AMD of the aging eye Vascular Changes with Age Structural Changes with Age Decreased thickness of choroid Decrease in choriocapillary density Decreased lumen diameter of choriocapillaries Increased resistance to flow Reduced choroidal flow Reduced choroidal perfusion Senescence of RPE cells Accumulation of waste products and formation of drusen Thickening of Bruch’s membrane Change in the composition of Bruch’s membrane Changes in the extracellular matrix Increase in oxidative stress Genetic Predisposition and Environmental Risk Factors AMD Figure 2 The vascular and nonvascular theory of AMD.The vascular theory, suggested by Friedman (1997), states that with increased resistance in the choroidal vessels, there is an increase in the osmotic gradient against which the retinal pigment epithelial cells must pump.This leads to retinal pigment epithelial cell dysfunction and the accumula- tion of metabolic debris and drusen formation. Furthermore, the decrease in choroidal perfusion causes ischemic/hypoxic injury and increased oxidative stress, which can signal choroidal neovascularization formation. On the other hand, in the nonvascular theory, senescent retinal pigment epithelial cells can lead to retinal pigment epithelial cell dysfunction, which in turn can cause choriocapillary atrophy. Over time, and individual’s genetic predisposition and environmental stressors in the setting of structural and vascular changes make the eye more susceptible to AMD development. 45% decrease in choriocapillary density and a 34% decrease in the lumen diameter of the choriocapillaries with advancing age (Ramrattan et al 1994). Reduced numbers of macular arterioles and decreased intensity of dye in the macular region have been demonstrated over time using indocyanine green angiography (Nishiyama et al 2001). These age-related changes were noted only in the arteries, but not in veins. Fur- thermore, choroidal blood ﬂow changes have been reported with advancing age (Ramrattan et al 1994). Pulsatile ocular blood ﬂow reﬂects the total pulsatile component of ocular blood ﬂow and since most of the ocular blood volume is present in the choroid, it mainly represents the choroidal circulation (Sandhu et al 2007). Ravalico et al (1996) and Lam et al (2003) both found a decline in the pulsatile ocular blood ﬂow with age. Animal models have shown a 35%–42% reduction in ocular blood ﬂow and a 57%–93% increase in ocular vascular resistance in aged rats compared with juvenile or adult rats (Salter et al 1998). Age-related changes in the Clinical Interventions in Aging 2008:3(3) reﬂexive choroidal vasodilatation following hypoperfusion have also been shown in rat models (Fitzgerald et al 2005). Neurogenic choroidal blood ﬂow control declines with age both in human and in animal studies (Fitzgerald et al 2005). With the use of laser Doppler ﬂowmetry, Grunwald et al (1998) reported age-related decreases in choroidal blood ﬂow in the fovea, which was related to decreases in blood volume but not velocity. The use of color Doppler imaging provides measure- ments of the retrobulbar vasculature, namely the ophthalmic, central retinal and short posterior ciliary arteries. Retro- bulbar changes have been demonstrated with advancing age. Age-related decreases in peak systolic velocity and end-diastolic velocity of the ophthalmic artery have been reported (Harris et al 2000; Lam et al 2003). Additionally, Pourcelot’s resistive index was increased in the ophthalmic artery (Harris et al 2000, Lam et al 2003). Groh et al (1996) found a decrease in central retinal artery blood ﬂow by 477