Histopathologic Assessment of Optic Nerves and Retina From a Patient With Chronically Implanted Argus II Retinal Prosthesis System

Abstract

Purpose To characterize histologic changes in the optic nerve and the retina of an end-stage retinitis pigmentosa (RP) patient after long-term implantation with the Argus II retinal prosthesis system. Methods Serial cross sections from the patient's both eyes were collected postmortem 6 years after implantation. Optic nerve from both eyes were morphometrically analyzed and compared. Retina underneath and outside the array was analyzed and compared with corresponding regions in the fellow eye. Results Although the optic nerve of the implant eye demonstrated significantly more overall atrophy than the fellow eye ( P < 0.01), the temporal quadrant that retinotopically corresponded to the location of the array did not show additional damage. The total neuron count of the macular area was not significantly different between the two eyes, but the tack locations and their adjacent areas showed significantly fewer neurons than other perimacular areas. There was an increased expression of glial fibrillary acidic protein (GFAP) throughout the retina in the implant eye versus the fellow eye, but there was no significant difference in the cellular retinaldehyde-binding protein (CRALBP) expression. Except for the revision tack site, no significant increase of inflammatory reaction was detected in the implant eye. Conclusion Long-term implantation and electrical stimulation with an Argus II retinal prosthesis system did not result in significant tissue damage that could be detected by a morphometric analysis. Translational Relevance This study supports the long-term safety of the Argus II device and encourages further development of bioelectronics devices at the retina-machine interface.

Factors affecting two-point discrimination in Argus II patients

“…Possible causes of retinal damage include severe disease-related degeneration, damage to the retina as a result of surgical implantation, or damage caused by the presence of the array. A variety of studies have found evidence suggestive of retinal damage in retinal prosthesis patients ( Gregori et al, 2018 ; Lin et al, 2019 ; Rizzo et al, 2019 ; Patelli et al, 2020 ). This damage seems to have a variety of causes including inflammation, “boggy” ( sic ) thickening, schisis and fibrosis, intraretinal fluid (IRF) cysts, as well as a “snowplow” effect of the electrode array pressing against the retina and causing adjacent thickening ( Gregori et al, 2018 ; Patelli et al, 2020 ).…”

“…This damage seems to have a variety of causes including inflammation, “boggy” ( sic ) thickening, schisis and fibrosis, intraretinal fluid (IRF) cysts, as well as a “snowplow” effect of the electrode array pressing against the retina and causing adjacent thickening ( Gregori et al, 2018 ; Patelli et al, 2020 ). While many of these conditions are common in late stage RP patients, they seem to be exacerbated in the implanted eye ( Lin et al, 2019 ). In addition, over time many patients also develop membranes (both adherent to and separated from the retina) between the retina and the array.…”

Retinal Ganglion Cell Death as a Late Remodeling Effect of Photoreceptor Degeneration

“…These conflicting results may be explained because the RGC population was analyzed too early (before a complete loss of photoreceptors had occurred [100,101]), which is a prerequisite for axonal compression and the sensibility of the techniques applied to identify and/or quantify the RGC population that occur in localized sectors, which could be missed by other authors [53]. Studies performed in humans have documented RGC loss in human patients with photoreceptor degenerations [102,103,104,105,106,107,108].…”

“…However, the treatment was applied before complete photoreceptor loss and therefore further studies are needed to clarify this fact. In addition, the glial seal formed by Müller cells may also contribute to the failure of attempts to replace lost photoreceptors [52,106], for example limiting the migration of transplanted cells [113] and perhaps the creation of new synaptic connections.…”

Prosthetic Visual Performance Using a Disparity-Based Distance-Filtering System

“…1 Furthermore, a recent study provided histopathologic evidence supporting the long-term safety of Argus II retinal implant using morphometric analysis. 2 The basic idea behind Argus II is to electrically stimulate the surviving ganglion cells in the retina to elicit visual percepts. However, it requires more than just perception of phosphenes to have any comprehensible visual experience.…”