In this study, we evaluated the contrast sensitivity deficits of a group of patients with RP within the framework of the MC and PC contrast-processing streams. The patients showed losses of contrast sensitivity for both the steady- and pulsed-pedestal paradigms, indicating that both the MC and PC contrast-processing streams can be affected in RP. Further, the patients’ deficits in contrast sensitivity were equivalent for the two paradigms. This result appears to be at odds with previous studies that evaluated contrast discrimination, rather than contrast sensitivity, in patients with RP.
18 19 In those earlier studies, some patients with RP showed no threshold elevation for the pulsed-pedestal paradigm despite discrimination thresholds that were elevated by as much as 0.5 log unit above the upper limit of normal for the steady-pedestal paradigm.
It is likely that this apparent disparity between studies is related to key differences in the stimulus configurations and psychophysical tasks involved. The previous studies of contrast discrimination required observers to identify the location of a pedestal square that differed in contrast from three other pedestal squares, all of which were relatively large (1° in width). A recent study of the spatial summation properties of contrast discrimination in visually normal observers
28 indicated that contrast discrimination within the pulsed-pedestal paradigm under these conditions is based on the luminance contrast at the edges of the targets. Further, according to that study, there is considerable spatial summation of such edge information, presumably at a cortical level. As a result, even if there were a substantial loss of receptive fields within the PC pathway in RP, the availability of abundant edge information in the pedestal squares of the previous studies
18 19 may have led to an underestimation of the loss of PC-pathway sensitivity. By comparison, the one-dimensional D6 patterns that were used in the present study, which were circular in shape, contained little edge information that could have contributed to detection. Thus, circular D6 patterns appear to provide a more sensitive measure of dysfunction within the PC pathway than do the large pedestal squares that were used in previous studies of contrast discrimination in patients with RP.
18 19 Consistent with this conclusion is our observation that the patients with RP showed significant correlations between their contrast sensitivities, as measured with D6 patterns, and their visual acuities and contrast sensitivities, as measured with letter optotypes.
For both the steady- and pulsed-pedestal paradigms, the patients’ contrast sensitivity losses occurred across a range of spatial frequencies, but the losses were most pronounced at the highest spatial frequency (8 cpd). This predominant loss of contrast sensitivity at high spatial frequencies is consistent with previous studies that did not use test conditions that were designed to emphasize selectively the MC and PC pathways.
3 4 5 6 7 8 9 Further, our results are in agreement with the previous observation that the contrast sensitivity functions of patients with RP are not simply shifted uniformly downward from normal.
9
It is presently uncertain why patients with RP show a greater loss of contrast sensitivity at high spatial frequencies. A reduced quantal catch by foveal cone photoreceptors, which has been described as a “dark-glasses” model of RP, does not appear to be an adequate explanation. Studies in which retinal densitometry and color matching have been employed have shown evidence of a reduced optical density of foveal cone photopigment
29 30 31 in patients with RP (although Swanson and Fish
32 found no evidence of reduced foveal cone optical density in patients with RP whose visual acuities were within the range of the patients in the present study). However, a reduced cone photopigment optical density would effectively decrease the mean retinal illuminance of the stimulus display but would not alter the stimulus contrast. Therefore, under adapting conditions for which Weber’s law holds, such as in the present study, a decreased retinal illuminance would not be expected to produce a contrast sensitivity loss at high spatial frequencies. This was confirmed in a pilot investigation in a control observer. Further, previous studies have concluded that a dark-glasses model of RP does not account for various aspects of foveal vision loss in these patients, including abnormalities in temporal contrast sensitivity,
33 increment thresholds,
34 probe-on-flash thresholds,
35 motion perception,
36 and symmetry discrimination.
37 Consequently, it seems unlikely that a decreased quantal catch due to a reduced foveal cone optical density accounts for the high-spatial-frequency deficits shown by patients with RP.
A reduced responsiveness of the foveal cone photoreceptors, which has been examined in previous studies as a potential explanation for foveal abnormalities in RP,
35 38 also does not appear to be an adequate explanation for the predominant loss of contrast sensitivity at high spatial frequencies. Reduced cone photoreceptor responsiveness would be expected to result in a uniform loss of contrast sensitivity across spatial frequencies, but this was not observed. Further, in these studies of a possible reduced photoreceptor responsiveness in patients with RP, a probe-on-flash paradigm was used, which is similar to the pulsed-pedestal paradigm used in the present study. This paradigm is thought to favor the PC pathway.
20 As a consequence, any reductions in maximum response amplitude (
R max) observed in studies of probe-on-flash thresholds may have represented the impact of cone photoreceptor degeneration on the response properties of the PC pathway, rather than the response properties of the cone photoreceptors per se. For example, one way in which a reduction in
R max could occur is through a dropout of foveal cone photoreceptors from a summation pool within the PC pathway. Therefore, a reduced responsiveness of the foveal cone photoreceptors does not appear to be a satisfactory explanation for the loss of contrast sensitivity at high spatial frequencies shown by these patients with RP.
A reduction in the spatial density of foveal cone photoreceptors owing to cone photoreceptor cell death seems a likely explanation for the predominant contrast sensitivity loss at high spatial frequencies in RP. Histologic studies have reported a reduced number of foveal cone photoreceptors in RP donor eyes, even in those eyes that had relatively good visual acuity.
39 40 41 Nevertheless, simulations of spatial sampling deficits that have been performed in visually normal observers have led to the conclusion that a random loss of foveal cone photoreceptors is not likely to be the major determinant of patients’ performance deficits at high spatial frequencies. For example, the visual acuity of control observers is relatively well preserved despite a substantial decrease in the number of visual samples, intended to mimic a loss of cone photoreceptors.
42 43 Further, a study of the effect of spatial undersampling on contrast sensitivity for D6 patterns in control observers,
44 in which random portions of the target were replaced by the background, found that contrast sensitivity was reduced equivalently at all spatial frequencies, rather than predominantly at high spatial frequencies. In addition, another form of undersampling produced by static visual noise that was presented simultaneously with a D6 test target (analogous to the pulsed-pedestal paradigm used in this study) resulted in a greater contrast sensitivity deficit at low than at high spatial frequencies in control observers,
45 contrary to the results of the present study. Thus, none of these various sampling paradigms predicts the relatively greater contrast sensitivity loss at high spatial frequencies observed in patients with RP. However, the extent to which these sampling paradigms accurately mimic a random loss of foveal cone photoreceptors remains to be determined.
On a practical note, it is often assumed that visual acuity that is better than 20/40 (0.3 log MAR), as seen in the patients with RP in the present study, provides a viable degree of visual function. For example, visual acuity of 20/40 or better is the criterion for a driver’s license in most U.S. states.
46 However, in individuals with retinal disease, our results emphasize that there can be a substantial reduction in sensitivity to contrast at these presumably modest levels of visual acuity loss. As an example, RP patient 12, whose Snellen visual acuity was slightly better than 20/40
(Table 1) , had an approximately 10-fold reduction in contrast sensitivity for the steady-pedestal paradigm at moderate to high spatial frequencies
(Fig. 4) as well as a similar reduction in letter contrast sensitivity
(Fig. 6) .
In conclusion, the patients with RP in this study showed equivalent contrast sensitivity deficits under testing conditions that targeted the MC and PC pathways. These results are in apparent disagreement with previous studies of contrast discrimination in RP in which greater deficits were found under conditions that favored the MC pathway.
18 19 This apparent discrepancy is likely to be due to the nature of the testing conditions that were used in the various studies. That is, contrast discrimination among large test stimuli, used in the prior studies, may not be as sensitive to damage to the PC pathway as is orientation discrimination of a spatially band-limited stimulus, used in the present study. Consistent with previous studies of contrast sensitivity in RP that did not specifically target the MC and PC pathways, we observed a greater loss of contrast sensitivity at high spatial frequencies in this group of patients with RP. The exact explanation for the high-spatial-frequency deficits in contrast sensitivity in patients with RP remains to be resolved, although a reduction in the spatial density of the foveal cone photoreceptors may be a major contributor.
The authors thank Linda Glennie for programming assistance, Dingcai Cao for statistical advice, and Deborah Derlacki for assistance in patient testing.