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.

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.

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.

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.

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.

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.

The categorisation of non-categorical colours: a novel paradigm in colour perception.

In this paper, we investigate a new paradigm for studying the development of the colour 'signal' by having observers discriminate and categorize the same set of controlled and calibrated cardinal coloured stimuli. Notably, in both tasks, each observer was free to decide whether two pairs of colors were the same or belonged to the same category. The use of the same stimulus set for both tasks provides, we argue, an incremental behavioural measure of colour processing from detection through discrimination to categorisation. The measured data spaces are different for the two tasks, and furthermore the categorisation data is unique to each observer. In addition, we develop a model which assumes that the principal difference between the tasks is the degree of similarity between the stimuli which has different constraints for the categorisation task compared to the discrimination task. This approach not only makes sense of the current (and associated) data but links the processes of discrimination and categorisation in a novel way and, by implication, expands upon the previous research linking categorisation to other tasks not limited to colour perception.

The detection of the motion of contrast modulation: a parametric study.

Despite a long and productive history as a focus of research interest, the details of how humans detect motion in an image remain controversial. This debate has not been helped by the lack of a clear parametric description of motion discrimination for some of the more simple visual stimuli employed in the literature to date. With this in mind, in the present work, we examined a peculiarity observed in the perception of the motion of second-order (contrast-modulated) stimuli: Under certain stimulus conditions, there is a reversal in the perceived direction of motion of the pattern. The aim was to quantify this phenomenon, relate the reversal to forward (veridical) and ambiguous motion, and place the behavioral data in the context of the window of visibility model of spatiotemporal contrast sensitivity. The direction of motion of contrast-modulated patterns was measured as a function of temporal frequency and carrier contrast, under different critical stimulus conditions. The stimulus properties manipulated were spatial frequency, spatial-phase relationship of carrier and sidebands, color, duration, and, most critically, the retinal location of the stimulus. On a purely empirical basis, the data reconciled several conflicts in the recent literature. From a theoretical standpoint, the data were well explained by the window of visibility approach in the majority of conditions and were partially explained in the remaining conditions. The results raise some interesting questions about underlying motion detection mechanisms and the assumptions embodied in our approach to motion modeling and the visual system in general. Supplemental materials for this article may be downloaded from app.psychonomic-journals.org/content/supplemental.

Supplementation with the carotenoids lutein or zeaxanthin improves human visual performance.

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.

The effects of supplementation with lutein and/or zeaxanthin on human macular pigment density and colour vision.

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.