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H.A. Shah, J.H. Chen, C.D. Herbert, J.F. Rizzo; Electrical Stimulation of the Rabbit Retina With a Sub–Retinal Electrode Array: Charge and Charge Density Limits for Safe Stimulation . Invest. Ophthalmol. Vis. Sci. 2005;46(13):1507.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose:To assess charge and charge density limits of tissue damage from sub–retinal electrical stimulation in the acute setting. Methods: A 1 x 5 activated iridium oxide electrode array was placed using an ab–externo surgical technique in the sub–retinal space of 7 Dutch–Belted rabbits. In 6 rabbits, electrical stimulation was performed for 8 hours using 400 µm diameter electrodes with non–biased, cathodal–first, symmetric waveforms at 45 Hz. Pulse duration was 1 ms/phase in all experiments. The levels of current, which was the only variable changed between each experiment, were 0.1, 0.2, 0.4, 0.6, 0.8, and 1.0 mA (charges of 0.1, 0.2, 0.4, 0.6, 0.8, and 1.0 µC per phase with corresponding charge densities of 0.08, 0.16, 0.32, 0.48, 0.64, and 0.80 mC/cm2). Animals were sacrificed and the eyes enucleated for standard histology. Integrity of the stimulating electrode was measured before and after stimulation by in vivo and in vitro cyclic voltammetry, and also by scanning electron microscopy (SEM) after each experiment. Results: Electrical stimulation did not produce any changes on funduscopy of the retina in any eye. Under light microscopy, there was no histological evidence of damage to the retina in the control experiment without stimulation in which there was an implant, and experiments that used 0.1 and 0.4 mA stimulation. At 0.2 mA, however, there was sub–retinal hemorrhage at the electrode array entry site. At 0.6 mA, there was localized hemorrhage near the stimulating electrode site. At 0.8 mA, there was retinal edema in addition to localized hemorrhage near the stimulating electrode site. At 1.0 mA, there was widespread sub–retinal hemorrhage along the length of the electrode array and the stimulating electrode was damaged. The neural retina in all eyes had normal gross cell morphology and laminar organization, although there was interstitial retinal edema at higher currents. Conclusions: The hemorrhages we observed that were localized to the site of the stimulating electrode at 0.6 mA and higher, are highly suggestive of stimulation induced damage. The possibility of retinal damage due to electrical stimulation during this acute study with lower charge/phase and charge density than has been used in some human experiments indicates the need for further study of safety limits for electrical stimulation.
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