Combination therapy for the treatment of ocular neovascularization

The growth of inappropriately regulated, leaky blood vessels is a prominent component of several debilitating eye diseases, such as age-related macular degeneration (AMD), proliferative diabetic retinopathy (PDR), and retinopathy of prematurity (ROP). New pharmacological therapies that target vascular endothelial growth factor-A (VEGF-A) have significantly enhanced the treatment of AMD by limiting the progression of the disease, and in some cases, by improving vision. Although anti-VEGF therapy will undoubtedly prove valuable in the treatment of other neovascular diseases of the eye, improvements with this type of therapy are still required. At present, anti-VEGF therapy requires intravitreal injection and a relatively frequent dosing regimen (4-6 weeks). Furthermore, in experimental models of neovascularization, anti-VEGF treatment becomes less effective at blocking vessel growth and at regressing vessels as the neovascularization develops over time. As such, the use of anti-VEGF therapy in late-stage AMD may be limited. An important strategy for improved treatment of neovascular diseases of the eye could be combination therapy. Combination therapy of anti-VEGF drugs with established treatments, such as photodynamic therapy with verteporfin (PDT-V), or with newly-developed drugs targeting specific kinases, presents opportunities for increased efficacy and improved therapeutic outcome. In this review, we evaluate the opportunities for combination therapy for the treatment of neovascular diseases of the eye.