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Purpose: Since the electrical function of the pigment epithelium (PE) may be severely impaired while only small fundoscopic alterations are visible, like in vitelliform dystrophy, we examined the PE by recording the electrooculogram (EOG) in a rare disease consisting of bilateral multiple small pigment epithelial detachments (PED) without age related macular changes.
Methods: Four healthy middle age with bilateral normal visual acuity, transparent ocular media in which fluorescein angiography revealed multiple PED in the posterior poles underwent EOG tests. After pupillary dilatation and light preadaptation, the EOG was recorded according to the standard protocol. The subjects seating in front of a full-field stimulator with silver disc fastened next to the canthin performed horizontal 30 degree alterating eye movements for 15 minutes in the dark, followed by 15 minutes in the light. The electrical potentials light peak/dark through amplitude ratio was calculated for each eye.
Results: The EOG lower normal value was considered 180%. In each examined eye the EOG determined ration was well above the lower normal limit indicating a normal functioning PE.
Conclusion: Our novel finding revealed in this rare retinal disease that despite multiple small PED the lesion seem to be confined to the affected areas while the overall electrical response is preserved.
Introduction Docosahexaenoic acid (DHA) is highly enriched in the phospholipids of retinal photoreceptor outer segments, comprising up to one-half of the fatty acids of phosphatidylethanolamine and phosphatidylserine in rod-dominated retinas. A deficiency in DHA is associated with a loss of discriminant learning ability and visual acuity. The current study was designed to investigate the protective effect of DHA on damaged retina by kainic acid (KA) in rat.
Methods Female Wistar rats aged 3 wks were used for this study. Following 14 days DHA dietary supplementation (1000mg/kg/day)( DHA group) and arabic gum solution in the same volume (control group), the right eyes of all rats were received intravitreal injection of KA in a dose of 3.12 nmol. An intensity series of ERG response was recorded on the 1, 7 and 14 days before and after KA injection. A cotton wick electrode placed on the cornea and a stainless steel needle electrode attached subcutaneously to the nasal bone as a reference. The amplitude and peak latency of the a- and b-wave and Oscillatory Potentials (OPs) were evaluated.
Results ERGs after KA injection essentially showed a negative type, i.e. normal a-wave with greatly attenuated b-wave in both groups. However, the attenuation of b-wave in DHA treated rats group was lesser compared with controls. OPs were recordable in the DHA treated rats, while they were non-recordable in the control groups. The differences between DHA group and control group were progressively decreasing with time after KA injection.
Conclusions The present results indicate that administration of DHA may prohibit the insult of glutamate neurotoxicity on the retina of rat.
Introduction: To investigate binocular summation of visually evoked cortical potentials (VECP) in normal tension glaucoma (NTG).
Methods: Eleven normal control subjects and 11 NTG patients were examined. VECPs to monocular and binocular stimulation were recorded with pattern reversal and multifocal stimulation. Pattern reversal VECPs were recorded by varying check sizes at 20% contrast levels for 3 (transient VECP) and 12 (steady-state VECP) reversal frequencies. Multifocal VECPs were recorded with a use of Sutter's program. Amplitude and peak latency of the P1 component were estimated.
Results: No binocular summation effects were found in the normal control group. A spatial frequency characteristic curve was found it's maxima at 15 minutes of arc both in monocular and binocular stimulation records. In patients with NTG the curve based on peak latency and phase of pattern reversal VECP showed a significant depression at higher spatial frequency range for binocular stimulation, although no difference was found with amplitude measurements. Multifocal VECP showed no significant difference between normal controls and patients with NTG.
Conclusions: Our results were controversial to the past reports which showed binocular enhanced effects on pattern reversal VECP in normals. Based on our results in normals, we found high spatial frequency deficit for binocular stimulation in patient with NTG. It was, thus, suggested functional deficiency in binocular vision in NTG.
Introduction. We describe the phenotype in the first patient diagnosed with Oguchi disease in Germany and a mutation in the gene encoding rhodopsin kinase (RHOK), and compare it with the phenotypes in (1) 3 unrelated patients with mutations in the same gene (Carr et al., Arch. Ophthalmol.73, 1965 and Carr et al, Invest. Ophthalmol. Vis. Sci.6, 1967) and (2) 8 patients from 6 families and a homozygous deletion (1147delA) in the arrestin gene (Nakazawa et al., Retina 17, 1997).
Methods. A 38 yrs old male was examined clinically including fundus photography in the light and dark adapted state. ERG was recorded according to the ISCEV Standard. Dark adaptation (DA) was tested with a short wavelength stimulus (500 nm cut-off filter, 64 mm2) 12(infinity) on the vertical below fixation until pre-bleach values were reached. Molecular results have been obtained as described earlier (Yamamoto et al., Nature Genet.15, 1997).
Results. The patient is the only child of unrelated parents. V.A. was 1.0 sc R.E. and 1.25 sc L.E. He was aware of problems with dark-adaptation since childhood. Funduscopy revealed a metallic-like reflex at the posterior pole o.u. that had vanished after 2.5 hours of dark adaptation. In the ERG the averaged rod-responses were non-recordable, the maximal-response of negative type with a low-normal a-wave and the OPs of low-normal amplitudes. Pre-bleach thresholds were reached after 2.5 hours of DA. SSCP analysis detected a homozygous 4-bp deletion in exon 7 in the RHOK gene: Ser536 (4-bp del) leading to a truncation of the C-terminus. Both parents were found to be heterozygous. The same mutation was previously reported in a compound heterozygote (Yamamoto et al., 1997).
Conclusions. The mutation in the RHOK gene in a German patient with Oguchi¥s disease confirms previous data on mutations in this gene to be frequent in patients of German origin compared to Asian patients with mutations in the arrestin gene (Fuchs et al., Nature Genet.10, 1995). The non-recordable averaged rod response, the negative maximal-response and the delayed dark adaptation are common functional features in patients with mutations in the arrestin and RHOK gene. Whereas cone responses were normal in patients with mutations in the RHOK gene, they had slightly reduced amplitudes in some patients with the arrestin 1147delA mutation. Further thorough electrophysiological and psychophysical examinations are needed in order to uncover the phenotypic differences in patients with mutations in the arrestin and RHOK gene.
Acknowledgement. Molecular genetic analysis was performed in Dr. Dryja's lab, Massachusetts Eye and Ear Infirmary, Harvard Medical School, 243 Charles Street, Boston, Massachusetts 02114-3096.
Introduction. The directional tuning of the motion-onset VEPs has not been systematically studied to date. We measured these potentials to motion in 8 directions around the full circle and obtained both baseline values and amplitudes after motion adaptation in one direction.
Methods. The stimuli were 10% contrast random dot patterns in a circular mask (dia 26(infinity)); when moving, then at a speed of 11(infinity)/s. Baseline blocks consisted of 2700 ms stationary pattern, 300 ms test motion sequences; adaptation blocks consisted of 2200 ms adapting motion to the right, 500 ms stationary pattern and 300 ms test motion. Eight test stimuli moving in 8 different directions in 45(infinity) steps were shown. Blockwise shuffling was employed to avoid sequential effects. In 11 subjects we recorded from occipital, occipito-temporal and central sites vs. linked ears. Eye movements were monitored with the EOG.
Results. Baseline amplitudes were around -4 microvolts and differed (non-significantly) by less than 15% between the eight directions. Adaptation reduced the N2-amplitude to 50% at all 7 non-adapting directions and down to 13% at the adapted direction. These effects were similar for all recording sites.
Conclusions. (1) Motion-onset VEPs are essentially symmetric "around the clock". (2) The marked adaptation in all non-adapting directions suggests that non-directional motion-evoked activity comprises about 50% of the response, while the remaining response arises mainly from direction-selective motion processing. Thus less than half of the motion response would reflect veridical motion processing.
This work was supported by the Deutsche Forschungsgemeinschaft.
Introduction: The multi-focal technique, introduced by Sutter, offers the opportunity to record Visual Evoked Potentials (VEPs) from multiple small areas of the visual field. Thus, it opens the possibility to resolve some of the problems of the large-field VEP, caused by the heterogeneity of the stimulated area and the topography of its cortical representation.
Methods: The first step was to relate the kernel waveforms of the VEP obtained by this technique to the traditional pattern onset and pattern reversal VEP, and that was the aim of this study. We used an 8 x 8 checkerboard stimulus array (produced by EDI Inc), with each element of the array having the capability to contain from 1 to 16 checks, and containing, for this work, 4 x 4 checks. The contrast (first experiment) or the luminance (second experiment) was changed in a step-wise manner so that the stimulus was changed, in steps, from being pure pattern reversal to pure pattern onset. VEPs were recorded from a central electrode 2.5 cm above the inion, referred to a mid-frontal electrode, in response to each stimulus type (10 in all).
Results: Clear waveforms were produced in response to stimulation of the central four elements of the 8 x 8 array, particularly those in the lower half-field. Smaller responses were produced by stimulation of the more peripheral areas and these were lost in the noise in some subjects. For all stimulus types, responses were visible in the second order kernels only for pure pattern reversal, but were visible in both first and second-order kernels in all of the others, even though the overall luminance was perfectly balanced for the pure pattern onset stimulus.
Conclusions: These results suggest that pattern onset and reversal responses may reflect fundamentally different visual processes.
Purpose. To investigate central abnormalities in the retinal function in patients with macular hole using SLO evoked and monitor stimulated multifocal ERG.
Methods. 10 patients with macular hole (Gass II-IV) underwent SLO induced and monitor stimulated multifocal ERG (m-ERG) testing. On all patients an ophthalmic examination with a slitlamp and ophthalmoscope was performed. Afterwards patients underwent a fluorescein angiogram. The monitor stimulated multifocal ERG was performed as described by Sutter and Tran. In addition, a scanning laser ophthalmoscope was used as a stimulator and trigger unit. The stimulus matrix, containing of 19, 37 or 61 hexagones, is generated by a helium-neon laser. For simultaneous fundusscopy a infrared laser is used. The SLO unit (Rodenstock, Mnchen) is connected to a multifocal ERG device (Roland Consult, Wiesbaden). According to a pseudorandom m-sequence, the different hexagones of the stimulus matrix were stimulated concurrently, with the average luminance kept constant during the whole examination. Unless a pupil diameter is less than 3mm, dilatation of the pupil is not necessary.
Results. In contrast to the monitor stimulated m-ERG the SLO induced m-ERG allows a real time fundus control during the investigation, which enables the clinician to perform examination under simultaneous control of fixation. The hexagones which cover the local defects in the retina can be precisely correlated to the fundus picture gained by the SLO. The patients underwent SLO evoked and monitor stimulated multifocal ERG testing. The results were compared to the control subjects (40 eyes). In patients with macular hole, the amplitudes of the foveal region were reduced, whereas the extrafoveal parts of the retina showed a normal response. Also the latencies of the central retina were delayed, whereas in the exrafoveal retina normal latencies were observed. These results were seen in SLO evoked and monitor stimulated m-ERG recordings.
Conclusion. The SLO evoked m-ERG allows an objective evaluation of retinal function under control of fixation. In patients with macular hole a central reduction of amplitudes and a delay of latencies could be shown. According to the pathology of macular hole, which affects only the central part of the macula, no pathological answers were found in the extrafoveal parts of the posterior pole.
Purpose. We previously characterized (Rousseau et al., ARVO 1995) a New Photopic Light Adaptation Effect (type II LAE) as the transient enhancement of the photopic ERG resulting from an abrupt decrease in illumination from a brighter to a dimmer rod-desensitizing background (BG). The purpose of this study was to investigate the relative contribution of S-, M-, and L-wavelength sensitive cones to this effect.
Methods. ERGs were obtained from 5 normal subjects. Following a 5-minute exposure to a white light BG of 30 cd.m-2, control responses were evoked to flashes of white-light of 8 cd.m-2.sec. in energy. Subjects were then light adapted for another 5 minutes to a brighter (330 cd.m-2) BG of white- , blue- (460nm), green- (500nm), or red- (635nm) light. Following this, the luminance was returned to the dimmer control BG and a series of ERGs were obtained.
Results. ERGs obtained within the first 30 seconds following exposure to the brighter BG, show that our procedure did not significantly effect the a-wave, irrespective of BG used. In contrast, all b-wave amplitudes were enhanced (p<0.05), where the white bg produced an average 39% increase compared to 41% for red, 24% green, and 23% for blue. op3 increased approximately 25%, regardless of background wavelength, while op4 increased substantially with white-, red-, and blue-light bgs. for all chromatic backgrounds, op2 was enhanced, with red-light showing the most dramatic increase.
Conclusions. Our results show that the type II LAE resulting from white light exposure can be replicated through cones that absorb light at long wavelengths. While blue- and green-wavelength sensitive cones might make a minor contribution to this effect, it appears that red-wavelength sensitive cones are solely responsible.
Supported by MRC grant 13383.
Purpose: In Germany, 2M patients suffer from glaucoma, and 40 K are blind. Early detection of patients with glaucoma helps prevent blindness if adequate treatment is applied. In addition to routine clinical methods colour vision are affected earlier than even computerised visual field tests. Sutter et al. reported that the second order Kernel may represent the function of the inner retina and the optic nerve head. Therefore we examined glaucoma patients with the M-ERG, PERG and Arden colour vision test.
Methods: a. M-ERG: 103 hexagons are presented on a 20 inch monochrome monitor driven at a rate of 60 Hz. Six cycles with a duration of 110 sec each were recorded. The luminance of the screen was 180 cd/m2 , the contrast nearly 98%. The m-ERG¥s were recorded with an contact-lens Jet-electrode. b. PERG: The PERG was recorded with 50 min of arc checks, presented at 2.2 Hz on a monochrome monitor with 16(infinity) diameter and 70 cd/m2. At least 100 responses were averaged and stored. The amplitudes of the P-50 and N-95 components were evaluated. The PERG was recorded with a gold foil electrode. c. Colour vision test: Colour vision was determined with the Arden colour vision test. Isoluminant letters lying either on the protan or tritan confusion line were presented in a binary search mode. (for details see Arden et al.,1988).
Patients: 25 patients with early glaucoma were examined. All patients with media opacities, systemic diseases and refractive errors > +/- 3 D. were excluded. None of the patients were treated with miotics. The patients received either betablockers or dorzolamid. None of the patients included in this study had severe visual field defects.
Results : The N-95 component of the PERG was significantly reduced in 12 of the patients. The other 13 patients had early glaucoma with so far no visual field defects and normal optic nerve head. Tritan colour vision defects were seen in 14 out 25 patients. In no patient was a protan defect observed. In 12 patients the 2nd. order Kernel was in the normal range. In all patients the amplitudes of the central hexagon as well as the first and second consecutive ring were in the normal range. However, in 13 patients the responses of the third and fourth ring were reduced in comparison to the normal subjects. A good correlation between colour vision, PERG and M-ERG was observed.
Conclusion: The m-ERG proved to be a helpful technique in controlling glaucoma patients.
Purpose: To investigate functional changes in x-linked juvenile retinoschisis by means of multifocal electroretinography.
Methods: Five young male patients with clinically defined x-linked juvenile retinoschisis were examined with the VERIS multifocal ERG system using a resolution of 61 elements within a 30(infinity) visual field. Peak amplitudes and implicit times of first order kernels were determined. Additionally, the b-a-ratio was analyzed and compared to Ganzfeld ERG results.
Results: Central responses were reduced most, but all other responses within the stimulated area were also subnormal. Similarly, implicit times were delayed most in the center and somewhat less in the periphery. The typical signs in Ganzfeld ERG of delayed photopic responses and a reduced b-a-ratio were also found in the multifocal waveforms.
Conclusions: These results characterize the functionally affected region in patients with x linked juvenile retinoschisis. The area of amplitude reduction and implicit time delay was larger than the funduscopically visible defect. The maximal delay in the central area suggests that this region is most affected. However, all other eccentricities also showed subnormal results especially in implicit time indicating a more widespread defect.
Introduction: To compare the differences in handling and measuring techniques of the two Multifocal-ERG-Recording-Systems VERIS and Retiscan from a technical point of view.
Methods: By adapting the recording parameters of both systems as far as possible we generated comparable recording conditions and recorded multifocal ERG's of 15 normal probands aged between 20 and 36 years. The adaptation of the recording parameters included the illuminance and contrast-settings of the Stimulus-Monitor, amplifier-frequency-settings, recording time, stimulus pattern and timing and the use of the same electrode type (i.e. DTL and Burian-Allen).
Results: (SIGMA) There are huge differences concerning the capability of the Stimulus-Monitors used in terms of illuminance and contrast (maximum illuminance level of the Retiscan-System is about 78% of our normal VERIS-stimulation illuminance).
(SIGMA) Burian-Allen-Electrodes cannot be used with the available Retiscan-amplifier-configuration: The pre-amplifier has to be AC-based.
(SIGMA) Special-shielded electrode-cables and fine-tuned amplifiers used in the Retiscan system lead to a reduction of interferences of the electromagnetic environment. Thus it is possible to record ERG-data without using an additional line-frequency-filter at 50 Hz.
Conclusion:One major difference between the two systems lies in the illuminance and contrast settings of the Stimulus-Monitors used. The amplifiers used differ from each other significantly concerning the attenuation of electromagnetic noise. Additionally, the error-reduction-handling of the recorded data is completely different in both systems, which is also an indication that Retiscan is working as a linear system.
Introduction: Formic acid is the metabolite of methanol which causes toxic reactions in humans and nonhuman primates. Formic acid accumulates and leads to metabolic acidosis and serious visual impairment or blindness. These effects appear when formic acid has reached 8-15 mM concentration. In nonprimates, however, formic acid is oxidised to carbon dioxide and does not accumulate. Therefore, methanol administration causes only a certain central nervous system depression in these species.
Methods: The corneal direct current electroretinogram was recorded during simultaneous perfusion of the vitreous cavity of albino rabbit eyes with
formic acid alternating with control solution.
Results: Perfusion with formic acid (10 mM) increased the c-wave amplitude significantly. This effect was reversible when the perfusion was changed back to the control solution after one hour. The a-wave was not significantly affected. The b-wave amplitude decreased somewhat during perfusion with 10 mM formic acid but this alteration did not reach statistical significance. However, when the perfusion was changed back to control solution, the b-wave
amplitude increased significantly. With 50mM concentration of formic acid, there was a severe reduction of the b- and c-wave amplitudes and there was very little recovery after one hour perfusion of the vitreous cavity.
Conclusion: Formic acid affects mainly the b- and c-wave amplitudes of the electroretinogram of the albino rabbit eye. At lower concentrations the
c-wave amplitude was elevated and the b-wave amplitude was somewhat decreased. The increase in c-wave amplitude may be caused either by an increase in the trans-pigment epithelial potential or by a reduction of the slow PIII from the Mller cells, or by both. The reduction in b-wave amplitude seems to indicate that formic acid is toxic mainly to the inner retina, presumably to the Mller cells. To further analyse the effect on the c-wave, intraretinal microelectrode experiments are in progress. Preliminary results show that the slow PIII is decreased while the trans-pigment epithelial potential is not affected. Thus, formic acid seems to have a direct effect on the Mller cells.
Introduction: Visual field loss has been reported in a minority of patients treated with Vigabatrin (VGB) for epilepsy (Elke et al., BMJ 314:181). VGB acts by elevating CNS GABA levels. The electroretinogram (ERG) is affected by elevated GABA levels in isolated retina (Gottlob et al, Vis Res 28:203). Our goal was to determine whether ERG changes following VGB administration are associated with changes in visual function.
Methods: 286 children (aged 2-16 yrs) with refractory seizures were enrolled in 2 double-blinded randomized clinical trials in which VGB or placebo was added on to the patients therapy regimen. Snellen visual acuity, Ishihara color plates, confrontation fields and ERGs (ISCEV standard protocol) were obtained during a pre-treatment baseline period and following 6 weeks of therapy.
Results: Blinded data indicated that in 36 of 140 patients with acceptable ERGs there were significant changes in the light-adapted response including a delay in the b-wave, reduction of b-wave amplitude, and marked reduction in oscillatory potentials. One of these patients had a change in visual field and one had a mild reduction in visual acuity from baseline. This rate of visual complication did not differ from that found in patients who did not show ERG changes or from that found in the total population.
Conclusions: Many patients treated with VGB have abnormal photopic ERGs. We find no evidence of increased incidence of visual dysfunction in these patients. The ERG changes are similar to those seen in isolated eyes perfused with GABA and probably represent normal physiologic effects of elevated retinal GABA.
Cancer associated retinopathy (CAR) is a rare, catastrophic condition which is marked by profound loss of function and retinal signals. However, we find that more subtle visual changes can be detected in many cancer patients. From 110 randomly-chosen volunteers with various neoplastic diseases, 13 have been tested to date and 11 report changes in visual function around the time of diagnosis and onset of treatment. In addition to routine clinical screening, measures were made of fields, color vision, dark adaptation and there were five types of photopic and scotopic electroretinal responses recorded. One of 26 eyes of cancer patients gave normal results on all tests. The clinical fundus examination was insensitive, with one eye showing pigmentary changes. One eye gave a Snellen acuity below 20/30. Among the psychophysical tests, Goldmann-type dark adaptation testing showed 25/26 eyes were abnormal. Among electrophysiological tests, supratheshold scotopic b-wave amplitude was least discriminating with 26/26 normal records. Most discriminating were photopic oscillatory potentials, where 15/26 RMS amplitudes were > 2 SD below the norm mean. Measures of cone-system function were generally more effected than those of rod systems. CARD is associated with many cancers or their treatment and produces quantifiable changes in large numbers of patients.
Assisted by Department of Ophthalmology and Research to Prevent Blindness.
If only the conservatives wanted to conserve and the liberals were in favor of liberty.
Purpose. As previously shown, newborn rats exposed to hyperoxia during the first 14 days of life exhibit dramatic and permanent changes in retinal structure and function, a condition known as OIR. The goal of this study was to investigate if we could demonstrate a window of oxygen hypersensitivity during those 14 days.
Methods. Litters of Sprague-Dawley rats were exposed daily to 80% O2, interrupted by 3x 0.5h of 21% O2. The first group of rats was exposed from birth to the 3rd, 6th, 9th, 12th and 14th day of life (i.e. intervals 0-3, 0-6, 0-9, 0-12, 0-14 days) and in the second group rats were exposed from the 3rd, 6th, 9th, and 12th to the 14th day of life (i.e. intervals 3-14, 6-14, 9-14, 12-14 days). Others groups were exposed between days 9-12, or from day 0 to 9 and day 12 to 14. Photopic and scotopic electroretinograms (ERGs) and oscillatory potentials (OPs) were obtained at 30 and 60 days of age. Retinal flat mounts and histology were also obtained at the above intervals. Rats which received the full treatment (0-14) showed a 70% decrease of ERGs amplitudes. The ERG data obtained for the other treatments were compared relative to the full treatment.
Results. Intervals 0-3 and 0-6 did not yield any significant ERGs alterations, while the 0-9 and 0-12 intervals resulted in 30% and 70% of maximal effect respectively. Similarly, the 3-14, 6-14 and 9-14 intervals produced 100%, 80% and 70% of maximal effect, while a 30% attenuation was observed with the 12-14 interval. Rats treated during the 9-12 interval yielded 30% of the maximal effect whereas those that combined the 0-9 and 12-14 intervals exhibited 40% of this effect. During the same intervals we observed a progressive reduction of all the OPs. At the maximum effect (0-14) OP2 was completely abolished, OP5 was reduced to 8%, while OP3 and OP4 were equally attenuated to 15% of normal. While present at all treatment intervals, the total amount of vasoconstriction and vasoobliteration obtained did not significantly differ between treatments. Histological analysis revealed that the retinas of rats exposed from 0-14 days failed to develop an outer plexiform layer. The same effect was observed for the 9-14 interval but not for the 0-9 one.
Conclusion. Our study suggests the existence of a critical period in OIR situated between the 9th and the 12th day since the exposures, which include this period, yielded major decline in ERG amplitudes, although a contribution of preceding and following periods must be considered. Our results also indicate that intraretinal damages more than the vascular changes are responsible for the functional anomalies reported. The differential effect of OIR on the OPs would also suggest that OP2, OP3-OP4 and OP5 are generated through three distinct retinal channels. MRC MT 13383
Introduction: The aim of this study was to characterise the phenotype of the 172 peripherin/RDS mutation.
Methods: 400 subjects with dominant macular and RP phenotypes were screened for peripherin/RDS mutations. Twelve families were identified with a 172 mutation. Nineteen representative patients underwent electrophysiological and psychophysical evaluation, including confocal scanning laser ophthalmoscopy (cSLO).
Results: Two mutations were identified: Arg172Trp in eleven families; Arg172Gln in the twelfth. Haplotype analysis demonstrated an ancestral relationship between all Arg172Trp families. Clinically, there was an age-dependent retinal degeneration confined to the macular region, usually presenting in the third decade. A typical granular appearance of the retinal pigment epithelium became apparent from early 20?s which developed into atrophic patches with increasing age, thence to larger areas of atrophy extending to the temporal superior and inferior arcades, and by the late 60?s becoming peripapillary. PERGs were affected early, and were often extinguished even with good preservation of acuity. All but one patient had normal EOG light rise and full field ERGs. There was high intrafamilial and interfamilial consistency. Autofluorescence on cSLO and PERG abnormality were shown to pre-date symptomatic presentation. One patient showed a different phenotype with a ?negative? Standard flash ERG, a delayed 30Hz flicker ERG and no EOG light rise.
Conclusions: The 172 peripherin/RDS mutation is usually associated with retinal degeneration confined to the macula. PERG abnormalities and autofluorescence on cSLO precede symptoms. Two different mutations showed markedly similar symptoms and signs.
Purpose. A photopic negative response (PhNR) peaking later than the b-wave of the macaque electroretinogram (ERG) is reduced in eyes with experimental glaucoma. We compared the development of these alterations in the PhNR with the progressive losses in visual sensitivity, and investigated the neuronal origin of the PhNR using pharmacological blockade of spiking activity of inner retinal neurons (ganglion and amacrine cells).
Methods. ERGs to brief (< 6 ms) and longer (200 ms) red ganzfeld flashes of various intensities under photopic conditions (3.6 log scot td blue background) were recorded differentially between dtl fiber electrodes in the two eyes of 14 anesthetized macaque monkeys. ocular hypertension (experimental glaucoma) was induced by argon laser lesions of the trabecular meshwork of one eye in each of ten monkeys. visual field sensitivity was assessed by static perimetry using the humphrey c24-2 full-threshold program. in four normal monkey eyes, tetrodotoxin (ttx: 3.8 microm) was injected intravitreally to block spiking activity of retinal neurons.
Results. ERGs, including the PhNR, were initially very similar in the two eyes of each animal. The PhNR peaked about 60 ms after a brief flash or 100 ms after the onset of a long flash. Following induction of experimental glaucoma in one eye, a- and b- waves remained unchanged even when the mean deviation (MD) over the visual field increased to -20 db. In contrast, experimental glaucoma greatly reduced the PhNR even when the MD was only -6db. As visual sensitivity continued to fall to lower levels than this, there was only a slight further reduction in the PhNR. Intravitreal TTX produced very much the same changes in the ERG as an experimental glaucoma involving a sensitivity loss of 6dB or more.
Conclusion. The results with TTX show that the PhNR of the macaque ERG depends upon the spiking activity of inner retinal neurons. However, the slow time course of the PhNR relative to the spiking response of ganglion cells raises the possibility that the response seen in the ERG is mediated by glial elements. Regardless of the mechanism of its generation, the PhNR, which also is present in the human ERG, holds promise for early non-invasive evaluation of retinal function in glaucomatous eyes.
Supported by NIH grants EY06671 (LJF), EY07751(UHCO), Wm. C. Ezell fellowship from AOF (SV).
Purpose. In a rat model of retinopathy of prematurity (ROP), test the hypotheses that 1) rod dysfunction persists in the mature retina and 2) the severity of dysfunction depends on the level of light in which the rats are reared.
Methods. Newborn albino rats were exposed to alternate high/low ambient oxygen until age 14 days. From 14 days onward, ROP rats and room air controls were reared in dim (2 lux) or bright (200 lux) cyclic light. As juveniles (30 days), and then again as adults (70 days), each rat had ERG studies of rod photoreceptor and postreceptoral function.
Results. Prior oxygen exposure and bright light cause significant attenuation of both the gain and saturated amplitude of the photoreceptor response. Furthermore, the interaction of oxygen exposure and bright light are significant. Age is not a significant factor.
Conclusions. In ROP rats, retinal dysfunction, primarily in the photoreceptors, persists in juvenile and mature rats reared in bright light. The dysfunction is similar to that observed in some children with resolved ROP. We suspect the retinopathy inducing and subsequent bright light exposures alter opsin expression and assembly of outer segment discs.
Supported by MA Lions Eye Research Foundation, EY10597 (ABF), EY07533 (JSP) and Research to Prevent Blindness (JSP).
Objectives: to observe the effect of pattern reversal stimulation on childhood amblyopia with modified pattern reversal visual evoked potential(PRVEP)equipment.
Methods: the modified pattern reversal stimulation from Dantec Cantata 1500 ( H:W 3:1, contrast 0.75, reversal frequency 2Hz,1000 times once a day, 10 days for a period )was used respectively on OD/OS in 35 children with ametropic or anisometropic amblyopia between the ages of 5 and 8 years. In the mono-ocular amblyopia group, 11 amblyopic eyes and the controls with normal visual acuity were stimulated with reversal pattern. In the biocular amblyopia group,14 patients were stimulated with reversal pattern one eye after another,while in their control group 10 patients were stimulated with animated cartoon. Before and after treatment the pattern reversal VEPs were recorded from a single central scalp Ag-AgCl electrode 2 cm above the inion using the routine patterns.
Results: visual acuity and PRVEPs were significantly improved, the visual acuity was improved over 2 lines,the total effective rate was 78.6% in the biocular amblyopia group ,and 81.8% in the mono-ocular amblyopia group(P<0.01); the latency of p100 from 112.5°¿12.72 ms to 101.72°¿5.86ms(p=0.0001), the amplitude of p100 from 7.03°¿2.35 uv to 8.08°¿2.40uv (p=0.0068) in the biocular amblyopia group ;the latency from 108.91°¿8.41 ms to 101.4°¿9.92 ms (p=0.0785) ,the interocular difference of latency decreased from 7.60°¿4.53 to 5.90 °¿3.93 (p<0.01),the amplitude increased from 6.34°¿2.63 uv to 7.58°¿2.25 uv in the mono-ocular amblyopia groups .no changes were found in the control groups with normal visual acuity or the amblyopic eyes stimulated with animated cartoon group.
Conclusion: the modified pattern reversal stimulation was effective in antiamblyopia according to the use of a physiological based functional biostimulation.Thus this method might be a new approach to treat yong childhood amblyopia.
Keyword: amblyopia,treatment,prvep,child
Purpose: In electrophysiology one needs an apropriate stimulus to measure the spectral sensitivity of an eye or of a single visual cell. Usually one uses monochromatic flashes, which have two disadvantages: First: It depends on the resolution how many single stimuli you have to apply to the system to cover a certain spectral range. Usually these stimuli start from dark to a certain intensity level. To keep the adaptational state of the eye stable you have to pause between the stimuli. Second: To compute a spectral sensitivity curve from the responses to these stimuli you also have to measure an additional intensity characteristics. Therefore a multispectral stimulation method called Fourier Interferometric Stimulation (FIS) was developed. With this stimulus linear and nonlinear components of the retinal reaction are simultaneously recorded and can be investigated, additionally a phase information is gained, which helps in analysing the processing of retinal signals. One can derive new information about the origin and the underlying retinal processes by comparing phase and amplitude spectra with other results.
Methods: The output of a xenon lightsource is modulated in time and spectral composition by a continuously scanning Michelson interferometer. The output of the interferometer is called an interferogram. This stimulus will be presented at the poster site on a noteboook computer. This stimulus can be used in many different ways. Electrophysiologically the light will be projected in an Ullbricht sphere in front of the eye and the ERG-response will be recorded with an eye cup electrode. The stimulus- and the reaction-interferograms of the eye are Fourier transformed and scaled. The result will be a complex sensitivity of the whole eye, which reflects the processing of the retinal signals as will be shown in a seperate poster by F. Siebert, R. Gemperlein. One can also mix the output of the interferometer with white light and determine a psychophysical color sensitivity curve.
Results up to now: Using FIS a spectral sensitivity with a fine structure in the UV for the photoreceptor of the Blowfly Calliphora erythrocephala was detected. Electrophysiologically the Purkinje shift of the human eye could be measured. Psychophysically a colour contrast sensitivity curve of the human eye could be determined.
Conclusion: The FIS is a versatile stimulus. Using the FIS stimulus one can measure spectral properties in short time and high precision thanks to the advantages of Fourierspectroscopy, like high light throughput and simultaneous measurement of all spectral components. Analysing nonlinear reaction and phase one can determine color opponent mechanisms in the retina.
The N200 amplitude of the motion VEP increases when the speed of an otherwise constant grating is enhanced. A positive slope of this function can be found at least for low speeds. For higher speed values the slope becomes shallower until saturation occurs. We asked whether the N200 amplitude is correlated with the perceived velocity in this range.
Gratings of vertical orientation, moving rightwards horizontally, were produced on a high resolution display having a frame rate of 100 Hz and an average luminance of 50 cd/m2. Reference and adaptation stimuli (spatial frequency = 2 c/deg) were presented parafoveally at an eccentricity between 0.5 and 3 deg left or right of the fixation point. The motion VEP of the reference stimulus was recorded from electrodes situated 10, 20, and 30 % left and right of Oz. The perceived velocity of the reference stimulus (speed = 2 deg/sec) was measured at the same time by speed comparison with a test stimulus presented in the other visual hemi-field (contrast of 4 %, spatial frequency of 1.2 c/deg, eccentricity of 3...7.2 deg). Individual maximum-likelihood estimates of the speed of the test grating which yielded 50 % "faster" judgment were determined by using a Best-PEST procedure according to Lieberman & Pentland.
Adaptation to stimuli drifting at 1, 2 or 4 deg/sec (contrast = 4 %) showed significant and nearly equal reduction of the N200 amplitude (Wilcoxon, p=0.05). The perceived speed, on the other hand, decreased after the fast adaptation condition whereas the perceived speed after the slow adaptation condition was significantly enhanced in comparison with the pre-adaptation judgment.
Our results can be explained by the channel hypothesis, i.e. neurons activated by a grating moving at 2 deg/sec contribute to the response level of either of two velocity channels, the "slow " or the "fast" channel. Whereas the motion VEP can only reflect the sum of both channel activities, simultaneous measurement of the perceived velocity can give additional information about the distribution of activity over both channels, and thus reduce the ambiguity in the motion VEP.
Pattern and motion VEPs can have a considerable similarity in their configuration. Stimulation with the same pattern could suggest the idea that the same neuronal population contributes to these potentials. The aim of this study is to explore the extent to which these potentials are affected by pattern or motion adaptation.
Pattern and motion VEPs were elicited sequentially by presenting subjects a stationary pattern for 1 sec, which is set into motion for another sec (speed = 2 deg/sec). The reference contrast of the gratings was varied between 0.5 and 64 %. The adaptation stimuli had a contrast of 4 %, a spatial frequency of 2 c/deg, and a speed of 0, 0.25, 1, 2, or 4 deg/sec. Adaptation and reference stimuli were situated in one of the visual hemi-fields at an eccentricity between 0.5 and 3 deg. EEG- electrodes were positioned 10, 20, and 30 % to the left and right of Oz.
Our results confirmed that pattern VEPs have a higher contrast threshold than motion VEPs. The amplitudes of the pattern VEPs, especially around 200 msec (N200), increased monotonically with increasing contrast up to 64 %. The final value was two- to fourfold the N200 amplitude of the motion VEPs. The latter was relatively independent of the stimulus contrast. The motion VEPs showed nearly equal N200 amplitudes in either hemisphere despite of visual hemi-field stimulation whereas the contralateral pattern VEPs exceeded the ipsilateral by a factor of 1.2 to 3.
Adaptation to stationary and to moving gratings reduced the N200 pattern VEP amplitude significantly (Wilcoxon, p=0.05). In contrast, the N200 motion VEP amplitudes remained constant after adaptation to stationary gratings, but diminished after adaptation to moving gratings.
The scalp distribution, contrast dependence, and adaptation effects support the view of an extensive independence of motion and pattern VEP generators. In addition, the experiments show that the extent of motion VEP amplitude reduction by moving grating adaptation is dependent on the contrast of the reference grating, with stronger reduction at lower contrast, in agreement with psychophysical results.
Purpose. To investigate the long-term behavior of the pigmented rabbit d.c. ERG after intravitreal injection of dopamine of different concentrations.
Methods. The ERG was studied in 24 pigmented rabbits. Four experiments were performed, each including six animals. One eye was injected intravitreally with 0.1 ml dopamine (DA) with a estimated concentration in the vitreous body of 0.0025 mM, 0.025 mM, 0.25 mM and 2.5 mM, respectively. The contralateral eye was injected with the same amount of saline. Following the injection the animals were dark adapted for 30 minutes and then exposed to repeated light stimuli of low intensity for almost 3 hours (series I: 1 stimulus per 3 min, 10 s duration, light intensity 6.8 x 102 lux). After another 30 min period of dark adaptation repeated light stimuli of high intensity were presented to the eyes (series II: 1 stimulus per 70 s, 10 s duration, light intensity 6.8 x 104 lux) for 33 min.
Results. In the control eyes, a slow increase with time of the a-, b-and c-wave amplitudes was observed during series I. During serie II, the amplitudes were markedly reduced between the first and the second light stimulus, but subsequently attained a peak. The development of the ERG in the dopamine-injected eye with the lowest drug concentration was not different from that of the control eyes. At higher concentration levels the b-and c-wave amplitudes were reduced compared with the control eyes, and did not follow the slow increase with time observed in these eyes during series I. The peak observed during series II in the control eyes was increasingly suppressed in the eyes treated with dopamine.
Conclusion. When judged with the ERG, dopamine seems to influence the retinal adaptation process in rabbits in a dose dependent way.
Introduction: Previous psychophysical studies report raised scotopic thresholds in dyslexia. This was attributed to a deficiency in docosahexaenoic acid (DHA). To further evaluate this we recorded simultaneous cone and rod electroretinograms (ERGs) in dyslexic subjects and controls.
Methods: Five dyslexics (mean 20.8 yrs, sd 3.1) were compared to age matched controls (mean 23.9 yrs, sd 4.3). All subjects were students from the same university. DTL fibres were inserted into the lower fornices and referenced to Ag/AgCl electrodes at the outer canthi, with vertex earth. After 30 minutes dark adaptation, monocular ERGs were recorded to square wave stimulation at 1.3 Hz. An improved separation of the responses was achieved by the introduction of longer wavelength light (a mixture of 700 and 660 nm LEDs illuminating a diffusing filter as a ganzfeld stimulus) and adjustment of the intensity of the stimulus (1.34 to 10.43 cdm-2).
Results: In controls, the ERG shows two eeonAE components (at 65 ms, sd 8 and 156 ms, sd 20), which have been attributed to the cones and rods respectively. A single eeoffAE component is seen at 523 ms (sd 15). At higher intensities, the cone component is larger than the rod. With decreasing intensity, the cone component decreases in amplitude until it is of a similar size to the rod component. Further decreases in intensity reduce the amplitude of both components. The rod and cone amplitudes may also be compared between subjects as a ratio, thus eliminating variations which may arise during recording, for example due to positioning of the DTL fibre . There is no significant difference in the latencies or absolute amplitudes of the cone, rod or off components, or in the cone:rod ratio, at any intensity for dyslexic and control subjects.
Conclusions: Separated cone and rod components in a single ERG are useful for comparing cone and rod activity and are applicable in many retinal pathologies. The use of a longer wavelength stimulus produces greatly improved responses. Dyslexics show no significant differences in amplitudes or latencies when compared with control subjects. This does not support the hypothesis of a retinal basis for raised psychophysical scotopic thresholds in dyslexia. Further investigations are currently being undertaken to consolidate these results.
Rhegmatogenous retinal detachment (RD) is still a one of the most serious sight-threatening retinal disorders, in which prognosis depends mainly on the duration and size of the disease. In order to find any objective prognostic factor of operative success (reattachment) in this study we correlated the electrophysiological data from patients with RD with their age, duration and size of the process in the context of result of the operation.
32 patients with RD in the age of 26-76 (mean 55.2), 13 women and 19 men, with the duration of RD of 10-168 days (mean 42.8) undergone standard ERG (according to ISCEV standards), including scotopic, oscillatory potentials, L cone, B cone, fotopic and flicker. For statistical analysis (Spearman correlation) we used both results of the measurements (presented in mV and ms) (I) and results of the measurements calculated as the percent of the fellow eye (presented in % of the results of the fellow eye) (II). Pre- and postoperative status (degree of RD or reattachment) was presented in 4 and 5 degree scale respectively.
No correlation between the age of patients, postoperative status (degree of reattachment) and studied ERG parameters (in both I and II) was found. However, we found that both L cone b wave implicit time and B cone b wave amplitude correlated with the duration of the RD (r=0.81 p<0.02 and r=-0.70 p<0.05 respectively) (ii). we also observed correlation between the preoperative size of rd and several erg parameters, i.e. scotopic a wave (r=-0.54 p<0.002), scotopic b wave (r=-0.68 p< 0.00002), fotopic a wave (r=-0.71 p< 0.00001), fotopic b wave (r=-0.51 p< 0.005), fotopic b wave implicit time (r=0.71 p< 0.00001), oscillatory potentials latency (r=0.56 p< 0.002), oscillatory potentials amplitude (r=-0.51 p< 0.005), flicker (r=-0.76 p< 0.00005) (ii). results for the i type of analysis were similar, although additional correlation was found between preoperative status, l cone a wave implicit time (r= 0,79 p< 0.05) and L cone b wave implicit time (r=0.90 p< 0.001).
Electrophysiologic parameters correlate with the preoperative size of RD, and thus may be used as the additional tool in RD diagnosis and treatment. However, the correlation between electrophysiologic parameters and postoperative effect was not found; the explanation of this is unclear. The correlation between duration of RD and two parameters obtained from colour stimuli need to be explored in detail in further studies since duration of RD is one of clinically used prognostic factors for reattachment.
Introduction: We have previously reported on the use of magnetoencephalography in localisation and functional analysis of the human cortical area V5 ( Anderson et al 1996 ). Using our developed techniques we are able to locate dipoles within one gyrus with constricted MonteCarlo similated elipses. These locations can be co-registered with MRI. We have been able to study one patient demonstrating blind sight following severe damaged to the stribe cortex of one hemisphere. In addition we have studied a further patient whose lesion was thought to be immediately adjacent to area B5 both prior to and at surgery.
Methods: The Aston 20 channel magnetometer was used by being positioned over the visual cortex. The most stimulations consisted of iso luminent red green siusolent gratings in a horizontal configuration which drifted in a vertical direction. CO-registration with the individual patients MRI was obtained using a bite bar as we have previously described (Singh et al 1997). The visual stimulus be presented in any area of the visual field. For the study of the patient with blind sight stimuli would presented both 2.5 and 5 degrees out from the central fixation spot.
Results: Blind sight patient - When the stationery stimulus was presented to the patient either 2.5 or 5 degrees out in the blind hemifield no response could be obtained. When motion stimuli was presented clear responses were obtained in the blind hemisfiled of vision 5 degrees out and the response is localised at the gyros below the superior temporal fisher approximately to the human equivalent of V5. these results gave the same location as a pet study of the same patient. Presurgical Patient - The patient showed clear localisation of the motions centres to the same equivalent area as V5. The electrode quartography surgery confirmed these localisations and enabled the surgeon to remove unepileptic germ zone immediately adjacent to this area.
Conclusions: MEG provides accurate localisation of motion centres in the human visual cortex the advantage of the technique is that if necessary psycho physical studies can be performed purely based on the responsiveness of this area of the visual cortex.
References: Anderson, S.J., Holliday, I.E., Singh, K.D., Harding, G.F.A. Localization and functional analysis of human cortical area V5 using magneto-encephalography. Proc. R. Soc. Lond 263, 423-431.
Singh, K.D., Holliday I.E., Furlong, P.L., Harding, G.F.A. Evalution of MRI-MEG/EEG co-registration strategies using Monte Carlo similation. Electorencephalography and Clinical Neurophysiology 102 (1997) 81 - 85.
Introduction: The purpose of this study was to detect whether there are asymmetries in contrast generated retinal response which could be attributed to asymmetric structural and functional organization of nasal and temporal half of the retina.
Methods: Pattern ERG was recorded with full fields and half fields in 21 healthy subjects (12 male, 9 female, mean age 28.0, SD=2.65). PERGs were elicited by checkerboard pattern projected onto translucent screen of 16(infinity)r reversing at 1.6 Hz and recorded simultaneously from both eyes by HK-loop electrodes placed in lower conjunctival fornix. Responses were averaged and analysed by Nicolet MS 2000 system.To determine differences in morphology of the waves recorded from temporal and nasal fields, amplitudes of P50 and N95 waves were measured from the point that crosses the baseline between P50 and N95 waves (BL point).
Results: Measured from the BL point, mean value for full field P50 amplitude was 4.12 mV, and for N95 it was 3.44 mV. Mean latency for the baseline point between P50 and N95 was 78.36 ms. In half field responses, it was found that the amplitude of P50 measured from the baseline was larger from temporal half fields, i.e. nasal retinas (P50 temporal half field: 2.16 mV, nasal 1.81 mV) whilst the amplitude of N95 was larger from nasal half fields, i.e. temporal retinas (N 95 temporal half field: 1.71 mV, nasal 2.3 mV). There were also differences in latency of BL point, being 81.25 ms from temporal fields and 73.3 ms from nasal fields respectively.
Conclusions: There are clear differences in morphology of the PERG responses recorded separately from temporal and nasal retinas. Whilst stimulation of the nasal retina yields larger P50 and smaller N95, the reverse is true for temporal retina, where N95 predominates. This asymmetry suggests differential contribution to PERG waveform which should be carefully considered in interpretation of selective diminution of respective waves which was proposed as a diagnostic tool to differentiate between macular or optic nerve lesions.
Introduction: We previously reported (ISCEV 1996), that PERG is better preserved than cone ERG in RP patients with good visual acuity. We further studied the responses obtained from the patients in different stages of the disease, to determine whether PERG could be used for follow-up when flash ERG responses are already absent.
Methods: ISCEV standard flash ERGs were recorded from 15 RP patients with various degrees of concentric field loss using Medilog OS2 Ganzfeld stimulator. Transient PERGs were elicited by 16(infinity)r checkerboard pattern reversing at 1.6 Hz. All responses were recorded by HK-loop electrodes placed in lower conjunctival fornix. Responses were averaged and analysed by Nicolet MS 2000 system. Results were compared with kinetic (Goldmann) and static (Octopus M1) perimetry, and visual acuity.
Results: Patients at advanced stage of RP with visual fields of less than 10(infinity) (II/4 mark) or mean defect (MD) of over 20 dB (Octopus M1) had absent both PERG and cone responses despite good visual acuity. In less severe affected patients, PERGs were still clearly preserved whilst the flash evoked responses were absent, despite the fact that they were elicited by a stimulus of much higher luminance than for PERG. This permitted follow-up by PERG which correlated well with with deterioration of the visual field. On the other hand, PERG was not recordable from RP patients in whom visual acuity was poor (i.e. below 0.3) despite relatively preserved fields, or in patients with cone-rod dystrophy with relative central scotoma despite wide fields and preserved flash responses. Likewise, recordable PERG in RP patients was extinguished by applying a +3.0 diopter defocusing lens.
Conclusions: Good visual acuity is essential for PERG to be recordable in RP patients indicating that PERG is a contrast-generated retinal response which may reflect activity of the relatively preserved inner retinal layers. PERG may provide a useful electrophysiological tool for monitoring the retinal function in RP patients with good visual acuity in whom standard flash responses are already extinguished.
Introduction: We investigated cone electroretinograms to white flash stimuli and to different color stimuli in eyes with retinal detachment.
Methods: 23 eyes of 23 patients, aged 17-71 years, with unilateral rhegmatogenous retinal detachment involving the macula were examined. Cone ERGs were recorded to Ganzfeld flash stimuli at 5 Hz in the presence of a bright white background illumination (50 cd/m2). Color flash stimuli were obtained by using Wratten color filters.
Results: The amplitude of the cone ERG b-wave, elicited by our brightest white flashes, was significantly correlated with the area of detached retina. Cone ERG b-wave implicit times to white stimuli were prolonged in most of detached eyes, compared with normal fellow eyes. The difference in implicit time was within 4 msec in cases with retinal detachment smaller than two quadrants. When the detachment covered more than half of the retina, however, the delay varied from 0-14.8 msec and did not correlated well with the area of detachment. In detached eyes, the short wavelength sensitive (S-) cone ERG, elicited by blue (450 nm) flashes, was more affected than the mixed long and middle wavelength (L,M-) cone ERG to red (633 nm) stimuli.
Conclusions: These results suggest that the non-detached retina may suffer from subclinical damages in eyes with larger retinal detachment.
Introduction: A paired-flash ERG technique, in which a test flash delivered at time zero is followed at time t by a rod-saturating probe flash, has recently been used in human subjects to derive the approximate full time course of rod responses to weak test flashes (1). Previous studies of normal and transgenic mice have employed a similar paired-flash method to analyze rod recovery after bright test flashes (2-4). As the mouse is well-suited for studying genetically engineered changes in phototransduction reactions, it is of interest to develop the paired-flash method for investigations of normal vs. abnormal transduction processes in vivo. The present study of normal (C57BL/6J) mice was undertaken as an approach to this goal. Specific aims were to determine the flash sensitivity and time course of the ERG-derived rod response.
Methods: Dark-adapted C57BL/6J mice, 5-16 weeks of age, were anesthetized with ketamine/xylazine. ERG responses to full-field flashes were corneally recorded and amplified (bandpass of 0.1-3,000 Hz). Probe flash responses obtained in a series of paired-flash trials were analyzed for amplitude to yield A(t), the derived rod response to the test flash (1).
Results: The derived response A(t) obtained with weak test flashes exhibited a near-peak value at t = 80 ms. The dependence of A(80) on the test flash intensity If was described by the relation, A(80)/ADmo = 1 - exp(-k80 If), where ADmo is the dark-adapted maximal value of A(t) and where the sensitivity parameter k80 = 7.0 (scotopic cd-s-m-2)-1. For t > 40 ms, the weak-flash derived response was well described by an expression containing a delayed Gaussian activation term (5,6) and an exponential decay (7): A(t)/ADmo = 1 - exp{-k80 If g [1-exp(-a(t-td)2)][exp(-t/tw)]} where g = 1.78, td = 3.1 ms, tw = 160 ms, and a = 4.66x10-4 (ms)-2. However, the preceding equation overestimated, by about four-fold, the initial portion (t < 15 ms) of the rod response (a-wave leading edge) determined in single-flash experiments.
Conclusions: The results provide in vivo information on the time course and sensitivity of phototransduction in the rods of normal mice. The kinetic data raise the possibility of a developing increase in transduction gain during the interval t -a15-40 ms.
References: (1) Pepperberg, Birch & Hood (1997) Visual Neurosci. 14:73-82. (2) Birch, Kedzierski, Nusinowitz, Anderson & Travis (1995) Invest. Ophthalmol. Vis. Sci. 36:S641. (3) Lyubarsky & Pugh (1996) J. Neurosci. 16:563-571. (4) Goto, Peachey, Ziroli, Seiple, Gryczan, Pepperberg & Naash (1996) J. Opt. Soc. Amer. A 13:577-585. (5) Lamb & Pugh (1992) J. Physiol. 449:719-758. (6) Breton, Schueller, Lamb & Pugh (1994) Invest. Ophthalmol. Vis. Sci. 35:295-309. (7) Pepperberg, Birch, Hofmann & Hood (1996) J. Opt. Soc. Amer. A 13:586-600.
Purpose: To study the clinical application of multi-channel VEPs topographies in patients suffering late-stage glaucoma.
Methods: The multi-channel VEPs topographies of 25 normal persons and 15 patients suffering late-stage glaucoma were recorded and analyzed. Humphrey perimetry was performed on all patients. The VEPs topographies were shown by computer proceeding of multi-channel VEP waves.
Results: In normal subjects, the topographies showed symmetric distribution by full-field pattern stimulation. In all patients with late-stage glaucoma, even whose visual field was severely damaged, multi-channel VEPs can be recorded, it showed irregular distribution simply "NPN" waveform, the reduced amplitudes of P1 waves and longer latency. The changes of topographies have observed.
Conclusions: The prognosis and evaluating treatment using multi-channel VEPs topographies is shown to be useful is late-stage glaucoma patients.
Objection:The binocular interaction was studied with transient VEP and steady-state VEP recorded with dichoptic checkboard reversal stimulation in 30 normal subjects and 22 cases with monocular amblyopia.
Methods:The dichoptic check-board stimulation were generated with a individual computer and a modulated haploscope. The binocular interaction was assessed as the binocular/monocular ratio (B/M) of the VEP amplitude.
Results:(1)In normal subjects,the amplitude of the binocular VEP is significantly reduced as comparing to that of the monocular VEP ,B/M ratio is 0.52°¿0.085.In patients,there was no significance variance in amplitude between the binocular VEP and the monocular VEP,B/M ratio is 8.9°¿0.112°#(2)The difference in VEP amplitude to monmocular stimulation of right and left eyes for both the normal subjects and the patients is not significant.(3)For the patients,the peak latency in the amblyopic eye is delayed 14°¿2.8ms than in the no-amblyopic eye,but there was no significant variance in VEP peak latency between the binocular VEP and the monocular VEP.Conclusion: there are binocular interaction in the visual system in the normal subjects,but for the binocular defects,the binocular interaction is lost or abnormal.Dichoptic VEP can be used to evaluate binocular function objectively.
Key words:binocular interaction,P-VEP,dichoptic stimulation,monocular amblyopia
Introduction: Qualitative relationship between VEP-amplitude and the luminance of colours in checkerboard used was investigated. Based on these results an automatic adjustment of isoluminance control loop has been developed.
Method: For stimulation red-green, blue-yellow and grayscaled checkerboards containing 64 squares (1.7deg) were used. The temporal shape consisted of two different stimuli. The contrast stimulus was a reversal between two luminance levels of colours with a period of 166ms and a pulswidth of 1/2. The structure stimulus was a reversal between the colours with a period of 83ms and a pulswidth of 1/3. Special matrix of five electrodes was placed over the visual cortex to obtain maximal VEP-amplitudes. The different evoked responses were separated in the spectral domain. The contrast-correlated VEP was used to controll the luminance of colours to minimize its amplitude.
Results: The study of the relationship between VEP and the luminance was performed on 10 volunteers. In general, a minimum of contrast-VEP was expected at the individual equiluminance point. This behavior was validated in 4 cases with red-green and 5 cases with blue-yellow and gray squares. At the equiluminance point the VEP showed a maximum correlated with the structure stimulus in 6 cases with red-green, 7 cases with blue-yellow and 5 cases with gray squares. In the automatic evaluation mode up to 5 iteration steps were needed to attain the equiluminance point.
Conclusions: The study shows, that it is possible to evaluate the equiluminance point of an individual by automatic controll loop in an objective way. The examination time is relatively short (about 15 minutes), but not optimized. Up to date, only the absolute value of the contrast but not its sign at the equiluminance point can be evaluated.
Purpose: Panretinal photocoagulation is a well known, routine therapeutic procedure of several eye diseases. The character, the degree and the cause of development of the electroretinographical changes following the photocoagulation is not well cleared up. Our purpose was the recognition of the functional changes of the retina following panretinal photocoagulation with electrophysiological methods.
Methods: 12 eyes of 6 rabbits were treated with indirect binocular laser ophthalmoscope: 6 right eyes with argon blue-green, 6 left eyes with argon green. We applied on an average 1200 laser burns per eye. Using different stimulation we measured the photopic and scotopic answers before, directly after, 1, 3, and 7 days and 1 month after the treatment. Results: Using the 0,25log SF stimulus we found significant decrease in the amplitudes directly after the laser treatment, which showed a similar pattern on the 1st and the 3rd day, but on the 7th day we observed an increasing tendency in the amplitudes. One month after the treatment the amplitudes were near to the pre-treatment values. Stimulating with standard flash we found quite similar tendencies, after the 7th day the amplitudes begun to rise. Under photopic conditions we observed a definite drop in the amplitudes as well, which showed a continuous increasing tendency. The implicit time values increased after treatment, their maximal values were measured generally on the 1st day, then they showed a slow regression. Considerable differences between the two eyes could be found only in the photopic a and b wave implicit time values, we found a smaller increase of implicit time in the eyes treated with argon green.
Conclusions: The electroretinographical changes (implicit time, amplitude) following the laser treatment showed an improving tendency from the 7th day. The above described electrophysiological changes can be explained by the damage of the blood-retina barrier due to the destructive treatment, which are nearly reversible after the pigmentation of the laser burns. It seems that argon green laser causes less photopic damage.
Introduction. To investigate the retinotopic distributions of On and Off-pathways , we compared the waveforms and the latencies of On and Off-responses of the Visual Evoked Potential (VEP) elicited from central and peripheral areas of the visual field by means of multi-focal technique.
Methods. Eight normal subjects took part in the study : 3 males and 5 females. We derived responses by using the VERIS II system and bio-amplifier. The stimulus was an array of 37 hexagonal elements, each independently alternating between black and white in pseudo-random achromatic stimulation (m-sequence=11). Each M-step comprised 20 frames and thus lasted for 266.67 msec. We divided 20 frames of M-step into On stimuli ( white ) and Off stimuli ( black ) and varied the duration of onset to give 6 timescales, 133.33msec, 106.66 msec, 79.99msec, 53.33msec, 26.66msec and 13.33msec. Inevitably as the duration of onset decreased shorter, the duration of offset increased longer. Total recording time was 8min. The active electrode was placed at 5% above Oz, referenced to the left ear lobe. The data were analyzed using VERIS Science 3.01 software. We compared between the average responses of the central elements out to 6.25 degrees (Group1); the next surrounding ring elements out to 12.5 degrees (Group2); the next ring elements out to 18.75 degrees (Group3) and the remaining ring elements out to 25.0 degrees (Group4).
Results. Both On and Off responses were observed in the1st-Kernel. The average latencies of the On-responses were, from Group1 to Group4 , 102.45 plus/minus 7.30 msec, 101.56 plus/minus 7.50 msec, 100.24 plus/minus 11.52 msec, 98.44 plus/minus 13.58 msec respectively. The corresponding values for the Off-responses were 120.80 plus/minus 6.88 msec, 121.08 plus/minus 8.34 msec, 116.86 plus/minus 10.36 msec and 114.30 plus/minus 12.32 msec. The average latency of Off-response was 17.59 msec greater than that of the On-response in each groups. The latency of On and Off response was shorter in Group4 than in Group1. The amplitude ratio of On / Off response were 3.99 plus/minus 5.19, 4.98 plus/minus 7.84, 2.47 plus/minus 3.05, 1.49 plus/minus 1.21 respectively. On the whole the amplitude ratio was largest in central area, decreasing towards the more peripheral areas.
Conclusion. The response in VEP of the On -pathway exhibit faster implicit time compared to that of the Off-pathway. The difference of the On / Off amplitude ratio between central and peripheral areas suggests a disproportionate distribution of On and Off dominant neurons from the retinal region.
Introduction:Ophthalmologists are generally discouraged from recording ERG during fluorescein angiography because of the possibility that the fluorescent substance may have a phototoxic effect on the retina. Recently, the advent of modern fluorescent materials that are entirely safe from phototoxic effect made possible the use of fluorescein-ERG. This presentation describes our findings with fluorescein-ERG in insulin-dependent-diabetes mellitus (IDDM) patients without any fluorescein leakage in FLAG examination.
Patients and Methods: Eleven patients (20-50 yrs of age, mean age 21 yrs) suffering from IDDM for 4-12 yrs were subjected to FLAG and repeated ERGs to investigate the effect of fluorescein. ERG was recorded before and five times during the 60 minutes interval after the injection. Thirteen eyes of good vision in volunteering patients with non-vascular damage of their fellow eye served as controls. ERGS were recorded with the help of gold foil electrodes. Responses to 50 flashes of blue light were averaged in each trial.
Results: In the control group there was a slight reduction in b wave amplitude immediately after fluorescein administration. We could not find any significant differences in ERG amplitude or latency values between the 0 min and 60 min recordings. In the IDDM group a considerable decrease than an intense rebound facilitation of the b wave was seen during the first 30 minutes. No complete recovery could be detected by the time of the 60 min recordings. Variance analysis showed significant differences between diabetic and control subjects in the time course of ERG amplitudes. No significant differences were found in the latency values. Significant differences were found between the diabetic values before and sixty minutes after fluorescein injection. No sign of any side-effects was detected.
Conclusions: Our study shows that ERG recording simultaneously with FLAG offers a rather sensitive diagnostic tool for detecting subclinical vascular damage in IDDM patients. The introduction of this diagnostic method in other vascular diseases of the eye is also recommended.
Introduction: It has long been recognised that colour vision defects may involve post receptoral abnormalities in addition to anomalies in the spectral absorption of the visual pigments. These anomalies cannot easily be elucidated by psychophysics alone, but can be investigated objectively by electroretinography. We report preliminary data on a series of subjects, varying from normality to cone monochromatism with excellent acuity, which has a prevalence of less than one in a million in the western population. Sustained stimulation is essential to isolate abnormalities of the off pathway and in this study two LED stimulators, one specially engineered and another commercially manufactured, were used to isolate the colour processing pathways.
Method: Nine colour defective subjects comprising four anomalous trichromats, four dichromats and one cone monochromat were compared with data from normal subjects. All subjects had good corrected visual acuity. ERGs were recorded with an interlocking square wave at 1.3 Hz and 30 Hz with 430, 525, 660 and 700 nm LEDs, and with 120 ms flashes at two second intervals with 450, 525 and 660 nm. Stimuli were applied over a diffusing field which closely approximated a Ganzfeld stimulus. To isolate responses from each cone pathway using three wavelengths, the active stimulus was applied intermittently in the presence of sustained background illumination consisting of the two complementary wavelengths, which were used to suppress the sensitivity of the remaining receptors including the rods. ERGs were recorded using DTL fibre electrodes with a Medelec Sapphire II 4E averaging system.
Results: In the normal subjects typical on and off responses for all three cones types are observed, with an attenuated off response in the case of the blue cone mechanism. Dichromats and anomalous trichromats produce characteristic waveforms with evidence of reduced sensitivity of L- or M-cone pathways. However in the case of the cone monochromat, relatively well formed responses were observed for S-, M- and L-cone types, however the off response of the L-cone appeared markedly attenuated.
Conclusions: The colour ERGs with intermittent stimulation with a rectangular temporal waveform and adapting complementary fields provided an objective test for comparison with conventional psychophysical data. Electroretinography allows investigation of both receptoral and post receptoral hypotheses in subjects with colour vision defects.
Introduction: In 1937 Bietti described a tapetoretinal dystrophy (BCD) characterized by deposits of crystals in the retina and the marginal cornea. Only a few patients have been observed over a long-term period of up to 26 years.
Methods: We represent the clinical findings, fluorescein angiography (FLA), adaptometry and electrophysiology (ERG and EOG) of 2 patients (P1, P2). Findings of P1 have been documented over a period of 30 years, and Transmission electron microscopy (TEM) of peripheral circulating blood lymphocytes has been performed.
Results: A 21-year-old-man (P1) revealed tiny crystals scattered throughout the posterior pole of the retina. Three years ago problems in dark- and light adaptation were noticed. At age of 24, FLA demonstrated local atrophy of the RPE and ChC. Photophobia, nyctalopia, arcuate paracentral scotomas and constricted visual fields appeared during the 3rd to 4th decade indicating progression of the disease. Rod- and cone-driven responses (ERG) were subnormal and revealed a "negative ERG? in response to the sotopic maximal flash. The ratio of light- peak/dark-baseline (EOG) was reduced. During the 5th to 6th decade diffuse choroidal atrophy was evident, masking most of the crystalline deposits. Biomicroscopically, crystalline deposits were detected in the marginal cornea. TEM revealed crystalloid inclusions in lysosomes of lymphocytes. In contrast P2, presented these advanced findings of choroideremia-like appearance at age of 26 already.
Conclusions: Deposits of the retina associated with a reduced light rise (EOG) and impaired rod- and cone-driven responses (ERG) are important findings in BCD, especially in final stages of disease. The occurrence of deposits in the limbal cornea during the course of the disease and detection of crystalloid deposits in the lysosomes of lymphocytes confirm the diagnosis of BCD. They may help to distinguish BCD from chorioretinal dystrophies, e.g. choroideremia. In P1, the course of the disease is documented over the longest follow-up until now. P1 and P2 may at least in part represent two patterns of the manifestation of CDB.
Purpose: M-ERG proved to be a useful technique for examination of patients with retinal diseases. The first order Kernel represents the function of the outer retinal layers, while the second order Kernel is thought to exhibit the function of the inner retina and the optic nerve head. However, there are is no available normal data for various age groups. available.
Methods: VGA monitor: 103 hexagons are presented on a 20 inch monochrome monitor driven on a rate of 60 Hz. Six cycles with a duration of 110 sec each were recorded. The luminance of the screen was 180 cd/m2 , the contrast nearly 98%.
SLO-system: The SLO (Rodenstock, Mnchen) is the trigger and stimulus unit of the m-ERG (Roland Consult, Wiesbaden). The frame rate is 50 Hz. The stimulus is generated by a helium-neon laser (633 nm, 0-200 (mW). The retina and therefore the fixation is controlled by an infrared laser (780 nm, 0-2000 (mW). The stimulation field covers 14(infinity) of the posterior pole. 61 hexagons are tested. The m-ERG¥s were recorded with an contact lens electrode (Jet) -electrode. The responses were analysed in regard to the absolute amplitude and latencies of each individual hexagon as well as for the central and the consecutive rings.
Patients: Patients were grouped into cohorts covering 6 decades, from 10-20, to 60-70 years. Six groups of patients in 10 years interval were examined from under 20 to over 60 years. Only patients with a normal ophthalmological status i.e. visual acuity equal or better 0.8 with an refraction not more than +/- 3 dpt., normal eye pressure and normal fundus were tested. All patients with systemic diseases such as diabetes, hypertonia etc. were excluded.
Results: The amplitudes of the second order Kernel were significantly smaller than for the first order Kernel. The amplitude ranged from 80 to 110 nV (mean 98 nV +/- 6.5 nV) for the central ring and 15 to 25 nV (mean 21 +/-2.4 nV) for the peripheral ring. The latencies of the central rings (mean 43 ms +/- 2.7 ms) are significant longer than for the peripheral rings (mean 35 ms +/- 2.6 ms). No significant difference between the age-groups 21 to 30 years and 51 to 60 years was observed.
Conclusions: We were able to demonstrate in a large group for normal subjects that the responses are highly reproducible and that the amplitudes for the second order Kernel are significantly smaller than for the first order Kernel.
Purpose: To evaluate development of retinal function following macular hole surgery.
Methods: In between May and December 1997 16 consecutive patients who underwent macular hole surgery (pars plana vitrectomy, peeling of the inner limiting membrane, thrombocyte concentrate application, intraocular gas tamponade) on one eye were examined with the multifocal ERG (VERIS Clinic II). Multifocal ERGs were recorded prior to treatment and 6 weeks after surgery. An additional examination at 4.5 months after surgery was performed in some of the patients. A stimulus pattern of 61 hexagons was used.
Results: Following surgery, in all 16 eyes the macular hole was closed. To compare multifocal ERGs the responses were summarized in rings as suggested in the VERIS software; ring 1 corresponds to the center of the stimulus, followed by rings 2-5 towards the periphery. In all eyes at all examinations detectable responses were present in rings 2 - 5. Prior to surgery in 5/16 eyes no definite response was detectable in ring 1. After surgery, detectable responses were recorded in 3 of these 5 eyes. In one of the other 2 eyes amlitudes increased in ring 2. In 11/16 detectable responses in ring 1 were present prior to surgery. Following surgery, increased amplitudes were seen in 5 eyes; amplitudes were unchanged in 3 eyes and were reduced in 3 eyes. Amplitude changes were evident 6 weeks after surgery without much change during further follow-up. Implicit times were unchanged in most cases following surgery.
Conclusion: Closure of macular holes was followed by improvement of multifocal ERG amplitudes in 9/16 eyes within 6 weeks after vitrectomy. Multifocal ERG amplitudes were unchanged in 3/16 eyes and deteriorated in 4/16 eyes.
Introduction: Motion perception as determined psychophysically can be disturbed in many glaucoma and glaucoma-suspect patients. In the present investigation, the usefulness of visual evoked potentials elicited by moving stimuli was investigated in glaucoma diagnosis.
Methods: Maxwellian-view system with an optical scanner. Retinal illumination 1000 Td, Stimulus duration 200ms, interstimulus interval 1800ms. Horizontal motion from right to left. Four different stimulus conditions were employed: 1.) Vertical square-wave stripe pattern (0.33 c/deg), low contrast of 0.04, field diameter 32(infinity), velocity 10(infinity)/s. 2.) 0.88 c/deg pattern, contrast 0.04, field diameter 32(infinity), velocity 5.9(infinity)/s. 3.) 0.88 c/deg pattern, high contrast of 0.93, field diameter 32(infinity), velocity 5.9 (infinity)/s. 4.) 0.33 c/deg pattern, contrast 0.93, annulus field 23(infinity)-32(infinity), velocity 10(infinity)/s. Recordings: Oz and P3 referenced to linked ear lobes. Amplification: 0.5Hz-70Hz, notch filter 50Hz. Sampling rate 250Hz, n=90. Evaluation of amplitude and peak time of N200 component. Testing of short-time reliabilty (2 measurements on the same day) and of long-time reliabilty (after 30 weeks). Three groups of subjects: 41 eyes of 34 normals (age range 21-72 years). 12 eyes of 12 pre-perimetric glaucoma patients (IOP > 21mmHg, papillometric defect, no perimetric defects). 28 eyes of 24 perimetric glaucoma patients (POAGs, SOAGs, LTGs, all with perimetric defects). Testing of validity by correlation analysis with perimetric MD value (Octopus 500).
Results: 1.) In normals N200 significantly larger at P3 than at Oz. 2.) Significant (p<0.05) negative correlation between n200 amplitude and age (r=-0.377) only under conditions 1 and 2 (low contrast), no significant gender differences. 3.) in perimetric glaucomas n200 at p3 significantly reduced under all 4 conditions, especially under conditions 1 and 4 (p<0.0001),peak times of n200 less significantly delayed under conditions 1 and 3. 4.) in pre-perimetric glaucomas non-significant trend of n200 reduction at p3 under all conditions tested. 5.) no significant differences in responses between oz and p3 in perimetric glaucomas. 6.) significant (p<0.05) negative correlation between n200 amplitude and perimetric md (r=-0.385) only under condition 4 (annular stimulus). 7.) good short-time reproducibility but poor long-time reproducibility of n200 amplitude at p3. 8.) sensitivity 70% at specificity 80% under conditions 1 and 4.
Conclusions: 1.) Motion VEPs obtained from a parietal recording site serve as an additional valid test in perimetric glaucomas, especially when a low contrast or an eccentric stimulation is used. 2.) The test seems better suitable for cross-sectional analyses than for longitudinal analyses.
Introduction: Intrauterine growth retardation (IUGR) is one of the major problems in neonatal medicine. IUGR results in higher risk of morbidity and mortality. The children were born small-for-gestational-age (SGA), although genetically small children could not be excluded from the group. Earlier experimental studies in IUGR rats and sheeps have shown that the visual evoked potential (VEP) was abnormal with increased potential latencies and with altered VEP waveforms. Our intention was to investigate whether SGA-children have VEP-abnormalities as well. The criteria of selection was children of less than -2 SD regarding to weight with adjustment for gestational age. In 15 SGA-children ophthalmological examination, flash light VEP-recordings and clinical examinations were performed repeatedly from the first week of life to their first birthday.
Results: The results showed that there were altered VEP-forms in the SGA-children compared with the controls at six months of age and at one year of age. The latencies to peaks appearing in the VEP at approximately 100 ms after stimulis were prolonged, and the later part of the responses were less complex in its waveform compared to the normal VEP of healthy AGA-children (appropriate-for-gestational-age). With one exception the SGA-children appeared normal in the basic clinical examinations.
Conclusions: These results indicate that the visual function is changed in this group of children. The common clinical techniques for examinations could not reveal this impairment, probably because they are too insensitive. The VEP seems to be a promising method in identifying the infants at risk in IUGR.
Objectives: To reveal useful information carried by motion-onset evoked potentials (M-VEPs) and to improve the EPs extraction, the time and frequency attributes of pre-stimulus EEG and M-VEPs were studied.
Methods: A group of five healthy volunteers was examined with linearly moving checkerboard (40'checks, 96% of contrast and mean luminance of 17 cd/sqm). To produce the typical N160 negative response, the following stimulus timing was used: the stationary pattern was presented for 3s, then moved at the velocity of 5deg/s for 600ms. We recorded twice 32 sweeps of 256 pre- and 256 post-stimulus samples with sampling frequency of 500 Hz from the leads Oz ,Or, Ol (5cm to the right (left) from Oz), Cz and Fz with A1 as the reference electrode. Data from pre- and post-stimulus parts of the M-VEPs were compared in frequency and time domain. We inspected changes in the power spectral density (PSD) and phase synchronisation.
Results: 1. We found a strong phase synchronisation to stimulus predominantly in the delta, theta and alpha band. 2. There was a high increase of PSD in the delta (90%) and theta (100%) bands and a slight increase of PSD (40) % in the alpha band of the post-stimulus interval. 3. We recorded a small decrease of post-stimulus PSD in the beta (18%) and gamma (10%) band. 4. In general, the post-stimulus PSD showed higher organisation (about 90% of variability was described by two independent components) when compared to the pre-stimulus PSD. 5. The diagnostic parameters (amplitude and latency of N160) obtained from the full M-VEPs frequency range were comparable with those estimated from delta and theta bands (1-8 Hz) only.
Conclusion: In healthy subjects, the evaluated M-VEPs components are generated mainly in theta and delta frequency bands. Reduction of the recorded frequency range can shorten recording time, decrease amount of data and improve "readability" of the M-VEPs. Specificity and sensitivity of the new M-VEPs parameters to the pathological processes remain to be evaluated.
Acknowledgments: Supported by the Grant Agency of the Charles University - Grant No. 56/97/C, by the Grant Agency of the Czech Republic (Grant No. 309/96/0959) and by the James S.McDonnell Foundation for Cognitive Neuroscience, USA.
Introduction: The 1st order kernel of the multifocal ERG reflects a linear response to light and is comparable to Ganzfeld-flash ERG. The 2nd order kernel is a response to a change in local luminance and might therefore show similarities to the PERG. We tested whether changes patients with optic nerve diseases are observable in the linear and non-linear ERG components.
Patients and Methods: Patients with clinical defined optic nerve diseases (n=25) were examined with the multifocal ERG of Sutter & Tran (Vis Res 32: 433-446, 1992) and compared with a control group (n=30). The stimulus contains 61 hexagons in a 30 degree visual field. The first and second order kernels were calculated. Both were measured as peak-to-peak amplitudes.
Results: In normals, the 1st order kernel was lower in the nasal retina (2-11°) than in the temporal retina (ratio 0.8). The opposite was true for the 2nd order kernel (ratio 1.5). This can be interpreted as a sign for a relevant contribution to the 2nd order response generated near or at the optic disc. Astonishingly, the macular 2nd order activity was higher in the patient group than in normals (9.2 +/- 4.3 compared to 6.3 +/- 2.2 nV/sqdeg), while in the same region a normal 1st order kernel was measured (26.4 +/- 6.6 compared to 27.3 +/- 5.7 nV/sqdeg). The global averages of linear and nonlinear activity differed only to a minor degree (28.8 +/- 6.1 µV in patients to 29.9 +/- 6.8 µV in normal for the 1st order kernel. 8.7 +/- 2.0 µV in patients to 9.4 +/- 2.1 µV in normals).
Conclusions: The distribution of the 2nd order activity shows an asymmetry across the visual field with higher response densities in the vicinity of the optic nerve head. This indicate a ganglion cell contribution to the 2nd order kernel. The elevated high 2nd order responses in patients with optic atrophy may be explained by unmasking the retinal component by the loss of a ganglion cell component. The 2nd order kernel cannot simply be used as a local PERG for the detection of ganglion cell loss.
Introduction: A routinely usable motion-related VEP technique was sought for with the aim of providing a method for better detection of magnocellular pathway disorders.
Methods: A large range of visual motion stimulation parameters (spatial frequency and contrast of the moving pattern; size of the stimulus and its location in the visual field; velocity, direction and duration of motion; interstimulus interval) was tested to specify their effect on the motion-onset/offset VEPs. An optical scanner system (moving mirror) and 21" PC monitor with 100 Hz picture frequency were used for visual stimulation. At the test distance of 0.6 m, the circular stimulus field subtended a visual angle of 30(infinity). VEPs from standard bipolar occipital leads were compared with those from unipolar lateral temporo-occipital leads.
Results and Discussion: Motion-onset VEPs are determined to be the preferable for clinical use because of their larger amplitudes and lower inter- and intraindividual variability in comparison with motion-offset and motion-reversal VEPs (Kuba, M.and Kubov, Z.: Doc. Ophthalmol., 80, 1992, p. 83 - 89. Kuba, M. et al.: Physiol. Res., 41, 1992, p. 369-373.). The shape of the positive-negative-positive complex of motion-onset VEP peaks varied substantially under the influence of stimulus conditions, displaying dominant (or exclusive) negativity at about 160 ms (SD of 9 ms) for the following optimum motion stimulus parameters and recording conditions:
- temporal frequency (multiple of the spatial frequency and velocity) of 3 - 6 c/deg
- contrast of 5 - 20%
- stimulus field >= 15(infinity) (with macular masking in some subjects)
- random change of motion direction or simultaneous multidirectional motion ( e.g. expansion)
- ratio of motion duration/interstimulus interval (stationary pattern) >= 5 (preferred timing is 200 ms of motion and at least 1s of interstimulus interval)
- unipolar symmetrical lateral leads with electrodes located about 5 cm left and right from Oz position
Changes of these parameters can cause dominance of the first positive peak at around 120-130 ms which seems to represent a pattern-disappearance component. It may be caused by a blur effect in high temporal frequency moving patterns, by activity of the parvocellular system in high contrast patterns(Kubov, Z. et.al.: Vision Research, 35, 1995, p. 197 - 205.), by exclusive stimulation of central retina or by adaptation to unidirectional and too long and frequently repeated motion. Since both the pattern-related positivity and the motion-onset specific negativity appear simultaneously, the magnocellular pathway reactions should preferably be recorded from lateral occipito-temporal leads that best represent an activity of the MT areas. Discrepant findings in some laboratories are explicable by differences in the methods used, and by low number of subjects, since subjects can differ substantially in their sensitivity to single stimulus parameters.
Conclusions: On the basis of motion-onset VEPs recorded from about 200 normal subjects, a method has been developed which provides reliable information about magnocellular system function. These VEPs are recordable in about 95% of the human population.
Acknowledgements: This work was supported by the research grants from the Grant Agency of the Czech Republic (grant 309/96/0959), the Grant Agency of the Ministry of Health of the Czech Republic (grant 3230-3), by the European Community (CIPACT 930220 PL 924816) and by the James S. McDonnell Foundation for Cognitive Neuroscience, USA.
Introduction: The previously-developed method for eliciting motion-onset VEPs (see previous abstract) was applied in the detection of magnocellular system involvement in various neuro-ophthalmological disorders.
Methods: In about 2,000 patients, latencies of the motion-onset specific negativity (N160) were measured (the upper limit of normal was 182 ms) in symmetrical lateral temporo-occipital leads, in addition to the standard pattern-reversal VEP recordings from Oz. Various moving stimuli, and repeat examinations, were used to estimate the clinical significance of motion-onset VEP findings.
Results and Discussion:
In patients with Multiple Sclerosis (without visual acuity reduction) it has been shown that demyelination can first selectively affect the magnocellular system (18% of delayed motion-onset VEPs accompanied by normal pattern-reversal latencies represent a substantial increase of the VEP examination sensitivity - Kubov, Z. et al.:Invest. Ophthalmol. Visual Sci., 35, 1995, p. 197.)
In Retrobulbar Neuritis, influencing mainly central fibres of the optic nerve, pattern-reversal VEPs which are always delayed, are less frequently accompanied by prolonged latency of the motion-onset VEP. This combination could be taken as a sign of demyeliniation.
Since the motion-onset VEPs are recordable to peripheral stimulation (up to about 40(infinity) from the fovea), they can be successfuly used for objective dynamic perimetry (Kuba, M. et al.: Vision Res. 35, Suppl., 1995, p. S166.) and for detection of early glaucomatous changes (Kubov, Z. et al.: Doc. Ophthalmol., 92, 1996, p. 211 - 221.)
Motion-onset VEPs do not display any distinct dependence on the visual acuity of subjects and they also seem to be unaffected by amblyopia (Kubov, Z. et al.: Vision Res., 36, 1996, p. 181 - 190.).Therefore they could be used for the testing of amblyopic eyes, when some additional neuro-ophthalmological disorder appears.
About 2/3 dyslexic children examined had prolonged motion-onset VEPs latencies, which supports the hypothesis of possible magnocellular system deficiency in some dyslexics (Kubov, Z. et al.: Physiol. Res., 44, 1995, p. 87 - 89.).
Motion-onset VEPs recorded from the secondary associate cortical sensory areas exhibit a higher sensitivity to subclinical encephalopathy and thus can be used in monitoring of CNS functions (Kuba, M. et al.: Acta Medica (Hradec Králové), 39, 1996, p. 21 - 26.).
Conclusions: The negative peak N160 of the motion-onset VEP provides new information on the functioning of the visual pathway. The clinical usefulness of this is clear. However, there remains a need for careful standardisation of numerous stimulus and recording parameters to avoid substantial differences between the laboratories.
Acknowledgments: This work was supported by the research grants from the Grant Agency of the Czech Republic (grant 309/96/0959), the Grant Agency of the Ministry of Health of the Czech Republic (grant 3230-3), by the European Community (CIPACT 930220 PL 924816) and by the James S. McDonnell Foundation for Cognitive Neuroscience, USA.
Objectives: Adaptation the measuring system for the purpose of different multifocal examination tasks and the coupling with various stimulation devices.
Methods: The derivation of the multifocal ERG requires a device for representing the stimulus pattern usually consisting of a field of hexagons. The hexagons are controlled by shifted m-sequences. One step of each m-sequence consists of one ore more frames. The timing of the frames depends on the examination task and the characteristics of the stimulus device. There are differences in the timing between a CRT display and a laser scanning ophtalmoscope. Therefore it is necessary to adapt the controlling of the frames to different conditions.
Results: The adaptation of the measuring system offers the possibility for different multifocal examinations and the use of a CRT displays as well as a laser scanning ophtalmoscope for the stimulation display.
Conclusion: RETIscan is a measuring device for the multifocal ERG that is able to work with a CRT display as well as a laser scanning ophtalmoscope and to realise different multifocal examination tasks.
Purpose. We have previously reported (ARVO 1997) that the scotopic ERG of the adult Guinea Pig had a negative morphology which became more pronounced with flashes of brighter photopic range. In order to further characterize this unique feature, we investigated if this unusual morphology was readily present at birth. We also compared the physiological properties of the Guinea pig's ERG with that of human.
Methods. Photopic and scotopic intensity-response functions were obtained from light-adapted (background 30 cd.m-2) and darkadapted (up to 3 hours) Guinea Pigs (n=5) from day 1 to day 35 and compared to 4 adults ( > 7 months). The scotopic ERGs were evoked to flashes of white and blue light covering a 7.0 log-unit range in intensity (maximal flash luminance: 8 cd.m-2.sec). Photopic ERGs covered a range of 1.2 log-units. Human ERGs were recorded according to a standard protocol.
Results. At birth the scotopic a:b wave ratio is 1.2 ± 0.13, a value not different from the 1.14 ± 0.09 measured in the adult responses, indicating that the negative ERG morphology is already present at birth. With maturation however there is a progressive growth in the prominence of the OPs as seen on the ascending limb of the b-wave. Fast Fourier Transform analysis of the maturating ERG signal reveals that while the OP power content does not change with age, the frequency domain of the OPs increases from 105 ± 9 hz at birth to 125 ± 15 hz in the adult Guinea Pig. The latter maturation process similarly modified both photopic and scotopic responses. Interestingly, of all the animal species studied in this laboratory and elsewhere, we found that the adult photopic ERG response of the Guinea pig closely resembles that of the human. Like in human, at maximal intensity the photopic ERG is composed of three major OPs where OP2 has the lowest threshold and OP3 the highest. Similarly, in the Guinea pig the a-wave accounts for 40±6% of the suprathreshold photopic ERG amplitude compared to 33±4.4% in human subjects. The above combination produce, in the Guinea pig, a photopic ERG which is almost identical in amplitude, morphology, timing and frequency content to that of the human ERG. Also the different forms of light adaptation effects previously shown in human to be specific to distinct OPs also demonstrate the same specificity in the guinea pigs.
Conclusions. Our findings indicate that: 1- the unique morphology of the Guinea pigs bright flash scotopic ERGs results from an unusual and pronounced contribution of the OPs which is not readily present at birth; 2- the unique similarity between human and Guinea pig photopic ERGs (probably a consequence of similar proportion of cone photoreceptors) also suggests that the latter would represent an excellent animal model to study normal and abnormal human ERG function. Supported by MRC grant MT13383, FCAR.
Introduction: carbonic anhydrase inhibitors have been shown to enhance the 'b' wave of the electro-oculogram both in humans and in experimental animals when injected intravenously. The mechanism of this effect is not known.
Methods: in this study the effect of the topical carbonic anhydrase inhibitor dorzolamide on the electro- oculogram was investigated. The EOG was measured in healthy volunteers after the application of either topical dorzolamide to one eye and saline to the other, or topical dorzolamide to one eye alone. At the time of testing the investigator was blind to which eye received the active drug. The same environmental conditions were present at each measurement. The effect of topical carbonic anhydrase inhibition on the EOG was evaluated by comparing the relative magnitude of the 'b' wave in the treated eye to the untreated eye.
Results and conclusions: no consistent effect on the standing corneo-retinal potential was found from topical dorzolamide. This suggests that the effect of carbonic anhydrase inhibitors on the EOG derives from an alteration to retinal activity. The clinical implications are discussed and the literature briefly reviewed.
Introduction: Triamcinolone Acetonide was shown to be an effectiveangiostatic agent in cases of experimental PVR and ischemic retinaldiseases, such as branch retinal vein occlusion. In this work, we evaluatedpossible retinal toxicity by commercial Triamcinolone Acetonide (Kenalog)and two pure angiostatic drugs.
Methods: Three groups of Albino rabbits were studied for retinal effectsof Kenalog, Triamcinolone Acetonide (TA), and Tetrahydrocortisol-S (THC-S).Each group was treated by intravitreal injection of the experimental drugto one eye, while the second eye, serving as a control, was injected withsaline. The eyes of the rabbits were examined ophthalmoscopically. ERGrecordings were done before, 4 hours, 1 week, 2 weeks and one month afterinjection. At the end of the ERG follow-up period, the retinas wereprepared for histologic examination at the light microscopic level.
Results: Kenalog induced about 60% reduction in the amplitude of the ERGb-wave but had a negligible effect on the ERG a-wave. These effects wereevident as soon as 4 hours after injection and slightly increased withinthe next day. No recovery was seen for 30 days of follow-up. Histologicalobservations supported the ERG findings. Pure TA and pure THC-S, at a dosesimilar to that in the commercial drug and at a double dose proved nontoxic to the rabbit retina as ass