Functional performance of a vibrotactile sensory substitution device in people with profound vision loss.

SIGNIFICANCE: This study has shown a vibrotactile sensory substitution device (SSD) prototype, VibroSight, has the potential to improve functional outcomes (i.e., obstacle avoidance, face detection) for people with profound vision loss, even with brief familiarization (<20 minutes). PURPOSE: Mobility aids such as long canes are still the mainstay of support for most people with vision loss, but they do have limitations. Emerging technologies such as SSDs are gaining widespread interest in the low vision community. The aim of this project was to assess the efficacy of a prototype vibrotactile SSD for people with profound vision loss in the face detection and obstacle avoidance tasks. METHODS: The VibroSight device was tested in a movement laboratory setting. The first task involved obstacle avoidance, in which participants were asked to walk through an obstacle course. The second was a face detection task, in which participants were asked to step toward the first face they detected. Exit interviews were also conducted to gather user experience data. Both people with low vision (n = 7) and orientation and mobility instructors (n = 4) completed the tasks. RESULTS: In obstacle avoidance task, participants were able to use the device to detect (p<0.001) and avoid (p<0.001) the obstacles within a significantly larger range, but were slower (p<0.001), when compared with without the device. In face detection task, participants demonstrated a great level of accuracy, precision, and sensitivity when using the device. Interviews revealed a positive user experience, although participants identified that they would require a lighter and compact design for real-world use. CONCLUSIONS: Overall, the results verified the functionality of vibrotactile SSD prototype. Further research is warranted to evaluate the user performance after an extended training program and to add new features, such as object recognition software algorithms, into the device.

Proportional recovery after stroke depends on corticomotor integrity.

OBJECTIVE: For most patients, resolution of upper limb impairment during the first 6 months poststroke is 70% of the maximum possible. We sought to identify candidate mechanisms of this proportional recovery. We hypothesized that proportional resolution of upper limb impairment depends on ipsilesional corticomotor pathway function, is mirrored by proportional recovery of excitability in this pathway, and is unaffected by upper limb therapy dose. METHODS: Upper limb impairment was measured in 93 patients at 2, 6, 12, and 26 weeks after first-ever ischemic stroke. Motor evoked potentials (MEPs) and motor threshold were recorded from extensor carpi radialis using transcranial magnetic stimulation, and fractional anisotropy (FA) in the posterior limbs of the internal capsules was determined with diffusion-weighted magnetic resonance imaging. RESULTS: Initial impairment score, presence of MEPs and FA asymmetry were the only predictors of impairment resolution, indicating a key role for corticomotor tract function. By 12 weeks, upper limb impairment resolved by 70% in patients with MEPs regardless of their initial impairment, and ipsilesional rest motor threshold also resolved by 70%. Resolution of impairment was insensitive to upper limb therapy dose. INTERPRETATION: These findings indicate that upper limb impairment resolves by 70% of the maximum possible, regardless of initial impairment, but only for patients with intact corticomotor function. Impairment resolution seems to reflect spontaneous neurobiological processes that involve the ipsilesional corticomotor pathway. A better understanding of these mechanisms could lead to interventions that increase resolution of impairment above 70%.

Bilateral priming accelerates recovery of upper limb function after stroke: a randomized controlled trial.

BACKGROUND AND PURPOSE: The ability to live independently after stroke depends on the recovery of upper limb function. We hypothesized that bilateral priming with active-passive movements before upper limb physiotherapy would promote rebalancing of corticomotor excitability and would accelerate upper limb recovery at the subacute stage. METHODS: A single-center randomized controlled trial of bilateral priming was conducted with 57 patients randomized at the subacute stage after first-ever ischemic stroke. The PRIMED group made device-assisted mirror symmetrical bimanual movements before upper limb physiotherapy, every weekday for 4 weeks. The CONTROL group was given intermittent cutaneous electric stimulation of the paretic forearm before physiotherapy. Assessments were made at baseline, 6, 12, and 26 weeks. The primary end point was the proportion of patients who reached their plateau for upper limb function at 12 weeks, measured with the Action Research Arm Test. RESULTS: Odds ratios indicated that PRIMED participants were 3× more likely than controls to reach their recovery plateau by 12 weeks. Intention-to-treat and per-protocol analyses showed a greater proportion of PRIMED participants achieved their plateau by 12 weeks (intention to treat, χ2=4.25; P=0.039 and per protocol, χ2=3.99; P=0.046). ANOVA of per-protocol data showed PRIMED participants had greater rebalancing of corticomotor excitability than controls at 12 and 26 weeks and interhemispheric inhibition at 26 weeks (all P<0.05). CONCLUSIONS: Bilateral priming accelerated recovery of upper limb function in the initial weeks after stroke. CLINICAL TRIAL REGISTRATION: URL: http://www.anzctr.org.au. Unique identifier: ANZCTR1260900046822.

Post-Saccadic Oscillations of the Pupil and Lens Reduce Fixation Stability in Retinitis Pigmentosa and Age-Related Macular Degeneration.

Purpose: Post-saccadic oscillations (PSOs) reflect movements of gaze that result from motion of the pupil and lens relative to the eyeball rather than eyeball rotations. Here, we analyzed the characteristics of PSOs in subjects with age-related macular degeneration (AMD), retinitis pigmentosa (RP), and normal vision (NV). Our aim was to assess the differences in PSOs between people with vision loss and healthy controls because PSOs affect retinal image stability after each saccade. Methods: Participants completed a horizontal saccade task and their gaze was measured using a pupil-based eye tracker. Oscillations occurring in the 80 to 200 ms post-saccadic period were described with a damped oscillation model. We compared the amplitude, decay time constant, and frequency of the PSOs for the three different groups. We also examined the correlation between these PSO parameters and the amplitude, peak velocity, and final deceleration of the preceding saccades. Results: Subjects with vision loss (AMD, n = 6, and RP, n = 5) had larger oscillation amplitudes, longer decay constants, and lower frequencies than subjects with NV (n = 7). The oscillation amplitudes increased with increases in saccade deceleration in all three groups. The other PSO parameters, however, did not show consistent correlations with either saccade amplitude or peak velocity. Conclusions: Post-saccadic fixation stability in AMD and RP is reduced due to abnormal PSOs. The differences with respect to NV are not due to differences in saccade kinematics, suggesting that anatomic and neuronal variations affect the suspension of the iris and the lens in the patients' eyes.

Cutaneous anesthesia of the forearm enhances sensorimotor function of the hand.

Temporary deafferentation of the upper limb, with ischemic or anesthetic nerve block, has rapid effects on sensorimotor cortex. Cutaneous anesthesia of the forearm has recently been found to improve sensory and motor function of the paretic hand in chronic stroke patients. However, the neurophysiological mechanisms are unknown. The aim of this study was to investigate the behavioral and neurophysiological effects of cutaneous forearm anesthesia. Twenty-five healthy right-handed adults participated in this double-blind, randomized study. Participants completed two sessions, with either a topical anesthesia cream (EMLA) or placebo applied to their left forearm in each session. Thresholds for cutaneous sensation and spatial acuity of the left hand were measured before and after the intervention. Transcranial magnetic stimulation was used to measure corticomotor excitability and short-interval intracortical inhibition in the left first dorsal interosseous and abductor digiti minimi muscles before and after the intervention. Manual dexterity was assessed with the grooved pegboard task after the intervention in each session. Left-hand dexterity improved to a greater extent after treatment with EMLA than placebo, and this was related to improved spatial acuity at the fingertips. Corticomotor excitability remained stable, and short-interval intracortical inhibition increased after EMLA treatment. We have confirmed and extended previous reports that cutaneous forearm anesthesia results in improved spatial acuity and manual dexterity of the ipsilateral hand. The neurophysiological mechanisms involve an increase in intracortical inhibition, which may improve the precision of voluntary movement. These results lend support to the therapeutic application of EMLA in movement rehabilitation.

The Saccade Main Sequence in Patients With Retinitis Pigmentosa and Advanced Age-Related Macular Degeneration.

Purpose: Most eye-movement studies in patients with visual field defects have examined the strategies that patients use while exploring a visual scene, but they have not investigated saccade kinematics. In healthy vision, saccade trajectories follow the remarkably stereotyped "main sequence": saccade duration increases linearly with saccade amplitude; peak velocity also increases linearly for small amplitudes, but approaches a saturation limit for large amplitudes. Recent theories propose that these relationships reflect the brain's attempt to optimize vision when planning eye movements. Therefore, in patients with bilateral retinal damage, saccadic behavior might differ to optimize vision under the constraints imposed by the visual field defects. Methods: We compared saccadic behavior of patients with central vision loss, due to age-related macular degeneration (AMD), and patients with peripheral vision loss, due to retinitis pigmentosa (RP), to that of controls with normal vision (NV) using a horizontal saccade task. Results: Both patient groups demonstrated deficits in saccade reaction times and target localization behavior, as well as altered saccade kinematics. Saccades were generally slower and the shape of the velocity profiles were often atypical, especially in the patients with RP. In the patients with AMD, the changes were far less dramatic. For both groups, saccade kinematics were affected most when the target was in the subjects' blind field. Conclusions: We conclude that defects of the central and peripheral retina have distinct effects on the saccade main sequence, and that visual inputs play an important role in planning the kinematics of a saccade.

Estimating Phosphene Locations Using Eye Movements of Suprachoroidal Retinal Prosthesis Users.

Purpose: Accurate mapping of phosphene locations from visual prostheses is vital to encode spatial information. This process may involve the subject pointing to evoked phosphene locations with their finger. Here, we demonstrate phosphene mapping for a retinal implant using eye movements and compare it with retinotopic electrode positions and previous results using conventional finger-based mapping. Methods: Three suprachoroidal retinal implant recipients (NCT03406416) indicated the spatial position of phosphenes. Electrodes were stimulated individually, and the subjects moved their finger (finger based) or their eyes (gaze based) to the perceived phosphene location. The distortion of the measured phosphene locations from the expected locations (retinotopic electrode locations) was characterized with Procrustes analysis. Results: The finger-based phosphene locations were compressed spatially relative to the expected locations all three subjects, but preserved the general retinotopic arrangement (scale factors ranged from 0.37 to 0.83). In two subjects, the gaze-based phosphene locations were similar to the expected locations (scale factors of 0.72 and 0.99). For the third subject, there was no apparent relationship between gaze-based phosphene locations and electrode locations (scale factor of 0.07). Conclusions: Gaze-based phosphene mapping was achievable in two of three tested retinal prosthesis subjects and their derived phosphene maps correlated well with the retinotopic electrode layout. A third subject could not produce a coherent gaze-based phosphene map, but this may have revealed that their phosphenes were indistinct spatially. Translational Relevance: Gaze-based phosphene mapping is a viable alternative to conventional finger-based mapping, but may not be suitable for all subjects.

Interobserver Agreement of Electrode to Retina Distance Measurements in a Second-Generation (44-Channel) Suprachoroidal Retinal Prosthesis.

Purpose: The electrode to retina (ER) distance is an important contributory factor to the safety and efficacy of a suprachoroidal retinal prosthesis. Measuring ER distance may be performed by different observers during multisite studies. The aim of this study was to assess the interobserver agreement in measuring ER distance. Methods: Three independent, trained observers measured ER distance from the center of each suprachoroidal electrode to the inner retinal pigment epithelium in spectral-domain optical coherence tomography (SD-OCT) B-scans. A total of 121 ER distance measurements from 77 B-scans collected over 5 months from one subject implanted with a second-generation 44-channel suprachoroidal retinal prosthesis (NCT03406416) were made by each observer. Results: ER distance ranged from 208 to 509 µm. Pearson's correlation coefficient (ρ) showed agreement of 0.99 (95% confidence interval [CI] = 0.98-0.99) in measuring ER for each pairwise comparison. The mean difference in ER distance between observers ranged from 2.4 to 6.4 µm with pairwise limits of agreement (95% CI) of ±20 µm (5.5% of mean). Intraclass correlation coefficient (ICC) showed agreement of 0.98 (95% CI = 0.97-0.99) between observers. Conclusions: There is high agreement in measuring ER distances for suprachoroidal retinal prostheses using our systematic approach between multiple, trained observers, supporting the use of a single observer for each image. Translational Relevance: High interobserver agreement outcomes indicate that multiple, trained observers can be used to take ER measurements across different images in suprachoroidal retinal prosthesis studies. This improves multisite study efficiency and gives confidence in interpreting results relating to the safety and efficacy of suprachoroidal retinal prostheses.

A Second-Generation (44-Channel) Suprachoroidal Retinal Prosthesis: Long-Term Observation of the Electrode-Tissue Interface.

Purpose: To report the long-term observations of the electrode-tissue interface and perceptual stability in humans after chronic stimulation with a 44-channel suprachoroidal retinal implant. Methods: Four subjects (S1-4) with end-stage retinitis pigmentosa received the implant unilaterally (NCT03406416). Electrode impedances, electrode-retina distance (measured using optical coherence tomography imaging), and perceptual thresholds were monitored up to 181 weeks after implantation as the subjects used the prosthesis in the laboratory and in daily life. Stimulation charge density was limited to 32 µC/cm2 per phase. Results: Electrode impedances were stable longitudinally. The electrode-retina distances increased after surgery and then stabilized, and were well-described by an asymptotic exponential model. The stabilization of electrode-retina distances was variable between subjects, stabilizing after 45 weeks for S1, 63 weeks for S2, and 24 weeks for S3 (linear regression; Pgradient > 0.05). For S4, a statistically significant increase in electrode-retina distance persisted (P < 0.05), but by the study end point the rate of increase was clinically insignificant (exponential model: 0.33 µm/wk). Perceptual electrical thresholds were stable in one subject, decreased over time in two subjects (linear model; P < 0.05), and increased slightly in one subject but remained within the predefined charge limits (P = 0.02). Conclusions: Chronic stimulation with the suprachoroidal retinal prosthesis over 3 years resulted in stable impedances, small individual changes in perceptual electrical thresholds, and no clinically significant increase in electrode-retina distances after a period of settling after surgery. Translational Relevance: Chronic stimulation with the 44-channel suprachoroidal retinal implant with a charge density of up to 32 µC/cm2 per phase is suitable for long-term use in humans.

Spectral features of cortical auditory evoked potentials inform hearing threshold and intensity percepts in acoustic and electric hearing.

Objective. Stimulus-elicited changes in electroencephalography (EEG) recordings can be represented using Fourier magnitude and phase features (Makeiget al(2004Trends Cogn. Sci.8204-10)). The present study aimed to quantify how much information about hearing responses are contained in the magnitude, quantified by event-related spectral perturbations (ERSPs); and the phase, quantified by inter-trial coherence (ITC). By testing if one feature contained more information and whether this information was mutually exclusive to the features, we aimed to relate specific EEG magnitude and phase features to hearing perception.Approach.EEG responses were recorded from 20 adults who were presented with acoustic stimuli, and 20 adult cochlear implant users with electrical stimuli. Both groups were presented with short, 50 ms stimuli at varying intensity levels relative to their hearing thresholds. Extracted ERSP and ITC features were inputs for a linear discriminant analysis classifier (Wonget al(2016J. Neural. Eng.13036003)). The classifier then predicted whether the EEG signal contained information about the sound stimuli based on the input features. Classifier decoding accuracy was quantified with the mutual information measure (Cottaris and Elfar (2009J. Neural. Eng.6026007), Hawelleket al(2016Proc. Natl Acad. Sci.11313492-7)), and compared across the two feature sets, and to when both feature sets were combined.Main results. We found that classifiers using either ITC or ERSP feature sets were both able to decode hearing perception, but ITC-feature classifiers were able to decode responses to a lower but still audible stimulation intensity, making ITC more useful than ERSP for hearing threshold estimation. We also found that combining the information from both feature sets did not improve decoding significantly, implying that ERSP brain dynamics has a limited contribution to the EEG response, possibly due to the stimuli used in this study.Significance.We successfully related hearing perception to an EEG measure, which does not require behavioral feedback from the listener; an objective measure is important in both neuroscience research and clinical audiology.

Functional Vision in the Real-World Environment With a Second-Generation (44-Channel) Suprachoroidal Retinal Prosthesis.

Purpose: In a clinical trial (NCT03406416) of a second-generation (44-channel) suprachoroidal retinal prosthesis implanted in subjects with late-stage retinitis pigmentosa (RP), we assessed performance in real-world functional visual tasks and emotional well-being. Methods: The Functional Low-Vision Observer Rated Assessment (FLORA) and Impact of Vision Impairment-Very Low Vision (IVI-VLV) instruments were administered to four subjects before implantation and after device fitting. The FLORA contains 13 self-reported and 35 observer-reported items ranked for ease of conducting task (impossible-easy, central tendency given as mode). The IVI-VLV instrument quantified the impact of low vision on daily activities and emotional well-being. Results: Three subjects completed the FLORA for two years after device fitting; the fourth subject ceased participation in the FLORA after fitting for reasons unrelated to the device. For all subjects at each post-fitting visit, the mode ease of task with device ON was better or equal to device OFF. Ease of task improved over the first six months with device ON, then remained stable. Subjects reported improvements in mobility, functional vision, and quality of life with device ON. The IVI-VLV suggested self-assessed vision-related quality of life was not impacted by device implantation or usage. Conclusions: Subjects demonstrated sustained improved ease of task scores with device ON compared to OFF, indicating the device has a positive impact in the real-world setting. Translational Relevance: Our suprachoroidal retinal prosthesis shows potential utility in everyday life, by enabling an increased environmental awareness and improving access to sensory information for people with end-stage RP.

A Second-Generation (44-Channel) Suprachoroidal Retinal Prosthesis: Interim Clinical Trial Results.

Purpose: To report the initial safety and efficacy results of a second-generation (44-channel) suprachoroidal retinal prosthesis at 56 weeks after device activation. Methods: Four subjects, with advanced retinitis pigmentosa and bare-light perception only, enrolled in a phase II trial (NCT03406416). A 44-channel electrode array was implanted in a suprachoroidal pocket. Device stability, efficacy, and adverse events were investigated at 12-week intervals. Results: All four subjects were implanted successfully and there were no device-related serious adverse events. Color fundus photography indicated a mild postoperative subretinal hemorrhage in two recipients, which cleared spontaneously within 2 weeks. Optical coherence tomography confirmed device stability and position under the macula. Screen-based localization accuracy was significantly better for all subjects with device on versus device off. Two subjects were significantly better with the device on in a motion discrimination task at 7, 15, and 30°/s and in a spatial discrimination task at 0.033 cycles per degree. All subjects were more accurate with the device on than device off at walking toward a target on a modified door task, localizing and touching tabletop objects, and detecting obstacles in an obstacle avoidance task. A positive effect of the implant on subjects' daily lives was confirmed by an orientation and mobility assessor and subject self-report. Conclusions: These interim study data demonstrate that the suprachoroidal prosthesis is safe and provides significant improvements in functional vision, activities of daily living, and observer-rated quality of life. Translational Relevance: A suprachoroidal prosthesis can provide clinically useful artificial vision while maintaining a safe surgical profile.

Smaller spared subcortical nuclei are associated with worse post-stroke sensorimotor outcomes in 28 cohorts worldwide.

Up to two-thirds of stroke survivors experience persistent sensorimotor impairments. Recovery relies on the integrity of spared brain areas to compensate for damaged tissue. Deep grey matter structures play a critical role in the control and regulation of sensorimotor circuits. The goal of this work is to identify associations between volumes of spared subcortical nuclei and sensorimotor behaviour at different timepoints after stroke. We pooled high-resolution T1-weighted MRI brain scans and behavioural data in 828 individuals with unilateral stroke from 28 cohorts worldwide. Cross-sectional analyses using linear mixed-effects models related post-stroke sensorimotor behaviour to non-lesioned subcortical volumes (Bonferroni-corrected, P < 0.004). We tested subacute (≤90 days) and chronic (≥180 days) stroke subgroups separately, with exploratory analyses in early stroke (≤21 days) and across all time. Sub-analyses in chronic stroke were also performed based on class of sensorimotor deficits (impairment, activity limitations) and side of lesioned hemisphere. Worse sensorimotor behaviour was associated with a smaller ipsilesional thalamic volume in both early (n = 179; d = 0.68) and subacute (n = 274, d = 0.46) stroke. In chronic stroke (n = 404), worse sensorimotor behaviour was associated with smaller ipsilesional putamen (d = 0.52) and nucleus accumbens (d = 0.39) volumes, and a larger ipsilesional lateral ventricle (d = -0.42). Worse chronic sensorimotor impairment specifically (measured by the Fugl-Meyer Assessment; n = 256) was associated with smaller ipsilesional putamen (d = 0.72) and larger lateral ventricle (d = -0.41) volumes, while several measures of activity limitations (n = 116) showed no significant relationships. In the full cohort across all time (n = 828), sensorimotor behaviour was associated with the volumes of the ipsilesional nucleus accumbens (d = 0.23), putamen (d = 0.33), thalamus (d = 0.33) and lateral ventricle (d = -0.23). We demonstrate significant relationships between post-stroke sensorimotor behaviour and reduced volumes of deep grey matter structures that were spared by stroke, which differ by time and class of sensorimotor measure. These findings provide additional insight into how different cortico-thalamo-striatal circuits support post-stroke sensorimotor outcomes.

On chirp stimuli and neural synchrony in the suprathreshold auditory brainstem response.

The chirp-evoked ABR has been regarded as a more synchronous response than the click-evoked ABR, referring to the belief that the chirp stimulates lower-, mid-, and higher-frequency regions of the cochlea simultaneously. In this study a variety of tools were used to analyze the synchronicity of ABRs evoked by chirp- and click-stimuli at 40 dB HL in 32 normal hearing subjects aged 18 to 55 years (mean=24.8 years, SD=7.1 years). Compared to the click-evoked ABRs, the chirp-evoked ABRs showed larger wave V amplitudes, but an absence of earlier waves in the grand averages, larger wave V latency variance, smaller FFT magnitudes at the higher component frequencies, and larger phase variance at the higher component frequencies. These results strongly suggest that the chirp-evoked ABRs exhibited less synchrony than the click-evoked ABRs in this study. It is proposed that the temporal compensation offered by chirp stimuli is sufficient to increase neural recruitment (as measured by wave V amplitude), but that destructive phase interactions still exist along the cochlea partition, particularly in the low frequency portions of the cochlea where more latency jitter is expected. The clinical implications of these findings are discussed.

Spectral and synchrony differences in auditory brainstem responses evoked by chirps of varying durations.

The chirp-evoked ABR has been termed a more synchronous response, referring to the fact that rising-frequency chirp stimuli theoretically compensate for temporal dispersions down the basilar membrane. This compensation is made possible by delaying the higher frequency content of the stimulus until the lower frequency traveling waves are closer to the cochlea apex. However, it is not yet clear how sensitive this temporal compensation is to variation in the delay interval. This study analyzed chirp- and click-evoked ABRs at low intensity, using a variety of tools in the time, frequency, and phase domains, to measure synchrony in the response. Additionally, this study also examined the relationship between chirp sweep rate and response synchrony by varying the delay between high- and low-frequency portions of chirp stimuli. The results suggest that the chirp-evoked ABRs in this study exhibited more synchrony than the click-evoked ABRs and that slight gender-based differences exist in the synchrony of chirp-evoked ABRs. The study concludes that a tailoring of chirp parameters to gender may be beneficial in pathologies that severely affect neural synchrony, but that such a customization may not be necessary in routine clinical applications.

Sensory augmentation to aid training with retinal prostheses.

OBJECTIVE: Retinal prosthesis recipients require rehabilitative training to learn the non-intuitive nature of prosthetic 'phosphene vision'. This study investigated whether the addition of auditory cues, using The vOICe sensory substitution device (SSD), could improve functional performance with simulated phosphene vision. APPROACH: Forty normally sighted subjects completed two visual tasks under three conditions. The phosphene condition converted the image to simulated phosphenes displayed on a virtual reality headset. The SSD condition provided auditory information via stereo headphones, translating the image into sound. Horizontal information was encoded as stereo timing differences between ears, vertical information as pitch, and pixel intensity as audio intensity. The third condition combined phosphenes and SSD. Tasks comprised light localisation from the Basic Assessment of Light and Motion (BaLM) and the Tumbling-E from the Freiburg Acuity and Contrast Test (FrACT). To examine learning effects, twenty of the forty subjects received SSD training prior to assessment. MAIN RESULTS: Combining phosphenes with auditory SSD provided better light localisation accuracy than either phosphenes or SSD alone, suggesting a compound benefit of integrating modalities. Although response times for SSD-only were significantly longer than all other conditions, combined condition response times were as fast as phosphene-only, highlighting that audio-visual integration provided both response time and accuracy benefits. Prior SSD training provided a benefit to localisation accuracy and speed in SSD-only (as expected) and Combined conditions compared to untrained SSD-only. Integration of the two modalities did not improve spatial resolution task performance, with resolution limited to that of the higher resolution modality (SSD). SIGNIFICANCE: Combining phosphene (visual) and SSD (auditory) modalities was effective even without SSD training and led to an improvement in light localisation accuracy and response times. Spatial resolution performance was dominated by auditory SSD. The results suggest there may be a benefit to including auditory cues when training vision prosthesis recipients.

An update on retinal prostheses.

Retinal prostheses are designed to restore a basic sense of sight to people with profound vision loss. They require a relatively intact posterior visual pathway (optic nerve, lateral geniculate nucleus and visual cortex). Retinal implants are options for people with severe stages of retinal degenerative disease such as retinitis pigmentosa and age-related macular degeneration. There have now been three regulatory-approved retinal prostheses. Over five hundred patients have been implanted globally over the past 15 years. Devices generally provide an improved ability to localize high-contrast objects, navigate, and perform basic orientation tasks. Adverse events have included conjunctival erosion, retinal detachment, loss of light perception, and the need for revision surgery, but are rare. There are also specific device risks, including overstimulation (which could cause damage to the retina) or delamination of implanted components, but these are very unlikely. Current challenges include how to improve visual acuity, enlarge the field-of-view, and reduce a complex visual scene to its most salient components through image processing. This review encompasses the work of over 40 individual research groups who have built devices, developed stimulation strategies, or investigated the basic physiology underpinning retinal prostheses. Current technologies are summarized, along with future challenges that face the field.

Harmonization of Outcomes and Vision Endpoints in Vision Restoration Trials: Recommendations from the International HOVER Taskforce.

Translational research in vision prosthetics, gene therapy, optogenetics, stem cell and other forms of transplantation, and sensory substitution is creating new therapeutic options for patients with neural forms of blindness. The technical challenges faced by each of these disciplines differ considerably, but they all face the same challenge of how to assess vision in patients with ultra-low vision (ULV), who will be the earliest subjects to receive new therapies. Historically, there were few tests to assess vision in ULV patients. In the 1990s, the field of visual prosthetics expanded rapidly, and this activity led to a heightened need to develop better tests to quantify end points for clinical studies. Each group tended to develop novel tests, which made it difficult to compare outcomes across groups. The common lack of validation of the tests and the variable use of controls added to the challenge of interpreting the outcomes of these clinical studies. In 2014, at the bi-annual International "Eye and the Chip" meeting of experts in the field of visual prosthetics, a group of interested leaders agreed to work cooperatively to develop the International Harmonization of Outcomes and Vision Endpoints in Vision Restoration Trials (HOVER) Taskforce. Under this banner, more than 80 specialists across seven topic areas joined an effort to formulate guidelines for performing and reporting psychophysical tests in humans who participate in clinical trials for visual restoration. This document provides the complete version of the consensus opinions from the HOVER taskforce, which, together with its rules of governance, will be posted on the website of the Henry Ford Department of Ophthalmology (www.artificialvision.org). Research groups or companies that choose to follow these guidelines are encouraged to include a specific statement to that effect in their communications to the public. The Executive Committee of the HOVER Taskforce will maintain a list of all human psychophysical research in the relevant fields of research on the same website to provide an overview of methods and outcomes of all clinical work being performed in an attempt to restore vision to the blind. This website will also specify which scientific publications contain the statement of certification. The website will be updated every 2 years and continue to exist as a living document of worldwide efforts to restore vision to the blind. The HOVER consensus document has been written by over 80 of the world's experts in vision restoration and low vision and provides recommendations on the measurement and reporting of patient outcomes in vision restoration trials.

Oculomotor Responses to Dynamic Stimuli in a 44-Channel Suprachoroidal Retinal Prosthesis.

Purpose: To investigate oculomotor behavior in response to dynamic stimuli in retinal implant recipients. Methods: Three suprachoroidal retinal implant recipients performed a four-alternative forced-choice motion discrimination task over six sessions longitudinally. Stimuli were a single white bar ("moving bar") or a series of white bars ("moving grating") sweeping left, right, up, or down across a 42″ monitor. Performance was compared with normal video processing and scrambled video processing (randomized image-to-electrode mapping to disrupt spatiotemporal structure). Eye and head movement was monitored throughout the task. Results: Two subjects had diminished performance with scrambling, suggesting retinotopic discrimination was used in the normal condition and made smooth pursuit eye movements congruent to the moving bar stimulus direction. These two subjects also made stimulus-related eye movements resembling optokinetic reflex (OKR) for moving grating stimuli, but the movement was incongruent with stimulus direction. The third subject was less adept at the task, appeared primarily reliant on head position cues (head movements were congruent to stimulus direction), and did not exhibit retinotopic discrimination and associated eye movements. Conclusions: Our observation of smooth pursuit indicates residual functionality of cortical direction-selective circuits and implies a more naturalistic perception of motion than expected. A distorted OKR implies improper functionality of retinal direction-selective circuits, possibly due to retinal remodeling or the non-selective nature of the electrical stimulation. Translational Relevance: Retinal implant users can make naturalistic eye movements in response to moving stimuli, highlighting the potential for eye tracker feedback to improve perceptual localization and image stabilization in camera-based visual prostheses.

Fully objective hearing threshold estimation in cochlear implant users using phase-locking value growth functions.

Cochlear implant users require fitting of electrical threshold and comfort levels for optimal access to sound. In this study, we used single-channel cortical auditory evoked responses (CAEPs) obtained from 20 participants using a Nucleus device. A fully objective method to estimate threshold levels was developed, using growth function fitting and the peak phase-locking value feature. Results demonstrated that growth function fitting is a viable method for estimating threshold levels in cochlear implant users, with a strong correlation (r = 0.979, p < 0.001) with behavioral thresholds. Additionally, we compared the threshold estimates using CAEPs acquired from a standard montage (Cz to mastoid) against using a montage of recording channels near the cochlear implant, simulating recording from the device itself. The correlation between estimated and behavioural thresholds remained strong (r = 0.966, p < 0.001), however the recording time needed to be increased to produce a similar estimate accuracy. Finally, a method for estimating comfort levels was investigated, and showed that the comfort level estimates were mildly correlated with behavioral comfort levels (r = 0.50, p = 0.024).