Table 2 Summary of significant risk factors for age-related macular degeneration Known risk factors Study Age Smoking Exposure to large quantities of visible spectrum, particularly blue light Nutrition and dietary habits Zinc High Intake of dietary fats Hypertension Klein et al 1992;Vingerling et al 1995 Christen et al 1996; Seddon et al 1996; Vingerling et al 1996 Hamm et al 1976;Taylor et al 1990 Seddon et al 1994 Newsome et al 1998 Seddon et al 2001 Abdelsalam et al 1999 females. Other risk factors associated with AMD include presence of soft drusen, macular pigmentary changes, CNV in the fellow eye, race, genetic predisposition, gender, iris color, obesity, and smoking (Table 2). Much is now known about the process for developing CNV in the wet (exudative) form of the disease. The multifaceted process of neovascularization can be broken down into several distinct stages (Clark 1997). A proangiogenic signal associated with late stage disease stimulates the production of trophic factors that initiates the growth of new blood vessels. The signal to release such growth factors is still speculative and may relate to hypoxia or inflammation associated with remodeling of the outer retina with immunologic phenomenons being involved as well (Kijlstra et al 2005). Synthesis of a variety of proangiogenic trophic factors has been proposed; with greatest evidence pointing to VEGF as an initiator of proliferation of CNV and subsequent vascular leakage. The trophic factors have been demonstrated to bind to receptors on vascular endothelial cells (VECs), leading to activation Introduction of C9-11 Double Bond Anecortave acetate in age-related macular degeneration of genetic machinery leading to the production and release of enzymes such as matrix metalloproteinases (MMPs), which degrade the basement membrane and extracellular matrix which surrounds the VECs. Degradation of the extracellular matrix has been shown to be a prerequisite for proliferation and migration of VECs and subsequent tube formation, the result of which leads to the establishment of an immature blood vessel. With the development of a new basement membrane, the new capillary is stabilized and is capable of transporting blood through its lumen (Figure 1). Anecortave acetate – chemical properties, mechanism of action New compounds known as cortisenes were discovered in 1985 and were found to have angiostatic properties in simple in vitro models of angiogenesis. These steroid-like compounds are devoid of clinically relevant glucocorticoid activity and therefore do not elevate IOP or cause cataracts (Crum et al 1985). Further research led to the identification of anecortave acetate which is an antiangiogenic analog of cortisol (Blei et al 1993). Anecortave acetate differs in structure from cortisol by the removal of 11-beta hydroxyl, addition of a double bond at the C9-11 position, and addition of an acetate group at the C21 position to enhance bioavailability. The resulting molecule is an angiostatic cortisene that imparts angiostatic activity, but does not exhibit typical glucocorticoid-receptor- mediated activity (Figure 2). Anecortave acetate demonstrated a broad range of antiangiogenic properties in both in vitro and in vivo models of ocular neovascularization (Table 3). In vitro data indicated that the proliferation of cultured human VECs is inhibited by anecortave acetate. Anecortave Addition of 21-Acetate Removal of 11b-Hydroxyl Figure 1 Schematic diagram of the anecortave acetate, a unique synthetic cortisene. Modifications made to the cortisol parent molecule are shown. Clinical Interventions in Aging 2006:1(3) 239