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PURPOSE: To assess the measurement properties of the Attitudes to Gene Therapy for the Eye (AGT-Eye) instrument among Australian adults with inherited retinal diseases (IRDs) and parents/caregivers of people with IRDs. Constructs of interest included sources of information, knowledge of treatment methods, awareness of treatment outcomes, and perceived value of gene therapy for IRDs. METHODS: A cross-sectional, self-reported, 30-item questionnaire was administered in English from January to June 2021. It was predominantly conducted online with phone and paper alternatives available. Rating scale models were generated separately for each of the four subscales to assess fit, discrimination, and differential item functioning of the items, as well as targeting, reliability, and precision of the subscales. Principal components analysis was used to assess dimensionality. RESULTS: Responses from 681 participants (87.1% online, 12.9% phone/mail) were included (ages 18-93 years; 51.7% female). Removal of two poorly performing items slightly improved subscale properties. Item reliability was high for each of the subscales; however, person reliability was suboptimal, with limited ability to stratify participants according to traits (person separation coefficient < 1.8 for each subscale). There was no evidence of differential item functioning by gender, online completion, or patient/caregiver status. Evidence of multidimensionality was detected for two subscales. CONCLUSIONS: Four subscales of the AGT-Eye will be used to analyze operational knowledge and perceived value of ocular gene therapy in Australia. Measurement properties may be improved with the generation of additional items. TRANSLATIONAL RELEVANCE: Physicians can use the AGT-Eye to assess knowledge and expectations of potential recipients of ocular gene therapy for IRDs.

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.

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.

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.

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 psychoph

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.

PURPOSE: The safety of chronic implantation of a retinal prosthesis in the suprachoroidal space has not been established. This study aimed to determine the safety of a wide-field suprachoroidal electrode array following chronic implantation using histopathologic techniques and electroretinography. METHODS: A platinum electrode array in a wide silicone substrate was implanted unilaterally in the suprachoroidal space in adult cats (n = 7). The lead and connector were tunneled out of the orbit and positioned subcutaneously. Postsurgical recovery was assessed using fundus photography and electroretinography (ERG). Following 3 months of passive implantation, the animals were terminated and the eyes assessed for the pathologic response to implantation. RESULTS: The implant was mechanically stable in the suprachoroidal space during the course of the study. The implanted eye showed a transient increase in ERG response amplitude at 2 weeks, which returned to normal by 3 months. Pigmentary changes were observed at the distal end of the implant, near the optic disc. Histopathologic assessment revealed a largely intact retina and a thin fibrous capsule around the suprachoroidal implant cavity. The foreign body response was minimal, with sporadic presence of macrophages and no active inflammation. All implanted eyes were negative for bacterial or fungal infections. A midgrade granuloma and thick fibrous buildup surrounded the extraocular cable. Scleral closure was maintained in six of seven eyes. There were no staphylomas or choroidal incarceration. CONCLUSIONS: A wide-field retinal prosthesis was stable and well tolerated during long-term suprachoroidal implantation in a cat model. The surgical approach was reproducible and overall safe.