TI	Cone isolating multifocal ERGs
AU	Albrecht JF
AU	Baseler HA
AU	Sharpe LT
AU	Jägle H
IN	Forschungsstelle für Experimentelle Ophthalmologie, Universitäts-Augenklinik
AD	Röntgenweg 11, D-72076 Tübingen, Germany
EM	jalbrecht@vision.eye.medizin.uni-tuebingen.de
AB	Purpose  To develop procedures for recording cone-isolating multifocal ERG responses in normal observers and clinical patients. Methods The VERIS system (Version 3.1) was used in combination with “silent substitution” techniques to isolate responses from individual cone classes in the human multifocal ERG.  The stimuli were generated on a flat-screen SONY Trinitron monitor, with a resolution of 1026 x 726 pixels, at a 67 Hz frame rate.  Corneal ERG responses were measured with a DTL fiber electrode.  The responses were amplified and filtered between 3 - 10 Hz and 100 Hz (Grass Instruments).  37, 61 or 103 locations were stimulated independently and concurrently in the visual field of view, which subtended 58° x 50° at a viewing distance of 32 cm.  The ERG response was sampled at 1072 Hz. To minimize rod input, a high photopic ambient illumination was maintained and the subject’s pupil was maximally dilated by application of a mydriatic (0.5% tropicamide).   The Stockman & Sharpe (1999) cone fundamentals were used to generate the cone-isolating stimuli.  Michelson contrasts of  46%, 46% and 79% were achieved for the isolated long-wave (L-), middle-wave (M-) and short-wave (S-) cone stimuli, respectively. A posteriori time-varying filtering was applied to the recorded signals to remove noise from the signals. Results  The corneal ERG responses to the pure cone modulation stimuli were recorded in normal observers (L-, M- and S-cone), protanopes (M- and S-cone), deuteranopes (L- and S-cones) and blue-cone monochromats (S-cones).  On average, the measurement error was less than 10% and 12% for the L- and M-cone isolating stimuli, respectively.  The latencies for the L- and M-cone responses in the central fovea were c. 30 ms with the M-cone preceding the L-cone response by c. 3 ms. Both M- and L-cone latencies increased with retinal eccentricity. Conclusions The topography of  the L- and M-cone signals can be measured in both color normal and congenital color-blind individuals, using multifocal ERG with cone-isolating stimuli.  However, the topography of the S-cone signals cannot be easily measured in blue-cone monochromats or normal observers, even after applying  a posteriori signal filtering to the multifocal ERG signals. To obtain robust S-cone responses, additional chromatic background adaptation, selective bleaching or high intensity SLO laser techniques must be adopted.

TI  	Laplacian Analysis Facilitates VEP Pattern Onset Acuity Estimates; Concomitant Snellen Acuity Equivalents in Paediatric Patients
AU	Apkarian P
AU	Bour LJ 
IN 	Department of Physiology, Erasmus Medical Centre Rotterdam, Department of                        Neurology, Academic Medical Centre Amsterdam 
AD	Dept of Physiology, EUR, PO Box 1738, 3000 DR, Rotterdam, The Netherlands 
EM	apkarian@fys.fgg.eur.NL 
AB	Purpose: We wished to establish VEP pattern onset acuity standards that yield accurate estimates of Snellen acuity. Emphasis was placed on determining VEP acuity measures in  pre-verbal and non-verbal patients and equating the resultant VEP acuity "thresholds" to Snellen acuity across the age span from birth to the elderly.  To facilitate identification of salient VEP response features, particularly for near threshold VEP response profiles and to enhance VEP signal to noise ratios, Laplacian analysis was implemented. Methods: Pattern onset VEP's were measured with an array of five electrodes positioned across the occiput, 1 cm above the inion. Pattern stimuli were generated via a high resolution (110 MHz) CRT monitor. The monitor generated pattern onset profile (40 msec onset/460 msec offset) consisted of checkerboard patterns ranging in check size from 1' to 430' (contrast = 90%).  Three channel Laplacian derivations were calculated for each VEP averaged response, facilitating detection of a reliable response for the smallest pattern size. For verbal patients, standard Snellen acuity measures and VEP acuity thresholds were compared and correlation functions across an acuity range from  0.03 (20/600) to 1.0 (20/20) were determined.  Results:  Pattern onset VEP acuity showed high co-variance with subjective Snellen acuity measures.  Variance of near threshold estimates was reduced and response component identification enhanced by Laplacian analysis.  The resultant VEP acuity versus Snellen acuity functions were successfully implemented in the accurate determination of comparable acuity estimates in pre-verbal and non-verbal patients. Conclusions:  In the present study, implementation of Laplacian analysis proved an efficient and reliable data analysis approach,  yielding an accurate electrophysiological protocol for the determination of pattern onset VEP acuity and Snellen acuity equivalents.  The latter has proven indispensable in the objective evaluation of visual function in pre-verbal and non-verbal patients.

TI	Alcohol and the EOG : clinical implications.
AU	Arden GB 
AU	Wolf JE
AD	City University London.
g.arden@city.ac.uk
Background: Light adapting the retina causes liberation of an unknown substance that binds to receptors on the apical RPE, and by liberating intracellular second messengers, increases the  basolateral chloride conductance that produces the "light rise" of the EOG. Other substances, notably alcohol, produce similar EOG voltage changes.  Methods:
Standard EOGs in man: administration of alcohol by oral, intragastric and i.v. routes. Results. 1: in normals brief pulses of alcohol and light produce identical stereotypical changes to the EOG. 2: submaximal responses to these agents sum, irrespective of time difference between administration. 3: increments of light on a light background, or alcohol increments on an alcohol background are ineffective. 4: The normal semisaturation oral dose of alcohol for the EOG is c.20mg/Kg corresponding to an active tissue concentration  << 1mM. 5: Saturating doses of alcohol and light do not sum but occlude.  6: in patients with RP alcohol produces no rise of voltage, but instead a slow, delayed fall, even though a small "light rise"  is still present. Conclusions . 1: Alcohol acts directly on the RPE, operating on the intracellular machinery that causes the light rise. 2: this machinery suffers secondary atrophy in RP.  

TI	Assessment of macular function by multifocal electroretinography and optical coherence tomography before and after panretinal photocoagulation in diabetic retinopathy
AU	Baba, T
AU	Sasaki, Y
AU	Hatta, S
AU	Kumagami, T
AU	Inoue, M
AU	Hasegawa, J
AU	Saeki, Y
AU	Tamai, A
IN	Department of Ophthalmology, Faculty of Medicine, Tottori University, Yonago, Japan.
AB	Purpose.  To evaluate macular function before and after panretinal photocoagulation (PRP) in diabetic retinopathy using multifocal electroretinograms (mERGs) and optical coherence tomograph (OCT). Methods.  Thirteen eyes of 10 patients with preproliferative or proliferative diabetic retinopathy were examined using a VERIS Science system for recording mERGs (MAYO Corp., Nagoya, Japan) and a Humphrey OCT scanner (Carl Zeiss Co., Ltd., Tokyo, Japan) before PRP and at 1, 3 and 6 months after the procedure.  Fourteen eyes of 14 normal subjects served as a control.  In mERGs, the P1 (the first positive wave) -N1 (the first negative wave) amplitude, the P1 peak latency and the mean response density were measured in 7, 37 and 103 hexagonal areas (areas 1,2 and 3) within a central radius of 5, 10 and 20 degrees, respectively.  The mean retinal thickness was estimated from 9 calculation points at the foveal region within 5 degrees; central and each other 4 points at the distance of 250 µm and 500 µm from the central portion on horizontal and vertical sections on OCT. Results.  The P1 latencies from the 3 areas were remarkably prolonged in the diabetic eyes before PRP compared with those in the control eyes, without a tendency of recovery throughout the course after PRP except for area 1.  The P1-N1 amplitudes and the mean response density levels from the 3 areas were remarkably decreased in the diabetic eyes before PRP compared with those in the control eyes, followed by the maximum decrease in both parameters at 3 months after PRP.  However, a tendency of recovery was detected in both decreased parameters from the 3 areas at 6 months after PRP.  The mean foveal retinal thickness on OCT was apparently increased in the diabetic eyes before PRP compared with the thickness in the control eyes.  The most remarkable, transient increase in the thickness was detected in the diabetic eyes at 1 month after PRP, followed by a tendency of recovery at 3 or 6 months after PRP. Conclusions.  These results indicate that the effects of PRP on the macular function in diabetic retinopathy seems to be reversible at the foveal region, although we need a further investigation in relation to the outcome of visual acuity.

TI	Motion-VEPs and VEPs associated with motion-based texture segregation differ in their contrast characteristic
AU	Bach M
AU	Schmitt C
IN	Univ.-Augenklinik Freiburg
AD	Univ.-Augenklinik, Killianstr. 5, D-79106 Freiburg, Germany
EM	bach@uni-freiburg.de		
AB	Purpose. An elementary process in Gestalt perception is called "texture segregation", for which an electrophysiological correlate has been isolated (the ‘tsVEP’). Texture segregation, a preattentive process, requires a gradient of a visual dimension, including luminance, orientation or motion. We studied the contrast characteristic of the tsVEP with the aim to classify the subserving mechanism as parvocellular or magnocellular.	Methods. In 7 volunteers we recorded VEPs from Oz, OT, FPz and averaged-ears leads. For the dimension ‘orientation’ we presented 	pattern-onset (330 ms on, 670 ms off) of oriented lines, arranged either homogeneously vertical / horizontal or in a checkerboard fashion at 10%, 20%, and 98% contrast. Motion stimuli were random dots which either moved (300 ms motion, 900 ms rest) homogeneously or 	differentially, revealing a checkerboard pattern; contrast was 1%, 	2%, 5%, 10%, 20%, 60% and 98%. We analyzed the contrast-transfer function of both the "low-level VEP" which is evoked by changes of 	the local feature (orientation or motion) and the tsVEP, which is  isolated by an appropriate linear combination from homogenous vs. 	differential stimulus patterns. Results. The low-level VEP showed a striking difference between the two dimensions: For the dimension ‘motion’ the contrast function was low threshold / early saturating (magno-like), for ‘orientation’ it was high threshold / late saturating (parvo-like). The tsVEP showed a clear parvo-like contrast transfer function.	Conclusions. The results suggest that motion-based texture segregation, while certainly based on motion detection with a 	magno-like contrast function, needs relatively high contrasts for boundary integration. If so, there should exist visual phenomena where motion is perceived locally, but not integrated into a perceptual gestalt.	

TI	Visual function abnormalities in epileptic children treated with vigabatrin
AU	*Banin E
AU	#Gross-Tsur V
AU	**Shachar E
AU	+Lahat E
AU	#Shalev RS
IN	*Department of Ophthalmology, Hadassah-Hebrew University Hospital,
Jerusalem, Israel
IN	#Neuropediatric Unit, Shaare Zedek Medical Center, Jerusalem, Israel
IN	**Rambam Medical Center, Haifa, Israel
IN	+Assaf Harofe Hospital, Zrifin, Israel
EM	banine@md2.huji.ac.il
AB	Purpose: To assess visual fields (VF), visual evoked potentials (VEP) and electroretinographic responses (ERG) in children treated with vigabatrin (VGB), an anti epileptic medication. Methods: Twenty-four children with epilepsy treated with VGB for at least six months and with no previously known ocular problems were included in the study. A clinical ophthalmological examination, static and/or kinetic perimetry, flash and/or pattern VEP, and ERG were performed according to the children’s abilities. Results: Thirteen patients showed abnormal results in at least one of the visual function laboratory exams. Visual field constriction was evident in 11 of the 17 children able to perform perimetry. Subnormal ERG b-wave amplitudes were found in 5 of 11, and delayed VEP implicit times in 5 of 16 patients. In children able to perform all tests, electrophysiologic abnormalities were found only among those manifesting VF constriction. Conclusions: More than 50% of children treated with VGB demonstrated VF constriction or abnormal ocular electrophysiological results. Perimetry appeared to be the most sensitive test in identifying significant ocular VGB toxicity. In a child unable to perform perimetry, the presence of an abnormal VEP and/or ERG may indicate a high probability that visual fields are compromised. In view of the high incidence of VGB-induced ocular toxicity in our patients, we feel that the use of this medication in children should be re-evaluated. 

TI	Temporal and adaptation effects in the multifocal visual evoked potential
AU	Barber C
AU	Wen Y
AU	Merigoux V
IN	Queen's Medical Centre 
AD	Nottingham, NG7 2UH, England 
EM	Colin.Barber@nottingham.ac.uk
AB	Purpose: To investigate the pattern adaptation properties of the pattern onset visual evoked potential (VEP) in multiple small, relatively homogenous, areas of the visual using the multi-focal stimulation and analysis technique. Methods:  A black and white checkerboard stimulus, containing a square 8x8 array of elements, was used. The pattern was viewed centrally, such that the whole stimulus field subtended 16°, and each element 2°. Each element consisted of checks subtending 20' of arc. The effective stimulus duration was varied between approximately 10–80 ms by varying the number of frames (1, 2, 3, 4, 5 or 6) in each m-step. In a second experiment, similar values were used, but with a polysilicon projector instead of a normal computer monitor, so that the pattern was actually present on the screen for the stated duration, rather appearing as multiple raster sweeps. First order kernels, and the first slice of the second order kernels of the responses were analysed, and differences due to the different. Stimulus systems investigated  Results:  Clear, characteristic waveforms, with a high degree of replicability, were seen for elements close to the centre of the visual field. The location of the largest response differs between individuals. The first order kernels contain components from both the onset and the offset of the pattern, with the latter dominating and showing a clear shift with stimulus duration. The second order kernels show a systematic change in amplitude, indicating the degree of pattern adaptation produced. The responses to projector, as opposed to monitor, stimuli were delayed, and this is believed to be due to the longer onset time of the pattern. There were no oservable effects due to the raster stimulus.  Conclusions: The effects of pattern adaptation can be clearly seen using the multi-focal technique, which permits a precision of measurement that was previously unattainable. Investigation of higher order responses may offer further insights into non-linear adaptation process occurring early in the visual pathways.

TI	Electrophysiological diagnosis of acute and inflamatory diseases.
AU	Beaumont, P.
AU	Vaegan
IN	The Eye & Vision Research Institute.
AD	187 Macquarie St, Sydney, Australia, 2000.
AB	Ocular electrophysiology is most commonly used in the differentiation of hereditary retinal dystrophies.  Clinically however, the most exciting use of ocular physiology is in the diagnosis of the rare inflammatory, immune mediated or toxic syndromes.  The classic findings reported by Thirkill in CAR/MAR (cancer associated retinopathy/melanoma associated retinopathy) and autoimmune retinopathy has been replicated in our electrophysiological laboratory.  In particular, we found in the early, but very symptomatic cases of auto immune retinopathy the loss of oscillatory potentials has been a very useful confirmatory diagnostic feature.  We found that the EOG has been better at differentiating or confirming a diagnosis of an acute zonal outer occult retinopathy (AZOOR) or multiple evanescent white dot syndrome (MEWDS) than the electroretinogram changes.  An asymmetry in the reduction of the EOG has also been a useful pointer to differentiate cancer-associated retinopathy (CAR) from hereditary disease.  The clinical appearances and the electrophysiological findings in the above diseases will be discussed.

TI	Visual field constriction and electrophysiological changes associated with Vigabatrin
AU	Besch D
AU	Kurtenbach A
AU	Apfelstedt-Sylla E
AU	Dietrich TJ
AU	Dennig D
AU	Asenbauer C
AU	Zrenner E
AU	Schiefer U
IN	University-Eye Hospital; Department of Pathophysiology of Vision and Neuro-ophthalmology; Schleichstr. 12-16; D-72076 Tübingen, Germany
EM	dorothea.besch@uni-tuebingen.de
AB	Purpose Approximately 5% of all people suffer at least one epileptic event during their lives, and 0.5% of the population have the diagnosis of epilepsy established. Visual field defects have been reported in epileptic patients receiving long term therapy with Vigabatrin. We therefore investigated ophthalmological changes. Methods Twelve epileptic patients treated with Vigabatrin (age range 35–65 years) have been investigated. Two patients had Vigabatrin monotherapy, all others had Vigabatrin (dose range 1000-3000mg/d) in combination with other antiepileptic drugs for between 2 months and 8 years. They were examined with psychophysical tests including color vision (Farnsworth D15), dark adaptation threshold, Goldmann visual fields and, in some cases, Tübingen Automated Kinetic Campimetry. A Ganzfeld ERG and an electrooculogram following the ISCEV standard protocol were also obtained. Patients were also examined with the VERIS multifocal ERG including recordings of multifocal oscillatory potentials (100-1000Hz). None of the patients reported visual complaints. Results Color vision and dark adaptation thresholds were normal in all patients. Two patients showed a severe visual field constriction (I/4e) of 10-20°, predominantly in the nasal quadrants, 8 patients a moderate constriction (20-45°) and 1 patient a mild constriction (40°-55°). In all patients oscillatory potentials in Ganzfeld electroretinography were attenuated, especially in those patients with marked field defects. Multifocal oscillatory potentials were also delayed. In 5 patients a delayed cone single flash response and subnormal multifocal ERG amplitude were found. Conclusions There were severe to moderate visual field defects in 10 out of 12 patients, while significant electrophysiological changes were observed in all patients with Vigabatrin therapy, especially of the oscillatory potentials, indicating a possible toxic effect of Vigabatrin on the inner retina layers. No relation between dosage and time of Vigabatrin intake has been found, however, both patients with marked constricted fields had a relatively high doses (2500mg/d and 3000mg/d for 5 and 6 years). Our results show the value of detailed visual field testing and electrophysiological diagnostics for detection and follow-up of ophthalmological abnormalities in patients with refractory epilepsy treated with Vigabatrin.

TI	Electrophysiological changes in children with poor vision and nystagmus
AU	Brecelj J
AU	Stirn-Kranjc B
IN	Institute of Clinical Neurophysiology, and Department of Ophthalmology,
AD	University Medical Centre Ljubljana, Slovenia
AB	Purpose: Ophthalmological examination may reveal the cause of nystagmus in some anomalies, e.g. congenital cataracts, glaucoma, aniridia, sclerocornea, Peter's anomaly, and therefore do not pose diagnostic problems. However, in infants with normal appearing fundus, some other diseases associated with nystagmus and poor vision may not be as easily diagnosed. Electrophysiology could, theoretically, be helpful, but it is not known, how sensitive and specific electrophysiological changes are for detecting causes of underlying nystagmus and impaired vision from birth. Our aim was, therefore, to investigate whether ERG and VEP changes in children with such an affection could reveal the origin of the dysfunction, either retinal or along the visual pathway. Methods: ERG and VEP activity to bright white, red, and dim flashes, as well as to 30 Hz and pattern-reversal stimulation were recorded in 30 children with nystagmus. ERG were detected by skin electrodes. Thorough neurological and ophthalmological examination were also carried out to exclude patients with neurodegenerative or metabolic diseases. Results: Simultaneous ERG and VEP recordings in alert children could differentiate several patterns of changes which seem to be related to idiopathic nystagmus, Leber's amaurosis, achromatopsia, and albinism. Conclusions: On the grounds of electrophysiological changes we could indicate the nature of the visual problem for diagnostic purposes.
TI 	On the mechanism of a picrotoxin effect on the ERG
AU	Chappell RL*#
AU	Schuette E*#
AU	Anton R*#^
AU	Ripps H*^
IN	*Marine Biological Laboratory, Woods Hole, MA; #Hunter College and Graduate School, CUNY, NY; ^University of Illinois at Chicago College of Medicine, Chicago, IL
AD	Hunter College, Dept. of Biological Sciences, 695 Park Avenue, NY, NY 10128 USA
EM	rchappell@gc.cuny.edu 
AB 	Purpose:  To examine whether GABA receptors (GABA(R)s) contribute to the picrotoxin-induced changes in the electroretinogram (ERG) of the skate, Raja erinacea. Methods:  The transretinal ERG of the skate eyecup preparation was monitored during superfusion of GABA(R) blockers.  Simultaneous intracellular recordings from horizontal cells (the S-potential) were used to monitor the effects on photoreceptor transmitter release.
Results: 50M Picrotoxin, a chloride channel blocker that suppresses the responses of both GABAA(R)s and GABAC(R)s, reduced the ON (b-wave) component of the ERG, whereas the OFF (d-wave) component of the response became more pronounced.  Conversely, picrotoxin had no effect on the light-evoked response of the horizontal cell.  Moreover, the GABAA(R) antagonist bicuculline (100M) produced no change in either the ERG or the S-potential.   Conclusions:   The observation that picrotoxin had no significant effect on the intracellularly-recorded horizontal cell response is a good indication that neither transmitter release from photoreceptors nor feedback to photoreceptors is responsible for the changes in the ERG waveform.  Consequently, the effect must involve more proximal retinal neurons.  In the skate retina, both bipolar and Müller cells have been implicated in the generation of ON and OFF components of the ERG, and GABA(R)s have been identified on both cell types from patch-clamp recordings of isolated cells.  However, only the bipolar cells are known to have GABAC(R)s as well as GABAA(R)s.  Since the GABAA(R) antagonist bicuculline had no effect on the ERG, it is possible that the ERG changes produced by picrotoxin are due to its ability to block the GABAC(R)s on retinal bipolar cells.  On the other hand, the effect on the ERG may have resulted from picrotoxin blockade of chloride channels on amacrine or ganglion cells, both of which appear to exert an influence on the b-wave of the ERG. The knowledge that such changes in the ERG could involve chloride channels or a specific class of GABA receptor may prove useful in the diagnosis of certain genetically related retinal disorders. 
CI 	None.    Support: NIH grants EY00777 and EY06516

TI	Electrophysiology in Epileptic Subjects Treated with Vigabatrin or Other Anti-Epileptic Drugs.
AU	Comaish IF
AU	Gorman C
AU	Barber C
AU	Galloway NR
IN	University Hospital, Queens Medical Centre, Nottingham, NG7 2UH, UK
AD	University Hospital, Queens Medical Centre, Nottingham, NG7 2UH, UK
EM 	Comaish@aol.com
AB 	Purpose. To compare the visual electrophysiology of patients taking Vigabatrin to the electrophysiology in epileptics controlled with other Anti-Epileptic Drugs (AEDs). Methods. Twenty epileptics treated with Vigabatrin and twenty subjects controlled with other AEDs underwent Standardised ERG and EOG.  Their results were compared qualitatively and quantitatively paying especial attention to the b-wave of the ERG and Oscillatory potentials. Results.  The b-wave of the ERG was consistently reduced in amplitude in Vigabatrin treated subjects with reduction in the Oscillatory index and Arden ratio.  Conclusions. The use of Vigabatrin reduces the ERG b-wave amplitude and oscillatory potentials and this effect may not recover even long after stopping the drug, being associated in many cases with visual loss.  The Arden ratio is reduced in subjects taking Vigabatrin but may recover after cessation. However, visual loss may persist in the presence of a recovered EOG.  These findings suggest other effects of the drug than purely those mediated by GABA receptors.  A metabolic mechanism is proposed.

TI	Visual electrophysiological correlates in  vigabatrin treatment 
AU	Coupland SG
AU	Zackon D
AU	Ross T
IN	University of Ottawa Eye Institute, Ottawa, ON, Canada.
AD	University of Ottawa Eye Institute, Ottawa Hospital-General Campus, 501 Smyth Road, Ottawa, ON, Canada  K1H 8L6
EM	scoupland@ogh.on.ca
AB	Purpose Anticonvulsant activity of Vigabatrin is achieved by elevating GABA levels in