Ocular neovascularization is the primary cause of blindness in a wide range of ocular diseases. The vascular endothelial growth factor A (VEGF-A) is the key factor involved in ocular angiogenesis, which can cause eye diseases through the development of pathological angiogenesis and increase of vascular permeability. There are two families of VEGF-A isoforms formed by alternative splicing, the angiogenic VEGF-A family (VEGF(xxx)), known to contribute to ocular neovascularization, and the anti-angiogenic VEGF-A family (VEGF(xxx)b), which is found in normal ocular tissues but downregulated in human diabetic retinopathy. The first member of the VEGF(xxx)b family to be isolated was VEGF(165)b. It can significantly reduce preretinal neovascularization without inhibition of physiological intraretinal angiogenesis. As the studies on the VEGF(xxx)b family proceed more deeply, controlling the balance of VEGF(xxx) to VEGF(xxx)b isoforms may be therapeutically valuable in the treatment of angiogenic eye diseases such as diabetic retinopathy and age-related macular degeneration.