Contrast Sensitivity of ON and OFF Human Retinal Pathways in Myopia.

The human visual cortex processes light and dark stimuli with ON and OFF pathways that are differently modulated by luminance contrast. We have previously demonstrated that ON cortical pathways have higher contrast sensitivity than OFF cortical pathways and the difference increases with luminance range (defined as the maximum minus minimum luminance in the scene). Here, we demonstrate that these ON-OFF cortical differences are already present in the human retina and that retinal responses measured with electroretinography are more affected by reductions in luminance range than cortical responses measured with electroencephalography. Moreover, we show that ON-OFF pathway differences measured with electroretinography become more pronounced in myopia, a visual disorder that elongates the eye and blurs vision at far distance. We find that, as the eye axial length increases across subjects, ON retinal pathways become less responsive, slower in response latency, less sensitive, and less effective and slower at driving pupil constriction. Based on these results, we conclude that myopia is associated with a deficit in ON pathway function that decreases the ability of the retina to process low contrast and regulate retinal illuminance in bright environments.

Luminance Contrast Shifts Dominance Balance between ON and OFF Pathways in Human Vision.

Human vision processes light and dark stimuli in visual scenes with separate ON and OFF neuronal pathways. In nature, stimuli lighter or darker than their local surround have different spatial properties and contrast distributions (Ratliff et al., 2010; Cooper and Norcia, 2015; Rahimi-Nasrabadi et al., 2021). Similarly, in human vision, we show that luminance contrast affects the perception of lights and darks differently. At high contrast, human subjects of both sexes locate dark stimuli faster and more accurately than light stimuli, which is consistent with a visual system dominated by the OFF pathway. However, at low contrast, they locate light stimuli faster and more accurately than dark stimuli, which is consistent with a visual system dominated by the ON pathway. Luminance contrast was strongly correlated with multiple ON/OFF dominance ratios estimated from light/dark ratios of performance errors, missed targets, or reaction times (RTs). All correlations could be demonstrated at multiple eccentricities of the central visual field with an ON-OFF perimetry test implemented in a head-mounted visual display. We conclude that high-contrast stimuli are processed faster and more accurately by OFF pathways than ON pathways. However, the OFF dominance shifts toward ON dominance when stimulus contrast decreases, as expected from the higher-contrast sensitivity of ON cortical pathways (Kremkow et al., 2014; Rahimi-Nasrabadi et al., 2021). The results highlight the importance of contrast polarity in visual field measurements and predict a loss of low-contrast vision in humans with ON pathway deficits, as demonstrated in animal models (Sarnaik et al., 2014).SIGNIFICANCE STATEMENT ON and OFF retino-thalamo-cortical pathways respond differently to luminance contrast. In both animal models and humans, low contrasts drive stronger responses from ON pathways, whereas high contrasts drive stronger responses from OFF pathways. We demonstrate that these ON-OFF pathway differences have a correlate in human vision. At low contrast, humans locate light targets faster and more accurately than dark targets but, as contrast increases, dark targets become more visible than light targets. We also demonstrate that contrast is strongly correlated with multiple light/dark ratios of visual performance in central vision. These results provide a link between neuronal physiology and human vision while emphasizing the importance of stimulus polarity in measurements of visual fields and contrast sensitivity.

Neuronal mechanisms underlying differences in spatial resolution between darks and lights in human vision.

Artists and astronomers noticed centuries ago that humans perceive dark features in an image differently from light ones; however, the neuronal mechanisms underlying these dark/light asymmetries remained unknown. Based on computational modeling of neuronal responses, we have previously proposed that such perceptual dark/light asymmetries originate from a luminance/response saturation within the ON retinal pathway. Consistent with this prediction, here we show that stimulus conditions that increase ON luminance/response saturation (e.g., dark backgrounds) or its effect on light stimuli (e.g., optical blur) impair the perceptual discrimination and salience of light targets more than dark targets in human vision. We also show that, in cat visual cortex, the magnitude of the ON luminance/response saturation remains relatively constant under a wide range of luminance conditions that are common indoors, and only shifts away from the lowest luminance contrasts under low mesopic light. Finally, we show that the ON luminance/response saturation affects visual salience mostly when the high spatial frequencies of the image are reduced by poor illumination or optical blur. Because both low luminance and optical blur are risk factors in myopia, our results suggest a possible neuronal mechanism linking myopia progression with the function of the ON visual pathway.

Individual differences in the shape of the nasal visual field.

Between-subject differences in the shape of the nasal visual field were assessed for 103 volunteers 21-85years of age and free of visual disorder. Perimetry was conducted with a stimulus for which contrast sensitivity is minimally affected by peripheral defocus and decreased retinal illumination. One eye each was tested for 103 volunteers free of eye disease in a multi-center prospective longitudinal study. A peripheral deviation index was computed as the difference in log contrast sensitivity at outer (25-29° nasal) and inner (8° from fixation) locations. Values for this index ranged from 0.01 (outer sensitivity slightly greater than inner sensitivity) to -0.7 log unit (outer sensitivity much lower than inner sensitivity). Mean sensitivity for the inner locations was independent of the deviation index (R2<1%), while mean sensitivity for the outer locations was not (R2=38%, p<0.0005). Age was only modestly related to the index, with a decline by 0.017 log unit per decade (R2=10%). Test-retest data for 21 volunteers who completed 7-10 visits yielded standard deviations for the index from 0.04 to 0.17 log unit, with a mean of 0.09 log unit. Between-subject differences in peripheral deviation persisted over two years of longitudinal testing. Peripheral deviation indices were correlated with indices for three other perimetric stimuli used in a subset of 24 volunteers (R2 from 20% to 49%). Between-subject variability in shape of the visual field raises concerns about current clinical visual field indices, and further studies are needed to develop improved indices.

Contrast sensitivity perimetry data from adults free of eye disease.

This data article contains data referenced in "Individual Differences in the Shape of the Nasal Visual Field" [1]. The data were gathered from volunteers free of eye disease ages 21-85 who were tested with Contrast Sensitivity Perimetry (CSP), which uses a stimulus resistant to effects of defocus and reduced retinal illumination. Some subjects were tested only once or a few times, and others were part of a longitudinal cohort with as many as 10 tests. Parameters from maximum likelihood estimation of psychophysical threshold at each tested location are included in the data file, along with the participant׳s sex, age at time of test, the center of their physiological blind spot, the duration of test, the time of day that the test was begun, and the starting contrast used for the psychophysical staircases.

Effect of Age and Glaucoma on the Detection of Darks and Lights.

PURPOSE: We have shown previously that normal observers detect dark targets faster and more accurately than light targets, when presented in noisy backgrounds. We investigated how these differences in detection time and accuracy are affected by age and ganglion cell pathology associated with glaucoma. METHODS: We asked 21 glaucoma patients, 21 age-similar controls, and 5 young control observers to report as fast as possible the number of 1 to 3 light or dark targets. The targets were positioned at random in a binary noise background, within the central 30° of the visual field. RESULTS: We replicate previous findings that darks are detected faster and more accurately than lights. We extend these findings by demonstrating that differences in detection of darks and lights are found reliably across different ages and in observers with glaucoma. We show that differences in detection time increase at a rate of approximately 55 msec/dB at early stages of glaucoma and then remain constant at later stages at approximately 800 msec. In normal subjects, differences in detection time increase with age at a rate of approximately 8 msec/y. We also demonstrate that the accuracy to detect lights and darks is significantly correlated with the severity of glaucoma and that the mean detection time is significantly longer for subjects with glaucoma than age-similar controls. CONCLUSIONS: We conclude that differences in detection of darks and lights can be demonstrated over a wide range of ages, and asymmetries in dark/light detection increase with age and early stages of glaucoma.

Choice of Stimulus Range and Size Can Reduce Test-Retest Variability in Glaucomatous Visual Field Defects.

PURPOSE: To develop guidelines for engineering perimetric stimuli to reduce test-retest variability in glaucomatous defects. METHODS: Perimetric testing was performed on one eye for 62 patients with glaucoma and 41 age-similar controls on size III and frequency-doubling perimetry and three custom tests with Gaussian blob and Gabor sinusoid stimuli. Stimulus range was controlled by values for ceiling (maximum sensitivity) and floor (minimum sensitivity). Bland-Altman analysis was used to derive 95% limits of agreement on test and retest, and bootstrap analysis was used to test the hypotheses about peak variability. RESULTS: Limits of agreement for the three custom stimuli were similar in width (0.72 to 0.79 log units) and peak variability (0.22 to 0.29 log units) for a stimulus range of 1.7 log units. The width of the limits of agreement for size III decreased from 1.78 to 1.37 to 0.99 log units for stimulus ranges of 3.9, 2.7, and 1.7 log units, respectively (F = 3.23, P < 0.001); peak variability was 0.99, 0.54, and 0.34 log units, respectively (P < 0.01). For a stimulus range of 1.3 log units, limits of agreement were narrowest with Gabor and widest with size III stimuli, and peak variability was lower (P < 0.01) with Gabor (0.18 log units) and frequency-doubling perimetry (0.24 log units) than with size III stimuli (0.38 log units). CONCLUSIONS: Test-retest variability in glaucomatous visual field defects was substantially reduced by engineering the stimuli. TRANSLATIONAL RELEVANCE: The guidelines should allow developers to choose from a wide range of stimuli.

Contrast sensitivity perimetry and clinical measures of glaucomatous damage.

PURPOSE: To compare conventional structural and functional measures of glaucomatous damage with a new functional measure-contrast sensitivity perimetry (CSP-2). METHODS: One eye each was tested for 51 patients with glaucoma and 62 age-similar control subjects using CSP-2, size III 24-2 conventional automated perimetry (CAP), 24-2 frequency-doubling perimetry (FDP), and retinal nerve fiber layer (RNFL) thickness. For superior temporal (ST) and inferior temporal (IT) optic disc sectors, defect depth was computed as amount below mean normal, in log units. Bland-Altman analysis was used to assess agreement on defect depth, using limits of agreement and three indices: intercept, slope, and mean difference. A criterion of p < 0.0014 for significance used Bonferroni correction. RESULTS: Contrast sensitivity perimetry-2 and FDP were in agreement for both sectors. Normal variability was lower for CSP-2 than for CAP and FDP (F > 1.69, p < 0.02), and Bland-Altman limits of agreement for patient data were consistent with variability of control subjects (mean difference, -0.01 log units; SD, 0.11 log units). Intercepts for IT indicated that CSP-2 and FDP were below mean normal when CAP was at mean normal (t > 4, p < 0.0005). Slopes indicated that, as sector damage became more severe, CAP defects for IT and ST deepened more rapidly than CSP-2 defects (t > 4.3, p < 0.0005) and RNFL defects for ST deepened more slowly than for CSP, FDP, and CAP. Mean differences indicated that FDP defects for ST and IT were on average deeper than RNFL defects, as were CSP-2 defects for ST (t > 4.9, p < 0.0001). CONCLUSIONS: Contrast sensitivity perimetry-2 and FDP defects were deeper than CAP defects in optic disc sectors with mild damage and revealed greater residual function in sectors with severe damage. The discordance between different measures of glaucomatous damage can be accounted for by variability in people free of disease.

Assessing spatial and temporal properties of perimetric stimuli for resistance to clinical variations in retinal illumination.

PURPOSE: To develop perimetric stimuli for which sensitivities are more resistant to reduced retinal illumination than current clinical perimeters. METHODS: Fifty-four people free of eye disease were dilated and tested monocularly. For each test, retinal illumination was attenuated with neutral density (ND) filters, and a standard adaptation model was fit to derive mean and SEM for the adaptation parameter (NDhalf). For different stimuli, t-tests on NDhalf were used to assess significance of differences in consistency with Weber's law. Three experiments used custom Gaussian-windowed contrast sensitivity perimetry (CSP). Experiment 1 used CSP-1, with a Gaussian temporal pulse, a spatial frequency of 0.375 cyc/deg (cpd), and SD of 1.5°. Experiment 1 also used the Humphrey Matrix perimeter, with the N-30 test using 0.25 cpd and 25 Hz flicker. Experiment 2 used a rectangular temporal pulse, SDs of 0.25° and 0.5°, and spatial frequencies of 0.0 and 1.0 cpd. Experiment 3 used CSP-2, with 5-Hz flicker, SDs from 0.5° to 1.8°, and spatial frequencies from 0.14 to 0.50 cpd. RESULTS: In Experiment 1, CSP-1 was more consistent with Weber's law (NDhalf ± SEM = 1.86 ± 0.08 log unit) than N-30 (NDhalf = 1.03 ± 0.03 log unit; t > 9, P < 0.0001). All stimuli used in Experiments 2 and 3 had comparable consistency with Weber's law (NDhalf = 1.49-1.69 log unit; t < 2). CONCLUSIONS: Perimetric sensitivities were consistent with Weber's law when higher temporal frequencies were avoided.

Blur-resistant perimetric stimuli.

PURPOSE: To develop perimetric stimuli that are resistant to the effects of peripheral defocus. METHODS: One eye each was tested on subjects free of eye disease. Experiment 1 assessed spatial frequency, testing 12 subjects at eccentricities from 2 to 7 degrees using blur levels from 0 to 3 diopters (D) for two (Gabor) stimuli (spatial SD, 0.5 degrees; spatial frequencies, 0.5 and 1.0 cycles per degree [cpd]). Experiment 2 assessed stimulus size, testing 12 subjects at eccentricities from 4 to 7 degrees using blur levels 0 to 6 D for two Gaussians with SD of 0.5 and 0.25 degrees and a 0.5-cpd Gabor with SD of 0.5 degrees. Experiment 3 tested 13 subjects at eccentricities from fixation to 27 degrees using blur levels 0 to 6 D for Gabor stimuli at 56 locations; the spatial frequency ranged from 0.14 to 0.50 cpd with location, and SD was scaled accordingly. RESULTS: In experiment 1, blur by 3 D caused a small decline in log contrast sensitivity for the 0.5-cpd stimulus (mean ± SE, 0.09 ± 0.08 log units) and a larger (t = 7.7, p < 0.0001) decline for the 1.0-cpd stimulus (0.37 ± 0.13 log units). In experiment 2, blur by 6 D caused minimal decline for the larger Gaussian, by 0.17 ± 0.16 log units, and larger (t > 4.5, p < 0.001) declines for the smaller Gaussian (0.33 ± 0.16 log units) and the Gabor (0.36 ± 0.18 log units). In experiment 3, blur by 6 D caused declines by 0.27 ± 0.05 log units for eccentricities from 0 to 10 degrees, by 0.20 ± 0.04 log units for eccentricities from 10 to 20 degrees, and 0.13 ± 0.03 log units for eccentricities from 20 to 27 degrees. CONCLUSIONS: Experiments 1 and 2 allowed us to design stimuli for experiment 3 that were resistant to effects of peripheral defocus.

Structure and function in patients with glaucomatous defects near fixation.

PURPOSE: To assess relations between perimetric sensitivity and neuroretinal rim area using high-resolution perimetric mapping in patients with glaucomatous defects within 10° of fixation. METHODS: One eye was tested in each of 31 patients with open-angle glaucoma enrolled in a prospective study of perimetric defects within 10° of fixation. Norms were derived from 110 control subjects free of eye disease, aged 21 to 81 years. Perimetric sensitivity was measured using the 10-2 test pattern with the Swedish Interactive Threshold Algorithm (SITA) standard algorithm on the Humphrey Field Analyzer (HFA) II-i; Carl Zeiss Meditec), stimulus size III. Area of the temporal neuroretinal rim was measured using the Heidelberg retina tomograph 3. Decibel values were converted into linear units of contrast sensitivity averaged across locations corresponding to the temporal rim sector. Both measures were expressed as percent of mean normal, and the Bland-Altman method was used to assess agreement. Perimetric locations corresponding to the temporal sector were determined for six different optic nerve maps. RESULTS: Contrast sensitivity was moderately correlated with temporal rim area (r2 >30%, p < 0.005). For all six optic nerve maps, Bland-Altman analysis found good agreement between perimetric sensitivity and rim area with both measures expressed as fraction of mean normal and confidence limits for agreement that were consistent with normal between-subject variability in control eyes. CONCLUSIONS: By using high-resolution perimetric mapping in patients with scotomas within 10° of fixation, we confirmed findings of linear relations between perimetric sensitivity and area of temporal neuroretinal rim and showed that the confidence limits for agreement in patients with glaucoma were consistent with normal between-subject variability.

Web-based training on weapons of mass destruction response for emergency medical services personnel.

OBJECTIVE: To develop, implement, and assess a web-based simulation training program for emergency medical services (EMS) personnel on recognition and treatment of ocular injuries resulting from weapons of mass destruction (WMD) attacks. DESIGN: The training program consisted of six modules: WMD knowledge and event detection, ocular anatomy, ocular first aid (ie, flushing, cupping, and patching), and three WMD simulations (ie, sarin gas release, anthrax release, and radioactive dispersal device). Pretest, post-test, and 1-month follow-up test and a program evaluation were used to measure knowledge gain and retention and to assess the effectiveness of the program. SETTING: New York State EMS. PARTICIPANTS: Four hundred and sixty-four individuals participated in the training program and all waves of the testing (86 percent retention rate). MAIN OUTCOME VARIABLES: The effectiveness of the training intervention was measured using pretest and post-test questionnaires and analyzed using dependent t-tests. RESULTS: Assessment scores for overall knowledge increased from the pretest (mean = 15.7, standard deviation [SD] = 2.1) to the post-test (mean = 17.8, SD = 1.3), p < 0.001, and from pretest (mean = 15.7, SD = 2.1) to 1-month follow-up test (mean = 16.6, SD = 2.0), p < 0.001. Ninety-two percent of respondents indicated that the program reinforced understanding of WMDs. CONCLUSIONS: This training method provides an effective and low-cost approach to educate and evaluate EMS personnel on emergency treatment of eye trauma associated with the use of WMD. Online training should also be supplemented with hands-on practice and refresher trainings.

Rapid pupil-based assessment of glaucomatous damage.

PURPOSE: To investigate the ability of a technique employing pupillometry and functionally-shaped stimuli to assess loss of visual function due to glaucomatous optic neuropathy. METHODS: Pairs of large stimuli, mirror images about the horizontal meridian, were displayed alternately in the upper and lower visual field. Pupil diameter was recorded and analyzed in terms of the "contrast balance" (relative sensitivity to the upper and lower stimuli), and the pupil constriction amplitude to upper and lower stimuli separately. A group of 40 patients with glaucoma was tested twice in a first session, and twice more in a second session, 1 to 3 weeks later. A group of 40 normal subjects was tested with the same protocol. RESULTS: Results for the normal subjects indicated functional symmetry in upper/lower retina, on average. Contrast balance results for the patients with glaucoma differed from normal: half the normal subjects had contrast balance within 0.06 log unit of equality and 80% had contrast balance within 0.1 log unit. Half the patients had contrast balances more than 0.1 log unit from equality. Patient contrast balances were moderately correlated with predictions from perimetric data (r = 0.37, p < 0.00001). Contrast balances correctly classified visual field damage in 28 patients (70%), and response amplitudes correctly classified 24 patients (60%). When contrast balance and response amplitude were combined, receiver operating characteristic area for discriminating glaucoma from normal was 0.83. CONCLUSIONS: Pupillary evaluation of retinal asymmetry provides a rapid method for detecting and classifying visual field defects. In this patient population, classification agreed with perimetry in 70% of eyes.

Assessment of contrast gain signature in inferred magnocellular and parvocellular pathways in patients with glaucoma.

PURPOSE: Contrast gain signatures of inferred magnocellular and parvocellular postreceptoral pathways were assessed for patients with glaucoma using a contrast discrimination paradigm developed by Pokorny and Smith. The potential causes for changes in contrast gain signature were investigated using model simulations of ganglion cell contrast responses. METHODS: Foveal contrast discrimination thresholds were measured with a pedestal-Delta-pedestal paradigm developed by Pokorny and Smith [Pokorny, J., & Smith, V. C. (1997). Psychophysical signatures associated with magnocellular and parvocellular pathway contrast gain. Journal of the Optical Society of America A, 14(9), 2477-2486]. Stimuli were 27 ms luminance increments superimposed on 227 ms pulsed Delta-pedestals. Contrast thresholds and contrast gain signatures mediated by the inferred magnocellular (MC) and parvocellular (PC) pathways were assessed using linear fits to contrast discrimination thresholds at either lower or higher Delta-pedestal contrasts, respectively. Twenty-seven patients with glaucoma were tested, as well as 16 age-similar control subjects free of eye disease. RESULTS: Contrast sensitivity and contrast gain signature mediated by the inferred MC pathway were lower for the glaucoma group, and reduced contrast gain signature was correlated with reduced contrast sensitivity (r(2)=45%, p<.0005). These two parameters mediated by the inferred PC pathway were little affected for the glaucoma group. Model simulations suggest that the reduced contrast sensitivity and contrast gain signature were consistent with the hypothesis that reduced MC ganglion cell dendritic complexity can lead to reduced effective retinal illuminance, and hence increased semi-saturation contrast of the ganglion cell contrast response functions. CONCLUSIONS: The contrast sensitivity and contrast gain signature of the inferred MC pathway were reduced in patients with glaucoma. The results were consistent with a model of ganglion cell dysfunction due to reduced synaptic density.

Development and evaluation of a contrast sensitivity perimetry test for patients with glaucoma.

PURPOSE: To design a contrast sensitivity perimetry (CSP) protocol that decreases variability in glaucomatous defects while maintaining good sensitivity to glaucomatous loss. METHODS: Twenty patients with glaucoma and 20 control subjects were tested with a CSP protocol implemented on a monitor-based testing station. In the protocol 26 locations were tested over the central visual field with Gabor patches with a peak spatial frequency of 0.4 cyc/deg and a two-dimensional spatial Gaussian envelope, with most of the energy concentrated within a 4 degrees circular region. Threshold was estimated by a staircase method: Patients and 10 age-similar control subjects were also tested on conventional automated perimetry (CAP), with the 24-2 pattern with the SITA Standard testing strategy. The neuroretinal rim area of the patients was measured with a retinal tomograph (Retina Tomograph II [HRT]; Heidelberg Engineering, Heidelberg, Germany). A Bland-Altman analysis of agreement was used to assess test-retest variability, compare depth of defect shown by the two perimetric tests, and investigate the relations between contrast sensitivity and neuroretinal rim area. RESULTS: Variability showed less dependence on defect depth for CSP than for CAP (z = 9.3, P < 0.001). Defect depth was similar for CAP and CSP when averaged by quadrant (r = 0.26, P > 0.13). The relation between defect depth and rim area was more consistent with CSP than with CAP (z = 9, P < 0.001). CONCLUSIONS: The implementation of CSP was successful in reducing test-retest variability in glaucomatous defects. CSP was in general agreement with CAP in terms of depth of defect and was in better agreement than CAP with HRT-determined rim area.

Variability of visual field measurements is correlated with the gradient of visual sensitivity.

Conventional static automated perimetry provides important clinical information, but its utility is limited by considerable test-retest variability. Fixational eye movements during testing could contribute to variability. To assess this possibility, it is important to know how much sensitivity change would be caused by a given eye movement. To investigate this, we have evaluated the gradient, the rate at which sensitivity changes with location. We tested one eye each, twice within 3 weeks, of 29 patients with glaucoma, 17 young normal subjects and 13 older normal subjects. The 10-2 test pattern with the SITA Standard algorithm was used to assess sensitivity at locations with 2 degrees spacing. Variability and gradient were calculated at individual test locations. Matrix correlations were determined between variability and gradient, and were substantial for the patients with glaucoma. The results were consistent with a substantial contribution to test-retest variability from small fixational eye movements interacting with visual field gradient. Successful characterization of the gradient of sensitivity appears to require sampling at relatively close spacing, as in the 10-2 test pattern.

Linearity can account for the similarity among conventional, frequency-doubling, and gabor-based perimetric tests in the glaucomatous macula.

PURPOSES: The purposes of this study are to compare macular perimetric sensitivities for conventional size III, frequency-doubling, and Gabor stimuli in terms of Weber contrast and to provide a theoretical interpretation of the results. METHODS: Twenty-two patients with glaucoma performed four perimetric tests: a conventional Swedish Interactive Threshold Algorithm (SITA) 10-2 test with Goldmann size III stimuli, two frequency-doubling tests (FDT 10-2, FDT Macula) with counterphase-modulated grating stimuli, and a laboratory-designed test with Gabor stimuli. Perimetric sensitivities were converted to the reciprocal of Weber contrast and sensitivities from different tests were compared using the Bland-Altman method. Effects of ganglion cell loss on perimetric sensitivities were then simulated with a two-stage neural model. RESULTS: The average perimetric loss was similar for all stimuli until advanced stages of ganglion cell loss, in which perimetric loss tended to be greater for size III stimuli than for frequency-doubling and Gabor stimuli. Comparison of the experimental data and model simulation suggests that, in the macula, linear relations between ganglion cell loss and perimetric sensitivity loss hold for all three stimuli. CONCLUSIONS: Linear relations between perimetric loss and ganglion cell loss for all three stimuli can account for the similarity in perimetric loss until advanced stages. The results do not support the hypothesis that redundancy for frequency-doubling stimuli is lower than redundancy for size III stimuli.

Evaluation of a two-stage neural model of glaucomatous defect: an approach to reduce test-retest variability.

PURPOSE: The purpose of this study is to model perimetric defect and variability and identify stimulus conditions that can reduce variability while retaining good ability to detect glaucomatous defects. METHODS: The two-stage neural model of Swanson et al. was extended to explore relations among perimetric defect, response variability, and heterogeneous glaucomatous ganglion cell damage. Predictions of the model were evaluated by testing patients with glaucoma using a standard luminance increment 0.43 degrees in diameter and two innovative stimuli designed to tap cortical mechanisms tuned to low spatial frequencies. The innovative stimuli were a luminance-modulated Gabor stimulus (0.5 c/deg) and circular equiluminant red-green chromatic stimuli whose sizes were close to normal Ricco's areas for the chromatic mechanism. Seventeen patients with glaucoma were each tested twice within a 2-week period. Sensitivities were measured at eight locations at eccentricities from 10 degrees to 21 degrees selected in terms of the retinal nerve fiber bundle patterns. Defect depth and response (test-retest) variability were compared for the innovative stimuli and the standard stimulus. RESULTS: The model predicted that response variability in defective areas would be lower for our innovative stimuli than for the conventional perimetric stimulus with similar defect depths if detection of the chromatic and Gabor stimuli was mediated by spatial mechanisms tuned to low spatial frequencies. Experimental data were consistent with these predictions. Depth of defect was similar for all three stimuli (F = 1.67, p > 0.19). Mean response variability was lower for the chromatic stimulus than for the other stimuli (F = 5.58, p < 0.005) and was lower for the Gabor stimulus than for the standard stimulus in areas with more severe defects (t = 2.68, p < 0.005). Variability increased with defect depth for the standard and Gabor stimuli (p < 0.005) but not for the chromatic stimulus (slope less than zero). CONCLUSIONS: Use of large perimetric stimuli detected by cortical mechanisms tuned to low spatial frequencies can make it possible to lower response variability without comprising the ability to detect glaucomatous defect.