Genetics and Epidemiology
Several ongoing projects are focused on age-related macular degeneration (AMD), a disease of the retina which is the leading cause of irreversible blindness in persons over age 50. The common goal of these studies is to learn more about the factors that cause macular degeneration, the extent to which it is genetic or environmental, the factors responsible for disease progression, and how best to treat the disease. Our ultimate goal is to save sight in individuals as they get older.
The Sibling Molecular Genetic Study of Macular Degeneration
The unit staff started the first national genetic, family study of Age-Related Macular Degeneration (AMD) at the Massachusetts Eye and Ear and Harvard Medical School, which was sponsored by the National Eye Institute. Our work in this area progressed and now includes the Sibling Study of Age-Related Macular Degeneration, also funded by the National Eye Institute (EY014458), and Dr. DeAngelis is the principle investigator. The goal of this study is to identify genetic variation involved in this eye disease so that effective treatments and preventive measures can be found. We are also evaluating the role of environmental factors, such as smoking, dietary supplementation and cardiovascular history, to determine how these factors modify our genetic predisposition. Once important factors contributing to macular degeneration are identified, we may be able to save the sight of future generations by treating and preventing the leading cause of visual disability in the U.S. We are actively recruiting patients and their siblings. Prospective participants must meet the following criteria:
• Macular Degeneration diagnosed at age 50 years of age or older
• At least one living sibling with or without age-related macular degeneration
If eligible, you and your family members will receive a free eye exam either at the Massachusetts Eye and Ear or at your local eye doctor's office. You do not need to come to Mass. Eye and Ear. If your family, or a family you know, is interested, call the Genetic Epidemiology Sibpair Study line for more information at: 617-573-2354.
The Age-Related Eye Disease Study (AREDS)
AREDS is a randomized clinical trial sponsored by the National Eye Institute, one of the divisions of the National Institutes of Health. Dr. Ivana Kim is the principle investigator for the MEEI site and Drs. Gragoudas, Loewenstein, Miller, Sobrin, Vavvas and Young are co-investigators for this project. Approximately 5000 patients have been enrolled at the 11 clinical centers participating in this nationwide study. The AMD clinical center at MEEI enrolled over 500 participants. Results show a 25% reduction in the rate of progression of AMD over 5 years among those patients taking the antioxidant and mineral formula (vitamins C, E, beta-carotene and zinc). This is the first known treatment for the “dry” form of AMD.
Research Findings and Reports
The following is a sample of important research findings which have furthered our understanding of the factors that contribute to age-related macular degeneration.
• DeAngelis MM, Lane A-M, Shah CP, Ott J, Dryja TP, Miller JW. Extremely discordant sib-pair study design to determine risk factors for neovascular age-related macular degeneration. Archives of Ophthalmology 2004; 122 (4):575-580. PMID: 15078676
• DeAngelis MM, Ji F, Kim I, Adams S, Capone A, Ott J, Miller JW, Dryja TP. Cigarette Smoking, CFH, APOE, ELOVL4, and Risk of Neovascular Age-Related Macular Degeneration. Archives of Ophthalmology 2007; 125(1):49-54. PMID: 17210851
• DeAngelis MM, Ji F, Adams SM, Morrison MA, Harring AJ, Sweeney MO, Capone A, Miller JW, Dryja, TP, and Kim, IK. Alleles in HTRA serine Peptidase 1 gene both reduce and increase risk of neovascular age-related macular degeneration independent of the Complement factor H gene and smoking. Ophthalmology In Press. PMID: 18164066
• DeAngelis, M.M. and Ji, F. (2008). Genetics of Age-related Macular Degeneration. In Albert & Jakobiec's Principles & Practice of Ophthalmology. Albert DM, Miller JW et al,. eds. Saunders, Philadelphia, PA, 3rd ed. Vol. 2 pp. 1881-1900
• Seddon, J.M., Cote, J., Rosner, B. Progression of Age-Related Macular Degeneration. Association with Dietary Fat, Transunsaturated Fat, Nuts, and Fish Intake. Arch. Ophthalmology (2003)121: 1728-1737
• Seddon, J.M., Cote, J., Davis, N., Rosner, B. Progression of Age-Related Macular Degeneration. Association with Body Mass Index, Waist Circumference, Waist-Hip Ratio. Arch. Ophthalmology (2003) 121: 785-792
• Age-Related Eye Disease Study Research Group. A Randomized, Placebo-Controlled, Clinical Trial of High-Dose Supplementation with Vitamins C and E, Beta- Carotene, and zinc for Age-Related Macular Degeneration and Vision Loss. Arch Ophthalmology (2001) 119:1417-1436v
• Seddon, J.M., Ajani, U.A., Braxton, M.D. Familial Aggregation of Age-related Maculopathy. Am. J. of Ophthalmology (1997) 123: 199-206
Glaucoma causes irreversible degeneration of the optic nerve, usually associated with elevated pressure in the eye. This disease is the third leading cause of blindness among all Americans, and is the leading cause of blindness in African Americans. Several of our research programs are directed at the identification of genetic and environmental factors that contribute to glaucoma.
Family History of Glaucoma Project
A family history is one of the most important risk factors for glaucoma, and this project has been studying families with glaucoma for over 15 years. This work has been supported by the National Eye Institute and is currently funded by two grants (NEI EY009847, and NEI EY0 015872). Dr. Wiggs is the principle investigators for this study. The overall goal of this project is to identify the genetic factors responsible for glaucoma. Genetic factors that are known to contribute to glaucoma can be used to develop novel methods to screen patients at risk for glaucoma and to diagnose and treat patients with glaucoma. We are actively recruiting patients and family members for this study. Eligible participants should meet the following criteria:
• Diagnosis of glaucoma
• At least one living relative who has also been diagnosed with glaucoma
If eligible, you and your family members will receive a free eye exam either at the Massachusetts Eye and Ear Infirmary. If your family, or a family you know, is interested, call the Family History of Glaucoma Project Study line for more information at: (800) 368-8143.
Gene-Environment Interaction in Glaucoma Project
For chronic progressive diseases such as glaucoma, genetic and environmental factors are likely to work together to cause blindness. The goal of this study is to identify environmental factors that contribute to glaucoma and to investigate the interactions between environmental factors and genetic factors in the disease. This project is funded by the National Eye Institute (EY015473). Dr. Pasquale is the principle investigator of the study.
Research Findings and Reports
The following is a sample of important research findings which have furthered our understanding of the factors that contribute to glaucoma.
• Kang JH, Willett WC, Rosner BA, Hankinson SE, Pasquale LR. Caffeine consumption and the risk of primary open-angle glaucoma: a prospective cohort study. Invest Ophthalmol Vis Sci. 2008 May;49(5):1924-31.
• Pasquale LR, Rosner BA, Hankinson SE, Kang JH. Attributes of female reproductive aging and their relation to primary open-angle glaucoma: a prospective study. J Glaucoma. 2007 Oct-Nov;16(7):598-605.PMID: 18091177
• Kang JH, Willett WC, Rosner BA, Hankinson SE, Pasquale LR. Prospective study of alcohol consumption and the risk of primary open-angle glaucoma. Ophthalmic Epidemiol. 2007 May-Jun;14(3):141-7.PMID: 17613849
• Kang JH, Pasquale LR, Willett WC, Rosner BA, Egan KM, Faberowski N, Hankinson SE. Dietary fat consumption and primary open-angle glaucoma. Am J Clin Nutr. 2004 May;79(5):755-64.PMID: 15113712
• Wiggs JL. Genomic promise: personalized medicine for ophthalmology. Arch Ophthalmol. 2008 Mar;126(3):422-3. No abstract available. PMID: 18332327
• Fan BJ, Pasquale L, Grosskreutz CL, Rhee D, Chen T, DeAngelis MM, Kim I, del Bono E, Miller JW, Li T, Haines JL, Wiggs JL.DNA sequence variants in the LOXL1 gene are associated with pseudoexfoliation glaucoma in a U.S. clinic-based population with broad ethnic diversity. BMC Med Genet. 2008 Feb 6;9:5.PMID: 18254956
• Wiggs JL. Genetic etiologies of glaucoma. Arch Ophthalmol. 2007 Jan;125(1):30-7. PMID: 17210849
• Wiggs JL, Lynch S, Ynagi G, Maselli M, Auguste J, Del Bono EA, Olson LM, Haines JL. A genomewide scan identifies novel early-onset primary open-angle glaucoma loci on 9q22 and 20p12.Am J Hum Genet. 2004 Jun;74(6):1314-20.
Diabetic retinopathy is a serious complication of diabetes, causing blindness in many individuals. Several projects are designed to identify the risk factors that specifically predispose to this important condition. Dr. Sobrin is the principal investigator for this program.
Fungal infection of the cornea (fungal keratitis)
Recent reports have indicated an increased incidence of infections in the cornea in contact lens wearers caused by fungus. These infections can be difficult to treat and can lead to permanent scarring of the cornea. Risk factors that predispose to these infections are currently being studied by Dr. Colby.