Chronic electrical stimulation with a suprachoroidal retinal prosthesis: a preclinical safety and efficacy study.
OBJECTIVE
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.
Bionics Institute, East Melbourne, Victoria, Australia; Department of Pathology, University of Melbourne, Parkville, Victoria, Australia.
David A X
DA
Nayagam
Department of Pathology, University of Melbourne, Parkville, Victoria, Australia; Department of Anatomical Pathology, St Vincent's Hospital Melbourne, Fitzroy, Victoria, Australia.
Richard A
RA
Williams
Centre for Eye Research Australia, University of Melbourne, East Melbourne, Victoria, Australia; Department of Ophthalmology, The University of Melbourne, East Melbourne, Victoria, Australia.
Penelope J
PJ
Allen
Bionics Institute, East Melbourne, Victoria, Australia; Medical Bionics Department, University of Melbourne, East Melbourne, Victoria, Australia.
Mohit N
MN
Shivdasani
Centre for Eye Research Australia, University of Melbourne, East Melbourne, Victoria, Australia.
Chi D
CD
Luu
Department of Anatomical Pathology, St Vincent's Hospital Melbourne, Fitzroy, Victoria, Australia.
Cesar M
CM
Salinas-LaRosa
Statistical Consulting Centre, The University of Melbourne, Parkville, Victoria, Australia.
Sue
S
Finch
Centre for Eye Research Australia, University of Melbourne, East Melbourne, Victoria, Australia.
Lauren N
LN
Ayton
Bionics Institute, East Melbourne, Victoria, Australia.
Alexia L
AL
Saunders
Bionics Institute, East Melbourne, Victoria, Australia.
Michelle
M
McPhedran
Bionics Institute, East Melbourne, Victoria, Australia.
Ceara
C
McGowan
Bionics Institute, East Melbourne, Victoria, Australia.
Joel
J
Villalobos
Bionics Institute, East Melbourne, Victoria, Australia; Medical Bionics Department, University of Melbourne, East Melbourne, Victoria, Australia.
James B
JB
Fallon
Bionics Institute, East Melbourne, Victoria, Australia; Department of Otolaryngology, The University of Melbourne, East Melbourne, Victoria, Australia; Medical Bionics Department, University of Melbourne, East Melbourne, Victoria, Australia.
Andrew K
AK
Wise
Centre for Eye Research Australia, University of Melbourne, East Melbourne, Victoria, Australia; Department of Ophthalmology, The University of Melbourne, East Melbourne, Victoria, Australia.
Jonathan
J
Yeoh
Bionics Institute, East Melbourne, Victoria, Australia; The HEARing Cooperative Research Centre, The University of Melbourne, East Melbourne, Victoria, Australia; Department of Otolaryngology, The University of Melbourne, East Melbourne, Victoria, Australia.
Jin
J
Xu
Bionics Institute, East Melbourne, Victoria, Australia; Department of Otolaryngology, The University of Melbourne, East Melbourne, Victoria, Australia.
Helen
H
Feng
Bionics Institute, East Melbourne, Victoria, Australia.
Rodney
R
Millard
Bionics Institute, East Melbourne, Victoria, Australia; Biomedical Engineering Department, Vanderbilt University, Nashville, Tennessee, United States of America.
Melanie
M
McWade
Bionics Institute, East Melbourne, Victoria, Australia.
Patrick C
PC
Thien
Bionics Institute, East Melbourne, Victoria, Australia; Department of Pathology, University of Melbourne, Parkville, Victoria, Australia; Medical Bionics Department, University of Melbourne, East Melbourne, Victoria, Australia.
Chris E
CE
Williams
Bionics Institute, East Melbourne, Victoria, Australia; Medical Bionics Department, University of Melbourne, East Melbourne, Victoria, Australia.
Robert K
RK
Shepherd
D000818:Animals; D002415:Cats; D017097:Electric Impedance; D004558:Electric Stimulation; D004567:Electrodes, Implanted; D004596:Electroretinography; D007150:Immunohistochemistry; D016014:Linear Models; D012160:Retina / Q000473:pathology / Q000502:physiology*; D041623:Tomography, Optical Coherence; D014793:Visual Cortex / Q000502:physiology*; D057488:Visual Prosthesis / Q000592:standards*