The Beaver Dam Eye Study

The Beaver Dam Eye Study is funded by the National Eye Institute, part of the National Institutes of Health. The purpose of the study is to collect information on the prevalence and incidence of age-related cataract, macular degeneration, and diabetic retinopathy, which are all common eye diseases in an aging population. The study also has examined other aging issues, such as overall health, quality of life, and environmental and medicinal exposures.

The study was funded initially in 1987. A private census was conducted and the study population of approximately 6,000 people aged 43 through 84 years in the city and township of Beaver Dam, Wisconsin were identified. Approximately 5,000 people participated in a baseline examination done between 1988 and 1990. The five-year follow-up examination (1993-1995) had approximately 4,500 participants. The cohort is being re-examined (10-year follow-up), with approximately 3,000 participants expected to be seen. The ten-year examinations conclude on May 31, 2000.

To date there have been over 100 publications describing the prevalence and incidence of visual loss, age-related macular degeneration, and cataract and associated risk factors. An important finding from the study was the association of cigarette smoking with both cataract and age-related macular degeneration. Another important findings is the description of relationship of early lesions such as retinal drusen and pigmentary abnormalities with the progression to late lesions of age-related macular degeneration. This information has been used to provide estimates of these conditions in the general population and has been used to develop protocols and estimates of sample size in large clinical trials.

Approaches developed to grade cataract and age-related macular degeneration have been used in other studies. Three such studies, the Blue Mountains Eye Study in Australia, the Rotterdam Study, and the Los Angeles Latino Eye Study, have used protocols similar to those used in the Beaver Dam Eye Study. Comparison of the data from Beaver Dam, Blue Mountains and Rotterdam demonstrated the differences in the frequency of late stages of macular degeneration around the world that was not explained by any of the associated environmental, demographic, and health factors studied to date. The strong association of cigarette smoking and macular degeneration was found in all three populations.

WESDR / WESCID

WESDR (the Wisconsin Epidemiologic Study of Diabetic Retinopathy) began in 1979. It was initially funded by the National Eye Institute. The purpose of the WESDR was to describe the frequency and incidence of complications associated with diabetes (eye complications such as diabetic retinopathy and visual loss, kidney complications such as diabetic nephropathy, and amputations), and to identify risk factors (such as poor glycemic control, smoking, and high blood pressure) which may contribute to the development of these complications. In addition, another purpose of the WESDR was to examine health care delivery for people with diabetes.

WESDR examinations were done in a large 40-foot mobile examining van in an eleven-county area in southern Wisconsin and involved all persons with younger-onset type 1 diabetes (996 people) and older-onset persons mostly with type 2 diabetes (1370 people) who were first examined from 1980 to 1982. The examinations were done near participants' residences. The van provided standardized conditions to examine participants and minimized participants' travel time. The examination involved refraction and measurement of best corrected visual acuity, examination of the front and back of the eye, measurement of the pressure in the eye, fundus photography, blood tests for glycosylated hemoglobin (a measure of recent blood sugar control) and random blood sugar, and urine protein analysis. The fundus photographs were masked for anonymity and then graded by trained graders. This provided objective information about the presence and severity of diabetic retinopathy (damage of the retinal blood vessels from diabetes) and macular edema (swelling of the center of the retina) in each eye. There were follow-up examinations of the cohort in 1984-86, 1990-92, and 1995-96 . Many reports have arisen from the WESDR which have demonstrated the associations of good control of blood sugar with less risk of incidence and progression of diabetic retinopathy and diabetic kidney disease. Data from the WESDR has been used in developing international guidelines for eye care for people with diabetes. These data have also been used in developing educational programs such as the National Eye Health Education Program. More information about the latter is available from the National Eye Institute.

In 1999, the National Heart, Lung, and Blood Institute funded the continuation of the WESDR, now known as the Wisconsin Epidemiologic Study of Cardiovascular Disease in Diabetes (WESCID) to examine the incidence of heart disease and its associations with various risk factors in people with type 1 diabetes. A paper from this study recently appeared in JAMA. This paper showed an association of alcohol with few cardiovascular disease deaths in the cohort. WESCID is being done in conjunction with the ECG staff of Bowman Grey Medical School.

It is hoped that the new emphasis on cardiovascular and peripheral vascular complications in people with diabetes will lead to development of more effective preventive and treatment options.

• Klein AP, Duggal P, Lee KE, Klein R, Bailey-Wilson JE, Klein BEK. Support for polygenic influences on ocular refractive error. Invest Ophthalmol Vis Sci 2005; 46:442-446.

• Duggal P, Klein AP, Lee KE, Iyengar S0K, Klein R, Bailey-Wilson JE, Klein BEK. A genetic contribution to intraocular pressure: the Beaver Dam Eye Study. Invest Ophthalmol Vis Sci 2005; 46(2):555-560.

• Wong TY, Klein R, Klein BEK, Knudtson MD, Hubbard LD. Medication use and retinal vessel diameters. Am J Opthalmol 2005; 139(2):373-5.

• Klein BE, Klein R, Knudtson MD. Intraocular pressure and systemic blood pressure: longitudinal perspective. The Beaver Dam Eye Study. Br J Ophthalmol 2005, 89(3):284-287.

• Klein AP, Duggal P, Lee KE, O=Neill JA, Klein R, Bailey-Wilson JE, Klein BEK. Polygenic effects and cigarette smoking account for a portion of the familial aggregation of nuclear sclerosis. Am J Epidemiol 2005;161:707-713.

• Klein BEK, Hubbard L, Ferrier NJ, Klein R, Klein DJ, Lee KL, Ewen A, Jensen K, Evans MD. Detecting progression of nuclear sclerosis by using human grading versus semi-automated computer grading. Invest Ophthalmol Vis Sci 2005; 46:1155-1162.

• Wong TY, Knudtson MD, Klein BEK, Klein R, Hubbard LD. Estrogen replacement therapy and retinal vascular caliber. Ophthalmology 2005; 112:553-558.

• Wong TY, Shankar A, Klein R, Klein BEK, Hubbard LD. Retinal arteriolar narrowing hypertension and subsequent risk of diabetes mellitus. Arch Int Med 2005; 165:1060-1065.

• Knudtson MD, Klein BE, Klein R, Cruickshanks KJ, Lee KE. Age-related eye disease, quality of life, and functional activity. Arch Ophthalmol 2005;123:807-814.

• Fisher SA, Abecasis GR, Yashar BM, Zareparsi S, Swaroop A, Iyengar SK, Klein BEK, Klein R, Lee KE, Majewski J, Schultz DW, Klein ML, Seddon JM, Santangelo SL, Weeks DE, Conley YP, Mah TS, Schmidt S, Haines JL, Pericak-Vance MA, Gorin MB, Schultz HL, Pardi F, Lewis CM, Weber BH. Meta-analysis of genome scans of age-related macular degeneration. Hum Mol Genet 2005; 14:2257-2264.

• Klein R, Klein BEK, Knudtson MD, Wong TY, Shankar A, Tsai MY. Systemic markers of inflammation, endothelial dysfunction, and age-related maculopathy. Am J Ophthalmol 2005;140:35-44.

• Klein R, Klein BEK, Knudtson MD. Frailty and age-related macular degeneration. The Beaver Dam Eye Study. Am J Ophthalmol 2005;140:129-131.

• Puent BD, Klein BEK, Klein R, Cruickshanks KJ, Nondahl DM. Factors related to vision care in an older adult cohort. Optom Vis Sci 2005;82:612-616.

• Nondahl DM, Klein BEK, Klein R, Cruickshanks KJ, Wiley TL. Factors predicting severity of tinnitus: a population-based assessment [Letter]. J Am Acad Audiol 2005;16(3):196.

• Knudtson MD, Klein BEK, Klein R, Shankar A. Associations with weight loss and subsequent mortality risk. Ann Epidemiol 2005; 15(7):483-491.

• Jun G, Klein BEK, Klein R, Fox K, Millard C, Humphrey J, Russo K, Lee, KE, Elston RC, Iyengar SK. Genome-wide analyses demonstrate novel loci that predispose to drusen formation. Invest Ophthalmol Vis Sci 2005; 46:3081-3088.

• Klein BEK, Klein R, Knudtson MD, Lee KE. Frailty, morbidity, and survival. Arch Gerontol Geriatr 2005; 41:141-149.

• Klein R, Meuer SM, Moss SE, Klein BEK, Neider MW, Reinke J. Detecting age-related macular degeneration: technologies are best compared when standardized [author reply]. Arch Ophthalmol 2005;123:1157-1158.

• Moss SE, Klein R, Klein BEK. Ankle-brachial index and the prevalence of age-related maculopathy. Am J Ophthalmol 2005; 140(6):1159-1161.

• Klein R, Klein BEK, Moss SE. Ten-year incidence of self-reported erectile dysfunction in people with long-term type 1 diabetes. J Diabetes Complications 2005;19:35-41.

• Zhou H, Isaman DJ, Messinger S, Brown MB, Klein R, Brandle M, Herman WH. A computer simulation model of diabetes progression, quality of life, and cost. Diabetes Care 2005;28(12):2856-2863.

• Klein BEK, Klein R, McBride P, Moss SE, Prineas R, Reinke J. Electrocardiographic abnormalities in persons with long duration type 1 diabetes. Diabetes Care 2005; 28(1):145-7.

• Klein BEK, Klein R, Lee KE, Knudtson MD, Tsai MY. Markers of inflammation, vascular endothelial dysfunction and age-related cataract. Am J Ophthalmol 2006; 141:116-122.

• Klein R, Klein BEK, Knudtson MD, Wong TY, Tsai M. Are inflammatory factors related to retinal vessel caliber? The Beaver Dam Eye Study. Arch Opthalmol 2006; 124(1):87-94.

• Xing C, Klein BEK, Klein R, Jun G, Lee KE, Iyengar S. A genome-wide linkage study of retinal vessel diameters in Beaver Dam Eye Study. Hypertension 2006; 47(4):797-802.

• Hall ER, Klein BEK, Meuer SM, Knudtson MD, Klein R. Age-related macular degeneration and optic disc cupping. Am J Ophthalmol 2006; 141(3):494-497.

• Knudtson MD, Klein R, Klein BEK. Age-related eye disease, visual impairment and survival: The Beaver Dam Eye Study. Arch Ophthalmol 2006;124(2):243-249.

• Klein R, Klein BEK. The epidemiology of eye disease: from glycemia to genetics. Invest Ophth Vis Sci 2006; 47(5):1747-1453.

• Klein BEK, Meuer S, Knudtson MD, Klein R. The relationship of cup to disc ratio to retinal vein occlusion: The Beaver Dam Eye Study. Am J Ophthalmol 2006; 141(5):859-862.

• Shankar A, Klein R, Klein BEK. The association between smoking, heavy drinking and chronic kidney disease. Am J Epidemiol 2006; 164(3):263-271.

• Wang JJ, Cugati S, Knudtson MD, Rochtchina E, Klein R, Klein BEK, Wong TY, Mitchell P. Retinal arteriolar emboli and long-term mortality: pooled data analysis from two older populations. Stroke 2006; 37:1833-1836.

• Klein BEK, Klein R, Lee KE, Grady LM. Statin use and incident nuclear cataract. JAMA 2006;295:2752-2758.

• Ewen A, Lee KE, Klein BEK, Meuer SM, Klein R. Comparability of cup and disc diameters measured from nonstereoscopic digital and stereoscopic film images. Am J Ophthalmol 2006;141(6):1126-1128.

• Klein BEK, Klein R, Knudtson MD. Lens opacities associated with performance-based and self-assessed visual functions. Ophthalmology 2006; 113(8):1257-1263.

• Klein BEK, Klein R, Knudtson MD. Frailty and age-related cataract. Ophthalmology 2006; 113(12):2209-2212.

• Shankar A, Klein R, Klein BEK, Nieto FJ. The association of between serum uric acid level and long-term incidence of hypertension: population-based cohort study. J Hum Hypertens 2006;20(12):937-945.

• Klein R, Klein BEK, Lee KE, Cruickshanks KJ, Gangnon RE. Changes in visual acuity in a population over a 15-year period. The Beaver Dam Eye Study. Am J Ophthalmol 2006;142(4):539-549.

• Knudtson MD, Klein R, Klein BEK. Physical activity and the 15-year cumulative incidence of age-related macular degeneration: The Beaver Dam Eye Study. Br J Ophthalmol 2006;90:1461-1463.

• Mosher AE, Knudtson MD, Jensen KN, Klein R, Hubbard LE, Ferrier NJ. Comparison of retinal image measurements in digital vs film images. Am J Ophthalmol 2006;142(5):875-8.

• Klein BEK, Klein R, Lee KE, Hoyer CJ. Does the intraocular pressure affect on optic disc cupping differ by age? Trans Am Ophthalmol Soc 2006; 104:143-148.

• Klein R, Klein BEK, Moss SE, Wong TY. The relationship of retinopathy in persons without diabetes to the 15-year incidence of diabetes and hypertension: Beaver Dam Eye Study. Trans Am Ophthalmol Soc 2006; 104:98-107.

• Nondahl DM, Cruickshanks KJ, Dalton DS, Klein BEK, Klein R, Tweed TS, Wiley TL. The use of hearing protection devices by older adults during recreational noise exposure. Noise Health 2006;8:147-53.

• Klein R, Klein BEK. The epidemiology of eye disease: from glycemia to genetics. Invest Ophth Vis Sci 2006; 47(5):1747-1453.

• Klein R, Klein BEK, Moss SE, Wong TY, Sharrett AR. Retinal vascular caliber in persons with type 2 diabetes. The Wisconsin Epidemiological Study of Diabetic Retinopathy. XX. Ophthalmology 2006;113(9):1488-1498.

• Lee K, Klein BEK, Klein R, Meuer S. Association of retinal vessel caliber to optic disc and cup diameters. Invest Ophthalmol Vis Sci 2007;48(1):63-67.

• Duggal P, Klein AP, Lee KE, Klein R, Klein BE, Bailey-Wilson JE. Identification of novel genetic loci for intraocular pressure: A genomewide scan of the Beaver Dam Eye Study. Arch Ophthalmol 2007;125(1):74-79.

• Klein R, Klein BEK, Knudtson MD, Meuer SM, Swift M, Gangnon R. The fifteen-year cumulative incidence of age-related macular degeneration: The Beaver Dam Eye Study. Ophthalmology 2007; 114(2):253-262.

• Cugati S, Wang JJ, Knudtson MD, Rochtchina E, Klein R, Klein BEK, Wong TY, Mitchell P. Retinal vein occlusion and vascular mortality: pooled-data analysis of two population-based cohorts. Ophthalmology 2007;114(3):520-524.

• Nondahl DM, Cruickshanks KJ, Dalton DS, Klein BEK, Klein R, Schubert CR, Tweed TS, Wiley TL. The impact of tinnitus and quality of life in older adults. J Am Acad Audiol 2007; 18(3):257-266.

• Klein R, Knudtson MD, Klein BEK. Statin use and the 15-year incidence and progression of age-related macular degeneration. Am J Ophthalmol 2007; 144(1):1-6.

• Knudtson MD, Klein R, Klein BEK. Alcohol consumption and the 15-year cumulative incidence of age-related macular degeneration. Am J Ophthalmol 2007;143(6):1026-1029.

• Thompson CL, Jun G, Klein BEK, Klein R, Capriotti J, Lee KE, Iyengar SK. Genetics of pigment changes and geographic atrophy. Invest Ophthalmol Vis Sci 2007; 48:3005-3013.

• Thompson CL, Klein BEK, Klein R, Xu Z, Capriotti J, Josh T, Leontiev D, Lee KE, Elston RC, Iyengar SK. Complement factor H and hemicentin-1 in age-related macular degeneration and renal phenotypes. Hum Mol Genet Revision 2007; 16(17):2135-2148.

• Hirai FE, Klein R, Klein BEK. Retinopathy and survival in a population without diabetes: The Beaver Dam Eye Study. Am J Epidemiol 2007; 166(6):724-30.

• Wang JJ, Liew G, Klein R, Rochtchina E, Knudtson MD, Klein BE, Wong TY, Burlutsky G, Mitchell P. Retinal vessel diameter and cardiovascular mortality: pooled data analysis from two older populations. Eur Heart J 2007; 28(16):1984-92.

• Trentham-Dietz A, Sprague, BL, Klein R, Klein BEK, Cruickshanks KJ, Fryback DG, Hampton, JM. Health-related quality of life before and after a breast cancer diagnosis. Breast Cancer Res Treat 2007 Aug. 3; [Epub ahead of print] <http://www.springerlink.com/content/p8278n1138q77w33/fulltext.pdf> December 14, 2007.

• Klein AP, Duggal P, Lee KE, Klein R, Bailey-Wilson JE, Klein BE. Confirmation of linkage to ocular refraction on chromosome 22q and identification of a novel linkage region on 1q. Arch Ophthalmol. 2007;125(1):80-5.

• Klein BEK, Lee KE, Klein R. Attained parental age and children’s survival at mid-life ages in a large population. Gerontology 2007; 53(6);161-165.

• Klein R. Overview of progress in the epidemiology of age-related macular degeneration. Ophthalmic Epidemiol 2007; 14:184-187.

• Knudtson MD, Klein R, Lee KE, Reinke JO, Danforth LG, Wealti AM, Moore E, Klein BEK. A longitudinal study of nonvitamin, nonmineral supplement use: prevalence, associations, and survival in an aging population. Ann Epidemiol 2007; 17:933-939.

• Klein BEK, Klein R. Lifestyle exposures and eye diseases in adults. Am J Ophthalmol 2007;144:961-69.

• Duggal P, Klein AP, Lee KE, Klein R, Klein BEK, Bailey-Wilson JE. The GLC1H glaucoma locus may reflect glaucoma with elevated intraocular pressure. Arch Ophthalmol 2007;125(12):1716-7.

• Shankar A, Klein R, Klein BEK, Nieto FJ, Moss SE. The relationship between low-normal blood pressure and kidney disease in type 1 diabetes. Hypertension 2007; 49:48-54.

• Hirai FE, Moss SE, Klein BEK, Klein R. Severe hypoglycemia and smoking in a long-term type 1 diabetic population: Wisconsin Epidemiological Study of Diabetic Retinopathy. Diabetes Care 2007; 30(6):1437-41.

• Shankar A, Klein R, Klein BEK, Moss SE. Association between glycosylated hemoglobin level and 16-year incidence of chronic kidney disease in type 1 diabetes. Exp Clin Endocrin Diabetes 2007; 115:203-206.

• Klein R, Klein BEK, Moss SE, Wong TY. The Relation of retinal vessel caliber to the long-term incidence of microvascular and macrovascular disease in persons with type 2 diabetes. XXI: The Wisconsin Epidemiologic Study of Diabetic Retinopathy. Ophthalmology 2007;114(10):1884-1892.

• Shankar A, Klein R, Klein BEK, Moss SE. Association between glycosylated hemoglobin level and cardiovascular and all-cause mortality in type 1 diabetes. Am J Epidemiol 2007; 166:393-402.

• Klein R, Klein BE, Moss SE, Wong TY. Retinal vessel caliber and microvascular and macrovascular disease in type 2 diabetes: XXI: the Wisconsin Epidemiologic Study of Diabetic Retinopathy. Ophthalmology 2007,114(10)1884-92.

• Klein BEK, Klein R. Lifestyle exposures and eye diseases in adults. Am J Ophthalmol 2007;144:961-69.

• Hirai FE, Moss SE, Klein BEK, Klein R. Relationship of glycemic control, exogenous insulin, and c-peptide levels to ischemic heart disease mortality over a 16-year period in persons with older-onset diabetes: The Wisconsin Epidemiologic Study of Diabetic Retinopathy. Diabetes Care 2008;31(3):493-7.

• Klein R, Knudtson MD, Cruickshanks KJ, Klein BEK. Further observations on the relationship of smoking to the long-term incidence and progression of age-related macular degeneration. The Beaver Dam Eye Study. Arch Ophthalmol 2008;126(1):115-21.

• Shankar A, Klein BEK, Klein R, Nieto FJ. Association between serum uric acid level and peripheral arterial disease. Atherosclerosis 2008;196:749-755.

• Klein R, Meuer SM, Knudtson MD, Iyengar SK, Klein BEK. The epidemiology of reticular drusen. Am J Ophthalmol 2008;145(2):317-26.