ABSTRACT Age-related macular degeneration (AMD) is a slowly progressing multifactorial disease involving genetic abnormalities and environmental insults. AMD is the leading cause of blindness for Americans over the age of sixty. As the population ages, the prevalence of AMD will continue to grow, reaching a maximum risk rate of ~30% by the age of 70 years. Since smoking increases the risk of AMD, and there is a 20% higher incidence of smoking in the Veteran population than in the U.S. adult civilian population, the U.S. Department of Veterans Affairs healthcare system will have to provide care for potentially up to 7 million or more AMD cases. Currently available treatments focus on the late stage of the disease (choroidal neovascularization); however, those treatments come with significant risks and only target subpopulations of AMD patients. No treatment is available for early AMD disease which includes >85% of all cases. Thus, it is of paramount importance that the investigators learn how to detect AMD early and develop treatments that allow for early disease prevention. While mechanistic studies have shown that inflammation and smoking are fundamental components of both the wet and dry forms of AMD, genetic studies have demonstrated that polymorphisms in different complement proteins each increase the risk for developing AMD. One of the most detrimental mutations occurs in factor H, an essential inhibitor in the complement cascade. Overall, it has been hypothesized that inadequate control of complement-driven inflammation may be a major factor in disease pathogenesis in AMD. Here the investigators wish to answer an essential question: do smoking and complement act synergistically in the AMD disease process. For this proposal the investigators will be guided by the investigators' overall hypothesis that pathological activation of the alternative complement pathway has direct effect on the retinal pigment epithelium, generating a permissive cellular environment for AMD pathology. Thus, the investigators will recruit case subjects with AMD and control subjects, selecting both smokers and non-smokers in both groups, to determine whether smoking influences complement activation, or whether smoking acts through a yet undefined pathway to promote AMD development. A complete eye exam to determine pathology and visual impairment will be performed on Day 1 of the study. Serum will be analyzed to measure complement factor H activity. Plasma will be analyzed to measure complement breakdown products such as C3a, C5a and Bb. The cells that remain will be used for genotyping.