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V. Ortmann; How to Define a "Therapeutic Window" of the Retina Stimulation . Invest. Ophthalmol. Vis. Sci. 2005;46(13):1531.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Effective clinical application of neural stimulation assumes a definition of "therapeutic window" – a set of safe stimulation parameters required to cause an excitation of neurons. The goal of this investigation was to define such window for retina stimulation. Methods: We performed a crude estimation of required stimulation parameters based on the analysis of published experimental results, describing different retina stimulation experiments involving patients and animal models. Analysis of several publications and technical reports describing cases of neural injury induced by electrical stimulation allowed us to obtain an estimate of safety levels. A comparison of these levels with the required stimulation parameters gives us information about the available "therapeutic window". Results: The stimulation thresholds were observed in the range of 40–2000 pC/phase and charge densities between 0.01 and 10mC/cm². The most probable stimulation threshold belongs to the stimulation window between 200–800 pC/phase and charge densities in the range of 100–800 µC/cm². The safety level is defined by two equations log(D)=1.7–log(C) and D<Dmax, where D – charge density, Dmax – charge density initiating the corrosion and C – charge per phase. The first equation is derived from neurophysiological experiments, investigating the safety issues of electrical neurostimulation. The second corresponds to the electrochemical stability of electrodes and is material dependent. Comparison of safety levels and stimulation thresholds shows, that more than 60% of published stimulation thresholds lie above the safety level and can cause a neural injury. The same patient may have a fraction of electrodes which meets the safety standards, whereas the rest of the electrodes is stimulated at potentially unsafe levels. Such a situation will result in only a part of electrodes being activated causing a greatly reduced quality of visual sensation. Conclusions: A series of long–term animal trials with stimulation levels adequate to the application should be performed in order to get objective measurements of the injury level of the retina. At the same time a significant improvement of the stimulation interface should be achieved, in order to win a gap of 6–20dB between the safety level and required stimulation thresholds. The "therapeutic window", based on the existing results, covers only a small part of potential patients and may be inadequate for clinical application.
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