Documenta Ophthalmologica 81: 189-196, 1992. 1992 Kluwer Academic Publishers. Printed in the Netherlands.

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Averaged steady-state visual evoked cortical potentials at artificially raised intraocular pressure STEPHAN KREMMER, RICHARD STODTMEISTER, ANNE TOLKSDORF, & LUTZ EMIL PILLUNAT Department of Ophthalmology, University of Ulm, Germany Accepted 17 March 1992

Key words: Artificially increased intraocular pressure, averager, glaucoma, pressure tolerance test, steady-state visual evoked cortical potentials Abstract. By recording steady-state visual evoked cortical potentials while intraocular pressure is artificially increased, information can be obtained on the pressure tolerance of the optic nerve head. Such experiments have previously been performed by a vector voltmeter technique. We studied the visual evoked cortical potentials in 30 healthy volunteers with artificially increased intraocular pressure, but we used an averager instead of a vector voltmeter. The results were similar except that the noise level in averaging was higher than with the vector voltmeter technique. This observation confirms that the signal-to-noise ratio is much better with the vector voltmeter technique than with the averaging technique. Our results show that averaging can be used in pressure tolerance testing, but the amplitude cannot be observed as far down as in the vector voltmeter technique. This limits the clinical value of averagers in this application.

Introduction The diagnosis of primary open-angle glaucoma may no longer depend on the measurement of the intraocular pressure (IOP) [1] because tonometry has a very low sensitivity and specificity. The appearance of visual field loss is a typical but late sign of glaucoma. In this stage of the disease, organic damage to the optic nerve head is already present and irreversible. Therefore, a clinical test is required that can disclose at an early stage which patients will develop glaucoma damage and which will not. For this purpose, a load test has been developed by Pillunat et al. [2]: the pressure tolerance test. In this test, the intraocular pressure is artificially raised and the function is assessed by visual evoked cortical potential (VECP) testing. Thus, the capability of the eye to withstand pressure enhancement can be evaluated. A stepwise rise in IOP does not result in a continuous decrease of the amplitude of the VECP in healthy subjects. The curves show a plateau or a kink that can be ascribed to the presence of autoregulation in the blood circulation of the optic nerve head. In patients with glaucoma, however, the

190 amplitude pressure curve goes continuously to the noise level. The test has a specificity of 86% and a sensitivity of 88% [3]. Therefore, it may be a valuable tool in the diagnosis of glaucoma. According to Hayreh [4], the prelaminar layer of the optic nerve head is most vulnerable to a rise in intraocular pressure, because in this anatomic region the blood circulation is affected first when the lOP rises. A rise in IOP enhances the resistance in end vessels of the optic nerve head more significantly than that in the choroid. Therefore, blood flows more easily through the choroid than through the prelaminar part of the optic nerve head [4]. Autoregulation of the circulation in the prelaminar part of the optic nerve head may counteract the influence of IOP on blood flow by changing the resistance in given limits. High intraocular pressures reduce the perfusion pressure, which drives the blood through the capillaries [5]. If the circulation stops, the ischemic optic nerve fibers cease to function. The change in function is recorded as a change in the amplitude of the VECP in the pressure tolerance test [2]. In the above context, we have pointed out the relationships between rise in IOP, blood flow in the optic nerve head, autoregulation and VECP amplitude. An artificial pressure rise by the suction cup method represents a short-time model of glaucoma. The suction cup method [6] mimics one of the damaging factors in glaucoma, the IOP. We believe that VECP recording is the fastest way to get sufficient information during a short-term rise in IOP. Our application of the suction cup method and VECP recording has a specificity of 86% and sensitivity of 88% [3]. This method is far more accurate in the diagnosis of glaucoma than tonometry, for example, which has a specificity of 50% to 60% and a sensitivity of 5% [7]. We believe that the pressure tolerance test is a suitable electrophysiologic method for the diagnosis of glaucoma. Until now we have done most of our examinations with a vector voltmeter [2, 8, 9]. The vector voltmeter is suitable for this purpose [3]. This instrument measures steady-state voltages as an alternating-current voltmeter does. The special characteristic of the vector voltmeter is that it measures the amplitude and the phase angle of a signal that is in synchrony with a trigger signal fed into the vector voltmeter. The output of the vector voltmeter i s two signals, which can be read from pointer instruments: amplitude and phase. The instrument does not show the signal itself. The tradeoff is that the signal-to-noise ratio is very high. Steady-state signals buried in a high noise level can easily be measured. Averagers, which are already in use for the recording of VECPs in many hospitals, may also be applied. According to Regan [10], with averaging [11, 12] the signal-to-noise ratio is worse than with vector voltmeters. From a theoretical point of view, we cannot predict whether the pressure tolerance test is also practicable with the already widely used averagers. To answer this question, we performed the following studies.

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Subjects and methods Thirty healthy volunteers between 21 and 42 years of age were examined (17 female and 13 male). Criteria for exclusion were as follows: lOP greater than 21 mm Hg; myopia greater than 5.1 diopters; suspected retinal detachment; a history of perforating injury; a history of intraocular surgery; infectious disease; glaucoma; epilepsy; and severe or chronic systemic diseases. Two gold cup surface electrodes were placed on the midline according to the 20/20 system [13]; the active electrode was placed 5 cm above the inion, and the reference electrode, 30% above the nasion. The common electrode was applied at the mastoid behind the right ear. The impedance of the isolated preamplifier was more than 2 times 10 Mft. Projected checkerboard pattern reversal stimuli (15 reversals per second; motion time, 3 ms; luminance of white checks, 320cd/m2; luminance of black checks, 10cd/m 2) were used. The contrast of the check pattern is calculated by the following formula: Contrast = ( I m a x - Imin)/(Imax + Imin), where I represents luminance. In our studies, the contrast of the check pattern was 0.94. The distance between the screen and the eye of the subject was 1.5 m. One eye was stimulated. VECPs were recorded at uninfluenced IOP at three checkerboard sizes; the angular subtense of the edge of a single check was 53, 27 and 13 minutes of arc. At every check size, 150 responses were averaged (Nicolet Pathfinder 1). We selected the pattern size that generated the largest VECP amplitude for the stimulation at increased fOP. After the application of a local anesthetic, a standardized suction cup (inner diameter, 11 mm) was placed at the temporal sclera. The anterior rim of the suction cup was located i mm from the limbus. The negative pressure difference in the suction cup was generated by a motorized suction pump. By this procedure, the sclera is sucked into the cup and the lOP rises [6]. The IOP was calculated according to the regression of Stodtmeister et al. [14]. The following steps of negative pressure difference were chosen: -80, -130, -160, -200, -250, -300, -350 and -400 mm Hg. At every pressure step, VECPs were recorded and the maximum amplitude was determined. The length of one recording epoch was 68 ms. These amplitudes were subsequently plotted versus the respective intraocular pressure in a diagram. These curves will be referred to as amplitude/ pressure curves. Amplitude/pressure curves recorded by this procedure can show the shapes as depicted in Fig. 1. These shapes can be classified mathematically as monotone, weakly monotone, and not monotone according to Batschelet [14]. However, the term monotone is used in mathematics as an adjective and an adverb; monotonic and monotonically would sound more familiar [14]. In a previous article, Pillunat and Stodtmeister [2] described the not-

192 NOT MONOTONE

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Fig. 1. Typical behavior of amplitude/pressure curves generated by the pressure tolerance test

[2]. monotone curves as having a kink and the weakly monotone curves as having an intermittent plateau. The monotone curves were described as going continuously to the noise level. The mathematical curve fitting procedure for this classification was given by Batschelet [15].

Results

Figure 2 shows the results for a single subject. There was an amplitude of 10.4 IxV at ambient intraocular pressure. At 37 mm Hg, the amplitude was diminished to 8.1 p~V. At 48 mm Hg, in the next pressure step, the amplitude increased to 8.9 ~V. At 54 mm Hg of IOP, the amplitude was practically unchanged (8.8 p~V). At 6 2 m m Hg, the amplitude was still unchanged (8.6 ~V). During a further rise of IOP (to 71 and 80 mm Hg), the amplitude went down to the noise level. At 88 mm Hg, the amplitude increased slightly. In the amplitude/pressure curve (Fig. 3), the relationship between intraocular pressure and amplitude is shown diagrammatically. This curve shows a kink. The amplitude of subject 23 was 10.3 IxV at uninfluenced IOP. At 37 mm H G , the amplitude decreased to 7.6 txV. A further increase to 48 mm Hg in IOP caused a plateau of the amplitude (7.4 IxV). During the next pressure steps (54, 62 and 71 mm Hg), the amplitude diminished continuously (5.0, 4.0 and 3.3 p~V). The increase at 80 mm Hg to 4.7 ~V was due to

193 AMPLITUDE,pV lOP, mmHg Z

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Fig. 3. Amplitude of the VECP (abscissa). This amplitude/pressure curve is not monotone. The amplitude of the potentials at ambient IOP is 100%.

artifacts. The amplitude/pressure curve (Fig. 4) of this volunteer shows a plateau. The amplitude of subject 24 was 9.3 t~V at ambient lOP. During increasing lOP, the amplitude fell continuously. The rise of the amplitude to 2.0 p,V at an IOP of 80 mm Hg was caused by artifacts. The amplitude/pressure curve (Fig. 5) in this subject continuously decreased to the noise level at artificially raised IOP. Therefore, no kink and no plateau can be seen. The amplitude/pressure curves of the 30 subjects were classified as follows: not monotone: 21 subjects, weak monotone: 2, monotone: 4, and not evaluable: 3. The noise level is defined as the voltage at which the visual signal can no longer be distinguished from noise (Fig. 6). This happens if the value of the

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Averaged steady-state visual evoked cortical potentials at artificially raised intraocular pressure.

By recording steady-state visual evoked cortical potentials while intraocular pressure is artificially increased, information can be obtained on the p...
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