The point-spread function of the eye from 0° to 100° and the pattern electroretinogram

In studies on the pattern electroretinogram the quality of the retinal image is a major concern. The use of contact lens electrodes was rejected since a good pattern could not be recorded. This is believed to be due to blurring of the retinal image. As indicator of image quality the patient's visual acuity is often used. We wondered whether this is a sufficient criterion. The retinal image is the product of the whole optical point-spread function of the eye whereas visual acuity refers only to the central portion of this function. On the basis of existing reports it can be estimated that for the young normal eye the outer edges of this function (straylight) causes considerable loss of contrast. The strength of the straylight can be much greater in older eyes. We studied the relation between the point-spread function including straylight and the pattern electroretinogram in normal eyes and some pathological cases. The measurements proved to follow the calculated contrasts on the basis of a local luminance model, with the exception of enhancement (tuning) around 60 checksize for the young normal eye. Because of the considerable differences in straylight in an older population one has to take into account that loss of pattern electroretinogram can be suffered in patients with otherwise good visual acuity.     

Computation of the luminance and pattern components of the bar pattern electroretinogram

Pattern onset electroretinograms (PERGs) were recorded from four normal subjects. Square-wave gratings of 75% contrast were presented in three approximately contiguous, concentric zones of outer angular radius, 5.1°, 12.6°, and 23.6°. The zones were calculated to give equal numbers of ganglion cell receptive fields. The recorded PERGs were considered to include luminance and pattern components which have low and bandpass spatial tuning functions respectively. These components combine in the PERG to produce a broad spatial tuning characteristic. The amplitude of PERGs in response to low spatial frequency stimuli is widely reported to be linearly related to contrast. The retinal illuminance response at every spatial frequency was computed from the eye's modulation transfer function. This function characterizes the reduction in contrast that occurs because of optical degradation. The computed retinal illuminance response was subtracted from the PERG waveform and a pattern-specific response was revealed. The latter had a highly tuned bandpass function which peaked at higher spatial frequencies than the PERG at corresponding peripheral angles.     

Pattern electroretinogram in glaucoma and ocular hypertension

We recorded the pattern electroretinogram (PERG) to small (0.8°) and very large (15°) check sizes in normal subjects, in patients with early-stage glaucoma, and in patients with ocular hypertension. In glaucoma, the PERG amplitude was reduced. This reduction was more prominent for a check size of 0.8° as compared with 15° stimuli and for high (16/s) as compared with low (7.8/s) reversal rates. Using a discriminant analysis of the amplitudes for two different check sizes, we could distinguish the normal and the glaucoma groups with a specificity of 96% and a sensitivity of 91%. Of the ocular hypertension patients, 43% were classified as pathologic by the discriminant analysis. Thus multivariate analysis of the PERG may increase its diagnostic value.     

Pattern electroretinogram: Effects of reference electrode position

The pattern electroretinogram has assumed greater clinical and experimental significance because of its inner retinal origins. However, clinical tests may be confounded by an artifact. We tested subjects varying reference electrode position and eye stimulated while employing the Dawson-Trick-Litzkow (DTL) fiber electrode as the active electrode. The presence of a statistically significant artifactual response could not be confirmed. However, the variability of responses elicited with the outer canthus was less and the signal-to-noise ratio greater than with other reference positions.     

Pattern electroretinogram and visual evoked cortical potential in ethambutol optic neuropathy

Forty-one eyes in 21 cases of ethambutol optic neuropathy were investigated for the pattern visual evoked cortical potential (VECP) and the pattern electroretinogram (ERG).In 21 of the eyes the disappearance VECP responses were not detectable. In the other 20 eyes the peak latency and amplitude of the disappearance VECP were delayed and decreased significantly compared with normal eyes. The recovery of the peak latency of the disappearance VECP in ethambutol optic neuropathy was faster than that of the amplitude.Twelve eyes in six patients were studied by pattern reversal ERG. Though the mean peak latency of the pattern ERG was within normal limits, the mean amplitude was decreased significantly.Our investigations indicated that ethambutol optic neuropathy disturbed not only the optic nerve but also the retina.     

Pattern electroretinogram for monitoring the efficacy of intravitreal triamcinolone injection in diabetic macular edema

Purpose: To investigate the efficacy of intravitreal triamcinolone (IVT) by evaluation of pattern electroretinogram (PERG) in diabetic patients with clinically significant macular edema (CSME). Methods: Forty eyes of 40 diabetic patients were treated with 8 mg of IVT injection as primary therapy for CSME. The main outcome measures included best-corrected visual acuity, fundus fluorescein angiography, P₅₀ amplitudes of pattern electroretinogram (PERG) and intraocular pressures before and after injection. Results: The mean follow-up time was 6.1 months. Mean visual acuity improved significantly from a mean LogMAR value of 1.14 ± 0.16 at baseline to a maximum of 0.73 ± 0.30. The mean baseline P₅₀ amplitude of PERG before intravitreal injection was 1.5 ± 0.9 V. After the treatment, it was 2.l ± 1.1 V at 1-month, 2.4 ± 1.0 V at 3-month and 2.1 ± 0.9 V at last visit and the differences were significant when compared with baseline values (for each, p < 0.001). Temporary increases in intraocular pressures were controlled with topical antiglaucomatous medications, if required. Conclusion: IVT injection provides rapid improvement in visual acuity of diabetic patients with CSME that has been supported by P₅₀ amplitudes of PERG. P₅₀ amplitudes of PERG may be used as novel predictive value in the evaluation of the effectiveness of IVT injection.     

Transient and steady state focal and pattern electroretinogram nerve section losses in cats with unilateral optic

This study shows the ketamine/xylazine anaesthetised cat is a useful model for the effect of unilateral optic nerve section on pattern electroretinograms (PERGs), especially if stimuli extending to previously untested low spatial frequencies and preferably down to the focal ERG (FERG) are included. The transient reversal rate, seldom used in animals, has advantages over steady state recording. Transient PERGs had signs of true spatial tuning, a higher amplitude and signal noise ratio and showed the effect of optic atrophy at low spatial frequencies more rapidly.     

Pattern electroretinogram as a function of spatial frequency after retrobulbar optic neuritis

Steady-state (8-Hz) pattern electroretinograms in response to counterphased sinusoidal gratings of variable spatial frequency (0.6–4.8 c/deg) were recorded in 17 patients who had had retrobulbar optic neuritis in one or both eyes (23 eyes with a clinical history of optic neuritis) and in 21 age-matched normal subjects. Amplitude and phase of the Fourier-analyzed pattern electroretinogram second harmonic were measured. The mean pattern electroretinogram amplitude of patients was significantly reduced compared with that of controls. Amplitude reductions were more marked at intermediate (1–1.4 c/deg) than at lower or higher spatial frequencies. Therefore, the average amplitude versus spatial frequency response function differed significantly in patients compared with controls, displaying a lowpass instead of a band-pass shape. No significant differences in the mean pattern electroretinogram phase were observed between groups at any spatial frequency. These results indicate spatial frequency-dependent abnormalities in the pattern electroretinogram amplitude after optic neuritis, suggesting a specific loss of retinal neurons sensitive to stimuli of intermediate spatial frequencies.Abbreviations ANOVA analysis of variance - SD standard deviation - SEM standard error of the mean     

Pattern electroretinogram as a function of spatial frequency in ocular hypertension and early glaucoma

Pattern electroretinograms (PERGs) in response to 8.3 Hz alternating gratings (16.6 rev/sec) of different spatial frequencies were recorded in normal subjects as well as in patients affected by early glaucoma and ocular hypertension. In normal subjects the PERG response is spatially tuned, with a maximum at about 1.5 cycles/deg and attenuation at higher and lower spatial frequencies. In all cases of early glaucoma and in the great majority of cases of ocular hypertension the PERG was reduced, as compared with that of normal subjects, mainly in the medium range of spatial frequencies (at which the PERG has its maximal amplitude).     

Variability of the pattern electroretinogram

Conflicting results have been obtained concerning the parametric properties of the pattern electroretinogram. These discrepancies may be due to the large amount of variability inherent in recording amplitudes. We have found the variability within a single stimulus condition to be so large (ranging from 30% to 67% of the mean value) that it could mask any underlying spatial frequency tuning. Changing the stimulus conditions failed to significantly reduce the observed variability, although changing recording conditions produced some reduction. The use of a narrower rejection band, a greater number of sweeps, and placement of the reference electrode on the ipsilateral ear (as opposed to the ipsilateral temple) combined to decrease variability of the pattern electroretinogram within a single recording session; however, intersession variability remained high. Therefore one must be careful in evaluating data from this technique, and caution is advised in its clinical use.     

Pattern visual evoked cortical potential measurement of luminance threshold in retinitis pigmentosa

We measured the luminance threshold in eight patients (12 eyes) with retinitis pigmentosa using pattern reversal visual evoked cortical potentials (PVECPs). With decreasing pattern luminance (0 to 3.0 log unit neutral density filters), the amplitude of the p 100 component decreased linearly. Luminance threshold was determined by extrapolating the regression line of amplitude as a function of luminance to 0 V. Our results showed that luminance threshold measured by PVECP was approximately 1.2 log units higher in patients with retinitis pigmentosa than in age-matched normal controls. Thus the PVECP may provide a way of quantitatively evaluating central retinal visual function in patients with retinitis pigmentosaAbbreviations RP retinitis pigmentosa - ERG electroretinogram - PVECP pattern visual evoked cortical potential - NDF neutral density filter     

The effect of 0.5% thymoxamine on the pattern-onset electroretinogram

Thymoxamine constricts the pupil without significant effect on accommodation and was used in this study because of the extreme sensitivity of the pattern electroretinogram (PERG) to defocus at high spatial frequencies. Pilocarpine, used in previous studies, can cause an unpredictable spasm of accommodation. A reduction in pupil size has two effects on the PERG due to illuminance and optical degradation. Illuminance differences can be compensated by neutral density filters. This allows the effects of optical degradation on the PERG to be examined under conditions of constant adaptation.Our studies on a group of 10 subjects have shown the PERG to be proportional to contrast. As constrast degradation is reduced with a smaller pupil, a larger PERG amplitude is predicted. However the tuning of neural elements under constant adaptation should not alter. Pattern onset ERGs were recorded from a further 10 subjects in response to checkerboards of various spatial frequencies under two conditions, a) with pupils miosed by thymoxamine hydrochloride 0.5% and b) with natural pupils. Adaptation level was equated by a 0.4 neutral density filter before the natural pupils. The group-averaged PERGs were analyzed into retinal illuminance and pattern-specific responses. A paired t-test showed the pattern-onset ERG amplitudes to be significantly different in the two conditions, but the computed pattern-specific responses were virtually identical. These results therefore support the theory and method used for the extraction of the pattern-specific response.     

Pattern electroretinogram association with spectral domain-OCT structural measurements in glaucoma

Purpose

To describe the association between pattern electroretinogram (PERG) amplitude and spectral domain-optical coherence tomography (SD-OCT) macular thickness, retinal nerve fibre layer (RNFL) thickness and optic disc topography measurements.

Subjects and methods

Both eyes (n=132) of 66 glaucoma patients (mean age=67.9 years) enroled in the University of California, San Diego, CA, USA, Diagnostic Innovations in Glaucoma Study (DIGS) were included. Eyes were tested with PERG (Glaid PERGLA, Lace Elettronica, Pisa, Italy), RTVue SD-OCT (Optovue Inc., Fremont, CA, USA) GCC, and NHM4 protocols on the same day. Of the 66 enroled patients, 43 had glaucoma defined by repeated abnormal standard automated perimetry (SAP) results in at least one eye and 23 were glaucoma suspects defined by a glaucomatous-appearing optic disc by physicians'' examination in at least one eye and normal SAP results in both eyes. Associations (R ²) were determined between PERG amplitude (μV) and SD-OCT macular ganglion cell complex (GCC) thickness (μm), macular thickness (μm), macular outer retinal thickness (macular thickness minus GCC thickness) (μm), RNFL thickness (μm), neuroretinal rim area (mm²), and rim volume (mm³).

Results

PERG amplitude was significantly associated with GCC thickness (R ²=0.179, P<0.001), RNFL thickness (R ²=0.174, P<0.001), and macular thickness (R ²=0.095, P<0.001). R ² associations with other parameters were not significant (all P>0.624). Significant associations remained for GCC and average RNFL thickness when age and intraocular pressure at the time of testing were included in multivariate models (both P≤0.030).

Conclusions

PERG amplitude is significantly (but weakly) associated with macular GCC thickness, RNFL thickness, and macular thickness. The lack of association between PERG amplitude and macular outer retinal thickness supports previous results, possibly suggesting that that the PERG is driven primarily by retinal ganglion cell (inner retinal) responses.     

Pattern electroretinogram plus visual evoked potential: A decisive test in patients suspected of malingering

Along the processing chain in the visual pathway the pattern electroretinogram (PERG) is a better indicator of the peripheral function than the visual evoked potential (VEP). Therefore the PERG and the VEP will be impaired equally by disturbances before the ganglion cell layer (e.g., blurred image or retinal disease) and differently by further centrally located diseases (e.g., tumor compression of the optic nerve). Thus in patients complaining of reduced visual acuity who show disturbed VEP but a normal PERG, malingering can be definitely ruled out. Representative combinations of PERG and VEP findings are described.     

Pattern electroretinogram peak times as a clinical means of discriminating retinal from optic nerve disease

Fifty-two patients with unilateral or bilateral retinal or optic nerve disease exhibited abnormal peak times and/or amplitudes in the pattern electroretinogram. While this abnormality in patients with optic nerve diseases was confined to an amplitude reduction, 40% of the eyes with retinal diseases exhibited additionally a peak time delay of the p and/or q component. We conclude that recording of pattern electroretinogram peak times provides an additional means to distinguish retinal from optic nerve diseases.     

The influence of early diabetes on the pattern electroretinogram

Pattern electroretinogram response and contrast sensitivity were evaluated in two groups of diabetic patients by means of psychophysical and electrophysiological methods. The first group consisted of subjects suffering from diabetic retinopathy in various stages of evolution; the second was composed of diabetic patients with no fundus alterations and with good visual acuity. In both groups of patients, when the pattern electroretinogram was altered, contrast sensitivity was also abnormal.     

Steady-state pattern electroretinogram following long term unilateral administration of timolol to ocular hypertensive subjects

To determine whether long-term reduction of intraocular pressure leads to a corresponding preservation of the pattern electroretinogram (PERG), PERGs were studied in 21 patients with ocular hypertension who had received unilateral timolol therapy for a minimum of 6 years. The mean difference in intraocular pressure (IOP) between the placebotreated and the timolol-treated eyes (over 6 years) was 2.4mm Hg. Steady-state PERGs (16.0 rps) were obtained simultaneously in both eyes of each patient, with four check sizes (0.25, 0.5, 1.0 and 2.0 degrees). Significant (p < 0.05) steady-state PERG deficits (i.e., amplitude more than two standard deviations below the mean value of age-matched controls) were observed in 16 eyes of 12 patients (10 placebo-treated and 6 timolol-treated eyes). The mean PERG amplitude did not differ significantly between the placebo-treated and timololtreated eyes. However, a significant correlation (r = - 0.423) in the IOP differences between the placebo-treated and timolol-treated eyes and the corresponding PERG amplitude differences was noted in three of the four test conditions (i.e. 0.25, 0.5, and 1.0 degrees). These results suggest that reducing IOP may preserve ganglion cell function in some patients with ocular hypertension.Abbreviations IOP intraocular pressure - PERG pattern electroretinogram This study was supported in part by a research fellowship awarded from the American Israeli Ophthalmology Society (RN), a research grant from the National Eye Institute EY-06046 (GLT), and a grant from Merck, Sharpe and Dohme Research Laboratories (MAK). Presented in part at the meeting of the Association for Research in Vision and Ophthalmology, 5 May 1988, Sarasota, Florida.     

The effect of background spatial contrast on electroretinographic responses in the human retina

The electroretinogram (ERG) was obtained to contrast modulation (CM). This stimulus is a product of temporal modulation of the contrast of a spatial sinusoid at constant mean luminance. Mean contrast (10-40%), and modulation depth (25-1.0) were modulated at 7.5 Hz to record the pattern electroretinogram (PERG). The spatial pattern was a foveally fixated grating pattern with sinusoidal luminance profile with spatial frequency of 4.6 c/deg. CM resulted in significant first and second harmonic ERG responses. First harmonic amplitude increases then flattens as a function of mean contrast with ΔC = constant, while the second harmonic response remains unaffected by mean contrast. Apparently the first harmonic represents summed signals of local luminance responses arising from on and off neurons. Mean spatial contrast signals modulate preganglionic local luminance responses.     

Absence of ganglion cell subcomponents in multifocal luminance electroretinograms

Multifocal flash electroretinograms (ERG) were recorded binocularly (n= 18). Areas were equal or scaled with excentricity. The latter were expected to increase the total amplitude if ganglion cell subcomponents were involved. Amplitudes were intercorrelated and the factor structure was established. Scaling had no influence on amplitudes or on factors. Reliability and sensitivity were high. The second kernel first slice from the nine hexagons across the midline showed differences near the macula but no component increasing in latency with distance from the disc. Thus, multifocal flash ERG have linear spatial summation and no ganglion cell subcomponents.     

Retest variability and diurnal effects in the pattern electroretinogram

Pattern electroretinograms were recorded to phase-reversing checkerboard stimuli with DTL electrodes under conditions close to those of the ISCEV pattern electroretinogram guidelines. Both transient (2 reversals/s) and steady-state (16 reversals/s) stimulation was used. The check sizes were 0.4°, 0.8° and 16°; the mean luminance 45 cd/m², the contrast 98%, and the field size 32°×27°. In 42 eyes of 21 subjects, measurements were repeated at the same time of day after 1 week. For each eye, the intersession coefficient of variation was calculated as a measure of reproducibility. We found a coefficient of variation (±standard deviation) of 7%±5% for the amplitude of the steady-state pattern electroretinogram, 9.5%±7% for the transient pattern electroretinogram and 1.5%±2% for the latency of the transient pattern electroretinogram. To assess the diurnal variability, during a 15-h period, three pattern electroretinograms were recorded in 10 subjects. No relationship was found between the P50 latency and the time of day. However, the mean amplitude showed a maximum in the morning (9∶30 am) and a minimum in the afternoon (2∶30 pm). This small effect (about 7%, p<0.001) was more pronounced for N95 and steady-state amplitudes than for P50 amplitudes (p<0.01). Diurnal contributions to the pattern electroretinogram ranged between 3% and 10%. We conclude that pattern electroretinogram amplitude reproduces within ±10% with a probability of 70%. The effect size of the diurnal variation is similar and might be relevant for longitudinal studies.