Faculty Bibliography

PURPOSE: To assess changes in measures of visual function in patients with retinitis pigmentosa (RP) over time. METHODS: Patients with RP and visual acuity of 20/40 or better and central visual fields of 10 degrees or larger were enrolled in a 9-year prospective study. The following measures of visual function were obtained annually over the follow-up period: visual acuity, Goldmann visual fields (V4e target), focal electroretinograms, and hue discrimination. RESULTS: Over the follow-up period, the averaged group data showed changes in all measures of visual function. The smallest amount of change occurred for visual acuity and hue discrimination, and the greatest amount of change occurred for visual field area. Examination of individual patient data over the follow-up period indicated that the rates of change varied among patients and that losses in function for one measure did not correlate well with losses on other measures. CONCLUSIONS: These results stress that although visual function deteriorated over time for this group of patients with RP, there were differences among our measures of visual function. Measures that primarily assess central retinal function change relatively slowly compared with measures that assess more peripheral retinal function

We tested alternative hypotheses concerning the locus of enhanced flicker sensitivity observed in response to stimuli presented to the peripheral retina. The first hypothesis attributes increased temporal frequency sensitivity to ganglion cell and higher-order neural processing, whereas the second hypothesis states that the locus of these temporal effects is at the cone photoreceptors. To test these alternative hypotheses we measured retinal electrophysiological and psychophysical temporal modulation thresholds. We found that sensitivity for temporal frequencies < 30 Hz did not vary as a function of retinal location for either the focal electroretinogram (ERG) or the psychophysical measure. However, for both measures, sensitivity for temporal frequencies > or = 30 Hz was greater in the peripheral retina than in the central retina. In addition, critical flicker frequency for the central retina was linear as a function of retinal illuminance for both the psychophysical and the electrophysiological measures. For the peripheral retina the slopes of critical flicker frequency versus log illuminance functions were steeper than the central slopes for both threshold measures. Eccentrically measured focal ERG and psychophysical critical flicker frequency values showed a relative saturation, deviating from the linear slope above 3.5 log Td. The findings of similar focal ERG and psychophysical temporal sensitivity changes with eccentricity support an outer retinal origin of this phenomenon

Rod-mediated electroretinograms (ERG's) were recorded from transgenic mice expressing a mouse opsin gene with three point mutations (V20G, P23H, and P27L; termed VPP mice) and from normal littermates. The leading edge of the alpha wave was analyzed in relation to a computational model of rod phototransduction [J. Physiol. 499, 719 (1992)], in which values for the maximum response (RmP3), transduction gain (S), and transduction delay (td) are derived from alpha-wave data. VPP mice exhibited an age-related decrease in RmP3. This decrease was consistent with reductions in the number of rod photoreceptors and in the length of rod outer segments observed in previous histological studies of the VPP retina. Values of S determined for the VPP mice were within the normal range, consistent with a normal amplification of the visual signal in VPP rods. At high stimulus intensities, both normal and VPP mice exhibited a decrease in S, which may reflect depletion of a phototransduction substrate at these stimulus levels. We examined the recovery of the alpha wave after a bright conditioning flash by measuring the rod alpha-wave response to a probe flash presented at varying times after the conditioning stimulus. In both normal and VPP mice a fourfold (0.6-log-unit) increase in conditioning stimulus intensity increased both T50%, the period required for half-maximal recovery, and tau, the exponential time constant describing recovery. However, the increases in T50% and tau were significantly greater in VPP mice, indicating an abnormally slow recovery of the flash response in VPP rods

The hypothesis that reductions in Snellen acuities in patients with retinitis pigmentosa are due solely to losses of photoreceptors was tested by measuring the effects of random losses of sampling elements on letter identification. Sampling element losses were mimicked by setting the luminance of randomly selected pixels equal to the luminance of the surround. The amount of pixel blanking ranged from 0 to 90%. Letters varying in retinal subtense from 5 to 17 min arc were presented for 500 msec. Although letter identification accuracy decreased with increasing pixel blanking for all letter sizes, performance remained relatively high even when a majority of the pixels was blanked. The data suggest that unless the loss of cone photoreceptors in greater than 80%, loss of sampling elements alone can not account for letter acuities poorer than 20/40. In addition to loss of cone photoreceptors in patients with RP, there are histological reports of photoreceptor abnormalities and psychophysical studies of visual sensory deficits. It is conceivable that these alone, or in combination with losses of photoreceptors, could account for decreased visual acuity. In a series of experiments, stimulus parameters were manipulated in order to mimic the effects of some of these abnormalities and deficits and the effects on letter identification were examined. The results of these experiments demonstrated that sampling element loss interacts with sensory factors (e.g. luminance and contrast sensitivity) and perceptual factors (e.g. set size and letter orientation) to reduce letter identification accuracy. The implication of these results is that decreases in letter acuity observed in patients with retinitis pigmentosa cannot be attributed solely to a random loss of sampling elements in the underlying retina, but may be due to the combination of photoreceptor degeneration and other sensory and perceptual factors

The aim of this study was to determine the relative effects of age and compromised vision on driving-related skills and on-road accidents. A total of 107 subjects were tested. They represented four groups that varied in age and visual status, as follows: (1) a younger, normally sighted group; (2) an older, normally sighted group; (3) a younger, visually compromised group; and (4) an older, visually compromised group. Driving performance was assessed by self-reported and state-recorded accident frequency and by an evaluation of performance on an interactive driving simulator. The older groups had poorer driving-related skills, as measured with our interactive driving simulator, than had the younger groups, but they did not have significantly higher on-road accident rates than the younger groups. The older subjects and those with compromised vision had reduced risk-taking scores, as measured with a self-report questionnaire. In addition, all older drivers had increased eye movements and had slower simulator driving speeds, which suggests that behavioral compensation is made for visuocognitive/motor deficits. Regression analyses showed that compromised vision and visual field loss predicted real-world accidents in our study population

To investigate the relative sensory and perceptual contributions to central visual function of patients with retinitis pigmentosa (RP), we tested symmetry discrimination using block patterns with varying types of symmetric organization. Eleven control subjects with normal vision and 11 patients with RP with 20/30 visual acuity or better, viewed patterns presented for 255 msec. The patterns differed in the type of symmetric organization and the subjects were required to identify the type. The control subjects performed significantly better (89.2%) than the patients (74.5%). Four hypotheses to account for these findings were tested and the results were as follows, (1) A reduction in pattern luminance did not change symmetry discrimination performance in the control subjects. (2) Large reductions in pattern contrast did not alter symmetry discrimination in the control subjects. (3) Reductions in stimulus duration, likewise, did not produce similar error patterns in the control subjects as those observed in the patients with RP. (4) Alterations in spatial sampling density did not completely account for the patients' deficits. None of the retinally based explanations alone was sufficient to account for our findings. Additionally, we suggest that alterations of sensory input may affect the perceptual encoding of the relationship among pattern elements.

We measured contrast processing as a function of spatial and temporal frequency using three measurement techniques: psychophysical thresholds, visual evoked potential (VEP) thresholds and VEP amplitudes. Measurements were made using the same stimulus parameters and on the same group of subjects. The agreement among these functions depended upon the particular spatio-temporal stimulus employed and in general, there were more differences than similarities among these measures. For example, VEP derived functions (both amplitude and threshold) peaked at 4 c/deg, whereas, the psychophysical functions peaked at 1 c/deg. VEP amplitude functions were maximum at > or = 3.5 Hz, whereas both psychophysical and VEP sensitivity were maximum at < or = 2.5 Hz. VEP thresholds were broad and low pass in shape and in contrast, the psychophysical and VEP amplitude functions were band pass. In summary, comparisons among these measures of contrast processing must be made with caution