Pattern-reversal Electroretinograms in Unilateral Glaucoma

Transcription

1 Pattern-reversal Electroretinograms in Unilateral Glaucoma Peter Wanger and Hans E. Persson Pattern-reversal and flash electroretinograms (ERG) and oscillatory potentials (OP) were recorded from patients with unilateral glaucoma. All glaucomatous eyes had reduced amplitudes both compared to the opposite eye in the same patient and to reference values. In 0 of the cases this reduction was below the level of normal variation. The difference in pattern-reversal ERG amplitude means from glaucomatous and opposite eyes was statistically significant. No differences were observed in flash ERGs or OPs. The histopathologic correlate to the visual field defects in glaucoma is retinal ganglion cell degeneration. The present electrophysiologic findings support the view, based on results from animal experiments, that the pattern-reversal ERG reflects ganglion cell activity. Invest Ophthalmol Vis Sci 24: , 983 It has been proposed that the pattern-reversal ERG is generated mainly by the retinal ganglion cells. This suggestion is based on results from animal experiments; the ERG to alternating gratings disappeared after retrograde degeneration of the ganglion cells in cats with sectioned optic nerves. This view was supported by findings in patients with unilateral retinal and/or optic nerve diseases. 2 ' 3 urthermore, a recent report described the absence of pattern-elicited ERG in a single patient with glaucoma. 4 Histopathologic studies have shown that the visual defects in glaucoma correspond to damage of the ganglion cells and their axons. 5 " 8 Thus, consistent changes in the pattern-reversal ERG from glaucomatous eyes would further corroborate the above-mentioned proposal. In the present study, the pattern-reversal ERGs were recorded from patients with unilateral glaucoma, the opposite eye serving as control. lash ERGs and oscillatory potentials (OP), considered to be generated by other retinal elements than the ganglion cells, 90 were also recorded. aterials and ethods Eleven patients, -76 years of age, were examined. Clinical data are given in Table. All patients rom the Departments of Ophthalmology and Clinical Neurophysiology, Karolinska Hospital, Stockholm, Sweden. Supported by grants from the Karolinska Institute and the Swedish edical Research Council (Project no B83-04X ). Submitted for publication June 28, 982. Reprint requests: Peter Wanger, D, Department of Ophthalmology, Sabbatsbergs Hospital, Box 640, S-3 82 Stockholm, Sweden. had unilateral manifest glaucoma according to the conventional criteria (elevated intraocular pressure, typical changes of the optic nerve head, and characteristic visual field defects). The opposite eyes were either normal or afflicted with ocular hypertension (increased intraocular pressure without optic nerve changes and visual field defects). Among the glaucomatous eyes, six had normalized intraocular pressure after surgery (trabeculectomy), two were treated with pilocarpine, two with timolol, and one with both types of eye drops. Two of the opposite eyes were treated with pilocarpine and two with topical timolol. Ophthalmologic examinations were made in all patients in connection with the electrophysiologic recordings. Pupil size was equal in 8 of the patients; two patients had miotics in the glaucomatous eye only and one in the opposite eye only. All patients had clear lenses or optically insignificant cataracts equal in both eyes. No clinical signs of other eye disorders were observed. The visual fields were tested in a Goldmann perimeter (Haag-Streit, type 940) using a static suprathreshold technique. A stimulus object (:) was presented in a random order at 52 predetermined locations within the central 30 field.if not perceived, the luminance of the object was increased log unit (:3) and the presentation repeated. The duration of each stimulus presentation was about s and the interval 5-0 s. Score 0 was noted if the stimulus object III: was perceived, - if the stimulus object :3 was perceived, and 2 if neither stimulus object was perceived at the tested location. Since 52 locations were examined, the score ranged from 0 to 04, ie, from the weaker stimulus perceived at all /83/0600/749/$.05 Association for Research in Vision and Ophthalmology 74Q

2 750 INVESTIGATIVE OPHTHALOLOGY & VISUAL SCIENCE / June 983 Vol. 24 Table. Clinical data. No. Pat. Age Sex eye Visual acuity / Visual field score (central 30 ) / Visual field score (central 0 ) / Treatment GW TS EA LK SL K JK ST JB SW H/.0 0.3/.0.0/ /.0 0.9/0.9.0/.0 0.7/ / /.0 0.9/.0 0.7/.0-04/0-04/0-4/-62-54/- -46/-6-4/0-4/- -36/0-22/-2-5/0-5/- 32/0 32/0 0/-4-5/0 6/- -6/0 -/0 0/0-3/0 0/0-3/0 + TI TI TI TI TI beculectomy, = pilocarpine treatment, TI = topical timolol treatment. The patients are arranged according to the degree of defect in the 30 visual field. = right eye; = left eye; H = hand movements; = tralocations to the stronger stimulus not perceived at any location. Visual fields from patient no. 6 are depicted in igure (right glaucomatous eye score 4, left eye score 0). The visual field scores of all glaucomatous and opposite eyes are presented in Table. Stimulation Stimulation was performed with a reversing checkerboard pattern and with unpatterned light flashes. The pattern-reversal stimulation was obtained with a commercially available television pattern generator (edelec Visual Stimulator"). A black and white checkerboard pattern was presented on a standard -inch television set placed in front of the patient at a distance of.5 m. The whole stimulating field corresponded to a visual angle of 5.2 in horizontal and 3.6 in vertical direction. Each square subtended a visual angle of 24 min of arc. The average luminance of the television screen was 45 cd/square.... \.... \ ::: \... \... :::./ ig.. Visual field charts (central 30 ) from one patient (no 6) ( = right eye; = left eye). Dot = stimulus object : perceived (score 0). Cross marked circle = stimulus object :3 perceived (score ). illed circle = neither stimulus object perceived (score -2). meter. Contrast setting on the pattern generator was 00%. The pattern-reversal frequency was 2 Hz. Unpatterned lightflasheswere delivered by a Grass S2 photostimulator placed at a distance of 50 cm in front of the eye to be examined. When recording the flash ERGs the stimulus frequency was Hz and relative intensity 8 on the photostimulator. When recording the OPs, flashes were given at a rate of 2/min and with a relative intensity of 6 on the photostimulator. Recording The ERGs were recorded with gold foil electrodes inserted under the lower lid (for detailed technical description, see ref. 2). The reference electrodes were placed 2 cm posterior to the lateral eye rim. The pattern-reversal and flash ERGs were fed into amplifiers with band width 0.8 Hz to 80 Hz; when recording OPs the band width was 32 Hz to 320 Hz. One hundred twenty-eight pattern-reversal ERGs, 6 or 32 flash-ergs, four or eight OPs were averaged and analyzed during 200 or 300 ms with a edelec DAV6 averager. The peak-to-peak amplitude of the patternreversal ERG was measured. The amplitudes of the a- and b-waves of the flash ERG were measured from the isoelectric line. The number of OPs was counted and their amplitude estimated. Procedure The pattern-reversal andflashergs and OPs were recorded in light-, semidark- and dark-adapted states, respectively. No mydriatic drops were used. Two or more recordings were made of the flash ERG and of the oscillatory potentials and, at least, five recordings of the pattern-reversal ERG from each eye. When recording the pattern-reversal ERG, refractive errors were corrected, and the subjects were requested to fixate a small spot of red light in the center of the

3 No. 6 PATTERN-VERSAL ERGs IN UNILATERAL GLAUCOA / Wanger and Persson 75 television screen. When recording the OPs, the patients were dark adapted, stimulus flashes were presented at a rate of 2/min, and special cut-off frequencies were used in the amplifiers. 3 The statistical significances were assessed by student's t-test and a P value of <0.05 was considered significant. Results Pattern-reversal and flash ERGs and OPs from 6ne patient (no. 6) are shown in igure 2. The ERG data from individual patients are given in Table 2. In a reference group from our laboratory that consisted often healthy individuals, 2-40 years of age, the mean pattern-reversal ERG amplitude was 4.9 +/-.3 nv and the interocular amplitude difference less than 20%. l4 In the present group (Table 2), the pattern-reversal ERG from five opposite (nonglaucomatous) eyes fell within this range and six below. All glaucomatous eyes showed reduced amplitudes both compared to the opposite eye in the same patient and to the reference values. In 0 of the cases the interocular difference was more than 20%, ie, outside our laboratory standard. The difference in patternreversal ERG amplitude means from glaucomatous and opposite eyes was statistically significant (Table 3). Regarding the flash-ergs, one patient (no. 8) had a-wave and another (no. ) both a- and b-wave amplitudes below the laboratory standard. No significant differences were observed in a- and b-wave amplitudes between glaucomatous and opposite eyes (Tables 2, 3). Oscillatory potentials, consisting of three to five wavelets, were recorded in nine of ten patients (one patient was not examined). In one patient (no. 9) no OPs were registered. Side asymmetry in amplitude was observed in two patients; one with lower amplitudes from the glaucomatous eye and the other from the opposite eye. Comparing clinical and electrophysiologic data, a clear relationship was observed between the visual field defect and the pattern-reversal ERG. High (negative) visual field scores corresponded to low amplitudes. The correlation coefficient (n = 22, r = 0.69) between the scores from the 30 visual fields and the pattern-reversal ERG amplitudes was statistically significant. Although the coefficient (n = 22, r = -0.54) was lower, the correlation between the 0 visual field scores and the pattern-reversal ERG amplitudes was also significant. The mean pattern-reversal ERG amplitude from both surgically (n = 6, mean = 0.8, SD = 0.7 ^V) and medically (n = 5, mean =.5, SD = 0.3 nv) treated glaucomatous eyes was significantly 50 ms ig. 2. lash ERGs (A), oscillatory potentials (B) and patternreversal ERGs (C) from one patient (no 6) ( = right eye; = left eye). lower than the mean amplitudes from corresponding opposite eyes (n = 6, mean = 2.6, SD = 0.9 nv and n = 5, mean = 2.8, SD =.0 fiv, respectively). Although the mean amplitude was lower from surgically than from medically treated eyes, this difference did not reach statistical significance. No relation was observed between age or visual acuity and electrophysiologic findings. Discussion The present results show that pattern-reversal ERGs from glaucomatous eyes were reduced in amplitude compared to those from the opposite eyes. A similar observation was reported in a recent study on

4 752 INVESTIGATIVE OPHTHALOLOGY & VISUAL SCIENCE / June 983 Vol. 24 Table 2. ERG-data. No. Pat. eye Pattern-reversal ERG amplitude i lash ERG amplitude (\LV) a-wave b-wave GW TS EA LK SL K JK ST JB SW 0 ( ; the pattern-reversal ERG in one patient with glaucoma 4 and also mentioned in a study of patients with diseases of the peripheral visual pathway. 2 The pattern-reversal ERG is likely to be influenced by factors such as age, pupil size, refractive error, opacities of ocular media, and treatment. In the present study, all patients had unilateral glaucoma and the opposite eye served as control. Pupil size was approximately equal in glaucomatous and opposite eyes. Refractive errors were corrected. No patient showed optically significant cataracts or signs of other ocular disorders. Among the glaucomatous eyes, only one more had pilocarpine or timolol treatment compared to the opposite eyes. Trabeculectomy was made in six patients giving normalized intraocular pressure, but no opacities. Thus, apart from glaucoma, the performed surgery was the only factor, which might influence the pattern-reversal ERG from the glaucomatous although not from the opposite eyes. However, there was a statistically significant amplitude reduction also from the unoperated glaucomatous eyes. Hence, the reduced amplitude of the patternreversal ERG is considered to be dependent on the glaucomatous damage. This view is further supported by the observation of a statistically significant relation between the pattern-reversal ERG amplitude reduction and the visual field defect. Histopathologic studies have demonstrated that Table 3. ean amplitudes of the pattern-reversal and flash ERGs. Pattern-reversal ERG Peak-to-peak amplitude lash ERG a-wave amplitude b-wave amplitude eye (n = ; mean ± SD nv) ± 0.6 ± 5 ± 52 Opposite eye (n = ; mean ± SD fiv) 2.7 ± ± ±63 the ganglion cells and their axons are damaged in glaucoma. 5 " 8 The finding of reduced pattern-reversal ERG amplitudes from the glaucomatous eyes supports the view, based on recent animal experiments, that this type of ERG reflects ganglion cell activity. lash ERGs and oscillatory potentials, considered to be generated by retinal elements peripheral to the ganglion cells 90 were equal in glaucomatous and opposite eyes, which is in agreement with the above mentioned view. With our technique, the pattern-reversal ERG tests the central 8 of the retina, where the ganglion cell layer is greater than one cell in thickness. 5 Loss of a number of ganglion cells in this area does not necessarily lead to a visual field defect 6 ' 76 since functioning neurons still remain. However, each ganglion cell probably contributes to the pattern-reversal ERG, which is assumed to be reduced in amplitude in proportion to the ganglion cell loss. The typical visual field defect in glaucoma is paracentral scotoma, corresponding to a retinal region with a single row of ganglion cells 57 where the loss of few neurons gives a detectable scotoma. Pattern-reversal ERG and visual field examination both reveal impaired function of the retinal ganglion cells. Thus, the observed correlation between visual field scores and pattern-reversal ERG amplitudes may be plausible, even though the two methods do not test the same retinal area. The pattern-reversal ERG examination may be useful as an objective method for detecting perhaps even subclinical ganglion cell damage in glaucoma. Key words: glaucoma, ganglion cell damage, ERG, pattern stimulus,flashstimulus, oscillatory potentials Acknowledgments The authors are grateful to Charlotta Johansson and Arne Wiberg for assistance during the ERG examinations and to Gerd Bogren for secretarial help.

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