Surgical Results and Microscopic Analysis of the Tissue Reaction following Implantation and Explantation of an Intraocular Implant for Epiretinal Stimulation in Minipigs.

AIMS: For the purpose of visual rehabilitation of subjects with photoreceptor degeneration, an implantable microelectronic device for epiretinal stimulation was developed. Our study aimed to show whether implantation and explantation could be conducted safely and to investigate tissue compatibility. METHODS: The device was implanted in 5 Göttinger minipigs. Four weeks later, the implant was surgical- ly removed. Histopathological examination that followed aimed at detecting inflammatory or proliferative changes. Stains used were hematoxylin and eosin, leukocyte common antigen, CD68 and glial fibrillary acidic protein. A grinding technique was used to visualize the retinal tissue in conjunction with the retinal tacks. RESULTS: The implantation of the devices was successful in all cases. The explantation was complicated by intraoperative hemorrhages. Complete explantation could only be achieved after modifying the implantation strategy. Histopathology revealed a mild degree of cystic disaggregation of the retina. Immunohistochemically, an increased glial fibrillary acidic protein expression of Müller cells was found, which shows a moderate glial cell activation. Inflammatory cells were absent. Using the grinding technique, tissue adjacent to the retinal tacks showed a mild gliosis. DISCUSSION: The viability of implantation and explantation of the implant in minipigs has been shown. The absence of immunoreactive cells or a considerable glial reaction suggest that the device may be considered safe and suitable for further implantation in humans.

Magnetic microparticles for endovascular aneurysm treatment: in vitro and in vivo experimental results.

OBJECTIVE: Endovascular treatment of intracranial aneurysms employing endosaccular coiling can be associated with aneurysm perforation, coil herniation or incomplete obliteration fueling the interest to investigate novel endovascular techniques. We aimed to test a novel embolization material in experimental aneurysms in vitro and in vivo whereby intra-arterially administered magnetic microparticles (MMPs) are navigated into the lumen of vascular aneurysms with assistance from an external magnetic field. METHODS: MMPs are core-shell particles suspended in saline that have a shell made of a polymeric material and a core made of magnetite (Fe3O4). They have a diameter of 1.4 µm. During MMP administration via a microcatheter, a magnetic field was applied externally to direct the particles with the use of a solid-state neodymium magnet. Experiments were performed in a perfused silicone vessel and aneurysm model to evaluate application techniques and fluid dynamics and in the elastase aneurysm model in rabbits to evaluate in vivo compatibility, including multiorgan histological examinations and long-term stability of aneurysm embolization. RESULTS: It was possible to steer and hold the MMPs within the aneurismal cavity where they occluded the lumen progressively. After removal of the external magnetic field, the results remained stable in vivo for the remainder of the observational period (30 minutes); after a 12-week observational period, recanalization of the aneurysm occurred. CONCLUSION: MMPs can be magnetically directed into aneurysms, allowing short-term obliteration. Although the method has yet to show reliable long-term stability, these experiments provide proof of concept, encouraging further investigation of intravascular magnetic compounds.

Implantation and explantation of a wireless epiretinal retina implant device: observations during the EPIRET3 prospective clinical trial.

PURPOSE: Visual sensations in patients with blindness and retinal degenerations may be restored by electrical stimulation of retinal neurons with implantable microelectrode arrays. A prospective trial was initiated to evaluate the safety and efficacy of a wireless intraocular retinal implant (EPIRET3) in six volunteers with blindness and RP. METHODS: The implant is a remotely controlled, fully intraocular wireless device consisting of a receiver and a stimulator module. The stimulator is placed on the retinal surface. Data and energy are transmitted via an inductive link from outside the eye to the implant. Surgery included removal of the lens, vitrectomy, and implantation of the EPIRET3 device through a corneal incision. The clinical outcome after implantation and explantation of the device was determined. The implant was removed after 4 weeks, according to the study protocol. RESULTS: Implantation was successful in all six patients. While the anterior part was fixed with transscleral sutures, the stimulating foil was placed onto the posterior pole and fixed with retinal tacks. The implant was well tolerated, causing temporary moderate postoperative inflammation, whereas the position of the implant remained stable until surgical removal. In all cases explantation of the device was performed successfully. Adverse events were a sterile hypopyon effectively treated with steroids and antibiotics in one case and a retinal break in a second case during explantation requiring silicone oil surgery. CONCLUSIONS: The EPIRET3 system can be successfully implanted and explanted in patients with blindness and RP. The surgical steps are feasible, and the postoperative follow-up disclosed an acceptable range of adverse events.

Experimental implantation and long-term testing of an intraocular vision aid in rabbits.

OBJECTIVE: To develop an intraocular vision aid to provide artificial vision in severely traumatized eyes, where neuroretinal function could be preserved but irreversible anterior segment opacification resulted in blindness. METHODS: The basis of an intraocular vision aid is in principle a telemetric circuit to bridge the opaque cornea and to allow for artificial light stimulation of the retina. The visual prosthesis comprises an external high-dynamic range complementary metal oxide semiconductor camera and digital signal processing unit and an intraocular miniaturized light-emitting diode array to project the image onto the retina. For in vivo testing of long-term function and biocompatibility, silicone-encapsulated active photodiodes were implanted in 13 pigmented rabbits and were followed up for up to 21 months. RESULTS: Lens extraction and stable fixation of the device in the ciliary sulcus were successful in all cases. For up to 21 months inductive energy transmission and wireless stimulation of the implants could be maintained. Electrophysiologic data and histology demonstrated a good tissue biocompatibility in the long-term follow-up. CONCLUSION: The results demonstrate the general feasibility and biocompatibility to implant and fixate an intraocular light-emitting diode prosthesis. Inductive energy transmission to the intraocular device and wireless light stimulation are assured in the long term but depend on meticulous water-impermeable encapsulation of the delicate microelectronic components. Clinical Relevance An intraocular vision aid compound system with a high-resolution light-emitting diode matrix might be a future treatment option to restore vision in blind eyes with severe anterior segment disorders.