Biocompatibility and surgical feasibility of the OPTO-EPIRET stimulation system

Objective: Degenerative retinal diseases, i.e. retinitis pigmentosa, cause a severe decline of the visual function up to blindness. To this day treating these diseases remains difficult. One way of conquering the eminent loss of vision is implanting retinal prostheses. In this study we investigated the surgical feasibility and biocompatibility of the OPTO-EPIRET retinal stimulator. Materials and methods: The OPTO-EPIRET retinal stimulator combines aspects of former projects of our group (epiretinal stimulation [EpiRet3], large stimulating array [VLARS]) and extends the functional range by adding an integrated circuit (IC) based optical capturing system. This solution allows capturing of visual information, visual processing, computing of a stimulus pattern and stimulating the ganglion cells all on the implanted 9mm array. Firstly, the biocompatibility of the OPTO-EPIRET was investigated in vitro using L-929 and R28 cells. Direct and indirect contact were analyzed in terms of cell proliferation, cell viability and gene expression. Next, we established an implantation surgery by implanting the OPTO-EPIRET in two cadaveric rabbit eyes. Afterwards the implantation method was transferred into an in-vivo model by implanting inactive arrays in 6 rabbits. In a 12 week follow-up, the rabbits were examined clinically and received funduscopic and OCT-imaging, if possible. Afterwards, histological examinations were performed. Results: 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 implantation surgery was successfully established. The implant was fixated on the posterior pole with a titanium retinal tack. Vitreal hemorrhage (1 subject), retinal tearing and detachment (3 subjects) occurred as main adverse effects. Transitional corneal edema caused difficulties in post-surgical imaging. Conclusion: The OPTO-EPIRET stimulator showed a good biocompatibility profile in vitro and no signs of cytotoxicity. Furthermore, the implantation surgery was shown to be feasible, yet challenging due to the size of the array. Further experiments will comprise the functional analysis of the OPTO-EPIRET stimulator in an acute setting, as well as novel implantation Methods