This project has two main objectives. The first is to develop vitreous implants and antiproliferative drug-delivery systems to treat complicated retinal detachments and proliferative vitreoretinopathy (PVR). Many patients who are blind from PVR are treated with silicone oil as a long-lasting vitreous implant, but this procedure often results in complications such as cataract, corneal decompensation, oil emulsification, and glaucoma. Intravitreous injections of air, inert gases, saline, and hyaluronan, combined with scleral buckling, give good results with some retinal detachments. However, these fluids last too short a time to be effective when a retinal tamponade is needed. Specifically, a new silicone-fluorosilicone (SiFO) copolymer oil denser than water will be investigated for use intraoperatively and as a temporary tamponade in retinal detachment surgery. SiFO is advantageous over silicone oil (SiO) in that SiFO is denser and, therefore, can be used to fix detached retinas posteriorly and inferiorly by displacing vitreous and subretinal fluid; SiFO has less of a tendency to emulsify intraocularly than fluorosilicone oil (FSiO). The relative low viscosity of SiFO (200 vs 5000 centistokes for the commonly used SiO and FSiO required to prevent intraocular emulsification) facilitates injection and post-surgical removal of SiFO from the eye. The advantage of using SiFO instead of the perfluorocarbon liquids (currently under investigation as intraoperative tools in retinal detachment surgery) is that SiFO can be retained as an intraocular tamponade for the time needed for a chorioretinal adhesion to form. In retinal detachments complicated by PVR, SiFO-soluble retinoids will be investigated as antiproliferative agents. The release retinoids from injectable microspheres of biodegradable polymers also will be investigated for use in PVR cases not treated with an intravitreous oil. The second objective is to investigate the prevention of contact lens (CL)-induced bacterial keratitis, the worst complication of CL wear. The incidence of infection is the highest with extended-wear hydrogel CLs. Because many people use this modality of visual correction despite the inherent dangers, it is desirable to eliminate or at least reduce the incidence of this devastating complication. Bacterial attachment is the initial step in the pathogenesis of bacterial keratitis. We discovered that certain inert water-soluble polymers of the poloxamer family [alpha-hydro-omega-hydroxypoly(oxyethylene)- poly(oxypropylene)-poly(oxyethylene) block copolymers] significantly decrease gram-negative bacterial adherence to lenses. The poloxamers will be investigated in an animal model of CL overwear to prevent bacterial keratitis.
