Reduced oscillatory potentials of the full-field electroretinogram of eyes with aphakic or pseudophakic cystoid macular edema

PURPOSE: To report reduced oscillatory potentials (OPs) in the full-field electroretinogram (ERG) of eyes with aphakic or pseudophakic cystoid macular edema (CME). DESIGN: Observational case series. METHODS: Bright white flash full-field ERGs were recorded from 19 eyes of 19 patients (ages, 53-84 years) with aphakic or pseudophakic CME. Seven of the cases had uncomplicated phacoemulsification (PE) with implantation of a posterior chamber intraocular lens (PC-IOL) and 6 had posterior capsular rupture during phacoemulsification and aspiration with implantation of a PC-IOL. Four additional patients had uncomplicated intracapsular cataract extraction (ICCE), and 2 had secondary anterior chamber intraocular lens after ICCE. Their fellow eyes without CME served as controls. Cystoid macular edema was diagnosed as clinically significant by slit-lamp examination and by fluorescein angiography. The grading for severity of CME was based on the fluorescein angiography. The visual acuity ranged from 20/200 to 20/16. RESULTS: There were no significant differences in the mean amplitudes and implicit times of the a-waves and b-waves between the affected eyes and the fellow eyes. The mean summed amplitude of the OPs was significantly reduced in the affected eyes (P =.0003, Wilcoxon signed rank test). This decrease was strongly correlated with visual acuity (r =.779, P <.0001). The mean implicit time of the first OP was significantly delayed in the affected eyes (P =.0089, Wilcoxon signed rank test). CONCLUSIONS: Because the peripheral retina contributes more significantly to full-field ERGs than the macula, the reduced OP amplitudes of the full-field ERGs in eyes with aphakic or pseudophakic CME suggest a functional impairment not only in the macula but also throughout the retina.     

Effect of spatial frequency of stimulus on focal macular ERGs in monkeys

Purpose To determine the effect of the spatial frequency of a small grating stimulus centered on the macula on the focal macular ERGs (fmacERGs) of monkeys.Methods fmacERGs were recorded from eight eyes of four adult monkeys (Macaca fuscata). The spatial frequency of the stimulus was changed from 0.25 to 8 cycles/degree. The luminance of the light bars was 10 cd/m², and the contrast was 95%. The stimulus was flashed on and off with an on duration of 100 ms and an off duration of 150 ms (4 Hz). The stimulus was centered on the fovea and subtended 12.7° at the cornea. The luminance of the steady light-adapting background was 3.5 cd/m². The location of the stimulus on the retina was monitored throughout the recordings. The effects of the spatial frequency of the stimulus on the amplitudes and implicit times of the a-waves, b-waves, and oscillatory potentials (OPs) were determined. fmacERGs were also recorded following intravitreal tetrodotoxin (TTX).Results The amplitudes of the a- and b-waves did not change with changes in the spatial frequency of the stimulus. The OPs, on the other hand, responded best to the lowest spatial frequency, and the OPs after the first two were attenuated at intermediate and higher frequencies (Wilcoxon signed-rank test: P < 0.05). TTX reduced all OP wavelets in monkeys.Conclusions The OPs of the photopic macular ERGs are affected by the spatial frequency of the stimulus and are reduced by TTX, consistent with their being generated by inner retinal neurons.     

Multifocal electroretinogram in occult macular dystrophy

PURPOSE: Occult macular dystrophy (OMD) is an unusual macular dystrophy presenting with an essentially normal fundus and fluorescein angiography but with progressive central visual loss. The authors studied the function of local retinal areas in the posterior pole of patients with OMD using multifocal electroretinograms (ERGs). METHODS: Multifocal ERGs were recorded using the Visual Evoked Response Imaging System with 61 hexagonal elements within a visual field of 30 degrees radius from 8 OMD patients and 20 age-matched, normal subjects. The amplitudes and implicit times of the patients and normal control subjects were compared at the various retinal eccentricities. RESULTs. The amplitudes of the multifocal ERGs in the OMD patients were markedly reduced in the central 7 degrees of the fovea. The difference of the ERG amplitudes between OMD and normal subjects became smaller toward the peripheral retina. Most OMD patients had slight but significantly delayed implicit times across the whole testing field, and the differences between the OMD and the normal subjects did not change with retinal eccentricity. CONCLUSIONS. Our results for multifocal ERG amplitudes support the idea that OMD patients have localized retinal dysfunction distal to the ganglion cells in the central retina. The delayed implicit times across the whole test field suggest that the retinal dysfunction has a broader boundary than expected by ERG amplitudes and psychophysical perimetric results.     

Focal cone ERGs of rhodopsin Pro347Leu transgenic rabbits

A rhodopsin P347L transgenic (Tg) rabbit, a model of retinitis pigmentosa, has been generated in our laboratory. The purpose of this study was to determine the properties of focal areas of the retina in this rabbit model during the course of retinal degeneration. To accomplish this, we recorded focal ERGs from wild-type (WT) and Tg rabbits at ages 3, 6, and 12 months. A 15° stimulus spot was used to elicit the focal ERGs from the center of the visual streak and from four surrounding areas. We found that the amplitudes of the focal cone ERG b-waves and oscillatory potentials (OPs) of the Tg rabbits in the five areas decreased progressively with increasing age and became almost non-recordable at 12 months. There were no significant regional differences in the b-waves of Tg rabbits recorded from the 5 areas. The amplitudes of the OPs were better preserved than the b-waves and the OPs/b-wave ratio was higher than that in WT rabbits at every recording area. The summed OPs amplitudes, which most likely originate from the amacrine and/or ganglion cells, recorded from the area superior to the optic disc was significantly larger than that from other areas at 3- and 6-months-old. This indicated that the inner retinal neurons were not altered equally after photoreceptor degeneration in this rabbit model.     

Comparisons of cone electroretinograms after indocyanine green-, brilliant blue G-, or triamcinolone acetonide-assisted macular hole surgery

Purpose

To compare the function of retinal ganglion cells (RGCs) using the photopic negative response (PhNR) in patients who had undergone indocyaine green (ICG)-assisted, brilliant blue G (BBG)-assisted, or triamcinolone acetonide (TA)-assisted internal limiting membrane (ILM) peeling during macular hole (MH) surgery.

Methods

Forty-eight eyes of 48 patients with a macular hole were randomly divided into those undergoing ICG-assisted, BBG-assisted, or TA-assisted vitrectomy (n?=?16 for each group). Full-field cone ERGs were recorded before and 1, 3, 6, 9, and 12 months postoperatively. The amplitudes and implicit times of the a-waves and b-waves and the amplitudes of the oscillatory potentials (OPs) and PhNRs were measured. The mean deviations (MDs) of standard automated perimetry and the best-corrected visual acuity (BCVA) were measured. The circumferential retinal nerve fiber layer (RNFL) thickness was evaluated by SD-OCT.

Results

All macular holes were closed with a significant improvement of the BCVA and MD without differences among the groups. There was no significant difference between the preoperative and postoperative RNFL thickness. The implicit times of the a-waves and b-waves were significantly prolonged, and the ΣOPs amplitude was significantly decreased postoperatively in all groups. These ERG changes were not significantly different among the groups. The postoperative PhNR amplitudes were significantly lower in the ICG group than in the BBG or TA group.

Conclusions

The results indicate that the PhNR may detect subclinical impairments of RGCs caused by the possible toxic effect of ICG. This finding adds to the data that BBG and TA may be safer than ICG for use during MH surgery.     

Macular oscillatory potentials in humans

Studies of the focal macular electroretinogram (ERG) have been made with special reference to oscillatory potentials (OPs) by using a fundus monitoring system in humans. Human macular OPs consist of 3 to 4 wavelets (mean peak interval, approximately 6.5 msec). The distribution of OPs in relation to those in a- and b-waves was studied. The amplitudes of a-waves, b-waves, and OPs of the upper macula were significantly larger than those of the lower macula. The distribution of OPs is relatively sparse in the fovea, becoming more dense than the a- and b-waves from the fovea toward the parafovea, and differing even more toward the perifovea. There was no statistical difference of amplitude in a- and b-waves between nasal and temporal macula. The amplitude of OPs in the temporal macula, however, was significantly larger than in the nasal macula. In some macular diseases, such as diabetic maculopathy, cystoid macular edema, or the convalescent stage of central serous chorioretinopathy, macular OPs were selectively reduced, leaving the a- and b-waves intact. Macular OPs can provide a new aspect of macular function and can be a sensitive indicator to assess that function in macular diseases.     

Oscillatory potentials of multifocal electroretinogram retinopathy

Purpose: To investigate the physiological function in the posterior pole of the retina in eyes with preproliferative diabetic retinopathy using the oscillatory potentials (OPs) of the multifocal electroretinogram (mfERG). Methods: Multifocal ERGs were recorded from 61 eyes of 61 patients with preproliferative diabetic retinopathy (pre-PDR) and 16 eyes of 16 age-similar normal control subjects. The amplitudes and implicit times of the first positive component, P1, and the OPs of the mfERGs, recorded with a slow m-sequence, from diabetics were compared with those in normal control subjects. Among the 61 eyes, the mfERGs were recorded before and after panretinal photocoagulation (PRP) in 19 eyes of 19 patients. Results: The amplitudes of P1 and OPs were significantly smaller in all tested areas in the diabetics as compared with those in the normal subjects, and the degree of reduction was greater for the OPs than P1. The implicit times of P1 and OPs were significantly delayed in the diabetics in the peripheral tested regions (20–40°) but not in the central area. After PRP, the amplitudes of P1 were markedly reduced in all areas tested; however, the changes of the P1 implicit time were not significant. The amplitudes of the OPs were significantly reduced in the peripheral regions after PRP; however, the changes in the implicit times were not significant. Conclusions: These results indicate that retinal function in the posterior pole is markedly impaired in eyes with pre-PDR. PRP altered the mfERGs significantly, however, the reductions were limited to the amplitude.     

Electroretinographic study of spontaneously diabetic Torii rats

Spontaneously diabetic Torii (SDT) rats are an inbred strain of rats with a non-obese type 2 diabetes mellitus that were isolated from an outbred colony of Sprague–Dawley (SD) rats. Electroretinograms (ERGs) were recorded from SDT and SD (controls) rats at 10- and 44-weeks-of-age to determine their retinal function. The amplitudes and implicit times of the ERGs of the right and left eyes were not significantly different indicating that the intra-individual variation was small. Both amplitudes and implicit times of the ERGs in the SDT rats were not significantly different from those of SD rats at 10-weeks-of-age. At 44-weeks-of-age, however, the a- and b-waves and the oscillatory potentials were significantly reduced with prolonged implicit times in the SDT rats compared to SD rats. These depressed ERGs may reflect vascular and neuronal damage throughout the retina as are seen in the advanced stages of human diabetic retinopathy. Thus, the SDT rat can be used to study the retinal physiology of diabetic retinopathy.     

Physiological development of the kitten's retina: an ERG study

The physiological development of the retina was followed by recording ERGs and OPs from kittens of different ages. We found that different properties of the retina attain adult values at different ages: the b-wave elicited by higher stimulus intensities became adultlike by five to seven weeks while the b-waves elicited by lower stimulus intensities required another 3-5 weeks; the implicit time for the b-waves elicited by the full intensity stimulus attained adult values by 10 weeks of age; and the oscillatory potentials did not become adultlike until 18 weeks of age. The physiological development of the ERG was related to the development of the photoreceptors and the ganglion cells as well as to the morphological development of the second order neurons. It was concluded that the physiological development, as the morphological development, proceeds in three stages: an initial slow phase during which the late receptor potential and the b-waves are first recorded; a second rapid phase, during which the amplitude of the b-waves and OPs increase rapidly; and a third slow differentiation phase during which the final development of the properties of the retina are attained.     

Multifocal electroretinograms in X-linked retinoschisis

PURPOSE: To study local retinal cone function in patients with X-linked retinoschisis (XLRS) by multifocal ERGs (mfERGs). METHODS: mfERGs were recorded from seven eyes of seven patients with XLRS (mean age +/- SD, 22.1 +/- 3.2 years; range, 18 to 25 years). Five eyes had microcystic changes in the macula and two eyes had nonspecific macular degeneration. Two eyes had peripheral retinoschisis, and some of the stimuli fell on this area. The stimulus array consisted of 103 hexagons and the total recording time was set at approximately 4 minutes. The amplitudes and implicit times of both focal and summed responses for the first- and second-order kernels were analyzed. RESULTS: The amplitudes of the first-order kernel were markedly reduced in the central retina in all eyes. A large variation was observed in the amplitudes outside the fovea. The amplitudes of the focal cone ERGs at the peripheral retinoschisis did not differ from those recorded from adjacent retinal loci without the retinoschisis. The implicit times of the first-order kernel were significantly delayed, and the amplitudes of the second-order kernels were more affected than the first-order kernels across the whole field in all XLRS eyes. CONCLUSIONS: The cone-mediated retinal responses were more impaired in the central than peripheral retina in eyes with XLRS. Delayed implicit times of the first-order kernel and reduced second-order kernel across the whole testing field in all XLRS eyes suggest that there is widespread cone-system dysfunction in XLRS.     

Regional variations in local contributions to the primate photopic flash ERG: revealed using the slow-sequence mfERG

PURPOSE: To determine the variations with eccentricity of the primate photopic ERG and to separate contributions by different retinal cells by using intravitreal pharmacologic agents. METHODS: Slow-sequence multifocal (mf)ERGs were obtained from 19 anesthetized adult rhesus monkeys and 5 normal human subjects. Recordings in monkeys were obtained before and after injections of tetrodotoxin citrate (TTX) to block sodium-dependent spiking; TTX+N-methyl-D-aspartic acid (NMDA)+picrotoxin (PTX) or gamma-aminobutyric acid (GABA) to block all inner retinal activity; L-2 amino-4-phosphonobutyric acid (APB) to block the On-pathway; and cis-2, 3 piperidine dicarboxylic acid (PDA) to block the Off-pathway and the otherwise unblocked inner retinal activity. The stimulus consisted of 103 equal-sized hexagons within 17 degrees of the fovea; every 200 ms (15 frames), each hexagon had a 50% chance of remaining at 20 cd/m(2) or increasing briefly to 4.7 cd-s/m(2). Oscillatory potentials (OPs; 90-300 Hz) were extracted. RESULTS: The slow-sequence mfERG summed over the stimulated area looked similar to a standard photopic, full-field ERG, with a- and b-waves and OPs. OPs in the foveal and temporal retina were larger than in the nasal retina. This nasotemporal asymmetry was removed by TTX, and the OPs were eliminated, either by blocking inner retina activity or by blocking the On-pathway. The summed mfERG waveform, including OPs, was shaped mainly by the more peripheral retinal regions. The foveal b-wave peak occurred about 5 to 6 ms later than in the periphery, with the depolarizing peak of the On-pathway/bipolar contribution occurring earlier than the depolarizing peak of the Off contribution at all eccentricities. The a-wave was composed of a small photoreceptor contribution and postreceptoral portion originating from hyperpolarizing neurons. CONCLUSIONS: The variations in the primate photopic ERG with eccentricity are due to spike-driven oscillatory activity that is more prominent in central and temporal retina than in nasal retina and to the slower timing of all responses in the central, compared with the peripheral, retina. The full-field, photopic ERG most closely resembles the mfERG responses to stimulation of peripheral regions.     

Function and morphology of macula before and after removal of idiopathic epiretinal membrane

PURPOSE: To study the function and morphology of the macula of the eye before and after the removal of unilateral idiopathic epiretinal membrane (ERM). METHODS: Focal macular electroretinograms (fmERGs) elicited by a 15 degrees stimulus were recorded in 37 eyes of 37 patients with a unilateral ERM. The amplitudes of the a- and b-waves and the oscillatory potentials (OPs) were compared with the corresponding waves in the normal fellow eyes before and after removal of the ERM. In 29 eyes followed up for more than 6 months after surgery, the fmERGs and foveal and parafoveal thicknesses, measured by optical coherence tomography (OCT), were evaluated. RESULTS: Before surgery, the mean amplitudes of all components of the fmERGs were significantly smaller than in the fellow eyes, with the decrease largest for the OPs, followed by the b-waves and then the a-waves. The eyes with less severely reduced a-wave amplitude (>70% of the fellow eyes) had significantly lower b-wave to a-wave (b/a) ratios. After surgery, the amplitudes of the b-wave and OPs were still significantly smaller in the affected eyes. The mean foveal and parafoveal thicknesses were significantly less after surgery; however, the thickness was still more in the affected eyes. The decrease of the OPs remained after surgery and correlated with increased parafoveal thickness (r = -0.460, P = 0.011). CONCLUSIONS: The decreased fmERGs indicate that macular function is impaired in eyes with ERM. The decrease of the b-wave and OPs in the 29 eyes examined after vitrectomy may be due to the still thickened macular retina.     

正常SD大鼠视网膜电图随生长发育变化的特点

目的研究正常SD大鼠视网膜电图(ERG)随生长发育的变化特点。方法分别测量40只(40眼)SD大鼠在出生后第14、21、28、35和56d(P14、P21、P28、P35、P56)的ERC。结果正常SD大鼠Max-ERGa波、OPsO1波潜伏期在各个时间点无明显差异;Rod-ERGb波、Max-ERGb波、Cone-ERGb波、OPsO2波潜伏期和波幅值以及OPsO1波和Max-ERGa波幅值、Flick-ERG幅值在P14分别和其他时间点有差异。结论实验在一定程度上证实了正常SD大鼠ERG中各波形的起源。明确了各波形的成熟时间,P21时正常SD大鼠ERG基本发育成熟。     

Effect of body temperature on electroretinogram of mice

PURPOSE: To investigate the ERG alterations induced by changes in body temperature in mice. METHODS: Three-week-old BALB/c mice were used. Rectal temperature was measured with a digital thermometer and taken as the body temperature. In experiment 1, the body temperature was kept at 33 degrees C, and the ERGs elicited by a constant stimulus intensity were recorded every 5 minutes. In experiment 2, the body temperature was lowered in five steps from 38 degrees C to 33 degrees C, 28 degrees C, 23 degrees C, and 18 degrees C. At each body temperature, ERGs elicited by different stimulus intensities were recorded. RESULTS: In experiment 1, the mean amplitudes and implicit times of both the a- and b-waves did not change significantly. In experiment 2, the amplitude of both the a- and b-waves decreased significantly with a decrease in body temperature, and the implicit times of the a- and b-waves were prolonged with a decrease in body temperature. CONCLUSIONS: Body temperature greatly affects the amplitude and timing of the ERG. Great care must be taken to maintain as normal a body temperature as possible when using the ERG to evaluate the retina, especially in small animals such as mice.     

Oscillatory potentials in electroretinograms of the human macular region

Using focal stimuli, we successfully recorded oscillatory potentials (OPs) in electroretinograms of the macular regions of 72 normal volunteers. The OPs consisted of three to four wavelets with a mean peak interval of approximately 6.5 msec, consistent with that recorded with conventional full-field stimuli over the entire retina. The changes of amplitude in response to the spot sizes and ring stimuli suggested that the distribution of OPs is different from that in a- and b-waves in human macular region.     

Changes of Oscillatory Potentials and Photopic Negative Response in Patients with Early Diabetic Retinopathy

Purpose

To investigate the clinical significance of the oscillatory potentials (OPs) and photopic negative response (PhNR) of the electroretinogram (ERG) in patients with early diabetic retinopathy.

Methods

One hundred two diabetic patients with diabetic retinopathy at different stages were examined. Thirty-two age-matched normal controls were also studied. Full-field maximal and photopic cone ERGs were recorded. The amplitudes and implicit times of the OPs, cone b wave, and PhNR were compared at the different stages of diabetic retinopathy.

Results

The a and b wave amplitudes of the maximal scotopic ERGs remained unchanged despite advancing stages of retinopathy, but the OP amplitudes were significantly attenuated even at an early stage of diabetic retinopathy. The amplitudes of both the PhNR and cone b wave were reduced at an early stage of diabetic retinopathy. Analysis of the receiver operating characteristic curves demonstrated that the amplitudes and implicit times of the OPs were more sensitive and specific than those of the PhNR in detecting changes of retinal function in the early stages of diabetic retinopathy.

Conclusions

The amplitudes of the OPs and PhNR progressively decrease with the progression of diabetic retinopathy. The PhNR amplitudes were reduced along with the cone b wave, indicating that earlier change of the PhNR in diabetic patients reflects reduced input to the retinal ganglion cell from the distal retina. The amplitudes and implicit times of the OPs are better indicators than those of the PhNR in detecting functional decreases in patients with early diabetic retinopathy.?Jpn J Ophthalmol 2006;50:367–373 © Japanese Ophthalmological Society 2006     

Contribution of N-methyl-dl-aspartic acid (NMDA)-sensitive neurons to generating oscillatory potentials in Royal College of Surgeons rats

Purpose

We investigated how the N-methyl-dl-aspartic acid (NMDA) receptor contributes to generating oscillatory potentials (OPs) of the electroretinogram (ERG) in the Royal College of Surgeons (RCS) rat.

Methods

Scotopic ERGs were recorded from dystrophic and wild-type congenic (WT) RCS rats (n = 20 of each) at 25, 30, 35, and 40 days of age. The stimulus intensity was increased from ?2.82 to 0.71 log cd-s/m² to obtain intensity-response function. NMDA was injected into the vitreous cavity of the right eyes. The left eyes were injected with saline as controls. The P3 obtained by a-wave fitting was digitally subtracted from the scotopic ERG to isolate the P2. For the OPs, the P2 was digitally filtered between 65 and 500 Hz. The amplitudes of OP1, OP2, OP3, and OP4 were then measured and summed and designated as ΣOPs. The implicit times of OP1, OP2, and OP3 were also measured. The frequency spectra of the OPs were analyzed using fast Fourier transform (FFT).

Results

The maximum ERG a- and b-waves as well as ΣOPs amplitudes reduced with age in dystrophic rats. Compared with intravitreal saline injection, administration of NMDA decreased ΣOPs amplitudes from 30 days of age in dystrophic rats, while it did not attenuate ΣOPs amplitudes in WT rats. The implicit times of the OPs of the maximum ERG were prolonged by NMDA injections in WT and dystrophic rats. NMDA/saline ratios of ΣOPs amplitudes area under the FFT curves were significantly lower in dystrophic rats from 30 days of age than that in WT rats.

Conclusion

In the early stage of photoreceptor degeneration, intravitreal NMDA injection attenuated OPs amplitudes in dystrophic rats. This indicates that NMDA receptors play a significant role in generating OPs amplitudes with advancing photoreceptor degeneration.     

Time-Dependent Course of Electroretinograms in the Spontaneous Diabetic Goto-Kakizaki Rat

Purpose

This study evaluates the relevance to human retinopathy of electroretinograms (ERGs) from the spontaneously diabetic Goto-Kakizaki (GK) rat.

Methods

Starting from 4 weeks of age, we obtained ERGs every 4 weeks from six GK rats and seven Wistar (control) rats, and from two GK and two Wistar rats at 14 days of age. The a-wave, b-wave, and oscillatory potentials (OPs) were recorded after stimulation with a single bright flash. We compared the amplitudes and implicit times and measured a-wave latencies to evaluate photoreceptor function.

Results

The amplitudes of the a-wave, b-wave, and OPs (O1 and O2) of the GK rats were reduced between 4 and 48 weeks of age. The time-dependent courses of change in a-wave, b-wave, and O2 amplitude did not differ between the two groups. The a-wave latencies in GK rats were significantly prolonged, but not the implicit times of OPs. At 14 days of age, the a-wave amplitudes were significantly smaller in GK than in Wistar rats.

Conclusion

Functional abnormalities of photoreceptors might be induced by inheritable degeneration at an early age in the GK rat. Although hyperglycemia would cause retinal hypoxia, it would not be severe enough to disturb the generation of OPs.?Jpn J Ophthalmol 2006;50:211–216 © Japanese Ophthalmological Society 2006     

Oscillatory potentials of local macular ERG in diabetic retinopathy

The oscillatory potentials (OPs) in electroretinogram (ERG) have clinical values in measuring retinal functions of the early stage of diabetic retinopathy. However, OPs have, until now, been evaluated as components of total ERG recorded with a full field stimulus over the entire retina. Therefore, little information could be obtained about the macular condition (diabetic retinopathy). Using focal stimuli, we successfully recorded OPs in the human macular region. We modified our previously reported system for recording local macular ERG under the fundus monitor with an infrared television fundus camera. We evaluated macular OPs with simultaneously recorded a- and b-waves in many patients with diabetic retinopathy. In some kinds of early diabetic maculopathy, the macular OPs were selectively reduced, leaving the a- and b-waves intact. The macular OPs can be a valuable indicator in assessing the macular function in diabetic maculopathy.