Chronic electrical stimulation with a suprachoroidal retinal prosthesis: a preclinical safety and efficacy study

PLoS One. 2014 May 22;9(5):e97182. doi: 10.1371/journal.pone.0097182. eCollection 2014.

Abstract

Purpose: To assess the safety and efficacy of chronic electrical stimulation of the retina with a suprachoroidal visual prosthesis.

Methods: Seven normally-sighted feline subjects were implanted for 96-143 days with a suprachoroidal electrode array and six were chronically stimulated for 70-105 days at levels that activated the visual cortex. Charge balanced, biphasic, current pulses were delivered to platinum electrodes in a monopolar stimulation mode. Retinal integrity/function and the mechanical stability of the implant were assessed monthly using electroretinography (ERG), optical coherence tomography (OCT) and fundus photography. Electrode impedances were measured weekly and electrically-evoked visual cortex potentials (eEVCPs) were measured monthly to verify that chronic stimuli were suprathreshold. At the end of the chronic stimulation period, thresholds were confirmed with multi-unit recordings from the visual cortex. Randomized, blinded histological assessments were performed by two pathologists to compare the stimulated and non-stimulated retina and adjacent tissue.

Results: All subjects tolerated the surgical and stimulation procedure with no evidence of discomfort or unexpected adverse outcomes. After an initial post-operative settling period, electrode arrays were mechanically stable. Mean electrode impedances were stable between 11-15 kΩ during the implantation period. Visually-evoked ERGs & OCT were normal, and mean eEVCP thresholds did not substantially differ over time. In 81 of 84 electrode-adjacent tissue samples examined, there were no discernible histopathological differences between stimulated and unstimulated tissue. In the remaining three tissue samples there were minor focal fibroblastic and acute inflammatory responses.

Conclusions: Chronic suprathreshold electrical stimulation of the retina using a suprachoroidal electrode array evoked a minimal tissue response and no adverse clinical or histological findings. Moreover, thresholds and electrode impedance remained stable for stimulation durations of up to 15 weeks. This study has demonstrated the safety and efficacy of suprachoroidal stimulation with charge balanced stimulus currents.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cats
  • Electric Impedance
  • Electric Stimulation*
  • Electrodes, Implanted
  • Electroretinography
  • Immunohistochemistry
  • Linear Models
  • Retina / pathology
  • Retina / physiology*
  • Tomography, Optical Coherence
  • Visual Cortex / physiology*
  • Visual Prosthesis / standards*

Grants and funding

This research was supported by the Australian Research Council (ARC) through its Special Research Initiative (SRI) in Bionic Vision Science and Technology grant to Bionic Vision Australia (BVA). Both the Bionics Institute and the Centre for Eye Research Australia (CERA) receive Operational Infrastructure Support from the Victorian Government. CERA is supported by the NH&MRC Centre for Clinical Research Excellence (#529923) – Translational Clinical Research in Major Eye Diseases. The Bionics Institute would also like to acknowledge support from the Bertalli Family Trust and the J T Reid Charitable Trust. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.