New epiretinal implant with integrated sensor chips for optical capturing shows a good biocompatibility profile in vitro and in vivo

Wilfried Mokwa,Jan Seifert,Pascal Raffelberg,Rainer Kokozinski,Tibor Lohmann,Claudia Ingensiep,Peter Walter,Florian Waschkowski,Kim Schaffrath,Sandra Johnen,Reinhard Viga

doi:10.1186/s12938-021-00938-9

Abstract

BackgroundRetinal degenerative diseases, e.g., retinitis pigmentosa, cause a severe decline of the visual function up to blindness. Treatment still remains difficult; however, implantation of retinal prostheses can help restoring vision. In this study, the biocompatibility and surgical feasibility of a newly developed epiretinal stimulator (OPTO-EPIRET) was investigated. The previously developed implant was extended by an integrated circuit-based optical capturing, which will enable the immediate conversion of the visual field into stimulation patterns to stimulate retinal ganglion cells.ResultsThe biocompatibility of the OPTO-EPIRET was investigated in vitro using the two different cell lines L-929 and R28. Direct and indirect contact were analyzed in terms of cell proliferation, cell viability, and gene expression. The surgical feasibility was initially tested by implanting the OPTO-EPIRET in cadaveric rabbit eyes. Afterwards, inactive devices were implanted in six rabbits for feasibility and biocompatibility testings in vivo. In follow-up controls (1–12 weeks post-surgery), the eyes were examined using fundoscopy and optical coherence tomography. After finalization, histological examination was performed to analyze the retinal structure. Regarding the in vitro biocompatibility, no significant influence on cell viability was detected (L929: < 1.3% dead cells; R-28: < 0.8% dead cells). The surgery, which comprised phacoemulsification, vitrectomy, and implantation of the OPTO-EPIRET through a 9–10 mm corneal incision, was successfully established. The implant was fixated with a retinal tack. Vitreal hemorrhage or retinal tearing occurred as main adverse effects. Transitional corneal edema caused difficulties in post-surgical imaging.ConclusionsThe OPTO-EPIRET stimulator showed a good biocompatibility profile in vitro. Furthermore, the implantation surgery was shown to be feasible. However, further design optimization steps are necessary to avoid intra- and postoperative complications. Overall, the OPTO-EPIRET will allow for a wide visual field and good visual acuity due to a high density of electrodes in the central retina.

Highlights

Retinal degenerative diseases, e.g., retinitis pigmentosa, cause a severe decline of the visual function up to blindness
Mutations in more than 70 genes encoding for basic visual processes can cause a progressive degeneration of photoreceptors and about 1 out of 4000 of the population is affected by Retinitis pigmentosa (RP) [3]
In vitro biocompatibility Effects of extractive media on cell survival For both cell lines, L-929 and R28, incubation with the extractive media of either the negative control reference material (RM) C or glass showed a constant luminescence at each applied dilution and no cytotoxic effect

Summary

Introduction

E.g., retinitis pigmentosa, cause a severe decline of the visual function up to blindness. Treatment still remains difficult; implantation of retinal prostheses can help restoring vision. Retinitis pigmentosa (RP) is an inherited neurodegenerative disease of the retina and leads to night blindness in early stage, followed by restriction of the visual field, reduction in contrast and color vision, reduced visual acuity and in end stage to blindness because of progressive photoreceptor degeneration [1,2,3]. Treatment is complex and difficult and still not solved It comprises symptomatic therapy, visual prostheses to replace the photoreceptors’ function, and one available gene therapy approach, which addresses biallelic RPE65 gene mutations in RP patients (Luxturna®, voretigene neparvovec-rzyl) [1]. One approach is epiretinal, which is represented by the former commercially available Argus II® Retinal Prosthesis System (Second Sight Medical Products, USA) or IRIS II (Intelligent Retinal Implant System, Pixium Vision, France) [4, 5]. The question of improving retinal prostheses is still not solved and needs to be addressed

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