activation, and are most conspicuous for reversal N80 and P100 components. Similarly, these components demonstrated the clearest differences when comparing binocular interaction effects between controls and amblyopic subjects.     

Utility of visual evoked potentials using hemifield stimulation and several check sizes in the evaluation of suspected multiple sclerosis

One hundred and eleven patients with suspected multiple sclerosis (64 possible, 47 probable) and 16 with a definite diagnosis of MS were evaluated with pattern-reversal visual evoked potentials (VEPs), employing monocular full-field checks subtending 7′, 14′ and 28′ of visual angle, and right and left hemifield 28′ checks. Thirty-seven patients (29%) had a completely normal study. Sixty-six patients (52%) had abnormal responses to full-field 28′ checks, and in 13 (10%) of these, additional abnormalities were found in one or more of the other test conditions, which indicated the presence of an additional site of dysfunction in the visual pathway. Twenty-four patients (19%) with ‘normal’ full-field 28′ response had abnormalities in one or more of the other test conditions; these included prolonged latency to small size (7′ and 14′) full-field checks, abnormal responses in homonymous hemifields, and abnormal responses limited to a hemifield of one eye. Thus, the use of several check sizes and hemifield stimulation not only increases the sensitivity of VEPs in the evaluation of patients with suspected demyelinating disease, but enhances the capability of the VEP to demonstrate more than one area of visual system impairment.     

Multifocal Electroretinograms

A limitation of traditional full-field electroretinograms (ERG) for the diagnosis of retinopathy is lack of sensitivity. Generally, ERG results are normal unless more than approximately 20% of the retina is affected. In practical terms, a patient might be legally blind as a result of macular degeneration or other scotomas and still appear normal, according to traditional full field ERG. An important development in ERGs is the multifocal ERG (mfERG). Erich Sutter adapted the mathematical sequences called binary m-sequences enabling the isolation from a single electrical signal an electroretinogram representing less than each square millimeter of retina in response to a visual stimulus¹.Results that are generated by mfERG appear similar to those generated by flash ERG. In contrast to flash ERG, which best generates data appropriate for whole-eye disorders. The basic mfERG result is based on the calculated mathematical average of an approximation of the positive deflection component of traditional ERG response, known as the b-wave¹. Multifocal ERG programs measure electrical activity from more than a hundred retinal areas per eye, in a few minutes. The enhanced spatial resolution enables scotomas and retinal dysfunction to be mapped and quantified.In the protocol below, we describe the recording of mfERGs using a bipolar speculum contact lens.Components of mfERG systems vary between manufacturers. For the presentation of visible stimulus, some suitable CRT monitors are available but most systems have adopted the use of flat-panel liquid crystal displays (LCD). The visual stimuli depicted here, were produced by a LCD microdisplay subtending 35 - 40 degrees horizontally and 30 - 35 degrees vertically of visual field, and calibrated to produce multifocal flash intensities of 2.7 cd s m^-2. Amplification was 50K. Lower and upper bandpass limits were 10 and 300 Hz. The software packages used were VERIS versions 5 and 6.     

Circadian regulation of visually evoked potentials in the domestic pigeon, Columba livia

The avian circadian and visual systems are integrally related and together influence many aspects of birds' behavior and physiology. Certainly, light cycles and their visual perception are the major zeitgebers for circadian rhythms, but do circadian rhythms affect vision? To assess whether visual function is regulated on a circadian basis, flash-evoked electroretinograms (ERGs) and vision-evoked potentials (VEPs) from the optic tectum (TeO) were recorded simultaneously in domestic pigeons at different circadian phases in a light-dark regime (LD) and in constant darkness (DD), while feeding activity was measured to determine circadian phase. In both LD and DD, the amplitudes of ERG b-waves were higher during the day than at night and latencies of a- and b-waves were longer at night. The median effective intensity for ERG a-wave was marginally higher during the day than during the night, indicating greater sensitivity at night, but this rhythm did not persist in DD. The amplitudes of TeO VEPs were also greater during the day, and latencies were greater at night in LD and DD. Together, the data indicate that a circadian clock regulates pigeon visual function at several integrative levels.     

Serial pattern evoked potential recording in a case of toxic optic neuropathy due to ethambutol

Visual evoked potentials (VEPs) were studied in a patient who developed visual impairment during ethambutol treatment. The ERG and the flash VEP were normal at the time of maximal visual loss, whereas pattern reversal VEPs 2 and 5 months after onset revealed evidence of severe bilateral optic nerve involvement, especially affecting macular fibres. Seven months after onset paramacular PNP complexes with a late positivity (scotomatous response) were recorded after pattern reversal and half-field stimulation, suggesting involvement of fibres subserving central vision. At the time when visual acuity was normal there was still electrophysiological evidence of a mild involvement of the anterior visual pathway. The papillomacular bundle seems to be especially involved in ethambutol eye toxicity.     

Clinical evaluation of VEPs to interleaved checkerboard reversal stimulation of central,hemi- and peripheral fields

The VEPs of 195 patients referred for supportive evidence of multiple sclerosis or optic neuritis were studied by a new method of interleaved checkerboard reversal stimulation of different areas of the visual field. In the first group of 95 patients checks of 40′ subtense reversed in the whole field (28° × 20°), alternately in the left and right hemifields and alternately in the central (5° radius) and peripheral fields. In the second group of 100 patients checks reversed in the whole field and in interleaved mode in 3 visual field areas, comprising the central (4° radius) and left and right hemisurround fields.In the first group abnormal responses were recorded from 52 eyes and there was partial disagreement among the stimulus conditions in 10 of the 52. Abnormalities were seen uniquely to central field stimulation in 3 eyes but never to whole field stimulation alone. In the second group abnormal responses were recorded in 58 eyes, again never uniquely to whole field stimulation, while abnormalities confined to one or two areas of the visual field were seen in 24, providing evidence of peripheral field involvement alone in 8 eyes.In the first group, waveforms created from the sum of the left and right hemifield and central and peripheral field responses showed quite close conformity to the whole field VEP, although amplitudes were significantly lower and latencies significantly shorter. In 7 eyes responses would have been differently classified (normal or abnormal) using the sum as compared with the whole fields. The sum of the 3 interleaved stimuli was less reliable, its morphology often not closely approximating whole field responses.It is suggested that interleaved stimulation of two or more areas of the visual field is a sensitive and reliable method which reduces the time necessary to perform the test and helps control the patients' concentration, fixation and alertness. Whole field stimulation is probably necessary only in patients with severely degraded responses.     

Pattern ERG: effects of reference electrode site,stimulus mode and check size

We studied monocular pattern ERG (PERG) in 10 normal subjects and a patient with optic neuritis. No clinically significant PERG could be recorded from the occluded eye with any reference (ipsilateral ear or temple, or midfrontal), indicating that cross-contamination is not present with binocular testing. Ipsilateral temple reference minimized VEP (P100/N100) contribution to the PERG N95 which occurred with ipsilateral ear or midfrontal reference. The conclusions were confirmed by results from the patient, who had marked monocular delay of a normal amplitude P100. Twenty-four subjects were tested with monocular and binocular stimulation using an ipsilateral temple reference. There were differences in PERG latencies and amplitudes although the interside amplitude ratio showed smaller differences with binocular stimulation. Increasing check size (17, 35 and 70 min) decreased P50 and N95 latencies and increased P50 amplitude.     

Eye closure affects flash VEP latency in dementia

In a group of 27 demented patients (21 with DAT and 6 with MID) with normal pattern VEP (PVEP), the latencies of the main flash VEP (FVEP) components (P1, N2, P2 and N3) were assessed both with open and closed eyes. At variance from controls, demented patients showed that both P2 and N3 components are significantly delayed with closed eyes while neither PI nor N2 timings are affected. Control studies ruled out the possibility that such an outcome might depend on a defective pupillary responsiveness and/or an impaired sensitivity to luminance changes. On these grounds it is suggested that the effect of mode of stimulation on FVEP latency in demented patients is more likely to depend on “central” than on “peripheral” mechanisms. The dependence of latency changes on closure of the eyes seems to negate the direct effect of lesions upon visual structures and suggests an impairment of the modulatory action of non-visual afferents upon the activity of the visual cortex.     

Factors that limit the use of flash visual evoked potentials for surgical monitoring

A study was conducted comparing the incidence with which the N2/P2/N3 was obtained after flash VEP in 3 groups: anterior visual pathway lesions, non-tumor craniotomies and non-cranial surgery. These groups allowed evaluation of the effects of anesthesia, visual pathway lesions and craniotomy on the stability of the flash VEP. It was found that the latency was not significantly affected in the 3 groups, whereas the incidence of obtainable peaks and the amplitudes were adversely affected by anesthesia, cranial surgical manipulation and especially by the presence of a visual pathway lesion. These adverse effects were so marked that the application of flash VEP for intraoperative monitoring seems of little use.     

Effects of Thiopentone Halothane-Nitrous Oxide Anaesthesia Compared to Ketamine-Xylazine Anaesthesia on the DC Recorded Dog Electroretinogram

Eleven ophthal-moscopically healthy dark adapted dogs were examined by DC ERG technique with single flash full field illumination starting with near b-wave threshold blue (tests 1-3) and white (tests 4-6) stimuli of different intensity and ending with 30 Hz photopic flicker smuli (test 7) after light adaptation. All animals were anaesthetized using 2 different anaesthetic methods: Anaesthesia I (A I): Induction with thiopentone sodium, continued with halothane and nitrous oxide in oxygen. Anaesthesia II (A II): Praemedication with xylazine hydrochloride followed by anaesthesia with ketamine hydrochloride. A minimum interval of 1 week was kept between all anaesthesias. The a- and b-wave amplitudes and latencies were determined. Statistical analysis of results indicated that the a- and b-waves were elicited by weaker intensities in A II. In Tests 3-6 the a-wave was highly significantly (P < 0.001), higher in amplitude in AII than in A I. Differencies in b-wave amplitudes were not statistically significant (except Test 1). The b-wave latencies were longer in AI in Test 2 (using low intensity blue light). The a-wave latencies were slightly shorter in AII in Test 6 (using high intensity white light). In additional experiments the selective action of the different agents (except N2O) used in AI and AII was studied. Thiopentone alone given to 3 dogs seemed to depress the a-wave selectively. Halothane given separately to 3 dogs lowered both the a- and b-wave amplitudes. Ketamine given with a neuromuscular blocking agent to three dogs resulted in responses almost identical to those in AII. Xylazine with vecuronium given to 4 dogs resulted in responses with slighly depressed a- and b-waves in comparison to ketamine with vecuronium. The results indicate that when developing an animal model for the electrophysiologic study of human retinal dystropies, the actions of different anaesthetics upon the ERG components are of great importante.