Macular Degeneration Epidemiology: Nature-Nurture, Lifestyle Factors, Genetic Risk, and Gene-Environment Interactions

Mildred Weisenfeld Award Lecture ARVO, Baltimore, Maryland - May 8, 2017

Johanna M. Seddon, M.D., Sc.M.

Professor of Director, Ophthalmic Epidemiology and Tufts University School of Medicine Genetics Service, New England Eye Center

Importance Anatomy of the Eye of AMD More People Research With This The Faces of the People DiseaseWe Love Older Population Expanding

The first female ophthalmologist

Isabel in the US Barrows (1845-1913)

Ross Rd. in Albert DM, The History of Ophthalmology. 1996, p. 276.

Mildred Weisenfeld (1921-1997)

1986 1936 - Diagnosed with retinitis Established the pigmentosa Mildred Weisenfeld Award for Excellence in Ophthalmology 1946 - Founded the Fight for Sight organization

Historical Vignettes

Epidemiology & Major Advances EPIDEMIOLOGY: the study of determinants and patterns of disease Epidemiology is logical, a science of common sense

Major advances: Germ theory, disease transmission, vaccination, study designs, risk factors: all are still used today.

Broad Framingham Smoking Smallpox Street Heart and Vaccine Pump Study Cancer

Perspectives on AMD

World War II Veterans Twin Registry

Classic twin study to dissect genes and environment NonNon-Genetic-Genetic Factors Factors

Genetic Factors

Gene-Environment Associations Can nutritional factors prevent or slow the progression of AMD?

The food frequency questionnaire used in this study provides reproducible dietary information.

Ajani U, et al. IOVS 1994; 35(6): 2725-2733

Dietary and Risk of AMD ♦ Higher total fat increased the risk of AMD ♦ Omega-3 fatty acids (fish and nuts) reduced risk of AMD ♦ Similar results in case- control and prospective cohort studies Mares-Perlman J, et al. Arch Ophthal 1995;113:1518-23 Seddon J, et al. IOVS 1994; 35: ARVO Abstract S2003 Smith W, Mitchell P, Leeder S. Arch Ophthal 2000;118:401-404 Seddon J, et al. Arch Ophthal 2001;119:1191-99 Cho E, et al. Am J Clin Nutr 2001;73:209-18 Seddon J, et al. Arch Ophthal 2003;121:1728-37 AREDS Research Group. 2004-2009 Seddon J, et al. Arch Ophthal 2006;124:995-1001 Cigarette Smoking, Fish, & Omega-3s

US Twin Study of AMD (WWII Veteran Twin Registry) ♦ Smoking: two-fold increased risk for current and past smokers ♦ Fish: decreased risk ♦ Omega-3 fatty acids: decreased risk Attributable risk: 32% for smoking, 22% for dietary omega-3 Seddon J, et al. Arch Ophthal 2006;124:995-1001

Supplement Recommendations from AREDS and AREDS2: Vitamin C, Vitamin E, Zinc, ,

Emily Chew

Rick Ferris

Arch Ophthalmol 2001;119:1417-36 Arch Ophthalmol 2007;125:1225-32