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.

Vision function testing for a suprachoroidal retinal prosthesis: effects of image filtering.

OBJECTIVE: One strategy to improve the effectiveness of prosthetic vision devices is to process incoming images to ensure that key information can be perceived by the user. This paper presents the first comprehensive results of vision function testing for a suprachoroidal retinal prosthetic device utilizing of 20 stimulating electrodes. Further, we investigate whether using image filtering can improve results on a light localization task for implanted participants compared to minimal vision processing. No controlled implanted participant studies have yet investigated whether vision processing methods that are not task-specific can lead to improved results. APPROACH: Three participants with profound vision loss from retinitis pigmentosa were implanted with a suprachoroidal retinal prosthesis. All three completed multiple trials of a light localization test, and one participant completed multiple trials of acuity tests. The visual representations used were: Lanczos2 (a high quality Nyquist bandlimited downsampling filter); minimal vision processing (MVP); wide view regional averaging filtering (WV); scrambled; and, system off. MAIN RESULTS: Using Lanczos2, all three participants successfully completed a light localization task and obtained a significantly higher percentage of correct responses than using MVP ([Formula: see text]) or with system off ([Formula: see text]). Further, in a preliminary result using Lanczos2, one participant successfully completed grating acuity and Landolt C tasks, and showed significantly better performance ([Formula: see text]) compared to WV, scrambled and system off on the grating acuity task. SIGNIFICANCE: Participants successfully completed vision tasks using a 20 electrode suprachoroidal retinal prosthesis. Vision processing with a Nyquist bandlimited image filter has shown an advantage for a light localization task. This result suggests that this and targeted, more advanced vision processing schemes may become important components of retinal prostheses to enhance performance. ClinicalTrials.gov Identifier: NCT01503576.

Mobility and low contrast trip hazard avoidance using augmented depth.

OBJECTIVE: We evaluated a novel visual representation for current and near-term prosthetic vision. Augmented depth emphasizes ground obstacles and floor-wall boundaries in a depth-based visual representation. This is achieved by artificially increasing contrast between obstacles and the ground surface via a novel ground plane extraction algorithm specifically designed to preserve low-contrast ground-surface boundaries. APPROACH: The effectiveness of augmented depth was examined in human mobility trials compared against standard intensity-based (Intensity), depth-based (Depth) and random (Random) visual representations. Eight participants with normal vision used simulated prosthetic vision with 20 phosphenes and eight perceivable brightness levels to traverse a course with randomly placed small and low-contrast obstacles on the ground. MAIN RESULTS: The number of collisions was significantly reduced using augmented depth, compared with intensity, depth and random representations (48%, 44% and 72% less collisions, respectively). SIGNIFICANCE: These results indicate that augmented depth may enable safe mobility in the presence of low-contrast obstacles with current and near-term implants. This is the first demonstration that an augmentation of the scene ensuring key objects are visible may provide better outcomes for prosthetic vision.

First-in-human trial of a novel suprachoroidal retinal prosthesis.

UNLABELLED: Retinal visual prostheses ("bionic eyes") have the potential to restore vision to blind or profoundly vision-impaired patients. The medical bionic technology used to design, manufacture and implant such prostheses is still in its relative infancy, with various technologies and surgical approaches being evaluated. We hypothesised that a suprachoroidal implant location (between the sclera and choroid of the eye) would provide significant surgical and safety benefits for patients, allowing them to maintain preoperative residual vision as well as gaining prosthetic vision input from the device. This report details the first-in-human Phase 1 trial to investigate the use of retinal implants in the suprachoroidal space in three human subjects with end-stage retinitis pigmentosa. The success of the suprachoroidal surgical approach and its associated safety benefits, coupled with twelve-month post-operative efficacy data, holds promise for the field of vision restoration. TRIAL REGISTRATION: Clinicaltrials.gov NCT01603576.

Oral folic acid and vitamin B-12 supplementation to prevent cognitive decline in community-dwelling older adults with depressive symptoms--the Beyond Ageing Project: a randomized controlled trial.

BACKGROUND: Evidence remains unclear as to whether folic acid (FA) and vitamin B-12 supplementation is effective in reducing depressive symptoms. OBJECTIVES: The objective was to determine whether oral FA + vitamin B-12 supplementation prevented cognitive decline in a cohort of community-dwelling older adults with elevated psychological distress. DESIGN: A randomized controlled trial (RCT) with a completely crossed 2 × 2 × 2 factorial design comprising daily oral 400 µg FA + 100 µg vitamin B-12 supplementation (compared with placebo), physical activity promotion, and depression literacy with comparator control interventions for reducing depressive symptoms was conducted in 900 adults aged 60-74 y with elevated psychological distress (Kessler Distress 10-Scale; scores >15). The 2-y intervention was delivered in 10 modules via mail with concurrent telephone tracking calls. Main outcome measures examined change in cognitive functioning at 12 and 24 mo by using the Telephone Interview for Cognitive Status-Modified (TICS-M) and the Brief Test of Adult Cognition by Telephone (processing speed); the Informant Questionnaire on Cognitive Decline in the Elderly was administered at 24 mo. RESULTS: FA + vitamin B-12 improved the TICS-M total (P = 0.032; effect size d = 0.17), TICS-M immediate (P = 0.046; d = 0.15), and TICS-M delayed recall (P = 0.013; effect size d = 0.18) scores at 24 mo in comparison with placebo. No significant changes were evident in orientation, attention, semantic memory, processing speed, or informant reports. CONCLUSION: Long-term supplementation of daily oral 400 µg FA + 100 µg vitamin B-12 promotes improvement in cognitive functioning after 24 mo, particularly in immediate and delayed memory performance. This trial was registered at clinicaltrials.gov as NCT00214682.

Substituting depth for intensity and real-time phosphene rendering: visual navigation under low vision conditions.

Navigation and way finding including obstacle avoidance is difficult when visual perception is limited to low resolution, such as is currently available on a bionic eye. Depth visualisation may be a suitable alternative. Such an approach can be evaluated using simulated phosphenes with a wearable mobile virtual reality kit. In this paper, we present two novel approaches: (i) an implementation of depth visualisation; and, (ii) novel methods for rapid rendering of simulated phosphenes with an empirical comparison between them. Our new software-based method for simulated phosphene rendering shows large speed improvements, facilitating the display in real-time of a large number of phosphenes with size and brightness dependent on pixel intensity, and with customised output dynamic range. Further, we describe the protocol, navigation environment and system used for visual navigation experiments to evaluate the use of depth on low resolution simulations of a bionic eye perceptual experience. Results for these experiments show that a depth-based representation is effective for navigation, and shows significant advantages over intensity-based approaches when overhanging obstacles are present. The results of the experiments were reported in [1], [2].

Mental health literacy, folic acid and vitamin B12, and physical activity for the prevention of depression in older adults: randomised controlled trial.

BACKGROUND: Few randomised controlled trials (RCTs) have examined potential preventive agents in high-risk community populations. AIMS: To determine whether a mental health literacy intervention, the promotion of physical activity, or folic acid plus vitamin B(12) reduce depression symptoms in community-dwelling older adults with elevated psychological distress. METHOD: An RCT with a completely crossed 2 x 2 x 2 factorial design: (400 mcg/d folic acid + 100 mcg/d vitamin B(12) v. placebo)x(physical activity v. nutrition promotion control)x(mental health literacy v. pain information control). The initial target sample size was 2000; however, only 909 adults (60-74 years) met the study criteria. Interventions were delivered by mail with telephone calls. The main outcome was depressive symptoms on the Patient Health Questionnaire (PHQ-9) at 6 weeks, 6, 12 and 24 months. The Clinicaltrials.gov registration number is NCT00214682. RESULTS: The drop-out rate was low (13.5%) from randomisation to 24-month assessment. Neither folic acid + B(12) (F(3,856) = 0.83, P = 0.476) nor physical activity (F(3,856) = 1.65, P = 0.177) reduced depressive symptoms at any time point. At 6 weeks, depressive symptoms were lower for the mental health literacy intervention compared with its control condition (t(895) = 2.04, P = 0.042). CONCLUSIONS: Mental health literacy had a transient effect on depressive symptoms. Other than this, none of the interventions significantly reduced symptoms relative to their comparator at 6 weeks or subsequently. Neither folic acid plus B(12) nor physical activity were effective in reducing depressive symptoms.

The effectiveness of distance interventions for increasing physical activity: a review.

OBJECTIVE: Evaluate the effectiveness of distance physical activity interventions to establish intervention features that are key to success. DATA SOURCE: Computerized searches for randomized controlled trials (RCTs) of distance physical activity interventions and visual scans of reference lists were performed between March 2004 and July 2006. STUDY INCLUSION AND EXCLUSION CRITERIA: Studies were included if they (1) employed a randomized controlled design, (2) encouraged physical activity in adults, and (3) had no face-to-face contact between participants and researchers or health educators. DATA EXTRACTION: Twenty-two studies were found that met the inclusion criteria. Authors assessed the quality of the studies and coded articles according to key intervention features. DATA SYNTHESIS: This review is a systematic narrative review. Heterogeneity and poor study quality made formal meta-analysis inappropriate. Nevertheless, effect sizes were calculated for studies comparing intervention with control. RESULTS: Overall, distance interventions increased physical activity in the short term (between-group effect size range, -.2 to .45). Print medium plus telephone contact was the most effective delivery mode. CONCLUSIONS: Poor study quality prevented firm conclusions. However, distance interventions were found to promote physical activity in the short term for some populations. This review provided limited support for the efficacy of distance exercise interventions and revealed limitations of the extant literature. Expansion of RCT research into distance approaches to promoting physical activity is warranted.

Ability perceptions, perceived control, and risk avoidance among male and female older drivers.

We used responses from telephone interviews conducted with a community sample of 304 older drivers to investigate associations between perceived control over driving, driving ability perception (an index of unrealistic optimism), and self-reported avoidance of high-risk driving situations. We also investigated associations between perceived control over driving, ability perception, and indices of well-being (life satisfaction and depressive symptoms). Our results indicated that perceived control and perceived ability were each associated with reduced risk avoidance and well-being, with these associations moderated by gender. We discuss the results in terms of potentially adaptive and maladaptive consequences of pervasive perceptual biases, gender differences in primary and secondary control strategies, and the importance of effective self-regulation for aging well.

Measuring quality of life in rheumatic conditions.

Musculoskeletal disorders often have associated pain, functional impairment and work disability, and, not surprisingly, are the most common reasons for utilizing healthcare resources. Rheumatoid arthritis (RA) and fibromyalgia (FM) are causes of musculoskeletal pain and disability. Research indicates that there is a widespread impact of RA and FM on physical, psychological and social factors in affected individuals, and thus, outcome measures that encompass multiple aspects of quality of life are needed. Generic measures of quality of life identify associations between physical conditions and mental health and highlight the need to address psychological functioning to ultimately improve the individuals' quality of life.

The impact of cataract surgery on visual functioning, vision-related disability and psychological distress: a randomized controlled trial.

PURPOSE: Determine whether there are changes in visual functioning, vision-related disability, health status and mood after cataract surgery. METHODS: 45 adults (mean age = 73.7 years) with bilateral cataract needing surgery for the first eye were recruited from public ophthalmology clinics. The Visual Functioning-14 survey assessed visual disability. Minimal angle of resolution tested visual acuity, and the Melbourne Edge Test examined contrast sensitivity. Demographic, psychological, health and medication use variables were examined. Participants were randomized to either an intervention or control arm. Controls were assessed on two occasions at a 3-month interval before having surgery. The intervention group was assessed 1-2 weeks before surgery and then reassessed 3 months after surgery. RESULTS: Visual functioning improved for those who had cataract surgery with better visual acuity in the better (P = 0.010) and worse (P = 0.028) eye compared with controls. The intervention group reported fewer difficulties with overall vision-related disability (P = 0.0001), reading (P = 0.004) and instrumental activities of daily living (P = 0.010) post-surgery compared with controls. People with improved depression scores (P = 0.048) after surgery had less difficulty with reading compared with those with unchanged or worsened depression scores. Cataract surgery did not improve health status. CONCLUSIONS: First eye cataract surgery is effective in improving outcomes in visual functioning and disability. Improved mood after surgery was related to less vision-related disability compared with unchanged or worse depression.

Cognitive, sensory and physical factors enabling driving safety in older adults.

We reviewed literature on cognitive, sensory, motor and physical factors associated with safe driving and crash risk in older adults with the goal of developing a model of factors enabling safe driving behaviour. Thirteen empirical studies reporting associations between cognitive, sensory, motor and physical factors and either self-reported crashes, state crash records or on-road driving measures were identified. Measures of attention, reaction time, memory, executive function, mental status, visual function, and physical function variables were associated with driving outcome measures. Self-monitoring was also identified as a factor that may moderate observed effects by influencing driving behavior. We propose that three enabling factors (cognition, sensory function and physical function/medical conditions) predict driving ability, but that accurate self-monitoring of these enabling factors is required for safe driving behaviour.

Models of adjustment to chronic illness: using the example of rheumatoid arthritis.

There are a number of theoretical frameworks that attempt to explain how individuals may adjust to threats to health and serious physical illness. The three major paradigms that attempt to organize key components of health and adaptation to illness include the following: the biomedical model which emphasizes disease; psychological models of adaptation to illness; and biopsychosocial models with the latter two emphasizing health, functioning, and well-being. Each of these three major paradigms, including biomedical, psychosocial, and biopsychosocial frameworks, is discussed and critiqued in turn, and contributions and theoretical issues in terms of adjustment to chronic illness, particularly rheumatoid arthritis (RA), are highlighted. Furthermore, a biopsychosocial framework for conceptualizing adjustment to physical illness is proposed that incorporates elements from key existing biomedical and psychosocial models of adaptation to chronic physical health issues.