Scotopic Threshold Response and Scotopic PII in Glaucoma - IOVS

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Scotopic Threshold Response and Scotopic PII in Glaucoma Matthias Korth,* Nhung X. Nguyen,* Folkert Horn* and Peter Martusf

Purpose. The value of the ERG scotopic threshold response (STR), which is known to originate in the proximal retina and of the near-threshold scotopic PII (B-wave), was studied in glaucoma. Methods. Full-field single flashes were presented under scotopic conditions in two subject groups, a glaucoma group (n = 30) and a normal control group (n = 35). The intensity level for evoking STR was where the maximum response occurs, whereas the intensity level for evoking scotopic PII was where the response begins to appear. Results. The STR is only slightly reduced in glaucoma (P = 0.046), but scotopic PII is significantly diminished (P < 0.0001). Conclusions. The relatively intact STR in glaucoma suggests that structures responsible for its generation are less damaged in glaucoma than those responsible for scotopic PII. Invest Ophthalmol Vis Sci. 1994;35:619-625.

J. he conventional human single-flash electroretinogram (ERG) has long been regarded as of low value in the diagnosis of chronic simple glaucoma,1"5 whereas in acute cases supernormal as well as subnormal responses have been noted. 235 ' 6 After the observation that ERGs evoked by pattern-reversal stimuli (PERG) can be abolished in cats7 or monkeys8 with complete optic atrophy after sectioning the optic nerve while the conventional luminance ERG remains normal, it has been concluded that the retinal ganglion cells play an important role in the generation of the PERG. Current-source-density analyses in the monkey showed that the PERG originates in proximal retinal layers, and the flash-evoked B-wave is generated in distal parts.9 In humans, it has been shown that in optic atrophy the PERG can be either missing10 or strongly altered.11 Because ganglion cell losses make glaucoma an optic nerve disease, the PERG has been applied successfully in many centers as an adjunct in glaucoma diagnosis.12"16 However, recent studies on the flash-ERG reported contradictory results. Thus, because Alvis17 From the *Deparlments of Ophthalmology and f Medical Statistics and Documentation, University of Erlangen-Niirnberg, Erlangen, Germany. Supported by the Alexander von Humboldt Foundation, the J. and F. Marohn Foundation, and the Deutsche Forschungsgemeinschaft (Bonn, Germany, N9 55/ 6-1). Submitted for publication April 22, 1993; revised July 12, 1993; accepted July 21, 1993. Proprietary interest category: P, C38. Reprint requests: Dr. Matthias Korth, Department of Ophthalmology, University of Erlangen-Niirnberg, Schwabachanlage 6, 91054 Erlangen, Germany.

Investigative Ophthalmology & Visual Science, February 1994, Vol. 35, No. 2 Copyright © Association for Research in Vision and Ophthalmology

and Lowitzsch and Welt18 found the photopic A-wave to be reduced, a disorder of the cones was assumed in glaucoma. Bartl19 observed that in an interocular comparison of patients with glaucoma, the amplitudes of the scotopic and photopic A- and B-waves tended to be smaller in the eye with the larger visual field defect. Similar results were observed with the scotopic B-wave by Vass et al.20 Fazio et al,21 using the standard ERG protocol,22 found in patients with glaucoma significantly reduced A-waves and delayed implicit times of the A-wave and of the scotopic B-wave. No significant reductions of the B-wave were found. Another ERG component that has recently received attention in glaucoma diagnosis is the oscillatory potential (OP) which, like the PERG, seems to originate in the proximal retina.23 Gur et al,24 Vass et al,20 and Vaegan et al25 found OP reductions in glaucoma that were correlated with the severity of the glaucomatous field defects.20'24 A further flash-evoked ERG component originating in the proximal retina is the scotopic threshold response (STR), a potential wave that has the lowest threshold of all components and, thus, depends on the rods. Because of its cornea-negative polarity, it has been mistaken for a long time as a receptor potential.26 However, Sieving et al27 and Wakabayashi et al28 were able to show in cat and monkey that the STR originates in the proximal retina. Similar properties of this response component have been shown to exist also in humans.29 The STR has been shown to be reduced or

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Investigative Ophthalmology & Visual Science, February 1994, Vol. 35, No. 2

absent in different retinal diseases, such as retinal dystrophic diseases,30 diabetes mellitus,31 and X-linked retinoschisis.32 The fact that the STR originates in inner retinal layers suggests that this response might be affected also in glaucoma. On the other hand, Sieving33 has demonstrated that in complete optic atrophy in the cat and in humans, the STR is still recordable while its time course looks altered, which led to the conclusion that ganglion cells are not involved in its generation. The STR has been shown to be closely correlated with the psychophysical absolute threshold in various eye diseases, including glaucoma.30 The present investigation addresses the question of whether and to what extent the STR is affected in glaucoma. In addition, stimuli were employed to examine small scotopic PII responses. The ERG response with the next higher threshold is Granit's34 positive component PII, which is probably composed of two parts, the direct current component and the B-wave.35 Because it could not be decided in the present study whether the response was a DC component or a Bwave, the term "PII" is used throughout this investigation.

ended inputs 12 bit resolution analog-to-digital-converter (Data Translation [Marlboro, MA] DT2821). The sampling rate was 500 Hz and the sweep length 400 ms. Twenty-five responses were averaged off-line. Amplitude and peak-time values were measured from the graphs made by an XY plotter (Philips [Eindhoven, Holland] PM8154). Off-line averaging allows visual identification of unwanted artefacts. In spite of the low stimulus intensities in many records, wink artefacts occurred. Approximately 15% of the subjects tested had to be excluded from the study because eye blinks could not be avoided. To be sure the "responses" obtained were in fact STRs, lid movements occurring simultaneously in both eyes were detected by recording from the eyelids of the patched, other eye (Fig. 1). When no artefacts occur (upper two records, Fig. 1), a clear STR can be seen with the lower and a PII with the higher stimulus intensity. Procedures Before the recordings, the pupil of the eye to be stimulated was dilated with mydriatic drops (tropicamide) to Stimulated eye

Patched eye

MATERIALS AND METHODS Stimulus The light of a 150W Xenon arc lamp (Cermax, Sunnyvale, CA) was transmitted via glass fiberoptics into a 58 cm diameter hemisphere to provide homogeneous, white, full-field stimuli. The hemisphere and the light source were in different rooms to protect the.subject from ambient light. Each flash had a length of 8 ms delivered by activating an electromagnetic shutter (Schwarzer) located between the lamp and the light guide. It was driven by a digital function generator (NF Electronics [Yokohama, Japan] DF-194A) via a power amplifier (Schwarzer, Miinchen, Germany). Rise and fall times of the flash were