Karen J. Cruickshanks

The Wisconsin epidemiologic study of diabetic retinopathy: XVII: The 14-year incidence and progression of diabetic retinopathy and associated risk factors in type 1 diabetes1

OBJECTIVE To examine the 14-year incidence and progression of diabetic retinopathy and macular edema and its relation to various risk factors. DESIGN Population-based incidence study. SETTING The study was conducted in an 11-county area in southern Wisconsin. PARTICIPANTS Six hundred thirty-four insulin-taking persons with diabetes diagnosed before age 30 years participated in baseline, 4-year, 10-year, and 14-year follow-up examinations. MAIN OUTCOME MEASURES The 14-year progression of retinopathy, progression to proliferative retinopathy, and incidence of macular edema were detected by masked grading of stereoscopic color fundus photographs using the modified Airlie House classification and the Early Treatment Diabetic Retinopathy Study retinopathy severity scheme. RESULTS The 14-year rate of progression of retinopathy was 86%, regression of retinopathy was 17%, progression to proliferative retinopathy was 37%, and incidence of macular edema was 26%. Progression of retinopathy was more likely with less severe retinopathy, being male, having higher glycosylated hemoglobin or diastolic blood pressure at baseline, an increase in the glycosylated hemoglobin level, and an increase in diastolic blood pressure level from the baseline to the 4-year follow-up. Increased risk of proliferative retinopathy or incidence of macular edema was associated with more severe baseline retinopathy, higher glycosylated hemoglobin at baseline, and an increase in the glycosylated hemoglobin between the baseline and 4-year follow-up examination. The increased risk of proliferative retinopathy was associated with the presence of hypertension at baseline, whereas the increased risk of a participant having macular edema develop was associated with the presence of gross proteinuria at baseline. Lower glycosylated hemoglobin at baseline was associated with improvement in retinopathy. CONCLUSIONS These data suggest relatively high 14-year rates of progression of retinopathy and incidence of macular edema. These data also suggest that a reduction of hyperglycemia and hypertension may result in a beneficial decrease in the progression to proliferative retinopathy.

The association of cardiovascular disease with the long-term incidence of age-related maculopathy: The Beaver Dam eye study

PURPOSE To examine the association between cardiovascular disease and its risk factors and the 10-year incidence of age-related maculopathy. DESIGN Population-based cohort study. PARTICIPANTS Persons 43 to 86 years of age at baseline examination from 1988 to 1990, living in Beaver Dam, Wisconsin, of whom 3684 persons participated in a 5-year follow-up examination and 2764 participated in a 10-year follow-up examination. METHODS Standardized protocols for physical examination, blood collection, administration of a questionnaire, and stereoscopic color fundus photography to determine age-related maculopathy. The Kaplan-Meier (product-limit) survival approach and discrete linear logistic regression were used in the data analysis. MAIN OUTCOME MEASURES Incidence and progression of age-related maculopathy. RESULTS When age, gender, and history of heavy drinking, smoking, and vitamin use were controlled for, higher systolic blood pressure at baseline was associated with the 10-year incidence of retinal pigment epithelial depigmentation (risk ratio [RR] per 10 mmHg systolic blood pressure, 1.10; 95% confidence interval [CI], 1.01-1.18; P = 0.02) and exudative macular degeneration (RR, 1.22; 95% CI, 1.06-1.41; P = 0.006). Higher pulse pressure at baseline was associated with the incidence of retinal pigment epithelial depigmentation (RR per 10 mmHg, 1.17; 95% CI, 1.07-1.28; P < 0.001), increased retinal pigment (RR, 1.10; 95% CI, 1.01-1.19; P = 0.03), exudative macular degeneration (RR, 1.34; 95% CI, 1.14-1.60; P < 0.001), and progression of age-related maculopathy (RR, 1.08; 95% CI, 1.01-1.17; P = 0.03). Higher serum high-density lipoprotein cholesterol at baseline was associated with pure geographic atrophy (RR per 10 mg/dl high-density lipoprotein cholesterol, 1.29; 95% CI, 1.05-1.58; P = 0.01). Physical activity at baseline was associated with the incidence of geographic atrophy (RR in those who worked up a sweat 5 times a week compared with those who did not, 0.12; 95% CI, 0.02-0.91; P = 0.04) exudative macular degeneration (RR, 0.27; 95% CI, 0.08-0.87; P = 0.05), and progression of age-related maculopathy (RR, 0.69; 95% CI, 0.47-1.00; P = 0.05). Neither a history of stroke nor heart attack was associated with the incidence or progression of age-related maculopathy. CONCLUSIONS These findings indicate relationships between higher pulse pressure (a presumed indicator of age-related elastin and collagen changes in Bruchs membrane) and systolic blood pressure with an increased 10-year incidence of some lesions defining early age-related maculopathy and exudative macular degeneration.

The Pittsburgh Insulin-dependent Diabetes Mellitus (IDDM) Morbidity and Mortality Study: Mortality Results

A follow-up study of 1966 patients with insulin-dependent diabetes mellitus (IDDM) who were diagnosed at Childrens Hospital of Pittsburgh (CHP) between 1950 and 1981 has been completed. The mean age of the population at follow-up was 21.2 yr with a mean duration of IDDM of 12.9 yr. Nine percent of the patients were deceased, a sevenfold excess in mortality compared with the U.S. population. The relative increase in mortality was greater for females than males and greater for blacks than whites. Before age 20, the primary excess in mortality was at onset of IDDM, or within 6 mo after onset, and was due to acute diabetic complications. After age 20, the annual mortality risk was approximately 2%, which was more than 20 times greater than for the U. S. population. Renal disease was responsible for the majority of these deaths. There was a reduced risk of dying for diabetic patients who were diagnosed between 1966 and 1971 compared with patients diagnosed during earlier years.

Performance-based and self-assessed measures of visual function as related to history of falls, hip fractures, and measured gait time: The Beaver Dam Eye Study

OBJECTIVE The purpose of the study is to report relationships between visual function parameters and falls, hip fractures, and gait time in adults. DESIGN Population-based study. PARTICIPANTS The 3722 persons who participated in the 5-year follow-up of the Beaver Dam Eye Study cohort. MAIN OUTCOME MEASURES The visual functions measured at the examination were best-corrected visual acuity, current binocular acuity, near acuity, contrast sensitivity, and visual threshold to light. Information on falls and hip fractures was obtained by structured interview. Gait time was measured by standardized protocol. RESULTS History of falls and hip fractures increased with age, as did time to walk a measured course. Falls were more commonly reported for all persons who had poorer visual function, although not all relationships were significant in persons less than 60 years of age. In persons 60 years of age and older, hip fractures after the age of 40 were significantly related to all measures of visual function. Time to walk a measured course was significantly related to all measures of visual function. CONCLUSIONS These data indicate a consistent relationship between falls, fractures, gait time, and visual functions. Longitudinal data are necessary to accurately determine temporal relationships and to determine the likelihood of a causal association. In the interim, these data suggest that improving visual function may have benefits such as decreased traumatic events and improved mobility.

Low Prevalence of Hearing Aid Use Among Older Adults with Hearing Loss: The Epidemiology of Hearing Loss Study

OBJECTIVES: To measure the prevalence of hearing aid use among older adults with hearing loss and to identify factors associated with those currently using hearing aids.

Ultraviolet light exposure and lens opacities: the Beaver Dam Eye Study.

OBJECTIVES Exposure to sunlight may be a risk factor for the development of cataract. The relationships between exposure to sunlight and to the ultraviolet-B (UVB) component of light and the prevalence of lens opacities were examined in the Beaver Dam Eye Study. METHODS Persons 43 to 84 years of age residing in Beaver Dam, Wisconsin, were examined using standardized photographic assessments of lens opacities. A questionnaire about medical history and exposure to light was administered. RESULTS After adjusting for other risk factors, men who had higher levels of average annual ambient UVB light were 1.36 times more likely to have more severe cortical opacities than men with lower levels. However, UVB exposure was not found to be associated with nuclear sclerosis or posterior subcapsular opacities in men. Moreover, no associations with UVB exposure were found for women, who were less likely to be exposed to UVB. CONCLUSIONS Exposure to UVB light may be associated with the severity of cortical opacities in men. However, the lack of an association in women, the group more likely to have cortical opacities, suggests that other factors may be more important in the pathogenesis of lens opacities.

Age-related maculopathy in a multiracial United States population: the National Health and Nutrition Examination Survey III.

OBJECTIVE To investigate the prevalence of and risk factors for age-related maculopathy (ARM) in three racial/ethnic groups: non-Hispanic whites, non-Hispanic blacks, and Mexican-Americans. DESIGN A nationally representative population-based, cross-sectional study. PARTICIPANTS A total of 8270 persons 40 years of age or older, a sample of the Third National Health and Nutrition Examination Survey. MAIN OUTCOME MEASURES Age-related maculopathy was determined by the grading of fundus photographs using a standardized protocol. RESULTS The prevalence of any ARM in the civilian noninstitutionalized United States population including those 40 years of age or older was 9.4% (95% confidence interval [CI], 8.2, 10.6) as estimated from the sample. After adjusting for age, there was no difference in the prevalence of early ARM (defined largely by the presence of soft drusen) by ethnic/racial group. However, for the less frequent component lesions of early ARM (increased retinal pigment and retinal pigment epithelial depigmentation), the odds ratios (95% CIs) comparing non-Hispanic blacks to non-Hispanic whites were 0.47 (0.31, 0.74) and 0.59 (0.33, 1.04), respectively, and for comparing Mexican-Americans to non-Hispanic whites, they were 0.41 (0.21, 0.81) and 0.72 (0.44, 1.19), respectively. For late ARM, the odds ratio (95% CI) for non-Hispanic blacks compared to non-Hispanic whites was 0.34 (0.10, 1.18) and for Mexican-Americans compared to non-Hispanic whites, it was 0.25 (0.07, 0.90). Other than age, none of the personal, medical, or physiologic variables studied were statistically significantly associated with any of the ARM endpoints in any of the three races/ethnic groups. CONCLUSION Overall, rates of any ARM (including all early and late lesions) are not significantly different among non-Hispanic blacks, Mexican-Americans, and non-Hispanic whites. However, the rates of individual lesions suggest that non-Hispanic whites and Mexican-Americans may be protected against retinal pigment abnormalities and lesions associated with late ARM. There appears to be little influence of personal, medical, and environmental factors studied on these results. Further studies in larger populations of older persons in these ethnic groups would likely clarify these relations.

The Prevalence of Age-Related Macular Degeneration and Associated Risk Factors

OBJECTIVES To determine the prevalence of age-related macular degeneration (AMD) and to examine how retinal drusen, retinal pigmentary abnormalities, and early AMD are related to age, sex, and other risk factors. PARTICIPANTS A total of 2810 people aged 21 to 84 years participating in the Beaver Dam Offspring Study. METHODS The presence and severity of various characteristics of drusen and other lesions typical of AMD were determined by grading digital color fundus images using the Wisconsin Age-Related Maculopathy Grading System. RESULTS Early AMD was present in 3.4% of the cohort and varied from 2.4% in those aged 21 to 34 years to 9.8% in those aged 65 years or older. In a multivariable model (expressed as odds ratio; 95% confidence interval), age (per 5 years of age, 1.22; 1.09-1.36), being male (1.65; 1.01-2.69), more pack-years of cigarettes smoked (1-10 vs 0, 1.31; 0.75-2.29; >or=11 vs 0, 1.67; 1.03-2.73), higher serum high-density lipoprotein cholesterol level (per 5 mg/dL, 0.91; 0.83-0.998), and hearing impairment (2.28; 1.41-3.71) were associated with early AMD. There were no associations of blood pressure level, body mass index, physical activity level, history of heavy drinking, white blood cell count, hematocrit level, platelet count, serum total cholesterol level, or carotid intimal-medial thickness with early AMD. CONCLUSIONS These data indicate that early AMD is infrequent before age 55 years but increases with age thereafter. Early AMD is related to modifiable risk factors, eg, smoking and serum high-density lipoprotein cholesterol level.

Prevalence of Self-Reported Erectile Dysfunction in People With Long-Term IDDM

OBJECTIVE The purpose of this report is to examine the prevalence of erectile dysfunction and relationships to other characteristics in men with younger-onset diabetes. RESEARCH DESIGN AND METHODS In a population-based cohort study in southern Wisconsin, prevalence of erectile dysfunction was measured based on self reports in men who were 21 years of age or older, were <30 years of age at diagnosis of diabetes, had 10 or more years of diabetes, and were taking insulin (n = 365). RESULTS Of the study group, 20% reported a history of erectile dysfunction. The prevalence of erectile dysfunction increased with increasing age (from 1.1% in those 21–30 years of age to 47.1% in those 43 years of age or older, P for trend < 0.0001) and with increasing duration of diabetes (P for trend < 0.0001). Erectile dysfunction was associated with presence of severe diabetic retinopathy, a history of peripheral neuropathy, amputation, cardiovascular disease, a higher glycosylated hemoglobin, use of antihypertensive medications, and higher BMI. CONCLUSIONS These data suggest that tighter glycemic control and careful selection of antihypertensive medications might prove beneficial.

Early Exposure to Cow's Milk and Solid Foods in Infancy, Genetic Predisposition, and Risk of IDDM

Using a case-control study design, we examined the hypothesis that early exposure to cows milk and solid foods increased the risk of IDDM. An infant diet history was collected from 164 IDDM subjects from the Colorado IDDM Registry with a mean birth year of 1973, and 145 nondiabetic population control subjects who were frequency matched to diabetic subjects on age, sex, and ethnicity. Early exposure was defined as exposure occurring before 3 mo of age. After controlling for ethnicity, birth order, and family income, more diabetic subjects were exposed early to cows milk (OR 4.5, 95% Cl 0.9–21.4) and solid foods (OR 2.5, Cl 1.4–4.3) than control subjects. To examine this association while accounting for the genetic susceptibility to IDDM, we defined individuals as high and low risk by an HLA-DQB1 molecular marker. Early exposure to cows milk was not associated with elevated risk for IDDM in low-risk individuals. Relative to unexposed low-risk individuals, early exposure to cows milk was strongly associated in individuals with a high risk marker (OR 11.3, Cl 1.2–102.0). Similar findings were observed for early exposure to solid foods. These data indicate that early exposure to cows milk and solid foods may be associated with increased risk of IDDM. The inclusion of HLA-encoded risk in the analyses demonstrates the combined effect of genetic and environmental factors.