Albrecht v. Graefes Arch. klin. exp. Ophthal. 206, 261--268 (1978)

Archiv Graefes filrkliniseheundexDerimenlelle Ophthalmologie 9 by Springer-Verlag 1978

The Influence of Coating Agents on the Electrode Circuit in Electroretinography Richard Stodtmeister z and Ingo Wilmanns 2 1 Univ.-Augenklinik (Direktor: Prof. Dr. W. Best), D-53OO Bonn-Venusberg 2 Klinisches Institut fiir experirnentelle Ophthalmologie (Direktor: Prof. Dr. E. Weigelin), D-5300 Bonn-Venusberg, Federal Republic of Germany

S u m m a r y . In electroretinography, coating agents are usually applied to improve the

contact between the contact-lens electrode and the eye. These agents influence electroretinographic responses. In this experimental study we show that the characteristic properties of the electrode circuit are not influenced by the coating agent. Thus we conclude that these coating agents influence the eye itself. The mechanism of this interaction m a y be physical, or m a y be an unknown pharmacologic drug side effect. Z u s a m m e n f a s s u n g . Bei der Elektroretinographie werden Augentropfen verwendet, die den Kontakt zwischen der Corneoscleralschalenelektrode und dem Auge verbessern. Seit kurzem ist bekannt, dalg diese Tropfen die elektroretinographischen Antworten ver~indern. Die hier vorgelegten Resultate unserer Experimente zeigen, dafg die charakteristischen Gr6gen des Elektrodenstromkreises dutch diese Augentropfen nicht ver~indert werden. Es mug sich deshalb um eine direkte Einwirkung auf das Auge handeln, die durch einen physikalischen Effekt oder eine bisher unbekannte Arzneimittelnebenwirkung hervorgerufen wird.

I ntroduction In clinical and experimental electroretinography (ERG), the amplitude of response serves as a quantitative parameter. Even if stimulus and adaptation conditions are held constant, amplitudes show large variations (Spivey and Pearlman, 1963 ; Peterson, 1968). A part of this variation seems to be due to the coating agent (Declercq, 1977), which is applied to improve the contact between the eye and the contact-lens electrode (Karpe,

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R. Stodtmeister and I. Wilmanns

1948). The mechanism by which the coating agent might influence ERG response amplitude is not yet known. We decided to first examine the interactions between the coating agents and the electrodes. According to presently accepted theories, there should be no interactions. The specific aim of our study was to experimentally examine this hypothesis.

Material and Methods Seven coating agents were tested (Table 1). Three kinds of experiments were done in the study: (1) measurements of specific conductivity, (2) evaluation of the characteristic properties of the electrode circuit as used in electroretinography, and (3) measurements of electrode resistance in vitro. Table 1. Coating agents tested (alphabetical order). Solutions marked with asterisks are not commercially available Name Gonioscopic prism solution @ Gonioscopic prism solution@ Lyteers| Methocel@ Methocel@ Methocel@ Oculose|

Solutions tested Main Constituent 0.2 % hydroxyethyl cellulose * 1.6 % hydroxyethyl cellulose 0.2 % hydroxyethyl c e l l u l o s e 0.2 % methyl cellulose * 1.6 % methyl cellulose * 2.0 % methyl cellulose 2.5 % hydroxyethyl cellulose

Manufacturer Burton, Parsons Burton, Parsons Barnes-Hind Dispersa Baeschlin Dispersa Baeschlin Dispersa Baeschlin Dr. Mann

The specific conductivity of these solutions at ambient temperature was measured with a Hedge AC bridge. The accuracy of the instrument was checked with 1 nKC1, 1/10 nKC1, and 1/100 nKC1 solutions as references. The bandpass of the amplification and recording system for electroretinography was 0 . 1 - 1 2 0 0 Hz ( - 3 db). The preamplifier was a Princeton Applied Research Model 113 with an input impedance of 100 M~2 paralleled by 15 pF. The traces were photographed from the screen of a Nicolet 1070 computer used as a digital storage oscilloscope. The ERG recordings in human subjects were done with a Burian-Allen contact-lens electrode for electroretinography (Lawwill and Burian, 1966). Chibro-Kerakain was used as a local anesthetic. For testing the characteristic properties of the electrode circuit, we used a batterypowered signal generator that drove square-wave and sawtooth pulses through the circuit (Wilmanns and Stodtmeister, 1977). A schematic diagram of the electrode circuit, with this generator in series with one of the electrode leads, is shown in Figure 1. The pulses generated by this instrument had to go through the electrode circuit in the same way as signals from the biologic signal source. For the accuracy required, the pulses were of an ideal shape. Deviations from this shape caused by the electrode circuit could easily be detected. By using signal-analysis techniques as used in electronic engineering (Czech, 1963) the characteristic properties of the electrode circuit could be described without difficulty. Electrode resistance was measured as described by Wilmanns and Stodtmeister (1977). For this measurement, the switch (Sw in Fig. 1) was closed. Electrode resistance was calculated as a function of signal amplitude and of Rrneas.

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Fig. 1. Schematic diagram of t h e electrode circuit. S B = Biologic signal source. S T = Test signal source. Z X = Electrode impedance. R m e a s = Resistor for m e a s u r e m e n t of electrode resistance. S w = Switch. If S T is activated, t h e 2 ~ resistor in connection with the signal generator acts as signal source. Current pulses are t h e n driven t h r o u g h the electrode circuit in the same w a y as current pulses from S B

Results Table 2 shows specific-conductivity values for the solutions tested. Excepting Oculose, t h e s o l u t i o n s h a d p r a c t i c a l l y t h e s a m e s p e c i f i c c o n d u c t i v i t y . In p a r t i c u l a r , t h e c o n d u c t i v i ties of Gonioscopic prism solution (1.6%) and of Lyteers, which were tested by Declercq (1977), were nearly equal. Table 2. Specific conductivity of t h e tested coating agents Specific conductivity [Siemens cm- i ] at ambient temperature Solution Gonioscopic. pr. sol. (0.2 %) Gonioscopic. pr. sol. (1.6 %) Lyteers Methocel (0.2 %) Methocel (1.6 %) Methocel (2.0 %) Oculose (2.5 %)

Conductivity [Siemens cm -1 ] 1.1 1.3 1.4 1.5 1.2 1.4 6.0

x x x x x x x

10 -2 10 -2 10 -2 10 -2 10 -2 10 -2 10 -3

Table 3. Electrode resistance of a Burian-Allen contact-lens electrode in vitro with various coating agents Solution

Z x [KY~]

Physiol. saline Gonioscopic. pr. sol. (0.2 %) Gonioscopic. pr. sol. (1.6 %) Lyteers Methocel (0.2 %) Methocel (1.6 %) Methocel (2.0 %) Oculose (2.5 %)

2.3 4.0 3.1 3.1 5.1 4.0 4.2 4.0

264

R. Stodtmeister and I. Wilmanns

Table 3 shows t h e real p a r t of t h e e l e c t r o d e i m p e d a n c e in vitro. F o r these m e a s u r e m e n t s t h e e l e c t r o d e s o f a Burian-Allen c o n t a c t lens were d i p p e d into t h e test s o l u t i o n so t h a t t h e central r i m o f t h e r e f e r e n c e e l e c t r o d e was n o t s u b m e r g e d . F o r t h e recordings s h o w n in Figures 2 - 5 , a Burian-Allen c o n t a c t tens was a t t a c h e d to a h u m a n eye and connecte.d w i t h t h e r e c o r d i n g system. T h e G o n i o s c o p i c prism s o l u t i o n used in these e x p e r i m e n t s c o n t a i n e d 1.6% h y d r o x y e t h y l cellulose. Square-wave a n d sawt o o t h c u r r e n t pulses were driven t h r o u g h t h e e l e c t r o d e circuit. T h e s e t w o signal f o r m s c o m p l e m e n t e d each o t h e r for a c o m p l e t e d e f i n i t i o n o f t h e circuit properties, i

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Fig. 2. Uppermost trace: Output of test-signal source (in square wave mode) directly connected to the input of the preamplifier. Traces, left and rigbt column: Test signal source in square-wave mode connected as shown in Figure 1. Human subject, Burian-Atlen contact-lens electrode. Left eye = Left column. Right eye = Right column. Coating agent applied as indicated. The recordings shown were made from 0--120 s after connecting the test-signal source

1 Square waves are particularly well suited to phase-response testing9 Phase shifts of 0.5 ~ are easily recognized. Sawtooth signals very clearly show even small nonlinearities in the amplitude-response tests

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Fig. 3. Same experiment as in Figure 2, test-signal source in sawtooth mode. The pulses displayed have an amplitude of 400 ~V: For Figure 3 the vertical display scale of the digital storage oscilloscope was halved

In the uppermost trace of Figures 2--5, applied pulses are directly fed into the input of the preamplifier. The pulses driven through the electrode circuit do not differ during the first 500 ms (Fig. 4) or during the first 120 s (Figs. 2 and 3) after applying the test signals to the circuit. Changing the coating agent (Figs. 2 - 5 ) and changing the position of reference electrode (Fig. 5) does not alter the pulses (without regard to biologic noise, which is superimposed on the pulses).

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Fig. 4. Sawtooth pulses 400 #V p-p immediately after connecting the test signal source. Upper trace: Output of the test-signal source directly connected to the input of the preamplifier. Human subject. Left trace = Left eye. Right trace = Right eye. Burian-Allen contact lens electrode. Testsignal source connected as shown in Figure 1. Coating agents applied as indicated. Vertical arrows indicate time of application of the test signal

Discussion The experiments presented here were done to test the hypothesis that changing the coating agent in electroretinography does not alter the characteristic properties of the electrode circuit, i. e., resistance, capacity, or dynamic range. Figures 2--5 clearly show that the test signals driven through the electrode circuit do not differ basically from signals that are directly fed into the input of the preamplifier. Visual-analysis techniques used in electronic engineering would detect the slightest deviation from the input waveform. Therefore we conclude that different coating agents do not change the above-mentioned properties of the electrode circuit. Time-dependent changes can be also excluded (Figs. 2 - 4 ) . The differences in specific conductivity or in electrode resistance in vitro (tables 2 and 3) have no influence. Declercq (1977) showed conclusively that various coating agents change the electroretinogram. We have shown that there can be no direct influences on the electrode circuit. Thus it must be concluded that the coating agents influence the eye itself. The mechanism of this interaction may be physical or may be an unknown pharmacologic drug side effect.

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Fig. 5. Sawtooth pulses recorded with different reference electrodes as indicated between the traces, The electrode on the forehead was a gold-cup electrode (Grass Instruments), the electrode on the earlobe was a gold-clip electrode (Grass Instruments). Left Column = Left eye. Right column = Right eye. Coating agents applied as indicated. Human subject

Acknowledgements. The solutions listed in Table 1 were provided by the manufacturers. The measurements of specific conductivity were carried out in the Institute for Biophysics of the University of Bonn. The Burian-Allen contact-lens electrode was placed at our disposal by the Max Planck Institute for Physiological and Clinical Research, W. G. Kerckhoff Institute (lI. Physiologische Abteilung, Bad Neuheim).

References Czech, J.: O s z i l l o g r a f e n - M e g t e c h n i k , Berlin: Verlag fiir R a d i o - F o t o - K i n o t e c h n i k , 1963 Declercq, S.S.: The coating agent on the corneal c o n t a c t lens in e l e c t r o r e t i n o g r a p h y . Am. J. O p h t h a l m o l . 8 3 , 2 6 7 - 2 7 1 (1977) Karpe, G.: A p p a r a t u s and m e t h o d for clinical records o f t h e e l e c t r o r e t i n o g r a m . D o c u m . O p h t h a l m o l . 2, 2 6 8 - 2 7 6 (1948)

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Lawwill, T., Burian, H.M.: A modification of the Burian-Allen contact-lens electrode for human electroretinography. Am. J. Ophthalmol. 61, 1506-1509 (1966) Peterson, H. : The normal b-potential in the single-flash clinical electroretinogram. Acta Ophthalmol. [Suppl.] (Kbh.) 99, 1 - 7 7 (1968) Spivey, B.E., Pearlmann, U.T.: Day-to-day variations in the ERG of humans and rabbits. Am. J. Ophthalmol. 55, 1 0 1 3 - 1 0 2 0 (1963) Wilmanns, I., Stodtmeister, R..: Ein neues Verfahren zur Kalibrierung elektrophysiologischer Untersuchungseinheiten. Albrecht v. Graefes Arch. klin. exp. Ophthalmol. 205, 3 3 - 3 9 (1977)

Received March 21, 1978

The influence of coating agents on the electrode circuit in electroretinography.

Albrecht v. Graefes Arch. klin. exp. Ophthal. 206, 261--268 (1978) Archiv Graefes filrkliniseheundexDerimenlelle Ophthalmologie 9 by Springer-Verlag...
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