June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
A Pre-clinical Model for Safe Retinal Stimulation
Author Affiliations & Notes
  • David A.X. Nayagam
    Bionics Institute, East Melbourne, Victoria, Australia
    Department of Pathology, University of Melbourne, Fitzroy, Victoria, Australia
  • Patrick C. Thien
    Bionics Institute, East Melbourne, Victoria, Australia
    Department of Medical Bionics, University of Melbourne, East Melbourne, Victoria, Australia
  • Carla J Abbott
    Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia
    Department of Surgery (Ophthalmology), University of Melbourne, East Melbourne, Victoria, Australia
  • Mohit Naresh Shivdasani
    Bionics Institute, East Melbourne, Victoria, Australia
  • Stephanie B Epp
    Bionics Institute, East Melbourne, Victoria, Australia
  • Joel Villalobos
    Bionics Institute, East Melbourne, Victoria, Australia
  • Ceara McGowan
    Bionics Institute, East Melbourne, Victoria, Australia
  • Richard Williams
    Department of Pathology, University of Melbourne, Fitzroy, Victoria, Australia
    Anatomical Pathology, St Vincent's Hospital Melbourne, Fitzroy, Victoria, Australia
  • Chi D Luu
    Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia
    Department of Surgery (Ophthalmology), University of Melbourne, East Melbourne, Victoria, Australia
  • Cesar Salinas-LaRosa
    Anatomical Pathology, St Vincent's Hospital Melbourne, Fitzroy, Victoria, Australia
  • Jonathan Yeoh
    Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia
    Department of Surgery (Ophthalmology), University of Melbourne, East Melbourne, Victoria, Australia
  • Owen Burns
    Bionics Institute, East Melbourne, Victoria, Australia
  • Alice A Brandli
    Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia
    Department of Surgery (Ophthalmology), University of Melbourne, East Melbourne, Victoria, Australia
  • Chris E Williams
    Bionics Institute, East Melbourne, Victoria, Australia
  • Penelope J Allen
    Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia
    Bionics Institute, East Melbourne, Victoria, Australia
  • Robert K Shepherd
    Bionics Institute, East Melbourne, Victoria, Australia
    Department of Medical Bionics, University of Melbourne, East Melbourne, Victoria, Australia
  • Footnotes
    Commercial Relationships   David Nayagam, None; Patrick C. Thien, None; Carla Abbott, None; Mohit Shivdasani, Bionics Institute (P); Stephanie Epp, None; Joel Villalobos, Bionics Institute (P); Ceara McGowan, None; Richard Williams, None; Chi Luu, None; Cesar Salinas-LaRosa, None; Jonathan Yeoh, None; Owen Burns, Bionics Institute (P); Alice Brandli, None; Chris Williams, Bionics Institute (P); Penelope Allen, Bionics Institute (P), 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 (BVA); NHMRC grant 1082358 to CIA Dr Penny Allen. The Centre for Eye Research Australia and the Bionics Institute wish to acknowledge the support of the Victorian Government through its Operational Infrastructure Support Program.
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 4204. doi:
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    • Get Citation

      David A.X. Nayagam, Patrick C. Thien, Carla J Abbott, Mohit Naresh Shivdasani, Stephanie B Epp, Joel Villalobos, Ceara McGowan, Richard Williams, Chi D Luu, Cesar Salinas-LaRosa, Jonathan Yeoh, Owen Burns, Alice A Brandli, Chris E Williams, Penelope J Allen, Robert K Shepherd; A Pre-clinical Model for Safe Retinal Stimulation. Invest. Ophthalmol. Vis. Sci. 2017;58(8):4204.

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

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Abstract

Purpose : Safety limits for electrical stimulation of the retina are unclear. We developed a model to determine safe retinal stimulation limits using a clinical electrode array driven by two independent current sources.

Methods : Normally sighted adult cats (n=13) were implanted, suprachoroidally, with a medical grade electrode array. The array contained 44 platinum (Pt) disc electrodes (1 mm diameter) and 2 large Pt return electrodes. The lead assembly was tunnelled to an exteriorised connector. Following recovery, the animals were fitted with a wearable harness containing two multichannel stimulators controlled by a custom designed and built processor allowing simultaneous (paired) electrode activation. Stimulation parameters were fully controllable, and electrode impedances monitored, wirelessly using custom software running on a laptop PC base station. Biphasic current pulses were delivered continuously at a range of defined charge levels (250-1450 nC), phase widths (145-580 µs) and rates (50-200 pps) to randomly assigned electrode pairs for up to 4 months (mean: 54 days). Eye health was assessed monthly with standard clinical testing. Pathohistological assessments were performed using our published protocols.

Results : Chronic stimulation was well tolerated by the subjects, as determined by veterinary consultation. The wireless control and monitoring system significantly reduced subject interactions. Following a clinically relevant stimulus of 500 nC per pair of electrodes at 50 Hz (phase width: 400 µs), retinal imaging revealed local increased reflectivity and a build-up of material in the outer retinal layers. Histology confirmed localised acute inflammation limited to the suprachoroidal pocket (Fig). However, no overt structural changes were observed in the retina by clinical imaging or histopathology. Higher charge levels and/or rates induced progressively more significant retinal tissue reaction including, ultimately, destruction of the photoreceptor outer segments and reorganisation of the outer nuclear layer (Fig).

Conclusions : An animal model for assessing the safety limits of chronic electrical stimulation of the retina has been developed and validated with clinical and histopathological outcomes. Future studies using this model will refine the safe stimulus parameter space and provide clinical imaging guidelines to facilitate management of retinal prosthesis recipients.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

 

Spectrum of Stimulus Induced Retinal Tissue Reaction

Spectrum of Stimulus Induced Retinal Tissue Reaction

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