Extended depth-of-field imaging employing integrated binary phase pupil mask and principal component analysis image fusion.

The imaging depth of field (DOF) of white-light illuminated objects is extended by carefully integrating two image-processing techniques, one optical and one digital. The optical technique makes use of a tailored phase mask positioned at the pupil of the imaging system to cause different color channels to have different focal lengths; accordingly, the phase-mask equipped imaging system acquires a high resolution and reasonably focused image in at least one of the three, red, green, blue (RGB), color channels at any location within the specified DOF. The digital processing comprises fusing the separate RGB images with an original technique that implements principal component analysis to deliver the overall sharpest grayscale composite image throughout the DOF region. The obtained experimental results agree well with the theoretical predictions and demonstrate the capability of the integrated technique to extend the DOF.

Benefits of thermal and distance-filtered imaging for wayfinding with prosthetic vision.

Visual prostheses such as the Argus II provide partial vision for individuals with limited or no light perception. However, their effectiveness in daily life situations is limited by scene complexity and variability. We investigated whether additional image processing techniques could improve mobility performance in everyday indoor environments. A mobile system connected to the Argus II provided thermal or distance-filtered video stimulation. Four participants used the thermal camera to locate a person and the distance filter to navigate a hallway with obstacles. The thermal camera allowed for finding a target person in 99% of trials, while unfiltered video led to confusion with other objects and a success rate of only 55% ([Formula: see text]). Similarly, the distance filter enabled participants to detect and avoid 88% of obstacles by removing background clutter, whereas unfiltered video resulted in a detection rate of only 10% ([Formula: see text]). For any given elapsed time, the success rate with filtered video was higher than with unfiltered video. After 90 s, participants' success rate reached above 50% with filtered video and 24% and 3% with normal camera in the first and second tasks, respectively. Despite individual variations, all participants showed significant improvement when using the thermal and distance filters compared to unfiltered video. Adding a thermal and distance filter to a visual prosthesis system can enhance the performance of mobility activities by removing clutter in the background, showing people and warm objects with the thermal camera, or nearby obstacles with the distance filter.

Add-on optical mask to declutter visual information based on depth for visual prostheses.

One of the challenges in retinal and cortical visual prostheses is decluttering the visual information of the scene. Current device use brightness information, therefore, bright faraway targets can dominate the perception and nearby obstacles may be missed. Therefore, the aim is to ensure that visual information of interest is delivered to the implant. To achieve this, it is essential to obtain information regarding the distance of each object in a scene. Owing to limited power requirements, it is problematic to use an active depth sensor such as Lidar, which requires strong illumination. specifically, in outdoor environments. Depth sensors based on stereo imaging require heavy computational resources, which is also problematic in wearable devices. There is a need for simple passive and robust depth sensor. Herein, we demonstrate the usability of an optical mask that can be placed in front of any RGB camera to create a depth sensor. The mask introduces chromatic aberrations and artificially separates the colors by creating pre-defined phase errors that shift the focal plane as a function of the wavelength. We designed and fabricated a mask that, in combination with the lens of the camera, allows each color to be in focus at a different distance. The red channel produces a focused image for objects that are in the near range, the green channel focuses objects at the mid-range, and the blue channel focuses distant objects. Because realistic targets contain radiation at all wavelengths, they appear in focus at the color channel that matches their distance. Finally, a standard deviation image filter is used to extract only the information that is in focus and to convert the color information to depth information. Clinical Relevance-The proposed method can enhance the usability and functionality of current and future visual prostheses, specifically in outdoor environments, by providing depth information using a passive miniature optical device.

Sequential epiretinal stimulation improves discrimination in simple shape discrimination tasks only.

Objective. Electrical stimulation of the retina can elicit flashes of light called phosphenes, which can be used to restore rudimentary vision for people with blindness. Functional sight requires stimulation of multiple electrodes to create patterned vision, but phosphenes tend to merge together in an uninterpretable way. Sequentially stimulating electrodes in human visual cortex has recently demonstrated that shapes could be 'drawn' with better perceptual resolution relative to simultaneous stimulation. The goal of this study was to evaluate if sequential stimulation would also form clearer shapes when the retina is the neural target.Approach. Two human participants with retinitis pigmentosa who had Argus®II epiretinal prostheses participated in this study. We evaluated different temporal parameters for sequential stimulation and performed phosphene shape mapping and forced choice discrimination tasks. For the discrimination tasks, performance was compared between stimulating electrodes simultaneously versus sequentially.Main results. Phosphenes elicited by different electrodes were reported as vastly different shapes. For sequential stimulation, the optimal pulse train duration was 200 ms when stimulating at 20 Hz and the optimal gap interval was tied between 0 and 50 ms. Sequential electrode stimulation outperformed simultaneous stimulation in simple discrimination tasks, in which shapes were created by stimulating 3-4 electrodes, but not in more complex discrimination tasks involving ≥5 electrodes. The efficacy of sequential stimulation depended strongly on selecting electrodes that elicited phosphenes with similar shapes and sizes.Significance. An epiretinal prosthesis can produce coherent simple shapes with a sequential stimulation paradigm, which can be used as rudimentary visual feedback. However, success in creating more complex shapes, such as letters of the alphabet, is still limited. Sequential stimulation may be most beneficial for epiretinal prostheses in simple tasks, such as basic navigation, rather than complex tasks such as novel object identification.

Glow in the dark: Using a heat-sensitive camera for blind individuals with prosthetic vision.

To date, retinal implants are the only available treatment for blind individuals with retinal degenerations such as retinitis pigmentosa. Argus II is the only visual implant with FDA approval, with more than 300 users worldwide. Argus II stimulation is based on a grayscale image coming from a head-mounted visible-light camera. Normally, the 11°×19° field of view of the Argus II user is full of objects that may elicit similar phosphenes. The prosthesis cannot meaningfully convey so much visual information, and the percept is reduced to an ambiguous impression of light. This study is aimed at investigating the efficacy of simplifying the video input in real-time using a heat-sensitive camera. Data were acquired from four Argus II users in 5 stationary tasks with either hot objects or human targets as stimuli. All tasks were of m-alternative forced choice design where precisely one of the m≥2 response alternatives was defined to be "correct" by the experimenter. To compare performance with heat-sensitive and normal cameras across all tasks, regardless of m, we used an extension of signal detection theory to latent variables, estimating person ability and item difficulty in d' units. Results demonstrate that subject performance was significantly better across all tasks with the thermal camera compared to the regular Argus II camera. The future addition of thermal imaging to devices with very poor spatial resolution may have significant real-life benefits for orientation, personal safety, and social interactions, thereby improving quality of life.

Eye movements and the perceived location of phosphenes generated by intracranial primary visual cortex stimulation in the blind.

BACKGROUND: Restoring sight for the blind using electrical stimulation of the visual pathways is feasible but demands an understanding of the spatial mapping of the visual world at the site of targeted stimulation, whether in the retina, thalamus, or cortex. While a visual cortex stimulator can bypass the eye and create visual percepts, there is an inherent dissociation between this stimulation and eye movements. It is unknown whether and how robustly the brain maintains the oculomotor circuitry in patients with bare- or no-light perception. OBJECTIVE: To critically and quantitatively evaluate the effect of eye movements have on phosphene locations elicited by cortical stimulation that bypasses the eyes in order to restore sight in blind subjects. METHODS: The NeuroPace Responsive Neurostimulator (RNS) and the Orion visual cortical prosthesis devices were used to electrically stimulate the visual cortex of blind subjects with bare or no light perception. Eye positions were recorded synchronized with stimulation and the location of the percepts were measured using a handheld marker. RESULTS: The locations of cortical stimulation-evoked percepts are shifted based on the eye position at the time of stimulation. Measured responses can be remapped based on measured eye positions to determine the retinotopic locations associated with the implanted electrodes, with remapped responses having variance limited by pointing error. CONCLUSIONS: Eye movements dominate the perceived location of cortical stimulation-evoked phosphenes, even after years of blindness. By accounting for eye positions, we can mimic retinal mapping as in natural sight.

Synchronization of a Removable Optical Element with an Eye Tracker: Test Case for Heterophoria Measurement.

Purpose: Heterophoria describes the deviation of the optical axes in the absence of binocular fusion. Eye trackers (ET) can provide an objective assessment but are not broadly used clinically. We examined the feasibility of combining an infrared (IR) pass-filter, IR detector, and an off-the-shelf ET. The proposed setup was validated against the broadly used cover test (CT). Furthermore, the setup was used to examine whether testing conditions can affect the measurements. Methods: An IR detector was attached to a handheld IR-pass filter that blocks visible light to provide occlusion while passing IR light for eye tracking. The detector senses the IR illumination of the eye tracker, creating a recordable signal of the occluder position synchronized with eye positions acquired by the SMI Red250 tracker. The mean of three measurements of each condition, three versus ten seconds occlusion, the occluded eye, and ET versus CT results were compared using the Wilcoxon test, correlation and Bland and Altman plots. Differences between measurements that were within 2Δ were considered clinically insignificant. Results: Thirty normally-sighted subjects (mean age 24.50 ± 2.20, range 20-28) with heterophoria ranging between 14Δ exophoria and 4Δ esophoria were recruited. There was no significant difference between the occluded eyes. However, there was a difference between 3 and 10 seconds' cover duration. The CT data were more similar to the 10 seconds cover duration, although differences were less than the clinical resolution of 2Δ. Conclusions: An inexpensive off-the-shelf ET can be used to measure heterophoria with controlled testing parameters. Translational Relevance: Our study demonstrated a robust technique for synchronization of an optical element such as an IR cover, with an off-the-shelf commercial eye tracker. The synchronization of optical elements with eye tracking, which has been described here for heterophoria, can be adapted for other clinical measurements.

The use of handheld marker to calibrate a field-programmable gate array based eye tracker for artificial vision system.

Tracking the eye of a blind patient can enhance the usability of an artificial vision system. In systems where the sensing element, i.e. the scene camera that captures the visual information, is mounted on the patient's head, the user must use head scanning in order to steer the line of sight of the implant to the region of interest. Integrating an eye tracker in the prosthesis will enable scanning using eye movements. The eye position will set the region of interest within the wide field-of-view of the scene camera. An essential requirement of an eye tracker is the need to calibrate it. Obviously, off-the-shelf calibration methods that require looking at known points in space cannot be used with blind users.Here we tested the feasibility of calibrating the eye-tracker based on pupil position and the location of the percept reported by the implant recipient, using a handheld marker. Pupil positions were extracted using custom image processing in a field-programmable-gate-array built into a glasses-mounted eye tracker. In the calibration process, electrodes were directly stimulated and the subject reported the location of the percept using a handheld marker. Linear regression was used to extract the transfer function from pupil position to gaze direction in the coordinates of the scene camera.In using the eye tracker with the proposed calibration method, patients demonstrated improved precision on a localization task with corresponding reduction of head movements.

Improved mobility performance with an artificial vision therapy system using a thermal sensor.

OBJECTIVE: To evaluate the benefit of integrating thermal imaging into an artificial vision therapy system, the Argus II retinal prosthesis, in simplifying a complex scene and improving mobility performance in the presence of other persons. APPROACH: Four Argus II retinal implant users were evaluated on two tasks: to locate and approach target persons in a booth, and to navigate a hallway while avoiding people. They completed the tasks using both the original Argus II system (the 'Argus II camera') and a thermal-integrated Argus II system (the 'thermal camera'). The safety and efficiency of their navigation were evaluated by their walking speed, navigation errors, and the number of collisions. MAIN RESULTS: Navigation performance was significantly superior when using the thermal camera compared to using the Argus II camera, including 75% smaller angle of deviation (p < 0.001), 48% smaller error of distance (p < 0.05), and 30% fewer collisions (p < 0.05). The thermal camera also brought the additional benefit of allowing the participants to perform the task in the dark as efficiently as in the light. More importantly, these benefits did not come at a cost of reduced walking speed. SIGNIFICANCE: Using the thermal camera in the Argus II system, compared to a visible-light camera, could improve the wearers' navigation performance by helping them better approach or avoid other persons. Adding the thermal camera to future artificial vision therapy systems may complement the visible-light camera and improve the users' mobility safety and efficiency, enhancing their quality of life.

Prosthetic Visual Performance Using a Disparity-Based Distance-Filtering System.

Purpose: At present, Argus II is the only retinal prosthesis approved by the US Food and Drug Administration that induces visual percepts in people who are blind from end-stage outer retinal degenerations such as retinitis pigmentosa. It has been shown to work well in sparse, high-contrast settings, but in daily practice visual performance with the device is likely to be hampered by the cognitive load presented by a cluttered real-world environment. In this study, we investigated the effect of a stereo-disparity-based distance-filtering system on four experienced Argus II users for a range of tasks: object localization, depth discrimination, orientation and size discrimination, and people detection and direction of motion. Methods: Functional vision was assessed in a semicontrolled setup using unfiltered (normal camera) and distance-filtered (stereo camera) imagery. All tasks were forced choice designs and an extension of signal detection theory to latent (unobservable) variables was used to analyze the data, allowing estimation of person ability (person measures) and task difficulty (item measures) on the same axis. Results: All subjects performed better with the distance filter compared with the unfiltered image (P  < 0.001 on all tasks except localization). Conclusions: Our results show that depth filtering using a disparity-based algorithm has significant benefits for people with Argus II implants. Translational Relevance: The improvement in functional vision with the distance filter found in this study may have an important impact on vision rehabilitation and quality of life for people with visual prostheses and ultra low vision.

Improved localisation and discrimination of heat emitting household objects with the artificial vision therapy system by integration with thermal sensor.

AIM: To demonstrate the potential clinically meaningful benefits of a thermal camera integrated with the Argus II, an artificial vision therapy system, for assisting Argus II users in localising and discriminating heat-emitting objects. METHODS: Seven blind patients implanted with Argus II retinal prosthesis participated in the study. Two tasks were investigated: (1) localising up to three heat-emitting objects by indicating the location of the objects and (2) discriminating a specific heated object out of three presented on a table. Heat-emitting objects placed on a table included a toaster, a flat iron, an electric kettle, a heating pad and a mug of hot water. Subjects completed the two tasks using the unmodified Argus II system with a visible-light camera and the thermal camera-integrated Argus II. RESULTS: Subjects more accurately localised heated objects displayed on a table (p=0.011) and discriminated a specific type of object (p=0.005) presented with the thermal camera integrated with the Argus II versus the unmodified Argus II camera. CONCLUSIONS: The thermal camera integrated with the artificial vision therapy system helps users to locate and differentiate heat-emitting objects more precisely than a visible light sensor. The integration of the thermal camera with the Argus II may have significant benefits in patients' daily life.

Enhanced depth imaging in swept-source optical coherence tomography: Improving visibility of choroid and sclera, a masked study.

PURPOSE: To compare enhanced depth imaging in swept-source optical coherence tomography and non-enhanced depth imaging optical coherence tomography in their ability to capture choroidal and scleral details. METHODS: Averaged foveal B-Scans were obtained from 40 eyes of 20 healthy volunteers by swept-source optical coherence tomography with and without enhanced depth imaging. Visibility and contrast of vascular details within the choroid, choroidoscleral junction, and sclera were evaluated by masked readers using an ordinal scoring scale. Outcomes were analyzed using the Wilcoxon signed rank-sum test. RESULTS: Visibility of the choroidal vascular details (Z = 5.94, p < .001), the choroidoscleral junction (Z = 5.85, p < .001), and the sclera (Z = 6.80, p < .001) was significantly higher with enhanced depth imaging than with non-enhanced depth imaging swept-source optical coherence tomography. Similarly, image contrast was significantly higher with enhanced depth imaging than with non-enhanced depth imaging swept-source optical coherence tomography for the choroidal vascular details (Z = 9.47, p < .001), for the choroidoscleral junction (Z = 9.28, p < .001), and for the sclera (Z = 9.42, p < .001). CONCLUSION: Enhanced depth imaging applied to swept-source optical coherence tomography-averaged foveal B-scans enhances visualization of the choroidal details, of the choroidoscleral junction, and of the sclera. This novel modality can easily be implemented in clinics and could improve our understanding of conditions involving the choroid or the sclera.

Trade-Off Between Field-of-View and Resolution in the Thermal-Integrated Argus II System.

PURPOSE: To investigate the effect of a wider field-of-view (FOV) of a retinal prosthesis on the users' performance in locating objects. METHODS: One female and four male subjects who were blind due to end-stage retinitis pigmentosa and had been implanted with the Argus II retinal prosthesis participated (aged 63.4 ± 15.4). Thermal imaging was captured by an external sensor and converted to electrical stimulation to the retina. Subjects were asked to localize and to reach for heat-emitting objects using two different FOV mappings: a normal 1:1 mapping (no zoom) that provided 18° × 11° FOV and a 3:1 mapping (zoom out) that provided 49° × 35° FOV. Their accuracy and response time were recorded. RESULTS: Subjects were less accurate and took longer to complete the tasks with zoom out compared to no zoom. Localization accuracy decreased from 83% (95% confidence interval, 75%, 90%) with no zoom to 76% (67%, 83%) with zoom out (P = 0.07). Reaching accuracy differed between the two mappings only in one subject. Response time increased by 43% for the localization task (24%, 66%; P < 0.001) and by 20% for the reaching task (0%, 45%; P = 0.055). CONCLUSIONS: Argus II wearers can efficiently find heat-emitting objects with the default 18° × 11° FOV of the current Argus II. For spatial localization, a higher spatial resolution may be preferred over a wider FOV. TRANSLATIONAL RELEVANCE: Understanding the trade-off between FOV and spatial resolution in retinal prosthesis users can guide device optimization.

Head-up tilt table testing in syncope: safety and efficiency of isosorbide versus isoproterenol in pediatric population.

BACKGROUND: The aim of this study was to compare the diagnostic value and safety of sublingual isosorbid dinitrate (ISDN) with intravenous isoproterenol (ISOP) during head-up tilt table testing (HUTT) in pediatric patients with suspected neurocardiogenic syncope. METHODS: One hundred thirty-six consecutive pediatric patients complaining of presyncope or syncope were submitted to HUTT for the first time. Those who did not develop syncope or presyncope during passive HUTT for 20 minutes underwent repeated HUTT with either 1.25 to 2.5 mg sublingual ISDN or intravenous ISOP (1-3 mug/min) for 20 minutes. There were 54 boys and 82 girls, aged 10 to 18 years with an average of 15.5 +/- 2.4 years and a median of 16 years. Among the patients with cardioinhibition or mixed responses, the severity of the bradyarrhythmia was scored 1 to 3 (restoration of effective rhythm within 10 seconds, 10-20 seconds, and >20 seconds while back to supine position, respectively). RESULTS: During the passive period, 24 (17.6%) of 136 patients had a positive response to HUTT. Syncope was observed in another 44 patients during either ISDN or ISOP period (14/58 [24.1%] and 30/54 [55.5%] with ISDN vs ISOP, respectively, P < .05). The time to symptoms was shorter with both ISDN and ISOP compared with passive period (6.5 +/- 2.9, 6.3 +/- 5.9, and 10.3 +/- 4.4, minutes, respectively, P < .05). The severity score for cardioinhibition response was significantly higher with ISDN compared with the passive period and ISOP (2 +/- 0.8, 1.25 +/- 0.45, and 1.26 +/- 0.45, respectively, P < .01). CONCLUSIONS: Sublingual ISDN is less sensitive and less safe compared to intravenous ISOP in assessing pediatric age patients with suspected neurocardiogenic syncope and with a negative result in tilt test without provocation. The simplicity of ISDN use should be weighed against the risk of longer symptoms with ISDN.

Eye Movement Control in the Argus II Retinal-Prosthesis Enables Reduced Head Movement and Better Localization Precision.

Purpose: Visual scanning by sighted individuals is done using eye and head movements. In contrast, scanning using the Argus II is solely done by head movement, since eye movements can introduce localization errors. Here, we tested if a scanning mode utilizing eye movements increases visual stability and reduces head movements in Argus II users. Methods: Eye positions were measured in real-time and were used to shift the region of interest (ROI) that is sent to the implant within the wide field of view (FOV) of the scene camera. Participants were able to use combined eye-head scanning: shifting the camera by moving their head and shifting the ROI within the FOV by eye movement. Eight blind individuals implanted with the Argus II retinal prosthesis participated in the study. A white target appeared on a touchscreen monitor and the participants were instructed to report the location of the target by touching the monitor. We compared the spread of the responses, the time to complete the task, and the amount of head movements between combined eye-head and head-only scanning. Results: All participants benefited from the combined eye-head scanning mode. Better precision (i.e., narrower spread of the perceived location) was observed in six out of eight participants. Seven of eight participants were able to adopt a scanning strategy that enabled them to perform the task with significantly less head movement. Conclusions: Integrating an eye tracker into the Argus II is feasible, reduces head movements in a seated localization task, and improves pointing precision.

Admission blood glucose level and mortality among hospitalized nondiabetic patients with heart failure.

BACKGROUND: The significance of admission blood glucose level in nondiabetic patients with heart failure (HF) is unknown. We examined the possible association between admission glucose levels and outcome in a large cohort of hospitalized patients with HF. METHODS: We analyzed the data of 4102 patients with HF, who were hospitalized during a prospective national survey. The present study focuses on a subgroup of 1122 nondiabetic patients with acute HF who were admitted because of acute HF or exacerbation of chronic HF. RESULTS: In-hospital mortality was twice as high in patients with admission blood glucose levels in the third tertile (7.2%) compared with the first (3%) and second (4%) tertiles (P = .02). Furthermore, mortality risk was correlated with admission glucose levels; each 18-mg/dL (1-mmol/L) increase in glucose level was associated with a 31% increased risk of in-hospital mortality (adjusted odds ratio, 1.31; 95% confidence interval, 1.10-1.57; P = .003) and a 12% increase in 60-day mortality (adjusted hazard ratio, 1.12; 95% confidence interval, 1.01-1.25; P = .04). Admission blood glucose levels remained an independent predictor of in-hospital and 60-day mortality even after the exclusion of 315 patients (28%) with acute myocardial infarction and HF. The 6- and 12-month mortality rates were similar in patients with and without abnormal admission blood glucose levels. CONCLUSIONS: Elevated admission blood glucose levels are associated with increased in-hospital and 60-day mortality, but not 6-month or 1-year mortality, in nondiabetic patients hospitalized because of HF.

Retinotopic to Spatiotopic Mapping in Blind Patients Implanted With the Argus II Retinal Prosthesis.

Purpose: To quantify the precision of mapping from retinotopic (retina-centered) to spatiotopic (world-centered) coordinates in blind humans implanted with a retinal prosthesis device. Additionally, to demonstrate that an eye tracker can be calibrated on sightless patients based on the percept from a visual implant. Methods: We directly activated epiretinal electrodes to create retinotopic stimuli and recorded the location of the percept at world-based coordinates. In contrast to normal Argus II use where stimulation is a function of the captured scene's image, in this research we directly controlled the waveform in each electrode and measured the percept's location using a trackable handheld marker. For eye tracking, pupil images were recorded with a timestamp synchronized to the stimulation and marker positions. Results: Remapping of the measured world locations to the position of the electrodes on the retina is feasible by accounting for eye orientation at the onset of stimulation. Transformation of pupil images to the eye's orientation (i.e., eye tracker calibration) can be done by solving for the variables that minimize the spread of the remapped retinal electrode locations. After mapping to retinal coordinates based on eye positions, the measured precision of pointing was 2° to 3°, which is comparable to open-loop pointing in sighted individuals. Conclusions: The brain accurately maps the artificial vision induced by a retinal prosthesis based on instantaneous gaze position. Remapping based on eye position is feasible and will increase visual stability in prosthetic vision.

Long-Term Effect of Endothelin Receptor Antagonism With Bosentan on the Morbidity and Mortality of Patients With Severe Chronic Heart Failure: Primary Results of the ENABLE Trials.

OBJECTIVES: The objective of this clinical trial was to evaluate the long-term effect of endothelin receptor antagonism with bosentan on the morbidity and mortality of patients with severe chronic heart failure. BACKGROUND: Endothelin may play a role in heart failure, but short-term clinical trials with endothelin receptor antagonists have reported disappointing results. Long-term trials are lacking. METHODS: In 2 identical double-blind trials, we randomly assigned 1,613 patients with New York Heart Association functional class IIIb to IV heart failure and an ejection fraction <35% to receive placebo or bosentan (target dose 125 mg twice daily) for a median of 1.5 years. The primary outcome for each trial was clinical status at 9 months (assessed by the hierarchical clinical composite); the primary outcome across the 2 trials was death from any cause or hospitalization for heart failure. RESULTS: Bosentan did not influence clinical status at 9 months in either trial (p = 0.928 and p = 0.263). In addition, 321 patients in the placebo group and 312 patients in the bosentan group died or were hospitalized for heart failure (hazard ratio [HR]: 1.01; 95% confidence interval [CI]: 0.86 to 1.18; p = 0.90). The bosentan group experienced fluid retention within the first 2 to 4 weeks, as evidenced by increased peripheral edema, weight gain, decreases in hemoglobin, and an increased risk of hospitalization for heart failure, despite intensification of background diuretics. During follow-up, 173 patients died in the placebo group and 160 patients died in the bosentan group (HR: 0.94; 95% CI: 0.75 to 1.16). About 10% of the bosentan group showed meaningful increases in hepatic transaminases, but none had acute or chronic liver failure. CONCLUSIONS: Bosentan did not improve the clinical course or natural history of patients with severe chronic heart failure and but caused early and important fluid retention.

Evidence for ocular motor deficits in developmental dyslexia: application of the double-step paradigm.

PURPOSE: Dyslexia is a language-based learning disability characterized by difficulties with reading, spelling, and writing. Persons with dyslexia often have deficits in processing rapid temporal sensory information. There is also evidence of sensorimotor deficits in persons with dyslexia. Whether these deficits include ocular motor problems is still an open question. Some previous studies have shown an increased saccadic latency in dyslexics, whereas others have not reproduced this finding. The purpose of the present study was to investigate saccadic latency in young adults with dyslexia during the double-step paradigm, a task that requires rapid sequential visual information processing and saccade generation. The study hypothesis was that dyslexics have a longer saccadic latency in the second orthogonal saccade, a task that nondyslexics parallel process and perform rapidly. METHODS: Eight students with dyslexia and eight age-matched control subjects participated in the study. Their eye movements were monitored with the scleral search coil technique in simple saccade trials and in the double-step paradigm. The second saccade was either orthogonal or colinear to the first. Intersaccadic interval and latency were calculated for the second saccade. RESULTS: No difference in saccadic latency was found for colinear second saccades; however, dyslexics had significantly longer latencies for orthogonal second saccades. This included a subset of subjects who had longer latencies for orthogonal than for colinear saccades. CONCLUSIONS: The findings indicate that under certain conditions, when the demand for rapid visual information processing is high and a rapid saccade sequence is required, some persons with dyslexia show ocular motor deficits manifested by longer saccadic latencies.

Eye movements as a marker for visual prosthesis spatial mapping - A feasibility study using a blind patient implanted with the Argus II retinal prosthesis.

Spatial mapping, the location in space of a perceived location due to an implanted electrode's electrical stimulation is important in the design of visual prostheses. Generally, a visual prosthesis system consists of an implanted electrode array, an external camera that acquires the image, and a transmitter that sends the information to the implanted electrodes. In cortical visual implant, the layout of the implanted array in most cases does not match the retinotopic map and it is necessary to find the location of the percept of each electrode in world coordinates. Herein, we show the feasibility of using eye movements as markers to construct the spatial map of the implanted electrodes. A blind patient implanted with the Argus II retinal prosthesis was instructed to conduct an eye movement to the location of a percept generated by an electrical stimulation at different retinal locations. By analyzing the eye movements triggered by the electrical stimulation, we were able to reconstruct the spatial map of the electrodes. Our experiment demonstrates that a blind person still maintains control of eye movements that can be used to map the percept location of the implanted electrodes.