compliance in the arterial vasculature (Sato et al 2006). Pulsatile ocular blood ﬂow has been found to be decreased in exudative AMD compared to nonexudative AMD or normal subjects (Mori et al 2001). Chen et al (2001) found that the pulsatile ocular blood ﬂow in eyes with drusen was lower than in eyes with choroidal neovascularization and higher in eyes with disciform scar, implying that hemodynamic changes can be partly responsible for asymmetry in some AMD patients. Nevertheless, a recent study of Caucasian patients by Sandhu et al (2007) demonstrated no differences between the pulsatile ocular blood ﬂow in asymmetric eyes of patients with AMD. Moreover, delayed choroidal ﬁlling time has been found in patients with dry AMD (Ciulla et al 2002). Prolonged choroidal ﬁlling phase was observed in 26% of eyes with early AMD using ﬂuorescein angiography and in 32% of eyes using indocyanine green (Pauleikoff et al 1999). This prolonged ﬁlling was also associated with conﬂuent drusen and geographic atrophy in the fellow eye (Pauleikoff et al 1999). Presence of macular watershed zones was also correlated with AMD and one study found that choroidal neovascularization arose from the macular watershed zone in 91% of cases (Ross et al 1998). Changes in the retrobulbar blood ﬂow can provide a better understanding of the primary or secondary role of decreased blood ﬂow in AMD. In an animal model, selective damage to retinal pigment epithelial cells caused degenerative changes to the choriocapillaris, suggesting that degeneration of cho- riocapillaries in AMD can be secondary to dysfunction of the retinal pigment epithelial cells (Henkind and Gartner 1983; Del Priore et al 1996). Therefore, secondary damage by retinal pigment epithelium is more likely to affect local blood vessels like the short posterior ciliary arteries and choriocapillaris than the ophthalmic or central retinal arteries. Changes in these vessels can support a more primary role of decrease in blood ﬂow in the development of AMD, although a secondary autoregulatory response to a primary change elsewhere can not be ruled out (Ciulla et al 1999). Friedman et al (1995) reported that there is elevated pulsatility within all vessels including the ophthalmic, central retinal, and short posterior ciliary arteries, which can indicate an increase in the resistive index. Hosal et al (1998) reported that patients with AMD have lower blood velocity and higher resistive index in all retrobulbar vessels including the ophthalmic artery. Studies have found that blood ﬂow velocity was lower in the ophthalmic artery and short posterior ciliary arteries of eyes with choroidal neovascularization compared with eyes without choroidal neovascularization (Uretmen et al 2003; Ciulla et al 1999). Various studies have reported decreases Clinical Interventions in Aging 2008:3(3) AMD of the aging eye in the velocity of the short posterior ciliary arteries in AMD patients (Friedman et al 1995; Dimitrova et al 2002). Ciulla et al (1999) also found a decrease in the end-diastolic velocity and an increase in the resistive index of the central retinal artery. There are a couple of hypotheses for this change in the central retinal artery blood ﬂow velocity. First, reductions in central retinal artery blood ﬂow may be due to global decreases in retrobulbar blood ﬂow from the ophthalmic artery and its branches. Secondly, decreased retinal blood flow may be related to retinal angiomatous prolifera- tion. Yannuzzi et al (2001) described retinal angiomatous proliferation as a phenomenon which occurs in a subgroup of neovascular AMD patients, where angiomatous prolif- eration originates from the retina and extends posteriorly into the subretinal space, occasionally communicating with choroidal new vessels. Increased ﬂow through new choroi- dal vessels could decrease ﬂow in the retina and the central retinal artery. Nevertheless, further studies are necessary to determine whether primary or secondary vascular changes play a role in AMD. Although the hemodynamic abnormalities do not directly indicate that the vascular abnormalities precede the devel- opment of AMD, they certainly suggest that hemodynamic changes play an important role in AMD pathogenesis. Fried- man (1997, 2004) uses vascular theory to help explain what is known about the AMD pathophysiology. With advancing age, there is vascular stiffening and increased resistance. As overall vascular resistance increases, cerebral vascular resistance rises and leads to decreased choroidal perfusion and increased osmotic gradients against which retinal pig- ment epithelial cells must pump. This leads to accumula- tion of debris in the form of drusen. Furthermore, high choriocapillary pressure in the presence of calciﬁcation and fracture of Bruch’s membrane and ischemic damage to retinal pigment epithelial cells can cause the secretion of vascular growth factors leading to the development of choroidal neovascularization (Friedman 1997, 2004). Although this theory has not been confirmed and does not elucidate the differences between races, it provides a well-rounded description of vascular alterations and how they contribute to the pathogenesis of AMD. Role of genetics in AMD Numerous population-based studies have reported differences in prevalence and incidence of AMD between various ethnic/racial groups (Klein et al 1999, 2006; Mitchell et al 1995; Vingerling et al 1995b). Several studies have demonstrated an increased incidence of 479