Faculty Bibliography

1. At stimulation frequencies near 10 Hz, the focal electroretinogram (FERG) is non-linear, containing significant second harmonic amplitude. 2. We performed a series of experiments directed at identifying the origin of this nonlinearity. Three hypotheses were tested: (a) The frequency doubling reflects the summed contribution of responses to stimulus onset and offset. (b) The frequency doubling reflects interactions between the responses of different cone systems. (c) The frequency doubling is due to temporally separated contributions from the rod and cone systems. 3. The results of the present experiments did not support either the first (off response) or the second hypothesis (cone difference signal). The third hypothesis received the most support

Temporal sensitivity was assessed in patients with primary open-angle glaucoma (POAG) and ocular hypertension (OHT). Three measures of flicker sensitivity were obtained: psychophysical modulation thresholds, visual-evoked potentials (VEPs), and focal electroretinograms (FERGs). We found elevated psychophysical thresholds at higher temporal frequencies (30-50 Hz) in patients with POAG, relative to thresholds for age-matched controls. The OHT patients had elevated psychophysical thresholds only at 50 Hz. On the other hand, VEP amplitudes in POAG patients were reduced at all temporal frequencies, with the magnitude of the loss increasing with temporal frequency. The OHT patients, however, showed no reductions in VEP amplitude at any temporal frequency. Finally, POAG patients' FERG amplitudes were reduced at 30-50 Hz; whereas FERG amplitudes in the OHT patients were normal at all temporal frequencies. These results indicate that OHT patients can exhibit psychophysical threshold losses at high temporal frequencies which are not observed in the suprathreshold electrophysiological amplitude measures. On the other hand, patients with POAG show both psychophysical and VEP losses across a range of temporal frequencies. In addition, the decreases in FERG amplitudes in POAG patients suggest changes in the functioning of the outer retina in this disease

The accuracy of phase sensitive signal detection (PSD) as applied to swept visual evoked potential retrieval depends upon phase stability. If large phase shifts occur over the course of a swept run, amplitude will be lost in any one PSD channel and threshold estimation may be inaccurate. We were able to demonstrate large latency shifts in the conventional computer averaged VEP and phase shifts in the Fourier-analyzed steady-state VEP, as a function of contrast and spatial frequency. However, the phase changes observed over the portion of a sweep where there is a visually driven response are much smaller than obtained from averaged VEPs to a series of fixed stimulus values. The difference between the observed phase shifts may be caused by a delay in phase response when stimuli are swept. This hypothesis was supported by the finding that the phase of the steady-state VEP response requires from 1 to 2 sec to stabilize following a change in contrast. Sweeping contrast or spatial frequency results in a physiologically different response than when averaged VEP responses are measured to discrete changes in stimulus parameters

We assessed the clinical utility of objectively measured acuity using visual-evoked potentials. The technique was first standardized in normal emmetropic subjects and then applied to uncorrected myopic subjects. We found that visual-evoked potential acuity could accurately indicate Snellen acuity in emmetropia and corrected myopia; however, the two measures were highly correlated only in those uncorrected myopic subjects with visual acuities of 20/100 or better. In subjects with poorer than 20/200 uncorrected visual acuity caused by myopia, estimates of visual-evoked potential acuity could not be obtained. The correlation between these two measures of visual acuity was also lower in patients with decreased Snellen acuity attributable to retinal or ocular disease. We found that patients with unexplainable claims of decreased visual acuity could be diagnosed as having functional visual loss based on objective visual-evoked potential acuities

Sensitivity losses in patients with retinitis pigmentosa (RP) have been attributed to a decrease in photopigment density, to a reduction in the number of photoreceptors, and also to a change in temporal response properties of the receptors. The sensitivity losses in patients with macular degeneration have also been attributed to a loss of photoreceptors. To test these explanations for sensitivity loss we obtained electrophysiological and psychophysical temporal modulation transfer functions (MTFs) on normal subjects in response to varying stimulus luminances and retinal loci. These stimulus manipulations did not duplicate the changes observed in the temporal MTFs of patients. The temporal response properties of the receptors were tested electrophysiologically by manipulating stimulus presentation interval. The results provided evidence for sensitivity losses in RP patients being due to alterations in the temporal response properties of the receptors

Flicker sensitivity increases in the peripheral retina when relatively large targets are used. This enhancement of cone system-mediated temporal sensitivity persists even when corrections are made for cortical magnification factors. It has been suggested that the differences in temporal frequency response characteristics across the retina are based on differences in receptor morphology between the peripheral and central cones. We have examined a possible retinal origin of this phenomenon by obtaining psychophysical and electroretinographic data at a variety of locations on the temporal retina. Psychophysical results show an increased sensitivity for high temporal frequency stimuli (above 30 Hz) with retinal eccentricity whether or not the stimulus size was scaled. Focal electroretinograms recorded with a constant size stimulus did not show an increase in amplitude with eccentricity. However, when an equal number of receptors were stimulated by scaling the target size, focal amplitudes were larger in the periphery. The electrophysiological findings are consistent with a possible retinal origin for this flicker enhancement phenomenon

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