Designing artificial senses: steps from physiology to clinical implementation.

Our senses are the main information channels through which we perceive and interact with the world. Consequently, the physical and social functioning of patients suffering from severe sensory disabilities is limited on several levels. This has motivated the development of a novel therapeutic alternative: “artificial senses”, more commonly known as sensory neuroprostheses. In order to restore lost function, sensory neuroprostheses attempt to take advantage of the information transfer pathway common to all senses: (i) transduction of the physical stimulus by sensory receptors, (ii) transmission of relevant information to primary sensory areas in the brain by sensory afferents, and (iii) analysis and integration of the information at multiple levels in the central nervous system. Neurosensory deficits might occur upon damage to any of the structures involved in this process. However, damage to the peripheral sensory receptor is often the cause of neurosensory loss. Most sensory neuroprostheses attempt to “replace” the malfunctioning or missing peripheral sensory organ by directly delivering basic sensory information to the brain using electrical currents. If the prosthesis is able to deliver enough consistent information, the brain will be able to correctly interpret it and useful rehabilitation can be achieved. This review presents the main challenges related to the development, implementation and translation to clinical practice of these devices: (i) sensory information needs to be efficiently delivered to specific neural targets (e.g., peripheral afferents or specific central nuclei); (ii) then the expected physiological response must be evoked and quantified; (iii) the restoration of basic sensory abilities can lead to useful rehabilitation in meaningful everyday activities; (iv) optimal prospects require specific rehabilitation therapy and lifelong medico-technical follow-up. To conclude, the current state and future of sensory neuroprostheses will be discussed. This will include current clinical and technical challenges, future prospects, and the potential of these devices to improve our fundamental knowledge of sensory physiology and neurosensory deficits.

Temporal properties of visual perception on electrical stimulation of the retina.

PURPOSE: To investigate the elementary temporal properties of electrically evoked percepts in blind patients chronically implanted with an epiretinal prosthesis. METHODS: Nine subjects were presented with isolated stimuli of variable duration and pulse rate. Stimulation amplitude was set to the upper comfortable level and a group of 2 × 2 adjacent electrodes was simultaneously activated. First, subjects were asked to verbally describe their visual perception paying particular attention to the time-course of brightness. Then, in subsequent trials, they described the brightness time dependence using a joystick while auditory feedback of joystick position was provided. RESULTS: All subjects described a bright, well-localized percept at stimulus onset. Only one subject reported such a bright, well-localized visual sensation during an entire 10-second stimulation trial. For the remaining eight subjects, it faded more or less rapidly (in four cases <0.5 second) and was often followed by a percept described as less bright, poorly localized, and having different color. Only initial percepts at stimulation onset seemed bright and localized enough to reconstruct a patterned image. Changing stimulation pulse rate influenced the time course of perception only in some cases but the effect was not systematic. CONCLUSIONS: Percepts differed considerably across subjects, probably because of the considerable variations in the progression and remodeling processes associated with the disease. Appropriate coding of a patterned image under such conditions appears challenging. Further research of the underlying mechanisms of visual perception upon electrical stimulation of the retina is required to optimize stimulation paradigms and to better establish patient selection criteria.

Reading with a simulated 60-channel implant.

First generation retinal prostheses containing 50-60 electrodes are currently in clinical trials. The purpose of this study was to evaluate the theoretical upper limit (best possible) reading performance attainable with a state-of-the-art 60-channel retinal implant and to find the optimum viewing conditions for the task. Four normal volunteers performed full-page text reading tasks with a low-resolution, 60-pixel viewing window that was stabilized in the central visual field. Two parameters were systematically varied: (1) spatial resolution (image magnification) and (2) the orientation of the rectangular viewing window. Performance was measured in terms of reading accuracy (% of correctly read words) and reading rates (words/min). Maximum reading performances were reached at spatial resolutions between 3.6 and 6 pixels/char. Performance declined outside this range for all subjects. In optimum viewing conditions (4.5 pixels/char), subjects achieved almost perfect reading accuracy and mean reading rates of 26 words/min for the vertical viewing window and of 34 words/min for the horizontal viewing window. These results suggest that, theoretically, some reading abilities can be restored with actual state-of-the-art retinal implant prototypes if "image magnification" is within an "optimum range." Future retinal implants providing higher pixel resolutions, thus allowing for a wider visual span might allow faster reading rates.

Simulation of artificial vision: IV. Visual information required to achieve simple pointing and manipulation tasks.

Retinal prostheses attempt to restore some amount of vision to totally blind patients. Vision evoked this way will be however severely constrained because of several factors (e.g., size of the implanted device, number of stimulating contacts, etc.). We used simulations of artificial vision to study how such restrictions of the amount of visual information provided would affect performance on simple pointing and manipulation tasks. Five normal subjects participated in the study. Two tasks were used: pointing on random targets (LEDs task) and arranging wooden chips according to a given model (CHIPs task). Both tasks had to be completed while the amount of visual information was limited by reducing the resolution (number of pixels) and modifying the size of the effective field of view. All images were projected on a 10 degrees x 7 degrees viewing area, stabilised at a given position on the retina. In central vision, the time required to accomplish the tasks remained systematically slower than with normal vision. Accuracy was close to normal at high image resolutions and decreased at 500 pixels or below, depending on the field of view used. Subjects adapted quite rapidly (in less than 15 sessions) to performing both tasks in eccentric vision (15 degrees in the lower visual field), achieving after adaptation performances close to those observed in central vision. These results demonstrate that, if vision is restricted to a small visual area stabilised on the retina (as would be the case in a retinal prosthesis), the perception of several hundreds of retinotopically arranged phosphenes is still needed to restore accurate but slow performance on pointing and manipulation tasks. Considering that present prototypes afford less than 100 stimulation contacts and that our simulations represent the most favourable visual input conditions that the user might experience, further development is required to achieve optimal rehabilitation prospects.

Primary vitrectomy without scleral buckling for pseudophakic rhegmatogenous retinal detachment.

PURPOSE: To report the anatomic and functional results of primary vitrectomy without scleral buckling for the treatment of pseudophakic rhegmatogenous retinal detachment (PsRD). DESIGN: Prospective, nonrandomized surgical technique study. METHODS: One hundred eyes of 98 patients with PsRD were operated by vitrectomy alone. Internal subretinal fluid drainage, cryocoagulation and/or endolaser and fluid-air exchange with sulfur hexafluoride 20% was applied in all cases. The preoperative and postoperative characteristics were analyzed. Main outcome measures were anatomic success rates after initial surgical intervention and after reoperation for primary failures, visual outcome at the last follow-up visit, and complications. RESULTS: Mean follow-up +/- standard deviation (SD) was 12 +/- 6.3 months (range, seven to 36 months). Mean final visual acuity +/- SD was 0.42 +/- 0.45 logarithm of the minimum angle of resolution (logMAR) compared with 0.95 +/- 0.73 logMAR before surgery (P < .01). Mean number +/- SD of retinal breaks found before surgery was 1.36 +/- 1.12 (range, zero to five), and an additional 1.58 +/- 2.26 (range, zero to 15) retinal breaks were found during surgery. The retina was reattached successfully after a single surgery in 92 eyes (92%). Recurrence of retinal detachment occurred in eight eyes (8%), caused by proliferative vitreoretinopathy in six eyes (75%) and by new breaks in two eyes (25%). Final anatomic reattachment was obtained in these cases after a mean of 1.75 subsequent operations. Three eyes required permanent silicone oil tamponade so that final anatomic success was achieved in 97 eyes (97%). The most common postoperative complication was ocular hypertonia of more than 21 mm Hg, observed in 36 (36%) eyes, which was managed successfully. CONCLUSIONS: Primary vitrectomy without scleral buckling provides a high anatomic success rate in eyes with PsRD and is associated with few complications.

Processes involved in oculomotor adaptation to eccentric reading.

PURPOSE: Adaptation to eccentric viewing in subjects with a central scotoma remains poorly understood. The purpose of this study was to analyze the adaptation stages of oculomotor control to forced eccentric reading in normal subjects. METHODS: Three normal adults (25.7 +/- 3.8 years of age) were trained to read full-page texts using a restricted 10 degrees x 7 degrees viewing window stabilized at 15 degrees eccentricity (lower visual field). Gaze position was recorded throughout the training period (1 hour per day for approximately 6 weeks). RESULTS: In the first sessions, eye movements appeared inappropriate for reading, mainly consisting of reflexive vertical (foveating) saccades. In early adaptation phases, both vertical saccade count and amplitude dramatically decreased. Horizontal saccade frequency increased in the first experimental sessions, then slowly decreased after 7 to 15 sessions. Amplitude of horizontal saccades increased with training. Gradually, accurate line jumps appeared, the proportion of progressive saccades increased, and the proportion of regressive saccades decreased. At the end of the learning process, eye movements mainly consisted of horizontal progressions, line jumps, and a few horizontal regressions. CONCLUSIONS: Two main adaptation phases were distinguished: a "faster" vertical process aimed at suppressing reflexive foveation and a "slower" restructuring of the horizontal eye movement pattern. The vertical phase consisted of a rapid reduction in the number of vertical saccades and a rapid but more progressive adjustment of remaining vertical saccades. The horizontal phase involved the amplitude adjustment of horizontal saccades (mainly progressions) to the text presented and the reduction of regressions required.

Simulation of artificial vision, III: do the spatial or temporal characteristics of stimulus pixelization really matter?

PURPOSE: In preceding studies, simulations of artificial vision were used to determine the basic parameters for visual prostheses to restore useful reading abilities. These simulations were based on a simplified procedure to reduce stimuli information content by preprocessing images with a block-averaging algorithm (square pixelization). In the present study, how such a simplified algorithm affects reading performance was examined. METHODS: Five to six volunteers with normal vision were asked to read full pages of text with a 10 degrees x 7 degrees viewing window stabilized in central vision. In a first experiment, reading performance with off-line and real-time square pixelizations was compared at different resolutions. In a second experiment, off-line square pixelization was compared with off-line Gaussian pixelization with various degrees of overlap. In a third experiment, real-time square pixelization was compared with real-time Gaussian pixelization. RESULTS: Results from the first experiment showed that real-time square pixelization required approximately 30% less information (pixels) than its off-line counterpart. Results from the second experiment, using off-line processing, revealed a restricted range of Gaussian widths for which performances were equivalent or significantly better than that obtained with square pixelization. The third experiment demonstrated, however, that reading performances were similar in both real-time pixelization conditions. CONCLUSIONS: This study reveals that real-time stimulus pixelization favors reading performance. Performance gains were moderate, however, and did not allow for a significant (e.g., twofold) reduction of the minimum resolution (400-500 pixels) needed to achieve useful reading abilities.

Simulation of artificial vision: II. Eccentric reading of full-page text and the learning of this task.

Reading of isolated words in conditions mimicking artificial vision has been found to be a difficult but feasible task. In particular at relatively high eccentricities, a significant adaptation process was required to reach optimal performances [Vision Res. 43 (2003) 269]. The present study addressed the task of full-page reading, including page navigation under control of subject's own eye movements. Conditions of artificial vision mimicking a retinal implant were simulated by projecting stimuli with reduced information content (lines of pixelised text) onto a restricted and eccentric area of the retina. Three subjects, naïve to the task, were trained for almost two months (about 1 h/day) to read full-page texts. Subjects had to use their own eye movements to displace a 10 degrees x 7 degrees viewing window, stabilised at 15 degrees eccentricity in their lower visual field. Initial reading scores were very low for two subjects (about 13% correctly read words), and astonishingly high for the third subject (86% correctly read words). However, all of them significantly improved their performance with time, reaching close to perfect reading scores (ranging from 86% to 98% correct) at the end of the training process. Reading rates were as low as 1-5 words/min at the beginning of the experiment and increased significantly with time to 14-28 words/min. Qualitative text understanding was also estimated. We observed that reading scores of at least 85% correct were necessary to achieve 'good' text understanding. Gaze position recordings, made during the experimental sessions, demonstrated that the control of eye movements, especially the suppression of reflexive vertical saccades, constituted an important part of the overall adaptive learning process. Taken together, these results suggest that retinal implants might restore full-page text reading abilities to blind patients. About 600 stimulation contacts, distributed on an implant surface of 3 x 2 mm2, appear to be a minimum to allow for useful reading performance. A significant learning process will however be required to reach optimal performance with such devices, especially if they have to be placed outside the foveal area.

Simulation of artificial vision: I. Eccentric reading of isolated words, and perceptual learning.

Simulations of artificial vision were performed to assess "minimum requirements for useful artificial vision". Retinal prostheses will be implanted at a fixed (and probably eccentric) location of the retina. To mimic this condition on normal observers, we projected stimuli of various sizes and content on a defined stabilised area of the visual field. In experiment 1, we asked subjects to read isolated 4-letter words presented at various degrees of pixelisation and at various eccentricities. Reading performance dropped abruptly when the number of pixels was reduced below a certain threshold. For central reading, a viewing area containing about 300 pixels was necessary for close to perfect reading (>90% correctly read words). At eccentricities beyond 10 degrees, close to perfect reading was never achieved even if more than 300 pixels were used. A control experiment using isolated letter recognition in the same conditions suggested that lower reading performance at high eccentricity was in part due to the "crowding effect". In experiment 2, we investigated whether the task of eccentric reading under such specific conditions could be improved by training. Two subjects, naive to this task, were trained to read pixelised 4-letter words presented at 15 degrees eccentricity. Reading performance of both subjects increased impressively throughout the experiment. Low initial reading scores (range 6%-23% correct) improved impressively (range 64%-85% correct) after about one month of training (about 1 h/day). Control tests demonstrated that the learning process consisted essentially in an adaptation to use an eccentric area of the retina for reading. These results indicate that functional retinal implants consisting of more than 300 stimulation contacts will be needed. They might successfully restore some reading abilities in blind patients, even if they have to be placed outside the foveal area. Reaching optimal performance may, however, require a significant adaptation process.

Effect of isometric exercise on choroidal blood flow in type I diabetic patients.

BACKGROUND: In healthy subjects, choroidal blood flow is regulated when the mean ocular perfusion pressure increases. Since capillary vascular beds are altered in diabetic patients, the regulation of choroidal blood flow could be affected by this pathology. PATIENTS AND METHODS: 10 type I diabetic patients without retinopathy (DNR group) and 7 type I diabetic patients with retinopathy (DR group) participated in the study. In NDR and DR groups, choroidal blood flow was measured while patients raised their mean arterial blood pressure by squatting. The results were compared to those of a previous study in normals. Pupillometry was performed at rest on the two diabetic groups and on seven normals during a modification of illumination (white/black screen transition). RESULTS: In the NDR and DR groups, mean ocular perfusion pressure raised by 61 and 50 % during squatting, respectively. Consecutively, choroidal blood flow did not change in NDR as in normals, but increased linearly in DR patients. The white/black screen transition produced an increase of the pupil diameter of 52 and 49 % in normals and NDR patients, respectively, while it increased by only 16 % in the DR patients. CONCLUSIONS: As already shown in healthy subjects, choroidal blood flow is regulated in NDR patients when the ocular perfusion pressure increases. In DR patients, the absence of this control could be due to a failure of the autonomic nervous system, as suggested by pupillometry results.