Intravitreal VEGF and bFGF produce florid retinal neovascularization and hemorrhage in the rabbit

Purpose. Vascular endothelial growth factor (VEGF) causes widespread retina l vascular dilation, produces breakdown of the blood-retinal barrier, and i s implicated in ocular neovascularization (NV). Basic fibroblast growth fac tor (bFGF) also has been implicated in the production of ocular NV. This st udy was performed to investigate the ability of simultaneous sustained intr avitreal release of both VEGF and bFGF to induce robust retinal NV in the r abbit. Methods. Intravitreal implantation of sustained-release Hydron polymeric pe llets containing both 20 mug of VEGF and 20 mug of bFGF was performed on ad ult male Dutch belted rabbits. In other animals either 20 mug or 50 mug bFG F-containing pellets was implanted intravitreally; also, either 20 mug VEGF or 50 mug VEGF-containing pellets was implanted. Control rabbits received either blank polymeric pellets or a pellet containing 30 mug bovine serum a lbumin. Eyes were examined by indirect ophthalmoscopy after surgery at 24 h rs, 48 hrs, 4 days, 7 days, 14 days, 21 days, and 28 days. Findings were do cumented by color fundus photography and fluorescein angiography (FA). Eyes were enucleated and prepared for histologic analysis at 28 days following intravitreal implantation of the VEGF/bFGF-containing pellets. Results. In all eyes implanted with VEGF/bFGF pellets, dilation and tortuos ity of existing blood vessels were observed within 48 hrs after pellet impl antation. The progression of retinal vascular changes was rapid and occurre d over the entire optic disk and medullary rays between 4 and 7 days. Hemor rhage occurred as early as 14 days after VEGF/bFGF pellet implantation. In eyes with massive hemorrhage, total traction retinal detachment developed a fter the second week. The presence of abnormal tissues at the vitreo-retina l interface within 28 days was demonstrated by light microscopy while FA sh owed profuse leakage of dye from anomalous vessels within the first week. N either bFGF-exposed eyes nor control eyes showed any vascular changes. Eyes that received only VEGF-containing pellets exhibited tortuosity of existin g vessels, but neither hemorrhaging nor retinal detachment occurred. Conclusions. These results demonstrate that retinal vascular changes leadin g to hemorrhaging is produced rapidly in the rabbit by simultaneous intravi treal release of both VEGF and bFGF. Understanding how these growth factors induce retinal NV may suggest novel therapeutic treatment strategies.