Worldwide Argus II implantation: recommendations to optimize patient outcomes.

BACKGROUND: A position paper based on the collective experiences of Argus II Retinal Prosthesis System investigators to review strategies to optimize outcomes in patients with retinitis pigmentosa undergoing retinal prosthesis implantation. METHODS: Retinal surgeons, device programmers, and rehabilitation specialists from Europe, Canada, Middle East, and the United States were convened to the first international Argus II Investigator Meeting held in Ann Arbor, MI in March 2015. The recommendations from the collective experiences were collected. Factors associated with successful outcomes were determined. RESULTS: Factors leading to successful outcomes begin with appropriate patient selection, expectation counseling, and preoperative retinal assessment. Challenges to surgical implantation include presence of staphyloma and inadequate Tenon's capsule or conjunctiva. Modified surgical technique may reduce risks of complications such as hypotony and conjunctival erosion. Rehabilitation efforts and correlation with validated outcome measures following implantation are critical. CONCLUSIONS: Bringing together Argus II investigators allowed the identification of strategies to optimize patient outcomes. Establishing an on-line collaborative network will foster coordinated research efforts to advance outcome assessment and rehabilitation strategies.

Long-Term Results from an Epiretinal Prosthesis to Restore Sight to the Blind.

PURPOSE: Retinitis pigmentosa (RP) is a group of inherited retinal degenerations leading to blindness due to photoreceptor loss. Retinitis pigmentosa is a rare disease, affecting only approximately 100 000 people in the United States. There is no cure and no approved medical therapy to slow or reverse RP. The purpose of this clinical trial was to evaluate the safety, reliability, and benefit of the Argus II Retinal Prosthesis System (Second Sight Medical Products, Inc, Sylmar, CA) in restoring some visual function to subjects completely blind from RP. We report clinical trial results at 1 and 3 years after implantation. DESIGN: The study is a multicenter, single-arm, prospective clinical trial. PARTICIPANTS: There were 30 subjects in 10 centers in the United States and Europe. Subjects served as their own controls, that is, implanted eye versus fellow eye, and system on versus system off (native residual vision). METHODS: The Argus II System was implanted on and in a single eye (typically the worse-seeing eye) of blind subjects. Subjects wore glasses mounted with a small camera and a video processor that converted images into stimulation patterns sent to the electrode array on the retina. MAIN OUTCOME MEASURES: The primary outcome measures were safety (the number, seriousness, and relatedness of adverse events) and visual function, as measured by 3 computer-based, objective tests. RESULTS: A total of 29 of 30 subjects had functioning Argus II Systems implants 3 years after implantation. Eleven subjects experienced a total of 23 serious device- or surgery-related adverse events. All were treated with standard ophthalmic care. As a group, subjects performed significantly better with the system on than off on all visual function tests and functional vision assessments. CONCLUSIONS: The 3-year results of the Argus II trial support the long-term safety profile and benefit of the Argus II System for patients blind from RP. Earlier results from this trial were used to gain approval of the Argus II by the Food and Drug Administration and a CE mark in Europe. The Argus II System is the first and only retinal implant to have both approvals.

Event-Based Modeling of Driver Yielding Behavior to Pedestrians at Two-Lane Roundabout Approaches.

Unlike other types of controlled intersections, drivers do not always comply with the "yield to pedestrian" sign at the roundabouts. This paper aims to identify the contributing factors affecting the likelihood of driver yielding to pedestrians at two-lane roundabouts. It further models the likelihood of driver yielding based on these factors using logistic regression. The models have been applied to 1150 controlled pedestrian crossings at entry and exit legs of two-lane approaches of six roundabouts across the country. The logistic regression models developed support prior research that the likelihood of driver yielding at the entry leg of roundabouts is higher than at the exit. Drivers tend to yield to pedestrians carrying a white cane more often than to sighted pedestrians. Drivers traveling in the far lane, relative to pedestrian location, have a lower probability of yielding to a pedestrian. As the speed increases the probability of driver yielding decreases. At the exit leg of the roundabout, drivers turning right from the adjacent lane have a lower propensity of yielding than drivers coming from other directions. The findings of this paper further suggest that although there has been much debate on pedestrian right-of-way laws and distinction between pedestrian waiting positions (in the street versus at the curb), this factor does not have a significant impact on driver yielding rate. The logistic regression models also quantify the effect of each of these factors on propensity of driver yielding. The models include variables which are specific to each study location and explain the impact size of each study location on probability of yielding. The models generated in this research will be useful to transportation professionals and researchers interested in understanding the factors that impact driver yielding at modern roundabouts. The results of the research can be used to isolate factors that may increase yielding (such as lower roundabout approach speeds), and can feasibly be incorporated into microsimulation algorithms to model driver yielding at roundabouts.

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.

Virtual reality as a means to explore assistive technologies for the visually impaired.

Visual impairment represents a significant health and economic burden affecting 596 million globally. The incidence of visual impairment is expected to double by 2050 as our population ages. Independent navigation is challenging for persons with visual impairment, as they often rely on non-visual sensory signals to find the optimal route. In this context, electronic travel aids are promising solutions that can be used for obstacle detection and/or route guidance. However, electronic travel aids have limitations such as low uptake and limited training that restrict their widespread use. Here, we present a virtual reality platform for testing, refining, and training with electronic travel aids. We demonstrate the viability on an electronic travel aid developed in-house, consist of a wearable haptic feedback device. We designed an experiment in which participants donned the electronic travel aid and performed a virtual task while experiencing a simulation of three different visual impairments: age-related macular degeneration, diabetic retinopathy, and glaucoma. Our experiments indicate that our electronic travel aid significantly improves the completion time for all the three visual impairments and reduces the number of collisions for diabetic retinopathy and glaucoma. Overall, the combination of virtual reality and electronic travel aid may have a beneficial role on mobility rehabilitation of persons with visual impairment, by allowing early-phase testing of electronic travel aid prototypes in safe, realistic, and controllable settings.

Orientation and mobility assessment in retinal prosthetic clinical trials.

PURPOSE: The purpose of this study was to develop an orientation and mobility (O&M) assessment protocol to implement in subjects who have been implanted with an artificial silicon retina (ASR), and to use this experience to propose a research agenda for O&M with prosthetic vision. METHODS: A controlled and naturalistic assessment was developed that included walking a prescribed obstacle course and travel to and from a hospital cafeteria. Subjects were tested before and 3 and 6 months after being implanted with the ASR. Outcome measures were walking speed and number of contacts with obstacles. The experiences from this study led to a proposed research agenda in O&M. RESULTS: Eight subjects with retinitis pigmentosa participated in this study. The vision status of the subjects ranged from <20/1600 to 20/80 visual acuity and visual fields of <5 to 40°. Using a repeated-measures analysis of variance, no differences were found in the primary outcome measures. Four subjects were observed to have reduced mobility after implantation. Three subjects self-reported enhancements of travel after implantation, but this enhancement was not observed. CONCLUSIONS: This study demonstrates that mobility might not be improved with prosthetic vision. The proposed research agenda emphasizes the importance of developing individualized assessments, identifying specific items of orientation rather than mobility for measuring the effect of prosthetic vision, and to develop and evaluate instructional programs that may be needed to obtain the full benefit of the technology.

Traffic gap detection for pedestrians with low vision.

PURPOSE: Pedestrians with low vision have identified crossing the street as a difficult task. With the increasing complexity of the crossing environment (actuated signals and roundabouts), the challenges are increasing. The purpose of this study was to evaluate the effect of two types of vision loss (central or peripheral) on the ability to detect gaps in traffic. METHODS: Forty-one subjects participated with 14 being fully sighted (FS), 10 having central vision loss from age-related macular degeneration (AMD), and 17 having peripheral vision loss from either retinitis pigmentosa or glaucoma. Standing at entry and exit lanes of a roundabout, subjects depressed a handheld trigger to indicate when there was a sufficient gap in traffic to cross the street. A total of twelve 2-min intervals were completed including four of those intervals with occluded hearing. RESULTS: No difference was found in the ability of the three subject groups to identify crossable or short gaps. There were significant differences in latency and safety margin. The AMD subjects did not perform as well as the FS or the subjects with retinitis pigmentosa/glaucoma. When hearing was occluded, the two vision loss groups did not show a change in sensitivity but the FS group did, being more sensitive when hearing was occluded. CONCLUSIONS: The purpose of this study was to evaluate the effect of low vision on the ability to detect crossable gaps in traffic. The findings suggest that subjects with AMD have an increased risk because they show significant latency in their identification of gaps and this in turn results in a reduction of safety margin.

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.

Estimating the amount of mental effort required for independent mobility: persons with glaucoma.

PURPOSE: To validate the use of the secondary-task method to estimate the amount of mental effort required for independent travel and to determine how the amount of mental effort varies with characteristics of the environment. METHODS: Reaction time (RT) to a secondary task (randomly presented vibrations) was obtained in 28 persons with glaucoma as they walked in four different environments: hallway, high-pedestrian area, approach-to-stairs area, and stairs. Cronbach's alpha was used to assess the reliability of the secondary-task RT measures from the split-half measures of the high-pedestrian area. The construct validity of the RT measures as an estimate of mental effort was assessed by (1) the association between the RT scores and the item measure scores for similar environments derived from a Rasch analysis of perceived difficulty ratings obtained in a separate group of 83 persons with glaucoma and (2) the association between the RT scores and the severity of visual field loss. RESULTS: Reliability was supported by a Cronbach's alpha coefficient of 0.89. Construct validity was also supported by the data: (1) Log RT scores were linearly related to the Rasch analysis item measures for comparable mobility situations (P = 0.008), and (2) the log RT, averaged across the four environments, was linearly related to the mean deviation score of the Humphrey Visual Field Analyzer (estimate of visual field loss; P = 0.003; Carl Zeiss Meditec, Inc., Dublin, CA). A comparison of the log RT scores obtained in the four environments showed significantly higher log RT scores in the stairs area than in the high-pedestrian and hallway environments, whereas the log RT scores in the high-pedestrian and hallway environments were not significantly different. CONCLUSIONS: The findings in this study demonstrate the reliability and construct validity of the secondary-task RT measure as an estimate of the amount of mental effort required to travel independently. It is sensitive to environmental characteristics and the loss in a walker's visual field. The method could be an objective way to document those who may benefit from professional intervention and to evaluate the effectiveness of an intervention.

An analysis of observer-rated functional vision in patients implanted with the Argus II Retinal Prosthesis System at three years.

OBJECTIVE: The purpose of this analysis was to compare observer-rated tasks in patients implanted with the Argus II Retinal Prosthesis System, when the device is ON versus OFF. METHODS: The Functional Low-Vision Observer Rated Assessment (FLORA) instrument was administered to 26 blind patients implanted with the Argus II Retinal Prosthesis System at a mean follow-up of 36 months. FLORA is a multi-component instrument that consists in part of observer-rated assessment of 35 tasks completed with the device ON versus OFF. The ease with which a patient completes a task is scored using a four-point scale, ranging from easy (score of 1) to impossible (score of 4). The tasks are evaluated individually and organised into four discrete domains, including 'Visual orientation', 'Visual mobility', 'Daily life and 'Interaction with others'. RESULTS: Twenty-six patients completed each of the 35 tasks. Overall, 24 out of 35 tasks (69 per cent) were statistically significantly easier to achieve with the device ON versus OFF. In each of the four domains, patients' performances were significantly better (p < 0.05) with the device ON versus OFF, ranging from 19 to 38 per cent improvement. CONCLUSION: Patients with an Argus II Retinal Prosthesis implanted for 18 to 44 months (mean 36 months), demonstrated significantly improved completion of vision-related tasks with the device ON versus OFF.

FLORA™: Phase I development of a functional vision assessment for prosthetic vision users.

BACKGROUND: Research groups and funding agencies need a functional assessment suitable for an ultra-low vision population to evaluate the impact of new vision-restoration treatments. The purpose of this study was to develop a pilot assessment to capture the functional visual ability and well-being of subjects whose vision has been partially restored with the Argus II Retinal Prosthesis System. METHODS: The Functional Low-Vision Observer Rated Assessment (FLORA) pilot assessment involved a self-report section, a list of functional visual tasks for observation of performance and a case narrative summary. Results were analysed to determine whether the interview questions and functional visual tasks were appropriate for this ultra-low vision population and whether the ratings suffered from floor or ceiling effects. Thirty subjects with severe to profound retinitis pigmentosa (bare light perception or worse in both eyes) were enrolled in a clinical trial and implanted with the Argus II System. From this population, 26 subjects were assessed with the FLORA. Seven different evaluators administered the assessment. RESULTS: All 14 interview questions were asked. All 35 tasks for functional vision were selected for evaluation at least once, with an average of 20 subjects being evaluated for each test item. All four rating options­impossible (33 per cent), difficult (23 per cent), moderate (24 per cent) and easy (19 per cent)­were used by the evaluators. Evaluators also judged the amount of vision they observed the subjects using to complete the various tasks, with 'vision only' occurring 75 per cent on average with the System ON, and 29 per cent with the System OFF. CONCLUSION: The first version of the FLORA was found to contain useful elements for evaluation and to avoid floor and ceiling effects. The next phase of development will be to refine the assessment and to establish reliability and validity to increase its value as an assessment tool for functional vision and well-being.

Oculomotor strategies for the direction of gaze tested with a real-world activity.

Laboratory-based models of oculomotor strategy that differ in the amount and type of top-down information were evaluated against a baseline case of random scanning for predicting the gaze patterns of subjects performing a real-world activity--walking to a target. Images of four subjects' eyes and field of view were simultaneously recorded as they performed the mobility task. Offline analyses generated movies of the eye on scene and a categorization scheme was used to classify the locations of the fixations. Frames from each subject's eye-on-scene movie served as input to the models, and the location of each model's predicted fixations was classified using the same categorization scheme. The results showed that models with no top-down information (visual salience model) or with only coarse feature information performed no better than a random scanner; the models' ordered fixation locations (gaze pattern) matched less than a quarter of the subjects' gaze patterns. A model that used only geographic information outperformed the random scanner and matched approximately a third of the gaze patterns. The best performance was obtained from an oculomotor strategy that used both coarse feature and geographic information, matching nearly half the gaze patterns (48%). Thus, a model that uses top-down information about a target's coarse features and general vicinity does a fairly good job predicting fixation behavior, but it does not fully specify the gaze pattern of a subject walking to a target. Additional information is required, perhaps in the form of finer feature information or knowledge of a task's procedure.

Fixation behavior while walking: persons with central visual field loss.

The aim of this study was to determine the effect of central visual field loss (CFL) on fixation patterns of a person walking towards a target. Subjects were four visually normal persons and 10 persons with CFL. Eye position on scene was recorded and classified into 20 scene categories. The distributions of fixations among scene categories were compared across the two subject groups. For all but two CFL subjects, who fixated primarily at the floor, the distributions of fixations for the CFL subjects ranged from being moderately to strongly correlated with that of the visually normal mean. An analysis of the similarity in the sequence of fixations (or gaze pattern) of the CFL subjects to the visually normal subjects showed a range of 7-66%. Excluding the one CFL subject who had a functioning fovea, sequence similarity was strongly correlated with the logarithm of the minimum angle of resolution (logMAR). The better a person's logMAR, the more closely his or her gaze pattern matched that of the visually normal subjects. Finally, the CFL data were tested against two current models of oculomotor strategy, visual salience and guided search. Similar to what was found with visually normal subjects, CFL subjects appear to use the expected features and general location of the target to guide their fixations, the guided-search strategy.

Traffic gap judgment in people with significant peripheral field loss.

PURPOSE: Subjects with significant peripheral field loss (PFL) self report difficulty in street crossing. In this study, we compared the traffic gap judgment ability of fully sighted and PFL subjects to determine whether accuracy in identifying crossable gaps was adversely affected because of field loss. Moreover, we explored the contribution of visual and nonvisual factors to traffic gap judgment ability. METHODS: Eight subjects with significant PFL as a result of advanced retinitis pigmentosa or glaucoma with binocular visual field <20 degrees and five age-matched normals (NV) were recruited. All subjects were required to judge when they perceived it was safe to cross at a 2-way 4-lane street while they stood on the curb. Eye movements were recorded by an eye tracker as the subjects performed the decision task. Movies of the eye-on-scene were made offline and fixation patterns were classified into either relevant or irrelevant. Subjects' street-crossing behavior, habitual approach to street crossing, and perceived difficulties were assessed. RESULTS: Compared with normal vision (NV) subjects, the PFL subjects identified 12% fewer crossable gaps while making 23% more errors by identifying a gap as crossable when it was too short (p < 0.05). The differences in traffic gap judgment ability of the PFL subjects might be explained by the significantly smaller fixation area (p = 0.006) and fewer fixations distributed to the relevant tasks (p = 0.001). The subjects' habitual approach to street crossing and perceived difficulties in street crossing (r > 0.60) were significantly correlated with traffic gap judgment performance. CONCLUSIONS: As a consequence of significant field loss, limited visual information about the traffic environment can be acquired, resulting in significantly reduced performance in judging safe crossable gaps. This poor traffic gap judgment ability in the PFL subjects raises important concerns for their safety when attempting to cross the street.

Gaze behavior of the visually impaired during street crossing.

PURPOSE: This study explored the gaze patterns of fully sighted and visually impaired subjects during the high-risk activity of crossing the street. METHODS: Gaze behavior of 12 fully sighted subjects, nine with visual impairment resulting from age-related macular degeneration and 12 with impairment resulting from glaucoma, was monitored using a portable eye tracker as they crossed at two unfamiliar intersections. RESULTS: All subject groups fixated primarily on vehicles and crossing elements but changed their fixation behavior as they moved from "walking to the curb" to "standing at the curb" and to "crossing the street." A comparison of where subjects fixated in the 4-second time period before crossing showed that the fully sighted who waited for the light to change fixated on the light, whereas the fully sighted who crossed early fixated primarily on vehicles. Visually impaired subjects crossing early or waiting for the light fixate primarily on vehicles. CONCLUSIONS: Vision status affects fixation allocation while performing the high-risk activity of street crossing. Crossing decision-making strategy corresponds to fixation behavior only for the fully sighted subjects.

Head movements while crossing streets: effect of vision impairment.

BACKGROUND: Crossing the street is an activity that requires gathering information over a large area. The challenge in safely crossing a street is to acquire the necessary information for a decision of when to cross within a limited window of time. The purpose of this study was to compare the head movement behavior of visually impaired pedestrians with fully sighted pedestrians at two types of complex intersections: a plus intersection and a roundabout. METHOD: We measured the head movement behavior of 12 subjects with normal vision, 11 subjects with age-related macular degeneration (AMD), and 10 subjects with glaucoma as they approached and crossed at the two intersections. The primary measures were the percentage of time the head was directed to the left, center, or right and the frequency of head turns. We compared measures across groups and relative to three criteria of head movement behavior for maximizing street-crossing safety. RESULTS: Crossing the street can be divided into three phases: walking to the curb, standing at the curb, and crossing the street. We found that while moving, the majority of subjects directed their head to the center. This was true at the plus intersection and roundabout. Group differences were found in the frequency of head turns at the plus intersection, with the AMD pedestrians having a lower frequency of head turns compared with the fully sighted pedestrians. However, the frequency of head turns increased for all the groups during the last 4 seconds before crossing, with the frequency being the greatest during the last second. Numerous subjects had head movements consistent with pedestrian safety, although there were subjects in each group who failed to demonstrate maximum safety. More of the visually impaired pedestrians exhibited less safe head movement behavior than the fully sighted pedestrians. CONCLUSIONS: The effects of visual impairment on head movement behavior were associated with pedestrian safety at critical moments in the street-crossing process. Mobility training programs aimed at teaching safe head movement behavior for street crossing could help to increase the safety of visually impaired pedestrians.

Gaze behavior while crossing complex intersections.

BACKGROUND: Crossing the street is a complex task that involves gathering, processing, and acting on information that is time dependent. The gaze behavior of subjects has been previously studied on increasingly complex and dynamic tasks such as making tea, walking indoors, and driving. The purpose of this study was to assess how normally sighted people use their vision to cross a street safely. Specifically, we identified the environmental features people look at when crossing two types of intersections. METHOD: We measured the eye movements and head directions of 12 normally sighted people as they approached, evaluated, and crossed a light-controlled "plus" intersection and a roundabout. The primary measures were percentage of fixations and head direction. RESULTS: Crossing the street can be divided into three phases, walking to the curb, standing at the curb, and crossing the street. We found that while moving, subjects fixated primarily on crossing elements and when standing at the curb, they fixated primarily on vehicles. At the plus intersection, fixation behavior corresponded with crossing strategy; the subjects who crossed early fixated on cars, and the subjects who waited for the light to change fixated on traffic controls. At the roundabout, all subjects determined an appropriate time to cross from vehicular traffic flow by directing the majority of their fixations on cars. When moving, the head position of subjects was predominately centered. Subjects also made head turns in both directions before crossing and directed the head toward the danger zone while crossing. CONCLUSION: Crossing the street is a complex task that can be described in three phases. Common head and eye behaviors were found near the critical moments of crossing the street. Fixation behavior was closely related to street crossing behavior.