Pegaptanib for the Treatment of Ischemic Retinopathy in Patients with Diabetes and Retinal Vascular Occlusive Disorders

March 2009 Retina Today by Michael D. Bennett, M.D.

Although of differing etiologies, both diabetic retinopathy (DR) and branch retinal vein occlusion (BRVO) are associated with vison loss resulting from retinal ischemia, edema, hemorrhage, and possibly retinal neovascularization. The ischema of BRVO commonly results from narrowing of arteriovenous crossings and consequent venous compression, while in DR retinal vascular leukostasis, leading to capillary blockage and damage to the retinal vasculature, is believed to be a major contributing factor. Until recently, the principal therapeutic option for BRVO has involved laser photocoagulation to reduce the associated macular edema, similarly laser approaches the retinal neovascularization that may accompany DR, as well as the associated diabetic macular edema (DME) that is a major contributor to vision loss.

Over the past 15 years, however, investigations into the underlying molecular and cellular mechanisms of ischemia-related vision loss have clarified the essential role of vascular endothelial growth factor (VEGF) in promoting both edema and retinal neovascularization. In addition to its importance in angiogenesis, VEGF is a potent promoter of vascular permeability and is especially important for the leukostasis that is key to the vascular damage associated with DR. Moreover, VEGF synthesis is upregulated by the hypoxia that accompanies retinal ischemia, and numerous retinal cell types sparing smaller isoforms such as VEGF and ranibizumab, a momoclonal antibody fragment that binds all VEGF isoforms. READ MORE