Comparison of unifocal, flicker, and multifocal pupil perimetry methods in healthy adults

To this day, the most popular method of choice for testing visual field defects (VFDs) is subjective standard automated perimetry. However, a need has arisen for an objective, and less time-consuming method. Pupil perimetry (PP), which uses pupil responses to onsets of bright stimuli as indications of visual sensitivity, fulfills these requirements. It is currently unclear which PP method most accurately detects VFDs. Hence, the purpose of this study is to compare three PP methods for measuring pupil responsiveness. Unifocal (UPP), flicker (FPP), and multifocal PP (MPP) were compared by monocularly testing the inner 60 degrees of vision at 44 wedge-shaped locations. The visual field (VF) sensitivity of 18 healthy adult participants (mean age and SD 23.7 ± 3.0 years) was assessed, each under three different artificially simulated scotomas for approximately 4.5 minutes each (i.e. stimulus was not or only partially present) conditions: quadrantanopia, a 20-, and 10-degree diameter scotoma. Stimuli that were fully present on the screen evoked strongest, partially present stimuli evoked weaker, and absent stimuli evoked the weakest pupil responses in all methods. However, the pupil responses in FPP showed stronger discriminative power for present versus absent trials (median d-prime = 6.26 ± 2.49, area under the curve [AUC] = 1.0 ± 0) and MPP performed better for fully present versus partially present trials (median d-prime = 1.19 ± 0.62, AUC = 0.80 ± 0.11). We conducted the first in-depth comparison of three PP methods. Gaze-contingent FPP had best discriminative power for large (absolute) scotomas, whereas MPP performed slightly better with small (relative) scotomas

The Trade-Off Between Luminance and Color Contrast Assessed With Pupil Responses

Purpose: A scene consisting of a white stimulus on a black background incorporates strong luminance contrast. When both stimulus and background receive different colors, luminance contrast decreases but color contrast increases. Here, we sought to charac-terize the pattern of stimulus salience across varying trade-offs of color and luminance contrasts by using the pupil light response. Methods: Three experiments were conducted with 17, 16, and 17 healthy adults. For all experiments, a flickering stimulus (2 Hz; alternating color to black) was presented super-imposed on a background with a complementary color to the stimulus (i.e., opponency colors in human color perception: blue and yellow for Experiment 1, red and green for Experiment 2, and equiluminant red and green for Experiment 3). Background luminance varied between 0% and 45% to trade off luminance and color contrast with the stimulus. By comparing the locus of the optimal trade-off between color and luminance across different color axes, we explored the generality of the trade-off. Results: The strongest pupil responses were found when a substantial amount of color contrast was present (at the expense of luminance contrast). Pupil response ampli-tudes increased by 15% to 30% after the addition of color contrast. An optimal pupillary responsiveness was reached at a background luminance setting of 20% to 35% color contrast across several color axes. Conclusions: These findings suggest that a substantial component of pupil light responses incorporates color processing. More sensitive pupil responses and more salient stimulus designs can be achieved by adding subtle levels of color contrast between stimulus and background. Translational Relevance: More robust pupil responses will enhance tests of the visual field with pupil perimetry

The Trade-Off Between Luminance and Color Contrast Assessed With Pupil Responses

Purpose: A scene consisting of a white stimulus on a black background incorporates strong luminance contrast. When both stimulus and background receive different colors, luminance contrast decreases but color contrast increases. Here, we sought to charac-terize the pattern of stimulus salience across varying trade-offs of color and luminance contrasts by using the pupil light response. Methods: Three experiments were conducted with 17, 16, and 17 healthy adults. For all experiments, a flickering stimulus (2 Hz; alternating color to black) was presented super-imposed on a background with a complementary color to the stimulus (i.e., opponency colors in human color perception: blue and yellow for Experiment 1, red and green for Experiment 2, and equiluminant red and green for Experiment 3). Background luminance varied between 0% and 45% to trade off luminance and color contrast with the stimulus. By comparing the locus of the optimal trade-off between color and luminance across different color axes, we explored the generality of the trade-off. Results: The strongest pupil responses were found when a substantial amount of color contrast was present (at the expense of luminance contrast). Pupil response ampli-tudes increased by 15% to 30% after the addition of color contrast. An optimal pupillary responsiveness was reached at a background luminance setting of 20% to 35% color contrast across several color axes. Conclusions: These findings suggest that a substantial component of pupil light responses incorporates color processing. More sensitive pupil responses and more salient stimulus designs can be achieved by adding subtle levels of color contrast between stimulus and background. Translational Relevance: More robust pupil responses will enhance tests of the visual field with pupil perimetry

Lessons Learned from 23 Years of Experience in Testing Visual Fields of Neurologically Impaired Children

We sought to investigate the reliability of standard conventional perimetry (SCP) in neurologically impaired (NI) children using the examiner-based assessment of reliability scoring system and to determine the difference in time to diagnosis of a visual field defect between SCP and a behavioural visual field (BVF) test. Patient records of 115 NI children were retrospectively analysed. The full field peritest (FFP) had best reliability with 44% ‘good’ scores versus 22% for Goldmann perimetry (p < .001). The mean age of NI children able to perform SCP was 8.3 years versus 4.6 years for the BVF test (p < .001). Use of the BVF test may significantly reduce time to diagnosis

Digital Tools for the Self-Assessment of Visual Acuity: A Systematic Review

Introduction: Numerous digital tools to self-assess visual acuity have been introduced. The recent COVID-19 pandemic underlined the need for high-quality remote care. This review gives a current overview of digital tools for remotely assessing visual function and reports on their accuracy. Methods: We searched the databases of Embase and Pubmed, and systematically reviewed the literature, conforming to PRISMA guidelines. Two preliminary papers were added from medRxiv.org. The main outcome was the agreement of the digital tools with conventional clinical charts, as expressed by mean differences and 95% limits of agreement (95% LoA). Results: Seventeen publications included studies reported on 13 different digital tools. Most of the tools focus on distance visual acuity. The mean differences of the digital tools ranged from − 0.08 to 0.10 logMAR, when compared to traditional clinical assessments. The 95% LoA differed considerably between studies: from ± 0.08 logMAR to ± 0.47 logMAR, though the variability was less pronounced for higher visual acuities. Conclusion: The low mean differences between digital visual acuity assessments and reference charts suggest clinical equivalence, though the wide 95% LoA identify a lower precision of digital self-assessments. This effect diminishes in individuals with better visual acuities, which is a common feature of visual acuity assessments. There is great potential for the digital tools to increase access to eye care and we expect the accuracy of the current tools to improve with every iteration in technology development

Blind spot and visual field anisotropy detection with flicker pupil perimetry across brightness and task variations

The pupil can be used as an objective measure for testing sensitivities across the visual field (pupil perimetry; PP). The recently developed gaze-contingent flicker PP (gcFPP) is a promising novel form of PP, with improved sensitivity due to retinotopically stable and repeated flickering stimulations, in a short time span. As a diagnostic tool gcFPP has not yet been benchmarked in healthy individuals. The main aims of the current study were to investigate whether gcFPP has the sensitivity to detect the blind spot, and upper versus lower visual field differences that were found before in previous studies. An additional aim was to test for the effects of attentional requirements and background luminance. A total of thirty individuals were tested with gcFPP across two separate experiments. The results showed that pupil oscillation amplitudes were smaller for stimuli presented inside as compared to outside the blind spot. Amplitudes also decreased as a function of eccentricity (i.e., distance to fixation) and were larger for upper as compared to lower visual fields. We measured the strongest and most sensitive pupil responses to stimuli presented on dark- and mid-gray backgrounds, and when observers covertly focused their attention to the flickering stimulus. GcFPP thus evokes pupil responses that are sensitive enough to detect local, and global differences in pupil sensitivity. The findings further encourage (1) the use of a gray background to prevent straylight without affecting gcFPPs sensitivity and (2) the use of an attention task to enhance pupil sensitivity

Effects of Stimulus Luminance, Stimulus Color and Intra-Stimulus Color Contrast on Visual Field Mapping in Neurologically Impaired Adults Using Flicker Pupil Perimetry

Purpose: We improve pupillary responses and diagnostic performance of flicker pupil perimetry through alterations in global and local color contrast and luminance contrast in adult patients suffering from visual field defects due to cerebral visual impairment (CVI). Methods: Two experiments were conducted on patients with CVI (Experiment 1: 19 subjects, age M and SD 57.9 ± 14.0; Experiment 2: 16 subjects, age M and SD 57.3 ± 14.7) suffering from absolute homonymous visual field (VF) defects. We altered global color contrast (stimuli consisted of white, yellow, cyan and yellow-equiluminant-to-cyan colored wedges) in Experiment 1, and we manipulated luminance and local color contrast with bright and dark yellow and multicolor wedges in a 2-by-2 design in Experiment 2. Stimuli consecutively flickered across 44 stimulus locations within the inner 60 degrees of the VF and were offset to a contrasting (opponency colored) dark background. Pupil perimetry results were compared to standard automated perimetry (SAP) to assess diagnostic accuracy. Results: A bright stimulus with global color contrast using yellow (p= 0.009) or white (p= 0.006) evoked strongest pupillary responses as opposed to stimuli containing local color contrast and lower brightness. Diagnostic accuracy, however, was similar across global color contrast conditions in Experiment 1 (p= 0.27) and decreased when local color contrast and less luminance contrast was introduced in Experiment 2 (p= 0.02). The bright yellow condition resulted in highest performance (AUC M = 0.85 ± 0.10, Mdn = 0.85). Conclusion: Pupillary responses and pupil perimetry’s diagnostic accuracy both benefit from high luminance contrast and global but not local color contrast

Effects of Stimulus Luminance, Stimulus Color and Intra-Stimulus Color Contrast on Visual Field Mapping in Neurologically Impaired Adults Using Flicker Pupil Perimetry

Purpose: We improve pupillary responses and diagnostic performance of flicker pupil perimetry through alterations in global and local color contrast and luminance contrast in adult patients suffering from visual field defects due to cerebral visual impairment (CVI).  Methods: Two experiments were conducted on patients with CVI (Experiment 1: 19 subjects, age M and SD 57.9 ± 14.0; Experiment 2: 16 subjects, age M and SD 57.3 ± 14.7) suffering from absolute homonymous visual field (VF) defects. We altered global color contrast (stimuli consisted of white, yellow, cyan and yellow-equiluminant-to-cyan colored wedges) in Experiment 1, and we manipulated luminance and local color contrast with bright and dark yellow and multicolor wedges in a 2-by-2 design in Experiment 2. Stimuli consecutively flickered across 44 stimulus locations within the inner 60 degrees of the VF and were offset to a contrasting (opponency colored) dark background. Pupil perimetry results were compared to standard automated perimetry (SAP) to assess diagnostic accuracy.  Results: A bright stimulus with global color contrast using yellow (p= 0.009) or white (p= 0.006) evoked strongest pupillary responses as opposed to stimuli containing local color contrast and lower brightness. Diagnostic accuracy, however, was similar across global color contrast conditions in Experiment 1 (p= 0.27) and decreased when local color contrast and less luminance contrast was introduced in Experiment 2 (p= 0.02). The bright yellow condition resulted in highest performance (AUC M = 0.85 ± 0.10, Mdn = 0.85).  Conclusion: Pupillary responses and pupil perimetry’s diagnostic accuracy both benefit from high luminance contrast and global but not local color contrast

The extent of angioid streaks correlates with macular degeneration in pseudoxanthoma elasticum

Purpose: To investigate whether the extent of Bruch's membrane calcification is associated with choroidal neovascularization (CNV) and macular atrophy in patients with pseudoxanthoma elasticum (PXE) by using the extent of angioid streaks as a surrogate marker for the degree of Bruch's membrane calcification. Design: Retrospective cross-sectional study. Methods: We investigated 301 patients with PXE (median age, 52 years; range, 9-79 years) in a tertiary referral center. For both eyes, we graded the extent of angioid streaks, that is, their distance from the optic disc, into 5 groups. Imaging was systematically assessed for signs of CNV and macular atrophy. Associations between the extent of angioid streaks and CNV or macular atrophy were investigated using regression analysis. Results: CNV was present in 148 patients (49%) and retinal atrophy in 71 patients (24%). The extent of angioid streaks was associated with older age (P for trend = 1.92 × 10 −15) and a higher prevalence of CNV and/or macular atrophy (P for trend = 4.22 × 10 −10 and P for trend = 5.17 × 10 −6, respectively). In addition, the extent of angioid streaks was associated with the presence of CNV when adjusted for age and sex (odds ratio, 1.9; 95% confidence interval, 1.3-2.9) and with more severe macular atrophy (proportional odds ratio, 2.3; 95% confidence interval, 1.5-3.6). Conclusions: In patients with PXE, longer angioid streaks are associated with an increased risk of CNV and macular atrophy, even after adjustment for age. These findings are relevant when counseling PXE patients on their visual prognosis