Gaze-contingent flicker pupil perimetry detects scotomas in patients with cerebral visual impairments or glaucoma

The pupillary light reflex is weaker for stimuli presented inside as compared to outside absolute scotomas. Pupillograph perimetry could thus be an objective measure of impaired visual processing. However, the diagnostic accuracy in detecting scotomas has remained unclear. We quantitatively investigated the accuracy of a novel form of pupil perimetry. The new perimetry method, termed gaze-contingent flicker pupil perimetry, consists of the repetitive on, and off flickering of a bright disk (2 hz; 320 cd/m; 4° diameter) on a gray background (160 cd/m) for 4 seconds per stimulus location. The disk evokes continuous pupil oscillations at the same rate as its flicker frequency, and the oscillatory power of the pupil reflects visual sensitivity. We monocularly presented the disk at a total of 80 locations in the central visual field (max. 15°). The location of the flickering disk moved along with gaze to reduce confounds of eye movements (gaze-contingent paradigm). The test lasted ~5 min per eye and was performed on 7 patients with cerebral visual impairment (CVI), 8 patients with primary open angle glaucoma (age >45), and 14 healthy, age/gender-matched controls. For all patients, pupil oscillation power (FFT based response amplitude to flicker) was significantly weaker when the flickering disk was presented in the impaired as compared to the intact visual field (CVI: 12%, AUC = 0.73; glaucoma: 9%, AUC = 0.63). Differences in power values between impaired and intact visual fields of patients were larger than differences in power values at corresponding locations in the visual fields of the healthy control group (CVI: AUC = 0.95; glaucoma: AUC = 0.87). Pupil sensitivity maps highlighted large field scotomas and indicated the type of visual field defect (VFD) as initially diagnosed with standard automated perimetry (SAP) fairly accurately in CVI patients but less accurately in glaucoma patients. We provide the first quantitative and objective evidence of flicker pupil perimetry's potential in detecting CVI-and glaucoma-induced VFDs. Gaze-contingent flicker pupil perimetry is a useful form of objective perimetry and results suggest it can be used to assess large VFDs with young CVI patients whom are unable to perform SAP

Winegrape berry skin thickness determination: comparison between histological observation and texture analysis determination.

We analyzed the relation between the assessment of grape berry skin thickness by means of histology sections and instrumental mechanical properties measurements. Berry skin of Vitis vinifera L. cultivar Corvina vineyards from Valpolicella Valpantena zone (Verona, Italy) were tested, evidencing a strong correlation between the two thickness determination methods. The middle or equatorial berry skin portion was found to be the less variable in instrumental skin thickness determination. In addition, unlike other studies, no correlation between the skin thickness and cell layers number was found

Maintaining fixation by children in a virtual reality version of pupil perimetry

The assessment of visual field sensitivities in young children continues to be a challenge. Children often do not sit still, fail to fixate stimuli for longer durations, and have limited verbal capacity to report visibility. We investigated the use of a head-mounted VR display, gaze-contingent flicker pupil perimetry (gcFPP), and three fixation stimulus conditions to determine best practices for optimal fixation and pupil response quality. A total of twenty children (3-11y) passively fixated a dot, counted the repeated appearance of an animated character, and watched an animated movie in separate trials of 80s each. We presented large flickering patches at different eccentricities and angles in the periphery to evoke pupillary oscillations (20 locations, 4s per location). The results showed that gaze precision and accuracy did not differ significantly across the fixation conditions but pupil amplitudes were strongest for the dot and count task. We recommend the use of the fixation counting task for pupil perimetry because children enjoyed it the most and it achieved strongest pupil responses. The VR set-up appears to be an ideal apparatus for children to allow free range of movement, an engaging visual task, and reliable eye measurements

Clinical-Cytological-Grading and phenotyping in patients with chronic rhinosinusitis with nasal polyps: the relevance in clinical practice

Chronic rhinosinusitis (CRS) includes two main phenotypes: without nasal polyps (CRSsNP) and with nasal polyps (CRSwNP). CRSwNP may be associated with comorbidity, mainly concerning asthma, aspirin intolerance, and allergy. CRSwNP patients may also be evaluated by clinical-cytological grading (CCG). The current study investigated the prevalence and characteristics of the different CCG and phenotypes in CRSwNP outpatients examined in clinical practice. This retrospective cross-sectional study enrolled 791 consecutive CRSwNP outpatients (424 males, mean age 48.8 years). In the total population, asthma was a common comorbidity (30.8%) as well as aspirin intolerance (24.8%), and allergy (50.8%). As concerns CCG-grading, 210 (26.5%) outpatients had low-grade, 366 (46.3%) medium, and 215 (27.2%) high. As regards cytological phenotypes, 87 (11%) had neutrophilic type, 371 (46.3%) eosinophilic, 112 (14.2%) mast cell, and 221 (27.9%) mixed. High-grade CCG was significantly associated with more frequent asthma, aspirin intolerance, allergy, recurrent surgery, and mixed cytological phenotype. Low-grade CCG was characterized by fewer comorbidities and operations, and neutrophilic phenotype. Therefore, the present study confirmed that CCG is a useful tool in the management of outpatients with CRSwNP. CRSwNP is frequently associated with asthma, aspirin intolerance, and allergy comorbidity. High-grade CCG is frequently characterized by a mixed cytological phenotype, thus, by more severe progress. These real-world outcomes underline that CRSwNP deserves adequate attention for careful management and optimal identification of the best-tailored therapy; CCG and cytological phenotyping could be fruitful tools in clinical practice. Asthma and aspirin intolerance should be adequately investigated in all CRS patients

Regulated splicing of the fibronectin EDA exon is essential for proper skin wound healing and normal lifespan

Fibronectins (FNs) are multifunctional high molecular weight glycoproteins present in the blood plasma and in the ECMs of tissues. The FN primary transcript undergoes alternative splicing in three regions generating up to 20 main different variants in humans. However, the precise role of the FN isoforms is poorly understood. One of the alternatively spliced exons is the extra domain A (EDA) or extra type III homology that is regulated spatially and temporally during development and aging. To study its in vivo function, we generated mice devoid of EDA exon-regulated splicing. Constitutive exon inclusion was obtained by optimizing the splice sites, whereas complete exclusion was obtained after in vivo CRE-loxP–mediated deletion of the exon. Homozygous mouse strains with complete exclusion or inclusion of the EDA exon were viable and developed normally, indicating that the alternative splicing at the EDA exon is not necessary during embryonic development. Conversely, mice without the EDA exon in the FN protein displayed abnormal skin wound healing, whereas mice having constitutive inclusion of the EDA exon showed a major decrease in the FN levels in all tissues. Moreover, both mutant mouse strains have a significantly shorter lifespan than the control mice, suggesting that EDA splicing regulation is necessary for efficient long-term maintenance of biological functions

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

Maintaining fixation by children in a virtual reality version of pupil perimetry

The assessment of the visual field in young children continues to be a challenge. Children often do not sit still, fail to fixate stimuli for longer durations, and have limited verbal ca-pacity to report visibility. Therefore, we introduced a head-mounted VR display with gaze-contingent flicker pupil perimetry (VRgcFPP). We presented large flickering patches at different eccentricities and angles in the periphery to evoke pupillary oscillations, and three fixation stimulus conditions to determine best practices for optimal fixation and pupil response quality. A total of twenty children (3-11y) passively fixated a dot, counted the re-peated appearance of an animated character(counting task), and watched an animated movie in separate trials of 80s each (20 patch locations, 4s per location).The results showed that gaze precision and accuracy did not differ significantly across the fixation conditions but pupil amplitudes were strongest for the dot and count task. The VR set-up appears to be an ideal apparatus for children to allow free range of movement, an engaging visual task, and reliable eye measurements. We recommend the use of the fixation count-ing task for pupil perimetry because children enjoyed it the most and it achieved strongest pupil responses

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

Gaze-Contingent Flicker Pupil Perimetry Detects Scotomas in Patients With Cerebral Visual Impairments or Glaucoma

Background: The pupillary light reflex is weaker for stimuli presented inside as compared to outside absolute scotomas. Pupillograph perimetry could thus be an objective measure of impaired visual processing. However, the diagnostic accuracy in detecting scotomas has remained unclear. We quantitatively investigated the accuracy of a novel form of pupil perimetry.Methods: The new perimetry method, termed gaze-contingent flicker pupil perimetry, consists of the repetitive on, and off flickering of a bright disk (2 hz; 320 cd/m2; 4° diameter) on a gray background (160 cd/m2) for 4 seconds per stimulus location. The disk evokes continuous pupil oscillations at the same rate as its flicker frequency, and the oscillatory power of the pupil reflects visual sensitivity. We monocularly presented the disk at a total of 80 locations in the central visual field (max. 15°). The location of the flickering disk moved along with gaze to reduce confounds of eye movements (gaze-contingent paradigm). The test lasted ~5 min per eye and was performed on 7 patients with cerebral visual impairment (CVI), 8 patients with primary open angle glaucoma (age >45), and 14 healthy, age/gender-matched controls.Results: For all patients, pupil oscillation power (FFT based response amplitude to flicker) was significantly weaker when the flickering disk was presented in the impaired as compared to the intact visual field (CVI: 12%, AUC = 0.73; glaucoma: 9%, AUC = 0.63). Differences in power values between impaired and intact visual fields of patients were larger than differences in power values at corresponding locations in the visual fields of the healthy control group (CVI: AUC = 0.95; glaucoma: AUC = 0.87). Pupil sensitivity maps highlighted large field scotomas and indicated the type of visual field defect (VFD) as initially diagnosed with standard automated perimetry (SAP) fairly accurately in CVI patients but less accurately in glaucoma patients.Conclusions: We provide the first quantitative and objective evidence of flicker pupil perimetry's potential in detecting CVI-and glaucoma-induced VFDs. Gaze-contingent flicker pupil perimetry is a useful form of objective perimetry and results suggest it can be used to assess large VFDs with young CVI patients whom are unable to perform SAP