Ruptured ocular capillaries are a fairly frequent occurrence that often resolve without treatment, but can be an indicator of more important pathologies.
Photovoltaic retinal prostheses: new hope for blind patients
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Retina
Our interview on the characteristics and development prospects of photovoltaic retinal prostheses, which Daniel Palanker and his research group have developed in the laboratories of Stanford University (California, USA).
How could a retinal prosthesis be helpful in restoring visual function in a patient with a degenerative retinal disease? Degenerative retinal diseases lead to the progressive loss of photoreceptors that 'capture images', while internal retinal neurons, which 'process images', remain largely intact [1]. Electrical stimulation of these neurons can generate visual sensations. An alternative pathway for visual perception can thus be hypothesised, giving rise to new hopes of restoring sight to blind patients.
In some recent clinical trials, electrode arrays have been implanted, both in the epiretinal (i.e. facing the ganglion cells) that in position subretinal (directed, instead, towards the photoreceptors) and succeeded in restoring visual acuity in the order of 20/1200 in patients blinded by retinal degenerative diseases [2, 3].
What are the main differences between photovoltaic retinal prostheses, on which your research group is working, and other prostheses, such as Argus II, which have already been implanted in humans in Pisa last year? The results, achieved by implanting the currently available prostheses in patients, constitute important proof of the validity of this experimental hypothesis, with important clinical implications; however, such devices require cables that must penetrate the eye in order to carry the energy to the retinal plates containing the electrodes.
Our design overcomes these problems by using pre-fabricated plates containing photovoltaically stimulated photodiodes. The retinal prosthetic system, depicted in Figure 1 A-B, comprises a miniaturised video camera that captures images of the visual scenario. The video stream, processed by a pocket computer, is displayed on a display very close to the eye, similar to common stereoscopic glasses.
These images are then projected onto the subretinal implant using pulsed near-infrared light (NIR: 880-915 nm) [4]. The photodiodes in each pixel of the plate convert this light into a pulsed electric current that passes through the retina and stimulates the inner retinal neurons.
The direct activation of each pixel of the sub-retinal implant eliminates the need for complex patterns, consisting of electrodes and connecting cables, and preserves the natural connection between image perception and eye movements.
This wireless system can be modulated up to a structure with thousands of electrodes.
The implant surgery is thus considerably simplified. We invite you to watch the video, posted on YouTube by Dr Palanker's team, in which the implantation technique is illustrated.
The modular structure of the system allows the field of vision to be expanded by placing the plates side by side.
How are these results possible with photovoltaic retinal implants? Photo pixels convert pulsed near-infrared light into pulses of electric current capable of stimulating the nearest inner retinal neurons. In order to maximise the stimulation while remaining within electro-chemical safety limits, each pixel is equipped with three photodiodes connected in series between the active central electrode and the return electrode in the circumference, both coated with SIROF. The smallest size that can be realised in current systems is 70 ?m, with a 20 ?m disc-shaped electrode in the centre, as illustrated in Figure 2.
A return electrode, located in each pixel, helps to limit the electric field and reduces inter-communication flows between the multiple simultaneously activated pixels in that plate. This is a key aspect in achieving high stimulation resolution.
However, a more pronounced lateral containment of the electric field reduces its depth of penetration into the retina, making the efficiency of the system more susceptible to variations near the target neurons.
Our research group demonstrated the functionality of this device by successfully stimulating the retinas of both healthy and degenerated mice. With 140 ?m pixels, the in-vitro stimulation threshold with 4 ms pulses was 0.3 mW/mm2 for the normal retina is 0.8 mW/mm2 for the degenerated retina.
These radiation peaks are about 1,000 times higher than the most intense ambient light that can reach the retina.
Since most legally blind patients maintain a slight light sensitivity, it is not possible to use sensitive light at higher intensity levels. In fact, our research group used near-infrared light with a wavelength in the range 880-915 nm, which is invisible to photoreceptors but can still activate silicon photodiodes. With a pulse repetition rate of 15 Hz the average irradiance is 0.05 mW/mm2two orders of magnitude below the safe limit for this wavelength range [5].
PV plates with a size of 0.8×1.2 mm and a thickness of 30 ?m were well tolerated in the subretinal space of the mice during the six-month follow-up. In-vivo Visual Evoked Potential recordings showed that brain activity was induced, with stimulation thresholds similar to the corresponding in-vitro values for normal and degenerated retinas. How could retinal responses be modulated? The induced responses could be modulated by both the intensity of the light and the amplitude of the pulse.
The optical system described uses a liquid crystal display (LCD) illuminated by a laser beam to form patterns of near-infrared light, allowing the intensity to be modulated within each video frame.
DLP technologyTMbased on a series of micro-mirrors activated at high speed, can be used to modify the retinal response by varying the pulse amplitude in each pixel. This device would allow precise control over both the duration and timing of exposures, enabling sequential activation of the closest pixels to further reduce inter-pixel communication. Furthermore, a holographic projection pattern using Spatial Light Modulators can handle a larger volume of data and allow precise control of the timing in each pixel.
The following can be summarised in a few wordsadvantages of photovoltaic retinal prostheses? Optical activation makes the photovoltaic retinal prosthesis completely different from other wire implants. The implantation is surgically quite simple, while multiple modules make it possible to create a scalar structure with up to thousands of electrodes and can provide a larger visual field. This prosthesis preserves the natural connection between eye movements and image perception and can function in all ambient lighting conditions.
This system is very versatile and, therefore, could be used to meet the very different needs of patients suffering from the various forms of retinal degeneration.
Future research will define the limits of resolution in retinal stimulation with photovoltaic plates in vitro and the corresponding visual acuity in vivo.
For more information: Daniel Palanker, PhD Associate Professor Department of Ophthalmology and Hansen Experimental Physics Laboratory StanfordUniversity E-mail: palanker@stanford.edu http://www.stanford.edu/~palanker/
Bibliography 1. Kim, S.Y., et al, Morphometric analysis of the macula in eyes with disciform age-related macular degeneration. Retina, 2002. 22(4): p. 471-7.
2. Zrenner, E., et al, Subretinal electronic chips allow blind patients to read letters and combine them to words. Proc Biol Sci, 2011. 278 (1711): p. 1489-97.
3. Ahuja, A.K., et al, Blind subjects implanted with the Argus II retinal prosthesis are able to improve performance in a spatial-motor task. Br J Ophthalmol, 2011. 95(4): p. 539-43.
4. Mathieson, K., et al, Photovoltaic retinal prosthesis with high pixel density. Nature Photonics, 2012. 6(6): p. 391-397.
5. Loudin, J.D., et al, Photodiode Circuits for Retinal Prostheses. Biomedical Circuits and Systems, IEEE Transactions on, 2011. 5(5): p. 468-480.
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