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Purpose: To assess the feasibility of a second-generation (44-channel) suprachoroidal retinal prosthesis for provision of functional vision in recipients with end-stage retinitis pigmentosa (RP) over 2.7 years., Design: Prospective, single-arm, unmasked interventional clinical trial., Participants: Four participants, with advanced RP and bare-light perception vision., Methods: The 44-channel suprachoroidal retinal prosthesis was implanted in the worse-seeing eye. Device stability, functionality, and adverse events were investigated at approximately 12-week intervals up to 140 weeks (2.7 years) postdevice activation., Main Outcome Measures: Serious adverse event (SAE) reporting, visual response outcomes, functional vision outcomes, and quality-of-life outcomes., Results: All 4 participants (aged 39-66 years, 3 males) were successfully implanted in 2018, and there were no device-related SAEs over the duration of the study. A mild postoperative subretinal hemorrhage was detected in 2 recipients, which cleared spontaneously within 2 weeks. OCT confirmed device stability and position under the macula. Improvements in localization abilities were demonstrated for all 4 participants in screen-based, tabletop, and orientation and mobility tasks. In addition, 3 of 4 participants recorded improvements in motion discrimination and 2 of 4 participants recorded substantial improvements in spatial discrimination and identification of tabletop objects. Participants reported their unsupervised use of the device included exploring new environments, detecting people, and safely navigating around obstacles. A positive effect of the implant on participants' daily lives in their local environments was confirmed by an orientation and mobility assessor and participant self-report. Emotional well-being was not impacted by device implantation or usage., Conclusions: The completed clinical study demonstrates that the suprachoroidal prosthesis raises no safety concerns and provides improvements in functional vision, activities of daily living, and observer-rated quality of life., Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (© 2024 by the American Academy of Ophthalmology.)

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.

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., Competing Interests: Disclosure: S.A. Titchener, Bionic Vision Technologies Pty Ltd (F); J. Kvansakul, Bionic Vision Technologies Pty Ltd (F); M.N. Shivdasani (P); J.B. Fallon, None; D.A.X. Nayagam, Bionic Vision Technologies Pty Ltd (F, P); S.B. Epp, Bionic Vision Technologies Pty Ltd (F); C.E. Williams, Bionic Vision Technologies Pty Ltd (F, P); N. Barnes, Bionic Vision Technologies Pty Ltd (F); W.G. Kentler, None; M. Kolic, Bionic Vision Technologies Pty Ltd (F); E.K. Baglin, Bionic Vision Technologies Pty Ltd (F); L.N. Ayton, None; C.J. Abbott, Bionic Vision Technologies Pty Ltd (F); C.D. Luu, Bionic Vision Technologies Pty Ltd (F, P); P.J. Allen, Bionic Vision Technologies Pty Ltd (F, P); M.A. Petoe, Bionic Vision Technologies Pty Ltd (F, P), (Copyright 2020 The Authors.)

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.

Background: Macular pigment (MP) is found in diurnal primate species when vision spans a range of ambient illumination and is mediated by cone and rod photoreceptors. The exact role of MP remains to be determined. In this study we investigate two new hypotheses for possible MP functions., Objective: As MP absorption coincides partly with that of rhodopsin, MP may reduce rod signal effectiveness in the mesopic range, thus extend the usefulness of cone-mediated vision into the mesopic range. Forward light scatter in the eye can reduce retinal image contrast. If blue light contributes significantly to intraocular scatter, selective blue light absorption by MP could reduce the effects of scatter., Design: We investigated 34 subjects from a carotenoid supplementation trial. The measurements included high mesopic contrast acuity thresholds (CATs), macular pigment optical density (MPOD), wavefront aberrations, and scattered light. The measurements were made after 6 months of daily supplementation with zeaxanthin (Z, OPTISHARP), lutein (L), a combination of the two (C), or placebo (P), and again after a further 6 months of doubled supplementation., Results: The data reveal a trend toward lower CATs in all groups supplemented, with a statistically significant improvement in the lutein group (p = 0.001), although there was no correlation with MPOD. Light scattering in the eye and the root-mean-square wavefront aberrations show decreasing trends as a result of supplementation, but no correlation with MPOD., Conclusions: The results suggest that supplementation with L or Z increases MPOD at the fovea and at 2.5 degrees , and that supplementation can improve CATs at high mesopic levels and hence visual performance at low illumination.

Background: Both yellow-blue (YB) discrimination thresholds and macular pigment optical density (MPOD) measurements in the eye exhibit large variability in the normal population. Although it is well established that selective absorption of blue light by the macular pigment (MP) can significantly affect trichromatic colour matches, the extent to which the MP affects colour discrimination (CD) sensitivity remains controversial., Objective: In this study, we assess whether the variability in YB thresholds is attributable to differences in MPOD, both at the fovea and in the paracentral visual field. We also investigated whether higher levels of MP offer any advantage in other visual functions such as red-green (RG) CD sensitivity., Design: CD thresholds and spatial MPOD profiles were measured in 24 normal trichromats supplemented with zeaxanthin (OPTISHARP) and/or lutein. Novel stimulus conditions that isolate YB and RG chromatic mechanisms were employed and MPOD profiles were measured up to an eccentricity of 8 degrees., Results: The data reveal an increase in MPOD in the supplemented subjects that was almost uniform within a centre region around the fovea subtending +/-4 degrees. RG sensitivity was high in all subjects with thresholds well within the normal range. Unexpectedly, YB thresholds were also normal and showed no correlation with MPOD. A model for threshold CD based on appropriate combinations of cone contrast signals was developed to explain the experimental findings., Conclusions: YB thresholds remain unaffected by supplementation with lutein and/or zeaxanthin rather, at increased MPOD levels, RG vision tends to be improved. The model accounts for the absence of correlation between MPOD and YB thresholds and predicts a marginal improvement in RG discrimination when MPOD is high.