Abstract
Purpose.:
To evaluate achromatic contrast sensitivity (CS) with magnocellular- (M) and parvocellular- (P) probing stimuli in type 2 diabetics, with (DR) or without (NDR) nonproliferative retinopathy.
Methods.:
Inferred M- and P-dominated responses were assessed with a modified version of the steady-/pulsed-pedestal paradigm (SP/PP) applied in 26 NDR (11 male; mean age, 55 ± 9 years; disease duration, 5 ± 4 years); 19 DR (6 male; mean age, 58 ± 7 years; disease duration = 9 ± 6 years); and 18 controls (CTRL; 12 male; mean age, 55 ± 10 years). Thresholds were measured with pedestals at 7, 12, and 19 cd/m2, and increment durations of 17 and 133 ms. The thresholds from the two stimulus durations were used to estimate critical durations (Tc) for each data set.
Results.:
Both DR and NDR patients had significant reduction in CS in both SP and PP paradigms in relation to CTRL (Kruskal-Wallis, P < 0.01). Patients' critical duration estimates for either paradigm were not significantly different from CTRL.
Conclusions.:
The significant reduction of CS in both paradigms is consistent with losses of CS in both M and P pathways. The CS losses were not accompanied by losses in temporal processing speed in either diabetic group. Significant CS loss in the group without retinopathy reinforces the notion that neural changes associated with the cellular and functional visual loss may play an important role in the etiology of diabetic visual impairment. In addition, the results show that the SP/PP paradigm provides an additional tool for detection and characterization of the early functional damage due to diabetes.
Decreased achromatic spatial contrast sensitivity (CS) in diabetic patients has been reported in several studies,
1 –6 and the impact of such losses on patients' quality of life is significant.
7,8
It is well known that CS impairments do not necessarily correlate with standard visual acuity measures, since they can occur in patients with normal acuity,
9 –11 and although CS changes correlate positively with the presence and the degree of diabetic retinopathy,
4,9 the functional impairment has been attributed to changes in retinal neural activity occurring before the onset of the diabetic retinopathy.
12 –15 Thus, a more complete or specific characterization of the pathways involved in diabetic visual loss can help further our understanding of the etiology and mechanisms of the disease, as well as in clinical management. Some achromatic spatial CS studies in type 1 diabetics found a general decrease of sensitivity across low, middle, and high spatial frequencies,
3,4,10 suggesting that responses mediated by both the parvocellular (P) and magnocellular (M) systems are affected by the disease. Other findings, suggest a possible bias toward losses in the P channel based on selective losses at high spatial frequencies. Di Leo et al.
3 found that CS loss in type 1 diabetics was more frequent when static stimuli were used compared to when gratings were modulated at 8 Hz. Furthermore, dyschromatopsia has been reported as a classic sign of diabetic visual impairment, also implicating impairment in the P pathway
16 –18 (see Refs.
4,
13 for a review).
Evidence of early (i.e., prevascular) neuronal damage in diabetics
1 –6,13,17 and the mixed findings in the literature, with some studies suggesting more damage to P-mediated responses and others consistent with a diffuse deficit affecting both P and M functions, prompted us to explore this question further. To investigate the possibility of a differential effect on the inferred P and M responses in type 2 diabetic patients, we used a psychophysical, achromatic contrast-discrimination test, originally designed by Pokorny and Smith.
19
Based on M and P responses at the level of retina and lateral geniculate nucleus to spatiotemporal luminance contrast modulation,
20 Pokorny and Smith
19 developed a psychophysical contrast-discrimination test designed to preferentially target each pathway.
The test is comprised of two protocols, the steady-pedestal (SP) and pulsed-pedestal (PP) paradigms that putatively target responses from the M and P pathways, respectively.
19 Modified versions of this method have been used to assess M and P responses in several diseases, such as retinitis pigmentosa,
21 Leber's hereditary optic neuropathy,
22 migraine,
23 glaucoma,
24 and anisometropic amblyopia.
25
Twenty-six diabetic patients with no retinopathy (NDR: 11 male; mean age, 55 ± 9 years; 5 ± 4 years since diagnosis), 19 diabetics with nonproliferative retinopathy (DR: 6 male; mean age, 58 ± 7 years; 9 ± 6 years since diagnosis), and 18 controls (CTRL: 13 male; mean age, 55 ± 10 years) participated in the study. Patients and controls underwent a complete clinical ophthalmic evaluation before the test session, including fluorescein angiography and color fundus photography. Inclusion criteria for controls were absence of diabetes or any eye disease. Inclusion criteria for the diabetics were diagnosis of type 2 diabetes, absence of any ophthalmic disease aside from the diabetic retinopathy (DR group). All subjects had 20/30 or better visual acuity with the best correction. The evaluation of all subjects was monocular with natural pupil size. The tested eye was randomly chosen.
The diabetic patients were referred from the University Hospital of the University of São Paulo and from a private practice (author FMD). Control subjects were staff and students from the Psychology Institute, University of São Paulo. Patient and control groups did not differ in educational and socioeconomic background.
The procedures used in this study complied with the tenets of the Declaration of Helsinki. Informed consent was obtained from the participants, and the study protocol was approved by the Committee on Research Ethics from the Psychology Institute of the University of São Paulo (Process 010605).
We used a variant of Pokorny and Smith PP and SP paradigm adapted for use with patients as in a previous study.
22
For both SP and PP, a four-square luminance pedestal array (x = 0.333; y = 0.333 chromaticity coordinates, 1° × 1° each, separated by 0.054°, viewed from 2.6 m) was presented on a constant 12-cd/m2 surround. For each of three pedestal luminances (7, 12, and 19 cd/m2), the luminance of one of the squares, the trial square (TS), was briefly incremented above the pedestal level for either 17 or 133 ms. A central black dot was used as the fixation point.
In the SP paradigm, the pedestal was presented at one of the three fixed luminances during the entire threshold measurement, and TS luminance was varied to determine the threshold. In the PP paradigm, the four-square array was presented transiently (for either 17 or 133 ms) at 7, 12, or 19 cd/m2 luminances. Simultaneously, with the pedestal, the TS was incremented above the pedestal luminance. During the interval between trials, the pedestal was maintained at the surround luminance (12 cd/m2).
Contrast thresholds were measured in a double-interleaved, four-alternative, forced-choice adaptive staircase,
22 in which the TS increment was randomly presented at any one of the four locations in the pedestal, and observers had to make a forced-choice decision (using control box CB3; CRS Ltd., Kent, UK) about the TS location. Subjects had 3 seconds to respond, and the interval between trials was 1 second. The threshold estimate for each staircase in each condition ended after the occurrence of 10 reversals. Thresholds were calculated as the average of the contrast at the last six reversals. This staircase proved to be efficient, with subjects reaching threshold after an average of 40 trials.
Because the stimulus parameters for the 12-cd/m2 condition are identical for the SP and PP paradigms, this threshold was tested only once for each stimulus duration. Thus, each subject was tested in 10 conditions.
The SP and PP tests were implemented with software code developed with visual Pascal (Delphi 7.0; Borland, Cupertino, CA). Stimuli were generated with a 15-bit VSG graphic board (2/5; CRS) and were presented on a γ-corrected display (FD Trinitron GDM-F500T9; Sony, Tokyo, Japan) with a 100-Hz frame rate and resolution of 800 × 600 pixels.
Figure 1 shows the mean thresholds from diabetics (squares, NDR; triangles, DR) and controls (circles) for the SP (
Figs. 1A,
1C) and PP (
Figs. 1B,
1D) paradigms. Data from the 17-ms conditions are shown in
Figures 1A and
1B as open symbols. The bottom row (
Figs. 1C,
1D) shows the 133-ms data as filled symbols.
The mean thresholds from the DR patient group were significantly different from control thresholds in all conditions except for the PP at the lower luminance and short duration (PP, 7 cd/m2, 17 ms). The NDR patient group had significantly different thresholds from the controls in 5 of the 10 conditions. There was no significant difference between the thresholds for the two patient groups, except for the PP at lower luminance and longer duration (PP, 7 cd/m2, 133 ms).
Significant losses were more prevalent in both groups when the stimulus had a longer duration (133 ms;
Table 1).
Table 1 shows the outcome of the statistical comparisons between the groups for both protocols.
Table 1. Between-Groups Comparisons for Steady- and Pulsed-Pedestal Contrast Data
Table 1. Between-Groups Comparisons for Steady- and Pulsed-Pedestal Contrast Data
Group Comparison | Pedestal Paradigm | Stimulus Condition |
7 cd/m2 | 12 cd/m2 | 19 cd/m2 | 7 cd/m2 | 12 cd/m2 | 19 cd/m2 |
17 ms | 133 ms |
NDR vs. Ctrl | Steady | 0.114 | 0.134 | <0.001 | 0.042 | 0.025 | 0.040 |
DR vs. Ctrl | | 0.305 | 0.013 | <0.001 | 0.096 | 0.069 | 0.001 |
NDR vs. DR | | 0.502 | 0.128 | 0.503 | 0.686 | 0.639 | 0.070 |
NDR vs. Ctrl | Pulsed | 0.302 | 0.138 | <0.001 | 0.403 | 0.037 | 0.026 |
DR vs. Ctrl | | 0.353 | 0.013 | <0.001 | 0.002 | 0.072 | 0.023 |
NDR vs. DR | | 0.938 | 0.125 | 0.222 | 0.002 | 0.781 | 0.037 |
To provide a gauge of the prevalence of CS loss across condition, for each condition we determined the number of patients whose contrast thresholds exceeded the 95th percentile of the controls' thresholds (
Table 2).
Table 2. Percentage of Patients with Thresholds above the 95th Percentile of the Control Data
Table 2. Percentage of Patients with Thresholds above the 95th Percentile of the Control Data
Pedestal Paradigm | Patient Group | Stimulus Condition |
7 cd/m2 | 12 cd/m2 | 19 cd/m2 | 7 cd/m2 | 12 cd/m2 | 19 cd/m2 |
17 ms | 133 ms |
Steady | NDR | 32.0 (8/25) | 23.1 (6/26) | 42.3 (11/26) | 38.5 (10/26) | 46.2 (12/26) | 30.8 (8/26) |
| DR | 58.8 (10/17) | 38.9 (7/18) | 73.7 (14/19) | 76.5 (13/17) | 26.3 (5/19) | 73.7 (14/19) |
Pulsed | NDR | 11.5 (3/26) | 23.1 (6/26) | 21.7 (5/23) | 15.4 (4/26) | 38.5 (10/26) | 40.0 (10/25) |
| DR | 15.8 (3/19) | 38.9 (7/18) | 33.3 (6/18) | 52.6 (10/19) | 26.3 (5/19) | 58.8 (10/17) |
Average Tc of both diabetic groups did not differ significantly from those of the controls for either paradigm (Kruskal-Wallis test, P > 0.05), consistent with no significant changes in temporal integration, even in the presence of retinopathy. In addition, the DR and NDR Tc estimates were not significantly different from each other for either paradigm.
Within groups, there was a significant difference between SP and PP Tc estimates only in the control group (P < 0.006, sign test). Average Tc for controls was 25.4 ± 1.2 ms (SE) for the SP and 37.1 ± 2.6 ms for the PP paradigm. For either the NDR or DR group, there was no significant difference between SP and PP Tc (P > 0.4). Average Tc for NDR diabetics was 31.4 ± 3.2 ms for the SP paradigm and 36.6 ± 2.9 ms for the PP paradigm. For the DR diabetic group, average Tc was 27.1 ± 1.6 ms for SP and 31.7 ± 2.4 ms for PP.