July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Histopathological Criteria for Evaluation of Chronically Stimulated Retina
Author Affiliations & Notes
  • David AX Nayagam
    Bionics Institute, East Melbourne, Victoria, Australia
    Pathology, University of Melbourne, Melbourne, Victoria, Australia
  • Richard A Williams
    Pathology, University of Melbourne, Melbourne, Victoria, Australia
    Anatomical Pathology, St Vincent's Hospital Melbourne, Melbourne, Victoria, Australia
  • Cesar Salinas La-Rosa
    Pathology, University of Melbourne, Melbourne, Victoria, Australia
    Anatomical Pathology, St Vincent's Hospital Melbourne, Melbourne, Victoria, Australia
  • Ceara McGowan
    Bionics Institute, East Melbourne, Victoria, Australia
  • Carla J Abbott
    Centre for Eye Research Australia, Melbourne, Victoria, Australia
    Surgery (Ophthalmology), The University of Melbourne, Melbourne, Victoria, Australia
  • Stephanie Epp
    Bionics Institute, East Melbourne, Victoria, Australia
  • Mohit Naresh Shivdasani
    Bionics Institute, East Melbourne, Victoria, Australia
    Medical Bionics, University of Melbourne, Melbourne, Victoria, Australia
  • Chi D Luu
    Centre for Eye Research Australia, Melbourne, Victoria, Australia
    Surgery (Ophthalmology), The University of Melbourne, Melbourne, Victoria, Australia
  • Joel Villalobos
    Bionics Institute, East Melbourne, Victoria, Australia
  • Patrick Thien
    Bionics Institute, East Melbourne, Victoria, Australia
    Medical Bionics, University of Melbourne, Melbourne, Victoria, Australia
  • Owen Burns
    Bionics Institute, East Melbourne, Victoria, Australia
  • Alice Brandli
    Centre for Eye Research Australia, Melbourne, Victoria, Australia
    Surgery (Ophthalmology), The University of Melbourne, Melbourne, Victoria, Australia
  • Chris Williams
    Bionics Institute, East Melbourne, Victoria, Australia
  • Penelope J Allen
    Centre for Eye Research Australia, Melbourne, Victoria, Australia
    Surgery (Ophthalmology), The University of Melbourne, Melbourne, Victoria, Australia
  • Robert Shepherd
    Bionics Institute, East Melbourne, Victoria, Australia
    Medical Bionics, University of Melbourne, Melbourne, Victoria, Australia
  • Footnotes
    Commercial Relationships   David Nayagam, None; Richard Williams, None; Cesar Salinas La-Rosa, None; Ceara McGowan, None; Carla Abbott, None; Stephanie Epp, None; Mohit Shivdasani, Bionics Institute (P); Chi Luu, None; Joel Villalobos, Bionics Institute (P); Patrick Thien, None; Owen Burns, Bionics Institute (P); Alice Brandli, None; Chris Williams, Bionics Institute (P); Penelope Allen, Centre for Eye Research Australia (P); Robert Shepherd, None
  • Footnotes
    Support  ARC Special Research Initiative in Bionic Vision Science and Technology grant to Bionic Vision Australia; NHMRC grant 1082358 to CIA A/Prof Allen; NHMRC grant 1120664 to CIA A/Prof Williams. The Centre for Eye Research Australia and the Bionics Institute wish to acknowledge the support of Bionic Vision Technologies for additional funding support and the Victorian Government through its Operational Infrastructure Support Program.
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 4562. doi:https://doi.org/
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    • Get Citation

      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. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : 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.

Methods : 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.

Results : 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%).

Conclusions : 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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