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David AX Nayagam, Richard A Williams, Cesar Salinas La-Rosa, Ceara McGowan, Carla J Abbott, Stephanie Epp, Mohit Naresh Shivdasani, Chi D Luu, Joel Villalobos, Patrick Thien, Owen Burns, Alice Brandli, Chris Williams, Penelope J Allen, Robert Shepherd; Histopathological Criteria for Evaluation of Chronically Stimulated Retina. Invest. Ophthalmol. Vis. Sci. 2018;59(9):4562.
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© ARVO (1962-2015); The Authors (2016-present)
Previously we described a model to determine safe retinal stimulation limits using a clinical suprachoroidal electrode array (Nayagam et al. ARVO 2017). Using results obtained from this model we have categorised the various histopathologies elicited by long-term electrical stimulation of the retina.
13 normally-sighted cats were unilaterally implanted, suprachoroidally, with a medical grade electrode array. The array contained 44 platinum (Pt) electrodes (1mm diameter) and 2 large Pt return electrodes. Biphasic current pulses were delivered continuously at a range of defined charge levels (250-1450nC/phase), phase widths (145-580µs) and rates (50-200pps) to randomly assigned electrode pairs for up to 4 months (mean: 54 days). Following chronic stimulation, subjects’ eyes were prepared for histopathology using tissue dyes as fiduciary markers. Paraffin embedded tissue samples were randomised and blindly evaluated by two pathologists using pair-matched controls from the non-implanted fellow eyes. Common histopathological characteristics were categorised to facilitate intra- and inter- experimental comparisons.
Chronic stimulation was well tolerated by the subjects. The tissue regions adjacent to stimulated-electrodes (n = 81) presented a variety of histopathologies. These were divided into four categories that were each scored on a 4-point scale corresponding with ‘no deviation’ (0) to ‘major deviation’ (3) from expected baseline: acute inflammatory response (0=37%, 1=35%, 2=21%, 3=7%); chronic inflammatory response (0=25%, 1=38%, 2=36%, 3=1%); fibroblastic response (0=33%, 1=59%, 2=7%, 3=0%); histiocytic/foreign-body multinucleated giant cell response (0=2%, 1=54%, 2=40%, 3=4%). Eight other features were assessed in a binary fashion: scarring (24%), trauma or external inflammation (5%), necrosis (5%), retinal detachment (13%), retinal pigmentary changes (70%), ganglion cell layer thinning (yes = 4%), neuronal (Nissl) changes (yes = 5%), outer nuclear layer changes (yes = 6%).
Using an animal model for assessing the safety limits of chronic electrical stimulation of the retina, a categorical histopathological scoring system has been developed to encompass the wide range of tissue responses to chronic electrical stimulation. Combining histopathological scores with individual electrode’s stimulation parameters will aid in the determination of safe stimulation limits for retinal prostheses.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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