Chronic Electrical Stimulation with a Suprachoroidal Retinal Prosthesis: A Preclinical Safety and Efficacy Study

Abstract

PurposeTo assess the safety and efficacy of chronic electrical stimulation of the retina with a suprachoroidal visual prosthesis.MethodsSeven 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.ResultsAll 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.ConclusionsChronic 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.

Comparative Study of Sevoflurane and Isoflurane Anesthesia for the Long-term Safety Evaluation of Visual Prosthesis with Rabbits

“…(3) However, it is considered that chronic stimulation and functional evaluation over time are also important. For that reason, the long-term safety evaluation for a visual prosthesis with functional devices was reported by Nayagam et al (30) We plan to perform 6-month chronic stimulation and assessments over time for the safety evaluation of our visual prosthesis by suprachoroidal transretinal stimulation. (2,6) The assessments include VEP, EEP, ERG, funduscopy, optical coherence tomography, measurement of ocular pressure, and histopathological evaluation.…”

A Flexible Wireless System for Preclinical Evaluation of Retinal Prosthesis

“…If it is not detected quickly and histological examination of the tissue shows that damage has occurred, it becomes harder to determine if the level of stimulation used is safe, as the damage may have been caused by unwanted DC stimulation. While chronic safety studies without continuous monitoring (6,11) can, and have, been carried out for preclinical devices, which have then gone on to human clinical trials, (4,12) continuous stimulation coupled with automated monitoring provides the benefit of a much quicker detection of problems. Manually collecting even daily measurements for an implanted device with our system would not only be very time consuming, but likely a significant source of stress for the subjects.…”

“…The system was tested with a 44-channel electrode array using methods described previously (6) in 13 normally sighted cats (weight range: 2.4−6.9 kg). Briefly, the electrode array was implanted in the suprachoroidal space of the left eye with a lead wire exiting percutaneously from the back of the neck.…”

“…This process is similar to the one used by Nayagam et al (6) In all cohorts, batteries were changed approximately twice a week to ensure that they were never depleted. In addition, the number of times the stimulation was adjusted or the subjects had to be handled to access the controller during their experimental period was recorded as summarised in Fig.…”

Techniques for Processing Eyes Implanted with a Retinal Prosthesis for Localized Histopathological Analysis: Part 2 Epiretinal Implants with Retinal Tacks

“…In the case of implantable stimulators, such as retinal prostheses, there is the additional consideration that the electrical parameters should be within safe limits. Patient safety is paramount, so devices must be rigorously tested in preclinical studies before advancing to a clinical setting [9][10][11][12][13][14][15] . In our companion article, we described a method for assessing the localized histopathology of the eye surrounding an implant positioned in the suprachoroidal space 16 The epiretinal location is the most commonly utilised position for locating a visual prosthesis.…”