Mitchell W. Dul

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.

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.

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.1 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° 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 Riccos 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° to 21° 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.

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.

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.

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.

Accommodative accuracy to harmonically related complex grating patterns and their components

Monocular steady‐state accommodation was measured to harmonically related complex grating patterns and their components to determine the contribution of the various spatial waveforms to accommodative accuracy. Accommodative accuracy was greater for those waveforms containing summed odd‐harmonic spatial components than for those waveforms with specific spatial components either removed or isolated. The results suggest that the contrast gradient produced by the summed waveforms, rather than the presence of any particular subset of spatial frequency components per se, was a critical factor for accurate accmmodation.

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.