Evaluation of phosphenes elicited by extraocular stimulation in normals and by suprachoroidal-transretinal stimulation in patients with retinitis pigmentosa

Department of Applied Visual Science, Osaka University Graduate School of Medicine, Osaka, Japan.
Albrecht von Graæes Archiv für Ophthalmologie (Impact Factor: 1.91). 10/2007; 245(10):1411-9. DOI: 10.1007/s00417-007-0563-z
Source: PubMed


To determine the efficient parameters to evoke electrical phosphenes is essential for the development of a retinal prosthesis. We studied the efficient parameters in normal subjects and investigated if suprachoroidal-transretinal stimulation (STS) is effective in patients with advanced retinitis pigmentosa (RP) using these efficient parameters.
The amplitude of pupillary reflex (PR) evoked by transcorneal electrical stimulation (TcES) was determined at different frequencies in eight normal subjects. The relationship between localized phosphenes elicited by transscleral electrical stimulation (TsES) and the pulse parameters was also examined in six normal subjects. The phosphenes evoked by STS were examined in two patients with RP with bare light perception. Biphasic pulses (cathodic first, duration: 0.5 or 1.0 ms, frequency: 20 Hz) were applied through selected channel(s). The size and shape of the phosphenes perceived by the patients were recorded.
The maximum PR was evoked by TcES with a frequency of 20 Hz. The brightest phosphene was elicited by TsES with a pulse train of more than 10 pulses, duration of 0.5-1.0 ms and a frequency of 20 to 50 Hz. In RP patients, localized phosphenes were elicited with a current of 0.3-0.5 mA (0.5 ms) in patient 1 and 0.4 mA (1.0 ms) in patient 2. Two isolated or dumbbell-shaped phosphenes were perceived when the stimulus was delivered through two adjacent channels.
Biphasic pulse trains (> or =10 pulses) with a duration of 0.5-1.0 ms and a frequency of 20-50 Hz were efficient for evoking phosphenes by localized extraocular stimulation in normal subjects. With these parameters, STS is a feasible method to use with a retinal prosthesis even in advanced stages of RPs.

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    • "Retinal ganglion cells (RGCs) survive in large numbers following neurodegenerative diseases [15]. These cells could be stimulated by extracellular electrical pulses to produce visual percepts in the blind [4]–[6], [24]. To examine how the anatomically complex RGC neuronal elements respond to extracellular electrical stimulation, we constructed morphologically and biophysically detailed models of large-field mammalian On and Off RGCs (Figure 1A). "
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    ABSTRACT: Retinal ganglion cells (RGCs), which survive in large numbers following neurodegenerative diseases, could be stimulated with extracellular electric pulses to elicit artificial percepts. How do the RGCs respond to electrical stimulation at the sub-cellular level under different stimulus configurations, and how does this influence the whole-cell response? At the population level, why have experiments yielded conflicting evidence regarding the extent of passing axon activation? We addressed these questions through simulations of morphologically and biophysically detailed computational RGC models on high performance computing clusters. We conducted the analyses on both large-field RGCs and small-field midget RGCs. The latter neurons are unique to primates. We found that at the single cell level the electric potential gradient in conjunction with neuronal element excitability, rather than the electrode center location per se, determined the response threshold and latency. In addition, stimulus positioning strongly influenced the location of RGC response initiation and subsequent activity propagation through the cellular structure. These findings were robust with respect to inhomogeneous tissue resistivity perpendicular to the electrode plane. At the population level, RGC cellular structures gave rise to low threshold hotspots, which limited axonal and multi-cell activation with threshold stimuli. Finally, due to variations in neuronal element excitability over space, following supra-threshold stimulation some locations favored localized activation of multiple cells, while others favored axonal activation of cells over extended space.
    PLoS ONE 12/2012; 7(12):e53357. DOI:10.1371/journal.pone.0053357 · 3.23 Impact Factor
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    • "Clinical studies with epiretinal electrode arrays were also performed by Koch et al. [29] and Richard et al. [30]. Other groups developed approaches with electrodes placed between sclera and choroid [8,10]. These groups argue that this ‘suprachoroidal’ approach may have the benefit of being less invasive, therefore bearing fewer risks in terms of surgical procedures. "
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    ABSTRACT: A light-sensitive, externally powered microchip was surgically implanted subretinally near the macular region of volunteers blind from hereditary retinal dystrophy. The implant contains an array of 1500 active microphotodiodes ('chip'), each with its own amplifier and local stimulation electrode. At the implant's tip, another array of 16 wire-connected electrodes allows light-independent direct stimulation and testing of the neuron-electrode interface. Visual scenes are projected naturally through the eye's lens onto the chip under the transparent retina. The chip generates a corresponding pattern of 38 × 40 pixels, each releasing light-intensity-dependent electric stimulation pulses. Subsequently, three previously blind persons could locate bright objects on a dark table, two of whom could discern grating patterns. One of these patients was able to correctly describe and name objects like a fork or knife on a table, geometric patterns, different kinds of fruit and discern shades of grey with only 15 per cent contrast. Without a training period, the regained visual functions enabled him to localize and approach persons in a room freely and to read large letters as complete words after several years of blindness. These results demonstrate for the first time that subretinal micro-electrode arrays with 1500 photodiodes can create detailed meaningful visual perception in previously blind individuals.
    Proceedings of the Royal Society B: Biological Sciences 11/2010; 278(1711):1489-97. DOI:10.1098/rspb.2010.1747 · 5.05 Impact Factor
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    • "Particularly, a phosphene will be referred to as a single, elementary spot of light in the visual field unless explicitly stated otherwise. This means that a cluster of dots elicited (Veraart et al., 2003) will be addressed as a cluster of phosphenes, and a merged patch of light from multiple electrodes (Brindley & Lewin, 1968; Brindley & Rushton, 1974; Fujikado et al., 2007; Horsager, Weiland, Greenberg , Humayun, & Fine, 2008; Zrenner et al., 2006, 2007) will be addressed as a combinatorial effect of multiple phosphenes. Table 1 Summary of the appearances of phosphenes elicited via electrical stimulation at various sites in chronic human trials of vision prosthesis devices. "
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    ABSTRACT: With increasing research advances and clinical trials of visual prostheses, there is significant demand to better understand the perceptual and psychophysical aspects of prosthetic vision. In prosthetic vision a visual scene is composed of relatively large, isolated, spots of light so-called "phosphenes", very much like a magnified pictorial print. The utility of prosthetic vision has been studied by investigators in the form of virtual-reality visual models (simulations) of prosthetic vision administered to normally sighted subjects. In this review, the simulations from these investigations are examined with respect to how they visually render the phosphenes and the virtual-reality apparatus involved. A comparison is made between these simulations and the actual descriptions of phosphenes reported from human trials of visual prosthesis devices. For the results from these simulation studies to be relevant to the experience of visual prosthesis recipients, it is important that, the simulated phosphenes must be consistent with the descriptions from human trials. A standardized simulation and reporting framework is proposed so that future simulations may be configured to be more realistic to the experience of implant recipients, and the simulation parameters from different investigators may be more readily extracted, and study results more fittingly compared.
    Vision research 07/2009; 49(12):1493-506. DOI:10.1016/j.visres.2009.02.003 · 1.82 Impact Factor
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