Age-related macular degeneration (AMD) is the leading cause of irreversible severe central visual loss in Caucasians older than 50 in the U.S. The incidence and progression of all the features of AMD are known to increase significantly with age. Approximately 10% of people 66 to 74 years of age will have findings of AMD, and the prevalence increases to approximately 30% in people 75 to 85 years of age. Recently in a large study with three racially similar populations of 14,752 participants from North America, Europe, and Australia, the prevalence of AMD is present in 0.2% of the combined population aged 55 to 64 years, rising to 13% of the population older than 85 years.

Epidemiological studies of candidate gene association and linkage disequilibrium suggest that AMD has a significant genetic component. Current evidence supports the hypothesis that variance of genes involved in DNA repair, oxidative stress, and inflammation play a role in aging and age-related diseases. Recently a few studies have documented the association between polymorphisms in oxidative stress, apolipoprotein E (ApoE), and angiotensin converting enzyme (ACE) genes and AMD. Single nucleotide polymorphism (SNP) in ApoE and ACE may protect AMD. On the other hand, SNP in manganese superoxide dismutate (oxidative stress) gene may be related to exudative AMD. In this study, we would like to test whether the variations of biologically plausible genes (or the modifying genes) listed above are differentially distributed in AMD patients and normal populations. To this end, we choose genes that are believed to play a crucial role in aging process and will analyze the frequency of SNPs specifically within the coding frames of biologically plausible genes responsible for aging and age-related disease.

Our aim will be to compare the allelic frequencies of candidate genes listed above in cohorts with AMD to the frequency in normal control subjects without AMD. With this study we hope to identify genetic risk factors that could have functional implications for understanding and treating AMD.

• INCLUSION CRITERIA:

Samples from volunteers meeting the following eligibility criteria will be included in the study.

AMD Patients (cases):

Diagnosis of advanced AMD defined by geographic atrophy (dry) and/or choroidal neovascularization (wet) with drusen of any size in at least one eye. (AMD cases only)

Age 50 years or older.

If sample previously donated in a different study, the patient has given their permission to use their sample (i.e. marked appropriate selection in the informed consent).

Control Patients (controls):

Absence of drusen or no more than 5 drusen less than 63 microns, absence of other diagnostic criteria for AMD.

Agrees to undergo study examinations.

EXCLUSION CITERIA:

Samples from volunteers meeting any of the following exclusion criteria will not be included.

Presence of retinal disease involving the photoreceptors and/or outer retinal layers other than AMD loss such as high myopia, retinal dystrophies, central serous retinopathy, vein occlusion, diabetic retinopathy and uveitis or similar outer retinal diseases that have been present prior to the age of 50.

Opacities of the ocular media, limitations of papillary dilation or other problems sufficient to preclude adequate stereo fundus photography. These conditions include occluded pupils due to synechiae, cataracts, vitreous haze and opacities due to ocular diseases.