A Portable Platform for Evaluation of Visual Performance in Glaucoma Patients

PurposeTo propose a new tablet-enabled test for evaluation of visual performance in glaucoma, the PERformance CEntered Portable Test (PERCEPT), and to evaluate its ability to predict history of falls and motor vehicle crashes.DesignCross-sectional study.MethodsThe study involved 71 patients with glaucomatous visual field defects on standard automated perimetry (SAP) and 59 control subjects. The PERCEPT was based on the concept of increasing visual task difficulty to improve detection of central visual field losses in glaucoma patients. Subjects had to perform a foveal 8-alternative-forced-choice orientation discrimination task, while detecting a simultaneously presented peripheral stimulus within a limited presentation time. Subjects also underwent testing with the Useful Field of View (UFOV) divided attention test. The ability to predict history of motor vehicle crashes and falls was investigated by odds ratios and incident-rate ratios, respectively.ResultsWhen adjusted for age, only the PERCEPT processing speed parameter showed significantly larger values in glaucoma compared to controls (difference: 243ms; P<0.001). PERCEPT results had a stronger association with history of motor vehicle crashes and falls than UFOV. Each 1 standard deviation increase in PERCEPT processing speed was associated with an odds ratio of 2.69 (P = 0.003) for predicting history of motor vehicle crashes and with an incident-rate ratio of 1.95 (P = 0.003) for predicting history of falls.ConclusionA portable platform for testing visual function was able to detect functional deficits in glaucoma, and its results were significantly associated with history of involvement in motor vehicle crashes and history of falls.     

Lateral Inhibition in the Human Visual System in Patients with Glaucoma and Healthy Subjects: A Case-Control Study

In glaucoma, the density of retinal ganglion cells is reduced. It is largely unknown how this influences retinal information processing. An increase in spatial summation and a decrease in contrast gain control and contrast adaptation have been reported. A decrease in lateral inhibition might also arise. This could result in a larger than expected response to some stimuli, which could mask ganglion cell loss on functional testing (structure-function discrepancy). The aim of this study was to compare lateral inhibition between glaucoma patients and healthy subjects; we used a case-control design. Cases (n = 18) were selected to have advanced visual field loss in combination with a normal visual acuity. Controls (n = 50) were not allowed to have symptoms or signs of any eye disease. Lateral inhibition was measured psychophysically on a computer screen, with (1) a modified illusory movement experiment and (2) a contrast sensitivity (CS) test. Illusory movement was quantified by nulling it with a real movement; measure of lateral inhibition was the amount of illusory movement. CS was measured at 1 and 4 cycles per degree (cpd); measure of lateral inhibition was the difference between log CS at 4 and 1 cpd. Both measures were compared between cases and controls; analyses were adjusted for age and gender. There was no difference between cases and controls for these two measures of lateral inhibition (p = 0.58 for illusory movement; p = 0.20 for CS). The movement threshold was higher in cases than in controls (p = 0.008) and log CS was lower, at both 1 (-0.20; p = 0.008) and 4 (-0.28; p = 0.001) cpd. Our results indicate that spatially antagonistic mechanisms are not specifically affected in glaucoma, at least not in the intact center of a severely damaged visual field. This suggests that the structure-function discrepancy in glaucoma is not related to a decrease in lateral inhibition.     

Driving Simulation in the Clinic: Testing Visual Exploratory Behavior in Daily Life Activities in Patients with Visual Field Defects

Patients suffering from homonymous hemianopia after infarction of the posterior cerebral artery (PCA) report different degrees of constraint in daily life, despite similar visual deficits. We assume this could be due to variable development of compensatory strategies such as altered visual scanning behavior. Scanning compensatory therapy (SCT) is studied as part of the visual training after infarction next to vision restoration therapy. SCT consists of learning to make larger eye movements into the blind field enlarging the visual field of search, which has been proven to be the most useful strategy¹, not only in natural search tasks but also in mastering daily life activities². Nevertheless, in clinical routine it is difficult to identify individual levels and training effects of compensatory behavior, since it requires measurement of eye movements in a head unrestrained condition. Studies demonstrated that unrestrained head movements alter the visual exploratory behavior compared to a head-restrained laboratory condition³. Martin et al.⁴ and Hayhoe et al.⁵ showed that behavior demonstrated in a laboratory setting cannot be assigned easily to a natural condition. Hence, our goal was to develop a study set-up which uncovers different compensatory oculomotor strategies quickly in a realistic testing situation: Patients are tested in the clinical environment in a driving simulator. SILAB software (Wuerzburg Institute for Traffic Sciences GmbH (WIVW)) was used to program driving scenarios of varying complexity and recording the driver''s performance. The software was combined with a head mounted infrared video pupil tracker, recording head- and eye-movements (EyeSeeCam, University of Munich Hospital, Clinical Neurosciences).The positioning of the patient in the driving simulator and the positioning, adjustment and calibration of the camera is demonstrated. Typical performances of a patient with and without compensatory strategy and a healthy control are illustrated in this pilot study. Different oculomotor behaviors (frequency and amplitude of eye- and head-movements) are evaluated very quickly during the drive itself by dynamic overlay pictures indicating where the subjects gaze is located on the screen, and by analyzing the data. Compensatory gaze behavior in a patient leads to a driving performance comparable to a healthy control, while the performance of a patient without compensatory behavior is significantly worse. The data of eye- and head-movement-behavior as well as driving performance are discussed with respect to different oculomotor strategies and in a broader context with respect to possible training effects throughout the testing session and implications on rehabilitation potential.     

Driving with Central Visual Field Loss II: How Scotomas above or below the Preferred Retinal Locus (PRL) Affect Hazard Detection in a Driving Simulator

We determined whether binocular central scotomas above or below the preferred retinal locus affect detection of hazards (pedestrians) approaching from the side. Seven participants with central field loss (CFL), and seven age-and sex-matched controls with normal vision (NV), each completed two sessions of 5 test drives (each approximately 10 minutes long) in a driving simulator. Participants pressed the horn when detecting pedestrians that appeared at one of four eccentricities (-14°, -4°, left, 4°, or 14°, right, relative to car heading). Pedestrians walked or ran towards the travel lane on a collision course with the participant’s vehicle, thus remaining in the same area of the visual field, assuming participant''s steady forward gaze down the travel lane. Detection rates were nearly 100% for all participants. CFL participant reaction times were longer (median 2.27s, 95% CI 2.13 to 2.47) than NVs (median 1.17s, 95%CI 1.10 to 2.13; difference p<0.01), and CFL participants would have been unable to stop for 21% of pedestrians, compared with 3% for NV, p<0.001. Although the scotomas were not expected to obscure pedestrian hazards, gaze tracking revealed that scotomas did sometimes interfere with detection; late reactions usually occurred when pedestrians were entirely or partially obscured by the scotoma (time obscured correlated with reaction times, r = 0.57, p<0.001). We previously showed that scotomas lateral to the preferred retinal locus delay reaction times to a greater extent; however, taken together, the results of our studies suggest that any binocular CFL might negatively impact timely hazard detection while driving and should be a consideration when evaluating vision for driving.     

Structural and Functional Brain Changes beyond Visual System in Patients with Advanced Glaucoma

In order to test the hypothesis that in primary open angle glaucoma (POAG), an important cause of irreversible blindness, a spreading of neurodegeneration occurs through the brain, we performed multimodal MRI and subsequent whole-brain explorative voxelwise analyses in 13 advanced POAG patients and 12 age-matched normal controls (NC). Altered integrity (decreased fractional anisotropy or increased diffusivities) of white matter (WM) tracts was found not only along the visual pathway of POAG but also in nonvisual WM tracts (superior longitudinal fascicle, anterior thalamic radiation, corticospinal tract, middle cerebellar peduncle). POAG patients also showed brain atrophy in both visual cortex and other distant grey matter (GM) regions (frontoparietal cortex, hippocampi and cerebellar cortex), decreased functional connectivity (FC) in visual, working memory and dorsal attention networks and increased FC in visual and executive networks. In POAG, abnormalities in structure and FC within and outside visual system correlated with visual field parameters in the poorer performing eyes, thus emphasizing their clinical relevance. Altogether, this represents evidence that a vision disorder such as POAG can be considered a widespread neurodegenerative condition.     

Predicting Risk of Motor Vehicle Collisions in Patients with Glaucoma: A Longitudinal Study

Purpose

To evaluate the ability of longitudinal Useful Field of View (UFOV) and simulated driving measurements to predict future occurrence of motor vehicle collision (MVC) in drivers with glaucoma.

Design

Prospective observational cohort study.

Participants

117 drivers with glaucoma followed for an average of 2.1 ± 0.5 years.

Methods

All subjects had standard automated perimetry (SAP), UFOV, driving simulator, and cognitive assessment obtained at baseline and every 6 months during follow-up. The driving simulator evaluated reaction times to high and low contrast peripheral divided attention stimuli presented while negotiating a winding country road, with central driving task performance assessed as “curve coherence”. Drivers with MVC during follow-up were identified from Department of Motor Vehicle records.

Main Outcome Measures

Survival models were used to evaluate the ability of driving simulator and UFOV to predict MVC over time, adjusting for potential confounding factors.

Results

Mean age at baseline was 64.5 ± 12.6 years. 11 of 117 (9.4%) drivers had a MVC during follow-up. In the multivariable models, low contrast reaction time was significantly predictive of MVC, with a hazard ratio (HR) of 2.19 per 1 SD slower reaction time (95% CI, 1.30 to 3.69; P = 0.003). UFOV divided attention was also significantly predictive of MVC with a HR of 1.98 per 1 SD worse (95% CI, 1.10 to 3.57; P = 0.022). Global SAP visual field indices in the better or worse eye were not predictive of MVC. The longitudinal model including driving simulator performance was a better predictor of MVC compared to UFOV (R² = 0.41 vs R² = 0.18).

Conclusions

Longitudinal divided attention metrics on the UFOV test and during simulated driving were significantly predictive of risk of MVC in glaucoma patients. These findings may help improve the understanding of factors associated with driving impairment related to glaucoma.     

The Impact of Structural and Functional Parameters in Glaucoma Patients on Patient-Reported Visual Functioning

Background

To evaluate the impact of structural changes of the retinal nerve fiber layer (RNFL), and visual field loss, on functional impairment assessed by patient-reported visual functioning in glaucoma.

Methods

Patients with glaucomatous optic nerve damage were enrolled in this cross-sectional study. Peripapillary RNFL thickness was obtained with spectral-domain optical coherence tomography (SD-OCT). Function was assessed by patient-reported visual functioning using the Rasch-calibrated Glaucoma Activity Limitation 9 (GAL-9) questionnaire and standard automated perimetry. The impact of peripapillary RNFL loss on functional impairment was analyzed with correlation and linear regression analyses.

Results

A total of 176 eyes from 88 glaucoma patients were included. The SD-OCT assessed temporal-superior and temporal-inferior RNFL sector of the worse eye revealed significant correlation with the GAL-9 scores (r=-0.298, p=0.011 and r=-0.251, p=0.033, respectively). In mutivariate regression analysis, the best predictors for patient-reported visual functioning were visual acuity of the better eye and mean defect of the worse eye (R²=0.334), while structural parameters could not enhance the prediction of GAL-9 scores.

Conclusions

Self-reported visual functioning of patients with glaucoma is better predicted by visual performance data than structural parameters. However, some structural changes of the worse eye are significantly correlated with patient-reported visual functioning.     

Acute Synthesis of CPEB Is Required for Plasticity of Visual Avoidance Behavior in Xenopus

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The Duration of a Co-Occurring Sound Modulates Visual Detection Performance in Humans

Background

The duration of sounds can affect the perceived duration of co-occurring visual stimuli. However, it is unclear whether this is limited to amodal processes of duration perception or affects other non-temporal qualities of visual perception.

Methodology/Principal Findings

Here, we tested the hypothesis that visual sensitivity - rather than only the perceived duration of visual stimuli - can be affected by the duration of co-occurring sounds. We found that visual detection sensitivity (d’) for unimodal stimuli was higher for stimuli of longer duration. Crucially, in a cross-modal condition, we replicated previous unimodal findings, observing that visual sensitivity was shaped by the duration of co-occurring sounds. When short visual stimuli (∼24 ms) were accompanied by sounds of matching duration, visual sensitivity was decreased relative to the unimodal visual condition. However, when the same visual stimuli were accompanied by longer auditory stimuli (∼60–96 ms), visual sensitivity was increased relative to the performance for ∼24 ms auditory stimuli. Across participants, this sensitivity enhancement was observed within a critical time window of ∼60–96 ms. Moreover, the amplitude of this effect correlated with visual sensitivity enhancement found for longer lasting visual stimuli across participants.

Conclusions/Significance

Our findings show that the duration of co-occurring sounds affects visual perception; it changes visual sensitivity in a similar way as altering the (actual) duration of the visual stimuli does.     

iStent as a Solo Procedure for Glaucoma Patients: A Systematic Review and Meta-Analysis

BackgroundGlaucoma is a leading cause of irreversible blindness. It is firmly entrenched in the traditional treatment paradigm to start with pharmacotherapy. However, pharmacotherapy is not benign and has been well documented to have a number of significant challenges. Minimally invasive glaucoma surgery (MIGS) that targets the outflow pathway with minimal to no scleral dissection has resulted in the need to reconsider the glaucoma treatment paradigm.PurposeTo perform a systematic review and meta-analysis to evaluate and quantify the effect on post-operative intraocular pressure (IOP) and number of topical glaucoma medications, in patients receiving the iStent MIGS device as the solo procedure without concurrent cataract surgery.MethodsA systematic review was conducted by searching various databases between January 1, 2000, and June 30, 2014. Studies reporting up to a maximum follow-up period of 24 months were retrieved and screened using the EPPI-Reviewer 4 gateway. Percentage reduction in IOP (IOPR%), and mean reduction in topical glaucoma medications after surgery were computed. Meta-analysis was performed using STATA v. 13.0. The standardized mean difference (SMD) was calculated as the effect size for continuous scale outcomes. Heterogeneity was determined using the I² statistics, Z-value, and χ² statistics. Fixed-effect and random-effect models were developed based on heterogeneity. Sub-group analysis was performed based on the number of iStents implanted and the follow-up period. The outcome measures were changes in the IOP and number of glaucoma medications.ResultsThe search strategy identified 105 records from published literature and 9 records from the grey literature. Five studies with 248 subjects were included for quantitative synthesis. A 22% IOP reduction (IOPR%) from baseline occurred at 18-months after one iStent implant, 30% at 6-months after two iStents implantations, and 40% at 6-months after implantation of three iStents. A mean reduction of 1.2 bottles per patient of topical glaucoma medications occurred at 18-months after one iStent implant, 1.45 bottles per patient at 6-months after two iStents, and one bottle of medication per patient was reduced at 6-months following placement of three iStents implants. Meta-analysis results showed a significant reduction in the IOP after one iStent (SMD = -1.68, 95% CI: [-2.7, -0.61]), two iStents (SMD = -1.88, 95% CI: [-2.2, -1.56]), and three iStents (SMD = -2, 95% CI: [-2.62, -1.38]) implantation. Results showed a significant drop in the topical glaucoma medications after one iStent (SMD = -2.11, CI: [-3.95, -0.27]), two iStent (SMD = -1.88, CI: [-2.20, -1.56]), and three iStents (SMD = -2.00, CI: [-2.62, -1.38]) implantation. The maximum reduction in IOP occurred at 12-months (SMD = -2.21, CI: [-2.53, -1.88]) and a significant reduction in post-operative topical glaucoma medications occurred even after 18-months of iStent implantation (SMD = -0.71, CI: [-1.15, -0.26]).ConclusioniStent implantation as a solo procedure without concurrent cataract extraction does lower IOP, and reduces the dependency on glaucoma medications. This effect seems to last at least 18 months.     

Identifying Areas of the Visual Field Important for Quality of Life in Patients with Glaucoma

PurposeThe purpose of this study was to create a vision-related quality of life (VRQoL) prediction system to identify visual field (VF) test points associated with decreased VRQoL in patients with glaucoma.MethodVRQoL score was surveyed in 164 patients with glaucoma using the ‘Sumi questionnaire’. A binocular VF was created from monocular VFs by using the integrated VF (IVF) method. VRQoL score was predicted using the ‘Random Forest’ method, based on visual acuity (VA) of better and worse eyes (better-eye and worse-eye VA) and total deviation (TD) values from the IVF. For comparison, VRQoL scores were regressed (linear regression) against: (i) mean of TD (IVF MD); (ii) better-eye VA; (iii) worse-eye VA; and (iv) IVF MD and better- and worse-eye VAs. The rank of importance of IVF test points was identified using the Random Forest method.ResultsThe root mean of squared prediction error associated with the Random Forest method (0.30 to 1.97) was significantly smaller than those with linear regression models (0.34 to 3.38, p<0.05, ten-fold cross validation test). Worse-eye VA was the most important variable in all VRQoL tasks. In general, important VF test points were concentrated along the horizontal meridian. Particular areas of the IVF were important for different tasks: peripheral superior and inferior areas in the left hemifield for the ‘letters and sentences’ task, peripheral, mid-peripheral and para-central inferior regions for the ‘walking’ task, the peripheral superior region for the ‘going out’ task, and a broad scattered area across the IVF for the ‘dining’ task.ConclusionThe VRQoL prediction model with the Random Forest method enables clinicians to better understand patients’ VRQoL based on standard clinical measurements of VA and VF.     

Staying Connected on the Road: A Comparison of Different Types of Smart Phone Use in a Driving Simulator

Previous research on smart phone use while driving has primarily focused on phone calls and texting. Drivers are now increasingly using their phone for other activities during driving, in particular social media, which have different cognitive demands. The present study compared the effects of four different smart phone tasks on car-following performance in a driving simulator. Phone tasks were chosen that vary across two factors: interaction medium (text vs image) and task pacing (self-paced vs experimenter-paced) and were as follows: Text messaging with the experimenter (text/other-paced), reading Facebook posts (text/self-paced), exchanging photos with the experimenter via Snapchat (image, experimenter -paced), and viewing updates on Instagram (image, experimenter -paced). Drivers also performed a driving only baseline. Brake reaction times (BRTs) were significantly greater in the text-based conditions (Mean = 1.16 s) as compared to both the image-based conditions (Mean = 0.92 s) and the baseline (0.88 s). There was no significant difference between BRTs in the image-based and baseline conditions and there was no significant effect of task-pacing. Similar results were obtained for Time Headway variability. These results are consistent with the picture superiority effect found in memory research and suggest that image-based interfaces could provide safer ways to “stay connected” while driving than text-based interfaces.     

Structural Alteration of the Dorsal Visual Network in DLB Patients with Visual Hallucinations: A Cortical Thickness MRI Study

Visual hallucinations (VH) represent one of the core features in discriminating dementia with Lewy bodies (DLB) from Alzheimer’s Disease (AD). Previous studies reported that in DLB patients functional alterations of the parieto-occipital regions were correlated with the presence of VH. The aim of our study was to assess whether morphological changes in specific cortical regions of DLB could be related to the presence and severity of VH. We performed a cortical thickness analysis on magnetic resonance imaging data in a cohort including 18 DLB patients, 15 AD patients and 14 healthy control subjects. Relatively to DLB group, correlation analysis between the cortical thickness and the Neuropsychiatric Inventory (NPI) hallucination item scores was also performed. Cortical thickness was reduced bilaterally in DLB compared to controls in the pericalcarine and lingual gyri, cuneus, precuneus, superior parietal gyrus. Cortical thinning was found bilaterally in AD compared to controls in temporal cortex including the superior and middle temporal gyrus, part of inferior temporal cortex, temporal pole and insula. Inferior parietal and supramarginal gyri were also affected bilaterally in AD as compared to controls. The comparison between DLB and AD evidenced cortical thinning in DLB group in the right posterior regions including superior parietal gyrus, precuneus, cuneus, pericalcarine and lingual gyri. Furthermore, the correlation analysis between cortical thickness and NPI hallucination item scores showed that the structural alteration in the dorsal visual regions including superior parietal gyrus and precuneus closely correlated with the occurrence and severity of VH. We suggest that structural changes in key regions of the dorsal visual network may play a crucial role in the physiopathology of VH in DLB patients.     

A New Stage in the Performance of a Human Immunogram: A Visual Streptavidin-Biotin Approach

The production of a reagent kit has been recently organized by DAKO, Immunotekh and other companies, for phenotyping of lymphocytes by the streptavidin–biotin method. The method needs no sophisticated equipment, is highly sensitive, and allows rapid staining of different lymphocyte subpopulations in capillary blood smears and subsequent observation of them under a light microscope. We have modified this method for staining leukocytes in the monolayer prepared with a plate cytorotor. Not decreasing the above-mentioned advantages of the method, this modification significantly cheapens and simplifies the staining procedure; the blood cells of 16 subjects can be stained concurrently, and the staining can be performed by a technician. The streptavidin–biotin method of lymphocyte phenotyping can be mastered in every immunological laboratory, thus improving its technical level.     

Abnormal Contextual Modulation of Visual Contour Detection in Patients with Schizophrenia

Schizophrenia patients demonstrate perceptual deficits consistent with broad dysfunction in visual context processing. These include poor integration of segments forming visual contours, and reduced visual contrast effects (e.g. weaker orientation-dependent surround suppression, ODSS). Background image context can influence contour perception, as stimuli near the contour affect detection accuracy. Because of ODSS, this contextual modulation depends on the relative orientation between the contour and flanking elements, with parallel flankers impairing contour perception. However in schizophrenia, the impact of abnormal ODSS during contour perception is not clear. It is also unknown whether deficient contour perception marks genetic liability for schizophrenia, or is strictly associated with clinical expression of this disorder. We examined contour detection in 25 adults with schizophrenia, 13 unaffected first-degree biological relatives of schizophrenia patients, and 28 healthy controls. Subjects performed a psychophysics experiment designed to quantify the effect of flanker orientation during contour detection. Overall, patients with schizophrenia showed poorer contour detection performance than relatives or controls. Parallel flankers suppressed and orthogonal flankers enhanced contour detection performance for all groups, but parallel suppression was relatively weaker for schizophrenia patients than healthy controls. Relatives of patients showed equivalent performance with controls. Computational modeling suggested that abnormal contextual modulation in schizophrenia may be explained by suppression that is more broadly tuned for orientation. Abnormal flanker suppression in schizophrenia is consistent with weaker ODSS and/or broader orientation tuning. This work provides the first evidence that such perceptual abnormalities may not be associated with a genetic liability for schizophrenia.     

Biofeedback and Dance Performance: A Preliminary Investigation

Alpha-theta neurofeedback has been shown to produce professionally significant performance improvements in music students. The present study aimed to extend this work to a different performing art and compare alpha-theta neurofeedback with another form of biofeedback: heart rate variability (HRV) biofeedback. Twenty-four ballroom and Latin dancers were randomly allocated to three groups, one receiving neurofeedback, one HRV biofeedback and one no intervention. Dance was assessed before and after training. Performance improvements were found in the biofeedback groups but not in the control group. Neurofeedback and HRV biofeedback benefited performance in different ways. A replication with larger sample sizes is required.     

Performance of Serum Biomarkers for the Early Detection of Invasive Aspergillosis in Febrile,Neutropenic Patients: A Multi-State Model

Background

The performance of serum biomarkers for the early detection of invasive aspergillosis expectedly depends on the timing of test results relative to the empirical administration of antifungal therapy during neutropenia, although a dynamic evaluation framework is lacking.

Methods

We developed a multi-state model describing simultaneously the likelihood of empirical antifungal therapy and the risk of invasive aspergillosis during neutropenia. We evaluated whether the first positive test result with a biomarker is an independent predictor of invasive aspergillosis when both diagnostic information used to treat and risk factors of developing invasive aspergillosis are taken into account over time. We applied the multi-state model to a homogeneous cohort of 185 high-risk patients with acute myeloid leukemia. Patients were prospectively screened for galactomannan antigenemia twice a week for immediate treatment decision; 2,214 serum samples were collected on the same days and blindly assessed for (1->3)- β-D-glucan antigenemia and a quantitative PCR assay targeting a mitochondrial locus.

Results

The usual evaluation framework of biomarker performance was unable to distinguish clinical benefits of β-glucan or PCR assays. The multi-state model evidenced that the risk of invasive aspergillosis is a complex time function of neutropenia duration and risk management. The quantitative PCR assay accelerated the early detection of invasive aspergillosis (P = .010), independently of other diagnostic information used to treat, while β-glucan assay did not (P = .53).

Conclusions

The performance of serum biomarkers for the early detection of invasive aspergillosis is better apprehended by the evaluation of time-varying predictors in a multi-state model. Our results provide strong rationale for prospective studies testing a preemptive antifungal therapy, guided by clinical, radiological, and bi-weekly blood screening with galactomannan antigenemia and a standardized quantitative PCR assay.