May 2014
Volume 55, Issue 5
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Glaucoma  |   May 2014
Rapid Contrast Adaptation in Glaucoma and in Aging
Author Notes
  • Department of Optometry and Vision Sciences, The University of Melbourne, Melbourne, Australia 
  • Correspondence: Allison M. McKendrick, Department of Optometry and Vision Sciences, The University of Melbourne, Parkville, 3010 Australia; allisonm@unimelb.edu.au
Investigative Ophthalmology & Visual Science May 2014, Vol.55, 3171-3178. doi:10.1167/iovs.13-13229
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      Jia Jia Lek, Algis J. Vingrys, Allison M. McKendrick; Rapid Contrast Adaptation in Glaucoma and in Aging. Invest. Ophthalmol. Vis. Sci. 2014;55(5):3171-3178. doi: 10.1167/iovs.13-13229.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose.: The visual system rapidly adapts to contrast changes, often with each fixation. One key anatomical site underpinning contrast adaptation is the retinal ganglion cell dendrites, where degenerative changes occur in glaucoma. This study investigated the effects of early glaucoma and aging on rapid contrast adaptation.

Methods.: Contrast detection and discrimination thresholds were measured in central vision for briefly presented (94 ms) Gabor patches with and without adaptation to 50% contrast Gabor patches (1000 ms). Fourteen people with glaucoma (aged 58–77 years), 17 age-similar controls (aged 50–72 years), and 19 younger adults (aged 20–31 years) participated. Detection thresholds were measured at various time points (47, 106, 200, 400, 600, and 1000 ms) post adaptation. Discrimination thresholds were measured post adaptation relative to a reference contrast below (30%), equivalent to (50%), or above (70%) the adaptor.

Results.: The glaucoma group demonstrated elevated unadapted detection (P < 0.0001) and discrimination (P = 0.01) thresholds relative to age-similar controls. In normal observers, aging elevated unadapted thresholds (detection: P < 0.0001; discrimination: P < 0.0001). At 47 ms post adaptation, the glaucoma group demonstrated reduced effects of adaptation relative to controls (P = 0.009). Adaptation was also reduced when the reference contrast (50%) was equivalent to the adaptor (P = 0.02). Aging did not alter adaptation of normal observers.

Conclusions.: Glaucoma alters rapid contrast adaptation while aging does not. Contrast adaptation is key to visual processing in natural visual environments. Our results imply that glaucoma produces abnormalities in natural visual experiences in central vision.

Introduction
Glaucoma is an eye disease characterized by retinal ganglion cell (RGC) degeneration leading to cell death 1 and irreversible vision loss. Clinically, a key tool used for diagnosing and monitoring glaucoma is static automated perimetry in which contrast sensitivity to small white-light targets is measured across the visual field. However, contrast sensitivity measures may hold limited relevance to natural vision. A natural visual experience commonly consists of differentiating objects of suprathreshold contrast (contrast discrimination), as well as adapting to changes in contrast (contrast adaptation), often with each fixational eye movement. Contrast adaptation allows the visual system's differential sensitivity to be maintained when such changes occur. Commonly used measures of visual function such as perimetry and visual acuity do not assess the patency of these processes. 
At a cellular level, contrast adaptation occurs in at least two distinct time scales: slow, lasting several seconds, 24 and rapid, acting within tens of milliseconds. 57 Active regulation of contrast according to these two time scales has been demonstrated in postreceptoral retinal neurons. 8,9 Retinal ganglion cells have been shown to adapt to rapid changes in contrast via dendritic inputs from bipolar and amacrine cells, as well as via intrinsic RGC processes. 1012  
It has been shown that some of the earliest consequences of glaucoma in animal models are changes to RGC dendritic morphology. 13,14 Weber et al. 13 and Weber and Harman 15 have demonstrated that neurophysiological deficits can be attributed to such morphological changes. Given that the dendrites are a key site for contrast adaptation, we hypothesized that contrast adaptation processes on a rapid time scale may be functionally affected early in human disease. 
There is already some evidence for impairments in functional contrast adaptation in people with glaucoma. Reduced contrast adaptation across a slow time scale has been demonstrated using contrast discrimination tasks. 16 In examining rapid contrast adaptation, several studies 1720 have adapted the Pokorny and Smith 21 pedestal paradigm, allowing the contrast responses of the inferred magnocellular (MC) and parvocellular (PC) pathways to be examined. Sun et al. 17 found abnormalities in the MC pathway contrast gain signature consistent with a model of ganglion cell dysfunction due to reduced synaptic density. Abnormal contrast discrimination post adaptation at central and midperiphery regions with normal sensitivity for standard automated perimetry has also been demonstrated in people with glaucoma. 18  
The purpose of our current study was to further understanding of the effects of glaucoma on aspects of contrast adaptation that occur over a very brief time scale, and to determine whether the effects of rapid contrast adaptation differ with time post adaptation. In natural vision, changes in fixation with saccadic eye movements occur every few hundred milliseconds. 22 Hence, contrast adaptation mechanisms are required to operate quickly and efficiently to optimize visual experience. Human behavioral studies have found poorer contrast detection thresholds post adaptation, 23,24 but most have failed to find any enhancement in contrast discrimination 16,25 (but see Greenlee and Heitger 26 ) near the adapting level. Poorer contrast discrimination post adaptation in human performance is unlike what is observed in single-cell recordings of visual neurons. 2,27 Recently, however, Wolfson and Graham 28 used a novel rapid adaptation paradigm and were able to show that discrimination performance improves for contrasts away and worsens for contrasts near the adapting contrast. Their study demonstrated the functional benefit of contrast adaptation, the highlighting of novel information and suppressing of responses to unchanged visual stimuli. 29  
In this study, we measured, using psychophysical methods, the time course of contrast detection recovery after a briefly presented contrast adapting stimulus. We also measured contrast discrimination thresholds after the brief presentation of a contrast stimulus with targets of higher, equivalent, and lower contrast using methods similar to those described by Wolfson and Graham. 28 We particularly investigated performance in the time window that is most relevant for natural visual tasks (within a few hundred milliseconds). Because normal aging may also affect the anatomical substrates involved in contrast adaptation 3032 (such as a reduction in RGC density 30 ), and because neurological alterations contribute to contrast deficits in older adults, 33 an additional group of young observers were included in the study to investigate the effects of aging on rapid contrast adaptation. 
Our experiments were designed to test the predictions that rapid contrast adaptation (magnitude of contrast detection and discrimination threshold shift post adaptation) would be reduced in older individuals relative to younger adults, and then further reduced in older adults with glaucoma. We examined rapid contrast adaptation in central vision because previous studies have demonstrated altered central contrast adaptation 1618 in glaucoma, and because foveal adaptation is of key importance to natural visual tasks in which saccadic eye movements bring a new stimulus of interest to the fovea. As we were interested in exploring relatively early glaucomatous damage, presenting our test patterns centrally also allowed us to examine an area with normal standard automated perimetry measurements. 
Methods
Participants
Fourteen people with glaucoma (12 with primary open-angle glaucoma, 2 with normal-tension glaucoma) aged 58 to 77 years (mean ± standard deviation [SD]: 69 ± 6 years) and 17 approximately age-matched control individuals aged 50 to 72 years (mean ± SD: 65 ± 7 years) participated. A third group of 19 young individuals aged 20 to 31 years (mean ± SD: 24 ± 3 years) were also included. Those with glaucoma were recruited from the Melbourne Optometry Clinic (Australian College of Optometry) or the Royal Victorian Eye and Ear Hospital or through advertisements via Glaucoma Australia (a patient support group). Those with healthy vision for age were recruited via responding to written advertisements placed in electronic newsletters associated with the University of Melbourne and in community newspapers. 
All participants had visual acuity of 6/7.5 or better in the tested eye, no more than ±6.00 diopters (D) of sphere or −2.00 D of cylindrical distance refractive error, and no ophthalmological (other than glaucoma for the glaucoma participants) or systemic conditions, or medications known to affect visual performance. As migraine has been shown to affect contrast processing, 34 participants were required to have a self-reported migraine-free history. Participants with healthy vision had normal findings in a comprehensive eye examination (slit-lamp biomicroscopy, applanation tonometry [<21 mm Hg], ophthalmoscopy, optic nerve head imaging, and visual fields). Age-related lens changes in all older observers (glaucoma and control) were required to be ≤NC1.5 as classified using the Lens Opacity Classification System III. 35 All participants with healthy vision were classified as within normal limits (within the one-tailed 95% range of the normative database) using Moorfields Regression Analysis (MRA) or Glaucoma Probability Score (GPS) tool of the Heidelberg Retinal Tomograph II (HRT; Heidelberg Engineering, Heidelberg, Germany). 
Visual fields were measured using the Medmont Central 30-2 test (Medmont Pty. Ltd.; Camberwell, VIC, Australia), which measures thresholds using a rapid ZEST procedure for size III luminance increment targets at 104 locations within the central 30°, including four points at 1° from fixation. All participants, including those with glaucoma, were required to have normal visual fields within the central 2° where the psychophysical testing was performed. Average defect (AD) and pattern defect (PD) scores for participants with healthy vision were required to fall within the one-tailed 95% range of normal, as defined by the normative database of the Medmont perimeter. All observers fulfilled the reliability indices (fixation loss, false positive, and false negative) criteria of ≤20%. 
All glaucoma participants had an ophthalmological diagnosis of primary open-angle glaucoma or normal-tension glaucoma and were treated at the time of testing. Current ophthalmological records were supplied to the study. At the first study visit, a further examination was conducted including assessment of the anterior chamber, optic nerve head, and retinal nerve fiber layer. Quantitative optic nerve head imaging (Heidelberg Retinal Tomograph II) and visual field examination (Medmont Central 30-2 test) were also conducted. The results of these examinations were compared to the supplied ophthalmological records, and only those participants with an unambiguous diagnosis of primary open-angle or normal-tension glaucoma were included. All glaucoma participants were flagged as having failed either the structural (MRA or GPS being ≥95% probability of falling outside the normative database) or functional (AD or PD being ≥95% probability of falling outside the normative database) tests. The levels of structural (HRT) and/or functional (Medmont Central 30-2 test) abnormalities are shown in the Table. Our patients have early glaucoma as indicated by AD values less than −6.10 dB. 
Table
 
Glaucoma Observer Characteristics: ID Number, Age, Diagnosis (POAG, NTG), MRA, GPS Tool of the HRT, and AD, PD of the Medmont Perimeter
Table
 
Glaucoma Observer Characteristics: ID Number, Age, Diagnosis (POAG, NTG), MRA, GPS Tool of the HRT, and AD, PD of the Medmont Perimeter
ID Age Diagnosis MRA GPS AD PD
G1 77 POAG Within normal limits Within normal limits −3.83* 8.24†
G2 67 POAG Outside normal limits Outside normal limits −2.95 12.45‡
G3 73 POAG Outside normal limits Outside normal limits −0.84 11.9‡
G4 77 POAG Outside normal limits Outside normal limits −3.96* 18.31‡
G5 63 POAG Outside normal limits Borderline −0.46 16.42‡
G6 73 POAG Outside normal limits Outside normal limits −1.72 12.13‡
G7 71 POAG Within normal limits Within normal limits −1.7 10.46†
G8 62 POAG Outside normal limits Outside normal limits −6.08† 0.65
G9 63 POAG Outside normal limits Outside normal limits −3.58* 17.43‡
G10 71 POAG Outside normal limits Outside normal limits −2.39 9.03†
G11 61 NTG Outside normal limits Borderline −0.98 5.62*
G12 69 NTG Outside normal limits Outside normal limits −0.65 4.58
G13 61 POAG Outside normal limits Borderline −0.39 0
G14 58 POAG Borderline Within normal limits −3.17* 1.07
All participants provided written informed consent before participation in the study, in accordance with a protocol approved by our institutional human ethics committee and with the tenets of the Declaration of Helsinki. 
Equipment for Psychophysical Testing
Stimuli were generated using custom software (written in MATLAB 7.0.4; the MathWorks, Natick, MA) via the ViSAGe System (Cambridge Research Systems, Kent, UK) and presented on a gamma-corrected 21-inch monitor (frame rate, 85 Hz; resolution, 1280 horizontally by 1024 vertically; Trintron G520; Sony, Tokyo, Japan). The mean luminance of the monitor was 50 cd/m2. The monitor was gamma corrected on a weekly basis (OptiCal photometer; Cambridge Research Systems). Participants wore individualized refractive correction appropriate for the viewing distance of 90 cm, which was maintained using a chin rest. Testing was performed monocularly with a translucent occluder to minimize the effects of ongoing luminance adaptation during the tests. 36 If both eyes met the inclusion criteria, the test eye was chosen at random. Participants attended two test visits, each approximately 1.5 hours in duration, which included task training and rest breaks as required. A subset of four participants attended one extra session for additional testing (see later). 
Contrast Detection Thresholds Pre and Post Adaptation
Adapting (adaptor) and target patterns comprised Gabor patches (example shown in Fig. 1). Each Gabor patch was truncated at 1° × 1° with a spatial frequency of 2 cyc/deg. Contrast of the Gabor was specified using Michelson contrast ([maximum luminance − minimum luminance]/average luminance). 
Figure 1
 
Sequences used to study the effects of rapid contrast adaptation. (A) Contrast detection was assessed at six different time points after the offset of the adaptor (x = 47, 106, 200, 400, 600, 1000 ms). (B) Contrast discrimination at three different target contrasts (x = 30%, 50%, 70%). The same procedure was used to measure baseline contrast detection and discrimination thresholds in the absence of an adaptor.
Figure 1
 
Sequences used to study the effects of rapid contrast adaptation. (A) Contrast detection was assessed at six different time points after the offset of the adaptor (x = 47, 106, 200, 400, 600, 1000 ms). (B) Contrast discrimination at three different target contrasts (x = 30%, 50%, 70%). The same procedure was used to measure baseline contrast detection and discrimination thresholds in the absence of an adaptor.
Figure 1A illustrates the experimental design. All patterns were presented to central vision, with four diagonal lines to aid fixation. The beginning of each trial was marked by a tone, after which the adaptor (2 × 2 grid of 50% contrast Gabor patches) was shown for 1000 ms. After the offset of the adaptor, a time delay was introduced to assess threshold using a 94-ms target contrast pattern (single Gabor patch). The time points used to assess threshold post adaptation were 47, 106, 200, 400, 600, and 1000 ms, with each condition recorded on a separate experimental run. Each run began with the target pattern contrast clearly suprathreshold. The observer's task was to identify the location of the target Gabor patch out of four possible locations (a four-alternate, spatial forced choice; example shown in Fig. 1A) using a CB6 (Cambridge Research Systems) response box. After the response, a blank screen of mean luminance was shown for 1000 ms, and the process started again until threshold was established. Observers received auditory feedback when the response was incorrect. A modified three-down, one-up staircase procedure was used to determine threshold. Initially, the contrast of the target stimulus was decreased by 20% with every correct response or increased by 20% for every incorrect response. After the first incorrect response, three sequential correct responses were required to decrease the contrast. Each experimental run comprised two interleaved staircases that each terminated after six reversals. The final threshold estimate from each staircase was calculated as the mean contrast at the last four reversals. The results from at least two experimental runs (four staircases) were averaged to give the final contrast detection threshold for each time point. 
Within a given trial (adaptor, time delay, target pattern), the orientation (horizontal or vertical) and phase (chosen at random) of the Gabor elements were kept constant; however, they were randomized from trial to trial within a run. 
Baseline contrast detection thresholds were measured using the same protocol but without the adaptor. 
Contrast Discrimination Thresholds Pre and Post Adaptation
The method used here was similar to that reported by Wolfson and Graham. 28 The stimuli and methods are illustrated in Figure 1B. The 50% contrast adaptor was presented for 1000 ms, immediately followed by the contrast discrimination target (94 ms), then followed by the 50% adaptor again, and finally a blank screen of mean luminance (1000 ms). The contrast discrimination target comprised four Gabor patches with the contrast of three of the four Gabor patches fixed (either 30%, 50%, or 70%). One of the four Gabor patches of the target had a different contrast, which was incremented for the 50% and 70% target contrasts and decremented for the 30% target contrast. Observers were required to indicate the patch location that was the “odd one out.” 
Contrast discrimination thresholds were measured in the presence and absence of a 50% contrast adaptor for the three target contrasts (30%, 50%, 70%). 
Contrast discrimination thresholds were collected with the staircase method previously described, with the mean threshold returned from the last two of four reversals. 
All participants received substantive training prior to the collection of formal data. The order of tasks was randomized within each group and counterbalanced among the three study groups to avoid order-dependent effects of learning or fatigue between groups. 
Statistical Analysis
All contrast detection and discrimination data were log base 10 transformed prior to analysis using SPSS, version 20 (SPSS, Inc., Chicago, IL, USA). Statistical analysis tested the following hypotheses: 
  1.  
    That unadapted contrast detection and discrimination thresholds are elevated in aging and in glaucoma;
  2.  
    That the between-group difference in contrast detection threshold post adaptation depends on the postadaptation time delay;
  3.  
    That the between-group difference in contrast discrimination threshold depends on contrast and adaptation state; and
  4.  
    That the magnitude of change in contrast detection and discrimination thresholds post adaptation is reduced in aging and in glaucoma.
In comparing group means for a single condition, independent t-test or Mann-Whitney U test was used as appropriate. To examine whether group means differed across time for the contrast detection task, or with contrast for the discrimination task, repeated-measures ANOVA was used. In testing of these hypotheses, results were considered statistically significant if P < 0.05. 
Results
Contrast Detection Thresholds Pre and Post Adaptation
Contrast detection thresholds pre and post adaptation are shown in Figure 2. In the absence of adaptation, the glaucoma mean threshold (mean ± 95% confidence interval [CI] = 1.11 ± 0.11) was elevated relative to that in old observers (mean ± 95% CI = 0.83 ± 0.04) (t(16.82) = −4.46, P < 0.0001; Fig. 2A, filled symbols). The mean threshold of older observers was elevated relative to younger adults (mean ± 95% CI = 0.69 ± 0.03) (t(34) = −5.48, P < 0.0001; Fig. 2B, filled symbols). For all groups, thresholds were elevated when the target was shown in close succession to the adaptor, and recovered to baseline by 400 ms. 
Figure 2
 
Contrast detection thresholds pre and post adaptation. Group mean performance (±95% confidence interval [CI] of the mean) before (filled symbols) and after (unfilled symbols) adaptation in (A) old (control) and glaucoma groups and (B) the young and old groups. Group mean change in threshold values (threshold 47 ms post adaptation − threshold before adaptation) (±95% CI of the mean) for (C) young, old, and glaucoma groups. Dotted lines represent baseline thresholds.
Figure 2
 
Contrast detection thresholds pre and post adaptation. Group mean performance (±95% confidence interval [CI] of the mean) before (filled symbols) and after (unfilled symbols) adaptation in (A) old (control) and glaucoma groups and (B) the young and old groups. Group mean change in threshold values (threshold 47 ms post adaptation − threshold before adaptation) (±95% CI of the mean) for (C) young, old, and glaucoma groups. Dotted lines represent baseline thresholds.
A repeated-measures ANOVA revealed a significant interaction between group (old and glaucoma) and time (F 3.12,90.39 = 5.60, P = 0.001), indicating that difference between groups varied with time post adaptation. This interaction can be visualized in Figure 2A, where thresholds in the glaucoma group return to baseline earlier (∼200 ms) as compared to thresholds of the old group (∼400 ms). On examining the first three time points (47, 106, 200 ms), no interaction effect was found (F 2,58 = 1.25, P = 0.29), implying a common time course but that the threshold elevation due to the presence of the adaptor was reduced in the glaucoma group (Fig. 2C). 
Baseline contrast detection threshold (before adaptation) was subtracted from the threshold after adaptation for each individual to emphasize the effect of the adaptor (Fig. 2C) at time point 47 ms, where maximal threshold elevation was expected. Adaptation in people with glaucoma (mean ± 95% CI = 0.12 ± 0.07) was significantly reduced relative to that in old controls (mean ± 95% CI = 0.22 ± 0.04) (t(29) = 2.79, P = 0.009). 
When the older and younger normal observers were compared, no significant interaction was found for group and time (47, 106, 200, 400, 600, 1000 ms) (F 3.35,113.78 = 2.17, P = 0.09) implying that thresholds were elevated similarly relative to baseline in both groups post adaptation. Consistent with Figure 2B, threshold change over the first three time points (47, 106, 200 ms) was also similar (F 2,68 = 2.62, P = 0.08) for the young and old groups, with thresholds returning to baseline at ∼400 ms. Despite having significantly different contrast detection thresholds before adaptation, Figure 2C shows that young (mean ± 95% CI = 0.24 ± 0.04) and old (mean ± 95% CI = 0.22 ± 0.04) observers did not adapt differently (t(34) = 0.58, P = 0.57). 
Although our stimuli were presented centrally in areas of normal standard automated perimetry outcomes, differences in baseline contrast detection thresholds were evident between groups of observers. Because adaptation effects are stronger for higher-contrast stimuli 24,37,38 and the 50% adaptor is closer to the contrast detection threshold of observers with poorer contrast sensitivity, there is a possibility that contrast sensitivity differences may, at least partially, explain differing adaptation effects between groups of observers. It is worth noting that despite the higher baseline contrast detection thresholds for older observers, no significant difference in adaptation was found when compared to that of the younger observers. This suggests that contrast sensitivity differences are not the dominant factor in establishing the magnitude of adaptation within observers with normal vision within the age range studied. 
To explore the potential magnitude of effect of differences in contrast sensitivity on adaptation strength in the glaucoma group, we measured threshold 47 ms after the offset of the brief (1000 ms) adaptor pattern that varied over a range of contrast (10%, 20%, 40%, 50%, 75%, or 98%) on a subset of four old observers (ages 67, 71, 71, and 76 years). 
Incremental thresholds measured against background contrast have been shown to exhibit a dipper function, 39,40 where thresholds are facilitated near the observer's detection threshold and rise steadily following a positive linear slope at suprathreshold contrasts. Here, we measured detection thresholds 47 ms after the offset of the adaptor. Previously, adaptation studies 24,37,38 demonstrated a linear increase of detection thresholds with increasing adapting contrasts. In considering previous literature 24,3740 and examining the trend in our data (Fig. 3A), we fit a linear function to the average thresholds (r 2 = 0.97). 
Figure 3
 
Contrast detection thresholds (47 ms post adaptation) plotted as a function of adaptor contrast (10%, 20%, 40%, 50%, 75%, or 98%) for (A) four old observers. (B) Measured and predicted contrast detection thresholds 47 ms post adaptation in glaucoma individuals presuming the normal relationship shown in (A).
Figure 3
 
Contrast detection thresholds (47 ms post adaptation) plotted as a function of adaptor contrast (10%, 20%, 40%, 50%, 75%, or 98%) for (A) four old observers. (B) Measured and predicted contrast detection thresholds 47 ms post adaptation in glaucoma individuals presuming the normal relationship shown in (A).
A contrast detection threshold (47 ms post adaptation, adaptor contrast = 50%) can be predicted using the old group linear model (slope = 0.004) for each glaucoma individual, with the y-intercept being each individual's contrast detection threshold before adaptation. 
The measured and predicted contrast detection thresholds (47 ms post adaptation) for the glaucoma group are shown in Figure 3B. 
Predicted mean contrast detection threshold was significantly higher (difference ± 95% CI = +0.12 ± 0.08) than the measured mean contrast detection threshold (t(13) = +2.26, P = 0.04). Figure 3B indicates that on average, the glaucoma group adapted less than predicted by their reduced contrast thresholds. 
Predicting thresholds post adaptation (47 ms) of old observers and young observers (data not shown) from Figure 3A did not reveal any statistically significant difference between the measured and predicted values (old: t(16) = 0.62, P = 0.52, young: t(18) = 1.74, P = 0.10). 
These results suggest that the differences in measured adaptation effects between groups cannot be fully explained by the reduced contrast sensitivity of glaucoma observers. 
Contrast Discrimination Thresholds Pre and Post Adaptation
Contrast discrimination thresholds pre and post adaptation are shown in Figure 4. In the absence of adaptation, the mean thresholds of the glaucoma group (mean ± 95% CI: 30% target = 0.99 ± 0.05, 50% target = 1.15 ± 0.08, 70% target = 1.15 ± 0.06) were elevated relative to the old controls across all contrasts (mean ± 95% CI: 30% target = 0.91 ± 0.06, 50% target = 0.98 ± 0.05, 70% target = 1.02 ± 0.04) (F 1,29 = 12.52, P = 0.01); Fig. 4A, filled symbols). Older observers also demonstrated higher thresholds than younger observers across all contrasts (mean ± 95% CI: 30% target = 0.72 ± 0.04, 50% target = 0.8 ± 0.04, 70% target = 0.85 ± 0.03) (F 1,34 = 43.68, P < 0.0001; Fig. 4B, filled symbols). 
Figure 4
 
Contrast discrimination thresholds pre and post adaptation. Group mean performance (± 95% CI of the mean) before (filled symbols) and after (unfilled symbols) adaptation in (A) the old and glaucoma groups and (B) the young and old groups. Data have been shifted horizontally for clarity. Group median (10th, 90th and 25th, 75th percentiles) change in threshold (threshold after adaptation − threshold before adaptation) values (target contrast: 50%) for (C) young, old, and glaucoma groups.
Figure 4
 
Contrast discrimination thresholds pre and post adaptation. Group mean performance (± 95% CI of the mean) before (filled symbols) and after (unfilled symbols) adaptation in (A) the old and glaucoma groups and (B) the young and old groups. Data have been shifted horizontally for clarity. Group median (10th, 90th and 25th, 75th percentiles) change in threshold (threshold after adaptation − threshold before adaptation) values (target contrast: 50%) for (C) young, old, and glaucoma groups.
For all groups, adaptation resulted in maximal threshold elevation when the target contrast was equivalent to the adaptor (50%), with slight improvement in thresholds observed when the target contrast was below (30%) or above (70%) the adaptor. These findings are consistent with the trend reported by Wolfson and Graham. 28 All participants were able to perform the task when the target contrast was below (30%) or above (70%) the adaptor. However, when target contrast was equivalent to the adaptor (50%), adapted thresholds reached a ceiling for one glaucoma and two older participants: They were unable to perform the task even with the contrast increment set at maximum value (49%). These three observers were awarded the maximum contrast of 49% for statistical analysis, and nonparametric statistics were used. Removing these data from the analysis does not distort our conclusion. 
A repeated-measures ANOVA (between-subjects factor of group, within-subjects factor of condition [with and without adaptation], and target contrasts [30%, 70%]) showed no significant interaction between group and adaptation states (F 1,29 = 0.002, P = 0.97). This indicates that despite the differences in discrimination threshold with glaucoma, threshold changes with adaptation were similar for the old and glaucoma groups for target contrasts 30% and 70%. People with glaucoma demonstrated a significantly reduced adaptation effect (adapted threshold − baseline threshold) (median = 0.42) at 50% contrast (U = 61, P = 0.02) relative to old observers (median = 0.52) as shown in Figure 4C. 
When the older and younger observers were compared, no statistically significant interaction (F 1,34 = 0.48, P = 0.49) was found between group and adaptation state using a repeated-measures ANOVA (between-subjects factor of group, within-subjects factor of condition [with and without adaptation], and target contrasts [30%, 70%]). Figure 4C shows that the magnitude of contrast threshold shift due to adaptation for target contrast 50% was not significantly different for the young (median = 0.46) and old (median = 0.52) groups (U = 110, P = 0.1). Thus, young and old observers did not adapt differently in contrast discrimination tasks even though the baseline (unadapted) contrast discrimination was higher for the older group. 
Discussion
This project was designed to consider if rapid adaptation to contrast is altered by glaucoma and/or aging within the central (2°) region of the visual field. As a group, people with early glaucoma demonstrated reduced adaptation relative to age-similar controls for contrast detection and for contrast discrimination when the adapting contrast matched the test contrast. Aging did not alter adaptation. Our experiments confirm contrast sensitivity differences between groups, but these do not explain the adaptation differences. Elevated contrast detection thresholds in the older adults did not result in differences in adaptation when compared to the younger group. Furthermore, within the glaucoma group, contrast detection thresholds post adaptation, predicted from the contrast sensitivities of individual observers, did not match the measured thresholds following adaptation (see Fig. 3B). These observations argue for some separation between the mechanism that sets the baseline state and that which regulates sensitivity following adaptation. 
Pokorny and Smith 21 have developed a psychophysical correlate characteristic of contrast gain and temporal integration signatures of the MC and PC pathways. The paradigm typically involves a short (∼1 minute) adaptation time with the target briefly pulsed (∼30 ms), requiring a contrast detection or discrimination judgment allowing a measurement of rapid contrast adaptation. Several studies 1720 adapting the paradigm found abnormalities of the inferred MC and PC pathways in contrast sensitivity and rapid contrast adaptation in glaucoma. Similar to the Pokorny and Smith 21 stimulus, our pattern stimulus was presented centrally; but instead of luminance patches, we used Gabor patches (of similar size, ∼1°) that minimize local retinal luminance adaption. Our study had different aims from these previous works as we tested abnormalities to adaptation that depend on the time post adaptation. The results of our study (reduced contrast sensitivity with aging and glaucoma, altered rapid contrast adaptation in glaucoma but not aging) are consistent with those of Sun et al. 17 and support their model of ganglion cell dysfunction due to reduced synaptic density. 
We set up the study to carefully test our hypotheses in patients having early glaucoma (Table), exploring specific mechanisms that required a detailed picture to be built up. As these experiments are lengthy, there is considerable self-selection of observers—volunteers who responded to our advertisements. We tested intensely in a small group of observers with sample size consistent with previous studies reporting similar contrast deficits. 1720 This experimental design is not suitable for generalization to a large clinical population; however, this type of study provides insight into a process that might prove useful in clinical settings, though more studies are required to explore this possibility. It is particularly important to explore the prospect of abnormal contrast adaptation in the periphery, where glaucoma contrast deficits commonly present. We tested only centrally in this study in order to constrain test time. 
Balancing of effective adaptor strength between observers posed a challenge in this study. This can be achieved by adjusting the adaptor contrast to a fixed multiple of each observer's contrast detection threshold. Such a method presents different challenges: It adds considerable time to an already lengthy experimental protocol and depends heavily on the accuracy of the results obtained early in the testing phase, which can be problematic in inexperienced observers. Instead, we chose to adopt a consistent suprathreshold adaptor in an area of normal visual field measurement. This experimental approach provides closer replication of a natural visual scene, where observers are presented with the same contrast. 
Elevated contrast detection and discrimination thresholds with aging have been previously reported. 41 Several studies have demonstrated that contrast deficits in aging cannot be fully explained by optical changes and that neurological alterations to the visual pathway played a significant role. 33,41 Alterations to anatomical substrates (RGC, 30 lateral geniculate nucleus (LGN), 31 and visual cortex (V1) 32 neurons) of contrast adaptation found in animal and human aging studies led us to hypothesize that rapid contrast adaptation might be altered in elderly humans. Using the Pokorny and Smith 21 pedestal paradigm, altered adaptation in the MC and PC pathways were found in older adults in one study 42 while another reported no difference in the MC pathway with aging. 17 We did not find any difference in rapid contrast adaptation with aging using our non-RGC–specific stimulus in this study in the presence of elevated baseline thresholds. 
Neural mechanisms involved in contrast adaptation are present at the retina, LGN, 3,43,44 and V1. 27,45 It has been proposed that the visual system could adjust to changes in contrast independently at each processing stage or that effects could be implemented early in processing and an altered representation passed forward. 7 At present, there is uncertainty as to whether signals reaching the cortex are already normalized for contrast, and it is likely that a combination of both approaches exists. Similarly in glaucoma, there is a possibility that alterations to contrast adaptation arise from multiple anatomical sites. 
The results of this study suggest that the active regulation of rapid contrast adaptation is altered in glaucoma but not with aging, consistent with previous work. 17 Measures of contrast discrimination and adaptation describe a different aspect of visual function compared with clinical measures of contrast detection thresholds. A natural visual experience consists of viewing and adapting to objects of suprathreshold contrasts. Contrast adaptation has recently been shown to improve performance in searching for a novel stimulus in visual scenes, 46 a commonly occurring task in natural visual experiences. Measures of suprathreshold contrast may thus be useful for the assessment of the real-world significance of glaucomatous visual impairment. Our finding for elevated thresholds and reduced adaptive magnitude of response in glaucoma (Fig. 2) suggests that glaucoma patients would require a greater contrast in a target to achieve a response similar to that of a person having normal contrast processing. Further work is required to determine if differences in these processes are related to differences in selecting targets for future fixational eye movements, and if abnormalities of suprathreshold contrast processing can explain performance anomalies in natural visual environments. Further work is also required to determine how contrast adaptation is altered in midperipheral locations. 
Acknowledgments
Supported by Australian Research Council Grant FT 0990930 (AMM). 
Disclosure: J.J. Lek, None; A.J. Vingrys, None; A.M. McKendrick, None 
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Figure 1
 
Sequences used to study the effects of rapid contrast adaptation. (A) Contrast detection was assessed at six different time points after the offset of the adaptor (x = 47, 106, 200, 400, 600, 1000 ms). (B) Contrast discrimination at three different target contrasts (x = 30%, 50%, 70%). The same procedure was used to measure baseline contrast detection and discrimination thresholds in the absence of an adaptor.
Figure 1
 
Sequences used to study the effects of rapid contrast adaptation. (A) Contrast detection was assessed at six different time points after the offset of the adaptor (x = 47, 106, 200, 400, 600, 1000 ms). (B) Contrast discrimination at three different target contrasts (x = 30%, 50%, 70%). The same procedure was used to measure baseline contrast detection and discrimination thresholds in the absence of an adaptor.
Figure 2
 
Contrast detection thresholds pre and post adaptation. Group mean performance (±95% confidence interval [CI] of the mean) before (filled symbols) and after (unfilled symbols) adaptation in (A) old (control) and glaucoma groups and (B) the young and old groups. Group mean change in threshold values (threshold 47 ms post adaptation − threshold before adaptation) (±95% CI of the mean) for (C) young, old, and glaucoma groups. Dotted lines represent baseline thresholds.
Figure 2
 
Contrast detection thresholds pre and post adaptation. Group mean performance (±95% confidence interval [CI] of the mean) before (filled symbols) and after (unfilled symbols) adaptation in (A) old (control) and glaucoma groups and (B) the young and old groups. Group mean change in threshold values (threshold 47 ms post adaptation − threshold before adaptation) (±95% CI of the mean) for (C) young, old, and glaucoma groups. Dotted lines represent baseline thresholds.
Figure 3
 
Contrast detection thresholds (47 ms post adaptation) plotted as a function of adaptor contrast (10%, 20%, 40%, 50%, 75%, or 98%) for (A) four old observers. (B) Measured and predicted contrast detection thresholds 47 ms post adaptation in glaucoma individuals presuming the normal relationship shown in (A).
Figure 3
 
Contrast detection thresholds (47 ms post adaptation) plotted as a function of adaptor contrast (10%, 20%, 40%, 50%, 75%, or 98%) for (A) four old observers. (B) Measured and predicted contrast detection thresholds 47 ms post adaptation in glaucoma individuals presuming the normal relationship shown in (A).
Figure 4
 
Contrast discrimination thresholds pre and post adaptation. Group mean performance (± 95% CI of the mean) before (filled symbols) and after (unfilled symbols) adaptation in (A) the old and glaucoma groups and (B) the young and old groups. Data have been shifted horizontally for clarity. Group median (10th, 90th and 25th, 75th percentiles) change in threshold (threshold after adaptation − threshold before adaptation) values (target contrast: 50%) for (C) young, old, and glaucoma groups.
Figure 4
 
Contrast discrimination thresholds pre and post adaptation. Group mean performance (± 95% CI of the mean) before (filled symbols) and after (unfilled symbols) adaptation in (A) the old and glaucoma groups and (B) the young and old groups. Data have been shifted horizontally for clarity. Group median (10th, 90th and 25th, 75th percentiles) change in threshold (threshold after adaptation − threshold before adaptation) values (target contrast: 50%) for (C) young, old, and glaucoma groups.
Table
 
Glaucoma Observer Characteristics: ID Number, Age, Diagnosis (POAG, NTG), MRA, GPS Tool of the HRT, and AD, PD of the Medmont Perimeter
Table
 
Glaucoma Observer Characteristics: ID Number, Age, Diagnosis (POAG, NTG), MRA, GPS Tool of the HRT, and AD, PD of the Medmont Perimeter
ID Age Diagnosis MRA GPS AD PD
G1 77 POAG Within normal limits Within normal limits −3.83* 8.24†
G2 67 POAG Outside normal limits Outside normal limits −2.95 12.45‡
G3 73 POAG Outside normal limits Outside normal limits −0.84 11.9‡
G4 77 POAG Outside normal limits Outside normal limits −3.96* 18.31‡
G5 63 POAG Outside normal limits Borderline −0.46 16.42‡
G6 73 POAG Outside normal limits Outside normal limits −1.72 12.13‡
G7 71 POAG Within normal limits Within normal limits −1.7 10.46†
G8 62 POAG Outside normal limits Outside normal limits −6.08† 0.65
G9 63 POAG Outside normal limits Outside normal limits −3.58* 17.43‡
G10 71 POAG Outside normal limits Outside normal limits −2.39 9.03†
G11 61 NTG Outside normal limits Borderline −0.98 5.62*
G12 69 NTG Outside normal limits Outside normal limits −0.65 4.58
G13 61 POAG Outside normal limits Borderline −0.39 0
G14 58 POAG Borderline Within normal limits −3.17* 1.07
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