Paul G. D. Spry

Identification of Progressive Glaucomatous Visual Field Loss

In normal individuals, visual field measures are not perfectly repeatable and individual test locations exhibit both short- and long-term sensitivity variations. This physiologic variability is greatly increased in glaucoma and confounds detection of real progressive loss in visual function. Distinguishing progressive glaucomatous visual field loss from test variability therefore represents a complex task. Procedures used for detection of glaucomatous visual field progression may be broadly grouped into four categories: 1) clinical judgment, which consists of simple subjective observation of sequential visual field test results; 2) defect classification systems, whereby specific criteria are used to stratify field loss by discrete score and define progression as score change over time, such as the Advanced Glaucoma Intervention Study scoring system; 3) trend analyses, which follow test parameters sequentially over time to determine the magnitude and significance of patterns within the data, for example linear regression; and 4) event analyses, which identify single events of significant change relative to a reference examination. All of these methods demonstrate distinct benefits and drawbacks, making each useful in specific circumstances, although no single method appears universally ideal. At the present time the best method of detection of progression may be to rely upon confirmation of change at successive examinations and also by correlation of visual field changes with other clinical observations. Alternative analysis methods may become available in the near future to help identify cases of progressive loss.

Psychophysical investigation of ganglion cell loss in early glaucoma.

Purpose:To evaluate ganglion cell loss in early glaucoma using a variety of psychophysical tests and to identify optimal perimetric technique(s) for detection of early glaucomatous visual function loss. Methods:Five perimetric tests, short wavelength automated perimetry (SWAP), temporal modulation perimetry (TMP), frequency doubling technology perimetry (FDT), detection acuity perimetry (DAP), and resolution acuity perimetry (RAP) were compared in their ability to discriminate between normal individuals and patients with early glaucoma or glaucoma suspects. Comparisons were also made by their ability to produce repeatable defects. The tests examined different visual functions that are likely to be mediated by different retinal ganglion cell subpopulations, thereby permitting examination of hypotheses of ganglion cell death in early glaucoma. Results:All visual field tests demonstrated high performance in separating glaucoma patients from normal individuals. SWAP, TMP, FDT, and DAP provided the greatest discrimination between normal individuals and high- and low-risk glaucoma suspects. However, SWAP, TMP, and FDT obtained better consistency across the various analysis approaches (global indices and pointwise) than DAP and RAP. Of all the test types, FDT exhibited the highest proportion of repeatable abnormal test locations, with poor confirmation rates achieved by DAP and RAP. Conclusion:The performance of SWAP, FDT, and TMP suggests that these test types may all be suitable for detection of early loss of visual function in glaucoma. Ganglion cell subpopulations with lower levels of redundancy and/or those with larger cell sizes offer the most parsimonious explanation for earliest ganglion cell losses occurring in glaucoma.

Senescent changes of the normal visual field: an age-old problem

Purpose. To examine the effect of normal aging on visual field sensitivity and identify the best-fitting function for normal populations. Methods. Full Threshold standard automated perimetry data (program 24-2, Humphrey Field Analyzer) was collated retrospectively from clinically normal subjects who had previously been recruited for studies of normal visual function. One eye of each subject was randomly selected for analysis. Linear, bilinear, and simple nonlinear candidate functions of mean sensitivity vs. age (independent variable) were applied to these cross-sectional population data. Differences in the aging effect by eccentricity and hemifield were also considered. Results. Data from 562 normal eyes were available for analysis. A significant negative relationship existed between age and mean visual field sensitivity within the cross-sectional population data. Coefficients of determination for the linear, bilinear, and nonlinear functions were 0.21, 0.20, and 0.26, respectively, indicating that the nonlinear function provided best characterization of the effect of age on mean sensitivity. A small but significant increase in the aging effect was present both peripherally (p < 0.001) and superiorly (p < 0.001). Discussion. The nonlinear function that provided the best fit to cross-sectional population data indicates that age exerts an increasing effect on perimetric sensitivity with age, which has implications for clinical devices that use linear age coefficients to correct for normal aging effects. A linear age correction will overestimate aging changes for younger subjects and, therefore, may miss early pathologic changes in visual sensitivity. Conversely, linear age correction will also underestimate aging changes for older subjects and, thus, may overcall pathological sensitivity loss in this group. The effect of age within subjects requires further investigation to provide reliable estimates of the effect of age on sensitivity.

Within-test variability of frequency-doubling perimetry using a 24-2 test pattern.

PurposeTo evaluate patient-response (within-test) variability for targets of the smaller frequency-doubling technology perimetry test that employs a 24–2 stimulus-presentation pattern. MethodsPatient-response variability was examined using the method of constant stimuli for standard (10°) and small (4°) customized frequency-doubling technology perimetry stimuli presented on a CRT screen. Small stimuli were designed for use in a 24–2 test pattern. Matched test locations were examined in 24 subjects (8 normal, 8 in whom glaucoma was suspected, and 8 glaucoma patients). Threshold sensitivity (in decibels for the 50% detection level) and variability (interquartile range in decibels) were obtained from frequency-of-seeing curves derived from data fitting with cumulative Gaussian functions. Groups were compared using a two-way ANOVA. ResultsThresholds obtained using standard and small stimuli were highly correlated (R = 0.94, P < 0.001, Pearson correlation), although smaller targets systematically estimated sensitivity to be 2.0 dB (95% CI, 1.7–2.4 dB) lower than standard targets. No significant difference in patient-response variability was observed between standard and small targets (P = 0.067), although both target sizes demonstrated small but significant increases in variability with reduced sensitivity. Mean (SD) patient-response variability for the normal, suspect, and glaucoma groups was 1.0 (0.6), 0.9 (0.4), and 1.8 (1.4) dB for standard-sized stimuli and 1.1 (0.8), 1.5 (1.2), and 2.0 (0.9) dB for small stimuli. ConclusionsSmall (4°) frequency-doubling technology perimetry targets have variability characteristics that are not statistically significantly different from those observed for standard-sized (10°) stimuli. Reduction in frequency-doubling technology perimetry stimulus size necessary to produce 24–2 test resolution is unlikely to affect test repeatability. Smaller, more numerous stimuli may offer clinical advantages both in terms of detecting small defects and identifying progressive loss.

Measurement error of visual field tests in glaucoma

Aim: Psychophysical strategies designed for clinical visual field testing produce rapid estimates of threshold with relatively few stimulus presentations and so represent a trade-off between test quality and efficiency. The aim of this study was to determine the measurement error of a staircase algorithm similar to full threshold with standard automated perimetry (SAP) and frequency doubling perimetry (FDP) in glaucoma patients. Methods: Seven patients with early open angle glaucoma (OAG) were prospectively recruited. All were experienced in laboratory based psychophysics. Three matched test locations were examined with SAP (externally driven Humphrey field analyser) and FDP (CRT) in a single arbitrarily selected eye of each subject. Each location was tested twice with a 4-2-2 dB staircase strategy, similar to full threshold, and then with the method of constant stimuli (MOCS). Accuracy (threshold estimation error) was quantified by determination of differences between “true” threshold measurements made by MOCS and single staircase threshold estimates. Precision (repeatability) was quantified by the differences between repeated staircase threshold estimates. Results: Precision was relatively high for both tests, although higher for FDP than SAP at depressed sensitivity levels. The staircase strategy significantly underestimated threshold sensitivity for both test types, with the mean difference (95% CI) between staircase and MOCS thresholds being 4.48 dB (2.35 to 7.32) and 1.35 dB (0.56 to 1.73) for SAP and FDP respectively. Agreement levels (weighted kappa) between MOCS and staircase thresholds were found to be 0.48 for SAP and 0.85 for FDP. Although this “bias” appeared constant for FDP across all sensitivity levels, this was not the case for SAP where accuracy decreased at lower sensitivity levels. Conclusion: Estimations of threshold sensitivity made using staircase strategies common to clinical visual field test instrumentation are associated with varying degrees of measurement error according to visual field test type and sensitivity. In particular, SAP significantly overestimates the “true” level of sensitivity, particularly in damaged areas of the visual field, suggesting that clinical data of this type should be interpreted with caution.

Normal age-related sensitivity loss for a variety of visual functions throughout the visual field.

Purpose. The purpose of this study is to compare the rate of age-related decline, the magnitude of practice effects, and test–retest variability among normal subjects using six different tests of visual function. Methods. One hundred normal subjects aged between 20 and 85 were enrolled in the study. Six visual field test procedures were used consisting of standard automated perimetry (SAP), short wavelength automated perimetry (SWAP), temporal modulation perimetry (TMP), frequency-doubling technology perimetry (FDT), detection acuity perimetry (DAP),and resolution acuity perimetry (RAP). To facilitate direct comparison, the results for each test were divided by that test’s estimated dynamic range. Results. Of the three tests used clinically most commonly, SWAP exhibited the greatest aging and practice effects and test–retest variability followed by FDT with SAP exhibiting the least. RAP was the most variable test followed by TMP. Conclusions. These results should be taken into account when evaluating glaucomatous loss using different functional tests and when comparing the performance, predictive power, and speed of detection of the different tests.

The effect of ocular dominance on visual field testing.

Purpose. During standard automated perimetry (SAP), some patients experience visual disturbances in the tested eye while the other eye is covered with an opaque occluder. It is possible that a binocular interaction producing an inhibitory response in the nonoccluded eye, such as rivalry or Ganzfeld blankout, may be the causative factor, particularly when the dominant eye is occluded. The objective of this experiment was to determine whether subjective visual disturbances occurring during conventional perimetric test conditions were related to ocular dominance and to investigate the effect of these disturbances on measurements made during threshold visual field analysis. Method. Ocular dominance was determined by questioning and objective testing on 55 normal subjects. Each subject underwent program 24-2 Full Threshold SAP on a Humphrey Field Analyzer, and an opaque black patch was used to occlude the nontested eye. After testing, patients were asked to report symptoms of visual disturbance characteristic of rivalry or blankout, and the relationship between ocular dominance and visual disturbances was investigated. To determine whether symptoms of rivalry or blankout had affected visual field quantification, comparisons of short-term fluctuation, mean deviation, and false-negative errors were performed between eyes with and without visual disturbances. Results. A total of 24 of 55 subjects reported visual disturbances consistent with rivalry or blankout (44%). Sixteen subjects complained of the phenomenon in one eye, and eight complained of the phenomenon in both eyes. Of the 16 experiencing disturbances in one eye only, nine cases occurred during occlusion of the dominant eye. The association between ocular dominance and visual disturbances was not found to be significant (p > 0.10). No significant differences in short-term fluctuation (p = 0.78), mean deviation (p = 0.64), or false-negative errors (p = 0.10) were found between eyes with and without visual disturbances. Conclusions. Patients undergoing standard automated perimetry with opaque patch occlusion of the nontested eye often experience visual disturbances consistent with rivalry or blankout, although these disturbances do not cause increased within-test variability or reduced sensitivity as quantified by visual field global indices. In terms of summary visual field indices, ocular dominance does not appear to affect visual field test results.

Sensitivity differences between real-patient and computer-stimulated visual fields.

PurposeThe authors sought to verify computer simulation of visual fields by comparing thresholds of real and corresponding simulated visual fields. MethodsFour patients with stable glaucomatous visual fields and three patients with progressing glaucomatous visual fields were chosen for the study. Visual fields had been recorded at 6-month intervals for 5 to 7.5 years. A previously described computer simulation program was used to generate a corresponding simulated visual field for each of the real fields. Twenty different levels of response variability and long-term variability were used in the simulations. Pointwise sensitivity differences between real and simulated fields were calculated. The average difference and 95% interval of the differences were analyzed for the different simulation conditions, for the pointwise sensitivities in the real patient fields, and to determine whether the field was stable or progressing. ResultsIn almost all simulation conditions, the average pointwise sensitivity differences ranged from −1 to 1 dB and were not significantly different among different simulation conditions. The 95% interval of the average difference increased significantly with response variability, whereas long-term variability failed to show any apparent effect. Average pointwise differences and the 95% intervals were greatest in locations where the real-patient field had reduced sensitivity of 14 dB or worse. ConclusionThe simulation program provided good estimates of visual field sensitivities. Increasing amounts of response, but not long-term variability, produced a linear increase in the variability of threshold sensitivities. This finding implies that short-term rather than long-term fluctuation is the most important factor determining the variability of thresholds.

Frequency doubling perimetry using a liquid crystal display

PURPOSE To compare frequency doubling contrast thresholds using a new liquid crystal window display with those obtained with the commercial video-based Frequency Doubling Technology perimeter. METHODS One eye of 49 glaucoma patients and one eye of 49 normal controls were tested with the liquid crystal window and Frequency Doubling Technology systems. Both displays employed identical stimulus conditions and test strategies, although the dynamic range of the liquid crystal window-based display was approximately 30% smaller than that of the Frequency Doubling Technology system. Measurements were repeated using the video-based Frequency Doubling Technology perimeter in a subset of 21 eyes. Relationships between and within displays were assessed using a chance-corrected agreement measure (quadratic weighted kappa) and paired measurement differences. Variability was quantified using standard deviation from the mean paired measurement difference. RESULTS Over the restricted operating range of the liquid crystal display system, between-display and within-video display variability was 2.3 dB and 3.2 dB, respectively, between-display agreement was 0.66, and within-display agreement (test-retest for Frequency Doubling Technology) was 0.65. CONCLUSIONS Levels of agreement and variability between the two frequency doubling displays were of similar magnitude to repeated (test-retest) Frequency Doubling Technology measures, suggesting that contrast threshold measurements made using the two displays may be used interchangeably. However, the operating range of the current liquid crystal window-based display is smaller.