Ehrlich et al AMD within families to provide further support for the role of genetics in AMD (Seddon et al 1997; Klaver et al 1998; Grizzard et al 2003). Therefore, it is important for investigators to continue to explore the role of genetics and environment on the development of AMD. Although genetic predisposition combined with environmental stressors seem to lead to disease development (Swaroop et al 2007), various studies have identiﬁed chromosomal abnormalities associated with AMD. Some of the chro- mosomal regions associated with AMD include 1q31–32, 6q21 and 10q26 (Gold et al 2006; Swaroop et al 2007). Within chromosome segment 10q26, speciﬁc gene regions include PLEKHA1, LOC387715 and HTRA1 (Swaroop et al 2007). Complement factor H, within chromosomal segment 1q31–32, is a key regulator in the alternative com- plement cascade and prevents uncontrolled complement activation (Yates et al 2007). Thakkinstian et al (2006) performed a meta-analysis between complement factor H Y402H polymorphism and AMD to ﬁnd that heterozygotes (TC) and homozygotes (CC) were, respectively, 2.5 and 6 times more likely to have AMD than homozygote patients with the TT genotype. Nevertheless, a Japanese study found that this complement factor H gene did not appear to increase risk of AMD within their population (Gotoh et al 2006). This appears to demonstrate that there are differences amongst various ethnic groups. Furthermore, within chromosome 6q21, polymorphisms of complement factor B and complement component 2 have been shown to be a risk predictor of AMD (Gold et al 2006). These correlations between complement-related genes and AMD further support the role of the inﬂammatory system in the development of AMD. In addition, a previous study by Mullins et al (2000) found that drusen can contain activated complement factors, acute phase reactants, coagulation proteins, immunoglobulins, and other proteins involved in the induction and activation of the immune response. Not only can an individual’s genetic predisposition inﬂuence the development of AMD, but it is also associated with the rate of disease progression. Seddon et al (2007) analyzed patients from the Age-Related Eye Disease Study (AREDS) to determine whether variations within the complement factor H gene and the LOC387715 gene have prognostic importance in AMD disease progression. Although genetic polymorphisms in the comple- ment factor H Y402H and LOC387715 A69S were associated with progression to more advanced AMD, the LOC387715 genotype was also correlated with neovascular disease more than geographic atrophy. Patients who were homozygous for the risk alleles had a nearly 50% probability for AMD progression 480 compared to the 5% risk in patients who are homozygous for the nonrisk alleles (Seddon et al 2007). Additionally, presence of the homozygous risk alleles combined with smoking and high body mass indices were associated with 19-fold increase of disease progression (Seddon et al 2007). Conversely, some genetic variations have been found to play a protective role in AMD development and progression. Apolipoprotein E is involved in transport and metabolism of lipid and cholesterol and in response to neural injury (Swaroop et al 2007). The ε4 allele of apolipoprotein E has been associated with the reduced prevalence of AMD. There is strong evidence for the role of genetics in AMD, but further research is necessary to determine how genetic differences can ultimately lead to AMD. Conclusion Several systemic and ocular diseases increase in incidence and prevalence in the elderly population. Although AMD development shares many correlations with normal aging processes, other factors, such as genetic predisposition or environmental stressors, may account for disease develop- ment (Figure 2). Furthermore, the similarities between drusen and atherosclerosis demonstrate that a vascular component may play a role in AMD development. Apart from the struc- tural changes, age-related alterations in ocular hemodynamics can precede and correlate with the AMD pathogenesis, which further supports the vascular theory of AMD. Although aging alone is not sufﬁcient to form AMD, it is apparent that the age-related changes and genetics are very important to the pathophysiology of AMD. Understanding the processes that develop with age and in age-related diseases can help guide new early treatment modalities. Further studies are warranted in order to learn how age-associated vascular and ocular structural changes lead to disease development. This will help generate the knowledge needed to identify target areas that may be useful to prevent disease progression through medical or surgical treatment. Acknowledgments Funded in part by an unrestricted grant from Research to Pre- vent Blindness, New York, NY. The authors would like to thank Lynne McCranor for her assistance with this manuscript. Disclosures None of the authors has any conﬂicts of interest to disclose. Reference Andreoli CM, Miller JW. 2007. Anti-vascular endothelial growth factor therapy for ocular neovascular disease. Curr Opin Ophthalmol, 18:502–8. Clinical Interventions in Aging 2008:3(3)