Subretinal Sustained Delivery of Rapamycin in the Rabbit Eye

Abstract

Abstract: : Purpose:To evaluate polymer–coated filaments as a means of delivering rapamycin to the subretinal space in a sustained release fashion. Methods:Six rabbits underwent surgery for subretinal implantation of nitinol filaments 2–3 mm in length coated with a rapamycin–impregnated polymer (26–89 mcg per filament). In 3 of the animals, no vitrectomy was performed prior to implantation. In the other 3 rabbits, a vitrectomy was performed, and in 2 of these a bleb of subretinal fluid was created using balanced salt solution on a 25–gauge needle. In all cases, forceps were used to place the filament beneath the retina, either through a pre–existing retinotomy or by puncturing the retina with the filament's sharp tip. Fundus photography, fluorescein angiography, and optical coherence tomography were performed at 1, 2 and 4 weeks post–op. Eyes were collected and processed for histology. Results:The drug–coated filaments were successfully implanted in the subretinal space of 3 rabbits and in the sub–RPE space of one rabbit. During the follow–up period, the eyes were quiet except for one eye in which anterior chamber inflammation led to posterior synechiae formation. The filaments did not migrate, and the retina remained attached. Fluorescein angiography and OCT suggested that there was no drug–related damage to adjacent tissue. H+E stained sections showed damage to photoreceptors immediately overlying the implant, similar to that seen previously with non–drug–coated filaments, but normal retinal anatomy elsewhere. In the remaining 2 rabbits, both of which did not undergo vitrectomy, the surgery could not be completed because of retinal damage that occurred during filament implantation. Conclusions:A polymer–coated implant for slow–release delivery of rapamycin appears to be tolerated in the subretinal space of rabbits during one month of follow–up. Toxicity may be limited to physical damage to photoreceptors directly overlying the implant.

Keywords: drug toxicity/drug effects • age-related macular degeneration • neovascularization