preceded by:

	The 4th ISCEV Course
	on Standard Techniques
	12-13 February

	The XXXIV ISCEV Symposium

	St John's College, Sydney, Australia

	13 – 17 February 2000

	followed by:

	optional Blue Mountains trip,18 February

	The 1st ever ISCEV Multifocal Course
	19-20 February

ISCEV BOARD OF OFFICERS

	President:		Y Miyake, (-2003/1)

	Vice-President: for Europe and Africa	N R Galloway, (-2000/2)
	
	Vice-President for Asia and Australia	vacant
	
	Vice-President or the Americas		W Dawson, (-2002/1)

	Secretary for Europe and Africa		Colin Barber, (2000)
	& Secretary-General:	
	
	Secretary for the Americas:		RG Weleber, (-2001/1)
	
	Secretary for Asia and Australia		Y Oguchi, (-2002/2)
	
	Treasurer: 		E Adachi, (-2003/1)
	
	Editor:			JV Odom, (-2001/1)
	
	Members at large:		M Bach, (-2000/1)
				GF Holder, (-2002/1)
				H Spekreijse, (-2000/2)
				L Wu, (-2002/2)

PROGRAMME INDEX

Information for Presenters			4
	
Outline programme listings:		SUNDAY 13 FEBRUARY	5
				MONDAY 14 FEBRUARY	6
				TUESDAY 15 FEBRUARY	7
				WEDNESDAY 16 FEBRUARY	8
				THURSDAY 17 FEBRUARY	9

Scientific Session listings	Oral Session 1	Expanding Diagnostic Methodology (1)	11
		Oral Session 2	The Multifocal Technique and Applications	21
		Oral Session 3	Visual Evoked Potentials	69
		Oral Session 4	Electro-oculogram and Electroretinogram	79
		Oral Session 5	Auto-immune and Inflammatory Responses	93
		Oral Session 6	Expanding Diagnostic Methodology (2)	103
		Oral Session 7	Paediatric Visual Electrophysiology	151
		Oral Session 8	Vigabatrin Minisymposium	161
		Oral Session 9	Electrophysiology in Animal Studies	171

		Poster Session 1		31
		Poster Session 2		113

Membership Meeting	Agenda		89

INFORMATION FOR PRESENTERS

Slide Presentations
Dual 35mm projection is provided. The slides reception and preview area is located in the ante-room of the Library where all Oral Sessions are held. Please take your slides there half an hour before the session is due to begin. Ensure that the slides themselves are all numbered and oriented correctly. Also, please ensure that the slide carrier is marked with the session number, your name, and the time of your presentation.

Computer Presentations
Computer projection facilities, but not a computer, are provided. Presenters are reminded to check the functioning of their own computer with the projection system well ahead of time, and to ensure that their computer/presentation is set in place during the break preceding their session.

Poster Presentations
Poster boards and fixing materials are provided. Posters should be of standard (A1) size, in "portrait" orientation. The Posters are to be displayed in the Cloister Room and, to facilitate discussion, will remain on display throughout the symposium. Presenters are asked to stand by their posters during their designated Poster Session. Poster set-up is during the afternoon/evening of Sunday 13 February, and tear-down may be either the evening of Wednesday 16 February, or the morning or Thursday 17 February.

EDITORS' NOTE

The abstracts in this book have been edited and re-set to a standard format. Every effort has been made to interpret and respect the intended meaning of the original submission. Sincere apologies are offered for any inadvertent misinterpretation herein.

Brian Brown PhD, Colin Barber PhD

Sunday 13 February

13.00	Registration Desk opens

18.00	Welcome Reception in the gardens of St John's College

20.00	CLINICAL CASES SESSION
	Chair:  Michael Marmor

Monday 14 February

08:00 - 08.30	Opening Ceremony:	Gabrielle Hollows	Fred Hollows Foundation
		Yozo Miyake		President of ISCEV

08.30 – 10.30	Scientific Session 1	EXPANDING DIAGNOSTIC METHODOLOGY (1)
	Chairs:	Vaegan;  Masayuki Horiguchi

10.30-11.00	Coffee Break

11.00 – 13.00	Scientific Session 2	THE MULTIFOCAL TECHNIQUE AND APPLICATIONS
	Chairs:  	Lehzeng Wu;  Don Hood

13.00–14.00	Lunch Break
Sign up for:	Multifocal Guidelines, lunch discussion

14.00 – 16.00	Posters Session 1	with coffee
	Chairs	Michael Bach;  Patrizia Tormene

16.00 – 18.00	Scientific Session 3	VISUAL EVOKED POTENTIALS
	Chairs:  	J Vernon Odom;  Ivan Bodis-Wollner

Evening:	Harbour Cruise and free evening in Sydney
Sign up for:	VEP Standard, discussion supper

Tuesday 15 February

Sign up for:	PERG Standard, discussion breakfast

08.00 – 10.00	Scientific Session 4	ELECTRO-OCULOGRAM & ELECTRORETINOGRAM
	Chairs:	Richard Weleber;  Ann Fulton

10.00-10.30	Coffee break

10.30 – 12.30	Membership Meeting

Afternoon	Visit to Kurring-gai National Park,
	with aboriginal dance demonstration and guide to rock-carved drawings.
	And the specially Antipodean ISCEV Olympics.

Evening	A choice of two options:
Action choice – travel back from Kurring-gai directly to Bronte Surf Club for informal Australian seafood barbecue and salad supper, beach sports, 
life-saving demonstration, and bar with drinks at club prices.
Relaxation choice – travel back from Kurring-gai to St John's College; make
your own way to the nearby Newtown district and enjoy its amazing array
of ethnic restaurants.

Wednesday 16 February

08.30 – 10.30	Scientific Session 5	AUTO-IMMUNE AND INFLAMMATORY RESPONSES 
	Chairs:	Yozo Miyake;  John Heckenlively

10.30-11.00	Coffee Break

11.00 – 13.00	Scientific Session 6	EXPANDING DIAGNOSTIC METHODOLOGY (2)
	Chairs:	Emiko Adachi;  Ido Perlman

13.00-14.00	Lunch Break

14.00 – 16.00	Posters Session 2	with coffee
	Chairs	Graham Holder;  Ulrich Kellner

16.00 – 17.45	Scientific Session 7	PAEDIATRIC VISUAL ELECTROPHYSIOLOGY
	Chairs:	Colin Barber;  Dianne Sharp

19.30 for 20.00	Symposium Dinner in the Holmes Building of Sydney University
	Including presentation of the Dodt Award by Professor Eberhart Zrenner
	And the ISCEV Olympics Trophy by Professor Colin Barber 

Thursday 17 February

08.30 – 10.45	Scientific Session 8	VIGABATRIN MINISYMPOSIUM
	Chair:  	Eberhart Zrenner; Günter Niemeyer

10.45-11.15	Coffee Break

11.15 – 13.15	Scientific Session 9	ELECTROPHYSIOLOGY IN ANIMAL STUDIES
	Chairs:  	Kristina Narfstrom;  Pierre Lachapelle

13.30	Farewell lunch on the lawns of St John's College

Monday 14 February

08:00 - 08.30	Opening Ceremony:	Gabrielle Hollows	Fred Hollows Foundation
		Yozo Miyake		President of ISCEV

08.30 – 10.30	Scientific Session 1	EXPANDING DIAGNOSTIC METHODOLOGY (1)
	Chairs:	Vaegan;  Masayuki Horiguchi

10.30-12.00	Coffee Break

11.00 – 13.00	Scientific Session 2	THE MULTIFOCAL TECHNIQUE AND APPLICATIONS
	Chairs:  	Lehzeng Wu;  Don Hood

13.00–14.00	Lunch Break
Sign up for:	Multifocal Guidelines, lunch discussion

14.00 – 16.00	Posters Session 1	with coffee
	Chairs	Michael Bach;  Patrizia Tormene

16.00 – 18.00	Scientific Session 3	VISUAL EVOKED POTENTIALS
	Chairs:  	J Vernon Odom;  Ivan Bodis-Wollner

Evening:	Harbour Cruise and free evening in Sydney
Sign up for:	VEP Standard, discussion supper

08.30 – 10.30	Monday 14 February

Scientific Session 1	EXPANDING DIAGNOSTIC METHODOLOGY (1)
Chairs:		Vaegan;  Masayuki Horiguchi

08.30	INVITED LECTURE:  Recent advances in the basic understanding of the nature of the ERG
	GB Arden (London, UK))
09.00	Subretinal electrical stimulation of intact and degenerated retinae
	E Zrenner, S Weiss, H Schwahn, A Stett (Tübingen, Germany)
09.15	Analysis of the photopic luminance-response function: defining the photopic hill
	P Lachapelle, M Rufiange, O Dembinska, R Koenekoop, J Little (Montréal, Québec, Canada)
09.30	Role of cooperation and motivation in the use of pattern reversal stimuli to elicit visual evoked cortical responses (PVECR) for assessment of visual acuity
	I Perlman, J Bahir, E Mezer, R Leibu (Haifa, Israel)
09.45	Centro-parietal cortical activation via moving visual stimuli
	M Kuba, J Kremlácek, Z Kubová, F Vít, J Szanyi, D Gayer (Hradec Králové, Czech Republic)
10.00	An alternative approach to disentangling magnocellular and parvocellular contributions to conventionally recorded VEPs
	I Rudvin, A Valberg (Trondheim, Norway)
10.15	Perceptual gating of the spatial frequency-doubling illusion
	T Maddess, MP Davey, S Bedford, AC James (Canberra, Australia)

RECENT ADVANCES IN THE BASIC UNDERSTANDING OF THE NATURE OF THE ERG

GB Arden

City University, London, UK

In this paper new views of the ERG will be discussed. Fundamental processes which contribute to the a-wave and the b-wave will be examined. What retinal sensitivity is and how it can be assessed will be discussed. In addition, the role of long flashes in the retina and their effects on adaptation will be assessed. Recent views of the pattern-ERG will be examined, and a review of findings over the past year and a half will suggest the way forward for the various aspects of the ERG.

g.arden@city.ac.uk

 SUBRETINAL ELECTRICAL STIMULATION OF INTACT AND DEGENERATED RETINAE

E Zrenner*, S Weiss*, H Schwahn*, A Stett#

*University Eye Hospital, #Natural and Medical Sciences Institute, Tübingen, Germany

Purpose: It is necessary for the successful development of a subretinal implantable visual prosthesis to understand the basic principles of electrical stimulation of the retina. The aim of our study was to find stimulation of distal retinal neurons. Methods: A) in-vitro experiments: Degenerated retinas of RCS-rats were positioned onto a microelectrode array (MEA). Voltage and current pulses were applied to the distal side of the retina and stimulus correlated ganglion cell activity was recorded. B) in-vivo experiments: A flexible electrode array was implanted subretinally in rabbit eyes. Electrically evoked cortical potentials (EECPs) were recorded after a voltage or current pulse was applied to the retina. Results: in-vitro experiments: Subretinal electrical stimulation evoked correlated ganglion cell activity even in highly degenerated RCS rat retinas. A charge density of 100-1000µC/m2 was required to elicit threshold responses. The spatial resolution was 100-200µm. In-vivo experiments: EECPs could be elicited in rabbits with either voltage or current pulses applied to the proximal side of the retina. Waveform and size of the EECPs varied with the amount of transferred charge and the stimulation mode (bipolar vs. monopolar). Conclusion: Design parameters for the development of an active subretinally implantable visual prosthesis can be extracted from the results obtained with the degenerated retinas in-vitro. The successful recording of EECPs elicited with subretinally applied electrical stimuli demonstrates that the subretinal approach of a visual prosthesis is very promising. 

ezrenner@uni-tuebingen.de

ANALYSIS OF THE PHOTOPIC LUMINANCE-RESPONSE FUNCTION: DEFINING THE PHOTOPIC HILL

P Lachapelle, M Rufiange, O Dembinska, R Koenekoop, J Little

McGill University-Montréal Children's Hospital Research Institute, Montréal, Québec, Canada

Purpose: While the parameters which describe the luminance response function of the scotopic ERG are well established, those regulating the photopic response await full description. The purpose of this study was to identify the parameters which best describe the photopic luminance-response function or "Photopic Hill", characterize their properties and examine their clinical utility. Methods: Photopic intensity-response functions were obtained from normal subjects and patients affected with selected retinal disorders. The responses were obtained with the use of the LKC UTAS-E-3000 stimulator with intensities ranging from -0.8 to 2.84 log cd.m-2.sec. delivered against a rod desensitising background of 30 cd.m-2. Data analysis was limited to a- and b-wave components only. Results: The photopic luminance response function adopts a unique shape where the b-wave initially grows with progressively brighter flashes, reaches a plateau and then starts to decline as the flash luminance is made stronger to reach an amplitude equivalent to that of the a-wave; the latter demonstrating an almost linear growth in amplitude. Based on the above we identified four basic descriptors. Vmax  or maximum b-wave voltage. K+ and K- representing the dimmer (ascending slope of the Hill) and brighter (descending slope of the Hill) flash luminance producing a b-wave 50% of Vmax and Ka=b describing the flash luminance at which the a- and b-wave are of the same voltage.  In normals these parameters vary as follows: Vmax (135.6 ± 16µvolts; flash: 0.4 ± 0.24 log cd.m-2.sec), K+ (-0.59 ± 0.1 log cd.m-2.sec), K- (+1.7 ± 0.2 log cd.m-2.sec) and Ka=b (between 1.9 and 2.4 log cd.m-2.sec).  Use of these parameters proved to be useful in interpreting the Photopic Hill obtained from patients affected with selected retinal disorders. Conclusion: Although the exact retinal mechanisms at the origin of the unique photopic luminance response function awaits to be further defined, our study reveals that it can be described with easily identifiable objective landmarks which can be used to further distinguish the functional consequences of numerous retinal disorders sharing similar symptoms and clinical signs . For those who have the technical possibility, the Photopic Hill should be part of their regular ERG protocol as it would appear to significantly improve the clinical evaluation of the photopic system which is, we believe, underestimated as per the current ISCEV standards. Supported by MRC.

mdpl@musica.mcgill.ca

ROLE OF COOPERATION AND MOTIVATION IN THE USE OF PATTERN REVERSAL STIMULI TO ELICIT VISUAL EVOKED CORTICAL RESPONSES (PVECR) FOR ASSESSMENT OF VISUAL ACUITY

I Perlman, J Bahir, E Mezer, R Leibu

Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel

Purpose: Pattern reversal stimuli are commonly used to elicit visual evoked cortical responses (VECR) in order to assess visual acuity. The PVECRs depend upon the ocular optical system and the functional integrity of the macular region, optical pathways and primary visual cortex as well as on motivation, attention and cooperation of the patients. This study was conducted to test the contribution of attention and cooperation to the PVECRs in order to improve our use of this electrophysiological test for objective assessment of visual performance. Methods: Two groups of volunteers with normal visual acuity (6/6) were studied. In one group, PVECRs were recorded while the subjects were viewing the stimulus and simultaneously performing an auditory task to draw their attention to another other modality. Subjects in the second group were asked to defocus the target by accommodating their fixation to a distance of 50cm or 25cm. PVECRs were recorded in response to checks of 60', 30', 15' and 7.5'. The implicit time and amplitude of P100 were measured and paired t-tests were performed to test the results. Results: In the "attention" group, PVECRs did not differ significantly between three recording conditions: (a) no auditory interference, (b) passive listening to a list of names or objects and (c) performing an auditory task and reporting its results.  In the "defocusing" group, our findings differed between young (20-25 years) and older (>30 years) volunteers. In the young group, the PVECRs elicited by checks of 60' and 30' were not affected by the distance of fixation. PVECRs with smaller checks (15' and 7.5') were characterized by smaller amplitudes and prolonged implicit times when the distance of fixation was reduced. For the older subjects, all PVECRs were similar regardless of check size and distance of fixation. Conclusions: Our data indicate that attention is not a prerequisite for normal PVECRs provided that the subject is viewing the stimulus. Defocus can affect the responses elicited by small checks but not those evoked by checks of medium size. Our findings are, therefore, supportive for the use of PVECRs for objective assessment of visual acuity.

iperlman@techunix.technion.ac.il

CENTRO-PARIETAL CORTICAL ACTIVATION VIA MOVING VISUAL STIMULI

M Kuba, J Kremlácek, Z Kubová, F Vít, J Szanyi, D Gayer

Charles University Faculty of Medicine, Hradec Králové, Czech Republic

Purpose:  Among all visual moving stimuli which we have previously tested in diagnostic applications of motion-onset visual evoked potentials, the centrifugal radial motion – "expansion" - produced the largest amplitudes of the responses. However, distribution of these potentials over the scalp and their latencies differ substantially in comparison to the other motion-onset VEP and so the interpretation of their pathological changes remains obscure. We present some clinical findings in these VEPs and suggest their diagnostic meaning. Methods: Altogether 850 neuro-ophthalmological patients were examined during the last 3 years with the "expansion" as an additional stimulus to our standard combination of pattern-reversal and motion-onset VEPs. 5 unipolar leads: Oz, Or, Ol (5 cm to the right and left from the Oz position), Cz, Fz,  and bipolar lead Oz-Cz were used.  Monocular stimulation (30°x40°) with expanding rectangular frames (spatial frequency of 1 - 0.2 c/deg, velocity 10 - 23 deg/s) consisted of 200 ms motion interrupted by 1s periods with stationery structure. Results: Retrobulbar neuritis, multiple sclerosis, brain ischemia, glaucoma and dementias produced different findings of latencies and maximum amplitude location related to the suspected level of visual pathway involvement.  Only in about 20% of pathologically prolonged motion-onset VEPs, were the "expansion" responses simultaneously delayed.  In about 7% of all patients, a delayed "expansion" response in Cz lead was the only pathological finding. Conclusions:  We believe that the data presented give evidence about a separate information stream from the visual pathway to the centro-parietal cortex, which might mediate early "warning" signals to the cognitive centers before completion of the visual information processing in the striate and extrastriate areas.  Involvement of these neural links in various pathological processes seems to be independent of the functional state of the other parts of the visual pathway  (according to the results of the usual variants of EPs). Acknowledgements: Supported by the Grant Agency of the Charles University, Czech Republic, by the James S. McDonnell Foundation for Cognitive Neurosience, USA and by the Grant Agency of the Czech Ministry of Health (grant No. 4800-3/98).

kuba@lfhk.cuni.cz

AN ALTERNATIVE APPROACH TO DISENTANGLING MAGNOCELLULAR AND PARVOCELLULAR CONTRIBUTIONS TO CONVENTIONALLY RECORDED VEPS

I Rudvin, A Valberg

Department of Physics, Norwegian University of Science and Technology, Trondheim, Norway

Purpose: Several studies have shown that in conventional VEP recordings using luminance-modulation only, the major contribution to the low-contrast and high-contrast waveforms can be ascribed to the magnocellular (MC) pathway or to the parvocellular (PC) pathway, respectively. However, the temporal overlap of the quickly saturating MC response and the less sensitive PC response prevents a straightforward identification of their separate contributions to the VEP waveform. Recognition of dual-pathway contributions has, for example, relied on identifying changes in the delay and amplitude (or gain) of the combined response as contrast is changed. Here we offer a different approach to unmasking the MC and PC contributions to VEP waveforms. Method: We used "difference waveforms", that is the difference between two temporal response waveforms for which stimulus contrast differed by a small amount, e.g. by 2, 5 or 10%. These difference waveforms, which are not easily assessed by simple visual inspection of the two response waveforms, can be described by quantifying the usual measurands such as peak-to-peak (p-p) amplitude and delay-to-peak. When waveforms change in shape or delay as a result of altered stimulus contrast, the p-p amplitude of the difference waveform is larger than the difference between the p-p amplitudes of the response pair. Similarly, the delay of the difference waveform is typically smaller or greater than the delay of either of the responses being compared. This method of analysis was successfully applied to recordings with a good signal to noise ratio. Results: By comparing difference waveforms for pairs of luminance-flicker responses in the low, medium and high-contrast range, we gained a more detailed picture of how contrast increments influence the VEP. At low contrasts, the difference waveforms were dominated by a positive peak with relatively short delays (MC-contribution). At intermediate contrasts, two smaller, temporally separate positive peaks could be seen (MC + PC). For higher contrasts, only the latter of these peaks was evident, with a delay lengthening with increasing contrast (PC). This picture served to underscore a trend observed in the delay plots of the response waveforms. The amplitudes of the difference waveforms clearly reflected the contrast dependent change in gain seen in the conventional contrast-response curves. Conclusion: This approach may offer a supplementary means of extracting and analyzing information on different sources in conventionally recorded VEPs.

rudvin@phys.ntnu.no

PERCEPTUAL GATING OF THE SPATIAL FREQUENCY DOUBLING ILLUSION

T Maddess, MP Davey, S Bedford, AC James

Centre for Visual Sciences, Canberra, Australia

Purpose:  The spatial frequency doubling (FD) illusion occurs for rapidly flickered low spatial frequency sinusoidal gratings. Under these conditions we perceive the gratings as having twice their original spatial frequency. The FD effect is now the basis for new methods of diagnosis of glaucoma. When the contrast modulation is instead the sum of both a fast and a slow flicker rate the FD illusion may disappear depending upon the frequency of the slower modulation. We investigated this apparent perceptual gating process. Methods: We first examined the stimulus conditions for which the perceptual gating occurs in up to 8 parts of the visual field. We then recorded simultaneous ERGs and VEPs for stimuli presented in the same regions. We examined contrast dependent phase changes in the evoked potentials previously shown to be associated with the FD effect. Results:. Visibility of the FD effect could be perceptually gated on or off by selecting a particular slow frequency component; however, we could not observe a change in either the VEP or ERG phase shifts.  Instead, the evoked potential data suggested that the FD percept should be present even when FD was not seen. Conclusions: The results indicate that we cannot observe the perceptual gating mechanism with evoked potentials examining mainly striate cortex. This may indicate that either (unrecorded) higher brain areas manage the gating, or that the gating occurs by changing what is read-out of V1 from a selection of possible valid percepts.

ted.maddess@anu.edu.au

Monday 14 February

08:00 - 08.30	Opening Ceremony:	Gabrielle Hollows	Fred Hollows Foundation
		Yozo Miyake		President of ISCEV

08.30 – 10.30	Scientific Session 1	EXPANDING DIAGNOSTIC METHODOLOGY (1)
	Chairs:	Vaegan;  Masayuki Horiguchi

10.30-13.00	Coffee Break

11.00 – 13.00	Scientific Session 2	THE MULTIFOCAL TECHNIQUE AND APPLICATIONS
	Chairs:  	Lehzeng Wu;  Don Hood

13.00–14.00	Lunch Break
Sign up for:	Multifocal Guidelines, lunch discussion

14.00 – 16.00	Posters Session 1	with coffee
	Chairs	Michael Bach;  Patrizia Tormene

16.00 – 18.00	Scientific Session 3	VISUAL EVOKED POTENTIALS
	Chairs:  	J Vernon Odom;  Ivan Bodis-Wollner

Evening:	Harbour Cruise and free evening in Sydney
Sign up for:	VEP Standard, discussion supper

11.00 – 13.00	Monday 14 February

Scientific Session 2	THE MULTIFOCAL TECHNIQUE AND APPLICATIONS
Chairs: 		Lehzeng Wu;  Don Hood

11.00	The complex dynamics of inner retinal ERG components facilitate mapping of ganglion cell function
	EE Sutter, Y Shimada, Y Li, AM Bearse (San Francisco, CA, USA)
11.15	Topographical changes of multifocal ERG waveforms across the retina
	MW Seeliger, D Raz, R Ofri, C Percicot, G Lambrou (Tübingen, Germany)
11.30	Wide field functional imaging of the retina using the multifocal ERG
	SW Parks, D Keating, AL Evans (Glasgow, UK)
11.45	Assessment of macular function by multifocal electroretinography and optical coherence tomography before and after panretinal photocoagulation in diabetic retinopathy
	T Baba, Y Sasaki, S Hatta, T Kumagami, M Inoue, J Hasegawa, Y Saeki, Y Atamai (Yonago, Japan)
12.00	Multifocal electroretinography in patients with adult-onset maculopathy
	B Feigl, A Haas (Graz, Austria)
12.15	Multifocal electroretinogram in patients with diabetes mellitus
	F Maruiwa, S Nakazaki, N Nao-I (Miyazaki, Japan)
12.30	First order kernel and flicker multifocal electroretinogram in rod monochromacy
	AB Jehn, G Niemeyer (Zürich, Switzerland)
12.45	The characteristics of glaucomatous changes in the multifocal ERG
	K Murayama, M Ito, S Yoneya (Saitama, Japan)

THE COMPLEX DYNAMICS OF INNER RETINAL ERG COMPONENTS FACILITATE MAPPING OF GANGLION CELL FUNCTION

EE Sutter, Y Shimada, Y Li, AM Bearse

Smith-Kettlewell Eye Research Institute, San Francisco, CA, USA

Purpose: Our goal is to identify and characterize inner retinal mechanisms and to isolate and map response components from ganglion cells. Cascading adaptive mechanisms in the retina are expected to lead to increasingly nonlinear response properties as the signals reach the innermost retinal layers. Thus, stimulation techniques that enhance second order response components are expected to provide information on as yet poorly understood inner retinal processes. New stimulation protocols of the multifocal nonlinear analysis technique (VERIS) are used to enhance and to study fast interactions between local retinal stimuli.  Methods:  Interleaving global flashes between the multifocal stimuli is a powerful means to amplify nonlinear effects such as interactions between consecutive stimuli at the same or different retinal locations.  In the derivation of the first order kernel, the responses of these periodic global stimuli are added when preceded by a focal flash and subtracted otherwise. Since both types of events occur the same number of times during the stimulus cycle, the global flash responses will only contribute if they are affected by the focal stimuli.  Their contribution (induced component) thus represents the difference in the response to the global stimulus  in the presence and absence of a preceding focal response. In this study not only one, but up to three, global stimuli are presented at specific intervals between the multifocal stimuli.  Results: 1. Focal stimuli can have a very large effect on the response to a following global stimulus, even when the small focal stimuli are relatively weak. 2. The topography of the induced component varies greatly with timing  (time lag between multifocal and global stimulus 13.3 to 80ms).  3. When pairs and triplets of global stimuli are interleaved, the effects induced by the focal stimuli can propagate to the second and third of the following global responses.  At some eccentricities, it increases in magnitude from the first to the last of the global stimuli suggesting a resonance-like mechanism. 4. Induced effects depend strongly on stimulus timing, luminance and retinal eccentricity.  5. The induced effects on specific components of the global responses  can be facilitating or inhibiting depending on the time lags between the focal and global stimuli.  6. The induced components contain a large contribution from the optic nerve head component (ONHC) that can be used for local estimation of ganglion cell function. Conclusions: The large ONHC contribution confirms the usefulness of the new stimulation protocols for mapping ganglion cell responses.

ees@ski.org

TOPOGRAPHICAL CHANGES OF MULTIFOCAL ERG WAVEFORMS ACROSS THE RETINA

MW Seeliger, D Raz, R Ofri, C Percicot, G Lambrou

University Eye Hospital, Tübingen, Germany

Purpose: To describe the topographical changes of multifocal ERG (MF-ERG) waveforms across the retina in humans and monkeys, and to present a descriptive model for the nature of these changes. Methods: Human probands and monkeys were examined with a VERIS MF-ERG system. The waveforms at each location were modeled with a set of two sinusoids of different frequency, each multiplied by a gaussian envelope. For each trace array, an amplitude relationship between these two components was established subjectively to obtain a good fit of the central response. Different waveform shapes then were produced by shifting the two sinusoids relative to each other, but keeping the amplitude relationship constant. Results: The waveform shapes differed considerably between different retinal locations, especially between the nasal and temporal side. The low-frequency component (LFC) was, compared to the high-frequency component (HFC), relatively smaller in monkey than in human. As a result, the changes in waveform shape were more prominent in the monkey.  Most local waveforms could be almost exactly simulated by the above method if the LFC was kept at the same temporal position and the HFC was shifted by different amounts. The typical "banana shape" of the peak implicit times of ring averages (slow central response, faster paracentral responses, slower peripheral responses) could also be simulated. Conclusions: The results suggest that there are two major components to the first order kernel response of the MF-ERG. The larger LFC is constant in implicit time across the retina and presumably represents the b-wave, whereas the smaller HFC whose implicit time changes with retinal location presumably represents the OPs. Due to the differences in waveform shape, most apparent in the temporal-nasal gradient, it appears not optimal to use ring or even overall averages of MF-ERG data for analysis. Given that the OP component indicates amacrine cell activity, it will be interesting to study changes of this component with diabetes and possibly glaucoma.
Supported by the DFG (SFB 430, project C2) and fortuene grant 517.

see@uni-tuebingen.de

WIDE FIELD FUNCTIONAL IMAGING OF THE RETINA USING THE MULTIFOCAL ERG

SW Parks, D Keating, AL Evans

Electrodiagnostic Imaging Unit, Tennent Institute of Ophthalmology, Glasgow, UK

Purpose: Previously we reported control information from standard CRT based stimulation using multifocal ERG. The purpose of this study is to measure the variation of amplitude density and implicit time of multifocal ERG responses from large field stimulation (120 degrees). Methods: Twenty normal healthy volunteers were examined using the multifocal ERG. A custom-built pc-based multifocal system was used to generate a variety of stimulus arrays in a similar format to the VERIS system. The stimulus was presented on a digital polysilicon back projection display positioned 30 cm from the subject's eye.  A 61-element hexagonal array was chosen, covering a field of stimulation of 120 degrees. A steady background luminance filled the periphery of the display and a central cross was used to maintain fixation. Each hexagon alternated between black and white (97% contrast). A gain of 100,000 and high/low pass filters of 1-300 Hz  and simultaneously 10-300Hz were recorded using gold-foil scleral electrodes. The recording period comprised sixteen intervals of 30 seconds providing a total recording time of 8 minutes. Results: Amplitude densities vary from 200 nv/deg2 at the central area to 2nV/deg2 at the periphery. Implicit time does not vary significantly across the field although the variation present is greater than we have measured previously using a standard multifocal field. Conclusions, A projection  stimulus delivery system offers greater flexibility than a conventional CRT stimulus. Wide field stimulation of over 120 degrees provides improvements in signal to noise ratio and could prove useful in the assessment of peripheral retinal disorders. 

s.w.parks@clinmed.gla.ac.uk

ASSESSMENT OF MACULAR FUNCTION BY MULTIFOCAL ELECTRORETINOGRAPHY
AND OPTICAL COHERENCE TOMOGRAPHY BEFORE AND AFTER
PANRETINAL PHOTOCOAGULATION IN DIABETIC RETINOPATHY

T Baba, Y Sasaki, S Hatta, T Kumagami, M Inoue, J Hasegawa, Y Saeki, Y Atamai

Department of Ophthalmology, Faculty of Medicine, Tottori University, Yonago, Japan

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: centrally and 4 other points, at each of 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 seem to be reversible at the foveal region, although we need a further investigation in relation to the outcome of visual acuity.

MULTIFOCAL ELECTRORETINOGRAPHY IN PATIENTS WITH ADULT-ONSET MACULOPATHY

B Feigl, A Haas

Department of Ophthalmology, University Graz, Austria

Purpose: To evaluate the diagnostic value of multifocal electroretinography in adult-onset vitelliform dystrophy in comparison to conventional examinations. Methods: We performed a multifocal electroretinogram, a full-field electroretinogram and an electrooculogram in 5 patients with adult-onset maculopathy. Multifocal responses were obtained by testing 61 hexagonal elements within a visual field of 30° radius by using the Retiscan. A control group was examined to obtain normative values. Results: The amplitudes of the central 2-10 degrees were reduced in two patients. In one patient amplitudes were also reduced in the more peripherial region (20-30 degrees). In two patients multifocal responses were within the normal range.  The full-field electroretinogram was normal in all of our patients. Conclusion: Multifocal electroretinogram may give additional information in patients with adult vitelliform maculopathy, a disease affecting the central retina and therefore be of help in differentiating pattern dystrophies.

beatrix.feigl@kfunigraz.ac.at

MULTIFOCAL ELECTRORETINOGRAM IN PATIENTS WITH DIABETES MELLITUS

F Maruiwa, S Nakazaki, N Nao-I

Department of Ophthalmology, Miyazaki Medical College, Japan

Purpose: To evaluate retinal function in diabetic patients with multifocal electroretinogram (ERG). Method: Thirty patients with diabetes mellitus, eight of whom had no diabetic retinopathy, thirteen of whom had simple retinopathy, nine of whom had proliferative retinopathy and sixteen healthy volunteers underwent multifocal ERG testing (VERIS III, TOMEY Corporation). The stimulus area consisted of 61 hexagonal elements within the central 20 degrees. The net recording time was 4 min. The first and second order responses, the responses in nasal and temporal fields, or in upper and lower fields were compared. Results: Responses of the first order and the second order in the diabetic patients with no retinopathy and in healthy volunteers were not significantly different. The first order responses in the patients with simple diabetic retinopathy and in healthy volunteers were not different, but the second order responses were significantly different in amplitude. The first and second order responses in patients with proliferative diabetic retinopathy were more significantly reduced than those in patients with simple diabetic retinopathy. The responses in the lower nasal area were significantly lower than those of the other areas in diabetic patients. Conclusion: Multifocal ERG testing was useful to evaluate the retinal function in diabetic patients.

maruiwa@post.miyazaki-med.ac.jp

FIRST ORDER KERNEL AND FLICKER MULTIFOCAL ERG IN ROD MONOCHROMACY

AB Jehn, G Niemeyer

Department of Ophthalmology, University Hospital, Zürich, Switzerland

Objectives: To compare First Order Kernel (FOK) and Flicker responses from Multifocal Electroretinogram (MF-ERG) recordings in normals and patients with rod monochromacy. Flicker MF-ERG is expected to yield valuable results due to focal information under exclusion of rod function. Methods: FOK and Flicker MF-ERG, using RETIscan (ROLAND CONSULT) were recorded in normal subjects (n=5) and patients with rod monochromacy (n=4). The central 30 degrees of the retina were stimulated by 61 hexagons. For comparison of amplitudes and latencies, data from the inner two rings and the outer three rings were grouped and averaged. Results: In the outer three rings good results could be obtained in rod monochromacy and in normal subjects. In rod monochromacy the mean P1 amplitude was nearly extinguished in FOK (2.8 +/- 1.8 nV/sqdeg) and Flicker MF-ERG (3.2 +/- 0.7 nV/sqdeg). The mean latencies in rod monochromats were prolonged in FOK (51.1 +/- 5 ms) and Flicker MF-ERG (51 +/- 0.5 ms) compared to normal subjects. In the inner two rings mean P1 amplitude was overestimated and variation of parameters was high (FOK P1 amplitude 24.6 +/- 20.6 nV/sqdeg, latency 50.5 +/- 3.6 ms) in rod monochromacy. In Flicker MF-ERG mean P1 amplitude was even higher and more variable in the inner two rings (37.7 +/- 41.8 nV/sqdeg, latency 50.5 +/- 8.7 ms) in rod monochromats and in normal subjects (P1 amplitude 47.2 +/-15.8 nV/sqdeg, latency 43.2 +/- 6.5 ms). Conclusions: We found differences in amplitudes and latencies between normals and rod monochromats. MF-ERG is a useful tool to demonstrate the reduction of cone function. In rod monochromacy, P1 amplitudes were over-estimated in inner rings by FOK and even more by Flicker MF-ERG. In outer rings results of Flicker MF-ERG were comparable to FOK measurements. Manual setting of cursors helped to reduce overestimation of P1 amplitudes. Therefore the evaluation of traces is essential for correct interpretation.

niemeyer@opht.unizh.ch	

THE CHARACTERISTICS OF GLAUCOMATOUS CHANGES IN THE MULTIFOCAL ERG

K Murayama, M Ito, S Yoneya

Department of Ophthalmology, Saitama Medical School, Japan

Purpose: To evaluate whether the multifocal electroretinogram (MERG) discloses the damage seen with glaucoma. Methods: Multifocal electroretinograms were recorded from 16 eyes of 8  patients affected by binocular glaucoma in different stages of the disease and 5 eyes of 5 healthy volunteers. The stimulus was composed of 61 hexagons and the responses from upper half, lower half and all areas were averaged together using the VERIS Science program.  Amplitudes and implicit times of the first order kernels and the first slice of the second order kernels were analysed. Humphrey perimetry (30-2) and Nerve Fiber analyzer (GDx, Laser Diagnostic Technology) were performed in all eyes. On the basis of sensitivity loss in Humphrey perimetry the glaucomatous eyes were divided into two groups: light and medium. Results: There were significant differences in amplitude of the first order kernel and the peak latency of the second, the third negative and the third positive waves of the second kernel between the normal and the glaucomatous eyes with medium sensitivity loss. There was a significant correlation between the amplitude of the first kernel and the mean deviation measured by Humphrey perimetry. There was a significant inverse correlation between the amplitude of the first kernel and the extent of loss of axons fibers measured by NFA. On the other hand, the results of MERG did not correspond with local visual field defects for individuals. Conclusions: MERG in the 25 degree of the central field was sensitive enough to disclose functional changes in glaucomatous eyes.

koichi@saitama.ac.jp

Monday 14 February

08:00 - 08.30	Opening Ceremony:	Gabrielle Hollows	Fred Hollows Foundation
		Yozo Miyake		President of ISCEV

08.30 – 10.30	Scientific Session 1	EXPANDING DIAGNOSTIC METHODOLOGY (1)
	Chairs:	Vaegan;  Masayuki Horiguchi

10.30-14.00	Coffee Break

11.00 – 13.00	Scientific Session 2	THE MULTIFOCAL TECHNIQUE AND APPLICATIONS
	Chairs:  	Lehzeng Wu;  Don Hood

13.00–14.00	Lunch Break
Sign up for:	Multifocal Guidelines, lunch discussion

14.00 – 16.00	Posters Session 1	with coffee
	Chairs	Michael Bach;  Patrizia Tormene

16.00 – 18.00	Scientific Session 3	VISUAL EVOKED POTENTIALS
	Chairs:  	J Vernon Odom;  Ivan Bodis-Wollner

Evening:	Harbour Cruise and free evening in Sydney
Sign up for:	VEP Standard, discussion supper

14.00 – 16.00	Monday 14 February	

Posters Session 1 (with coffee)	Chairs:  Michael Bach;  Patrizia Tormene
		
P1.1	Electrophysiological evaluation of eyes of insulin-dependent diabetic patients without retinopathy
	MAS Abdel Megeed (Alexandria, Egypt)
P1.2	Pattern electroretinography and visual evoked potential in glaucoma
	MAS Abdel Megeed (Alexandria, Egypt)
P1.3	Prognostic value of electroretinography in central retinal vein occlusion
	MAS Abdel Megeed (Alexandria, Egypt)
P1.4	Sensitivity of VEPs versus ERGs in diagnosis of macular disorders
	OMM Al-Nahrawy (Suez, Egypt)
P1.5	Preoperative electroretinography for predicting the visual outcome of vitrectomy in proliferative diabetic retinopathy and proliferative vitreoretinopathy
	O Badie, A Shoeir (Giza, Egypt)
P1.6	Checkup of amplitudes and timing of responses recorded with a multifocal system
	M Bock, C Gerth, B Lorenz (Regensburg, Germany)
P1.7	Calibration of flicker intensity
	MC Brown, G Dean, PA Wareing (Liverpool, UK)
P1.8	Congenital absence of the chiasm: demonstration of an uncrossed visual pathway using monocular flash VEP
	MC Brown, C Hallet, A Anbarusu, SB Kaye (Liverpool, UK)
P1.9	Extraction and modelling of oscillatory potentials in human and animal electroretinogram
	BV Bui, JA Armitage and AJ Vingrys (Melbourne, Australia)
P1.10	Visual function in intra-uterine growth-restricted guinea-pigs
	BV Bui, JA Armitage, J Caddy, AE Rehn, SM Rees, AJ Vingrys (Melbourne, Australia)
P1.11	A comparative study of services, techniques, referral patterns and equipment in a representative sample of visual electrophysiology centres in Australasia
	E Chelva, JM Atkinson, JN De Roach, SMS Kay, TL McLaren, RI Price (Perth, Australia)
P1.12	Proposal for an international normative ERG database using the ISCEV standard for clinical ERG
	SG Coupland (Ottawa, Ontario, Canada)
P1.13	Serial visual electrophysiological correlates in birdshot retinochoroidopathy
	SG Coupland, W Hodge, P Kertes, A Bawazeer  (Ottawa, Ontario, Canada)
P1.14	Variation in the location and angle of the calcarine sulcus referenced to cranial landmarks
	NE Epstein, R Silverglide, X Zhang, N Karin, S Kangovi, DC Hood (New York, NY, USA)
P1.15	The role of functional testing in differential diagnosis of congenital achromatopsia
	A Farkas, K Wenzel, R Vamos, J Gyory (Budapest, Hungary)
P1.16	Complementary value of full field and multifocal ERG recordings
	Inna Goub, JK Grigg, FA Billson (Sydney, Australia)
P1.17	Evidence for EOG abnormalities in patients with pigment dispersion syndrome and pigmentary glaucoma
	VC Greenstein, W Seiple, R Ritch (New York, USA)
P1.18	Visual evoked potentials in epilepsy patients on Carbamazepine (Finlepsin)
	AB Guekht, AA Shpak (Moscow, Russia)
P1.19	The functional evaluation of retinal vascular occlusion with the electroretinogram
	SZ Huang, LZ Wu, TQ Luo, DZ Wu (Guangzhou, China)
P1.20	S-cone topography in normals and blue-cone monochromats	
	H Jägle, JF Albrecht, HA Baseler, M Seeliger, LT Sharpe (Tübingen, Germany)
P1.21	Separation of USH syndrome I and II by ERG implicit time
	GB Jaissle, MW Seeliger (Tübingen, Germany)
P1.22	Electrooculography and pattern ERG in the diagnosis of Best's disease
	M Jarc-Vidmar, P Popovic, J Brecelj, M Hawlina (Ljubljana, Slovenia)
P1.23	Acquired non-vascular unilateral inner retinal dysfunction
	S Kaushal, AH Koh, CR Hogg, GE Holder (London, UK)
P1.24	Multifocal VEPs in normal tension glaucoma
	I Kimura, H Ohde, T Tanino, K Ohtake, Y Betsuin, K Kita, Y Mashima, Y Oguchi, D Hood (Tokyo, Japan)
P1.25	A case of congenital stationary night blindness (CSNB) with previously-undescribed ERGs: a new entity?
	K Kita, Y Shirao, K Kawasaki (Kanazawa, Japan)
P1.26	Objective perimetry in glaucoma
	A Klistorner, SL Graham (Sydney, Australia)
P1.27	Supernormal ERG a-wave in birdshot chorioretinopathy: novel observations and the effect of treatment
	AHC Koh, C Pavesio, GE Holder (Los Angeles, CA, USA)
P1.28	Functional and structural assessment of the macula in solar eclipse maculopathy
	KA Kolkailah, OMM Al-Nahrawy, HA El-Koumi (Suez, Egypt)
P1.29	Visual evoked potentials simulation
	J Kremlácek, M Kuba, J Holcík, F Vít (Hradec Králové, Czech Republic)
P1.30	ERG and VEP in 2 siblings with Wolfram syndrome and a homozygous splice site mutation in the WFS1 gene
	B Lorenz, C Gerth, M Bock (Regensburg, Germany)
P1.31	Clinical observation of EOG test in central chorioretinitis
	Y Lu, S Bi, Q Wang, S Tan (Guangdong, China)
P1.32	Does adaptation or room lighting affect the multifocal ERG?
	MF Marmor, AV Chappelow (Stanford, CA, USA)
P1.33	Value of oscillatory potentials in diabetic patients
	W H Massoud (Minia, Egypt)

ELECTROPHYSIOLOGICAL EVALUATION OF EYES OF INSULIN-DEPENDENT DIABETIC PATIENTS WITHOUT RETINOPATHY

MAS Abdel Megeed 

Ophthalmology Department, Alexandria University, Egypt

Purpose: To evaluate different electrophysiological changes in eyes of insulin dependent diabetic patients without retinopathy. Methods: The study was conducted on 74 eyes of 37 patients with insulin dependent diabetes mellitus (IDDM) without diabetic retinopathy. Fifty (50) eyes of 25 normal controls were also examined. All subjects were in the age group 7-29 years. All eyes had best corrected visual acuity of 6/6 , a refractive error < 2.0 D sphere or cylinder, clear media and normal anterior and posterior segments examination with no evidence of diabetic retinopathy. The fasting blood glucose level, and HbA1c in IDDM patients were determined. Electrophysiological examination included: Full field flash electroretinography (ERG) using a standard protocol, electrooculography (EOG) testing with determination of Light peak/Dark trough (Lp/Dt) ratio and pattern electroretinography (PERG) and pattern visual evoked potential (VEP) examination using a black and white checkerboard pattern with 60o check size reversing at 1.9 Hz. Results:  P100 of the VEP showed significant delay in eyes of IDDM patients even in those with IDDM < 5 years (105.21 ± 3.12 msec) when compared to controls (101.85 ± 3.64 msec). There was a significant correlation between P100 implicit time and duration of IDDM. The oscillatory potential amplitudes were significantly reduced in eyes of IDDM patients (266.62 ± 59.61µV) when compared to eyes of the control group (288.45 ± 33.15 µV) especially with duration of IDDM ≥ 10 years. PERG amplitudes were significantly reduced in those with IDDM ≥ 10 years while Lp/Dt of the EOG was reduced in those with IDDM ≥ 15 years (2.04 ± 0.71) when compared to controls (2.49 ± 0.29). Conclusions: Eyes of IDDM patients show significant electrophysiological functional changes even before the appearance of any retinopathy. 

Mashrafs@cns-egypt.com

PATTERN ELECTRORETINOGRAPHY AND VISUAL EVOKED POTENTIAL IN GLAUCOMA

MAS Abdel Megeed

Ophthalmology Department, Alexandria University, Egypt

Purpose: to evaluate the pattern electroretinography (PERG) and pattern visual evoked potential (VEP) changes in glaucoma and ocular hypertension, and to identify the most reliable and sensitive stimulus spatial and temporal characteristics for testing. Methods: The study was conducted on 30 eyes with primary open angle glaucoma, 20 eyes with ocular hypertension and 20 normal control eyes. All subjects were in the age group 40 - 70 years with no history of other significant ocular or systemic diseases. All eyes had best corrected visual acuity ≥ 6/9, a refractive error < 1.0 D sphere or cylinder and clear media.  The cases were subjected to ophthalmological examination and automated perimetry. PERG and VEP were determined using a reversing black and white checkerboard pattern. Three check sizes (15¢, 60¢ and 240¢) and three temporal frequencies (1.9 Hz, 7.5 Hz and 15 Hz) were used. The amplitudes and implicit times were determined at each check size and repetition rate. Results: Eyes with glaucoma showed significant reduction of amplitudes and delay in implicit time at all spatial and temporal frequencies. Eyes with ocular hypertension showed significant changes only with low spatial frequency (240¢ check size) reversing at high temporal frequency stimulation (7.5 Hz and 15 Hz). In eyes with glaucoma, the PERG and VEP amplitudes showed a significant correlation with the mean deviation of automated perimetry. At 100% specificity, PERG and VEP had a sensitivity of 100% in identifying eyes with glaucoma and 45% in identifying eyes with ocular hypertension. Conclusions: PERG and VEP are simple, rapid and objective tests that can reveal abnormalities in eyes with glaucoma and OHT, even in the absence of cupping or visual field defects. The use of low spatial frequency checkerboard patterns reversing at high temporal frequency increases the sensitivity of these tests in identifying eyes with glaucoma and ocular hypertension. 

Mashrafs@cns-egypt.com 

PROGNOSTIC VALUE OF ELECTRORETINOGRAPHY IN CENTRAL RETINAL VEIN OCCLUSION

MAS Abdel Megeed

Ophthalmology Department, Alexandria University, Egypt

Purpose: to evaluate the prognostic value of electroretinography (ERG) in predicting the development of neovascularization (NV) in eyes with central retinal vein occlusion (CRVO). Methods: An ERG protocol was used at patient presentation for 23 eyes with unilateral CRVO and their fellow eyes to define an intensity-response  (I-R) function, scotopic a and b waves implicit times, b/a amplitude ratio, oscillatory potential amplitudes, photopic b wave and 30 Hz flicker implicit times and amplitudes. A Naka-Rushton function was fitted to the I-R data to obtain values for Rmax and logK. Fluorescein angiography was performed within 2 months of presentation. Results: On the basis of fluorescein angiography, 9 eyes (39.1%) were classified into ischemic and 14 eyes (60.9 %) into non-ischemic types. During 9 months follow up, 11 eyes (47.8%) developed NV; 6 (66.7%) in ischemic type and 5 in non-ischemic type (35.7%). Compared to eyes with no-NV, eyes with NV had significantly reduced amplitudes, sensitivity, b/a ratio and significant delays in a wave, b wave and 30 Hz flicker implicit times even in eyes of non-ischemic CRVO that developed NV. Fellow eyes of NV group showed some significant differences from fellow eyes of no-NV group.  Conclusions:  Different ERG parameters obtained early in the course of CRVO can identify eyes at risk of developing neovascularization. 

Mashrafs@cns-egypt.com

SENSITIVITY OF VEPS VERSUS ERGS IN DIAGNOSIS OF MACULAR DISORDERS

OMM Al-Nahrawy

Ophthalmology Dept, Faculty of Medicine, Suez Canal University, Egypt

Objectives: To study how and when the VEPs and the ERG responses become abnormal in a group of macular disorders. Their sensitivity to macular changes and knowledge of these changes could be used in diagnosis of macular diseases if present behind corneal opacity, cataract or vitreous hemorrhage. Methods: Flash and pattern reversal VEPs and ERGs were tested according to ISCEV standard protocol in 15 eyes with macular disorders. These eyes were as follows: 6 eyes with age related macular degeneration, 2 eyes with cone-rod dystrophy, 2 eyes with acute posterior placoid multifocal pigment epitheliopathy (APPMPPE), and 5 eyes with solar foveal burns. Fundus photography and Fluoroscein angiography documented these lesions. Results:  Macular diseases produced disturbances of the waveforms of both flash and pattern VEP responses. Also there were some small latency delays and reductions in amplitude of responses. This was proportionate with the area and depth of maculopathy. Photopic ERG responses were less sensitive to macular pathology than VEP responses. Reduction of amplitudes of a and b-waves and some waveform distortion are the main findings. Conclusion: If Fundus oculi is invisible, like in cases of dense cataract, VEPs are a more sensitive tool than whole field ERG in diagnosis of  macular disorders. This is useful in predicting the post-operative visual outcome. 

onahrawy@yahoo.com

PREOPERATIVE ELECTRORETINOGRAPHY FOR PREDICTING THE VISUAL OUTCOME
OF VITRECTOMY IN PROLIFERATIVE DIABETIC RETINOPATHY
AND PROLIFERATIVE VITREORETINOPATHY

O Badie, A Shoeir

Research Institute of Ophthalmology, Giza, Egypt

Purpose: We aimed to evaluate the prognostic value of electroretinography (ERG) in predicting the visual outcome of vitrectomy in proliferative diabetic retinopathy (PDR) and proliferative vitreoretinopathy (PVR) cases. Methods:Vitrectomy was performed on 30 eyes (of 28 patients), 16 with PVR and 14 with PDR. Only patients without surgical or postoperative complications were included. Preoperative ERG was performed for all patients 24 hours prior to surgery. The correlation of the ERG findings to the postoperative visual acuities were analysed. Results: A positive predictive value was found between the preoperative ERG findings and the postoperative visual outcome in vitrectomy cases; the better the preoperative ERG b wave, the better the postoperative visual acuity was improved in the PDR cases. On the other hand, PVR cases did not strictly obey this finding in all the cases. Conclusion: Preoperative ERG can predict the visual outcome of vitrectomy in PDR and PVR cases. Recordability of the b-wave especially gave the best prediction for viability of the retina. Also a non-recordable ERG response in PVR has a better prognosis than that for PDR.

CHECKUP OF AMPLITUDES AND TIMING OF RESPONSES RECORDED WITH 
A MULTIFOCAL SYSTEM

M Bock, C Gerth, B Lorenz

Department of Pediatric Ophthalmology, Strabismology and Ophthalmogenetics, 
University of Regensburg, Germany

Purpose: To verify both amplitudes and timing of multifocal responses recorded with a VERIS III system. Methods: To be able to record multifocal responses of high reproducibility an electronic circuit was implemented which generates defined electrical pulses after each active m-frame displayed on the VERIS stimulus monitor. Artificial responses were recorded for different recording setups and detector locations on the screen of the stimulus monitor. The results were compared to get more detailed information about amplitudes and timings recorded with multifocal systems. Results: Because of a software problem in the VERIS software versions 3.01 and 3.11 there is an asymmetry between the amplitudes recorded from hexagons on the left and on the right side of the stimulator screen which leads to amplitude changes of the calculated response density values. The biggest difference is found in the most peripheral regions (21% difference if hexagon 27 is related to hexagon 35 and the result of software 3.1 is compared to software  3.3; parameters: 61 stretched hexagon pattern, distance to screen parameter = 30 cm). For standard setups (e.g. 61 hexagons, sample rate 16/frame) the timing of the recorded responses shows minor deviations of a single sample point (0.8ms) at maximum. If combinations of high sampling rates and stimulus patterns with small numbers of hexagons are used (e.g. 32 samples/frame with 7 hexagons), the timing of recordings from different locations of the same hexagon varies up to 3.8 ms. Conclusions: The reason for the asymmetry of the response density values is a pure solid angle calculation problem of earlier software versions. The recorded data is not affected and the error can be corrected by the use of the evaluation routines of VERIS software 3.3. The correction of the timing differences is handled with the internal "scan delay" parameter. For standard recording protocols, there are 16 samples per frame at least. The more hexagons are displayed on the screen, the more effective the scan delay option gets as the area of single hexagons is reduced and the number of different correction locations rises.

markus.bock@klinik.uni-regensburg.de

CALIBRATION OF FLICKER INTENSITY

MC Brown, G Dean, PA Wareing

Clinical Engineering Department, Royal Liverpool University Hospital, UK

Purpose: To improve the method of calibration of 30Hz flicker intensity. Methods: The suggested method of measuring flicker intensity in the ISCEV guidance notes for stimulator calibration is using an integrating photometer over a fixed number of flashes.  It is acknowledged that rapid flashes at 30Hz may produce lower output than for individual flashes because of the recharge/recovery time of the stimulus device.  Also the method proposed is not applicable to all electrodiagnostic systems because the number of flashes cannot be set.  A more simple method is proposed and examined which requires a simpler calibration device showing only continuous output.   In this method the stimulator is set for a particular rate (e.g. 30Hz) and is run for a few seconds and the recording device is a photometer set in its continuous monitoring mode but with time constant long enough to average the light intensity. Results: We demonstrate the results of this method applied to two very commonly used Ganzfeld stimulators to show how the flicker intensity differs from the individual flash intensity at the same settings.  We also demonstrate how this compares with the integrating method as set out in the ISCEV calibration guidance notes. Conclusion: The method proposed appears to be a reliable and simpler method of determining flicker intensity than those currently proposed.  The ratio between flicker and individual flash intensities deviates in some proportion to the nominal individual flash intensities.

MalcolmBrown@btinternet.com

CONGENITAL ABSENCE OF THE CHIASM: DEMONSTRATION OF AN UNCROSSED VISUAL PATHWAY USING MONOCULAR FLASH VISUAL EVOKED POTENTIAL

MC Brown, C Hallet, A Anbarusu, SB Kaye

Clinical Engineering Department, Royal Liverpool University Hospital, UK

Purpose: To demonstrate flash visual evoked potential testing to diagnose absence of the chiasm.  A two year old girl was referred at Alder Hey Children's Hospital, Liverpool with nystagmus associated with head oscillation and poor visual acuity recorded at 6/19 in each eye.  The patient was referred for possible cone dystrophy.  Methods: Flash VEP was employed with two-channel recording between Fz and O1, O2 placed 4 cm each side of Oz.  Results: Responses to flashes with binocular viewing showed symmetrical and normal looking responses over each lobe of the visual cortex.  However when each eye was patched in turn, stimulation of the right eye produced responses similar to the binocular response on the right occipital electrode with a poorly discernable response over the left occipital electrode.  These responses were reversed when the left eye was stimulated.  This is the opposite to the results obtained in preceding patients with similar test conditions with albinism in which the better response was obtained over the contra-lateral hemisphere and an abnormal response from the ipsilateral hemisfield.  We discuss here the  possible explanation that the patient had a reduction in the proportion of fibres decussating at the chiasm compared with the increased decussation in the albino patients. An MRI of our patient subsequently showed the absence of the chiasm. Conclusions: The abnormality of the absence of the chiasm was shown first by the VEP findings.  To our knowledge this is one of only a few cases reported with congenital absence of the chiasm detected in this way.

MalcolmBrown@btinternet.com

EXTRACTION AND MODELLING OF OSCILLATORY POTENTIALS IN HUMAN AND ANIMAL ERG

BV Bui, JA Armitage, AJ Vingrys

Department of Optometry and Vision Sciences, University of Melbourne, Australia

Purpose: To develop a model to describe intensity-response characteristics of the oscillatory potentials (OPs) in human and common laboratory animals. Methods: OP visualisation is hampered by artefacts produced by the a-wave, which can contain a Fourier spectrum that overlaps the OPs themselves. To minimise this, OPs can be extracted using a method suggested by Bui et al. (1998). Such extraction yields waveforms that resonate with Gabor-like characteristics. We fitted these extracted OPs using a Gabor function, which is a convolution of a gaussian envelope with a sine wave carrier. The OP extraction and modelling was performed on electroretinographic responses achieved with a Ganzfeld stimulus (discharge source Vivitar 285) on a cohort of 5 humans and 6 guinea-pigs (English-Shorthair) over a range of 6 log units of light (unattenuated 5.5 log cd-s.m-2 in 0.4 log unit steps) with an interstimulus interval of 180 seconds. Human subjects were dark adapted for forty-five minutes prior to experimentation and data were acquired at 2kHz using the UTAS-2000 (LKC technologies). A jet electrode was used with an amplification of x1000 and bandpass filtering (0.5-3000Hz). Animals were dark adapted overnight and anaesthetised with a standard mix of Ketamine (5mg/kg) and Xlyazine (35mg/kg).  Signals were collected using a Burian-Allen electrode also acquired at 2kHz, amplified x10000 (Grass P55) and bandpass filtered (0.5-3000Hz). Results: Oscillatory potentials were observed across a stimulus range of 2 log units, and show intensity-response characteristics analogous to other ERG components. The extraction paradigm returned timings and amplitudes that closely resembled the raw OPs for both human and guinea pig waveforms. Further evaluation (Q-statistic) suggests that the Gabor model provides an accurate description of both human and guinea pig OPs. In addition, we show that the model can be applied across a range of intensities. Conclusions: Extraction of the b-wave leading edge and modelling the resultant waveform using a Gabor function provided accurate descriptions of OPs. The modelling gave good fits in terms of the Q-statistic. In addition, we show that such a model provides a reliable description of OPs present in both human and animal waveforms across a range of intensities.

Bui BV, Weisinger HS, Sinclair AJ, Vingrys AJ. (1998) Doc Ophthalmol. 95:15-34.

VISUAL FUNCTION IN INTRA-UTERINE GROWTH-RESTRICTED GUINEA-PIGS

BV Bui*, JA Armitage*, J Caddy#, AE Rehn#, SM Rees#, AJ Vingrys*

Departments of Optometry and Vision Science*; Anatomy and Cell Biology#,
University of Melbourne, Australia

Purpose: To evaluate the retinal function (ERG) of spontaneously and surgically induced intra-uterine growth-restricted mammals. Methods: Three spontaneously growth-restricted and three surgically induced growth-restricted guinea-pigs (English-Shorthair) had their ERGs measured at 8 weeks of post-natal age and were compared to a cohort of seven age-matched siblings. The surgical induction was achieved by ligating the intra-uterine artery at 30 days gestation (term 67 days) thus severely restricting uterine arterial supply as described by Rees et al. (1992). Two responses to white flashes (strobe discharge (Vivitar 285) Ganzfeldt) were collected over 7.5 log units of light attenuation with an inter-stimulus interval of 90 sec after prior overnight dark adaptation and anaesthesia (Xylazine 5mg/kg, Ketamine 35mg/kg). Signals (250msec epochs) were recorded using a custom made Burian-Allen bipolar electrode via a Grass amplifier (P55: x10,000, 3dB down, 0.1-10,000 Hz) and digitised at 2kHz. We present data on a-wave, b-wave (peak-to-peak) and oscillatory potential (OP) amplitudes and implicit times. OP amplitudes were extracted (55-200 Hz) and modelled using a Gabor function. One normal animal had ERGs recorded after ON-bipolar cell isolation with APB (2mM at the retina). Results:  One surgically induced growth-restricted guinea-pig showed no post-receptoral response with the resultant waveform (P3) resembling that of the APB isolated animal. The rest of the group showed more subtle deficits. On average, their a-wave amplitudes were normal but implicit times were delayed (1.98 msec, p<0.05). The b-wave amplitudes were normal for both cone and rod mediated functions, but the rod implicit time was significantly (3.93 msec, p<0.05) delayed in the presence of a normal cone timing. OPs showed deficits in both amplitude (51%, p<0.01) and timing (2.72 msec, p<0.05). Conclusion:  We believe that our findings can be interpreted as indicating for subtle photoreceptoral damage that produces the aberrant timing and an inner-retinal deficit produces the OP abnormality.

Ress S, Bainbridge A (1992). Int J Dev Neurosci. 10:93-108.

A COMPARATIVE STUDY OF SERVICES, TECHNIQUES, REFERRAL PATTERNS AND EQUIPMENT IN A REPRESENTATIVE SAMPLE OF VISUAL ELECTROPHYSIOLOGY CENTRES IN AUSTRALASIA

E Chelva, JM Atkinson, JN De Roach, SMS Kay , TL McLaren, RI Price

Department of Medical Technology and Physics, Sir Charles Gairdner Hospital, Perth, Australia

Purpose: To compare tests performed, techniques applied, referral patterns, and types of equipment used, in visual electrophysiology centres throughout Australasia. Methods:. A questionnaire was sent to 24 centres known to us that carried out visual electrophysiology, and results from each section of the questionnaire were then tabulated. Results: Fourteen questionnaires were returned completed. Also, 3 centres indicated that they no longer carried out electrophysiology. Of the 14 responses, 2 centres carried out VERs only, 2 had access to multi-focal techniques only, and the remaining 10 provided a broad range of visual electrophysiological services. These 10 centres typically performed standard ERGs (including flicker ERGs), VEPs and EOGs. Oscillatory potential ERGs were routinely carried out in 7 centres, and transient PERGs in 5 centres. Other tests that were available but rarely requested included focal ERG, steady state PERG, and sweep VEP. Four centres had multi-focal techniques available, but only one used this technique routinely. Approximately two-thirds of responses indicated that retinal dystrophies and unexplained visual loss were the main referral diagnoses. Two outliers were one laboratory with 40% glaucoma patients, and another with 50% drug toxicity assessments. Most centres used gold foil, DTL fibre or skin electrodes for ERG. Four centres used contact lens electrodes, but 2 of these centres performed ERGs predominantly under sedation. HK loop, DTL fibre or gold foil electrodes were all in use for PERG. A total of 13 data collection systems were in operation at the 10 general sites, 8 of which were assigned a level of satisfaction (out of 10) of 7 or better. Two centres rated their equipment as less than 5. Research interests varied greatly, and there was no collaboration noted between any of the respondents. Conclusions: General visual electrophysiology centres around Australasia tend to provide ERGs, flicker ERGs, VEPs and EOGs as standard tests, while approximately half also routinely perform transient PERGs and oscillatory potential ERGs. Tests that are available but seldom requested include sweep VEPs, focal ERGs, steady state PERGs and multi-focal VEPs or ERGs. This study highlights the desirability for the establishment of a special interest group, for the sharing of research interests, equipment experiences, possible new service opportunities (such as retinal toxicity and glaucoma studies), with a view to further improving and strengthening the contribution of diagnosis of eye disease through visual electrophysiology.

Johnd@mtp.pd.uwa.edu.au

PROPOSAL FOR AN INTERNATIONAL NORMATIVE ERG DATABASE USING THE ISCEV STANDARD FOR CLINICAL ELECTRORETINOGRAPHY

SG Coupland

University of Ottawa Eye Institute, Ontario, Canada

Purpose: Over a decade has passed since a basic ERG protocol was standardized so that certain responses could be recorded comparably throughout the world (Marmor et al., 1989).  The ERG standard has since been updated in 1994 and 1999.  Recommendations have been made that commercial recording equipment have the capability to record the standard five ERG responses and numerous commercially available electrodiagnostic systems conform. Unfortunately, there are serious impediments to collecting laboratory normative data.  The practice is both labor intensive, time consuming and expensive. This is especially true when another or different electrodiagnostic system is purchased.  A co-operative multi-center collaboration at normative data collection would have several advantages including reduction in cost, resources and testing time to the participants.  Recently, a new visual electrodiagnostic system, the Espion (Diagnosys LLC) has become available.  The purpose here is to propose the establishment of an international normative ERG database for Espion users conforming to the ISCEV Standard.  Methods: An ERG protocol conforming to the ISCEV Standard for clinical electroretinography (1999 update) will be distributed to those centres having an Espion system and choosing to participate. The software will allow identification and flagging of "normal" subjects to distinguish them from patients and will also implement web access capability to allow the exporting of normative ERG waveforms from individual users to a central user website. Patient anonymity will be maintained, but site identification and additional information including subject's age, gender, race, dilated pupil size and refraction will be included with the ERG waveforms. Once exported to the website the individual waveforms will be visually inspected to maintain quality control. Waveforms will be processed and appropriate summary descriptive statistics for ERG parameters under the standardised ISCEV conditions will be developed.  Results: Normative values will be made available to participants through the user website, which can be downloaded to authorised users and incorporated into their operating system software to automatically flag those parameters that exceed normal limits.. Conclusions: The establishment of a multi-center collaboration at normative data collection in clinical electroretinography using the ISCEV standards would have significant advantages to participants in time saved, resources spent and access to larger sample size. 

scoupland@ogh.on.ca

SERIAL VISUAL ELECTROPHYSIOLOGICAL CORRELATES IN BIRDSHOT RETINOCHOROIDOPATHY

SG Coupland, W Hodge, P Kertes, A Bawazeer

University of Ottawa Eye Institute, Ontario, Canada

Purpose: Birdshot retinochoroidopathy is a rare, chronic posterior uveitis with a distinctive clinical presentation. Visual electrophysiology findings indicate varying degrees of middle, retina, photoreceptor and possible RPE involvement. The ERG may be supernormal in the early stages; however, with disease progression the ERG b-wave diminishes followed by the a-wave until the ERG is completely extinguished. The EOG Arden ratios have also been reported as subnormal in 50 to 75% of patients with Birdshot retinochoroidopathy. Herein we report the serial ERG and EOG findings in two treated patients.  Methods: Two patients (Cases 1 and 2) presented with Birdshot retinochoroidopathy.  The diagnosis of Birdshot retinochoroidopathy was based upon fundoscopic, clinical examination findings along with positive HLA A29 typing.  Both cases were treated with corticosteroids. ERGs were recorded through dilated pupils with DTL fiber electrodes under scotopic (blue) flash, photopic 30 Hz. flicker and white flash conditions, using the Pathfinder II (Nicolet Instruments) visual electrodiagnostic system. EOGs were recorded during 12 minutes of dark and light adaptation according to the ISCEV standard. Results: In Case 1, in both eyes, initially the scotopic ERG b-waves were reduced in amplitude and had delayed implicit time. The photopic flash ERG b-wave was normal in amplitude but delayed in implicit time.  The a-waves were normal with regards to amplitude and implicit timing for both scotopic and photopic flash conditions.  30 Hz flicker trough-to-peak amplitude was reduced.  Follow-up ERG after 5 months steroid therapy were essentially unchanged.  By 10 months, scotopic ERG b-wave amplitudes were borderline normal in amplitude and had normal implicit timing. The photopic flash and 30 Hz flicker had normalized.  There was concomitant improvement in the patient's color vision and symptoms.  In Case 2, initially the ERG was normal but EOG showed reduced Arden ratio in both eyes. Four repeat visual electrodiagnostic studies were performed over the 10 months of steroid therapy.  ERGs remained normal during that time and EOG Arden ratio improved.  There was also concomitant improvement in the patient's color vision and symptoms. Conclusions: Serial ERG and EOG recordings can be valuable in recording the progressive course of this disease as well as in documenting response to drug therapy.

scoupland@ogh.on.ca

VARIATION IN THE LOCATION AND ANGLE OF THE CALCARINE SULCUS 
REFERENCED TO CRANIAL LANDMARKS

NE Epstein, R Silverglide, X Zhang, N Karin, S Kangovi, DC Hood

Dept of Psychology, Columbia University; Long Island Neurosurgical Assoc, New York, NY, USA 

Purpose: To measure the location and angle of the calcarine sulcus relative to the placement of electrodes for multifocal VEP recording. The mVEP responses recorded from control subjects show a wide variation in amplitude and waveform. Some of this variability must be due to the location of the calcarine sulcus relative to the recording electrodes. Methods: Normal MRI scans were obtained from 50 individuals (age: 61.6 +/- 17.2 yrs, range 18 to 87 yrs) as part exams to rule out cranial pathology. An experienced neuroradiologist marked the inion (technically the occipital protuberance) on a midsagittal view and located the calcarine sulcus on paramedian sagittal images. Our bipolar electrodes for multifocal VEP records are placed at the inion and 4 cm above this point. The points on the skin at which these electrodes are placed were marked as I0 and I4 on the saggital view of the calcarine sulcus. A straight line was drawn through the posterior portion of the calcarine sulcus and extended to a point, C, on the margin of the skin. The distance between C and I0 was measured, as was the angle the line made with a vertical line extending between I0 and I4. Both multifocal VEPs and MRI scans were obtained from 6 individuals. Results: Point C fell between 1.9 cm below and 3.5 cm above the inion, I0, (mean=0.95, s.d.=1.17). The angle of the calcarine sulcus relative to the electrode placements varied from 30° to over 70° (mean=53.5°, s.d.=12.3°) and was positively correlated with point C. As point C moved higher, the calcarine became more perpendicular (90°) to the line between I0 and I4. The multifocal VEPs with the most extreme ratios of upper to lower field amplitudes exhibited the most extreme locations of the calcarine sulcus. Conclusions: The location of the calcarine sulcus in reference to the inion varies widely among individuals1. In addition, there is considerable variation in the angle of the calcarine sulcus. These cranio-occipital variations affect the topography of the multifocal VEP. 

1. Steinmetz et al, Electroencephalogr Clin Neurophysiol 1989 72:499-506.

don@psych.columbia.edu

THE ROLE OF FUNCTIONAL TESTING IN DIFFERENTIAL DIAGNOSIS OF CONGENITAL ACHROMATOPSIA

A Farkas, K Wenzel*, R Vamos, J Gyory

2nd Dept. of Ophthalmology, Semmelweis University of Medicine, Budapest;
*Dept. of Precision Mechanics and Optics, Technical University of Budapest, Hungary

Purpose: To characterise different types of congenital achromatopsia through the use of electrophysiological and psychophysical measures. Methods: Clinical, electrophysiological and psychophysical examinations were carried out in three patients with congenital achromatopsia: a 31 year-old male, a 58 year-old female and a 6 year-old boy. The clinical test battery included visual acuity, anterior segment and fundus examination. The electrophysiological test employed was the ERG. The psychophysical tests used were: color vision, dark adaptation, spectral luminosity, visual field and CFF examinations. Results: The clinical examinations demonstrated classical signs of typical congenital achromatopsia, which had been present in all patients since early childhood: poor visual acuity, photoaversion, absent color discrimination, nystagmus and maculopathy. The diagnosis was confirmed by definitely subnormal photopic flash, and extinguished photopic flicker, ERG responses, which indicated severe deterioration in cone function. There was a striking difference between both the dark adaptation curves and spectral luminosity curves of the patients. The male patient (case 1) had a monophasic dark adaptation curve and maximal spectral luminosity at 507 nm. He can thus be considered a complete achromat. The dark adaptation curve of the female patient (case 2), however, was biphasic and her spectral luminosity curve had a maximum at 527 nm, a value between that of the rods and the middle wave sensitive (MWS) cones. These data suggest the presence of other functioning photoreceptors, which exhibit cone-like characteristics, in addition to rods. This case represents a variation of incomplete achromatopsia. The boy's (case 3) dark adaptation curve had a slightly biphasic shape and the peak of his spectral luminosity curve was at 467 nm, which corresponds that of the blue (SWS) cones. This patient appears to be a blue cone monochromat. Conclusion: Due to its typical symptoms, congenital achromatopsia can be suspected on the basis of clinical examinations, but an ERG is essential to confirm the diagnosis. Complete and incomplete forms can be differentiated by a dark adaptation test. Further differentiation of the incomplete form is possible by spectral luminosity measurements. The importance of an early diagnosis will be stressed.     

farkasag@szem2.sote.hu

COMPLEMENTARY VALUE OF FULL FIELD AND MULTIFOCAL ERG RECORDINGS

Inna Goub, JK Grigg, FA Billson

Save Sight Institute, Department of Clinical Ophthalmlogy, University of Sydney

Purpose: To investigate complementary value of fullfield and multifocal ERGs tests in patients with retinal dysfunction. Methods: Fullfield and multifocal ERGs were recorded simultaneously from 193 patients with retinal diseases. Normal reference values for fullfield and multifocal ERGs were previously established for adults aged between 18 and 50 years old. Fullfield ERGs were performed using Ganzfeld flashes using skin electrodes under both scotopic and photopic conditions; 90° of the retina was stimulated. Multifocal ERGs were recorded using the VERIS-3 system using a gold contact lens electrode under photopic conditions. The central 50° of the retina was stimulated. Results: Four major groups of patients were revealed:
1	The patients with abnormal fullfield ERG and abnormal multifocal ERG,
2	The patients with normal fullfield ERG and abnormal multifocal ERG,
3	The patients with flat fullfield ERG and remaining macular responses in multifocal ERGs,
4	The patient with abnormal, but still recordable, fullfield ERG and flat multifocal ERGs.
Conclusions: Fullfield ERGs and multifocal ERGs performed simultaneously in most patients with retinal dysfunctions demonstrate diagnostic importance in clinical practice and allows close monitoring in advanced cases of the diseases.

inna@eye.usyd.ed.au

EVIDENCE FOR EOG ABNORMALITIES IN PATIENTS WITH PIGMENT DISPERSION SYNDROME AND PIGMENTARY GLAUCOMA

VC Greenstein, W Seiple, R Ritch

New York University School of Medicine, Department of Ophthalmology, New York, NY, USA

Purpose: Pigment dispersion syndrome (PDS) and pigmentary glaucoma (PG) are characterized by disruption of the iris pigment epithelium, deposition of the dispersed pigment granules throughout the anterior segment and an increased incidence of lattice degeneration of the retina. The pigment epithelium of the anterior and posterior segments of the eye have a common embryological origin and it has been suggested that the retinal pigment epithelium (RPE) is also involved in PDS1,2. The purpose of this study was to test the hypothesis that the integrity of the retinal pigment epithelial (RPE)/photoreceptor complex is affected in patients with PDS or PG. Methods: The integrity of the RPE was assessed with electro-oculography. Electro-oculograms (EOGs) were recorded from patients with the following diagnoses: PDS, PG, primary open-angle glaucoma (POAG), and ocular hypertension (OHT). Pupils were dilated and eyes were pre-adapted to room light levels of 60 lux for 20 minutes. EOG values were then recorded during 15 minutes of dark adaptation followed by 15 minutes of light adaptation (2700 cd/m2). For each subject, dark-trough amplitudes, dark-trough latencies, light-peak amplitudes, light-peak latencies and ratios of the light-peak amplitude to dark-trough amplitude (Arden ratios) were calculated. Results: One-way analysis of variance of the Arden ratios indicated significant differences among the groups, p<0.001. A post-hoc Newman-Keuls test revealed that the mean Arden ratios of the PDS group and the PG group were significantly lower than the mean Arden ratios of the control group, the POAG and the OHT group. Conclusion: The decreased ratios suggest that the integrity of the RPE/photoreceptor complex is affected in PDS and PG
. 
1. Cardillo, Piccolino, Calabria et al. (1989) Graefe's Arch. Clin. Exp. Ophthalmol. 2. Scuderi, Ricci, Nucci et al. (1998) Ophthalmic Res. 

vcg1@is3.nyu.edu

VISUAL EVOKED POTENTIALS IN EPILEPSY PATIENTS ON CARBAMAZEPINE (FINLEPSIN)

AB Guekht, AA Shpak

Russian State Medical University, Moscow, Russia

Purpose: The goal of this study was to evaluate the role of visual evoked potentials (VEP) in prognosis of Carbamazepine (Finlepsin) efficacy in epilepsy patients. Methods: Transient VEPs were elicited by checkerboard pattern of 30' checks reversing 1 once per second. Monocular stimulation was performed. The active electrodes were located at Oz, O1 and O2. VEPs were registered in 35 newly diagnosed patients (age range 25-52 years) with symptomatic localization-related epilepsy and 25 healthy controls. Patients were studied before and 1, 3 and 6 months after the initiation of treatment with Finlepsin. Results: Twenty-five patients were successfully treated with Finlepsin: 18 were without seizures and in 7 patients the frequency of seizures reduced significantly. The other 10 patients had almost no changes in the frequency of seizures on therapeutic doses. Before treatment VEPs had normal latency, and their most characteristic features were increased mean amplitude of P200, and after-discharge (in 57% of patients). Patients on Finlepsin demonstrated prolonged (by 25-30 ms) latency of main VEP peaks as compared to initial data and controls. At the same time the dynamics of amplitudes of VEP peaks was different in patients with different efficacy of Finlepsin. In successfully treated patients the mean P100 amplitude tended to decrease, with this change occurring in several cases even before the control of seizures was obtained. At the same time, in some drug-resistant patients the amplitude of most peaks, especially that of P100, increased slightly or significantly in spite of treatment. The mechanisms and clinical relevance of VEP peaks amplitude changes in epilepsy patients need further investigation, though results of this study suggest the prognostic significance of these changes early in the course of antiepileptic treatment. Conclusions: Increased amplitude of P200 and after-discharge was found in patients with epilepsy. The latency of principal VEP peaks increased in all epilepsy patients treated with Carbamazepine (Finlepsin). Decrease of P100 amplitude could be an early prognostic sign of the efficacy of the drug. Assessment of pattern-reversal VEP could be useful in the examination of epilepsy patients.

1575.g23@g23.relcom.ru

THE FUNCTIONAL EVALUATION OF RETINAL VASCULAR OCCLUSION WITH THE ERG

SZ Huang, L-Z Wu, TQ Luo, D-Z Wu

Zhongshan Ophthalmic Center, Guangzhou, China

Purpose: To evaluate the functional change of retinal vascular occlusion with electroretinogram, 30 cases (31 eyes) of central retinal vein occlusion (CRVO), 15 cases (15 eyes) of branch retinal vein occlusion (BRVO), 7 cases (7 eyes) of central retinal artery occlusion (CRAO) and 6 cases (6 eyes) of branch retinal artery occlusion (BRAO), were tested with ganzfeld electroretinogram. Method: The scotopic ERG was evaluated with I1 blue light and I16 white light stimulation. The photopic ERG was tested with I16 red light and I8 white light stimulation (ISCEV ERG standard). The amplitudes and latencies of a waves and b waves were measured. Results: ERG abnormalities were most obvious in CRVO, followed by CRAO and BRVO. The rate of ERG abnormalities was the lowest in BRAO. The comparison between the affected eyes and the fellow eyes with normal visual acuity showed that statistically significant amplitude differences in SI1B b, SI16W a, SI16W b, PI8W a and PI8W b in CRVO, SI1B b and PI8W b in BRVO and all stimulation conditions except the SI16W a and SI16W b for CRAO and BRAO. The comparison between the affected and normal fellow eyes showed statistically significant difference of latencies in all of the stimulation conditions for CRVO and BRVO, and all of the stimulation conditions except the PI16R a, PI16R b and PI8W a for CRAO and BRAO. Conclusion: The fact that b waves were more affected suggests that retinal vascular occlusion produces more severe abnormal function in middle retinal layers than in outer retina layers.

shizhouh@163.net

S-CONE TOPOGRAPHY IN NORMALS AND BLUE-CONE MONOCHROMATS

H Jägle, JF Albrecht, HA Baseler, M Seeliger, LT Sharpe

Dept. of Pathophysiology of Vision & Neuro-Ophthalmology, University Eye Clinic, 
Tübingen, Germany

Purpose: To develop a standard procedure for measuring short-wavelength sensitive (S-) cone topography in normals and clinical patients. Methods: Subjects were four normals, two S-cone monochromats and a rod monochromat. Their multifocal ERGs (mERGS, VERIS) were measured with a DTL fiber electrode, using black/white or colored stimuli generated on CRT monitors and LCD displays.  The stimuli were 61- or 103-element arrays of hexagonal cells, subtendeding 58° x 50° of visual angle. The monitors and displays were spectrally and photometrically calibrated. To selectively stimulate S-cones, a silent substitution method was combined with adjustable constant adaptation fields. Selective pigment bleaching techniques designed to reduce the long-wavelength sensitive (L-) and mid-wavelength sensitive (M-)-cone responses as well as the rod responses were also employed. Additionally, an SLO based system (RETIscan driving a HRA Heidelberg SLO) with a blue laser (488nm) was used to record S-cone mERGs. To reduce L- and M-cone and rod contributions to the signal, between each m-sequence, a bright yellow light (572nm; 6100cd/m2) was used to bleach c. 60% of the L- and M-cone and 99% of the rod pigment. Results were analyzed by averaging data in iso-eccentric rings or over the entire array. We also applied a time-varying filter to remove noise from the signals. Results: The topography of S-cone ERG responses could be revealed for the normals and S-cone monochromats using either a combination of cone-substitution and chromatic field adaptation or using the SLO based system combined with a pigment bleaching procedure. The delay of the b-wave peak of the S-cone response was related to the effective cone contrast as well as the adaptation-state.  Depending on the contrast and intensity conditions, it was 50-60 ms with the SLO system and 50-80 ms with the CRT or LCD displays. Conclusions: For S-cone isolating stimuli presented on standard color monitors, S-cone responses have a very low amplitude.  They are clearly identified only by using additional chromatic adapting fields selected to reduce the L- and M-cone as well as the rod contribution to the signals. The 488 nm laser of the SLO provides a much better signal.  However, because it also stimulates the L- and M-cones, it must be used in conjunction with a pigment bleaching procedure. The SLO system also has the disadvantage of a very slow frame rate. To routinely obtain robust S-cone signals, very bright cone-isolating stimuli combined with an adaptation field are required.

herbert.jaegle@uni-tuebingen.de

SEPARATION OF USH SYNDROME I AND II BY ERG IMPLICIT TIME

GB Jaissle, MW Seeliger

University Eye Hospital, Tübingen, Germany

Purpose: To describe ERG implicit time differences between Usher syndrome (USH) patients, and to propose a new clinical test for the electrophysiological separation of USH I and II. Methods: Standard ERG and a 33 Hz photopic microflicker were obtained from each of 15 controls, USH I, USH II, and RP patients. In selected patients, multifocal ERGs (MF-ERGs) were also recorded using the Tuebingen standard conditions. The 33 Hz flicker waveforms consistently showed 3 peaks, whose implicit times were determined separately. For testing, a score S was calculated as the sum of the three peak implicit time values of each subject. The sensitivity, specificity, and receiver operating characteristic (ROC) of the proposed test were calculated. Results: The MF-ERG revealed a lack of implicit time delay in USH I patients that is typical for RP. Verification of this finding in standard ERG data was difficult because the signals were often too small. Thus, the 33 Hz microflicker, the response that is preserved longest, was evaluated. Although the 33 Hz flicker showed some variability in shape, three peaks were more or less clearly discernible in all subjects. Peak implicit times of the USH I patients were similar to normal, whereas the implicit times of the USH II patients were similar to those of the RP group. The overlap between normal/USH I and RP/USH II was minimal, and the respective group differences highly significant. We calculated a sum score S for each subject to reduce variability in the determination of peak times. The ROC curve for a test between USH I and II based on the score S yielded a sensitivity and specificity of about 95% with a cutoff of 73 ms. Conclusions: In contrast to RP and USH II, implicit time delay is low or absent in USH syndrome type I despite substantial amplitude reduction. This difference can be used diagnostically to separate USH I and II with a high degree of sensitivity and specificity. One might speculate that USH I progresses so that there are only functional or non-functional cones, but no "suffering" cones to produce the delay.
Supported by the DFG (SFB 430, project C2) and fortuene grant 517.

see@uni-tuebingen.de

ELECTRO-OCULOGRAPHY AND PATTERN ERG IN THE DIAGNOSIS OF BEST'S DISEASE

M Jarc-Vidmar, P Popovic, J Brecelj, M Hawlina

University Eye Clinic and University Institute for Clinical Neurophysiology, Ljubljana, Slovenia

Objectives: It is still an unresolved question whether the primary site of the lesions in patients with Best's disease is at the level of the retinal pigment epithelium or in the neurosensory retina. The aim of the study was to assess the function of inner retinal layers in patients with different stages of Best's disease using pattern ERG, as there is increasing evidence that pattern ERG is abnormal in defined forms of macular degenerations. Methods: ISCEV standard electrooculography, photopic and scotopic ERG, pattern ERG and VEP were recorded in 12 patients (24 eyes) with different stages of Best's disease. Results were compared to visual acuity and visual fields measured with kinetic and static perimetry. Results: In 14 eyes with initial stages of the disease (visual acuity better than 0.6) PERG responses were normal despite clinically evident macular changes, whereas in eyes with advanced forms of the disease (visual acuity less than 0.6) there were reduced PERG responses in 6 eyes. Full field photopic and scotopic ERGs on the other hand were normal in all the patients. Visual field measured with static perimetry showed small central scotoma and pathologic values of MD and CLV already in patients with good visual acuity and still normal PERG responses. Conclusions: It seems that the primary site of lesion in patients with Best's disease lies at the level of RPE, with the neurosensory retina being affected secondarily. Besides electrooculography, static perimetry is a very sensitive indicator of initial stages of Best's disease where other electrophysiological tests (PERG and ERG) are still in the normal range.

ACQUIRED NON-VASCULAR UNILATERAL INNER RETINAL DYSFUNCTION

S Kaushal, AH Koh, CR Hogg, GE Holder

Moorfields Eye Hospital, London, UK

Purpose: To describe the clinical features in seven patients with unilateral negative ERG in whom a vascular aetiology has been excluded. Methods: Retrospective review. 128 of 2640 ERGs showed a negative waveform. Seven of these patients had a unilateral negative ERG, with exclusion of a vascular aetiology. Electrophysiological examination incorporated routine ganzfeld ERGs and pattern ERGs supplemented in six patients by examination of ON- and OFF- responses using extended duration stimuli. Some patients also underwent further investigation such as fundus fluorescein angiography or fundus autofluorescence imaging. Results: All seven patients had markedly abnormal cone derived ERGs. In the six cases where ON- and OFF- response examination was performed the OFF- response was relatively or completely spared, suggesting principle involvement of the depolarising bipolar cell pathway. Inflammatory disease was suggested on history and/or examination in five patients. Biochemical and immunological investigation failed to reveal a definite cause in any patient. Conclusions:  Non-vascular unilateral negative ERG is rare. One previous report has described acquired unilateral night blindness with selective involvement of the ON- bipolar cells (Fishman et al, Ophthalmology, 1996; 103: 96). Our patients, when specifically questioned, reported difficulty with night vision, but in no case was this the presenting symptom. The term "acquired unilateral inner retinal dysfunction" is proposed as a clinical description. 

graham.holder@moorfields.nthames.nhs.uk

MULTIFOCAL VEPS IN NORMAL TENSION GLAUCOMA

I Kimura, H Ohde, T Tanino, K Ohtake, Y Betsuin, K Kita, Y Mashima, Y Oguchi, D Hood

Keio University School of Medicine, Tokyo, Japan

Purpose: To examine the visual field of normal tension glaucoma (NTG) patients objectively, multifocal VEPs were recorded and compared with the results of Humphrey Visual Field Analyzer. Method: 15 NTG patients were tested. The dartboard stimulus was used for recording with the VERIS Scientific System (Electro-Diagnostic Imaging, San Francisco, CA). Each of the 60 segments contains a black and white checkerboard pattern, which is alternated according to a binary m-sequence. Bipolar occipital-straddle electrode positions were used. The visual field up to 25°of eccentricity was investigated.  The 1st slices of 2nd order kernels of responses were calculated. One eye's responses were subtracted from those of the fellow eye, and the same procedure was followed with the data of the Humphrey Field Analyzer. Result: The multifocal VEPs corresponded well with Humphrey visual field defects, showing reduced amplitude in the scotoma area in 10 cases. There were 5 cases in which VERIS responses did not correspond with Humphrey visual field defect. In these cases, the conditions of fixation were poor in 2 cases. One was a case in which an operation for rhegmatogenous retinal detachment was performed. The causes of discrepancy in the remaining cases were not clear.  Conclusion: These results show the possibility of practical objective detection of visual field defects in NTG using multifocal VEPs.

kimura@mc.med.keio.ac.jp

A CASE OF CONGENITAL STATIONARY NIGHT BLINDNESS (CSNB)
WITH PREVIOUSLY UNDESCRIBED ERGS: A NEW ENTITY?

K Kita, Y Shirao, K Kawasaki

Department of Ophthalmology, Kanazawa University School of Medicine, Japan

Purpose: To report an unusual case of CSNB. Methods: A 25-year-old man who had noticed night blindness from early childhood on, underwent ophthalmological examination including Goldmann perimetry, color vision test, dark adaptometry, routine full-field rod and cone ERGs and an ERG intensity series from the scotopic threshold response (STR). Results: He presented with normal visual acuity and mild myopia (-1.0D). Ophthalmoscopic fundi, visual field and color vision appeared normal. Dark adaptometry revealed a normal time course and a depth for the rod-cone break and prolonged time course to the normal rod threshold. The conventional full-field ERGs showed extremely attenuated rod-ERG, normal cone-ERG and normal flicker-ERG. The cone-rod mixed single-bright-flash ERG (maximal response) showed the negative configuration typical of conventional CSNB. ERG intensity series showed a normal threshold and a normal peak time for the STR but markedly higher (1.7 log unit) threshold for the scotopic b-wave compared to our controls. Conclusions: These results suggest that the present case does not fall in any conventional categories of CSNB.

OBJECTIVE PERIMETRY IN GLAUCOMA

A Klistorner, SL Graham

Save Sight Institute, Department of Ophthalmology, Sydney University, Australia

Purpose: Objective perimetry in glaucoma has been described using the multi-focal pattern visual evoked potential (VEP).  A multi-channel recording technique was utilised to improve signal detection in normals and assess its ability to detect glaucoma and early changes in suspects. Method: 35 normals, 32 patients with glaucomatous visual field defects and 30 glaucoma suspects were tested. The VEP was recorded using cortically scaled multi-focal pseudo-randomly alternated pattern stimuli with the VERIS system. An array of four bipolar occipital electrodes provided four differently oriented channels for simultaneous recording. Signals were compared for different locations within the field up to 26° of eccentricity. Normals, glaucoma suspects and glaucoma patients with established visual field defects were tested and results compared to Humphrey visual fields performed on the same day. To assess reproducibility five normals were each tested on four separate days. In addition, one glaucoma patient was tested 3 times over a two-year period. Data from glaucoma suspects were analysed for inter-eye asymmetry and compared to the asymmetry values of normals. Results: Multiple recording channels significantly enhanced the recording of signals from parts of the visual field not reliably sampled with a single channel technique in all normal subjects, particularly along the horizontal meridian (p<0.001). Signal amplitude did not decline with age in normals. Recordings showed good reproducibility within individuals.  In all 32 cases of glaucoma the Humphrey visual field defects were well demonstrated by the VEP and topographic location was correlated strongly (r=0.72). Despite large inter-individual variations in amplitude, scotomas were well demonstrated when compared to normal values. In the glaucoma suspects, smaller changes in signal amplitude could be identified in parts of the field still normal on perimetry, using inter-eye asymmetry analysis. Conclusions: The multi-focal multi-channel VEP can objectively detect glaucomatous visual field defects. The nasal step region can be more reliably tested using multiple channels. Asymmetry analysis has the potential to detect early defects. This technique represents a significant step towards the clinical application of objective perimetry in glaucoma. 

sasha@eye.usyd.edu.au

SUPERNORMAL ERG A-WAVE IN BIRDSHOT CHORIORETINOPATHY:
NOVEL OBSERVATIONS AND THE EFFECT OF TREATMENT

AHC Koh, C Pavesio, GE Holder

Moorfields Eye Hospital, London, England; Jules Stein Eye Institute, UCLA, Los Angeles, CA, USA

Purpose: To describe a case of birdshot chorioretinopathy with novel electroretinogram (ERG) findings. Methods: Serial ERGs (ISCEV standard) were obtained from a patient with birdshot chorioretinopathy. The first examination was performed prior to the onset of visual symptoms but at a stage when the fundus appearance was abnormal. Subsequent testing charted the progress of disease and the response to systemic corticosteroid treatment. Results: At first examination, ERGs from both eyes showed an electronegative waveform. Vision subsequently deteriorated and the a-wave in one eye became profoundly supernormal with an amplitude of almost 1000µV accompanied by no detectable b-wave. Following treatment, ERGs from both eyes improved. In one eye the ERGs became normal; in the other, although there was improvement, the profoundly supernormal a- wave remained. Treatment was therefore continued for a further six months after which the ERG in the second eye had also returned almost to normal. Conclusions:  This case report not only describes novel and remarkable ERG findings, but also illustrates the potential for the ERG to become an integral part of the overall management of patients with birdshot chorioretinopathy.

ahckoh@yahoo.com

FUNCTIONAL AND STRUCTURAL ASSESSMENT OF THE MACULA IN 
SOLAR ECLIPSE MACULOPATHY

KA Kolkailah *, OMM Al-Nahrawy *, HA El- Koumi *

*Ophthalmlogy Department, Suez Canal University; 
# Ophthalmology Department, Tanta University, Egypt

Objectives: The entire world witnessed the solar eclipse during August 1999. Warnings throughout the media against hazards of exposure to sun radiations were intense. The aim of this work is to study structural and functional damage in eyes with solar maculopathy.  Methods:  We recorded solar maculopathy in six eyes of three subjects. Macular structure of eyes involved was assessed using fundus photography and fluoroscein angiography. Laser measurements of the thickness of the macula were done using optical coherence tomography (OCT). Functional assessment was done using photopic and flicker ERG, flash and pattern reversal VEP and analysis of the central five and ten degrees of the visual field. Results: Photography revealed burns localized to the fovea of all eyes.  Intensity of these burns differed. Fluoroscein fundus angiography was unremarkable.  Macular visual field revealed central and paracentral points with reduction of sensitivity of five to six dB. VEP responses were within normal and similar in both eyes. ERG (ISCEV protocol) responses were within normal limits and similar in four eyes of two subjects. In the third subject, there was a significant difference between cone responses of the eyes, whereas the rod responses of the eyes were mirror images. OCT revealed macular thickening up to 300 microns in both eyes. Conclusion: Solar radiation can produce functional as well as structural damage for the macula. OCT and macular field were able to show structural and functional damage and were superior to fluoroscein angiography, full-field ERG and VEP.

onahrawy@yahoo.com

VISUAL EVOKED POTENTIALS SIMULATION

J Kremlácek, M Kuba, J Holcík, F Vít

Charles University Faculty of Medicine, Hradec Králové, Czech Republic

Purpose:  We present an attempt to model an electrophysiological response to motion-onset and pattern reversal visual stimuli. Methods:  On the basis of decomposition of the specified visual evoked potentials (VEPs) into three independent components (Kremlácek J, Kuba M, Physiol. Res., 303-308, 1999) a three stage model was developed. The model consisted of serially connected non-linear second order damped oscillators of identical construction. The first oscillator was driven by the firing density of the lateral geniculate nuclei (Watson A, Nachmias J, Vision Res., 893-902, 1977). The model parameters were tuned for a particular stimulus by the Nelder-Mead simplex algorithm (Lagarias JC et. al., SIAM Jour. Optim. 112-147, 1997). Results:  The difference between the simulated signals and the VEPs (assessed by normalised root mean square error) was less than 12.9%, while an expected amount of noise in the VEPs reached at least 13.2% (counted as ± average: Schimmel H, Science, 92-93, 1967). The switch from motion-onset to pattern-reversal generation was caused by doubling of the first two oscillator frequencies (from 7 and 4 Hz for motion to 15 and 7 Hz for reversal). The third oscillator, following slow changes in the VEPs, was dependent on the antecedent ones and it was tuned to 3 Hz or 1 Hz for motion and reversal respectively. The first oscillator contributed mainly to the pattern-reversal VEPs, while in the motion-onset the second one dominated. Three oscillators were activated at 29, 72 and 155 ms on average. Conclusions: The proposed model seems to be a good approximation to a macroscopic electrophysiological manifestation of brain processing of the visual stimuli used. Separate oscillators, corresponding to the described parameters, reflect sequential activation of the primary (striate), secondary (extrastriate) and higher (cognitive) mechanisms.
Acknowledgement: Supported by the Grant Agency of the Charles University, Czech Republic and by the James S. McDonnell Foundation for Cognitive Neuroscience, USA.

jan.kremlacek@lfhk.cuni.cz

ERG AND VEP IN 2 SIBLINGS WITH WOLFRAM SYNDROME 
AND A HOMOZYGOUS SPLICE SITE MUTATION IN THE WFS1 GENE

B Lorenz, C Gerth, M Bock

Department of Pediatric Ophthalmology, Strabismology and Ophthalmogenetics,
University of Regensburg, Germany

Purpose: To describe the ocular phenotype of a homozygous splice site mutation in the recently identified nuclear WFS1 gene (460, G-A, +1, Strom et al., Hum Molec Genet 1998) associated with Wolfram syndrome (DIDMOAD). Methods: The patients: a boy aged 17 yrs (TH) and his sister aged 19 yrs (TZ) from a consanguinous marriage, were examined clinically as well as by Ganzfeld ERG, MERG (first and second order kernel: FOK and SOK), flash VEP and pattern VEP. Results: In both patients, VA was severely reduced. Visual fields showed significant peripheral constriction with relative central scotomas. The lenses had spokelike opacities with otherwise normal anterior segments. There was temporal pallor of the optic disc, but also some RPE irregularity in the macula with otherwise normal retinae. Ganzfeld ERGs (ISCEV standard) were normal. The amplitudes of the FOK of the MERG were reduced and the latencies prolonged in the center only. Central changes in the SOK were also observed. Pattern VEP could be elicited in the boy only with prolonged latencies and reduced amplitudes. Flash VEP in the sister revealed reproducible responses on both sides. Conclusion: In contrast to a recent report on 45 patients with Wolfram syndome (Barrett et al., Eye 1997) both patients showed macular changes associated with circumscribed changes in the multifocal ERG which may indicate a retinal origin of the optic atrophy which is one of the features of Wolfram syndrome.

birgit.lorenz@klinik.uni-regensburg.de

CLINICAL OBSERVATION OF EOG TEST IN CENTRAL CHORIORETINITIS

Y Lu, S Bi, Q Wang, S Tan

Ophthalmic Centre, Zhangjiabian Hospital, Zhongshan Guangdong, China

Objective: To conduct the EOG test on 82 eyes in 73 cases of central chorioretinitis and observe the EOG changes before and after treatment. Methods: The 73 cases, in which patients are aged between 30 and 50 years, are divided into two groups according to the time in which symptoms are shown. 45 eyes in 45 cases are classified into the first group. Patients in this group have shown symptoms for 3 to 15 days. EOG test discovers: Dark trough potential (DTP) increases in all cases with a notable increase in 10 cases; Light peak potential (LPP) rise in 10 cases, remains normal in 25 cases and falls in other 10 cases; Arden ratio drops in 30 cases and remains normal in the remaining 15 cases.  37 eyes in 28 cases belong to the second group. Patients in this group have shown symptoms for 30 to 45 days. EOG test shows: All eyes suffer notable drop in both DTP and LPP; even the fellow eye of the patients in five cases suffers a drop of different degree in the above-mentioned items; only six cases indicate a decrease in Arden ratio while others show abnormal values. Results:  EOG test after 30 days of medication shows the following: In the first group, 18 cases, of the total return to normal with patients' eyesight improving to 1.0 and symptoms having disappeared; 27 cases witness improvement with eyesight ranging between 0.6 and 0.8 and vision distortion having eased. In the second group, improvements of different degree have been seen in the patients with Arden ratio remaining within the normal range and eyesight getting better.  Conclusion:   In EOG test of early central chorioretinitis patients, DTP shows a marked increase and Arden ration shows a marked increase and Arden ration shows abnormality. DTP and LPP also indicate a noticeable drop while Arden ratio may remain normal. Patients usually present after symptoms have shown for quite period of time. EOG test can provide objective indices which can be used in patients' clinical treatment and rehabilitation.

DOES ADAPTATION OR ROOM LIGHTING AFFECT THE MULTIFOCAL ERG?

MF Marmor, AV Chappelow

Stanford University Department of Ophthalmology, Stanford, CA, USA

Purpose:  To evaluate the effects of pre-adaptation, room-illumination, and background screen luminance on the multifocal ERG (MERG).  Methods:  MERGs were recorded with a VERIS System using EDI Scientific software.  Recordings were made using Burian-Allen electrodes, and 61 or 103 hexagon stimulus arrays with a mean luminance of 100 cd/m2.  Normal volunteers (n=22, average age 32) had sequential MERGs recorded under different conditions of lighting and adaptation.  Results:  Changing pre-adaptation conditions between darkness for 20 min, or light at 27 cd/m2 for 10 min, had essentially no effect on the MERG, regardless of ambient room lighting.  There was also no difference between MERG results with a background screen luminance (i.e., surrounding the stimulus) of 50 or 100 cd/m2.  However, the MERG was quite sensitive to the level of room illumination.  A-wave and b-wave amplitudes were maximal in very dim lighting (≤ -1.25 log cd/m2) and fell by roughly 25% when the room luminance was raised above 0.5 log cd/m2.  The b-wave time-to-peak also diminished with increasing illumination.  These effects were observed in both central and peripheral regions of the macula.  Conclusions:  The MERG is largely independent of pre-adaptation conditions and background screen luminance, but waveform amplitudes and time-to-peak diminish with increasing levels of room illumination.  We suggest that average room illumination be ≤ -1.25 log cd/m2 to maximize MERG response amplitude and minimize variability.  

marmor@stanford.edu

VALUE OF OSCILLATORY POTENTIALS IN DIABETIC PATIENTS

W H Massoud

Ophthalmic Department, Minia Univerity, Minia, Egypt

Objectives: To determine if oscillatory potentials (OPs) can play a role in detection of diabetic retinopathy, before detection by fluoroscein injection or other clinical methods. Methods: We used the UTAS system in two ways: first we measured the flash ERG with the low cut filter of the amplifiers set to 75Hz, and then the flash ERG with the low cut filter set normally and the software filtering system used to extract the OPs. Forty diabetic patients attending ophthalmic and medical outpatient clinics of the University Hospital were selected to represent our sample; they had the following criteria:
17 male, 23 female patients
Ages ranged from 23- 69 years
Duration of diabetes diagnosis ranged from a few months to more than 10 years
20 patients (40 eyes) had no fundus changes; neither ophthalmoscopically nor by fluorescein angiography.
20 patients (37) eyes) had different stages of retinopathy either ophthalmoscopically (by fundus examination) or by fluorescein angiography Results:  In the group with no fundus changes, OP values were significantly lower than control values, ranging from 50-61 µV compared to the minimum normal value of 75 µv. In the group with fundus changes, OPs were absent in more than 50% of patients, while in the other 50% values were too low to be compared with the control group or with the first group. Conclusion: OPs proved to be a useful diagnostic tool for early detection of cellular retinal hypoxic insult in diabetic retinopathy.

Monday 14 February

08:00 - 08.30	Opening Ceremony:	Gabrielle Hollows	Fred Hollows Foundation
		Yozo Miyake		President of ISCEV

08.30 – 10.30	Scientific Session 1	EXPANDING DIAGNOSTIC METHODOLOGY (1)
	Chairs:	Vaegan;  Masayuki Horiguchi

10.30-15.00	Coffee Break

11.00 – 13.00	Scientific Session 2	THE MULTIFOCAL TECHNIQUE AND APPLICATIONS
	Chairs:  	Lehzeng Wu;  Don Hood

13.00–14.00	Lunch Break
Sign up for:	Multifocal Guidelines, lunch discussion

14.00 – 16.00	Posters Session 1	with coffee
	Chairs	Michael Bach;  Patrizia Tormene

16.00 – 18.00	Scientific Session 3	VISUAL EVOKED POTENTIALS
	Chairs:  	J Vernon Odom;  Ivan Bodis-Wollner

Evening:	Harbour Cruise and free evening in Sydney
Sign up for:	VEP Standard, discussion supper

16.00 – 18.00	Monday 14 February

Scientific Session 3	VISUAL EVOKED POTENTIALS
Chairs:  	J Vernon Odom;  Ivan Bodis-Wollner

16.00	Objective VEP perimetry in glaucoma: asymmetry analysis to identify early deficits
	SL Graham, AI Klistorner, JR Grigg, FA Billson (Sydney, Australia)
16.15	Relationship of morphological and electrophysiological changes in primate eyes with laser-induced glaucoma
	AM Komaromy, DE Brooks, ME Kallberg, WW Dawson, MB Sherwood, GN Lambrou (Gainesville, FL, USA)
16.30	Impact of traumatic brain injury on visual processing in the retino-cortical pathways
	M McKerral, J Lachapelle, F Champoux, P Lachapelle (Montréal, Québec, Canada)
16.45	Correlation of electrophysiological and clinical features of albinism
	JJ Sloper, S Dorey, M Neveu, L Burton, G Holder (London, UK)
17.00	Do P100 and N100 evoked by ERP task reflect primary visual processing in Parkinson's disease?
	L Wang, Y Kuroiwa, T Kamitani, M Li, J Wang (Yokohama; Okazaki, Japan)
17.15	Motion-VEPs and VEPs associated with motion-based texture segregation differ in contrast characteristics
	M Bach, C Schmitt (Freiburg, Germany)
17.30	Temporal and adaptation effects in the multifocal visual evoked potential
	C Barber, Y Wen, V Merigoux (Nottingham, England)
17.45	A comparison of multifocal VEPs to field defects due to optic nerve damage
	DC Hood, X Zhang, JG Odel, D Miele, VC Greenstein (New York, NY, USA)

OBJECTIVE VEP PERIMETRY IN GLAUCOMA:
ASYMMETRY ANALYSIS TO IDENTIFY EARLY DEFICITS

SL Graham, AI Klistorner, JR Grigg, FA Billson

Save Sight Institute, Department of Ophthalmology, Sydney University, Australia

Purpose:  The multifocal visual evoked potential (VEP) shows markedly symmetrical responses between the two eyes of normal subjects. Patients with glaucoma and high-risk suspects were examined to determine if VEP asymmetry could be identified in these cases and used for diagnosis and detection of early damage. Methods: Multifocal pattern VEP recordings were performed using a single channel bipolar occipital electrode position and the VERIS system. There were 125 subjects including 24 normals, 70 glaucomas and 31 high-risk suspects. A between-eye relative asymmetry coefficient (RAC) was determined for each of the sixty test points in the VEP field. Glaucomas and suspects were compared with normal values. Correlation between Humphrey thresholds and RAC scores was performed. Results:  Both the suspects and glaucomas showed significantly larger mean quadrant RAC values. When point by point analysis was performed, 69/70 scotomas were identified with a cluster of at least 3 points of p<0.05 probability. In the suspects, 10/31 cases had abnormal areas in the VEP field. There was a strong correlation (r=0.82) between quadrantic RAC mean values and Humphrey quadrant threshold scores in an asymmetric glaucoma subgroup. Abnormal VEP responses were identified in parts of the visual field that were still normal on perimetry. Conclusions: Asymmetry analysis correctly identifies patients with glaucomatous field loss and shows abnormalities in many high risk suspects with still normal fields. It is able to objectively identify the extent of glaucomatous damage and may be able to detect changes before subjective field loss occurs.

stuart@eye.usyd.edu.au

RELATIONSHIP BETWEEN MORPHOLOGICAL AND ELECTROPHYSIOLOGICAL CHANGES IN PRIMATE EYES WITH LASER-INDUCED GLAUCOMA

AM Komaromy, DE Brooks, ME Kallberg, WW Dawson, MB Sherwood, GN Lambrou

University of Florida, Dept. of Small Animal Clinical Sciences, Gainesville, USA

Purpose: To describe morphological and functional changes of the optic nerve head (ONH) in rhesus macaques (Macaca mulatta) with laser-induced glaucoma (LIG) during the first 4 months of intraocular pressure (IOP) elevation. Methods: Elevated IOP was induced in the right eye of 9 male monkeys (age; mean ± standard deviation: 62 ± 14 months) using argon laser photocoagulation of the trabecular meshwork. Examinations utilizing confocal scanning laser tomography (Heidelberg Retina Tomograph, HRT) of the ONH and recording of pattern evoked retinal and cortical potentials were performed during the 1st month (9 monkeys; IOP: 33 ± 9 mmHg) and 4th month (seven monkeys; IOP: 40 ± 10 mmHg) after IOP elevation (IOP about 25 mmHg). A grating pattern of alternating light and dark, vertically oriented bars was projected onto the macula by a stimulating ophthalmoscope (temporal frequency: 6 Hz; contrast: 82%). The pattern image was 30 degrees in overall diameter, and consisted of 8 different grating sizes (0.04 –5 cpd). Mean luminances used for projection were 300 cd/m2 (bright field) and 0.82 cd/m2 (dark field). 175 responses were averaged and RMS amplitudes calculated for each spatial frequency. The contralateral eyes served as normal references. All parameters were logarithmically transformed and compared between baseline measurements and either 1-month or 4-month measurements using the t-test and the Wilcoxon matched pairs signed rank test. Changes in pattern EPs and HRT parameters were compared by correlation analysis. Results: Heidelberg Retina Tomograph determined ONH topographic alterations were detected during the 1st and more dramatically during the 4th month of IOP elevation and included: larger cup and cup/disc ratio; decreased disc area, rim area and volume, height variation contour, cup shape measure, and retinal nerve fiber layer thickness (p<0.05). Significant decreases in bright field cortical pattern evoked potentials occurred after 1 month (0.08 and 0.15 cpd; p<0.05) and 4 months (0.08, 0.15, and 0.6cpd; p<0.05) while dark field retinal pattern evoked potentials were decreased after 4 months (0.04, 0.08, and 0.3 cpd; p<0.05). Significant correlations were found between pattern EPs and multiple HRT parameters (p<0.05). Conclusions: Morphological changes preceded decreased pattern evoked cortical and retinal potentials in LIG. Decreases in pattern EPs occurred predominantly for larger grating sizes. The functional and morphological changes of the ONH were significantly correlated.

komaromya@mail.vetmed.ufl.edu

IMPACT OF TRAUMATIC BRAIN INJURY ON VISUAL PROCESSING 
IN THE RETINO-CORTICAL PATHWAYS

M McKerral, J Lachapelle, F Champoux, P Lachapelle

Programme d'Intégration dans la Communauté, Centre de Réadaptation Lucie-Bruneau; 
Department of Ophthalmology, Montréal Children's Hospital, Montréal, Québec, Canada

Purpose:  Traumatic brain injury (TBI), which is one of the major causes of brain damage in humans, frequently produces deficits in visual function.  50% - 60% of individuals with mild to moderate TBI show some sort of long-term impairment in visual function (binocular dysfunction, blurred vision, ocular motility problems, visuo-perceptual deficits).  However, because of the dynamics of TBI (forces of acceleration, deceleration and rotation that cause microscopic damage to brain tissue at neuronal and axonal levels), many visual symptoms associated with this condition cannot be explained with traditional neuro-ophthalmic methods or with neuro-imaging data.  Since such deficits can have important impacts on the rehabilitation and socio-professional reintegration processes of TBI individuals, it is important to develop techniques which permit adequate description of these problems, to identify the best treatment possible.  Methods: Visual evoked potentials (VEP) and motor reaction times (RT) were used to determine markers that better characterise the nature of visual deficits in TBI.  They were obtained simultaneously to reversal and random movement of a black/white checkerboard screen (check sizes: 0.12°, 0.5° and 3° of visual angle; contrast: 93% and 3%) from individuals with TBI who were 12-36 months post-trauma at testing, and from normals.  All subjects received a complete ophthalmological examination and no visual anomaly was identified with traditional diagnostic methods.  Results:  VEP amplitude for reversal and motion is reduced in TBI subjects compared to normals.  In some subjects VEP latency shows a dissociation between the two parallel visual systems, with the motion-VEP lengthened, but not the reversal-VEP, suggesting intact visual acuity and form vision, but altered motion vision. The RT is slower than normals for both reversal and movement stimuli in most TBI subjects, but not always in the presence of a longer VEP latency. This discrepancy suggests intact primary visual analysis, but increased cognitive processing time in some subjects, and overall deficits in others.  Conclusions:  Altered VEP and/or RT measurements in TBI subjects correlate well with subjective complaints and specific difficulties in tasks implicating vision or visuo-perception. More refined techniques, such as the VEP and RT, represent specific and reproducible means to identify dysfunctions in cerebral processing in the acquired brain injury.

mmckerral@videotron.ca

CORRELATION OF ELECTROPHYSIOLOGICAL AND CLINICAL FEATURES OF ALBINISM

JJ Sloper, S Dorey, M Neveu, L Burton, G Holder

Moorfields Eye Hospital, London, UK

Purpose: To study the relationship of the latency and amplitude asymmetries of the pattern appearance VEP to the clinical features of albinism. Methods: Pattern appearance VEP examinations using a 1.1 98% contrast check and a posteriorly situated chain of electrodes have been performed in 40 patients referred with a probable or possible clinical diagnosis of albinism. Results: There was a strong correlation between the degree of latency asymmetry of the C1 component of the pattern appearance VEP and the number of clinical signs of albinism. The closest correlation with an individual feature was with foveal hypoplasia, with strong correlations also with iris transillumination, nystagmus and reduced acuity and stereoacuity. Some patients with mild ocular pigmentary abnormalities showed small, but significant latency asymmetries, sometimes only to stimulation of one eye. Conclusions: Latency asymmetry of the pattern appearance VEP strongly correlates with the clinical signs of albinism.

john.sloper@dial.pipex.com

DO P100 AND N100 EVOKED BY ERP TASK REFLECT PRIMARY VISUAL PROCESSING
IN PARKINSON'S DISEASE?

L Wang1, Y Kuroiwa2, T Kamitani2, M Li2, J Wang2

1Department of Integrative Physiology, National Institute for Physiological Science, Okazaki; 2Department of Neurology, Yokohama City University School of Medicine, Japan

Purpose: To evaluate whether P100 and N100 evoked by ERP tasks could properly reflect primary visual processing in Parkinson's disease (PD) or not. Methods: 13 PD patients with duration of illness less than 5 years and 18 age-matched normal control subjects participated in the study. P100 and N100 from Oz were evoked by a visual oddball and a delayed matching S1-S2 task. P100 and N100 differences between the patient group and the control group were compared. All patients were given an ECD-SPECT examination. In order to investigate relatively accurate blood flow in each cerebral cortex, SPECT results were overlaid on the 3D-MRI. The correlation of P100 or N100 to the blood flow of the occipital, parietal, temporal, and frontal lobe were studied. Results: N100 latency during the oddball task in patients was significantly shorter than that in the normal control group. (P100-N100) amplitude during the oddball task in PD patients was significantly attenuated compared with that in the normal control group. N100 amplitude during the oddball task in PD was significantly correlated with the blood flow in the left occipital lobe. P100 latency during the S1-S2 task in PD was significantly correlated with the blood flow of bilateral occipital and the right parietal lobe. N100 latency during the S1-S2 task was significantly correlated with the blood flow of the right parietal and the temporal lobe. Conclusions: Shortened N100 in the PD group might be due to the medication effect of levodopa. The correlation between P100 latency and occipital lobe in PD suggests that P100 might reflect the primary visual processing whereas N100 might be involved in both primary and cognitive processing. 

lihong@nips.ac.jp

MOTION-VEPS AND VEPS ASSOCIATED WITH MOTION-BASED TEXTURE SEGREGATION
DIFFER IN THEIR CONTRAST CHARACTERISTIC

M Bach, C Schmitt

Univ.-Augenklinik Freiburg, Germany

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.	

bach@uni-freiburg.de

TEMPORAL AND ADAPTATION EFFECTS IN THE MULTIFOCAL VISUAL EVOKED POTENTIAL

C Barber, Y Wen, V Merigoux

Queen's Medical Centre, Nottingham, England

Purpose: To investigate the pattern adaptation properties of the pattern onset visual evoked potential (VEP) in multiple small, relatively homogenous, areas of the visual field 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 than 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 observable 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 processes occurring early in the visual pathways.

Colin.Barber@nottingham.ac.uk

A COMPARISON OF MULTIFOCAL VISUAL EVOKED POTENTIALS TO FIELD DEFECTS
DUE TO OPTIC NERVE DAMAGE

DC Hood, X Zhang, JG Odel, D Miele, VC Greenstein

Department of Psychology; Department of Ophthalmology, Columbia University,
New York, NY, USA

Purpose: Visual field defects can be localized with the multifocal visual evoked potential (mVEP) technique.1,2 In fact, if the set of mVEP responses obtained from monocular stimulation of both eyes are compared, then local monocular damage to the ganglion cells or optic nerve can be quantified3. Here we make a quantitative comparison between defects identified with Humphrey visual fields and changes in mVEP responses recorded from patients with optic nerve damage secondary to glaucoma, ischemic optic neuropathy (ION), or optic neuritis (ON). Methods: Monocular mVEPs were recorded for both eyes of 17 patients [7 glaucoma (4 NT, 3 OAG); 5 ION, and 5 ON] and 15 control subjects. The patients exhibited significantly more damage in one eye as measured with Humphrey 24-2 fields. Electrodes were placed at the inion, 4 cm above the inion, and the forehead (ground). Sixty mVEP responses were obtained to sectors of a scaled checkerboard pattern1. The amplitude of each response was obtained using a root mean square measure. For each of the 60 pairs of monocular responses, the ratio between the response amplitudes from the two eyes was determined. For each location, a z-score for this ratio was obtained by comparing it to the distribution of control values. Latency was measured based upon the leading edge of "P100". Estimates of visual field changes in the 60 sectors of the mVEP array were extrapolated from Humphrey 24-2 fields. Results: For all disease states (and all patients), the relative amplitude of the responses from the more affected eye was reduced, in many cases in regions with relatively small field losses (< 4 dB). Responses from the patients with optic neuritis showed the largest increases in implicit time, in some cases in regions without identifiable field defects. For individual responses in some patients, the mVEP appeared to detect defects not seen in the visual field. For other responses (typically with low signal to noise), the mVEP did not show a defect while the field did. Conclusions: The disease states studied here all produce localizable changes in mVEP amplitude. It is possible to make a quantitative comparison of these changes to visual field defects. From these, it is clear that the relationship between these measures will depend upon the disease and whether amplitude or latency is measured.
1. Baseler et al (1998) Electro Cl Neurophysiol 2. Klistorner et al, (1998) IOVS. 3. Hood et al (under review)

don@psych.columbia.edu

Tuesday 15 February

Sign up for:	PERG Standard, discussion breakfast

08.00 – 10.00	Scientific Session 4	ELECTRO-OCULOGRAM & ELECTRORETINOGRAM
	Chairs:	Richard Weleber;  Ann Fulton

10.00-10.30	Coffee break

10.30 – 12.30	Membership Meeting

Afternoon	Visit to Kurring-gai National Park,
	with aboriginal dance demonstration and guide to rock-carved drawings.
	And the specially Antipodean ISCEV Olympics.

Evening	A choice of two options:
Action choice – travel back from Kurring-gai directly to Bronte Surf Club for informal barbecue, salad supper, beach sports, life-saving demonstration,
and bar with drinks at club prices.
Relaxation choice – travel back from Kurring-gai to St John's College; make
your own way to the nearby Newtown district and enjoy its amazing array
of ethnic restaurants.

08.00 – 10.00	Tuesday 15 February

Scientific Session 4	ELECTRO-OCULOGRAM & ELECTRORETINOGRAM
Chairs:		Richard Weleber;  Ann Fulton

08.00	Alcohol and the EOG: clinical implications
	GB Arden, JE Wolf (London, UK) 
08.15	Maximal ERG response in retinitis pigmentosa due to distinct rhodopsin mutations: 
physio-pathogenetic and prognostic implications
	A Iannaccone (Memphis, TN, USA)
08.30	On the mechanism of a picrotoxin effect on the ERG
	RL Chappell, E Schuette, R Anton, H Ripps (Woods Hole, MA; New York, NY; Chicago, IL, USA) 
08.45	The focal macular ERG: a new approach to the study of the Stiles-Crawford effect
	CS Matsumoto, K Nakatsuka, M Imaizumi, M Furushima (Oita, Japan)
09.00	Choriocapillaris atrophy in late-onset chorioretinal dystrophy
	U Kellner, H Kraus, MH Foerster (Berlin, Germany)
09.15	Assessment of retinal ischaemia in central retinal vein occlusion
	BJ Lunt, DM Sharp, JI Sissingh (Auckland, New Zealand)
0930	Progressive rod/cone ganzfeld abnormalities in the hereditary central retinal degenerations
	'Zermatt' macular dystrophy and Lalattia Leventinese
	G Niemeyer, F Munier, B Piguet (Zürich; Lausanne, Switzerland)
09.45	Macular ERG and OCT before and after vitrectomy in diabetic macular edema
	Y Miyake, H Terasaki, T Kojima, T Suzuki, K Hori (Nagoya, Japan)

ALCOHOL AND THE EOG: CLINICAL IMPLICATIONS

GB Arden, JE Wolf

City University, London, 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.  

g.arden@city.ac.uk

MAXIMAL ERG RESPONSE IN RETINITIS PIGMENTOSA DUE TO DISTINCT RHODOPSIN MUTATIONS: PHYSIOPATHOGENETIC AND PROGNOSTIC IMPLICATIONS

A Iannaccone

Retinal Degeneration Research Center, Department of Ophthalmology, University of Tennessee, Memphis, TN, USA

Purpose: To report the ERG findings in two families affected with autosomal dominant retinitis pigmentosa (adRP) due to two distinct missense rhodopsin mutations (G188R and R135W). Methods: Two adRP pedigree were investigated. Maximal ERG responses were recorded according to ISCEV standards in 13 subjects, and longitudinal measurements were obtained in three. Response characteristics and their relationship to the age of the patients were analyzed. Results: In patients with the R135W mutation, maximal ERG responses were measurable in the youngest patients, but signals became undetectable after the age of 18. A 50% yearly reduction rate of the residual ERG response was seen in two young subjects. ERG b-wave amplitudes varied linearly as a function of age. The phenotype associated with the G188R mutation was very different. In the first decade of life, patients with the G188R mutation were asymptomatic, although maximal ERG responses were reduced to 50-60% of normal. Also, a splitting of the b-wave was apparent. The second peak was suppressed by a light bleach, while the first was unaffected, indicating that the first peak (b1) was exclusively mediated by cone activity, whereas the second peak (b2) was rod-driven in origin. ERG signs of residual rod activity in G188R patients were lost in the third decade, and maximal ERG responses were reduced to 2% of normal by age 60. Good central retinal function was retained by most patients at all ages. A 25% yearly reduction rate of the residual ERG response was appreciated in one subject from this pedigree. When plotted as a function of age, ERG b-wave amplitudes were fitted by an exponential decay function. Conclusions: Patients with adRP caused by G188R mutations are born with a virtually intact complement of functioning cones, retain sizable yet impaired rod function and remain asymptomatic at least until the first decade of life. Patients with the R135W mutation show only ERG evidence of residual cone activity, severely compromised within the first decade of life. The kinetics of the disease appear to be different in the two phenotypes, suggesting differences in the pathophysiologic mechanisms underlying the disease. Rate of progression appears to be twice as fast for the G188R form of adRP. These observations have significant prognostic and therapeutic implications and emphasize the role that ERGs can play in elucidating genotype-phenotype correlations in patients with retinal degenerations.

iannacca@mail.eye.utmem.edu

ON THE MECHANISM OF A PICROTOXIN EFFECT ON THE ERG

RL Chappell*#, E Schuette*#, R Anton*#^, H Ripps*^

*Marine Biological Laboratory, Woods Hole, MA; #Hunter College and Graduate School, CUNY, NY; ^University of Illinois at Chicago College of Medicine, Chicago, IL;
Hunter College, Dept. of Biological Sciences, NY, USA

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: 50μM 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 (100μM) 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.

rchappell@gc.cuny.edu

THE FOCAL MACULAR ERG: 
A NEW APPROACH TO THE STUDY OF THE STILES-CRAWFORD EFFECT

CS Matsumoto, K Nakatsuka, M Imaizumi, M Furushima

Department of Ophthalmology, Oita Medical University, Japan

Purpose: The Stiles-Crawford effect of the first kind (SCE) is often invoked by psychophysical tests and reflects the directional sensitivity of cones to light stimulus. The SCE has been studied in many macular diseases, but its implications for the electroretinogram (ERG) are poorly studied. Methods: A spot photostimulator device (Folia Ophthalmol Jpn, 1999), modified to change the projection angle of the spotlight stimuli, was used to record focal macular ERGs under direct fundus observation in two normal volunteers. Results: The stimulus irradiated vertically to the macula, showed the highest focal ERG amplitudes. However, a- and b-waves of the focal ERGs decreased in amplitude when the spotlight was irradiated far from the vertical angle of the macula using white and red stimulus. This effect was not so evident under short wavelength (green and blue) light stimuli. Conclusion:  Our results suggest that directional sensitivity of the cones (SCE) can be detected objectively by using focal macular ERG recorded by white or long wavelength light stimulus. The focal macular ERGs approach to the SCE may be useful in the study of macular function.

celso@oita-med.ac.jp

CHORIOCAPILLARIS ATROPHY IN LATE-ONSET CHORIORETINAL DYSTROPHY

U Kellner, H Kraus, MH Foerster

Dept. of Ophthalmology, UKBF, Free University, Berlin, Germany

Purpose: Except for choroideremia, gyrate atrophy and central areolar choroidal dystrophy disorders with predominant involvement of the choriocapillaris are ill defined. The purpose of the current study was to evaluate the retinal function in chorioretinal dystrophies with patchy choriocapillaris atrophy as a predominant morphological sign. Methods: A database including 796 consecutive patients with photographic fundus documentation and electrophysiologic evaluation was screened for patients with patchy choriocapillaris atrophy. Patients with disorders as mentioned above were not included. Fourteen unrelated patients (7 females, 7 males) could be included. Electrophysiologic examination consisted of full-field ERG (ISCEV standard, 14/14), EOG (ISCEV standard, 3/14) and multifocal ERG (VERIS, 6/14). Results: The mean age was 58 years (49-76 years) at first examination. Patches of choriocapillaris atrophy with fuzzy borders were present either at the posterior pole or in the mid-periphery. Visual acuity ranged between 20/20 and 5/200 depending on foveal involvement. Visual field defects were in accordance to the visible atrophic changes. Color vision (Panel D15) was moderately to severely disturbed. Full-field ERGs showed moderately to severely reduced responses; however, in some cases the dark-adapted, in other cases the light adapted responses were predominantely reduced. Three cases presented with a'negative' type ERG. Multifocal ERG responses were similarily reduced. EOGs showed a reduced or missing light rise. Conclusions: The group of patients who present with non-classical choriocapillaris atrophy as a predominant morphological sign have in common a late onset chorioretinal dystrophy. Otherwise, the functional findings in this group were heterogenous. Thus these patients do not constitute a single well-defined disease entity.

kellneru@zedat.fu-berlin.de

ASSESSMENT OF RETINAL ISCHAEMIA IN CENTRAL RETINAL VEIN OCCLUSION

BJ Lunt, DM Sharp, JI Sissingh

Vision Assessment Clinic, Auckland Hospital, New Zealand

Purpose: Central retinal vein occlusion (CRVO) is a common retinal disorder with iris neovascularisation as a frequent complication. Neovascularisation arises in response to hypoxia in the ischemic form of the disease. The common method for differentiating between ischaemic and non-ischaemic CRVO has been fundus fluoroscein angiography (FFA). This involves subjective evaluation of capillary perfusion from fundus images and is limited by retinal haemorrhages and lens opacities. Larsson et al identified flicker latency greater than 37 ms and Morrell et al identified inter-ocular difference greater than 5 ms of high predictive significance for ischaemia. Both authors reported a significant difference between prognosis based on FFA and ERG. A study was undertaken at our facility to determine whether prognostic differences between electrodiagnostic evaluation using B-wave latency of a 30 Hz flicker ERG and FFA were of the same magnitude as reported. Methods: Assessment of 60 normal patients established the normal ranges to validate comparisons with published data. Flicker ERG results of 50 patients with CRVO were assessed against these criteria and compared with their FFA findings. Results: 28 patients were identified with ischaemic CRVO using both flicker latency and inter-ocular difference criteria. On reviewing the FFA reports of these patients, 14 were reported as ischaemic, 9 non-ischaemic and 5 undetermined. Conclusions: B-wave latency of a 30 Hz flicker improves the sensitivity of diagnosing ischaemic CRVO over FFA alone.

akvision @ahsl.co.nz

PROGRESSIVE ROD/CONE GANZFELD ABNORMALITIES IN THE HEREDITARY CENTRAL RETINAL DEGENERATIONS 'ZERMATT' MACULAR DYSTROPHY AND MALATTIA LEVENTINESE

G Niemeyer, F Munier*, B Piguet*

Department of Ophthalmology, University Hospital Zürich;
*Hôpital Jules Gonin, University of Luasanne, Switzerland

Purpose: Dominant 'Zermatt' macular dystrophy (ZMD) and Malattia Leventinese (ML; dominantly inherited drusen) share centrifugal expansion beginning frequently in the fourth to fifth decade of life. Does the Ganzfeld ERG show functional changes in these conditions? Methods: Ganzfeld rod-/cone-ERGs, including ISCEV standard stimuli, were recorded in 10 patients with advanced ML and in 8 patients presenting with late stages of ZMD. Results: Very late stages in ML much like advanced stages (III and IV) in ZMD share progressive central scotomas with relatively well-maintained peripheral vision. Early changes in ML with drusen at the posterior pole, metamorphopsia and reduced visual acuity reveal minor changes in the cone ERG (A. Scarpatetti, S. Forni, and G. Niemeyer. Klin Monatsbl Augenheilkd 172:590-597, 1978; G. Niemeyer. Doc Ophthalmol Proc Ser 17:337-344, 1978) ZMD has been described clinically in association with an Arg-172-Trp mutation (B.Piguet et al, Ophthalmic genetics 17:175-186,1996), developing expanding geographic-degenerative changes in the central retina. Primarily the cone single flash- and 30Hz-ERGs indicated functional loss in both diseases in advanced stages, whereas subtle changes in amplitude and implicit time were recorded in early stages. The selective rod-ERGs revealed subnormal to markedly reduced b-wave amplitudes in advanced ZMD, but less notable changes in ML. Conclusion: In general the changes in Ganzfeld ERG parameters paralleled the extent of the ophthalmoscopic changes as well as the visual field defects in both macular dystrophies. The generally larger expansion of the retinal lesion in ZMD is reflected in comparatively more dramatic reductions in the ERG.
Supported in part by the Swiss Foundation to Prevent Blindness and by a fund from H.Messerli

niemeyer@opht.unizh.ch

MACULAR ERG AND OCT BEFORE AND AFTER VITRECTOMY IN DIABETIC MACULAR EDEMA

Y Miyake, H Terasaki, T Kojima, T Suzuki, K Hori

Department of Ophthalmology, Nagoya University School of Medicine, Japan

Background: It has been reported that diabetic macular edema can be resolved by vitrectomy including detachment of the posterior hyaloid membrane from the macular surface. However there is no report comparing the focal macular ERG (MERG) and ocular coherence tomography (OCT) before and after surgery in diabetic macular edema. Methods: We evaluated MERG and OCT in 19 eyes of 14 patients with diabetic macular edema before and after vitrectomy. The follow-up period after surgery was 2 to 15 months (mean 8 months). Results:  The fovea showed thinning in 14 of 19 eyes, there was no change in one eye and there was greater thickening in four eyes after vitrectomy. Of the 16 eyes examined using MERG, only three eyes improved significantly. Ten eyes showed no change, and three eyes worsened. The three eyes with worse MERG performance also showed worse visual acuity. The eyes with improved MERG also showed better visual acuity. Conclusion: Although many eyes with diabetic macular edema showed morphological improvement after vitrectomy, only a limited number of eyes showed improved MERG. The functional recovery, particularly as evaluated with MERG, may not occur or may be delayed.

ymiyake@med.nagoya-u.ac.jp

Tuesday 15 February

Sign up for:	PERG Standard, discussion breakfast

08.00 – 10.00	Scientific Session 4	ELECTRO-OCULOGRAM & ELECTRORETINOGRAM
	Chairs:	Richard Weleber;  Ann Fulton

10.00-10.30	Coffee break

10.30 – 12.30	Membership Meeting

Afternoon	Visit to Kurring-gai National Park,
	with aboriginal dance demonstration and guide to rock-carved drawings.
	And the especially Antipodean ISCEV Olympics.

Evening	A choice of two options:
Action choice – travel back from Kurring-gai directly to Bronte Surf Club for informal barbecue, salad supper, beach sports, life-saving demonstration,
and bar with drinks at club prices.
Relaxation choice – travel back from Kurring-gai to St John's College; make
your own way to the nearby Newtown district and enjoy its amazing array
of ethnic restaurants.

MEMBERSHIP MEETING AGENDA

1.	Opening by the President
2.	Minutes of the 1999 Membership Meeting
3.	Report of the Secretary-General for 1999
4.	Report of the Treasurer for 1999
5.	Report of the Editor for 1999
6.	Proposals to change the Bye-laws  (see following pages)
7.	Elections
	7.1 	for Vice-president: (Asia/Australia)	position vacated by Miyake (Not eligible for re-election)
	7.2 	for Vice-president: (Europe/Africa)	position vacated by Galloway (Not eligible for re-election)
	7.3 	for Secretary, Europe & Africa:	position vacated by Barber (Not eligible for re-election)
	7.4	for Members-at-Large:	position vacated by Bach (Eligible for re-election)
			position vacated by Spekreijse (Not eligible for re-election)
8.	Future Symposia
	8.1	Reminder about 2001
	8.2	Dates and Topics for 2002
8.3	Location for 2003
8.4	Location for 2004
9.	Standards
9.1	Adoption of revised PERG Standard
9.2	Review of VEP Standard
9.3	Multifocal Guidelines
10.	Report of this year's Symposium Organisers
11.	Any other items arising from the Board Meeting
12.	Any other business (previously notified to Secretary-General)
13.	Close of the meeting

PROPOSALS TO CHANGE THE BYE-LAWS

1.	Proposal to define the number of Members-at-Large on the Board of Officers
This proposal specifies the number of Members-at-Large, and introduces some regional constraint.

Proposer:  W W Dawson	Seconder:  C Barber		
The proposal is as follows:
Article VI: Officers
Section 1
Delete:	the phrase: "Members-at-Large".
Add:	the phrase: "six Members-at-Large, at least one from each of ISCEV's three geographical areas"

1A.	Rider to Proposal 1: Implementation
The position of Board Member-at-Large exists to provide experience of working on and with the Board to members who may wish to serve ISCEV as executive Officers. The aim of this proposal is to ensure a steady supply of such experienced members, and with a reasonably uniform geographical distribution. However, if the proposal were enacted immediately, it would cause problems with phasing: too many Board Members-at-Large would change at the same time, which would be contrary to the spirit of the proposal. It is therefore suggested that, taking into account the existing number of Members-at-Large, and their expiry dates, one additional Member-at-Large be elected in 2001, and another in 2003. 

Proposer:  W W Dawson	Seconder:  C Barber					The rider is as follows:
Election of additional Board Members-at-Large:
Each of the existing four positions of Member-at-Large shall be refilled upon completion of the current terms of office and, in addition, a new Member-at-Large shall be elected in 2001, and another in 2003.

2.	Proposal to change the status of the position of Secretary-General
This proposal changes the status of Secretary-General from an elected to an appointed Officer of the Board.

Proposer:  M Marmor & Y Miyake	Seconder:  C Barber			
The proposal is as follows:
Article VI: Officers
Section 1
Add:	the title "Secretary-General" to the list of officers.
Delete:	the phrase "(one of the three Secretaries will be Secretary-General)".
Add the following new Sections: 	
Section 2
The Officers of the Board shall be elected as specified in Article XII, except for the Secretary-General, who shall be appointed as specified in Section 3, below. 
Section 3
A President-elect shall nominate one or more candidates for Secretary-General during the period between election and taking up office, informing the Board of Officers at least three months prior to its regular annual meeting. The Board shall appoint a Secretary-General from among the candidates nominated by the President-elect and the decision shall be ratified by a majority vote of the membership (either in attendance at the next regular meeting or by mail).
Renumber the existing Section 2 as Section 4 and add the phrase: ", except the Secretary-General,"
Add the following new Section:
Section 5
The term of office of the Secretary-General shall be linked to that of each newly-elected President.  It shall commence one year after the beginning of the Presidential term, and extend one year beyond the Presidential term.  In the event that a Presidential term is shortened, the term of the Secretary-General will be shortened as well, so that the office ends one year after the next newly-President takes office.

Wednesday 16 February

08.30 – 10.30	Scientific Session 5	AUTO-IMMUNE AND INFLAMMATORY RESPONSES 
	Chairs:	Yozo Miyake;  John Heckenlively

10.30-11.00	Coffee Break

11.00 – 13.00	Scientific Session 6	EXPANDING DIAGNOSTIC METHODOLOGY (2)
	Chairs:	Emiko Adachi;  Ido Perlman

13.00-14.00	Lunch Break

14.00 – 16.00	Posters Session 2	with coffee
	Chairs	Graham Holder;  Ulrich Kellner

16.00 – 17.45	Scientific Session 7	PAEDIATRIC VISUAL ELECTROPHYSIOLOGY
	Chairs:	Colin Barber;  Dianne Sharp

19.30 for 20.00	Symposium Dinner in the Holmes Building of Sydney University
	Including presentation of the Dodt Award by Professor Eberhart Zrenner
	And presentation of the ISCEV Olympics Trophy by Professor Colin Barber 

08.30 – 10.30	Wednesday 16 February

Scientific Session 5	AUTO-IMMUNE AND INFLAMMATORY RESPONSES 
Chairs:		Yozo Miyake;  John Heckenlively

08.30	INVITED LECTURE:  Electrophysiological diagnosis of acute and inflammatory diseases
	P Beaumont, Vaegan (Sydney, Australia)
09.00	Electrophysiological features of melanoma associated retinopathy (MAR)
	GE Holder (London, UK)
09.15	Melanoma associated retinopathy (MAR) may start as a unilateral disease
	H Wildberger, A Milam, G Niemeyer  (Zürich Switzerland; Philadelphia, PA, USA) 
09.30	Clinical and ERG features of hereditary pigmented paravenous chorioretinal atrophy (PPCRA)
	S Jalali, PSR Reddy (Hyderabad, India)
09.45	Retinal function in mitochondrial diseases without retinitis pigmentosa
	C Macaluso, E Spaggiari, N Bresolin, P Nicolini, M Camparini (Parma, Italy)
10.00	S-cone electroretinogram in multiple evanescent white dot syndrome
	S Yamamoto, M Hayashi, S Takeuchi (Sakura, Japan)
10.15	Transient increased latency in PERG and bipolar on-off responses with DMXAA, a new anticancer drug
	MB Jameson, DM Sharp, JI Sissingh, CR Hogg (Auckland, New Zealand)

ELECTROPHYSIOLOGICAL DIAGNOSIS OF ACUTE AND INFLAMMATORY DISEASES

P Beaumont, Vaegan

The Eye & Vision Research Institute, Sydney, Australia

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.

vaegan@unsw.edu.au

ELECTROPHYSIOLOGICAL FEATURES OF MELANOMA ASSOCIATED RETINOPATHY (MAR)

GE Holder

Moorfields Eye Hospital, London, UK

Purpose: Further to characterise the electrophysiological features of melanoma associated retinopathy (MAR). Methods: Standard ERG recording was performed in six patients with melanoma associated retinopathy (MAR). All had a history of cutaneous malignant melanoma and had subsequently developed visual symptoms, particularly marked in reduced lighting conditions. "Shimmering" of vision was a common symptom. Four patients had examination of photopic ON- and OFF- responses using long duration stimuli. Central retinal function was assessed by PERG in five patients, and by colour contrast sensitivity (CCS) measurement in two patients. Results: All six patients had markedly "negative" ERGs with bright white stimulation. There were consistent but relatively subtle photopic ERG abnormalities in all patients, with a broadening of the photopic a-wave and a sharply rising b-wave. In the four cases where ON- and OFF- response examination was performed there was a negative ON- response but sparing of the OFF- response, consistent with selective involvement of the depolarising cone bipolar cell pathway. PERG was markedly abnormal in 5/5 patients with reduction in the P50 component. CCS showed marked threshold elevation in the tritan axis with relative sparing in protan and deutan axes. Conclusions:  Previous full-field ERG findings of a negative maximal response are confirmed by this series, the largest to date. The two previous case reports of ON- and OFF- responses (Alexander et al., IOVS 1992; 33: 477; Kellner et al., BJO; 79; 746) are confirmed. These data are consistent with ON- bipolar cell dysfunction in both rod and cone systems. The PERG data confirm marked central retinal dysfunction even though no ophthalmoscopic macular abnormality was present, and extend the observations in the 2 patients of Kim et al. (Ophthalmology, 1994; 101: 1837).

graham.holder@moorfields.nthames.nhs.uk

MELANOMA ASSOCIATED RETINOPATHY (MAR) MAY START AS A UNILATERAL DISEASE

H Wildberger*, A Milam#, G Niemeyer*

*University Eye Clinic, Zurich, Switzerland; #Scheie Eye Institute, Philadelphia,PA, USA

Purpose: To follow the course of a MAR over a period of several months. Methods: Case report: a 67 year old female patient with an earlier removed cutaneous melanoma reported a unilateral left visual disturbance with shimmering and with acquired unilateral night blindness. About 10 weeks later similar visual disturbances appeared also in the right eye; there were metastases in axillary lymph nodes. Immunofluorescence produced specific labelling of the bipolar cells in the inner nuclear layer of a normal rat retina (A. Milam). Several test series were performed including ganzfeld ERG, pattern ERG for retinal function in small areas of the visual field centre and pattern VEP.  Results: During an early stage, the left eye only was affected. The right eye followed with functional objective and subjective deficits about ten weeks later. The most distinct result was an early total lack of rod function in the ERG, while cone function was less disturbed. The PERG declined slowly in both visual field centres. The VEP continued to show constant amplitudes only for small check sizes. Goldmann visual field testing showed a rather constant relative depression of sensitivity in the centre and midperiphery over time with intact outer borders; automated perimetry (with a different background illumination used) resulted in deep central scotomata but with a very small preserved most central island.  Conclusions: MAR may start as a unilateral disease, thus masquerading as a unilateral retinal or neural disease. Visual dysfunctions reached similar levels in both eyes after some months with a tendency to further deterioration. The autoimmune process was obviously confined to one eye only at the beginning. There was evidence from electrophysiological and psychophysical data that the most central areas of the visual fields were less involved.

eyemile@bluewin.ch 

CLINICAL AND ERG FEATURES OF HEREDITARY 
PIGMENTED PARAVENOUS CHORIORETINAL ATROPHY (PPCRA)

S Jalali, PSR Reddy

Kannuri Shantamma Retina-Vitreous Center, L.V Prasad Eye Institute, Hyderabad, India
            
Abstract: PPCRA is generally sporadic, asymptomatic and non-progressive retinal degeneration. To our knowledge, only four families have so far been described in the literature with the heritable form of the disease. We report the clinical and ERG changes in a fifth family with PPCRA. Methods: Two out of five offspring from a consanguineous marriage were referred for evaluation, with a diagnosis of Retinitis Pigmentosa. Detailed evaluation of all family members revealed additionally, affected mother and son who were asymptomatic. Complete clinical evaluation, visual fields and ERG were done to ascertain the inheritance pattern and nature of the disease. The results were compared to those reported in four earlier families with PPCRA. Results: The mother and three of her children, two males and one female were found to be affected clinically and also on ERG and visual fields evaluation. However the extent of involvement was variable from mild decrease in the photopic and scotopic ERG in the asymptomatic mother and one son, to unrecordable ERG in the most severely affected son. The daughter was moderately affected on ERG recording and had nyctalopia. The worst affected son showed progressive loss of vision while the condition is stable so far in other members affected. Earlier reported heritable cases had mostly involvement of the scotopic waveforms with normal photopic recordings. Phenotypic variability was a feature in earlier reported cases as also in this family. Conclusions: Detailed pedigree analysis and ERG evaluation of the family members helped to identify the asymptomatic affected members and establish the pseudo-autosomal recessive nature of inheritance. The presentation is compatible with an X- linked Dominant or Recessive inheritance. ERG also helped to give a better prognosis to the family, which was erroneously earlier diagnosed as having Retinitis Pigmentosa.

RETINAL FUNCTION IN MITOCHONDRIAL DISEASES WITHOUT RETINITIS PIGMENTOSA

C Macaluso, E Spaggiari, N Bresolin, P Nicolini, M Camparini

Ophthalmology, University of Parma, Italy

Purpose:  To evaluate retinal function in patients with mitochondrial diseases without associated retinitis pigmentosa.  Methods:  7 consecutive patients with mitochondrial diseases (Progressive External Ophthalmoplegia, MERFF, MELAS), confirmed by muscle biopsy and genotype determination, underwent ophthalmological assessment, ERG examination according to the ISCEV guidelines, and evaluation of dark adaptation with the Goldmann-Weekers adaptometer. Results:  Only two patients showed mild abnormalities of the ERG: one had a normal fundus, while the other had only macular hard drusen and no sign of retinal degeneration. On the other hand, dark adaptation was moderately altered in all subjects, with an elevation of the final rod threshold by 1 to 2 log units.  Conclusions: Patients affected by mitochondrial diseases without retinitis pigmentosa do not show major retinal function problems, with ERG parameters falling within normal limits. A moderate problem in dark adaptation has been observed consistently. This could be interpreted as the failure of a defective oxidative metabolism to fulfill the high metabolic demand of rods in the dark. 

cmacalus@unipr.it

S-CONE ELECTRORETINOGRAM IN MULTIPLE EVANESCENT WHITE DOT SYNDROME

S Yamamoto, M Hayashi, S Takeuchi

Department of Ophthalmology, Toho University Sakura Hospital, Sakura, Japan

Purpose: To examine the short-wavelength-sensitive (S-) cone function in patients with multiple evanescent white dot syndrome (MEWDS).  Methods: Cone electroretinograms (ERGs) to different chromatic flashes were examined under bright white background illumination in 5 patients with MEWDS.  Ophthalmoscopically, multiple irregular-shaped white dots were observed in the acute stage, and then disappeared within one or two weeks in all patients.  Indocyanine green angiography showed multiple hypofluorescent dots, indicating the disturbance of the choroidal circulation.  Results: The S-cone b-wave amplitude of the affected eyes relative to that of the fellow eye was 0.53 (sd 0.35), and significantly smaller than the relative L,M-cone b-wave amplitude (p=0.01).  The difference of the b-wave implicit time between affected eye and fellow eye was 2.96  (sd 4.91) msec in the S-cone b-wave, and 0.52  (sd 2.12) msec in the L,M-cone b-wave (p=0.20).  Conclusions:  In MEWDS, the S-cone ERG was more affected than the L,M-cone ERG, probably due to the disturbance of the choroidal circulation.  However, the S-cone function may be preserved in the macula, because our patients did not show any significant color vision deficit.

shuyama@med.toho-u.ac.jp

TRANSIENT INCREASED LATENCY IN PERG AND BIPOLAR ON-OFF RESPONSES WITH DMXAA,
A NEW ANTI-CANCER DRUG

MB Jameson, DM Sharp, JI Sissingh, CR Hogg, PI Thompson*

Vision Assessment Clinic, Auckland Hospital, New Zealand;
*Phase I/II Trials Committee of the Cancer Research Campaign (UK) 

Purpose: 5,6-dimethylxanthenone-4-acetic acid (DMXAA) is a new anticancer drug developed at the Auckland Cancer Society Research Centre which causes selective reduction in tumour blood flow and induces production of several cytokines including tumour necrosis factor and interferons. Patients receiving DMXAA in a phase I clinical trial have experienced an acute, transient visual disturbance affecting sensitivity to bright light and colour perception (confirmed on serial Farnsworth-Munsell 100 hue testing). Further clarification of the nature of this disturbance was sought. Methods: Pattern electroretinography (PERG) and bipolar on-off responses were evaluated in several patients immediately prior to a dose of DMXAA (given as a 20-minute infusion every 3 weeks), then repeated as soon as possible after the infusion and again about 1 hour later. Results: Latencies of the PERG P50 and bipolar on and off responses were increased at 20–30 minutes after the DMXAA infusion, then returned toward the baseline value 1–1.5 hours later. The increase in latency of the PERG P50 wave varied from 5–23ms above baseline values. Bipolar on response (b-wave) latency increased by 3–16ms and bipolar off response (d-wave) latency increased by 9–35ms above baseline values. Recordings in 2 patients performed 1-3 weeks later showed complete resolution of these changes, but in a third patient the changes had not quite resolved at 24 hours. Conclusions: DMXAA induces transient changes in retinal electrical activity that may reflect disturbance of amacrine and bipolar cell function. These changes have not previously been described and may offer insights into the generation of the PERG. Further studies are underway to examine the mechanism by which DMXAA induces these changes.
Supported in part by the Auckland Cancer Society and Auckland Healthcare Ltd. 

akvision@ahsl.co.nz

Wednesday 16 February

08.30 – 10.30	Scientific Session 5	AUTO-IMMUNE AND INFLAMMATORY RESPONSES 
	Chairs:	Yozo Miyake;  John Heckenlively

10.30-11.00	Coffee Break

11.00 – 13.00	Scientific Session 6	EXPANDING DIAGNOSTIC METHODOLOGY (2)
	Chairs:	Emiko Adachi;  Ido Perlman

13.00-14.00	Lunch Break

14.00 – 16.00	Posters Session 2	with coffee
	Chairs	Graham Holder;  Ulrich Kellner

16.00 – 17.45	Scientific Session 7	PAEDIATRIC VISUAL ELECTROPHYSIOLOGY
	Chairs:	Colin Barber;  Dianne Sharp

19.30 for 20.00	Symposium Dinner in the Holmes Building of Sydney University.
	Including presentation of the Dodt Award by Professor Eberhart Zrenner.
	And presentation of the ISCEV Olympics Trophy by Professor Colin Barber. 

11.00 – 13.00	Wednesday 16 February

Scientific Session 6	EXPANDING DIAGNOSTIC METHODOLOGY (2)
Chairs:		Emiko Adachi;  Ido Perlman

11.00	The effect of stimulus delivery methods on the multifocal ERG
	D Keating, SW Parks, C Malloch, AL Evans, AT Elliott (Glasgow, UK)
11.15	Dichoptic kernels using short binary and ternary sequences
	AC James, T Maddess, NSC Price (Canberra, Australia)
11.30	Abnormal macular function in human glaucoma revealed by 3 different modes of multifocal ERG stimulation
	B Fortune, CA Johnson, GA Cioffi (Portland, OR, USA)
11.45	S-cone ERG elicited by hue substitution
	M Horiguchi, T Sigino, A Morimoto (Toyoake, Japan)
12.00	Cone-isolating multifocal ERGs
	JF Albrecht, HA Baseler, LT Sharpe, H Jägle (Tübingen, Germany)
12.15	Multifocal cone and rod responses in patients with progressive cone dystrophy
	K Holopigian, W Seiple, VC Greenstein, DC Hood, RE Carr (New York, NY, USA)
12.30	Improving recording quality by using infrared video inside the ganzfeld stimulator
	MC Brown (Liverpool, UK)
12.45	The P50 and N95 components of the pattern-ERG show different naso-temporal asymmetries
	T Meigen, H Heine (Würzburg, Germany)

THE EFFECT OF STIMULUS DELIVERY METHODS ON THE MULTIFOCAL ERG

D Keating, SW Parks, C Malloch, AL Evans, AT Elliott

Tennent Institute of Ophthalmology, Gartnavel General Hospital, Glasgow, UK

Purpose: To compare and evaluate the multifocal response from CRT and Digital Projection stimulus delivery systems. Methods: A custom-built p.c. based multifocal system was used to generate a 61 hexagonal element stimulus array. The stimulus was presented on a high luminance CRT display and on a digital polysilicon back-projection display. In addition to standard m-sequence control, an adapting full field filler flash was inserted in alternate frames to study adaptive mechanisms as previously reported (Sutter & Bearse, IOVS, 39, 4, S243, 1998). First and second order kernel responses to onset and offset components were retrieved. A fast response photodiode was used to analyse the stimulus pulses for both systems. Six control subjects were used to evaluate the linear and non-linear components of the multifocal response from each system. Results: The pulse duration for a CRT system is dependent on the phosphor for a particular monitor which in this case produces a pulse of 50sec duration. Each stimulus element is composed of several raster lines which increases the effective pulse width to typically 2 msec. The Digital Projection system produces a 13 msec pulse equivalent to the frame rate of the system. In terms of conventional multifocal measurements, the first order CRT response is almost twice the amplitude of the digital system. Conversely the second order response is significantly larger from the digital system. In the adaptive response, differences in waveform shape were found between the CRT and Digital stimuli. Conclusions: Digital stimulus delivery offers a different way of performing multifocal measurements. Wide field stimulation of over 120 degrees is possible. The non-linear part of the response to digital stimuli is different to that of CRT systems and could prove useful for assessing this aspect of multifocal responses.    

d.keating@clinmed.gla.ac.uk

DICHOPTIC KERNELS USING SHORT BINARY AND TERNARY SEQUENCES

AC James, T Maddess, NSC Price

Centre for Visual Sciences, RSBS, ANU, Canberra, Australia

Purpose: We wished to investigate the practicalities of estimating Wiener Kernels from visual evoked potentials (VEPs) recorded in response to short (30 s) pseudorandom noise sequences presented dichoptically. Dichoptic presentation has the advantage that kernels for the two eyes are estimated simultaneously and also binocular interaction kernels  (BIKs) can be obtained. Simultaneous recording of signals from the two eyes is statistically much more powerful. Also, the BIKs isolate information from each hemi-cortex. Methods: Using a liquid-crystal shutter, pseudorandom sequences of 30 s duration were presented simultaneously to the two eyes at 50 frames/s/eye in 8 visual field locations, covering the inner and outer field in the four quadrants. The total display spanned 26 deg vertically by 32 deg horizontally. The 8 contiguous stimulus regions contained checkerboard patterns, and the region size and the checkerboards were M-scaled. Both binary (black/white) and ternary (black\grey\white) stimuli were tested. Stimulating left and right eyes with separate signals, visual cortex can be modelled as a system receiving 16 input channels and producing the VEP as output. Kernels were estimated by a regression method permitting kernel coefficients to be presented as t-statistics. Results: Reliable kernels, as measured by t-statistics, could be obtained in 4 to 10 repeats of the 30s stimulus sequences. BIKs obtained without fixed disparities were less reliable than kernels for each eye. Different delays were obtained for different stimulus regions. Compared to kernels from binary sequences those from ternary sequences permitted the diagonal elements of the second order self-quadratic kernels to be estimated. Conclusions: The dichoptic method coupled with ternary stimuli appears to provide several advantages over recording from each eye individually. Not only is half the time required but the statistical power of the data is improved, and interocular interactions within each hemi-cortex can be estimated.

andrew.james@anu.edu.au

ABNORMAL MACULAR FUNCTION IN HUMAN GLAUCOMA REVEALED BY THREE DIFFERENT MODES OF MULTIFOCAL ERG STIMULATION

B Fortune, CA Johnson, GA Cioffi

Discoveries In Sight Research Labs; Devers Eye Institute, Portland, Oregon, USA

Purpose: To identify MERG abnormalities in glaucoma; and compare the relative effectiveness of three modes of MERG stimulation for detection of abnormal function. Methods: Glaucoma patients with well-documented asymmetric hemifield loss across the horizontal midline had MERGs for three different stimuli recorded using VERIS Science™ with Burian-Allen bipolar contact lens electrodes. Residual refractive error was corrected to the nearest 0.50 D for the 40 cm test distance. All stimuli were viewed with natural pupils and contained 103 hexagonal elements subtending a total field of ~400. The 'standard' stimulus consisted of m-sequence modulation between light (200 cd/m2) and dark (2.0 cd/m2) at a frame rate of 75 Hz. The 'pattern reversal' stimulus contained 24 triangular 'checks' within each hexagon; the spatial phase of the pattern modulated at full contrast (~98%) according to a similar m-sequence. The 'global flash' stimulus1 had 3 additional frames inserted between each successive m-sequence step: a full-screen dark frame, a full-screen, or 'global' light flash (2X luminance of local flash), and another dark frame. Total recording time was 8 minutes per stimulus. Signals were amplified (106), band-pass filtered (10-300 Hz) and sampled 16 times per frame. Topographic changes in MERGs were compared with Humphrey standard automated perimetry (SAP) findings. Results: Mean defect and pattern standard deviation ranged from -4.7 to -18.0 dB and 9.0 to 16.0 dB, respectively, reflecting large differences between upper and lower visual field sensitivity for each patient. Differences between upper and lower hemifield MERG responses were neither consistent (across patients or stimuli) nor outside the range of normal variability. In contrast, the distinguishing characteristic, among all patients and for all three stimuli, was decreased response amplitude density within the central 10 degrees. Conclusions: This result is consistent with the findings of one other recent report.2 However, abnormalities of MERG responses (to several different stimuli) for these eyes with glaucoma do not correspond topographically with even advanced VF changes. At least two hypotheses arise: behavioral sensitivity (measured using SAP) is a highly nonlinear representation of underlying ganglion cell function/population; and/or abnormal neuronal function in these eyes with glaucoma is not limited to ganglion cells.
1. Sutter EE. Invest Ophthalmol Vis Sci. 1999; 40(4): s15.; 2. Chan HL, Brown B. Ophthal Physiol Opt. 1999; 19(4): 306-316.

bfortune@discoveriesinsight.org

S-CONE ERG ELICITED BY HUE SUBSTITUTION

M Horiguchi, T Sigino, A Morimoto

Department of Ophthalmology, Fujita Health University, Toyoake, Japan

Purpose: To record short wavelength sensitive cone electroretinogram (S-cone ERG) by hue substitution. Method: We used a new light emitting diode (LED) built-in contact lens electrode developed for silent substitution. This electrode provides full-field white, blue and yellow illumination from 3 LEDs (white, 470nm, 575nm). White light was used for background illumination (100 cd/m2), and yellow and blue lights for stimulation. The experiment was performed as follows: (1) recording 30 Hz yellow flicker ERG (generated by LM-cones, because S-cone ERG does not follow 30Hz stimuli) (2) recording 30 Hz blue flicker ERG (generated by LM-cones) (3) measuring intensities of yellow and blue lights which produce the same amplitude in 30 Hz flicker ERGs (LM-cone match) (4) recording 30 Hz subsitution of yellow and blue lights matched in experiment (3). (5) recording 5 Hz subsitution of yellow and blue lights matched in experiment (3).  Results: In experiment (1) and (2), normal flicker ERGs were recorded indicating that both yellow and blue lights elicited LM-cone ERGs. In experiment (3), we could match the intensities of yellow and blue lights for the 30 Hz flicker ERG. However, the intensities of yellow and blue lights producing the same amplitude slightly varied even in normals. In experiment (4), 30 Hz substitution of matched lights produced no detectable response. In experiment (5), 5 Hz substitution of matched lights elicited the b-wave, 5-10mV in amplitude and 40-50 ms in peak time. Conclusion: White background suppressed rod response, and substitution of yellow and blue light matched for 30Hz flicker ERG did not stimulate LM-cones, because 30Hz substitution produced no response. Therefore, the b-wave observed in experiment (5) must be generated by the S-cone system. This simple technique may be very useful in study of human S-cone pathway. This study also suggests that, when silent substitution is used in human ERG, matched intensities should be measured in individual subjects, because they varied in experiment (3).

masayuki@fujita-hu.ac.jp

CONE-ISOLATING MULTIFOCAL ERGS

JF Albrecht, HA Baseler, LT Sharpe, H Jägle

Forschungsstelle für Experimentelle Ophthalmologie, Universitäts-Augenklinik, Tübingen, Germany

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.

jalbrecht@vision.eye.medizin.uni-tuebingen.de

MULTIFOCAL CONE AND ROD RESPONSES IN PATIENTS WITH 
PROGRESSIVE CONE DYSTROPHY

K Holopigian, W Seiple, VC Greenstein, DC Hood, RE Carr

New York University School of Medicine, Department of Ophthalmology, New York, NY, USA

Purpose:  The purpose of this study was to examine local cone and rod psychophysical and electrophysiological function in patients with progressive cone dystrophy (CD). Methods: Cone-mediated threshold visual fields, cone multifocal ERGs, rod-mediated threshold visual fields and rod multifocal ERGs were measured in a group of patients with CD. Results: Cone-mediated threshold fields were elevated, with the central retinal areas most affected. The cone multi-focal ERGs were significantly reduced in amplitude and markedly delayed throughout much of the area tested. There were significant correlations between cone amplitude and cone implicit time for the majority of the patients. The correlations between the cone multifocal ERG parameters and visual field loss were not significant. Rod-mediated thresholds were elevated in some areas of the visual field, consistent with the involvement of the rod system in these patients. In addition, rod multifocal ERG responses were reduced in amplitude and delayed at some retinal locations. Rod multi-focal ERG losses were typically greatest at the more peripheral locations. The rod multi-focal ERG results were poor predictors of rod visual field thresholds. Conclusions: Patients with CD have local cone-mediated threshold and multifocal ERG deficits. The electrophysiological abnormalities were more extensive than the threshold abnormalities. The patients with CD also demonstrated local rod threshold and ERG deficits. The rod system losses were less severe and more localized than the cone system losses. There was little correspondence between the topography of the cone and rod system losses in these patients. 

kh19@is3.nyu.edu

IMPROVING RECORDING QUALITY BY USING INFRARED VIDEO 
INSIDE THE GANZFELD STIMULATOR

MC Brown

Clinical Engineering Dept., Royal Liverpool University Hospital, Liverpool, UK

Purpose:  To investigate the benefits of using infrared video inside the Ganzfeld stimulator for recording ERG, EOG and flash VEP.  Methods:  A CCD camera was fitted to a ganzfeld stimulator to view the face of the patient through a pinhole.  Infrared LEDs were fitted facing inwards to reflect from the coating of the bowl onto the face of the patient.  The patient's face was viewed from a TV monitor on the operator's console and a video recorder and microphone were employed to log the essential events of the session.  Results:  A sequence of video examples has been assembled which show the deviations in the behaviour of patients from that desired, and I will discuss their effects on the validity of the results. I will also show how the view of the patient enabled these problems to be corrected by directly instructing the patient.  A number of the examples are with children and show that considerable improvement in behaviour within the bowl can be obtained if the operator has a good view of the patient's eyes and the recording electrodes.  Conclusions: Considerable improvement in recording quality, and confidence in the results, can be achieved by the use of direct video viewing of a patient who has the head within the Ganzfeld bowl.  Examples are where the patient looks away from the fixation light, where they close or partially close their eyes in response to the stimulus (particularly flicker), where the electrodes become displaced, and in the case of the EOG where they do not follow the instructions or deliberately ignore them.

MalcolmBrown@btinternet.com

THE P50 AND N95 COMPONENTS OF THE PATTERN-ERG SHOW DIFFERENT 
NASO-TEMPORAL ASYMMETRIES

T Meigen, H Heine

Universitaets-Augenklinik, Wuerzburg, Germany

Purpose: It is known that nasal retina has a higher ganglion cell density than temporal retina[1], but there are contradictory findings concerning the existence and direction of naso-temporal asymmetries in PERG recordings. We asked (a) whether the P50 and N95 components of the transient PERG show similar naso-temporal asymmetries, and (b) whether these may be explained by the difference in ganglion cell density. Methods: 50 visually normal subjects were presented with. checkerboard patterns with a check size of 0.8˚, a contrast of 100%, and a mean luminance of 40 cd/m2 within a stimulus field of 36˚x27˚,. which was divided horizontally in two hemifields of identical size. Stimulus pattern reversal was performed separately for the two hemifields. Transient PERG responses (f = 2.2 Hz) were recorded binocularly with DTL electrodes. Amplitude and latency values of the P50 and N95 components were estimated. For each subject, the nasal and temporal components were averaged across both eyes. Paired t-tests were performed to obtain the statistical significance of naso-temporal differences. Results: While no significant differences were found for P50 amplitude, the N95 of the temporal hemiretina showed larger amplitudes than the nasal hemiretina. Significant latency differences were found for P50, but not for N95.
Mean±SEM (n=50)	P50 Amplitude	P50 Latency	N95 Amplitude	N95 Latency
Nasal	2.92±0.13µV	54.0±0.4 ms	3.23±0.13 µV	100.8±0.9 ms
Temporal	2.81±0.13µV	52.4±0.4 ms	4.08±0.18 µV	100.5±1.1 ms
Significance	p=0.14	p<0.0001	p<0.0001	p=0.79
Conclusions: (a) The P50 and N95 PERG components show different naso-temporal asymmetries. This may reflect different generators for the P50 and N95 components. (b) PERG amplitudes cannot be linked to ganglion cell density in a simple way. The larger number of ganglion cells in the nasal hemiretina does not lead to an increased P50 amplitude, while the N95 amplitude is even reduced compared to that of the temporal hemiretina.
[1] Curcio, CA & Allen, KA (1990) Topography of Ganglion Cells in Human Retina. J Comp. Neurol. 300:5-25

t.meigen@augenklinik.uni-wuerzburg.de
Wednesday 16 February

08.30 – 10.30	Scientific Session 5	AUTO-IMMUNE AND INFLAMMATORY RESPONSES 
	Chairs:	Yozo Miyake;  John Heckenlively

10.30-11.00	Coffee Break

11.00 – 13.00	Scientific Session 6	EXPANDING DIAGNOSTIC METHODOLOGY (2)
	Chairs:	Emiko Adachi;  Ido Perlman

13.00-14.00	Lunch Break

14.00 – 16.00	Posters Session 2	with coffee
	Chairs	Graham Holder;  Ulrich Kellner

16.00 – 17.45	Scientific Session 7	PAEDIATRIC VISUAL ELECTROPHYSIOLOGY
	Chairs:	Colin Barber;  Dianne Sharp

19.30 for 20.00	Symposium Dinner in the Holmes Building of Sydney University
	including presentation of the Dodt Award by Professor Eberhart Zrenner
	and presentation of the ISCEV Olympics Trophy by Professor Colin Barber 

14.00 – 16.00		Wednesday 16 February

Posters Session 2 (with coffee)	Chairs:  Graham Holder;  Ulrich Kellner

P2.1	Acquisition and implementation of a commercial visual electrophysiology system
	TL McLaren, JM Atkinson, MR Bottomley, E Chelva, JN De Roach, RH Fisher, SMS Kay, RI Price 
	(Perth, Australia)
P2.2	Flash and pattern ERGs in Stargardt's disease
	KW Mitchell, MP Clarke (Newcastle upon Tyne, UK)
P2.3	A case with neuroretinopathy caused by heavy charged particle irradiation
	A Mizota, S Suehiro, E Adachi-Usami, J Mizoe (Chiba, Japan)
P2.4	A trial of objective visual field measurement by pupillary reaction
	K Mizukawa, A Tabuchi (Kurashiki-city, Japan)
P2.5	Visual function of three cases with intraocular tumor
	K Morimoto, M Yoshii, S Okisaka (Tokorozawa, Japan)
P2.6	Multi-focal ERG in retinal detachment surgery 
	M Moschos, J Malias, G Theodossiadis (Athens, Greece)
P2.7	Pigmentary retinopathy with leopard-spot pattern of unknown etiology
	T Nakamura, O Miyauchi, A Mizota, E Adachi-Usami (Chiba, Japan)
P2.8	Retinal function after panretinal photocoagulation in diabetic patients assessed by electroretinogram
	YH Ohn, YK Han (Seoul, Korea)
P2.9	Multifocal electroretinogram in occult macular dystrophy
	C-H Piao, M Kondo, A Tanikawa, H Terasaki, Y Miyake (Nagoya, Japan)
P2.10	Pattern ERG in relation to kinetic and static perimetry and visual acuity in retinitis pigmentosa
	P Popovic, M Jarc-Vidmar, J Brecelj, M Hawlina (Ljubljana, Slovenia)
P2.11	An indigenous inexpensive new electrode for recording the ERG
	LSM Ram, R Reddy, S Jalali, VS Rao, T Das (Hyderabad, India)
P2.12	A kinetic model of the contribution of the rod photocurrent to the electroretinogram
	JG Robson, LJ Frishman (Houston, TX, USA)
P2.13	A multi-channel and shape-independent detector for multi-focal VEPs in objective perimetry
	K Schellhorn, F Schlegelmilch, G Henning (Ilmenau, Germany)
P2.14	Functional peripheral visual performance in patients with RP
	W Seiple, K Holopigian, RE Carr, (New York, NY, USA) 
P2.15	Severe amblyopia: what is it?
	AM Shamshinova, IM Mosin, AA Krivosheev, HL Barseghyan, AP Dvorianchikova (Moscow, Russia)
P2.16	The pattern electroretinogram (PERG) as an indicator of early Hydroxychloroquine toxicity
	DM Sharp, JI Sissingh, B Lunt (Auckland, New Zealand)
P2.17	L and M cone signal contributions to the multifocal ERG: interdividual and topographical variation
	LT Sharpe, JF Albrecht, H Jägle (Tübingen, Germany)
P2.18	Amplitude-check size function of pattern reversal visual evoked response in patients with macular diseases
	AA Shihab (Giza, Egypt)
P2.19	Primary open angle glaucoma: a study using multi-tests approach of electrophysiology, ultrasonography and fluorescein angiography
	AA Shihab (Giza, Egypt) 
P2.20	Assessment of the degree of amblyopia in children with partial cataracts
	AA Shpak (Moscow, Russia)
P2.21	Human retinal color processing steps revealed by phase and amplitude ERG response to sinusoidal stimuli
	F Siebert, R Gemperlein (München, Germany)
P2.22	Oscillatory potentials of the electroretinogram in the follow-up of hypertensive patients with four different pharmacological treatments
	N Solimano, G Rinaldi, G Ravalico (Trieste, Italy)
P2.23	Fast and slow oscillation electrooculography in Harada's disease 
	A Tamai, J Hamamoto, Y Sasaki, K Iba, A Setogawa, T Nakamura, A Amasaki, M Inoue, M Nagata 
	(Yonago, Japan)
P2.24	Cone electroretinograms recorded under the clinical slit-lamp examination
	A Tanikawa, M Kondo, S Suzuki, Y Miyake (Nagoya, Japan)
P2.25	Spatial and temporal profile of visual evoked magnetic field (VEF) to pattern-reversal stimulation
	H Tanikawa, H Ohde, Y Kurobe, Y Haruta, Y Mashima, Y Oguchi (Tokyo, Japan)
P2.26	Pseudoretinitis pigmentosa: a diagnosis sometimes easy, sometimes complicated
	AP Tormene, R Busana, C Riva (Padova, Italy)
P2.27	Functional and electrophysiological correlates of visual loss with Vigabatrin 
	K van der Torren, H Graniewski, BCP Polak (Dordrecht, The Netherlands)
P2.28	The fast spiking STR: A photophobic oculomotor artifact occurring near absolute scotopic threshold
	Vaegan (Sydney, Australia)
P2.29	The visual function of idiopathic macular hole before and after surgery
	D-Z Wu, T Zhao, R Gao, S Zhang, L Wu, J Liang (Guangzhou, China)
P2.30	The appearance of multifocal ERG in primary and secondary maculopathies
	L Wu, SZ Huang, D-Z Wu, JM Ma (Guangzhou, China)
P2.31	Visual electrophysiology for alcoholic ocular changes
 	W Yin, X Guo, Y Dong, M Wang  (Zhengzhou, China)
P2.32	Multifocal electroretinogram is distorted by artifact removal procedure
	M Yoshii, K Yanashima, S Suzuki, S Okisaka (Tokorozawa, Japan)
P2.33	Multifocal critical flicker fusion frequency in diagnosis of visual field defects
	MV Zueva, IV Tsapenko, KV Golubtsov, GJu Zakharova, M Khashaev (Moscow, Russia)

ACQUISITION AND IMPLEMENTATION OF A COMMERCIAL 
VISUAL ELECTROPHYSIOLOGY SYSTEM

TL McLaren, JM Atkinson, MR Bottomley, E Chelva, JN De Roach, RH Fisher, SMS Kay, RI Price

Department of Medical Technology and Physics, Sir Charles Gairdner Hospital, Perth, Australia

Purpose: To describe the acquisition and implementation of a commercial visual electrophysiology system by a department with over 20 years experience in providing visual electrophysiology services. A primary objective of the new system was to provide electrophysiological testing in full accordance with ISCEV standards. Methods: We surveyed Australian users of various electrophysiology systems regarding selection, purchase, performance, technical support, and adherence to ISCEV standards. Tenders were invited and the LKC UTAS-E 3000 Visual Electrophysiology System was subsequently purchased. Implementation was planned to include photometry, system calibrations, interfacing to the departmental network, writing of software for report production to our standard and the collection of normal data. A hospital ethics committee approved project has been established to collect age based normative data on approximately 80 individuals for EOG, ERG, PERG and VEP. Results: Hardware and software faults have arisen continuously for fifteen months post-installation requiring many hours of in-house technician time and a number of component replacements.  Soon after the apparently successful installation we experienced unacceptable 60 Hz contamination of VEP and PERG data which we overcame by replacing the supplied pattern generator monitor with one of superior quality. The ganzfeld unit has generated a number of faults, and both the ganzfeld flash unit and power supply have been replaced. Photometric measurements revealed low and unstable background light levels necessitating replacement of the lamp housing. Other faults have included system start-up taking 15 minutes and various system failures. The computer boards have consequently been reseated. Filter board failures have resulted in boards being replaced on two occasions.  At 12 months post-installation an extended warranty period of a further 12 months was negotiated. Conclusions: It is essential to thoroughly investigate the exact model, in operation by experienced users, of any system under consideration for purchase.  Spare parts and technical support must be locally available. However, this implementation process gave us the opportunity to examine and re-evaluate our work practices such that we are confident that when the system is operational to our requirements our visual electrophysiology services will be fully ISCEV compliant. 

terri@mtp.pd.uwa.edu.au

 FLASH AND PATTERN ERGS IN STARGARDT'S DISEASE

KW Mitchell, MP Clarke

Regional Department of Medical Physics & University Department of Ophthalmology, 
Royal Victoria Infirmary, Newcastle upon Tyne, UK

Purpose: To investigate the Flash ERG and pattern ERG in a cohort of patients with Stargardt's disease. Methods: Eleven patients were studied using standardised approaches (ISCEV ERG Standard 94, ISCEV PERG Guidelines 96) and compared to
Laboratory control data elicited under the same conditions. Results: All showed some form of electrophysiological abnormality, 9 of the 11 (82%) in relation to the FERG and 9 of 9 (100%) in the PERG. The predominant effect was amplitude reduction but implicit time effects were observed in both responses also. Conclusion: Stargardt's disease not only affects macular function as signalled by the PERG but also panretinal function as declared by the FERG. The temporal progression of events in the photoreceptor-midretinal layer complex also appears likely to be compromised.

K.W.Mitchell@ncl.ac.uk

A CASE WITH NEURORETINOPATHY CAUSED BY HEAVY CHARGED PARTICLE IRRADIATION

A Mizota#, S Suehiro#, E Adachi-Usami#, J Mizoe*

#Department of Ophthalmology, Chiba University School of Medicine;
*National Institute of Radiological Science, Chiba, Japan

Purpose: Heavy charged particles have begun to be used to treat certain kinds of malignant tumors such as malignant melanoma.  To date, no case with ocular side effects has been reported.  We wish to report the funduscopic, fluorescein angiographic and electrophysiologic findings in a patient with squamous cell carcinoma before and after treatment with heavy charged particle irradiation which resulted in a neuroretinopathy.  Case and Results: A forty-seven-year-old man was diagnosed with squamous cell carcinoma of the paranasal sinus in September, 1997. The tumor originated from the ethmoid sinus and invaded the left orbit, frontal sinus and maxillary sinus.  He underwent chemotherapy but no significant improvement was seen.  Heavy charged carbon particle irradiation therapy was then applied from January 23 to February 20, 1998.  Totally, the tumor including the optic nerve and retina of his left eye was irradiated with 16 Gy.  Ocular examination and electrophysiological examination before and 1, 6, 12 months after the therapy did not reveal any abnormalities except for myopic fundus changes.  In April, 1999, 15 months after the irradiation, the patient noticed a decrease of vision in his left eye.  On April 26, 1999, his best corrected visual acuity  was 0.8 and cotton wool patches were seen around the left optic disk.  Fluorescein angiography revealed prolonged circulation time in the choroid and optic disk.  P100 peak latency of the pattern VECP was prolonged from 120 to 140 ms. The amplitudes of the a- and b-wave of single flash ERGs were normal.  On May 26, the vision in his left eye decreased to hand motion and retinal arteries were almost occluded.  The amplitudes of both a- and b-wave of single flash ERG were markedly decreased. Conclusions: Both the retina and optic nerve were damaged by 16 Gy of heavy charged carbon particle irradiation therapy.  The changes in his retina and optic nerve were similar to retinal and optic nerve changes induced by X-ray irradiation. The P100 peak latency of PVECP was delayed even at the early stage of the disease. 

mizota@ophthalm.m.chiba-u.ac.jp

A TRIAL OF OBJECTIVE VISUAL FIELD MEASUREMENT BY PUPILLARY REACTION

K Mizukawa, A Tabuchi

Department of Ophthalmology, Kawasaki Medical School, Okayama, Japan

Purpose: All enforced visual field tests depend on a subjective reply. Because subjective replies are vague in small children and / or non-cooperative patients, the reliability of such tests in these patients is low. If we could measure a visual field objectively, it would be very useful for these patients. In this experiment, we produced a pupil perimetry created by the Visual Evoked Response Imaging System (VERIS) and an infrared pupillometer, and investigated its clinical application. Methods: We examined 10 normal volunteers (mean age; 26 y.o.) under three kinds of room illumination; i.e., room light, 5 asb and dark, with a stimulus intensity of white (100cd/m2) - gray (20cd/m2), and a stimulus frequency of about 2 Hz.  The 19 elements for ERG according to the Veris Science 4.1 were used for stimulation on a central 15-degree visual field. To establish a suitable stimulus intensity, we also examined 22 normal volunteers (mean age; 38.0 y.o.) with a condition of white (100cd/m2) black (0cd/m2) and white-gray with room illumination of 5 asb. The wave patterns obtained were analyzed with the Veris Science 4.1, and changes in the amplitude of the maximum diameter of the pupil and coefficient variations were calculated. The stimulated area was divided into three parts; i.e., central, midcentral and peripheral, and was also divided into four quadrants; superior-temporal, superior-nasal, inferior-temporal and inferior-nasal. For pathological conditions, we examined six hemianopia patients (mean age; 52.0 y.o.). Results: The smallest coefficient variation was obtained under the condition of room illumination of 5 asb (central; 23.3% ~ peripheral; 34.7%), and the stimulus intensity of white-black (central; 21.0% ~ peripheral; 29.5%). Pupil responses tended to be biggest in the superior-temporal quadrant, and smallest in the inferior-nasal quadrant. In the hemianopia patients, the pupillary responses in the blind field were deteriorated as compared with those of the normal field. Conclusions: At least in the central area within 15 degrees, the objective perimetry of pupillary responses is clinically applicable. Further study is necessary, however, for an ordinary visual field test, which requires a wider range field. 

mike@med.kawasaki-m.ac.jp

VISUAL FUNCTION OF THREE CASES WITH INTRAOCULAR TUMOR

K Morimoto, M Yoshii, S Okisaka

Department of Ophthalmology, National Defense Medical College, Tokorozawa, Japan

Purpose: To study the electrophysiological function of three cases with intraocular tumor (retinal cavernus hemangioma, melanocytoma and tuberous sclerosis). Methods: Multifocal electroretinogram (ERG), pattern ERG and pattern visual evoked potential were recorded from these three cases. Multifocal ERGs were elicited using the Veris III system (Mayo Corporation). The stimuli consisted of densely arranged arrays of 103 hexagonal elements. The pupils were fully dilated and a bipolar contact lens electrode was used. It took 4 minutes to obtain one mERG record. Pattern stimulation was done using a checkerboard pattern (34min of arc check, 3rev/s, 95% contrast, 43.1cd/m2 mean luminance). 300 signals were summated. The high cut and low cut filters were 50 Hz and 1Hz, respectively. Case 1: 44 year-old male. Retinal cavernus hemangioma. Case 2: 54 year-old male. Melanocytoma. Case 3: 25 year-old male. Tuberous sclerosis. Results: Pattern ERG responses were reduced more than multifocal ERG responses in these cases. A delay in pattern VEP latency was more pronounced for tuberous sclerosis. The central visual field abnormality was detected in the melanocytoma case. A discrepancy was observed between the Humphrey data and the electrophysiological findings. However, SLO examination revealed no abnormal subretinal vessels around the optic disc of the affected eye. Conclusions: Multifocal ERG, pattern ERG and pattern VEP are useful clinical tools for understanding the visual function in the cases of the intraocular tumors, when the other ophthalmic findings are evaluated together with the electrophysiological data.

masaruy@mb.infoweb.ne.jp

MULTIFOCAL ERG IN RETINAL DETACHMENT SURGERY

M Moschos, J Malias, G Theodossiadis

Athens University Eye Department, Athens, Greece

Purpose:  To investigate whether the Multi-focal ERG can be helpful in clinical practice for following the evolution of retinal function in eyes operated on for retinal detachment. Method: For the multi-imput technique, a stimulus pattern consisting of 61 hexagons was presented by a VERIS program in a computer system  (Tomey Nagoya, Japan). MF ERG was recorded in eyes suffering from rretinal detachment operated on by a Lincoff Custodis method. All the eyes had a visual acuity 20/20. Results:  The peripheral scotoma due to retinal surgery is monitored better and more accurately than by the classical methods of monitoring the visual fields. Conclusion:   Multi-focal ERG is an objective and creditable tool in clinical practice for monitoring and quantifying the functional abnormalities affecting the peripheral vision in eyes operated on for detachment of the retina.

PIGMENTARY RETINOPATHY WITH LEOPARD-SPOT PATTERN OF UNKNOWN ETIOLOGY

T Nakamura, O Miyauchi, A Mizota, E Adachi-Usami

Department of Ophthalmology, Chiba University School of Medicine, Japan

Objectives: :To report a patient with pigmentary retinopathy with leopard-spots on the whole retina of both eyes which has never been observed in the past.  Subject and methods:: A 76-year-old man referred to our clinic to have an ophthalmic examination before receiving hemodialysis therapy, though he had no visual complaints.  The patient was diagnosed for 2 years as chronic nephritis after suffering from hypertension. In the past, no chemotherapic agents have been received, and no history of eye complaints. Funduscopic examination of both eyes disclosed freckle-like brown pigment diffusely scattering from adjacent to the optic disc to the periphery on the whole retina.  The fluorescein angiography demonstrated window defects that reflected a severe loss of the retinal pigment epithelium and choriocapillaris.  The pigmentary spots were very similar to a leopard-spot pattern seen in uveal effusion. Visual acuity was 0.3 right eye and 0.3 (0.4) left eye. Results: Both photopic and scotopic electroretinograms (ERG) were abnormal, i.e. both a- and b-wave reduced to half of normal values, while pattern visual evoked cortical potentials were normal.  Dark adaptometry showed an increase of approx.1.0 log unit in the rod curve. Goldmann perimetry revealed normal.  Conclusions: The leopard-spot pattern of pigment clumping seen in our patient with chronic nephritis is a new observation.  The case revealed a decrease of both scotopic and photopic function by ERG, while the optic nerve function was proved to be normal by VECPs.  The patient could be a new type of atypical retinitis pigmentosa. The mechanism of the retinopathy is uncertain.

Taniai＠ophthalm.m.chiba‐u.ac.jp

RETINAL FUNCTION AFTER PANRETINAL PHOTOCOAGULATION IN DIABETIC PATIENTS ASSESSED BY ELECTRORETINOGRAM

YH Ohn, YK Han

Department of Ophthalmology, Soonchunhyang University Hospital, Seoul, Korea

Purpose: To evaluate the effect of panretinal photo-coagulation (PRP) on the electroretinogram, comparing the anatomical and functional changes of retina after PRP. Methods: Retrospective study was performed on 58 eyes of 29 patients with proliferative diabetic retinopathy (PDR) who underwent panretinal photocoagulation. Fluorescein angiography (FAG) and electroretinograms (ERG) were examined in each patient before and after PRP. ERG results after PRP (mean 2.4 months) to one group of 38 eyes showing obvious new vessels regression and  the other group of  20 eyes showing poor regression were compared. Results:  Marked reduction in amplitude and delay in implicit time were observed in all the patients in which b-waves were more reduced than a-waves. There were no significant differences in ERG changes after PRP between the two groups (p>0.05). Conclusions: These results suggest that PRP treatment in diabetic patients may affect the whole retinal layers. However, ERG is not a good indicator for the regression of retinal neovascularization. PRP treatment may recover the anatomical integrity, but not correct the functional impairment of the retina.

yhohn@hosp.sch.ac.kr

MULTIFOCAL ELECTRORETINOGRAM IN OCCULT MACULAR DYSTROPHY

C-H Piao, M Kondo, A Tanikawa, H Terasaki, Y Miyake

Department of Ophthalmology, Nagoya University School of Medicine, Nagoya, Japan

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

piao@med.nagoya-u.ac.jp

Pattern erg in relation to kinetic and static perimetry and visual acuity
in retinitis pigmentosa

P Popovic, M Jarc-Vidmar, J Brecelj, M Hawlina

University Eye Clinic and University Institute for Clinical Neurophysiology, Ljubljana, Slovenia

Objectives: We have previously shown (ISCEV 1996,1998) that pattern ERG has its diagnostic value in testing the progression of retinitis pigmentosa when flash responses are already absent. This study was conducted to determine how PERG, reflecting the activity of inner retinal layers that are least affected in retinitis pigmentosa, is related to visual acuity and the extent of remaining visual field. Methods: An analysis was performed on 50 eyes of 25 patients with rod-cone retinitis pigmentosa. Transient pattern ERGs were elicited by checkerboard pattern projected onto translucent screen of 16° r reversing at 1.6 Hz and recorded simultaneously from both eyes by HK-loop electrodes. Responses were averaged and analyzed using a Nicolet MS 2000 system. Flash ERG responses were measured according to ISCEV standards. Visual field sensitivity using Octopus M2 and Goldmann (II4e, V4e) was tested. Amplitudes of PERG P50 and N95 were compared to results of visual acuity and visual field testing. Results: In our group of RP patients with visual acuity ranging from 0.2 to 1.0, PERG responses were preserved much better than full field ERGs. Out of 50 eyes, 32 of them had still recordable PERG responses, while 24 had cone and only 16 maximal responses. Scotopic rod responses were absent in all eyes. All patients with preserved PERG responses had visual acuity 0.4 or better. A strong correlation of both P50 and N95 amplitudes with Octopus mean defect was found (r = -0.76, r = -0.68, respectively). In kinetic perimetry the correlation with PERG amplitudes was also moderately high, and it was better with II4e than with V4e target. A linear agreement between visual acuity and PERG amplitudes was also found, PERG responses disappearing at visual acuity of 0.3 or less. Conclusions: Amplitudes of both PERG P50 and N95 are linearly related to the remaining functional retina in patients with rod-cone retinitis pigmentosa. The agreement can be found in patients with good visual acuity (better than 0.3) and is more pronounced in static than kinetic perimetry. Pattern ERG can therefore be used as a sensitive test in evaluating the functional visual loss in retinitis pigmentosa.

Petra.Popovic@MF.UNI-LJ.Sl
AN INDIGENOUS INEXPENSIVE NEW ELECTRODE FOR RECORDING THE ERG

LSM Ram, R Reddy, S Jalali, VS Rao, T Das

Kanuri Shanthamma Retina Vitreous Centre, L V Prasad Eye Institute, Hyderabad, India

Objective: To report pattern electroretinogram (PERG) recordings obtained by using a locally made gold-coated thread (Zari - Used for embroidery in India) and its comparison to the conventional DTL electrode. Methods: In 14 normal subjects (age range 18-30 years) we recorded PERG using the new electrode in one eye and the DTL electrode in the fellow eye and compared the recordings. PERG was performed as per the ISCEV guidelines (1996). Pattern stimulation was performed with check sizes of 30' and 60' with frequencies of 3.7 Hz and 15 Hz respectively. Amplitude and latency was measured for P50 and N95 components of transient PERG. The magnitude and phase characteristics were also measured for the steady state PERG. Results: A significant  (P<0.01) correlation (r > 0.63) was found between the DTL electrode and the new electrode for all components of pattern ERG, except N95 latency component of 30' check size (r =0.45) where the correlation was not significant. Conclusion: This inexpensive, indigenous material appeared as good as the DTL electrode in giving consistent, measurable waveforms for PERG. Further studies are needed to confirm these findings, both in healthy and disease states.  

A KINETIC MODEL OF THE CONTRIBUTION OF THE ROD PHOTOCURRENT 
TO THE ELECTRORETINOGRAM

JG Robson, LJ Frishman

College of Optometry, University of Houston, TX, USA

Purpose: To provide a model that describes the entire timecourse of the rod contribution to the electroretinogram (ERG).  Specifically, this model should describe the early part of the a-wave as well as the later timecourse of the rod response (derived P3) as determined using the high-energy probe-flash technique introduced by Birch et al (1995).   Methods:  ERG responses to brief flashes with luminous energies between 0.3 and 700 scot td.s were recorded from anaesthetised macaque monkeys and cats.  The timecourse (to 600 ms) of the rod response to the weaker flashes was determined using a probe-flash of about 15000 scot td.s. Results:  The basis of our proposed model is the assumption that the rod photoresponse results from compression by an instantaneous nonlinearity of a signal generated by a linear mechanism.   In this respect, as well as in the formulation of the basic response of the linear mechanism, our model can be considered to be a modification of Hetling and Pepperberg's (1999) model for the mouse.  However, to obtain good fits to our data without introducing a time-dependent gain factor, we have modified their model so that a) the linear system includes an extra low-pass filter element with a time constant of 15 to 20 ms, b) the non-linear characteristic is modelled as a weighted sum of exponential and hyperbolic functions (making the saturation less abrupt than a simple exponential function) and c) the transport delay is reduced to < 1ms (from about 3ms).  Conclusions: We have generated a model that provides a good description of both the early (<10ms), low amplitude (< two-thirds max.) portion of ERG a-waves and the complete time course of derived P3 to flashes of all energies studied. This model describes the response, r(t), of the rods by:
r(t) = rmax{F[1‑exp(‑s(t))]+(1‑F)s(t)/(1+s(t))},  0>F>1 and s(t) = {kI[1‑exp(‑(t‑td)2/TE2)]exp(‑t/TR)}*exp(‑t/TX),  t>td 
where rmax is the maximum response, F determines the abruptness of the saturation, td is a transport delay, k is a constant, TE and TR characterise the time of excitation and recovery and TX is an additional time constant. The * indicates convolution. This model should improve our ability to analyse the ERG into its basic components and provide a better estimate of the timecourse of the signal transmitted from rods to bipolar and more proximal cells. 
References Birch, Hood, Nusinowitz & Pepperberg (1995) IOVS 36,1603-1614;  Hetling & Pepperberg (1999) J. Physiol. 516.2, 593-609.

Jgr11@cam.ac.uk

A MULTI-CHANNEL AND SHAPE-INDEPENDENT DETECTOR FOR 
MULTI-FOCAL VISUAL EVOKED RESPONSES IN OBJECTIVE PERIMETRY

K Schellhorn, F Schlegelmilch, G Henning

Department of Biomedical Engineering, Ilmenau Technical University, Germany

Purpose: To detect the monoocular visual field, an objective perimetry based on the local stimulation of the retina and the recording of the visual evoked responses (VER) was developed. Since the VER gives very weak signals their shape and projection over the visual cortex varies, so a multi-channel and shape-independent detector is required. Methods: The retina is stimulated multi-focally by white LED flashes inside a visual field of 60° using the sparse M-sequence stimulation technique. The EEG is recorded over the cortex using an array of 32 electrodes. From the raw EEG at each channel an M-sequence matrix is read out synchronously to the beginning of the inter-stimulus interval. Each resulting realization of the M-sequence matrix is normalized, filtered and transformed to normal scores before weighting by the M-sequence coefficients and averaging over all realizations. Thereby the inter- and intra-individual variability during EEG recording can be reduced significantly. Further, the transformation to normal scores allows a comparison of empirical and theoretical test statistics. Results: The global field strength and the topography of first and second order kernels are highly dependent on the stimulus location. From non-stimulated EEG data of 10 volunteers a reference of over 300000 quasi-independent samples is found resulting in a Chi-square distribution with one degree of freedom after squaring the values. Considering the length of the applied filters a sensible combination of quasi-independent samples over the relevant time-range increases the degrees of freedom of the Chi-squared distributed test values according to the theory. If a VER is present the quadratic test values show significant deviation from the distribution of the non-stimulus reference data. Thus signal (VER) and noise (no VER) can be distinguished statistically. Conclusions: Amplitude and latency as a reference for cortical M-sequence VER can only be used within small stimulation areas where the projection at the cortex is approximately the same. If a large visual field is scanned simultaneously, the use of a shape and projection independent detector is necessary. The proposed method allows the investigation of different M-sequence parameters like size and luminance of the LED, background luminance, length of M-sequence, stimulus on-time and inter-stimulus interval with regard to achieving a sufficient SNR for perimetric investigations. Furthermore, an electrode combination can be derived allowing a reliable detection of VER inside a visual field of 60 degree using only four electrodes. 

ksc@informatik.tu-ilmenau.de

FUNCTIONAL PERIPHERAL VISUAL PERFORMANCE IN PATIENTS WITH RP

W Seiple, K Holopigian, RE Carr

New York University School of Medicine, Department of Ophthalmology, New York, NY, USA

Purpose: To assess peripheral electrophysiological responses and psychophysical function for detection, discrimination, and identification in patients with RP.  Methods: Ten patients with RP who had >20/40 visual acuity were studied. Psychophysical performance was assessed on the following tasks: grating acuity, grating contrast sensitivity, grating discrimination and letter identification at eccentricities from 0o to 20o in the temporal retina.  Also, cone multi-focal ERG responses (103 hexagons; 0F condition) and Humphrey visual field thresholds were obtained for the same retinal areas. Results: Peripheral thresholds were closer to normal values (lower thresholds and larger field area) for grating discrimination than for letter identification thresholds or for Humphrey visual field thresholds. Peripheral performance was poorest for grating acuity and grating contrast thresholds. Multi-focal ERG responses were markedly abnormal in amplitude and timing at many retinal locations where psychophysical performance was normal or near normal. Conclusions: When assessing peripheral performance in patients with RP, responses to functional tasks may show less impairment than indicated by detection tasks such as Humphrey visual fields or by local electrophysiological responses. 

whs4@is3.nyu.edu

SEVERE AMBLYOPIA: WHAT IS IT?

AM Shamshinova, IM Mosin, AA Krivosheev, HL Barseghyan, AP Dvorianchikova

Helmholtz Research Institute of Eye Diseases, Moscow, Russia

Purpose: To study why visual functions do not improve in patients with "severe" amblyopia, in spite of treatment. Methods: 20 children aged from 4-7 years with severe amblyopia were investigated. Visual acuity was reduced from the birth on one or both eyes (0.3-0.03) in these patients. These patients had a history of perinatal complications etc. The fundus of the eye as a rule was normal. Ganzfeld ERG, local ERG and VEP were used to examine the visual system. VEP maps, and localization of bioelectrical source activity were realized using a computer program "Brainlock"(MBN, Russia). Spatial contrast sensitivity, colour vision and on/off-activity of the cone system research were realized by using original computer programs, and a high resolution color monitor. All functional data were compared with results of computed tomography and magnetic resonance imaging. Results: A range of refractive errors was found. Ganzfeld and local ERG were normal or slightly reduced and color sensitivity was considerably reduced for red and green. Most of the patients had reduced on/off-activity both for light  (on), and for dark (off) channels in comparison with normal subjects. The spatial contrast sensitivity was reduced throughout the range of frequencies in both eyes with large losses at high spatial frequencies, and reductions at low and middle spatial frequencies. The source of bioelectrical activity was absent in the occipital lobe or was poorly expressed in the contralateral occipital lobe in patients with "severe" amblyopia. All the patients had changes in the VEP: they had poor responses to patterns with 7-55 min check sizes, with increased latency and decreased amplitude of the P100 component. The dominant activity was not in the occipital lobe, but was shown in other areas of the brain (hypothalamus, parietal and frontal lobe). These findings suggested abnormal processes in the area of the calcarine sulcus. Magnetic resonance imaging showed congenital brain malformation or diffuse brain tissue loss in different areas in 15 of these patients. Conclusion: Impaired development of the central visual pathway, of various causes, was present in most of these cases with "severe amblyopia".

diblag@cityline.ru

THE PATTERN ELECTRORETINOGRAM (PERG) AS AN INDICATOR OF 
EARLY HYDROXYCHLOROQUINE TOXICITY

DM Sharp, JI Sissingh, B Lunt

Eye Department, Auckland Hospital, Auckland, New Zealand

Purpose: While Chloroquine toxicity has been well recognized, Hydroxychloroquine toxicity and the potential for progression after cessation of treatment has been poorly documented. This study aimed to identify early signs of Hydroxychloroquine toxicity using a practical monitoring protocol.    Methods:  Based on reported retinopathy in the international literature, a Hydroxychloroquine monitoring protocol was established. Baseline tests included visual acuity, Ishihara colour vision, Humphrey 10-2 central visual field and dilated fundus examination. The recommended dosage was 6.5mg/kg with a cumulative dose < 700g. A PERG was performed on patients with abnormalities noted on the visual field test or fundus examination and on patients who had exceeded the recommended dosage.  Results: Decreased visual acuity, Ishihara colour vision defects and clinically obvious fundus changes occurred as a late stage of toxicity.  The computerised visual field testing of the central 10 degrees identified reduced paramacular sensitivity with ring scotomas 3 to 8 degrees from fixation as the classic defect in Hydroxychloroquine toxicity.  Subtle visual field defects were often more difficult to interpret. The PERG was able to identify abnormal macular function at an early stage of toxicity and to differentiate potential toxicity from localised retinal pigment epithelial abnormalities. A patient with significant progression of toxicity over a three-year follow-up highlighted the urgency for early recognition.  Conclusions: Case studies suggest the PERG provides an early indicator of macular dysfunction in Hydroxychloroquine therapy. In combination with computerised central visual field testing it is a valuable tool for early detection of a potentially progressive toxic maculopathy.

akvision@ahsl.co.nz

L AND M CONE SIGNAL CONTRIBUTIONS TO THE MULTIFOCAL ERG:
INTERDIVIDUAL AND TOPOGRAPHICAL VARIATION

LT Sharpe, JF Albrecht, H Jägle

Forschungsstelle für Experimentelle Ophthalmologie, Universitäts-Augenklinik, Tübingen, Germany

Purpose: To estimate interindividual and topographical variation in the distribution of long-wave (L-) and middle-wave (M-) sensitive cones in normal observers, using the multifocal ERG. Methods: Subjects were 15 males and 4 females.  Their multifocal ERGs were measured with a DTL fiber electrode; the responses of which were amplified and filtered between 10 and 100 Hz (Grass Instruments).  The Stockman & Sharpe (1999) cone fundamentals were used, in combination with "silent substitution" techniques, to generate L- and M-cone-isolating stimuli, which had a maximum Michelson contrast of 46%. The stimuli were generated on a flat-screen SONY Trinitron CRT monitor, using a 37-element array of hexagonal cells (VERIS system Version 3.1) which subtended 58° x 50° of visual angle at a viewing distance of 32 cm.  The recorded signals were analyzed according to retinal quadrant (nasal, temporal, superior, inferior), whole rings, and half-rings oriented along the horizontal meridian at 0° (+2.5°), 6° (+3.5°), 14° (+4.5°), and 23.75° (+5.25°) of retinal eccentricity.  L-cone to M-cone ratios were estimated at the various retinal locations by model fits and compared with psychophysical estimates obtained from heterochromatic flicker photometry for centrally and peripherally fixated 2° fields.  Results: For the whole field stimulus, the L/M cone ratio ranged from approximately 0.88±0.085 to 2.5±0.19 with a mean of 1.7.  An extreme (inverted) value was found in a female carrier for protanopia, whose L/M cone ratio was 0.12±0.03. The foveally and peripherally determined L/M cone ratio values correlated highly with those determined from heterochromatic flicker photometry.  No consistent differences in L/M cone ratio were found between the two eyes of any observer nor between the superior and inferior retinal hemifields in each eye.  However,  the L/M cone ratio was approximately 35%±22% times greater in the nasal than in the temporal retinal half-fields.  In general, the ratio increased with eccentricity from the fovea. The maximum variation in the L/M cone ratio with retinal eccentricity, in a normal male observer, was 1.3 (fovea) to 3.1 (23.75° nasally); the minimal variation was 0.82 (fovea) to 1.0 (23.75° nasally) in a female observer. Conclusions: The topography of  the L- and M-cone signals can be measured in color normal observers by the multifocal ERG. The derived L/M cone ratios correlate with those obtained from psychophysical estimates and are similar to those derived from L- to M-cone pigment mRNA ratios in human and Old World monkeys. 

ted.sharpe@uni-tuebingen.de

AMPLITUDE-CHECK SIZE FUNCTION OF PATTERN REVERSAL VISUAL EVOKED RESPONSE IN PATIENTS WITH MACULAR DISEASES

AA Shihab

International Eye Hospital, Cairo, Egypt

Purpose: The aim of the present work is to interpret PVER in an unconventional way so as to examine its efficacy in detecting macular lesions and early macular problems. Methods: 20 normal subjects (35 eyes) and 15 patients (21eyes) were included in the study. The patients were from the International Eye Hospital. The normal subjects were volunteers from hospital staff and were matched in age to the patient group. All had complete ophthalmic examinations. Only patients had fundus photography on both eyes. All had PVER test. The steady-state PVER was recorded with five check sizes (36.6, 73.2, 90.9, 120, 150 minutes of arc). The amplitude-check size function was plotted for each patient. The maximum and minimum PVER amplitudes were calculated. The area under the function was calculated (spatial tuning area). Results: Values for the patients with macular lesions were significantly smaller than those for normal subjects, and the shape of the function was distorted. Conclusion: The two dimensional analyses of PVER provided a tremendous amount of information about the visual system. It proved useful in diagnosing patients with macular lesions and in separating normal subjects and patients with early macular lesions. 

dshihab@hotmail.com

PRIMARY OPEN ANGLE GLAUCOMA: A STUDY USING MULTI-TESTS APPROACH OF ELECTROPHYSIOLOGY, ULTRASONOGRAPHY AND FLUORESCEIN ANGIOGRAPHY

AA Shihab

Ophthalmology Dept, Minia University School of Medicine, Egypt

Purpose: The aim of the present work is to study cases with primary open angle glaucoma (POAG) depending mainly on objective tools instead of common subjective ones. Electrophysiology, ultrasonography and fluorescein angiography (FA) were chosen. Methods: Twenty normal subjects (40 eyes) and twenty patients (38 eyes) of a similar age group were studied. All were attending Minia University outpatient clinic. Patients and normal subjects had a full ophthalmic examination and underwent ultrasonography and electrophysiology testing. FA was performed only on the patients. The hypothesis of retinal ischemia as an underlying mechanism of visual loss in POAG was studied. Critical fusion frequency was detected using the full field flicker ERG. FA was performed to detect optic nerve head ischemia. The extent of nerve fiber death or atrophy was assessed as a decrease in the echographic optic nerve diameter. The obtained data were statistically analyzed using t-test. Results: Retinal ischemia monitor results were highly significant in differentiating glaucoma patients from normals (p<0.000). The critical fusion frequency for patients was much lower than for normals and the difference was highly significant (p<0.0002). The echographic measurement of optic nerve diameter in POAG subjects was significantly smaller than in normal subjects (p<0.001). Peripapillary optic atrophy and absolute filling defect were constant findings among the examined group of patients. Conclusion: : A multi-test approach using objective tests is very useful and reliable in establishing the diagnosis of POAG and in pointing out the underlying pathology. It is useful in early detecting glaucomatous damage especially in difficult cases with opaque media or optic disc anomalies.

dshihab@hotmail.com 

ASSESSMENT OF THE DEGREE OF AMBLYOPIA IN CHILDREN WITH PARTIAL CATARACTS

AA Shpak

IRTC "Eye microsurgery", Moscow, Russia

Purpose: The goal of this study was to develop the method for the assessment of the degree of amblyopia in children with partial cataracts. Methods: Pattern-reversal visual evoked potentials (VEP) elicited by 4 patterns of different checksizes (60' and 20') and contrasts (90% and 30%) were used for the rough evaluation of contrast sensitivity at low spatial frequencies. VEP were registered in 60 children (96 eyes) with partial cataracts (55 eyes) or stimulus deprivation amblyopia after cataract extraction (41 eyes) and 41 controls. Results: Three 'types' (degrees of deterioration) of VEP were established in patients with stimulus deprivation amblyopia after the cataract extraction. In VEP of type I all 4 evoked responses were present but could be of slightly decreased amplitude. In VEP of type II 1 or 2 responses were absent and in type III only pattern of 60' checks and 90% contrast evoked the VEP. A direct relationship was found between the VEP types and the degree of amblyopia (the degree of visual acuity loss). Similar relationships were established in patients with cataracts of different intensity (slight or pronounced). Conclusions: The proposed VEP-method might be useful in objective evaluation of the degree of amblyopia in children with partial cataracts.

A.Shpak@g23.relcom.ru

HUMAN RETINAL COLOR PROCESSING STEPS REVEALED BY PHASE AND AMPLITUDE ERG RESPONSE TO SINUSOIDAL STIMULI

F Siebert, R Gemperlein

Zoologisches Institut, Ludwig-Maximilians-Universität, München, Germany

Purpose: Human ERG is recorded under photopic conditions using coloured sinusoidal Ganzfeld stimuli. By analyzing the amplitude and phase response and by the comparison of the responses to different color stimuli the characteristics of the underlying processes can be revealed. Methods: Output of a xenon lightsource is sinusoidally intensity modulated (2-30Hz) by a mechanical scanner. In addition different color filters (red, green, violet and white (no filter) in appearance) are applied. Each result is combined from 4 single measurements (2-3, 4-7, 8-16, 17-31Hz) to avoid nonlinear interference effects. The ERG response to ganzfeld conditions (Ulbricht sphere) is recorded using an eyecup electrode (Nicolet). After applying the FFT the linear amplitude and phase spectra of the 4 measurements for each color stimuli were combined to full range response. Results: Amplitude responses to white, green and violet show a dominant peak at 2-3Hz and the maximum of white light response is reduced to approximately 50% of the colored responses. All curves but the response to red show a shoulder from 4Hz to 8Hz, which only for violet extends up to 15Hz. Red response shows nearly no distinct shoulder at all. Unexpectedly all responses are constant on different levels from 15Hz to 30Hz. The overall shapes of white and green response are very similar. Each of the phase responses to white, green and violet stimuli is nearly linear, decreasing for increasing frequency, but showing a different offset which remains constant over all measured frequencies. Only the red response shows a divided shape: for 2-12Hz it is linear with maximum offset of all measurements, but for 16-30Hz it is nearly similar to the white phase curve. The offset for green phase response in comparison to white response is about 50 degrees, for violet response about 90 degrees, for red response about 130 degrees (2-12Hz) and about 20 degrees (15-30Hz). Conclusion: The parallel shifted phase characteristics of green and violet compared to white seems to reflect processing of color stimuli, because differences in temporal processing would cause divergent phases for higher frequencies. Thus the amplitude spectrum is obviously generated not only by the receptors, but also by related color opponent systems. The measured response is the result of the superimposed output of several generators that are summed up by vector addition. Further studies will deal with this addition to explain e.g. the amplitude spectra and the striking shape of the red phase spectrum.

rg@zi.biologie.uni-muenchen.de

OSCILLATORY POTENTIALS OF THE ELECTRORETINOGRAM IN THE FOLLOW-UP OF HYPERTENSIVE PATIENTS WITH FOUR DIFFERENT PHARMACOLOGICAL TREATMENTS

N Solimano, G Rinaldi, G Ravalico

University Eye Clinic of Trieste, Italy

Purpose: Oscillatory potentials of the electroretinogram are useful to confirm the diagnosis of essential hypertension. The oscillatory index can be considered an early marker of retinal vasculature damage. Our purpose is to find any differences in the oscillatore potentials among the groups of hypertensive patients with four different pharmacological treatments.  Methods: Forty-six hypertensíve patients underwent primary antihypertensive therapy with four different pharmacological treatments: angiotensin-converting enzyme inhibitors (12 subjects); angiotensin AT1 receptor antagonists (11 subjects); betablockers (12 subjects); calcium antagonists (11 subjects). Oscillatory potentials were recorded before the treatment and after twenty-four months with Lace Erev 2000 (ISCEV Standards).  Results:The oscillatory index increased in a statistically significant manner in the angiotensin-converting enzyme inhibitor group and in the calcium antagonist group.Conclusion: Probably angiotensin-converting enzyme inhibitors and calcium antagonists increase the retinal blood flow with a mechanism of vasodilatation.

FAST AND SLOW OSCILLATION ELECTRO-OCULOGRAPHY IN HARADA'S DISEASE

A Tamai, J Hamamoto, Y Sasaki, K Iba, A Setogawa, T Nakamura, A Yamasaki, M Inoue, M Nagata

Department of Ophthalmology, Faculty of Medicine, Tottori University, Yonago, Japan

Purpose:  To assess clinical utility of fast oscillation (FO) and slow oscillation (SO) of the electrooculogram (EOG) in Harada's disease (posterior uveitis type of Vogt-Koyanagi-Harada syndrome). Methods:  In 8 eyes of 4 female patients aged 18 to 77 years (average: 40.8 years) with Harada's disease, FO and SO were recorded using a newly devised automated electrooculograph, Nidek EOG-2 (Nidek, Gamagori, Japan), in the acute period before treatment and in the remission period under corticosteroid therapy.  In 10 pairs of FO measurements (dark-light period of 1 minute each), FO parameters, namely Rf value (average ratio in % of the maximum amplitude in the dark period (AD) / the minimum amplitude in the light period (AL)) and df value (average difference in µV between AD and AL) were evaluated. In the SO recording of 20 minutes darkness followed by 20 minutes illumination (a background luminance of 1270 lux at the location of the subject's eyes), the light peak / dark trough ratio of the SO (L/D ratio) was calculated as an SO parameter. Results:  In all 8 eyes, the Rf and df values, low in the acute period, increased remarkably in the remission period.  The L/D ratio, low in the acute period, also increased in the remission period in 3 of the 4 cases (6 eyes). However, in 1 case (77 years of age), in which the L/D ratio had been in the normal range in the right eye and subnormal in the left eye in the acute period, slightly decreased L/D ratios were detected in the remission period in both eyes. Conclusions:  The FO may therefore be well reflected in Harada's disease, in contrast to the SO.  However, further observation is required, using more Harada's disease patients.

CONE ELECTRORETINOGRAMS RECORDED UNDER THE CLINICAL SLIT-LAMP EXAMINATION

A Tanikawa, M Kondo, S Suzuki, Y Miyake

Department of Ophthalmology, Nagoya University School of Medicine, Japan

Purpose:  To determine the clinical usefulness of a new contact lens electrode, which is attached to the Goldmann applanation tonometer, for recording full-field cone electroretinograms (ERGs).  Methods:  A high-brightness, white light-emitting diode (LED) (peak, 440 and 540 nm) was incorporated into a contact lens electrode which was attached to the Goldmann applanation tonometer of the slit-lamp.  The white LED served as the source for both stimulus and background.  A white diffuser was placed between the LEDs and cornea to produce a homogeneous stimulus and background illumination to the retina.  Full-field photopic ERGs and 30 Hz flicker ERGs were recorded with stimulus intensity of 9200 (photopic ERG) and 1100 (flicker ERG) cd/m2 on a steady background of 41 cd/m2 from five normal subjects (age, 18 to 62 years) and a patient with cone dystrophy.  Results:  We successfully recorded reliable photopic ERGs and 30 Hz flicker ERGs from normals and a patient with cone dystrophy.  Mean (± SD) amplitudes of photopic ERG (b-wave) and flicker ERG for normals were 106.7 (± 41.3) and 85.6 (±18.2) uV, respectively.  Mean (+- SD) implicit times of photopic ERG (b-wave) and flicker ERG for normals were 30.9 (±1.7) and 37.7 (± 3.2) msec, respectively. In a patient with cone dystrophy, severely reduced responses were recorded.  Conclusions: Our system made it possible to record photopic and 30 Hz flicker ERGs immediately after the clinical slit-lamp examination.  The compactness and ease of using this system suggest that it will be clinically useful for the screening of retinal disorders.

tani@med.nagoya-u.ac.jp

SPATIAL AND TEMPORAL PROFILE OF VISUAL EVOKED MAGNETIC FIELD (VEF)
TO PATTERN-REVERSAL STIMULATION

H Tanikawa, H Ohde, Y Kurobe, Y Haruta, Y Mashima, Y Oguchi

Keio University, Tokyo, Japan

Purpose: Magnetoencephalography (MEG) is one of the non-invasive methods developed for studying human-brain function and has been applied to many studies of human visual function. In this report, we used MEG to study spatial and temporal profile of the VEF following the pattern reversal stimulus. Methods: The VEF of three normal adults were recorded in a magnetically shielded room using a 150-channel whole-head type gradiometer. The visual stimulation of sinusoidal grading pattern reversal was carried out with temporal frequencies from 4Hz to 16Hz and spatial frequencies from 1cycle/degree (c/d) to 10c/d. This stimulus were presented in front of the subject. The sources of the VEF components were estimated using the equivalent current-dipole (ECD) estimation method. To analyze the VEF components, the data were classified by Fast Fourier Transform (FFT) analysis, and the power of the fundamental frequency component and the second harmonic component were measured. Results: The VEF changed alternately at the right and left hemisphere of the posterior region with the same frequency as the stimulus rate. The two ECDs were estimated at the primary visual cortex, and the directions of these two ECDs were symmetrical. The power of the fundamental frequency component was maximal when the stimulus temporal frequency was 8Hz and spatial frequency was 1c/d. The power of the second harmonic was maximal when the stimulus temporal frequency was 8Hz and the spatial frequency was 6c/d. The VEF became very small when the temporal frequency was over 16Hz. There was a modulation transfer function-like profile of the spatial frequency at the second harmonic, but not the fundamental frequency. Conclusions: The second harmonic component should depend on the pattern stimulus. It was interesting that the two ECDs appeared at right and left visual cortex alternately with the sinusoidal grading pattern reversal stimulation, otherwise the two ECDs were estimated simultaneously at both visual cortexes with the transient stimulation.

czb03025@alles.or.jp

PSEUDORETINITIS PIGMENTOSA: A DIAGNOSIS SOMETIMES EASY, SOMETIMES COMPLICATED

AP Tormene, R Busana, C Riva

Ophthalmic Institute of Padova University, Italy

Introduction: Pseudoretinitis pigmentosa offers a series of clinical pictures that are, ophthalmoscopically, similar to those of an hereditary degenerative illness but which, however, have a different etiology, and hence different clinical development. Methods: The clinical picture and medical histories of 10 subjects are described. All subjects were thought to suffer from hereditary retinal or choroidal degeneration. All subjects underwent ERG Maximal Combined Response, Rod Response and Cone Response which were recorded in line with the stimulation and recording guidelines set out by the ISCEV. Results: ERG was normal or reduced proportionally to the ophthalmoscopically visible degree of retinal damage. Pseudoretinitis pigmentosa or pseudo heredodegeneration of the choroid was diagnosed on the basis that ERG was normal despite the condition of the fundus, but in some cases alterations in ERG made it more difficult to diagnose the illness; in these cases the patient's medical history was crucial for diagnosis. Conclusions: The clinical picture of the fundus or the fact of night blindness sometimes suggest the diagnosis of tapetoretinal degeneration but only the use of ERG in conjunction with careful investigation of medical histories are important for the correct clinical assessment and diagnosis. The possibility of excluding the illness in some subjects who belong to families where real retinitis pigmentosa exists is crucial for genetic study. 

tormene@ux1.unipd.it

FUNCTIONAL AND ELECTROPHYSIOLOGICAL CORRELATES OF VISUAL LOSS WITH VIGABATRIN (SABRIL)

K van der Torren, H Graniewski, BCP Polak

Ophthalmology Dept, Merwerdeziekenhuis Dordrecht, The Netherlands

Vigabatrin (Sabril) is an anti-epileptic agent which has been used for about 10 years as an adjunct treatment for patients with epilepsy and the West syndrome when there are difficulties in regulating the treatment. At the end of 1997 the first announcements were made in the neurological literature about vigabatrin-associated visual field constriction. It seems now after ERG and visual field examination, that there is serious vision field constriction and related vision function loss on the ERG examination.

THE FAST SPIKING STR: A PHOTOPHOBIC OCULOMOTOR ARTIFACT OCCURRING NEAR ABSOLUTE SCOTOPIC THRESHOLD

Vaegan

VisionTest Australia, The Eye and Vision Research Institute, Sydney, Australia

Aim: To explain the generator for a peculiar, rare form of scotopic threshold response STR. Background: The STR is an apparently simple, small (<15uV), broad (ca 30msec wide) negative-going ERG wave with a peak time of about 85-140 msec depending on intensity. It can be recorded with increasing amplitude for about 3 Log Units above absolute threshold. This STR is now known to have at least two components of about equal size, one of which is generated by ganglion cells. For 8 years I have occasionally observed, mainly in patients with early or late onset slowly progressive cone dystrophies, an STR with a very fast swtiching PNPNP shape, which increased in amplitude with intensity. A similar pattern has never been seen in any animal study. Methods: An STR amplitude intensity series was routinely recorded in all ERG patients for 9 years. Initial studies, for 4.5 years in a hospital clinic, used gold foil electrodes. In the second 4.5 years DTL electrodes were used in over 600 suceessive patients. Results: The fast switching pattern was seen in about 20 patients in the first series, including a father and daughter. In the latter series it was seen about 8 times. The fast switching form was less complex with DTL electrodes and the shape was sometimes just NP. One patient in the latter series had early RP. In 2 others the response continued to grow right up to the maximum intensity flash and could be seen in the ongoing record to be an eye movement artifact. Conclusion: The fast switching STR is more complex and frequent with electrodes which contact the cornea. It is mainly unusual because it is generated near threshold. It is probably an artifact of habitual photophobia and due to a heavily damped oculomotor response, either from eye movements, lid tightening, or the retractor bulbi. It is not a new type of evoked response or a useful clinical sign.

vaegan@unsw.edu.au

 THE VISUAL FUNCTION OF IDIOPATHIC MACULAR HOLE BEFORE AND AFTER SURGERY

DZ Wu, T Zhao, R Gao, S Zhang, L Wu, J Liang

Zhongshan Ophthalmic Center, Sun Yat-sen University of Medical Sciences, Guangzhou, China

Purpose: To investigate visual function in idiopathic macular hole (IMH) before and after macular surgery. Methods: Vitreous-retinal surgery was performed in 19 patients (19 eyes) with IMH. Among them, 3 eyes were stage 2, 10 eyes were stage 3 and 6 eyes were stage 4. Visual functions including visual acuity, laser retinal visual acuity, photopic ERG intensity responses and Humphrey 30o-2 visual field were tested and compared before and after surgery. The mean time of follow-up was 4 months. Results:  best-corrected visual acuity was from 0.01 to 0.1 before operation, and from 0.04 to 0.4 after operation; there was no statistically significant difference between pre- and post-operation (p>0.05).  laser retinal visual acuity: was from 0.12 to 0.4 before operation, and from 0.2 to 0.63 after operation; there was statistically significant difference between pre- and post-operation (p<0.05).   in the region from 0.5log units to 3 log units of stimulus intensity, the photopic ERG intensity intensity-response of theb-wave exhibited the S-shaped curve which fits the Naka-Rushton equation. The value for Log K was decreased after surgery; there was a statistically significant difference between pre- and post-operation (p<0.05). There was no statistically significant difference between pre- and post-operation for Rmax and n.  the visual field thresholds for 0-10o area increased after surgery; there was a statistically significant difference between pre- and post-operation (p<0.05), but there was no statistically significant difference between pre- and post-operation for 15-30o area. Conclusions: The visual function of cones in the macular region is increased by macular surgery for IMH.

wdzzoc@gzsums.edu.cn

THE APPEARANCE OF MULTIFOCAL ERG IN PRIMARY AND SECONDARY MACULOPATHIES

L Wu, SZ Huang, D-Z Wu, JM Ma

Zhongshan Ophthalmic Center, Sun Yat-Sen Univesity of Medical Sciences, Guangzhou, China

Purpose:  To observe and compare the differences of multifocal ERG (MF-ERG) in primary and secondary maculopathies. Methods:  Testing with VERIS Science Tm 4.0 System, the MF-ERGs from 11 eyes of age-related macular degeneration, 7 eyes of idiopathic macular hole, 6 eyes of diabetic retinopathy and 2 eyes of central retinal vein occlusion were analyzed and compared.  Results:  Comparing with primary maculopathies as dry form age-related macular degeneration and idiopathic macular hole, the MF-ERGs of secondary maculopathies had wider and more irregular changes in the peripheral responses.  The longer latencies and abnormal average response densities of MF-ERGs were related to the retinal lesion field and conditions of system or original diseases. Conclusion:  The different appearances of MF-ERG between primary and secondary maculopathies will help to evaluate the visual function and prognosis in macular diseases.

lwuicv@gzsums.edu.cn

VISUAL ELECTROPHYSIOLOGY FOR ALCOHOLIC OCULAR CHANGES

Yin Weijing, Guo Xirang, Dong Yingli, Wang Mei

Henan Institute of Ophthalmology, Zhengzhou, China

Objective: We observed and followed-up the ocular damage of acute or chronic alcoholics with visual electrophysiologic detection and studied its pathologic mechanism. Method:  Scotopic ERG, flash- or pattern-VEP (F-VEP or P-VEP) and visual field, fluorescein angiography with fundus photography (FFA) were performed for 9 cases  (18 eyes) with alcoholic ocular changes. Maximal combined response of ERG and P-VEP were detected according to international standard protocols. Pattern VEP stimulation was with 32 minute of arc checks, with contrast of 80%. Amplitudes of a-b ERG wave and the implicit times of the VEP P100 component were analysed. Results: 2 of 3 cases (4 of 6 eyes) presented normal ERG response and irrecorded F- or P-VEP P100 component in acute alcoholics. They returned to normal after treatment. One case (2 eyes) showed permanent ERG a-b wave amplitude and P-VEP P100 components changes. Irreversible visual field abnormalities of a-, b-wave amplitudes and P100 latency were found in chronic alcoholics. Extensive retinal pigment layer damage was demonstrated by FFA examination in acute and chronic alcoholics. Conclusion:  Acute or chronic alcoholism can damage retinal pigment epithelium and the ERG and VEP can monitor these ocular changes.

MULTIFOCAL ELECTRORETINOGRAM IS DISTORTED BY ARTIFACT REMOVAL PROCEDURE

M Yoshii, K Yanashima, S Suzuki, S Okisaka

Department of Ophthalmology, National Defence Medical College, Tokorozawa, Japan

Purpose: To study whether the 'Artifact Removal' procedure that is thought to remove artifacts effectively in the multifocal electroretinogram system (mERG) works correctly or not.  Methods: A test wave was made only in the center part of the stimulus elements using a photo-diode circuit. mERGs were recorded using the Veris III system (Mayo corporation) from a well-trained normal subject, and were analyzed by the Artifact Removal procedure that is included in the Veris Science software program. The stimuli consisted of densely arranged arrays of 103 or 37 hexagonal elements. The pupils were fully dilated and a bipolar contact lens electrode was used. It took 8 minutes to obtain one mERG record, and 16 segments were required to perform this record. The second order kernel response components were extracted by Veris Science software, and the artifact removal procedure was done for both first and second order kernel response components. Results: Artifact removal procedure influenced both the test wave on the center element as well as the 'immediate neighbor' traces. After repeating the artifact removal procedure, the shape of the test wave changed considerably. Some of the traces of the second order kernel response components elicited from a normal subjects changed irregularly when the Artifact Removal procedure was repeatedly used. Conclusions: mERG is distorted by the Artifact Removal procedure.

masaruy@mb.infoweb.ne.jp

MULTIFOCAL CRITICAL FLICKER FUSION FREQUENCY IN DIAGNOSIS OF 
VISUAL FIELD DEFECTS

MV Zueva, IV Tsapenko, KV Golubtsov, GJu Zakharova, ZKh-M Khashaev

Helmholtz Research Institute of Eye Diseases, Moscow, Russia

Introduction: Methods for examination of visual field defects include different modifications of computer perimetry and estimation of critical flicker fusion frequency (CFFF). In this paper, the new method of diagnosis of visual field defects - multifocal CFFF - is presented, which may have the advantage of being more specific for particular types of defects. Methods: The method is based on the use of a new diagnostic device which includes a light-tight mask with eye-glass stimulator in the form of  two hemispheres. Inside each eye-glass hemisphere, 39 (or more) multi-colour (red, blue or green) light-emitting-diods (LEDs) are inserted  centrally and in several paracentral and peripheral rings. The examination of CFFF is carried out at all the points successively using a different intensity and colour of stimulation. The data in multifocal maps are registered by means of computer program.  Results: The multifocal mapping of CFFF was performed in 8 healthy subjects and in patients: with flat rhegmatogenous retinal detachment (RD) in the upper part of fundus, disciform stage of age-related macular dedeneration  (AMD) and with a tumor in the left visual cortex. In the maps of CFFF in healthy subjects, the non-homogeneous distribution of sensitivity to flicker was shown for different local zones of the visual fields. All the patients were also tested with a Rodenstock Perimat field analyzer.  We observed similar results of field loss (altitudinal hemianopsia) from both methods in the patient with RD. The correlation between the data of multifocal CFFF and the threshold visual field was subjectively judged to be good in this case. However, in the patient with a tumor in the left brain hemisphere, a right side homonymous hemianopsia was shown in threshold perimetry and a left side loss of flickering sensitivity was revealed with multifocal CFFF. The patient with AMD had a central scotoma in the visual field but showed a general decrease of CFFF in multifocal mapping.  Conclusion: The data of multifocal CFFF and threshold visual field may differ in different visual system pathologies. The method of CFFF mapping is a new, independent test to measure fine defects in the visual field and has potential for clinical use.  

Wednesday 16 February

08.30 – 10.30	Scientific Session 5	AUTO-IMMUNE AND INFLAMMATORY RESPONSES 
	Chairs:	Yozo Miyake;  John Heckenlively

10.30-11.00	Coffee Break

11.00 – 13.00	Scientific Session 6	EXPANDING DIAGNOSTIC METHODOLOGY (2)
	Chairs:	Emiko Adachi;  Ido Perlman

13.00-14.00	Lunch Break

14.00 – 16.00	Posters Session 2	with coffee
	Chairs	Graham Holder;  Ulrich Kellner

16.00 – 17.45	Scientific Session 7	PAEDIATRIC VISUAL ELECTROPHYSIOLOGY
	Chairs:	Colin Barber;  Dianne Sharp

19.30 for 20.00	Symposium Dinner in the Holmes Building of Sydney University
	Including presentation of the Dodt Award by Professor Eberhart Zrenner
	And presentation of the ISCEV Olympics Trophy by Professor Colin Barber 

16.00 – 17.45	Wednesday 16 February

Scientific Session 7	PAEDIATRIC VISUAL ELECTROPHYSIOLOGY
Chairs:		Colin Barber;  Dianne Sharp

16.00	The Activation of Rod Phototransduction in ROP Subjects
	AB Fulton, RM Hansen (Boston, MA, USA)
16.15	Multifocal ERG in children
	C Gerth, M Bock, B Lorenz (Regensburg, Germany)
16.30	Electrophysiological development of dyslexia
	Z Kubová, D Gayer, J Szanyi, M Kuba, J Kremlácek (Hradec Králové, Czech Republic)
16.45	Electrophysiological changes in children with poor vision and nystagmus
	J Brecelj, B Stirn-Kranjc (Ljubljana, Slovenia)
17.00	Development and maturation of the major visual pathways: VEP measures
	MA Crognale (Reno, NV, USA)
17.15	Laplacian analysis facilitates VEP pattern onset acuity estimates: concomitant Snellen acuity equivalents in paediatric patients
	P Apkarian, LJ Bour (Rotterdam; Amsterdam, The Netherlands)
17.30	Monitoring outcomes in a pediatric electroretinography clinic
	CM Panton, CAWestall (Toronto, Ontario, Canada)

THE ACTIVATION OF ROD PHOTOTRANSDUCTION IN ROP SUBJECTS

AB Fulton, RM Hansen

Department of Ophthalmology, Children's Hospital, Boston, MA, USA

Purpose:  To test the hypothesis that the more severe the acute phase retinopathy of prematurity (ROP) was in the preterm weeks, the more severely compromised is the activation of phototransduction in the rods after the ROP has resolved.   Methods:  The rod isolated responses of 25 children (ages 10 weeks post-term to 14 years) were recorded and compared to those of normal controls (n=71).   S, the parameter reflecting the molecular processes in the disc membrane that result in closure of the channels in the outer segment membrane, and Rmp3, reflecting the number of channels available for closure by light, were calculated using the Hood & Birch modification of the Lamb & Pugh model of the activation of phototransduction. The children were categorized by maximum, acute phase ROP (None to Very Severe).   Results:   S and Rmp3 were normal for age in the None category.    In the Severe group, attenuation of S and Rmp3 exceeded that predicted by loss of retinal tissue due to laser treatment.  Among those in the Mild, Moderate and Severe categories, the degree of compromise of both S and Rmp3 were significantly related to the severity of acute phase ROP.   Responses in the Very Severe category were too attenuated to calculate S and Rmp3.  Conclusion:   In ROP subjects, the processes involved in the activation of phototransduction appear less efficient, perhaps due to disorganized rod outer segments such as have been documented in a rat model of ROP.   The results are consistent with the hypothesis that the developing rods, with escalating demands for oxygen and energy, are instigators of acute phase ROP.

fulton_a@A1.tch.harvard.edu

MULTIFOCAL ERG IN CHILDREN

C Gerth, M Bock, B Lorenz

Department of Pediatric Ophthalmology, Strabismology and Ophthalmogenetics,
University of Regensburg, Germany

Purpose: To establish age-matched normal multifocal ERG (MERG) values in children up to 10 yrs and to evaluate the importance of MERG in patients of this age group with reduced visual function and/or morphological changes in the posterior pole. Methods: MERGs (VERIS, 103 hexagons) were recorded in 7 healthy subjects (7 eyes, 7 recordings) aged 6-10 yrs (mean 8.7 yrs, median 9 yrs) and in 35 patients (39 eyes, 42 recordings) aged 4-10 yrs (mean 8 yrs/median 8 yrs). Burian-Allen (BA) electrodes (size 20x19, 21x20) were used in all subjects. In patients, BA (21/42, recording time 3:38) or DTL electrodes (21/42, recording time 7:28) were used. Different fixation crosses (4.8°-21°, 5-8 %) were selected depending on VA and visual field defects. The normal values based on concentric ring analysis were compared to the corresponding values of older age groups. The data recorded in the patients were also analyzed. Indications for MERG in the 35 patients were: decreased VA of unknown etiology (18), retinal/macular disease (12), chloroquine therapy (3) and disturbed color vision (2). Results: Compared to normal values in older age groups response density amplitudes (N1-P1) in the 7 subjects were lower in all concentric rings. Age-matched normal values of response density amplitudes increase up to the age of 20 and decrease in older ages. Faster P1 peak times in all concentric rings were found in the 7 subjects compared to older age groups. In 13/42 MERGs recorded in 12 patients (10/21 DTL, 3/21 BA) concentric ring analysis was impossible because local peaks (N1, P1, N2) could not be identified. 6/42 MERGs showed reduced P1-N1amplitudes and prolonged P1 peak times, 12/42 only reduced P1-N1 and 2/42 only prolonged P1. 9/42 MERGs were within normal values. Conclusions: MERG recordings with BA electrodes were more reliable in children who were less compliant to prolonged recording times. Normal values in children < 10 yrs were significantly different from those of the next age group (11-20 yrs.).

christina.gerth@klinik.uni-regensburg.de

ELECTROPHYSIOLOGICAL DEVELOPMENT OF DYSLEXIA

Z Kubová, D Gayer, J Szanyi, M Kuba, J Kremlácek

Charles University Faculty of Medicine, Hradec Králové, Czech Republic

Purpose;  In our previous study (Kubová et al., Physiol. Res., 44:87-89, 1995) we revealed a significant delay of motion-onset VEPs (M-VEPs) in 70% of dyslexics (mean age of 10 years), which implied a magnocellular system dysfunction (pattern-reversal VEPs were completely normal in the entire group). Now, after four years we re-examined the same group of children to verify an eventual magnocellular system development. Simultaneously a new group of dyslexics (n=17, mean age of 10 years) was tested with the aim to find out whether the hypothesised effect of background colour during reading (reported e.g. by Irlen, Avery Publ. Group, New York, 1991) can be objectively assessed with electrophysiological tests. Methods: Linear motion of low contrast isolated checks and radial centrifugal motion ("expansion") was used for monocular stimulation of both eyes. Responses to black-white, pink, yellow, green and blue stimuli (with the same average luminance and 10% contrast) were compared in Oz, Or, Ol, and Cz leads (with earlobe reference). Results:  The re-examined dyslexic children displayed normalisation of the motion-onset VEP latencies, but 60 % of them had not significantly improved their reading quotients. The new group of dyslexics displayed prolonged (or split) motion-onset negative peak in about 40% of cases. There was no change in pathological latencies when colour stimulation was used. However, the yellow variant of the stimulus provided significantly larger amplitudes. Conclusions:  The smaller proportion of the deficient magnocellular system in this study confirms multifactorial etiology of dyslexia. Profitable application of blue colour was not proved and the found magnification of the motion-onset VEPs in yellow stimuli is not explained as yet.  More data (preferably from adult dyslexics) is needed to verify possible links between VEP pathology and the origin of dyslexia.
Acknowledgements Supported by the James S. McDonnell Foundation for Cognitive Neuroscience, USA and by the Grant Agency of the Czech Ministry of Health (grant No. 4800-3/98)

kubova@lfhk.cuni.cz

ELECTROPHYSIOLOGICAL CHANGES IN CHILDREN WITH POOR VISION AND NYSTAGMUS

J Brecelj, B Stirn-Kranjc

Institute of Clinical Neurophysiology, and Department of Ophthalmology,
University Medical Centre, Ljubljana, Slovenia

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 a condition 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 examinations 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.

jelka.brecelj@kclj.si
DEVELOPMENT AND MATURATION OF THE MAJOR VISUAL PATHWAYS: VEP MEASURES

MA Crognale

University of Nevada, Reno, NV; University of Washington, Seattle, WA, USA

Purpose:  We investigated the relative time course of changes and characteristics of the changes in VEP waveform that occur during development and maturation of the two major visual pathways.  Methods:  Visual evoked potentials were recorded from subjects ranging in age from 1 week to adulthood in response to patterned stimuli presented on a CRT.  Patterns were 0.5 cpd horizontal sinusoidal gratings presented either in an onset-offset mode (200 ms on, 800 ms off) or as pattern reversals (1Hz).  To preferentially modulate the magnocellular (M) pathway, the stimuli were achromatic patterns presented as reversals, and to preferentially activate the parvocellular (P) pathway the stimuli were isoluminant chromatic patterns presented in the onset-offset mode.  Results:  The main component of the achromatic pattern reversal response attains adult latency early in life (ca. 3-4 months). Changes in the waveform are simple and systematic.  The changes in the waveform shapes of the responses to chromatic pattern onset stimuli are much more complex during the first year of life than those for the chromatic reversal stimuli.  More simple changes continue to occur over a prolonged time period and adult-like waveform shapes are not attained until adolescence.   During adolescence the chromatic onset waveform shapes shift from a positive-negative complex to a negative-positive complex or just a negative wave.  These changes can be modeled by a change in major components, one positive and one negative.  The model suggests that the negative component decreases in latency with age while the amplitude of both positive and negative components decreases.  Wavelet analysis of these changes reveals additional features.  Conclusions:  There are long-term changes in the chromatic onset waveforms (P-pathway) that continue through adolescence.  In contrast the waveform shapes generated by low spatial frequency achromatic reversals (M-pathway) do not change appreciably after the first year of life. 

mikro@unr.edu

LAPLACIAN ANALYSIS FACILITATES VEP PATTERN ONSET ACUITY ESTIMATES: CONCOMITANT SNELLEN ACUITY EQUIVALENTS IN PAEDIATRIC PATIENTS

P Apkarian, LJ Bour

Department of Physiology, Erasmus Medical Centre, Rotterdam;
Department of Neurology, Academic Medical Centre, Amsterdam, The Netherlands

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.

apkarian@fys.fgg.eur.NL

MONITORING OUTCOMES IN A PEDIATRIC ELECTRORETINOGRAPHY CLINIC

CM Panton, CA Westall

Visual Electrophysiology Unit, Department of Ophthalmology, Hospital for Sick Children,
University of Toronto, Toronto, Ontario, Canada

Purpose: Pediatric electroretinography is challenging. We have shown previously a success rate of 72% in children less than twelve months and 90% in those older. Our purpose was to examine the results of those children tested sequentially to determine repeatability, reliability and progression of disease. Methods: Between 1996 and 1999 ERGs were recorded in 387 children (aged from 10 days to 15 years) to a predetermined range of stimulus intensities using current ISCEV standards. Appropriately sized Burian Allen electrodes were used. Pupils were checked regularly to ensure their correct dilation and positioning at the centre of the lens. Most babies under 7 months were swaddled and tested lying supine; most children between 7 months and five years were tested in the same way after chloryl hydrate sedation. Those over 5 years sat with a parent or alone. In a few specific cases ERGs were performed under general anesthesia. In all cases ERG results were compared with age-matched control data (Westall, Panton and Levin, Time courses for the maturation of electroretinogram responses from infancy to adulthood. Doc Opthalmol In Press).  A short video will demonstrate these techniques. Results: Of these 387 children, 341 (88 %) were seen on one occasion with 30% of them having normal ERGs. Sequential ERGs were performed on 47 children, 26% of these showed similarity of results and 36% showed progression of disease. Eleven percent showed an inconsistent but still abnormal response, which was attributed to increased compliance at the second test and by enhanced testing protocols determined by age and condition. Results from two children (4%) were considered unreliable. Ten children (23%) showed a reversal from an abnormal to normal result with some exhibiting a greater rate of maturation than that predicted by normal growth curves. Conclusions: By adapting and refining testing protocols and analysis to different ages and conditions, the ERG provides a reliable tool to monitor retinal function over time, in children of all ages. 

cpanton@sickkids.on.ca

Thursday 17 February

08.30 – 10.45	Scientific Session 8	VIGABATRIN MINISYMPOSIUM
	Chair:  	Eberhart Zrenner

10.45-11.15	Coffee Break

11.15 – 13.15	Scientific Session 9	ELECTROPHYSIOLOGY IN ANIMAL STUDIES
	Chairs:  	Kristina Narfstrom;  Pierre Lachapelle

13.30	Farewell lunch on the lawns of St John's College

08.30 – 10.45	Thursday 17 February

Scientific Session 8	VIGABATRIN MINISYMPOSIUM
Chair:  		Eberhart Zrenner

08.30	Electrophysiological methods for assessing field losses associated with Vigabatrin
	GFA Harding (Birmingham, UK)
09.00	Visual field defects: pattern and epidemiology
	C Martinez, S Rietbrock (Bridgewater, NJ, USA; Cologne, Germany)
09.15	Differences in cellular sites of accumulation of Vigabatrin in central versus peripheral primate retina
	DV Pow (Brisbane, Australia)
09.30	The Hospital for Sick Children, Toronto, longitudinal ERG study of children on Vigabatrin
	CA Westall, WJ Logan, JR Buncic, K Smith, CM Panton (Toronto, Ontario, Canada)
09.45	Electrophysiology in epileptic subjects treated with Vigabatrin or other anti-epileptic drugs
	IF Comaish, C Gorman, C Barber, NR Galloway (Nottingham, UK)
10.00	Visual electrophysiological correlates in Vigabatrin treatment
	SG Coupland, D Zackon, T Ross (Ottawa, Canada)
10.15	Visual field constriction and electrophysiological changes associated with Vigabatrin
	D Besch, A Kurtenbach, E Apfelstedt-Sylla, TJ Dietrich, D Dennig, C Asenbauer, E Zrenner, U Schiefer
	(Tübingen, Germany)
10.30	Visual function abnormalities in epileptic children treated with Vigabatrin
	E Banin, V Gross-Tsur, E Shachar, E Lahat, RS Shalev (Jerusalem; Haifa; Zrifin Israel)

ELECTROPHYSIOLOGICAL METHODS FOR ASSESSING FIELD LOSSES 
ASSOCIATED WITH VIGABATRIN

GFA Harding

Aston University, Birmingham, UK

From earliest reports of vigabatrin-attributed visual field defects, abnormalities of visual electrophysiological parameters have been identified.  The interest in identifying electrophysiological markers is (1) at least 20% of adult patients with epilepsy are unable to satisfactorily perform visual field testing; (2) formal perimetry cannot be performed in children below the developmental age of 9 years; (3) electrophysiological markers might indicate both the mechanism of the field defect and might occur before the field loss becomes established. Abnormalities have been reported of the Arden Index of the EOG, photopic b wave of the ERG, OPs of the ERG and the 30Hz flicker response.  We have carried out a number of studies, both on the dilated eyes of patients and normal controls to elucidate which characteristics of visual electrophysiology are associated with vigabatrin therapy, and which characteristics are associated with the visual field defect.  The patients studied included those receiving vigabatrin currently, those with vigabatrin-attributed visual field defects and patients who had never received vigabatrin, but only other AEDs who did not show any abnormalities.  It is apparent that the Arden Index of the EOG, the photopic b wave of the ERG, the latency of the 30Hz b wave and all variables of the scotopic ERG were unrelated to the presence of the visual field loss.  However, the Arden Index and photopic b wave are associated with current vigabatrin therapy, and improvement on withdrawal of this therapy is unrelated to any change in field defect.  The 30Hz flicker response is clearly related both to the presence and severity of the visual field defect, and therefore implicates cone function in the retina.  These variables could provide a screening method for identifying patients who have vigabatrin visual field defects and are unable to produce reliable perimetry.  As visual field testing in young children is problematic, a special field-specific VEP technique has been developed.  The VEP response, separately to both central and peripheral stimuli can be used to identify vigabatrin-attributed visual field defects in young adults.  The technique has been studied on normal children who produce clear responses to both central and peripheral stimulation, down to 3 years of developmental age.  Below this age the technique becomes unreliable and therefore, for very young children following treatment with vigabatrin for infantile spasms, only the ERG can be used.

g.f.a.harding@aston.ac.uk
VISUAL FIELD DEFECTS: PATTERN AND EPIDEMIOLOGY

Carlos Martinez1, Stephan Rietbrock2

1 HMR, Bridgewater, New Jersey, USA; 2 University of Cologne, Germany

There is strong evidence for a unique and characteristic vigabatrin-associated visual field defect pattern (VGB-VFD) in association with the use of vigabatrin. In order to estimate the frequency of VFD in association with vigabatrin, HMR assessed and analyzed the visual fields of more than 400 subjects originating from more than 10 cross-sectional cohorts and one longitudinal study. A reference cohort of 122 epilepsy patients who never used vigabatrin was included.
In the pooled cohort of previous or current vigabatrin users, there were 105 subjects who exhibited the VGB-VFD. VGB-VFDs ranged from a localized nasal defect between approximately 27 and 40 degrees eccentricity to a concentric constriction. The defect seems to initially occur within the nasal visual field and to extend in an annulus to the superior and inferior regions and to exhibit a relative sparing of the temporal field. Only 4.4% had spontaneously complained of symptoms that could be related to the visual field defects. VGB-VFDs appear to be irreversible. Visual acuity is not impaired. 
The prevalence of VGB-VFD is 31% (95% CI: 25% - 37%) and for subjects with more than three years of treatment is 36% with 95% CI: 29% to 43%. No VGB-VFDs were observed in the reference cohort of epilepsy subjects treated with other antiepilepsy drugs and never exposed to vigabatrin.
Duration of treatment up to 3 years, cumulative vigabatrin dose up to 3 kg and male gender, were strongly associated with an increasing prevalence of VGB-VFD.

DIFFERENCES IN CELLULAR SITES OF ACCUMULATION OF VIGABATRIN 
 IN CENTRAL VERSUS PERIPHERAL PRIMATE RETINA

DV Pow

Department of Anatomical Sciences, School of Biomedical Sciences,
University of Queensland, Brisbane, Australia

Purpose: This study examined the cellular sites of uptake of the antiepileptic drug Vigabatrin in the primate retina.  As Vigabatrin acts at an intracellular locus, to inhibit the enzyme GABA transaminase, only those cells that accumulate the drug can be directly pharmacologically targeted. Methods: Stereospecific antibodies were raised against Vigabatrin using standard techniques.  Isolated retinae from four marmosets and one macaque were directly exposed to 10 µm Vigabatrin in vitro for 30 min-8 hours under photopic and scotopic conditions.  Thereafter the retinae were fixed and immunolabelled either with antisera to Vigabatrin, for GABA or for GABA transporter proteins.   Results: The pattern of accumulation of Vigabatrin differed significantly between the central retina and the peripheral retina.  In the central retina, accumulation was solely into the GABAergic amacrine cells and displaced amacrine cells.   By contrast, in the peripheral retina, significant accumulation was observed into Müller glial cells.  This was associated with higher levels of GABA immunoreactivity in the peripheral retina in comparison to the central retina.  Conclusions:  Differential accumulation of Vigabatrin into central retina versus peripheral retina appears to directly influence the detectable levels of GABA in these regions.  This probably arises because most GABA transaminase is in glial cells rather than neurones.   This preferential effect on the peripheral retina may be a significant factor in the reported side effects of this drug on peripheral retinal function in some patients. 

d.pow@mailbox.uq.edu.au

THE HOSPITAL FOR SICK CHILDREN, TORONTO, LONGITUDINAL ERG STUDY
OF CHILDREN ON VIGABATRIN

CA Westall, WJ Logan, JR Buncic, K Smith, CM Panton

Department of Ophthalmology, University of Toronto and Hospital for Sick Children Toronto, Toronto, Ontario, Canada

Purpose: There have been reports of visual problems in some adults taking the antiepileptic drug Vigabatrin.  At HSC over 200 children have been prescribed Vigabatrin in the management of seizure disorders. We undertook this study to assess retinal function in infants and toddlers. Methods: As part of the HSC longitudinal Vigabatrin study ERGs were recorded from 16 infants (5 weeks to 16 months of age; median 6.5 months) before Vigabatrin was started; 13 out of the 16 were on no previous medications. By September 1999 ERGs had been measured on eight infants at 6 monthly intervals after initiation of Vigabatrin.  Another 19 infants/toddlers already taking Vigabatrin (5-30 months of age) were also tested; to date 4 of these have been tested on more than one occasion. ERGs were recorded according to ISCEV standards and included assessment of scotopic and photopic OPs. Results: All data were analyzed relative to the expected normal aged matched values. Paired t-tests showed no significant differences (alpha = 0.05) in ERG amplitudes and implicit times between pre- and post-Vigabatrin ERG results except for the summed photopic OP amplitude.  OP-sum was significantly reduced (p<0.02) after 6 months of Vigabatrin treatment. The earlier photopic OPs (OP2, OP3) were reduced; OP4 amplitude was unchanged. In a cross sectional analysis from 27 infants taking Vigabatrin the photopic OP-sum was decreased in 68% of children, scotopic OP-sum reduced in 59% of children and rod response reduced in 37% of children. Implicit time was delayed for scotopic OP2 in 48% of children. Importantly, in 13 medication-free infants tested before Vigabatrin, only 5 (39%) had all ERG response parameters within normal age matched limits. ERG rod amplitudes were decreased in 46% of these infants/toddlers. Rod-cone b-wave responses, scotopic and photopic OP-sums were each reduced in 36%. Implicit times were delayed for scotopic OP2 in 31% of infants/toddlers tested before Vigabatrin. Conclusions: Longitudinal assessment allows identification of ERG deficits that occur as a result of Vigabatrin. The only ERG response to have deteriorated as a result of treatment is the photopic OP-sum. ERG deficits occur in some infants with seizure disorder, which are not associated with seizure medication. 

Carol@sickkids.on.ca

ELECTROPHYSIOLOGY IN EPILEPTIC SUBJECTS TREATED WITH VIGABATRIN OR OTHER ANTI-EPILEPTIC DRUGS

IF Comaish, C Gorman, C Barber, NR Galloway

University Hospital, Queen’s Medical Centre, Nottingham, UK

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.

Comaish@aol.com

VISUAL ELECTROPHYSIOLOGICAL CORRELATES IN VIGABATRIN TREATMENT

SG Coupland, D Zackon, T Ross

University of Ottawa Eye Institute, Ottawa, Ontario, Canada

Purpose: Anticonvulsant activity of Vigabatrin is achieved by elevating GABA levels in the CNS. Early reports of ERG changes in patients on Vigabatrin therapy have suggested primarily cone involvement in 3 symptomatic patients (Johnson et al., 1998) demonstrated under photopic conditions. A larger pediatric group studied following 6 weeks Vigabatrin therapy also demonstrated photopic ERG changes (Duckett et al, 1998).  Recently, we reported significant rod system involvement in 28 adult patients on Vigabatrin therapy (Coupland et al., 1999). Herein we report visual electrophysiological correlates (ERG, EOG and VEP) in a larger group of patients on long term Vigabatrin therapy. Methods: 86 eyes of 43 patients (aged 14-58 years, mean=34 yr.) receiving Vigabatrin for 6-84 months (mean =32.5 months) had ERGs recorded through dilated pupils with DTL fibre electrodes according to the ISCEV ERG standard using the Espion (Diagnosys LLC) visual electrodiagnostic system. Pattern VEPs were obtained to 30' checkerboard reversal stimulation and EOGs were recorded during 12 minutes of dark and light adaptation according to the ISCEV standard.     Results: Diminished b-wave amplitude of the rod ERG was noted in 35% of eyes; whereas, photopic ERG b-wave was reduced in 32% of eyes tested. Photopic oscillatory potentials were abnormally reduced in 17% of eyes tested.  In addition, subnormal Arden ratio in the EOG was observed in 33% of eyes. Pattern VEP abnormalities were noted in 10% of eyes. Conclusions: These data confirm our earlier reported findings of significant rod system involvement in patients on Vigabatrin therapy. These electrophysiological abnormalities suggest a dysfunction extending beyond the inner retina and possibly involving the RPE.  

scoupland@ogh.on.ca

VISUAL FIELD CONSTRICTION AND ELECTROPHYSIOLOGICAL CHANGES
ASSOCIATED WITH VIGABATRIN

D Besch, A Kurtenbach, E Apfelstedt-Sylla, TJ Dietrich, D Dennig, C Asenbauer, 
E Zrenner, U Schiefer

Department of Pathophysiology of Vision and Neuro-ophthalmology, University Eye Hospital, Tübingen, Germany

Purpose: Approximately 5% of all people suffer at least one epileptic event during their life, 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 investigated ophthalmological changes. Methods: Twelve epileptic patients treated with Vigabatrin (age range 35-65 years) were 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 (OPs) (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 of 12 patients, while significant electrophysiological changes were observed in all patients on Vigabatrin therapy, especially of the OPs, 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 relatively high doses (2500mg/d and 3000mg/d for 5 and 6 years). Our results show the value of detailed visual field testing and diagnostic electrophysiology for detection and follow-up of ophthalmological abnormalities in refractory epilepsy patients treated with Vigabatrin.

dorothea.besch@uni-tuebingen.de

VISUAL FUNCTION ABNORMALITIES IN EPILEPTIC CHILDREN TREATED WITH VIGABATRIN

E Banin*, V Gross-Tsur#, E Shachar**, E Lahat+, RS Shalev#

*Department of Ophthalmology, Hadassah-Hebrew University Hospital;
#Neuropediatric Unit, Shaare Zedek Medical Center, Jerusalem; **Rambam Medical Center, Haifa; +Assaf Harofe Hospital, Zrifin, Israel 

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. 

banine@md2.huji.ac.il

Thursday 17 February

08.30 – 10.45	Scientific Session 8	VIGABATRIN MINISYMPOSIUM
	Chair:  	Eberhart Zrenner

10.45-11.15	Coffee Break

11.15 – 13.15	Scientific Session 9	ELECTROPHYSIOLOGY IN ANIMAL STUDIES
	Chairs:  	Kristina Narfstrom;  Pierre Lachapelle

13.30	Farewell lunch on the lawns of St John's College

11.15 – 13.15	Thursday 17 February

Scientific Session 9	ELECTROPHYSIOLOGY IN ANIMAL STUDIES
Chairs:  		Kristina Narfstrom;  Pierre Lachapelle

11.15	Background adaptation in a rat model of ROP
	C Jiang, R Hansen, A Fulton (Boston, MA, USA)
11.30	The effect of betaxolol on L-type calcium channel in horizontal cells
	T Sasaki, Y Shirao (Kanazawa City, Japan)
11.45	The changes of OPs and ERG in STZ induced diabetic rats
	JG Duan, HJ Ye (Chengdu, China)
12.00	Restoring oscillatory potentials and retinal blood velocity by insulin in streptozotocin-induced diabetic rats
	H Sakai, Y Shirao, K Kawasaki (Kanazawa, Japan.)
12.15	The experimental acute intraocular hypertension model in the rabbit, and the changes of f-ERG
	X Wang, W Yin, X Han (Zhengzhou, China)
12.30	Flash visual evoked potentials in diabetic rats
		H Wang, JP Zhao, ZZ Ma, Y Yao (Beijing, China)
12.45	Dose-response of heavy charged particles irradiation on the rat retina as estimated by flash ERG
	M Taniai, E Sato, A Mizota, E Adachi-Usami, T Nakano (Chiba, Japan)
13.00	Electrophysiological and pathological features of a recessive canine cone-rod dystrophy
	C Hogg, NHV Chong, L Waters, KC Barnett, AC Bird, PJ Luthert, GE Holder (London, UK)

BACKGROUND ADAPTATION IN A RAT MODEL OF ROP

C Jiang*, R Hansen, A Fulton 

Department of Ophthalmology, Children's Hospital, Boston, MA, USA

Purpose:  Test the hypothesis that the photoreceptors are the site of the retinal dysfunction that causes the reported reduction in b-wave sensitivity in the rat model of retinopathy of prematurity (ROP).  According to accepted theory, abnormalities of photoreceptor function, before the site of adaptation, reduce sensitivity for both test and background lights so that the relation between log b-wave sensitivity and log background intensity will be shifted by equal amounts along horizontal and vertical axes.   Methods:   ERG stimulus/response functions were obtained using full-field stimuli in the dark adapted state, and in the presence of steady background light.  In each adaptation condition, the test flash that produced a half-maximum b-wave amplitude was calculated for each rat.  Results:  Dark adapted b-wave sensitivity of ROP rats was half a log unit lower than in controls, a significant difference.  The background light reduced b-wave sensitivity of both ROP and control rats by equal amounts.  Conclusions:  The effect of the background lights  is consistent with a receptoral origin of the low sensitivity in the ROP retina.
Supported by the Massachusetts Eye Research Fund.

*Current Address: Department of Ophthalmology, Red Cross Hospital, Kunming, Yunnan 650021 PRC

fulton_a@A1.tch.harvard.edu

THE EFFECT OF BETAXOLOL ON L-TYPE CALCIUM CHANNEL IN HORIZONTAL CELLS

T Sasaki, Y Shirao

Dept of Ophthalmology, Kanazawa University School of Medicine, Kanazawa City, Japan

Purpose: Betaxolol is known as an anti-glaucoma agent and L-type Ca channel blocker. The purpose of this study was to investigate the effect of betaxolol on an L-type Ca channel directly in solitary horizontal cells. Methods: Eyes were excised from goldfish. Horizontal cells were dissociated from isolated retina. Cells were recorded by patch clamp technique in conventional whole cell configuration. Results: 10 µM betaxolol blocked voltage-gated Ca current reversibly. The blocking action of betaxolol reached plateau within 2 min. 100 µM betaxolol blocked voltage-gated Ca current irreversibly. The blocking effect of betaxolol on voltage-gated Ca current was dose-dependent. 15% of voltage-gated Ca current was inhibited by 3 µM betaxolol. 10 µM nifedipine also blocked voltage-gated Ca current of horizontal cells. Conclusions: Low concentration betaxolol suppressed voltage-gated Ca current reversibly. The reported concentration in the retina of the pigmented rabbit following topical application of betaxolol was 2.45 µM. The present results demonstrate a significant decrease of Ca current of goldfish horizontal cells by 3 µM betaxolol. Therefore topical betaxolol could relieve the intracellular Ca increase in horizontal cells caused by membrane depolarization.

THE CHANGES OF OPS AND ERG IN STZ INDUCED DIABETIC RATS

JG Duan, HJ Ye

Eye Laboratory, Chengdu University of TCM, China

Purpose: It is known that oscillatory potentials (OPs) are a sensitive index for diagnosis of diabetic retinopathy. It is certain there are remarkable changes of OPs in diabetic animal models. But reports are different about the time of abnormality after an inducer is used. The purpose of the paper is to try to know the timeliness of abnormal OPs and ERGs in STZ induced diabetic rats. Methods: 80 rats were used for experiments. 2% Streptozotocin (STZ) was injected per 50mg/kg body weight for 50 rats. Electrophysiologic experiments were done if blood sugar was above 16.7mmol/L. OPs and flash ERGs were recorded monthly for six month after injection. Results:  At the fourth month after STZ injection little change was seen on amplitudes and latencies of O1 and b wave. At the seventh month amplitudes of all components of OPs and ERG decreased remarkably and latencies were delayed excluding that of the a-wave. At the same time the basement membrane of retina capillaries were thickened and the amount of pericytes was evidently reduced. Conclusions: Electrophysiological abnormality occurs in STZ induced diabetic rats some three months after inducer injection. Morphological abnormalities can be observed at six months. 

jduan@mail.sc.cninfo.net   or   djg@cdutcm.edu.cn

RESTORING OSCILLATORY POTENTIALS AND RETINAL BLOOD VELOCITY BY INSULIN IN STREPTOZOTOCIN-INDUCED DIABETIC RATS

H Sakai*, Y Shirao#, K Kawasaki#

*Ophthalmic Research Division, Santen Pharmaceutical Co. Ltd;
#Department of Ophthalmology, Kanazawa University School of Medicine, Japan

Purpose: We previously reported that insulin restores the changes of the oscillatory potentials (OPs) of the electroretinogram in streptozotocin (STZ)-induced diabetic rats. The present study aims to probe the possibility that the OPs and the retinal blood flow (RBF) co-vary during STZ-induced diabetes and subsequent insulin supplement. In addition, the effects of oxygen tension on the OPs were examined. Methods: The OPs were followed for 3 weeks in 3 groups of Brown-Norway rats; non-diabetic control (A): STZ (60 mg/kg, i.p.) diabetic without insulin supplement (B): STZ-diabetic with daily insulin 5.0 U/kg supplement starting 2 weeks after STZ injection (C). RBF was measured with a scanning laser ophthalmoscope before, 2 weeks after and 3 weeks after STZ injection. ERGs of perfused rabbit eye cups were recorded in 100%, 99.5% and 95% oxygen bubbling at 15-min intervals. Results: No changes were noted during the follow-up period for the OP amplitude and for the a- and b-wave peak latency and amplitude. The peak latencies of the 2nd and 3rd OP peaks (OP2 and OP3), as well as the interval between the OPs 1 and 2 (T1), were significantly prolonged as early as 1 week after STZ injection in the rats B and C compared with the rats A. However, in the rats C, the OP2 and OP3 peak latencies, as well as the T1, were restored to those in the rats A in 1 week of insulin supplement. The RBF velocity was significantly reduced in the rats B and C compared with the rats A 2 weeks after STZ injection but in the rats C it improved with a 1-week insulin supplement. In the rabbit in-vitro ERG, the OPs but not the a- or b-waves were consistently delayed in response to minute decreases in the oxygen tension. Conclusions: The OPs depict extremely early subtle alterations in diabetic retinas and most likely result from RBF reduction (or presumably consequent hypoxia) in the retina.

shirao@kenroku.ipc.kanazawa-u.ac.jp

THE EXPERIMENTAL ACUTE INTRAOCULAR HYPERTENSION MODEL IN THE RABBIT
AND THE CHANGES OF F-ERG

X Wang, W Yin, X Han 

Henan Institute of Ophthalmology, Zhengzhou, China

Background: Three experimental acute intraocular hypertension (IOHT) models in rabbits were made using different drugs, and used to detected the effect of acute intraocular hypertension on the changes on the F-ERG. Method: 1.Ocular examinations were performed in 25 normal rabbits before the experiment; their intraocular pressures averaged 20.5mmHg and they showed normal F-ERG a and b waves. 2. The acute intraocular hypertension models were made: alpha-chymotrypsin 0.2ml; 2% methylcellulose 0.2ml; china ink 0.05ml with 0.9% sodium chloride 0.15ml respectively were injected into the anterior chambers. Intraocular pressures were measured each hour on the day of operation and 2 times each day after operation. F-ERG was tested on the 21st day after experiment. 3. F-ERG examinations were performed before and after experiment under non-sedation. Scotopic ERGs were utilized to produce the Full-field electroretinography. The active electrode was a contact lens electrode and an Ag-AgCl electrode was used as a reference electrode. A needle-electrode was used as the ground electrode. The F-ERG data before and after the experiment were compared. Results: 1. Intraocular pressures were evidently higher after experiment than before. The F- ERG changes of eye with acute intraocular hypertension: The latency of a-b waves were significantly shorter in different IOHT groups after the experiment than before (p<0.05-0.001), the amplitudes of the a and b wave were significantly lower in different IOHT group after experiment than before (p<0.05-0.001). Conclusion: These acute IOHP models can induce retinal neural tissue damage and it is suggested that the F-ERG can be useful in monitoring retinal damage due to acute intraocular hypertension.

FLASH VISUAL EVOKED POTENTIALS IN DIABETIC RATS

H Wang, JP Zhao, ZZ Ma, Y Yao

Dept. of Ophthalmology, General Hospital of PLA, Beijing, China

Purpose:  To explore visual function in diabetic rats by means of flash visual evoked potentials (F-VEP). Methods:  Twenty male Wistar rats weight from 190-200 gram were randomly divided into two groups.  One group (n=10) was made diabetic (model) by injection STZ (streptozotocin) solution into the tail vein.  The control group (n=10) was injected with the same amount of pH adjusted normal saline.  After injection the blood sugar was ≥ 16.67mmol/L (300mg/dl), the water input and the urine output were all more than 40 ml every 24 hours; the haematuria was over +++, and body weight decreased gradually for more than three weeks. F-VEP was recorded three months later.  The electrodes were put in the anterior and posterior fontanel and the earlobe of the rats.  Sensitivity ICH was 2  v/DIV, high cut 100 Hz, low cut 2 Hz, sweep time 10 ms, stimulation rate 1 Hz; 64 sweeps were averaged. Results:  There was no difference in F-VEP latency between the two groups; F-VEP amplitude in the diabetic group decreased slightly, but there was no statistical difference between the two groups (p>0.05). Conclusion:  Distinct pathology changes were observed in each tissue at three months, but there was no significant F-VEP difference in the two groups.  The reasons may be as follows:  (1) F-VEP was normal at three months.  (2) The choice of parameters was not sufficiently sensitive.  (3) The positive rate of F-VEP is low when the optic nerve of diabetic rat is damaged.

DOSE-RESPONSE OF HEAVY CHARGED PARTICLES IRRADIATION ON THE RAT RETINA
AS ESTIMATED BY FLASH ERG

M Taniai*, E Sato*, A Mizota*, E Adachi-Usami*, T Nakano#

*Department of Ophthalmology, Chiba University School of Medicine;
#National Institute of Radiological Science, Chiba, Japan

Purpose: Heavy charged particles are one of several kinds of radiation and have begun to be used for the treatment of certain types of malignant tumors. This type of treatment has never been applied to the eye although a trial study on orbital malignant tumors has just started in Japan. Because no report is available on its influence on the retina, we examined the effect of heavy charged particles irradiation on the retina by means of electroretinograms (ERGs). Methods: Thirty eyes of 8 week-old Wister rats, 150 g, were exposed to heavy charged carbon (12C) particle irradiation in 5 different single doses (1, 2, 4, 8 and 16 Gy) under ketamine, xylazine and ethyl carbamate anesthesia. Six animals without irradiation were used as controls. An intensity series of single flash ERGs was recorded at 1, 3, 6 and 12 months after the irradiation, and the threshold intensities and amplitudes of the a- and b-waves were evaluated. Result:  At 1 and 3 months after the irradiation, there were no significant changes in the thresholds and amplitudes for both the a- and b-waves for any dose.  At 6 months after 16 Gy irradiation, the amplitudes of both the a- and b-waves were significantly smaller for the whole range of stimulus intensities. But with lower doses, there were no significant changes. Conclusions: The retinae were not damaged with low doses (1, 2, 4 and 8 Gy) of heavy charged particles. But at 16 Gy, there was functional retinal damage that was seen only at a late stage.  These results should be considered by those using 12C particle irradiation on the eye clinically.

taniai@ophthalm.m.chiba-u.ac.jp

ELECTROPHYSIOLOGICAL AND PATHOLOGICAL FEATURES OF A RECESSIVE
CANINE CONE-ROD DYSTROPHY

C Hogg, NHV Chong, L Waters, KC Barnett, AC Bird, PJ Luthert, GE Holder

Institute of Ophthalmology (UCL), Moorfields Eye Hospital, London, UK

Purpose: To characterise an autosomal recessive retinal dystrophy in the Miniature Longhaired Dachshund (MLHD) dog. Methods: Electroretinography was performed in 10 animals (4 affected and 6 heterozygotes) between 6 weeks and 24 weeks of age including the ISCEV standard protocol. Pathological and immunohistochemical studies were carried out in 2 affected animals at 6 weeks and 24 weeks of age and 1 control animal at 8 weeks of age. Results: The maximal bright white flash ERG (mixed rod - cone response) of the heterozygotes at 24 weeks of age showed normal a- and b-waves. The 30Hz flicker ERG was also normal. In the affected animals, the maximal ERG was not significantly different from that of the heterozygotes at 10 weeks of age. However, 30Hz flicker ERG was found to be substantially reduced as early as 6 weeks of age and became indistinguishable from noise at 14 weeks of age. The maximal ERG also showed progressive reduction, and by 24 weeks of age it was severely reduced. In the affected animal, pyknotic nuclei of rods and cones were seen as early as 6 weeks of age. The thickness of the outer retinal layer was substantially reduced by 24 weeks of age. Immunohistochemical staining of opsin was almost entirely restricted to the outer segments in the normal animals. In the affected animal, opsin labelling was present in both outer and inner segments, and there was also accumulation of opsin in the outer nuclear layer and within the presumed photoreceptor cell synaptic terminals in the outer plexiform layer. Synaptophysin is a synaptic vesicle protein. In the control animals, immunolabeling with anti-synaptophysin was largely restricted to the outer and inner plexiform layers. In the affected animals, the immunolabelling of the outer plexiform layer was reduced with age in parallel with the reduction of photoreceptor cells. No significant change in labelling of the inner plexiform layer with anti-synaptophysin was seen. Glial fibrillary acidic protein (GFAP) was expressed predominantly by the astrocytes in the normal control. In the affected animals, markedly increased immunostaining of GFAP in Muller cells was observed. Conclusions: The pathological and immunohistochemical features are consistent with an outer retinal dystrophy. The ERG findings demonstrate the MLHD has a cone-rod dystrophy (CORD). This presents the first animal model of CORD.

chris.hogg@moorfields.nthames.nhs.uk