Techniques for Subretinal Prosthesis Implantation With Concomittant Intravitreal Drug–Delivery in the RCS Rat

Abstract

Abstract: : Purpose: To develop a rat model of subretinal implant (SI) combined with intravitreal drug–release device implant (IDDI) surgery. Methods: 20 RCS rats aged 5.5 weeks were used in the study. Inactive flexible polyimide SI’s were 1.4 x 2.5 mm, 25.4µm thick. IDDI’s were 300µm polyamide tubes, 1.5mm long, containing a polymer matrix loaded with 75µg of Fluocinolone Acetonide (FA) released at 3µg per day. IDDI’s without drug were also implanted with SI’s. Five animals received the SI alone, 5 received a SI and an inactive IDDI, and 10 received a SI and a FA–loaded IDDI. Surgery was performed under sterile conditions during Isofluorane mask. SI’s were slid into the subretinal space of the superior temporal quadrant using a trans–scleral, pars plana approach. IDDI’s were injected intravitreally using a 25–gauge injector. Wounds were closed with a cyanoacrylate–fixed polyimide patch. Pre– and postoperative OCT and fundus photographs were performed. Animals were euthanized 2 or 4 weeks after surgery. Retinal histology was performed on all eyes. Results: Intraoperative choroidal bleeding developed in all animals. This was mild in 17 animals (85%), and resolved during surgery. Three animals (15%) developed severe choroidal bleeding with vitreous hemorrhage that resolved within 7–10 days. One animal developed a hyphema that resolved within three–days. Fundus photographs and OCT showed no retinal detachment. Histology of the SI–group revealed no cell proliferation or retinal atrophy relative to the fellow, un–operated eyes. Pharmacological effects of FA implants will be discussed in detail in an accompanying paper. Conclusions: We have developed a rat model for subretinal implantation of flexible polyimide retinal prostheses. We have combined this with the surgical implantation of an IDDI. This model will be useful in examining the biocompatibility of various subretinal prosthetic devices. Using this model, the pharmacological effects of various drugs such as neuroprotectants and inflammatory modulators can also be studied in the presence of a subretinal device in the RCS rat.

Keywords: retina • vitreoretinal surgery • neuroprotection