- Email: [email protected]
Symmetry discrimination in patients with retinitis pigmentosa
Vol. 35, No. 11, pp. 1633-1640, 1995 Copyright © 1995 Elsevier Science Ltd Printed in Great Britain. All rights reserved 0042-6989/95 $9.50 + 0.00
Vision Res.
Pergamon
0042-6989(94)00275-4
Symmetry Discrimination in Patients with Retinitis Pigmentosa JANET P. SZLYK,*J" WILLIAM SEIPLE,~ WEI XIE* Received 16 August 1993; in revised form 3 February 1994; in final form 25 October 1994
To investigate the relative sensory and perceptual contributions to central visual function of patients with retinitis pigmentusa (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. Visual perception
Retinitis pigmentosa Foveal function Symmetry discrimination
Sloan letters, grating patterns, bar offsets, and Amsler grids are typically used to assess foveal spatial function in patients with central vision loss. Because of the inherent redundancy of these stimuli and perceptual completion processes such as "filling in" (Bergen, 1991; Ramachandran & Gregory, 1991; Schuchard, 1993), these tests may not be sensitive enough to detect changes in the retinal sampling mosaic. An alternative to these types of stimuli is spatially random block patterns, similar to patterns that have been used to test symmetry discrimination (Royer, 1981). These block patterns consist of elements of a constant size, and the intensity of each element is randomly chosen to be either maximum or minimum. The spatial organization of these black and white elements ranges between symmetric distributions and asymmetric distributions (Fig. 1). Due to the unpredictable location of each pattern element, subjects must detect each element to accurately judge symmetry and cannot rely on perceptual completion processes. We tested whether a symmetry paradigm is useful to assess changes in central visual function that have been
reported in patients with retinitis pigmentosa (RP) (Sandberg & Berson, 1983; Farber, Fishman & Weiss, 1985; Marshall & Heckenlively, 1987; Flannery, Farber, Bird & Bok, 1989; Madreperla, Palmer, Massof & Finkelstein, 1990). RP, a group of hereditary retinal degenerations, is characterized by the progressive degeneration of rod photoreceptors resulting in a loss of peripheral visual field and nightblindness (Newsome, 1988). Secondarily, cone photoreceptors degenerate causing reduced central visual function (Farber et al., 1985; Madreperla et al., 1990). In the initial study, we compared symmetry discrimination of subjects with normal vision to that of patients with RP. We found that patients with RP performed this symmetry discrimination task less accurately than observers with normal vision. Four hypotheses that could account for these data were evaluated. These hypotheses are based on the reported anatomic and physiologic changes in retinas of patients with RP. Hypothesis 1 states that the loss of accuracy in symmetry discrimination in patients with RP may be due to a decrease in photopigment optical density (Perlman & Auerbach, 1981; Van Meel & Van Norren, 1983; Kilbride, Fishman, Fishman & Hutman, 1986). A quantal catch reduction would reduce the effective luminance of the patterns. In Expt 1 we compared symmetry discrimination in subjects with normal vision with and without a neutral-density filter. Hypothesis 2 states that the results may be ac-
*Department of Ophthalmology and Visual Sciences, UIC Eye Center, University of Illinois at Chicago College of Medicine, Chicago, IL 60612, U.S.A. tWest Side Veterans Administration Medical Center, Chicago, IL 60612, U.S.A. ~Department of Ophthalmology, New York University Medical Center, New York, NY 10016, U.S.A. 1633
1634
JANET P. SZLYK et al.
counted for by a loss in spatial contrast sensitivity, such as that observed in some patients with RP (Lindberg, Fishman, Anderson & Vasquez, 1981; Marmor, 1986). In Expt 2 we tested the effects of reduced contrast on symmetry discrimination in subjects with normal vision using patterns of reduced contrast levels. Hypothesis 3 states that the losses of symmetry discrimination accuracy in patients with RP may be due to reductions in temporal frequency sensitivity such as observed in some patients with RP (Kawazawa, Yamamota & Itoi, 1982; Tyler, Ernst & Lyness, 1984, Seiple, Siegel, Carr & Mayron, 1986; Dagnelie & Massof, 1993). In Expt 3 we examined symmetry discrimination in subjects with normal vision and patients with RP as a function of stimulus duration. Hypothesis 4 states that these losses in accuracy of symmetry discrimination in the patients with RP may be accounted for by decreased photoreceptor spatial density (Sandberg & Berson, 1983; Marshall & Heckenlively, 1987; Flannery et al., 1989). We measured symmetry discrimination in Expt 4 by presenting targets at increasing eccentricities in subjects with normal vision. We also tested symmetry discrimination in subjects with normal vision with patterns where visual information was reduced by randomly blanking individual pixels.
INITIAL STUDY Materials and methods
Subjects. Eleven subjects with normal vision, including patients' unaffected family members and clinic staff, participated in the study. These subjects had 20/20 (0.0 LogMar) or better visual acuity in their tested eye, as evaluated with the Lighthouse ETDRS charts (Lighthouse, Inc., Long Island City, N.Y.) Their ages ranged from 24 to 44 yr (mean age, 31 yr). Eleven patients with RP who had 20/30 (0.2 LogMar) or better visual acuity in their tested eye also participated. Their ages ranged from 25 to 48 yr (mean age, 32 yr). Their visual fields extended at least 20deg on either side of the fovea to the Goldmann 4-e-III test target. The patients showed minimal or no media opacities on fundus examination and no evidence of macular edema on fluorescein angiography. All subjects gave informed consent to participate. Testing was conducted in fill compliance with the Declaration of Helsinki. Stimuli. We used 32 symmetric patterns that were either horizontally symmetric (elements organized symmetrically on either side of a horizontally oriented axis), vertically symmetric (elements organized symmetrically on either side of a vertically oriented axis), doubly symmetric (elements organized symmetrically on either side of both horizontally and vertically oriented axes), or centrosymmetric (the pattern is identical when oriented upright or rotated 180 deg) or 32 asymmetric patterns. An example of each type of symmetry and an example of an asymmetric pattern are shown in Fig. 1. Each pattern consisted of 64 elements (0.5 × 0.5 deg) that were either white (70 cd/m 2) or black (4.6 cd/m2). The patterns were presented on a computer monitor (Apple) and viewed at a distance of 189 cm. The background luminance was 79 cd/m 2 (as measured with a H V Spectra Spotmeter, Kollmorgen, Newburgh, N.Y.), and the stimulus contrast was 93%. Procedure. The subjects were initially shown printed representatives of each type of symmetry and an asymmetric pattern in order to familiarize them with the stimuli. All subjects were then given 10 practice trials (two representatives of each of the five pattern types) with feedback using the video monitor. An auditory signal was provided for l sec preceding each stimulus presentation, along with a cross hair marker that was D C intended to localize the subject's fixation on the center of the screen. Stimuli were presented for 255 msec, and the subjects were required to respond by stating the type of symmetry or whether the pattern was asymmetric. The control subjects and patients were tested monocularly and were best corrected for the distance. The nontested eye was occluded. We tested each of our subjects twice (both controls and patients). There was no evidence of a consistent improvement in accuracy between the two trials for either group. The control A FIGURE 1. Examplesof the types of symmetricpatterns (horizontally subjects averaged a 3.9% difference on the second trial symmetric labelled H; vertically symmetricV; doubly symmetricD: (with a range from - 1 . 9 % to 6.7%), and the patients centrosymmetricC) and an asymmetricpattern A. averaged a 1.6% difference (with a range from - 2 . 1 %
S Y M M E T R Y
100
DISCRIMINATION IN RP
--
90 -
80 ÷ +
70
In contrast, the patients with RP either correctly identified the type of symmetry or demonstrated a bias towards labelling the pattern as "asymmetric". When the RP patients were presented with symmetrical patterns and the responses were incorrect, they were 5 times more likely to label the pattern asymmetrical than another type of symmetry (X2 = 48.38, P ~<0.001, d.f. = 1). Having identified these differences in symmetry discrimination between the control subjects and the patients with RP, we tested four hypotheses to determine the locus of this deficit.
--
+ + +
6o
1635
I
I
Control
RP
FIGURE 2. Distribution of the percent correct scores for both the control and patient populations. RP indicates patients with retinitis pigmentosa.
to 2.6%). Therefore, only the data from the first trial were used in the analysis.
EXPERIMENT 1: CHANGES IN PATTERN LUMINANCE
Rationale It has been reported that patients with RP with good acuity can have reductions of cone photopigment optical density up to 1.0 log unit (Perlman & Auerbach, 1981; Van Meel & Van Norren, 1983; Kilbride et al., 1986). To examine the effects that a reduction in target luminance of this magnitude has on symmetry discrimination, we tested normally-sighted subjects with and without a 1.0 log unit neutral-density filter.
Results The findings of the initial study are shown in Fig. 2. The control subjects had an average of 89.2 + 5.2% correct symmetry identification, whereas the patients with RP had an average of 7 4 . 5 + 8 . 8 % correct. The difference in means was statistically significant (t = 4.8, e < 0.001, d.f. = 20). Figure 3(a) shows the percentage of errors for each type of symmetry for the control subjects and the patients with RP. The control subjects had a greater percentage of errors on the centrosymmetric patterns than on the other types of patterns (Newman-Keuls post-hoc tests--centrosymmetric vs horizontally symmetric, P <~0.02; centrosymmetric vs vertically symmetric, P ~<0.005; centrosymmetric vs doubly symmetric, P <~0.01; centrosymmetric vs asymmetric, P ~<0.01). The patients with RP had a greater percentage of errors in response to all of the symmetric pattern types relative to their error rate on the asymmetric patterns (NewmanKeuls post hoc tests--asymmetric vs horizontally symmetric, P ~<0.02; asymmetric vs vertically symmetric, P ~<0.05; asymmetric vs doubly symmetric, P ~< 0.05; asymmetric vs centrosymmetric, P ~<0.004). We next examined the distribution of error responses to the symmetrical patterns for both groups [Fig. 3(b)]. When the control subjects were presented with symmetrical patterns and the responses were incorrect, they were twice as likely to label the pattern symmetrical as asymmetrical (Z2 = 5.3, P ~< 0.025, d.f. = 1). These data demonstrate a symmetric bias similar to that observed in other types of symmetry tasks (Rock, 1984). For example, this means that when the control subjects were presented with a vertically symmetric pattern and were uncertain, they were more likely to respond erroneously with another type of symmetry than with "asymmetric".
o 100 ~" 80 ~ 60 ~'o ~' 40 ~ 20 ~, 0
Horiz
Vert
Double
Centro
Asymm
~ 100 ~ ~ o .~ ~
80 60 40
20 0
Symm Control
Asymm ~
RP
FIGURE 3. (a) The average percent errors for each pattern type for the control subjects and for the patients with RP. Horiz indicates horizontally symmetric; Vert indicates vertically symmetric; Asymm indicates asymmetric. RP indicates patients with retinitis pigmentosa. (b) The average percent of incorrect responses by type demonstrating a symmetry bias in error responding for the control subjects and an asymmetry bias in error responding for the patients with RP.
1636
JANET P. SZLYK et al.
Materials and methods
Two subjects with normal vision ages 32 yr (referred to as Subject 32a) and 43 yr were tested. The same 64 patterns and procedure from the initial study were used. Testing was performed monocularly with and without a 1.0 neutral-density filter placed in front of the tested eye (Oriel, Stratford, Conn.).
loo (a)
E X P E R I M E N T 2: C H A N G E S IN P A T T E R N C O N T R A S T
Materials and Methods
Three subjects with normal vision ages 32 yr (referred to as Subject 32b), 35, and 37 yr were tested. The same 64 patterns from the initial study were used. In this experiment, pattern contrast (Michelson) was either 93%, 50%, 25%, or 5%.
±
80 T
RP
Patients
~
70 60 50
O
o
0
I
I
I
10
20
30
I
I
I
40 50 60 Contrast (%)
|
I
I
I
70
80
90
100
100
80 60 40 20
Rationale
RP patients have been reported to have elevated contrast sensitivities (Lindberg et aL 1981; Marmor, 1986). If deficits remain at all contrast levels then the patients with RP may be viewing the patterns at effectively reduced contrast. To test the effects of pattern contrast, we tested symmetry discrimination in normally-sighted subjects at different contrast levels.
i
I
~,~
Results
A 1.0log unit reduction in the luminance of the patterns did not significantly alter symmetry discrimination. The means and SDS for the control subjects were the following: 87.8 + 1.0% with the neutral density filter, and 86.5 + 3.0% without the filter, t = 1.76, P = n.s., d.f. = 1. Reduction of luminance did not produce a similar deficit in accuracy to those observed in our patient group in the initial study nor did the manipulation produce an asymmetric response bias.
T
•
90
~' g o,5
0 Symm Control 5%
Asymm ~
RP
FIGURE 4. (a) Average percent correct responses for three control subjects as a function of pattern contrast. RP indicates the average percent correct for the patients with retinitis pigrnentosa from Fig. 2. (b) The average percent of incorrect responses for the control subjects with patterns of 5% contrast and for the patients with RP with patterns of 93% contrast. Even with patterns of 5% contrast, the control subjects do not exhibit the asymmetricalbias observed with the patients with patterns of 93% contrast from Fig. 3(b). discrimination in subjects with normal vision and in patients with RP.
Results
The findings of Expt 2 are shown in Fig. 4(a). Reduction of the pattern contrast to 50% had no effect on the accuracy of symmetry discrimination. Even with patterns of 5% contrast (88% reduction in contrast), the control subjects had more accurate symmetry discrimination than did the patients with RP when presented with patterns of 93% contrast. At 5% contrast the control subjects did not show the asymmetrical bias in error responses exhibited by the subjects with RP with patterns of 93% contrast [Fig. 4(b)].
E X P E R I M E N T 3: CHANGES IN STIMULUS DURATION
Rationale
RP patients have been reported to have temporal sensitivity deficits (Kawazawa et al., 1982; Tyler et al., 1984; Seiple et al., 1986; Dagnelie & Massof, 1993). This reduction in temporal sensitivity might account for the errors observed in patients with RP. Therefore we tested the effects of presentation duration on symmetry
Materials and methods
Three subjects with normal vision ages 27, 35 (same subject as in Expt 2), and 45 yr were tested. In addition, five subjects with RP ages 26, 28, 31, 37, and 40 yr, who met the same vision requirements as those patients in the initial study, but who did not participate in the initial study, were also tested. The same 64 patterns from the initial study were presented at a contrast of 93%. The order of presentation duration (255, 500 or 1000 msec) was counterbalanced across subjects. Results
The findings of Expt 3 are shown in Fig. 5(a). For the normally-sighted control subjects, there was only a 5% decrease in the accuracy of symmetry discrimination over the range of presentation durations tested. There was no change in accuracy across the three durations tested for the patients. Patients with RP did worse at 255, 500, and 1000 msec than the control subjects did at 16 msec.
SYMMETRY DISCRIMINATION IN RP I n addition, the distribution o f errors made by the control subjects and the patients with R P differed [see Fig. 5(b)] at all durations tested. Even at 16 msec, when an error was made, the control subjects were m o r e likely to respond with a symmetrical response than an asymmetrical response (X2= 17.3, P ~<0.001, d.f. = 1). In contrast to this pattern, the patients with R P tested at 255 msec were m o r e likely to error by calling the pattern asymmetrical (X 2 = 48.38, P ~< 0.001, d.f. = 1). A n asymmetrical bias was also observed for the patients at 500 and 1000 msec durations.
100
1637
(a)
90 ~,
80
~" 70 60
RP central fixation I
0
I
10
20
Retinal eccentricity (temporal) • 9°
4: CHANGES IN THE SPATIAL
EXPERIMENT
s 4
*M
DISTRIBUTION OF SAMPLING ELEMENTS
Rationale R e p o r t s based on the histology o f the retinas o f patients with R P have described decreased cone p h o t o receptor density (see review by Marshall & Heckenlively, 1987). Reduced sampling element density might alter s y m m e t r y discrimination in patients with RP. W e tested the effects o f reduced sampling element density in three ways. First, we examined s y m m e t r y discrimination in
b?......................................
40
~ 100
8 O o
(a)
T L
80
0
T
I
T
60
0
.-"
2
~J
Symm
Control 20°
70
50
"
I
I
I
,I,
I
2O0
400
600
800
1000
Duration (msec)
1
Asymm
~
RP
FIGURE 6. (a) Average percent correct responses for four control subjects as a function of retinal eccentricity. The data for three pattern sizes are presented: 9 x 9deg (squares), 4 × 4deg (circles), and m-scaled (diamonds). RP indicates the average percent correct for the patients with retinitis pigmentosa from Fig. 2. (b) The average percent of incorrect responses by type for the control subjects with patterns presented at a 20 deg eccentricity and for the RP patients with centrally presented targets [from Fig. 3(b)]. The control subjects exhibit the asymmetrical response bias at 20 deg that the patients show with centrally-presented targets. the periphery o f normally-sighted subjects where cone density is reduced. Secondly, we r a n d o m l y removed pictorial elements from the patterns themselves.
O r~
Experiment 4a: Effects of Retinal Eccentricity Materials and methods
100 80
O
60 40 20 0
Symm [~
Control
Asymm ~
RP
16 msec FIGURE 5. (a) Average percent correct responses for three control subjects (circles) and five patients with RP (triangles) as a function of presentation duration. (b) The average percent of incorrect responses by type for the control subjects at 16 msec and for the patients with RP at 255 msec. Even at the 16 msec duration, the control subjects do not exhibit the asymmetrical bias observed with the patients.
F o u r subjects with n o r m a l vision ages 27 (same subject as in Expt 3), 31, 32b, and 36 yr were tested. In this experiment, the patterns subtended either 4 0 d e g ( 0 . 5 x 0 . 5 d e g elements) or 9 d e g (1.125 × 1.125deg elements), or the element size was m-scaled. The m-scaled patterns were magnified according to the cortical magnification factor o f R o v a m o and Virsu (1979). The patterns o f 93% contrast were presented to the central retina, 10 or 20 deg in the temporal retina, for 255 msec.
Results Symmetry discrimination accuracy as a function o f retinal eccentricity is shown in Fig. 6(a). Regardless o f
1638
JANET P. SZLYK et al.
the pattern size, accuracy decreased with increasing eccentricity. Performance accuracy in the peripheral retina did not improve with the larger pattern size or with m-scaling of the pattern element size. Interestingly, subjects with normal vision reached a similar level of performance at a 20 deg eccentricity as the patients' performance with centrally presented targets. We examined the response patterns of control subjects at a 20deg eccentricity as a function of the type of symmetry. In Fig. 6(b), these are compared with the patients' patterns of response to centrally presented patterns from the initial study. At a 20 deg eccentricity, the control subjects demonstrated an asymmetric bias (X2 = 38.76, P ~<0.001, d.f. = l) that was similar to that exhibited by the patients. The decreased performance of the control subjects at peripheral retinal eccentricities may have been due to slower pattern processing. To test this we compared performance at a 20 deg eccentricity with patterns presented for 1 sec and 255 msec durations. The average performance of three control subjects (aged 33, 35, and 45 yr) did not differ significantly for the two durations (t = 0.95, P = n.s., d.f. = 2).
teristics of central retinal losses in RP that could adversely affect patients' performance. (1) A reduction in photopigment density (Perlman & Auerbach, 1981; Van Meel & Van Norren, 1983; Kilbride et al., 1986) would effectively reduce the target luminance. (2) Contrast sensitivity losses (Lindberg et aL, 1981; Marmor, 1986) would reduce the distinguishability among the individual target elements. (3) Losses of temporal sensitivity (Kawazawa et al., 1982; Tyler et al., 1984; Seiple et al., 1986; Dagnelie & Massof, 1993) could reduce the effective stimulus duration. (4) Decreases in cone photoreceptor density (Sandberg & Berson, 1983; Marshall & Heckenlively, 1987; Flannery et al., 1989) would result in pattern degradation due to undersampling. A 1.0 log unit reduction in pattern luminance did not produce similar deficits in symmetry discrimination to those observed in our patient group. Therefore reductions in the effective luminance of the pattern do not alone account for the patients' deficits. Likewise large reductions in stimulus contrast did not change performance in subjects with normal vision. In addition, the 1oo
(a)
~ J.
Experiment 4b: Effects of Pattern Degradation 80
Materials and methods Two subjects with normal vision ages 32a and 44yr were tested. Only the patterns subtending 4deg (0.5 x 0.5 deg elements, 50% contrast) were used in Expt 4b. We investigated the effects f sampling changes by setting a percentage of randomly-selected pixels to black. In separate trials, either 0%, 50%, 75%, or 88% of the pixels were randomly set to black.
~
RP
60 40 2O
0 0
I
i
i
I
i
20
40
60
80
100
Results
P e r c e n t o f array intact
Figure 7(a) shows the averaged symmetry discrimination for the two subjects under each of the sampling conditions as a function of the percent of pixels remaining intact. Accuracy did not change with a 50% loss of elements. With only 25% of the elements remaining, control subjects' performance matched the performance of patients with RP with non degraded patterns. However, a symmetric bias was observed for the control subjects [Fig. 7(b)] even with 12% of the pixels remaining intact (~2 = 10.8, P ~<0.001, d.f. = 1).
el00
~ 8o ~ 60 .~
N 2o ~
DISCUSSION We have demonstrated that patients with RP who have 20/30 or greater visual acuity make significantly more errors in symmetry discrimination than a control group with normal vision. In addition, patients with RP exhibited an asymmetric bias in their error responses compared with the symmetry bias observed in the control group's error responses. Because these differences may be due to sensory-based losses that are characteristic of RP, we tested a number of retinally based explanations for our findings. In designing these experiments, we addressed the functional and clinical charac-
40
0 Symm Control
Asymm ~
RP
12% FIGURE 7. (a) Average percent correct responses for two control subjects as a function of the percentage of the stimulus remaining intact (12% up to 100%). RP indicates the average percent correct for the patients with retinitis pigmentosa from Fig. 2. (b) The average percent of incorrect responses by type for the control subjects with patterns that were 12% intact for the RP patients with 100% intact patterns [from Fig. 3(b)]. The control subjects exhibit a symmetrical response bias with the 12% intact patterns as compared to the asymmetrical bias exhibited by the RP patients with the 100% intact patterns.
SYMMETRY DISCRIMINATION IN RP
elevations in contrast thresholds reported for patients with RP are relatively small and should not have affected the performance on the suprathreshold patterns (93% contrast). Therefore it is unlikely that the reported reductions in contrast sensitivity contributed to the patients' poorer performance. When stimulus duration was reduced to 16 msec, subjects with normal vision did not show the decrease in accuracy or the pattern of error responses (i.e. asymmetrical bias) observed in the patients with RP tested with a range of stimulus durations from 255 to 1000msec. Consistent with this finding, Alexander, Derlacki, Fishman and Szlyk (1993) reported that, for the task of high-contrast letter identification, patients with RP (with visual acuities 20/40 or better) did not show an improvement relative to a normally-sighted control group with stimulus durations ranging from 16 msec to 4 sec. Therefore it is unlikely that temporal duration contributed to the rate, or to the pattern of errors, observed in the patients with RP. We found a deficit in the control subjects' performance when the targets were presented at a 20 deg retinal eccentricity. Likewise at this eccentricity the control subjects exhibited an asymmetric bias. What characteristics of the normal retina at a 20 deg eccentricity could account for these findings? One obvious factor is that the density of the cone photoreceptors and post-receptoral representation are less than in the central retina. This undersampling may be similar to what is occurring in the patients' central retinas. If performance is an index of cone density alone, then the equivalent performance of patients with RP with centrally-presented targets to the performance of normally-sighted subjects with eccentrically-presented targets would mean equivalent cone densities at the two retinal loci. The density of cones in the normal retina at a 20 deg eccentricity is less than 10% of that observed in the normal fovea (Osterberg, 1935; Curcio, Sloan, Kalina & Hendrickson, 1990). Although there is a correspondence between symmetry perception in normal observers at a 20 deg eccentricity and that of the patients with RP with central fixation, an explanation based on cone sampling density reductions would also predict changes in other measures of visual function. For example, visual acuity would be expected to be reduced in proportion to the reduction in sampling density. It has been shown that the visual acuity of subjects with normal vision at a 20 deg eccentricity is 20/100 or less (Luduigh, 1941), and we have demonstrated that letter acuity in the control subjects is greatly reduced when only 10% of the sampling input is available to the central retina (Seiple, Holopigian, Szlyk & Greenstein, 1995. Because the patients with RP in our study had central visual acuity of 20/30 or greater and intact central fields, it is unlikely that decreased cone density alone can account for our results. Furthermore, compensating for decreases in post-receptoral sampling by m-scaling the pattern size did not equate performance at all eccentricities for the control subjects. Therefore, it is unlikely that post-receptoral mapping alone can account for the poorer performance at 20 deg in subjects with normal vision. Likewise it is unlikely that the
1639
poorer performance of the control subjects in the periphery is due to temporal processing, since performance was no better with 1 sec presentation durations than with 255 msec durations. An explanation based solely on reductions in receptor sampling density may also be rejected based on the findings reported in Expt 4b. Reducing the amount of information in the patterns by as much as 50% did not significantly alter symmetry discrimination in subjects with normal vision. These findings are not unexpected, given the largc element size (0.5 x 0.5 deg) for the patterns presented. Although the visual fields of the patients with RP were tested by a trained ophthalmic technician using a Goldmann Perimeter 4-e-III test target (which is an elliptical target of approx. 0.5 deg), it is possible that smaller scotomas in the central visual field could have been missed by using this method. Given the high luminance, high contrast, and 0.5 deg element size of the patterns, it is unlikely that these small scotomas, if present, would have affected the subject's perception of the overall stimulus. In support, Barlow and Reeves (1979) noted the robustness of the perception of symmetry when the positions of the small elements of their dot patterns were manipulated. Subjects in their study were able to detect symmetry in the patterns even when 60% of the dots were randomly displaced. Thus we conclude that even if very minute scotomas exist in our patients, this should not have obliterated the perception of symmetry given its previously demonstrated robustness. We found an asymmetric error response bias in the patients with RP. If the responses were based on an uncertainty regarding the type of symmetry, then a symmetric error response bias should have been observed as it was in the control subjects (Rock, 1984; Szlyk, Rock & Fisher, 1995). A symmetric bias would be expected given the instructions to the subjects. In the pre-trial training, subjects were shown two representatives of each of the five pattern types (asymmetrical, horizontally symmetric, vertically symmetric, doubly symmetric, and centrosymmetric). Therefore, the probabilities of presentation of any of these pattern types, as far as the subjects could deduce, was 0.2. Because there were four symmetrical pattern types, the probability of guessing a type of symmetry, when uncertain, would be 4 x 0.2 or 0.8; the probability of guessing asymmetric would be 0.2. Therefore when uncertain, a symmetrical error bias should have been observed, unlike the asymmetrical error bias observed in the patients with RP. In summary, there is no retinally based explanation which alone can account for the poorer performance of the patients with RP on the symmetry discrimination task. Perhaps, the deficits in symmetry discrimination may result from a combination of retinally based factors, or from a spatially heterogeneous loss of retinal function. Alternatively, alterations of sensory input may affect the perceptual encoding of the relationship among pattern elements. This is supported by the asymmetric bias in the responses of the patients.
JANET P. SZLYK et al.
1640
In support of this latter explanation, the findings of a number of neurophysiologic studies involving adult mammals have demonstrated dramatic changes in the cortical representation following experimental alterations of retinal input (Kaas, Krubitzer, Chino, Langston, Policy & Blair, 1990; Heinen & Skavenski, 1991; Chino, Kaas, Smith, Langston & Cheng, 1992). It has been noted that alterations of retinal input may also impact visual perception in patients with retinal disease (Temme, Mano & Noell, 1985; Turano, 1991). In the Turano (1991) study, some patients with RP had poor spatial-position precision on a bisection task that could not be predicted by their visual acuities. In addition, Temme et al. (1985) reported a perceptual magnification of the central visual field in patients with RP. In conclusion, our findings emphasize that the interpretation of tests of visual function in patients must consider both sensory and perceptual components. REFERENCES Alexander, K. R., Derlacki, D. J., Fishman, G. A. & Szlyk, J. P. (1993). Temporal properties of letter identification in retinitis pigmentosa. Journal of the Optical Society of America A, tO, 1631 1636. Barlow, H. B. & Reeves, B. C. (1979). The versatility and absolute efficiency of detecting mirror symmetry in random dot displays. Vision Research, 19, 783-793. Bergen, J. R. (1991). Theories of visual texture perception. In Regan, D. (Ed.), Spatial vision (pp. 114-134). Boca Raton, Fla: CRC Press. Chino, Y. M., Kaas J. H., Smith, E. L. Ill, Langston, A. L. & Cheng, H. (1992). Rapid reorganization of cortical maps in adult cats following restricted deafferentation in retina. Vision Research, 32, 789 796. Curcio, C. A., Sloan, K. R., Kalina, R. E. & Hendrickson, C. K. (1990). Human photoreceptor topography. Journal ~f Comparative Neurology, 292, 497-523. Dagnelie, G. & Massof, R. W. (1993). Foveal cone involvement in retinitis pigmentosa progression assessed through psychophysical impulse response parameters. Investigative Ophthalmology and Visual Science, 34, 243 255. Farber, M. D., Fishman, G. A. & Weiss, R. A. (1985). Autosomal dominantly inherited retinitis pigmentosa: Visual acuity loss by subtype. Archives of Ophthalmology, 103, 524 528. Flannery, J. G., Farber, D. B., Bird, A. C. & Bok, D. (1989). Degenerative changes in a retina affected with autosomal dominant retinitis pigmentosa. Investigative Ophthalmology and Visual Science, 30, 191-211. Heinen, S. J. & Skavenski, A. A. (1991). Recovery of visual responses in foveal V1 neurons following bilateral foveal lesions in adult monkey. Experimental Brain Research, 83, 67(~674. Kaas, J. H., Krubitzer, L. A., Chino, Y. M., Langston, A. L., Policy, E. H. & Blair, N. (1990). Reorganization of retinotopic cortical maps in adult mammals after lesions of the retina. Science, 248, 229-231. Kawazawa, F., Yamamota, T. & ltoi, M. (1982). Temporal modulation transfer functions in patients with retinal disease. Ophthalmic Research, 14, 409-416. Kilbride, P. E., Fishman, M., Fishman, G. A. & Hutman, L. P. (1986). Foveal cone pigment density difference and reflectance in retinitis pigmentosa. Archives of Ophthalmology 104, 220 224.
Lindberg, C. R., Fishman, G. A., Anderson, R. J. & Vasquez, V. (1981). Contrast sensitivity in retinitis pigmentosa. British Journal o[" Ophthalmology, 65, 855 858. Luduigh, E. (1941). Extrafoveal visual acuity as measured with Snellen test letters. American Journal of Ophthalmology, 24, 303 310. Madreperla, S. A., Palmer, R. W., Massof, R. W. & Finkelstein, D. (1990). Visual acuity loss in retinitis pigrnentosa: Relationship to visual field loss. Archives of Ophthalmology, 108, 358 361. Marmor, M. F. (1986). Contrast sensitivily versus acuity in retinal disease. British Journal of Ophthalmology, 70, 553-559. Marshall. J. & Heckenlively J. R. (1987). Pathological findings and putative mechanisms in retinitis pigmentosa. In Heckenlively, J. R. (Ed.), Retinitis pigmentosa (pp. 3747). Philadelphia, Pa: Lippincon. Newsome, D. A. (1988). Retinitis pigmentosa, usher's syndrome, and other pigmentary retinopathies. In Newsome, D. A. (Ed.), Retinal d.vstrophies and degenerations (pp. 161-194). New York: Raven Press. Osterberg, G. A. (1935). Topography of the layer of rods and cones in the human retina. Acta Ophthalmologica, 6, 1 102. Perlman, I. & Auerbach, E. (1981). The relationship between visual sensitivity and rhodopsin density in RP Investigative Ophthalmology and Visual Science, 20, 758 765. Ramachandran, V. S. & Gregory, R. L. (1991). Perceptual filling-in of artificially induced scotomas in human vision. Nature, 25, 699-702. Rock, I. (1984). Perception. New York: Freeman. Rovamo, J. & Virsu, V. (1979). An estimation and application of the human cortical magnification factor. Experimental Brain Research, 37, 495 510. Royer, F. L. (1981). Detection of symmetry. Journal of Experimental Psychology, 7, 1186 1210. Sandberg, M. A. & Berson, E. L. (1983). Visual acuity and cone spatial density in retinitis pigmentosa. Investigative Ophthalmology and Visual Science, 24, 1511 1513. Schuchard, R. A. (1993). Validity and interpretation of amsler grid reports. Archives of Ophthalmology, 111, 776 780. Seiple, W., Holopigian, K., Szlyk, J. P., & Greenstein, Y. C. (1995). The effects of random element loss on letter identification: Implications for visual acuity loss in patients with retinitis pigmentosa. Vision Research. In press. Seipte, W., Siegel, I. M., Carr, R. E. & Mayron, C. (1986). Evaluating macular function using the focal ERG. Investigative Ophthalmology and Visual Science, 27, 1123 1130. Szlyk, J. P., Rock, I. & Fisher, C. B. (1995). The level of processing of symmetrical forms tilted in depth. Spatial Vision. In press. Temme, L. A., Mano, J. H. & Noell, W. K. (1985). Eccentricity perception in the periphery of normal observers and those with retinitis pigmentosa. American Journal of Optometry and Physiological Optics, 62, 736 743. Turano, K. (1991). Bisection judgments in patients with retinitis pigmentosa. Clinical Vision Science, 6, 119-130. Tyler, W., Ernst, W. & Lyness, A. L. (1984). Photopic flicker sensitivity losses in simplex and multiplex retinitis pigmentosa. Investigative Ophthalmology and Visual Science, 25, 1035 1042. Van Meel, G. J. & Van Norren, D. (1983). Foveal densitometry in retinitis pigmentosa. Investigative Ophthalmology and Visual Science, 24, 1123 1130.
Acknowledgements--This work was supported in part by the AARP Andrus Foundation, Washington D.C.; center grants from the National RP Foundation Fighting Blindness, Inc. Baltimore, Md; and by unrestricted research grants from Research to Prevent Blindness, Inc., New York, N.Y.
Vision Res.
Pergamon
0042-6989(94)00275-4
Symmetry Discrimination in Patients with Retinitis Pigmentosa JANET P. SZLYK,*J" WILLIAM SEIPLE,~ WEI XIE* Received 16 August 1993; in revised form 3 February 1994; in final form 25 October 1994
To investigate the relative sensory and perceptual contributions to central visual function of patients with retinitis pigmentusa (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. Visual perception
Retinitis pigmentosa Foveal function Symmetry discrimination
Sloan letters, grating patterns, bar offsets, and Amsler grids are typically used to assess foveal spatial function in patients with central vision loss. Because of the inherent redundancy of these stimuli and perceptual completion processes such as "filling in" (Bergen, 1991; Ramachandran & Gregory, 1991; Schuchard, 1993), these tests may not be sensitive enough to detect changes in the retinal sampling mosaic. An alternative to these types of stimuli is spatially random block patterns, similar to patterns that have been used to test symmetry discrimination (Royer, 1981). These block patterns consist of elements of a constant size, and the intensity of each element is randomly chosen to be either maximum or minimum. The spatial organization of these black and white elements ranges between symmetric distributions and asymmetric distributions (Fig. 1). Due to the unpredictable location of each pattern element, subjects must detect each element to accurately judge symmetry and cannot rely on perceptual completion processes. We tested whether a symmetry paradigm is useful to assess changes in central visual function that have been
reported in patients with retinitis pigmentosa (RP) (Sandberg & Berson, 1983; Farber, Fishman & Weiss, 1985; Marshall & Heckenlively, 1987; Flannery, Farber, Bird & Bok, 1989; Madreperla, Palmer, Massof & Finkelstein, 1990). RP, a group of hereditary retinal degenerations, is characterized by the progressive degeneration of rod photoreceptors resulting in a loss of peripheral visual field and nightblindness (Newsome, 1988). Secondarily, cone photoreceptors degenerate causing reduced central visual function (Farber et al., 1985; Madreperla et al., 1990). In the initial study, we compared symmetry discrimination of subjects with normal vision to that of patients with RP. We found that patients with RP performed this symmetry discrimination task less accurately than observers with normal vision. Four hypotheses that could account for these data were evaluated. These hypotheses are based on the reported anatomic and physiologic changes in retinas of patients with RP. Hypothesis 1 states that the loss of accuracy in symmetry discrimination in patients with RP may be due to a decrease in photopigment optical density (Perlman & Auerbach, 1981; Van Meel & Van Norren, 1983; Kilbride, Fishman, Fishman & Hutman, 1986). A quantal catch reduction would reduce the effective luminance of the patterns. In Expt 1 we compared symmetry discrimination in subjects with normal vision with and without a neutral-density filter. Hypothesis 2 states that the results may be ac-
*Department of Ophthalmology and Visual Sciences, UIC Eye Center, University of Illinois at Chicago College of Medicine, Chicago, IL 60612, U.S.A. tWest Side Veterans Administration Medical Center, Chicago, IL 60612, U.S.A. ~Department of Ophthalmology, New York University Medical Center, New York, NY 10016, U.S.A. 1633
1634
JANET P. SZLYK et al.
counted for by a loss in spatial contrast sensitivity, such as that observed in some patients with RP (Lindberg, Fishman, Anderson & Vasquez, 1981; Marmor, 1986). In Expt 2 we tested the effects of reduced contrast on symmetry discrimination in subjects with normal vision using patterns of reduced contrast levels. Hypothesis 3 states that the losses of symmetry discrimination accuracy in patients with RP may be due to reductions in temporal frequency sensitivity such as observed in some patients with RP (Kawazawa, Yamamota & Itoi, 1982; Tyler, Ernst & Lyness, 1984, Seiple, Siegel, Carr & Mayron, 1986; Dagnelie & Massof, 1993). In Expt 3 we examined symmetry discrimination in subjects with normal vision and patients with RP as a function of stimulus duration. Hypothesis 4 states that these losses in accuracy of symmetry discrimination in the patients with RP may be accounted for by decreased photoreceptor spatial density (Sandberg & Berson, 1983; Marshall & Heckenlively, 1987; Flannery et al., 1989). We measured symmetry discrimination in Expt 4 by presenting targets at increasing eccentricities in subjects with normal vision. We also tested symmetry discrimination in subjects with normal vision with patterns where visual information was reduced by randomly blanking individual pixels.
INITIAL STUDY Materials and methods
Subjects. Eleven subjects with normal vision, including patients' unaffected family members and clinic staff, participated in the study. These subjects had 20/20 (0.0 LogMar) or better visual acuity in their tested eye, as evaluated with the Lighthouse ETDRS charts (Lighthouse, Inc., Long Island City, N.Y.) Their ages ranged from 24 to 44 yr (mean age, 31 yr). Eleven patients with RP who had 20/30 (0.2 LogMar) or better visual acuity in their tested eye also participated. Their ages ranged from 25 to 48 yr (mean age, 32 yr). Their visual fields extended at least 20deg on either side of the fovea to the Goldmann 4-e-III test target. The patients showed minimal or no media opacities on fundus examination and no evidence of macular edema on fluorescein angiography. All subjects gave informed consent to participate. Testing was conducted in fill compliance with the Declaration of Helsinki. Stimuli. We used 32 symmetric patterns that were either horizontally symmetric (elements organized symmetrically on either side of a horizontally oriented axis), vertically symmetric (elements organized symmetrically on either side of a vertically oriented axis), doubly symmetric (elements organized symmetrically on either side of both horizontally and vertically oriented axes), or centrosymmetric (the pattern is identical when oriented upright or rotated 180 deg) or 32 asymmetric patterns. An example of each type of symmetry and an example of an asymmetric pattern are shown in Fig. 1. Each pattern consisted of 64 elements (0.5 × 0.5 deg) that were either white (70 cd/m 2) or black (4.6 cd/m2). The patterns were presented on a computer monitor (Apple) and viewed at a distance of 189 cm. The background luminance was 79 cd/m 2 (as measured with a H V Spectra Spotmeter, Kollmorgen, Newburgh, N.Y.), and the stimulus contrast was 93%. Procedure. The subjects were initially shown printed representatives of each type of symmetry and an asymmetric pattern in order to familiarize them with the stimuli. All subjects were then given 10 practice trials (two representatives of each of the five pattern types) with feedback using the video monitor. An auditory signal was provided for l sec preceding each stimulus presentation, along with a cross hair marker that was D C intended to localize the subject's fixation on the center of the screen. Stimuli were presented for 255 msec, and the subjects were required to respond by stating the type of symmetry or whether the pattern was asymmetric. The control subjects and patients were tested monocularly and were best corrected for the distance. The nontested eye was occluded. We tested each of our subjects twice (both controls and patients). There was no evidence of a consistent improvement in accuracy between the two trials for either group. The control A FIGURE 1. Examplesof the types of symmetricpatterns (horizontally subjects averaged a 3.9% difference on the second trial symmetric labelled H; vertically symmetricV; doubly symmetricD: (with a range from - 1 . 9 % to 6.7%), and the patients centrosymmetricC) and an asymmetricpattern A. averaged a 1.6% difference (with a range from - 2 . 1 %
S Y M M E T R Y
100
DISCRIMINATION IN RP
--
90 -
80 ÷ +
70
In contrast, the patients with RP either correctly identified the type of symmetry or demonstrated a bias towards labelling the pattern as "asymmetric". When the RP patients were presented with symmetrical patterns and the responses were incorrect, they were 5 times more likely to label the pattern asymmetrical than another type of symmetry (X2 = 48.38, P ~<0.001, d.f. = 1). Having identified these differences in symmetry discrimination between the control subjects and the patients with RP, we tested four hypotheses to determine the locus of this deficit.
--
+ + +
6o
1635
I
I
Control
RP
FIGURE 2. Distribution of the percent correct scores for both the control and patient populations. RP indicates patients with retinitis pigmentosa.
to 2.6%). Therefore, only the data from the first trial were used in the analysis.
EXPERIMENT 1: CHANGES IN PATTERN LUMINANCE
Rationale It has been reported that patients with RP with good acuity can have reductions of cone photopigment optical density up to 1.0 log unit (Perlman & Auerbach, 1981; Van Meel & Van Norren, 1983; Kilbride et al., 1986). To examine the effects that a reduction in target luminance of this magnitude has on symmetry discrimination, we tested normally-sighted subjects with and without a 1.0 log unit neutral-density filter.
Results The findings of the initial study are shown in Fig. 2. The control subjects had an average of 89.2 + 5.2% correct symmetry identification, whereas the patients with RP had an average of 7 4 . 5 + 8 . 8 % correct. The difference in means was statistically significant (t = 4.8, e < 0.001, d.f. = 20). Figure 3(a) shows the percentage of errors for each type of symmetry for the control subjects and the patients with RP. The control subjects had a greater percentage of errors on the centrosymmetric patterns than on the other types of patterns (Newman-Keuls post-hoc tests--centrosymmetric vs horizontally symmetric, P <~0.02; centrosymmetric vs vertically symmetric, P ~<0.005; centrosymmetric vs doubly symmetric, P <~0.01; centrosymmetric vs asymmetric, P ~<0.01). The patients with RP had a greater percentage of errors in response to all of the symmetric pattern types relative to their error rate on the asymmetric patterns (NewmanKeuls post hoc tests--asymmetric vs horizontally symmetric, P ~<0.02; asymmetric vs vertically symmetric, P ~<0.05; asymmetric vs doubly symmetric, P ~< 0.05; asymmetric vs centrosymmetric, P ~<0.004). We next examined the distribution of error responses to the symmetrical patterns for both groups [Fig. 3(b)]. When the control subjects were presented with symmetrical patterns and the responses were incorrect, they were twice as likely to label the pattern symmetrical as asymmetrical (Z2 = 5.3, P ~< 0.025, d.f. = 1). These data demonstrate a symmetric bias similar to that observed in other types of symmetry tasks (Rock, 1984). For example, this means that when the control subjects were presented with a vertically symmetric pattern and were uncertain, they were more likely to respond erroneously with another type of symmetry than with "asymmetric".
o 100 ~" 80 ~ 60 ~'o ~' 40 ~ 20 ~, 0
Horiz
Vert
Double
Centro
Asymm
~ 100 ~ ~ o .~ ~
80 60 40
20 0
Symm Control
Asymm ~
RP
FIGURE 3. (a) The average percent errors for each pattern type for the control subjects and for the patients with RP. Horiz indicates horizontally symmetric; Vert indicates vertically symmetric; Asymm indicates asymmetric. RP indicates patients with retinitis pigmentosa. (b) The average percent of incorrect responses by type demonstrating a symmetry bias in error responding for the control subjects and an asymmetry bias in error responding for the patients with RP.
1636
JANET P. SZLYK et al.
Materials and methods
Two subjects with normal vision ages 32 yr (referred to as Subject 32a) and 43 yr were tested. The same 64 patterns and procedure from the initial study were used. Testing was performed monocularly with and without a 1.0 neutral-density filter placed in front of the tested eye (Oriel, Stratford, Conn.).
loo (a)
E X P E R I M E N T 2: C H A N G E S IN P A T T E R N C O N T R A S T
Materials and Methods
Three subjects with normal vision ages 32 yr (referred to as Subject 32b), 35, and 37 yr were tested. The same 64 patterns from the initial study were used. In this experiment, pattern contrast (Michelson) was either 93%, 50%, 25%, or 5%.
±
80 T
RP
Patients
~
70 60 50
O
o
0
I
I
I
10
20
30
I
I
I
40 50 60 Contrast (%)
|
I
I
I
70
80
90
100
100
80 60 40 20
Rationale
RP patients have been reported to have elevated contrast sensitivities (Lindberg et aL 1981; Marmor, 1986). If deficits remain at all contrast levels then the patients with RP may be viewing the patterns at effectively reduced contrast. To test the effects of pattern contrast, we tested symmetry discrimination in normally-sighted subjects at different contrast levels.
i
I
~,~
Results
A 1.0log unit reduction in the luminance of the patterns did not significantly alter symmetry discrimination. The means and SDS for the control subjects were the following: 87.8 + 1.0% with the neutral density filter, and 86.5 + 3.0% without the filter, t = 1.76, P = n.s., d.f. = 1. Reduction of luminance did not produce a similar deficit in accuracy to those observed in our patient group in the initial study nor did the manipulation produce an asymmetric response bias.
T
•
90
~' g o,5
0 Symm Control 5%
Asymm ~
RP
FIGURE 4. (a) Average percent correct responses for three control subjects as a function of pattern contrast. RP indicates the average percent correct for the patients with retinitis pigrnentosa from Fig. 2. (b) The average percent of incorrect responses for the control subjects with patterns of 5% contrast and for the patients with RP with patterns of 93% contrast. Even with patterns of 5% contrast, the control subjects do not exhibit the asymmetricalbias observed with the patients with patterns of 93% contrast from Fig. 3(b). discrimination in subjects with normal vision and in patients with RP.
Results
The findings of Expt 2 are shown in Fig. 4(a). Reduction of the pattern contrast to 50% had no effect on the accuracy of symmetry discrimination. Even with patterns of 5% contrast (88% reduction in contrast), the control subjects had more accurate symmetry discrimination than did the patients with RP when presented with patterns of 93% contrast. At 5% contrast the control subjects did not show the asymmetrical bias in error responses exhibited by the subjects with RP with patterns of 93% contrast [Fig. 4(b)].
E X P E R I M E N T 3: CHANGES IN STIMULUS DURATION
Rationale
RP patients have been reported to have temporal sensitivity deficits (Kawazawa et al., 1982; Tyler et al., 1984; Seiple et al., 1986; Dagnelie & Massof, 1993). This reduction in temporal sensitivity might account for the errors observed in patients with RP. Therefore we tested the effects of presentation duration on symmetry
Materials and methods
Three subjects with normal vision ages 27, 35 (same subject as in Expt 2), and 45 yr were tested. In addition, five subjects with RP ages 26, 28, 31, 37, and 40 yr, who met the same vision requirements as those patients in the initial study, but who did not participate in the initial study, were also tested. The same 64 patterns from the initial study were presented at a contrast of 93%. The order of presentation duration (255, 500 or 1000 msec) was counterbalanced across subjects. Results
The findings of Expt 3 are shown in Fig. 5(a). For the normally-sighted control subjects, there was only a 5% decrease in the accuracy of symmetry discrimination over the range of presentation durations tested. There was no change in accuracy across the three durations tested for the patients. Patients with RP did worse at 255, 500, and 1000 msec than the control subjects did at 16 msec.
SYMMETRY DISCRIMINATION IN RP I n addition, the distribution o f errors made by the control subjects and the patients with R P differed [see Fig. 5(b)] at all durations tested. Even at 16 msec, when an error was made, the control subjects were m o r e likely to respond with a symmetrical response than an asymmetrical response (X2= 17.3, P ~<0.001, d.f. = 1). In contrast to this pattern, the patients with R P tested at 255 msec were m o r e likely to error by calling the pattern asymmetrical (X 2 = 48.38, P ~< 0.001, d.f. = 1). A n asymmetrical bias was also observed for the patients at 500 and 1000 msec durations.
100
1637
(a)
90 ~,
80
~" 70 60
RP central fixation I
0
I
10
20
Retinal eccentricity (temporal) • 9°
4: CHANGES IN THE SPATIAL
EXPERIMENT
s 4
*M
DISTRIBUTION OF SAMPLING ELEMENTS
Rationale R e p o r t s based on the histology o f the retinas o f patients with R P have described decreased cone p h o t o receptor density (see review by Marshall & Heckenlively, 1987). Reduced sampling element density might alter s y m m e t r y discrimination in patients with RP. W e tested the effects o f reduced sampling element density in three ways. First, we examined s y m m e t r y discrimination in
b?......................................
40
~ 100
8 O o
(a)
T L
80
0
T
I
T
60
0
.-"
2
~J
Symm
Control 20°
70
50
"
I
I
I
,I,
I
2O0
400
600
800
1000
Duration (msec)
1
Asymm
~
RP
FIGURE 6. (a) Average percent correct responses for four control subjects as a function of retinal eccentricity. The data for three pattern sizes are presented: 9 x 9deg (squares), 4 × 4deg (circles), and m-scaled (diamonds). RP indicates the average percent correct for the patients with retinitis pigmentosa from Fig. 2. (b) The average percent of incorrect responses by type for the control subjects with patterns presented at a 20 deg eccentricity and for the RP patients with centrally presented targets [from Fig. 3(b)]. The control subjects exhibit the asymmetrical response bias at 20 deg that the patients show with centrally-presented targets. the periphery o f normally-sighted subjects where cone density is reduced. Secondly, we r a n d o m l y removed pictorial elements from the patterns themselves.
O r~
Experiment 4a: Effects of Retinal Eccentricity Materials and methods
100 80
O
60 40 20 0
Symm [~
Control
Asymm ~
RP
16 msec FIGURE 5. (a) Average percent correct responses for three control subjects (circles) and five patients with RP (triangles) as a function of presentation duration. (b) The average percent of incorrect responses by type for the control subjects at 16 msec and for the patients with RP at 255 msec. Even at the 16 msec duration, the control subjects do not exhibit the asymmetrical bias observed with the patients.
F o u r subjects with n o r m a l vision ages 27 (same subject as in Expt 3), 31, 32b, and 36 yr were tested. In this experiment, the patterns subtended either 4 0 d e g ( 0 . 5 x 0 . 5 d e g elements) or 9 d e g (1.125 × 1.125deg elements), or the element size was m-scaled. The m-scaled patterns were magnified according to the cortical magnification factor o f R o v a m o and Virsu (1979). The patterns o f 93% contrast were presented to the central retina, 10 or 20 deg in the temporal retina, for 255 msec.
Results Symmetry discrimination accuracy as a function o f retinal eccentricity is shown in Fig. 6(a). Regardless o f
1638
JANET P. SZLYK et al.
the pattern size, accuracy decreased with increasing eccentricity. Performance accuracy in the peripheral retina did not improve with the larger pattern size or with m-scaling of the pattern element size. Interestingly, subjects with normal vision reached a similar level of performance at a 20 deg eccentricity as the patients' performance with centrally presented targets. We examined the response patterns of control subjects at a 20deg eccentricity as a function of the type of symmetry. In Fig. 6(b), these are compared with the patients' patterns of response to centrally presented patterns from the initial study. At a 20 deg eccentricity, the control subjects demonstrated an asymmetric bias (X2 = 38.76, P ~<0.001, d.f. = l) that was similar to that exhibited by the patients. The decreased performance of the control subjects at peripheral retinal eccentricities may have been due to slower pattern processing. To test this we compared performance at a 20 deg eccentricity with patterns presented for 1 sec and 255 msec durations. The average performance of three control subjects (aged 33, 35, and 45 yr) did not differ significantly for the two durations (t = 0.95, P = n.s., d.f. = 2).
teristics of central retinal losses in RP that could adversely affect patients' performance. (1) A reduction in photopigment density (Perlman & Auerbach, 1981; Van Meel & Van Norren, 1983; Kilbride et al., 1986) would effectively reduce the target luminance. (2) Contrast sensitivity losses (Lindberg et aL, 1981; Marmor, 1986) would reduce the distinguishability among the individual target elements. (3) Losses of temporal sensitivity (Kawazawa et al., 1982; Tyler et al., 1984; Seiple et al., 1986; Dagnelie & Massof, 1993) could reduce the effective stimulus duration. (4) Decreases in cone photoreceptor density (Sandberg & Berson, 1983; Marshall & Heckenlively, 1987; Flannery et al., 1989) would result in pattern degradation due to undersampling. A 1.0 log unit reduction in pattern luminance did not produce similar deficits in symmetry discrimination to those observed in our patient group. Therefore reductions in the effective luminance of the pattern do not alone account for the patients' deficits. Likewise large reductions in stimulus contrast did not change performance in subjects with normal vision. In addition, the 1oo
(a)
~ J.
Experiment 4b: Effects of Pattern Degradation 80
Materials and methods Two subjects with normal vision ages 32a and 44yr were tested. Only the patterns subtending 4deg (0.5 x 0.5 deg elements, 50% contrast) were used in Expt 4b. We investigated the effects f sampling changes by setting a percentage of randomly-selected pixels to black. In separate trials, either 0%, 50%, 75%, or 88% of the pixels were randomly set to black.
~
RP
60 40 2O
0 0
I
i
i
I
i
20
40
60
80
100
Results
P e r c e n t o f array intact
Figure 7(a) shows the averaged symmetry discrimination for the two subjects under each of the sampling conditions as a function of the percent of pixels remaining intact. Accuracy did not change with a 50% loss of elements. With only 25% of the elements remaining, control subjects' performance matched the performance of patients with RP with non degraded patterns. However, a symmetric bias was observed for the control subjects [Fig. 7(b)] even with 12% of the pixels remaining intact (~2 = 10.8, P ~<0.001, d.f. = 1).
el00
~ 8o ~ 60 .~
N 2o ~
DISCUSSION We have demonstrated that patients with RP who have 20/30 or greater visual acuity make significantly more errors in symmetry discrimination than a control group with normal vision. In addition, patients with RP exhibited an asymmetric bias in their error responses compared with the symmetry bias observed in the control group's error responses. Because these differences may be due to sensory-based losses that are characteristic of RP, we tested a number of retinally based explanations for our findings. In designing these experiments, we addressed the functional and clinical charac-
40
0 Symm Control
Asymm ~
RP
12% FIGURE 7. (a) Average percent correct responses for two control subjects as a function of the percentage of the stimulus remaining intact (12% up to 100%). RP indicates the average percent correct for the patients with retinitis pigmentosa from Fig. 2. (b) The average percent of incorrect responses by type for the control subjects with patterns that were 12% intact for the RP patients with 100% intact patterns [from Fig. 3(b)]. The control subjects exhibit a symmetrical response bias with the 12% intact patterns as compared to the asymmetrical bias exhibited by the RP patients with the 100% intact patterns.
SYMMETRY DISCRIMINATION IN RP
elevations in contrast thresholds reported for patients with RP are relatively small and should not have affected the performance on the suprathreshold patterns (93% contrast). Therefore it is unlikely that the reported reductions in contrast sensitivity contributed to the patients' poorer performance. When stimulus duration was reduced to 16 msec, subjects with normal vision did not show the decrease in accuracy or the pattern of error responses (i.e. asymmetrical bias) observed in the patients with RP tested with a range of stimulus durations from 255 to 1000msec. Consistent with this finding, Alexander, Derlacki, Fishman and Szlyk (1993) reported that, for the task of high-contrast letter identification, patients with RP (with visual acuities 20/40 or better) did not show an improvement relative to a normally-sighted control group with stimulus durations ranging from 16 msec to 4 sec. Therefore it is unlikely that temporal duration contributed to the rate, or to the pattern of errors, observed in the patients with RP. We found a deficit in the control subjects' performance when the targets were presented at a 20 deg retinal eccentricity. Likewise at this eccentricity the control subjects exhibited an asymmetric bias. What characteristics of the normal retina at a 20 deg eccentricity could account for these findings? One obvious factor is that the density of the cone photoreceptors and post-receptoral representation are less than in the central retina. This undersampling may be similar to what is occurring in the patients' central retinas. If performance is an index of cone density alone, then the equivalent performance of patients with RP with centrally-presented targets to the performance of normally-sighted subjects with eccentrically-presented targets would mean equivalent cone densities at the two retinal loci. The density of cones in the normal retina at a 20 deg eccentricity is less than 10% of that observed in the normal fovea (Osterberg, 1935; Curcio, Sloan, Kalina & Hendrickson, 1990). Although there is a correspondence between symmetry perception in normal observers at a 20 deg eccentricity and that of the patients with RP with central fixation, an explanation based on cone sampling density reductions would also predict changes in other measures of visual function. For example, visual acuity would be expected to be reduced in proportion to the reduction in sampling density. It has been shown that the visual acuity of subjects with normal vision at a 20 deg eccentricity is 20/100 or less (Luduigh, 1941), and we have demonstrated that letter acuity in the control subjects is greatly reduced when only 10% of the sampling input is available to the central retina (Seiple, Holopigian, Szlyk & Greenstein, 1995. Because the patients with RP in our study had central visual acuity of 20/30 or greater and intact central fields, it is unlikely that decreased cone density alone can account for our results. Furthermore, compensating for decreases in post-receptoral sampling by m-scaling the pattern size did not equate performance at all eccentricities for the control subjects. Therefore, it is unlikely that post-receptoral mapping alone can account for the poorer performance at 20 deg in subjects with normal vision. Likewise it is unlikely that the
1639
poorer performance of the control subjects in the periphery is due to temporal processing, since performance was no better with 1 sec presentation durations than with 255 msec durations. An explanation based solely on reductions in receptor sampling density may also be rejected based on the findings reported in Expt 4b. Reducing the amount of information in the patterns by as much as 50% did not significantly alter symmetry discrimination in subjects with normal vision. These findings are not unexpected, given the largc element size (0.5 x 0.5 deg) for the patterns presented. Although the visual fields of the patients with RP were tested by a trained ophthalmic technician using a Goldmann Perimeter 4-e-III test target (which is an elliptical target of approx. 0.5 deg), it is possible that smaller scotomas in the central visual field could have been missed by using this method. Given the high luminance, high contrast, and 0.5 deg element size of the patterns, it is unlikely that these small scotomas, if present, would have affected the subject's perception of the overall stimulus. In support, Barlow and Reeves (1979) noted the robustness of the perception of symmetry when the positions of the small elements of their dot patterns were manipulated. Subjects in their study were able to detect symmetry in the patterns even when 60% of the dots were randomly displaced. Thus we conclude that even if very minute scotomas exist in our patients, this should not have obliterated the perception of symmetry given its previously demonstrated robustness. We found an asymmetric error response bias in the patients with RP. If the responses were based on an uncertainty regarding the type of symmetry, then a symmetric error response bias should have been observed as it was in the control subjects (Rock, 1984; Szlyk, Rock & Fisher, 1995). A symmetric bias would be expected given the instructions to the subjects. In the pre-trial training, subjects were shown two representatives of each of the five pattern types (asymmetrical, horizontally symmetric, vertically symmetric, doubly symmetric, and centrosymmetric). Therefore, the probabilities of presentation of any of these pattern types, as far as the subjects could deduce, was 0.2. Because there were four symmetrical pattern types, the probability of guessing a type of symmetry, when uncertain, would be 4 x 0.2 or 0.8; the probability of guessing asymmetric would be 0.2. Therefore when uncertain, a symmetrical error bias should have been observed, unlike the asymmetrical error bias observed in the patients with RP. In summary, there is no retinally based explanation which alone can account for the poorer performance of the patients with RP on the symmetry discrimination task. Perhaps, the deficits in symmetry discrimination may result from a combination of retinally based factors, or from a spatially heterogeneous loss of retinal function. Alternatively, alterations of sensory input may affect the perceptual encoding of the relationship among pattern elements. This is supported by the asymmetric bias in the responses of the patients.
JANET P. SZLYK et al.
1640
In support of this latter explanation, the findings of a number of neurophysiologic studies involving adult mammals have demonstrated dramatic changes in the cortical representation following experimental alterations of retinal input (Kaas, Krubitzer, Chino, Langston, Policy & Blair, 1990; Heinen & Skavenski, 1991; Chino, Kaas, Smith, Langston & Cheng, 1992). It has been noted that alterations of retinal input may also impact visual perception in patients with retinal disease (Temme, Mano & Noell, 1985; Turano, 1991). In the Turano (1991) study, some patients with RP had poor spatial-position precision on a bisection task that could not be predicted by their visual acuities. In addition, Temme et al. (1985) reported a perceptual magnification of the central visual field in patients with RP. In conclusion, our findings emphasize that the interpretation of tests of visual function in patients must consider both sensory and perceptual components. REFERENCES Alexander, K. R., Derlacki, D. J., Fishman, G. A. & Szlyk, J. P. (1993). Temporal properties of letter identification in retinitis pigmentosa. Journal of the Optical Society of America A, tO, 1631 1636. Barlow, H. B. & Reeves, B. C. (1979). The versatility and absolute efficiency of detecting mirror symmetry in random dot displays. Vision Research, 19, 783-793. Bergen, J. R. (1991). Theories of visual texture perception. In Regan, D. (Ed.), Spatial vision (pp. 114-134). Boca Raton, Fla: CRC Press. Chino, Y. M., Kaas J. H., Smith, E. L. Ill, Langston, A. L. & Cheng, H. (1992). Rapid reorganization of cortical maps in adult cats following restricted deafferentation in retina. Vision Research, 32, 789 796. Curcio, C. A., Sloan, K. R., Kalina, R. E. & Hendrickson, C. K. (1990). Human photoreceptor topography. Journal ~f Comparative Neurology, 292, 497-523. Dagnelie, G. & Massof, R. W. (1993). Foveal cone involvement in retinitis pigmentosa progression assessed through psychophysical impulse response parameters. Investigative Ophthalmology and Visual Science, 34, 243 255. Farber, M. D., Fishman, G. A. & Weiss, R. A. (1985). Autosomal dominantly inherited retinitis pigmentosa: Visual acuity loss by subtype. Archives of Ophthalmology, 103, 524 528. Flannery, J. G., Farber, D. B., Bird, A. C. & Bok, D. (1989). Degenerative changes in a retina affected with autosomal dominant retinitis pigmentosa. Investigative Ophthalmology and Visual Science, 30, 191-211. Heinen, S. J. & Skavenski, A. A. (1991). Recovery of visual responses in foveal V1 neurons following bilateral foveal lesions in adult monkey. Experimental Brain Research, 83, 67(~674. Kaas, J. H., Krubitzer, L. A., Chino, Y. M., Langston, A. L., Policy, E. H. & Blair, N. (1990). Reorganization of retinotopic cortical maps in adult mammals after lesions of the retina. Science, 248, 229-231. Kawazawa, F., Yamamota, T. & ltoi, M. (1982). Temporal modulation transfer functions in patients with retinal disease. Ophthalmic Research, 14, 409-416. Kilbride, P. E., Fishman, M., Fishman, G. A. & Hutman, L. P. (1986). Foveal cone pigment density difference and reflectance in retinitis pigmentosa. Archives of Ophthalmology 104, 220 224.
Lindberg, C. R., Fishman, G. A., Anderson, R. J. & Vasquez, V. (1981). Contrast sensitivity in retinitis pigmentosa. British Journal o[" Ophthalmology, 65, 855 858. Luduigh, E. (1941). Extrafoveal visual acuity as measured with Snellen test letters. American Journal of Ophthalmology, 24, 303 310. Madreperla, S. A., Palmer, R. W., Massof, R. W. & Finkelstein, D. (1990). Visual acuity loss in retinitis pigrnentosa: Relationship to visual field loss. Archives of Ophthalmology, 108, 358 361. Marmor, M. F. (1986). Contrast sensitivily versus acuity in retinal disease. British Journal of Ophthalmology, 70, 553-559. Marshall. J. & Heckenlively J. R. (1987). Pathological findings and putative mechanisms in retinitis pigmentosa. In Heckenlively, J. R. (Ed.), Retinitis pigmentosa (pp. 3747). Philadelphia, Pa: Lippincon. Newsome, D. A. (1988). Retinitis pigmentosa, usher's syndrome, and other pigmentary retinopathies. In Newsome, D. A. (Ed.), Retinal d.vstrophies and degenerations (pp. 161-194). New York: Raven Press. Osterberg, G. A. (1935). Topography of the layer of rods and cones in the human retina. Acta Ophthalmologica, 6, 1 102. Perlman, I. & Auerbach, E. (1981). The relationship between visual sensitivity and rhodopsin density in RP Investigative Ophthalmology and Visual Science, 20, 758 765. Ramachandran, V. S. & Gregory, R. L. (1991). Perceptual filling-in of artificially induced scotomas in human vision. Nature, 25, 699-702. Rock, I. (1984). Perception. New York: Freeman. Rovamo, J. & Virsu, V. (1979). An estimation and application of the human cortical magnification factor. Experimental Brain Research, 37, 495 510. Royer, F. L. (1981). Detection of symmetry. Journal of Experimental Psychology, 7, 1186 1210. Sandberg, M. A. & Berson, E. L. (1983). Visual acuity and cone spatial density in retinitis pigmentosa. Investigative Ophthalmology and Visual Science, 24, 1511 1513. Schuchard, R. A. (1993). Validity and interpretation of amsler grid reports. Archives of Ophthalmology, 111, 776 780. Seiple, W., Holopigian, K., Szlyk, J. P., & Greenstein, Y. C. (1995). The effects of random element loss on letter identification: Implications for visual acuity loss in patients with retinitis pigmentosa. Vision Research. In press. Seipte, W., Siegel, I. M., Carr, R. E. & Mayron, C. (1986). Evaluating macular function using the focal ERG. Investigative Ophthalmology and Visual Science, 27, 1123 1130. Szlyk, J. P., Rock, I. & Fisher, C. B. (1995). The level of processing of symmetrical forms tilted in depth. Spatial Vision. In press. Temme, L. A., Mano, J. H. & Noell, W. K. (1985). Eccentricity perception in the periphery of normal observers and those with retinitis pigmentosa. American Journal of Optometry and Physiological Optics, 62, 736 743. Turano, K. (1991). Bisection judgments in patients with retinitis pigmentosa. Clinical Vision Science, 6, 119-130. Tyler, W., Ernst, W. & Lyness, A. L. (1984). Photopic flicker sensitivity losses in simplex and multiplex retinitis pigmentosa. Investigative Ophthalmology and Visual Science, 25, 1035 1042. Van Meel, G. J. & Van Norren, D. (1983). Foveal densitometry in retinitis pigmentosa. Investigative Ophthalmology and Visual Science, 24, 1123 1130.
Acknowledgements--This work was supported in part by the AARP Andrus Foundation, Washington D.C.; center grants from the National RP Foundation Fighting Blindness, Inc. Baltimore, Md; and by unrestricted research grants from Research to Prevent Blindness, Inc., New York, N.Y.