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

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

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

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age  6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score  652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

What is the role of the placebo effect for pain relief in neurorehabilitation? Clinical implications from the Italian Consensus Conference on Pain in Neurorehabilitation

Background: It is increasingly acknowledged that the outcomes of medical treatments are influenced by the context of the clinical encounter through the mechanisms of the placebo effect. The phenomenon of placebo analgesia might be exploited to maximize the efficacy of neurorehabilitation treatments. Since its intensity varies across neurological disorders, the Italian Consensus Conference on Pain in Neurorehabilitation (ICCP) summarized the studies on this field to provide guidance on its use. Methods: A review of the existing reviews and meta-analyses was performed to assess the magnitude of the placebo effect in disorders that may undergo neurorehabilitation treatment. The search was performed on Pubmed using placebo, pain, and the names of neurological disorders as keywords. Methodological quality was assessed using a pre-existing checklist. Data about the magnitude of the placebo effect were extracted from the included reviews and were commented in a narrative form. Results: 11 articles were included in this review. Placebo treatments showed weak effects in central neuropathic pain (pain reduction from 0.44 to 0.66 on a 0-10 scale) and moderate effects in postherpetic neuralgia (1.16), in diabetic peripheral neuropathy (1.45), and in pain associated to HIV (1.82). Moderate effects were also found on pain due to fibromyalgia and migraine; only weak short-term effects were found in complex regional pain syndrome. Confounding variables might have influenced these results. Clinical implications: These estimates should be interpreted with caution, but underscore that the placebo effect can be exploited in neurorehabilitation programs. It is not necessary to conceal its use from the patient. Knowledge of placebo mechanisms can be used to shape the doctor-patient relationship, to reduce the use of analgesic drugs and to train the patient to become an active agent of the therapy

Bilateral population receptive fields in congenital hemihydranencephaly

PURPOSE: Congenital hemihydranencephaly (HH) is a very rare disorder characterised by prenatal near-complete unilateral loss of the cerebral cortex. We investigated a patient affected by congenital right HH whose visual field extended significantly into the both visual hemifields, suggesting a reorganisation of the remaining left visual hemisphere. We examined the early visual cortex reorganisation using functional MRI (7T) and population receptive field (pRF) modelling. METHODS: Data were acquired by means of a 7T MRI while the patient affected by HH viewed conventional population receptive field mapping stimuli. Two possible pRF reorganisation schemes were evaluated: where every cortical location processed information from either (i) a single region of the visual field or (ii) from two bilateral regions of the visual field. RESULTS: In the patient affected by HH, bilateral pRFs in single cortical locations of the remaining hemisphere were found. In addition, using this specific pRF reorganisation scheme, the biologically known relationship between pRF size and eccentricity was found. CONCLUSIONS: Bilateral pRFs were found in the remaining left hemisphere of the patient affected by HH, indicating reorganisation of intra-cortical wiring of the early visual cortex and confirming brain plasticity and reorganisation after an early cerebral damage in humans

Bilateral population receptive fields in congenital hemihydranencephaly

Purpose: Congenital hemihydranencephaly (HH) is a very rare disorder characterised by prenatal near-complete unilateral loss of the cerebral cortex. We investigated a patient affected by congenital right HH whose visual field extended significantly into the both visual hemifields, suggesting a reorganisation of the remaining left visual hemisphere. We examined the early visual cortex reorganisation using functional MRI (7T) and population receptive field (pRF) modelling. Methods: Data were acquired by means of a 7T MRI while the patient affected by HH viewed conventional population receptive field mapping stimuli. Two possible pRF reorganisation schemes were evaluated: where every cortical location processed information from either (i) a single region of the visual field or (ii) from two bilateral regions of the visual field. Results: In the patient affected by HH, bilateral pRFs in single cortical locations of the remaining hemisphere were found. In addition, using this specific pRF reorganisation scheme, the biologically known relationship between pRF size and eccentricity was found. Conclusions: Bilateral pRFs were found in the remaining left hemisphere of the patient affected by HH, indicating reorganisation of intra-cortical wiring of the early visual cortex and confirming brain plasticity and reorganisation after an early cerebral damage in humans