Kristine E. Lee

The Wisconsin Epidemiologic Study of Diabetic Retinopathy XXII. The Twenty-Five-Year Progression of Retinopathy in Persons with Type 1 Diabetes

OBJECTIVE To examine the 25-year cumulative progression and regression of diabetic retinopathy (DR) and its relation to various risk factors. DESIGN Population-based study. PARTICIPANTS A total of 955 insulin-taking persons living in an 11-county area in southern Wisconsin with type 1 diabetes diagnosed before age 30 years who participated in a baseline examination (1980-1982) and at least 1 of 4 follow-up (4-, 10-, 14-, and 25-year) examinations or died before the first follow-up examination (n = 64). METHODS Stereoscopic color fundus photographs were graded using the modified Airlie House classification and the Early Treatment Diabetic Retinopathy Study retinopathy severity scheme. MAIN OUTCOME MEASURES Progression and regression of DR status. RESULTS The 25-year cumulative rate of progression of DR was 83%, progression to proliferative DR (PDR) was 42%, and improvement of DR was 18%. Progression of DR was more likely with less severe DR, male sex, higher glycosylated hemoglobin, an increase in glycosylated hemoglobin level, and an increase in diastolic blood pressure level from the baseline to the 4-year follow-up. Increased risk of incidence of PDR was associated with higher glycosylated hemoglobin, higher systolic blood pressure, proteinuria greater body mass index at baseline, and an increase in the glycosylated hemoglobin between the baseline and 4-year follow-up examinations. Lower glycosylated hemoglobin and male sex, as well as decreases in glycosylated hemoglobin and diastolic blood pressure during the first 4 years of follow-up, were associated with improvement in DR. Persons diagnosed most recently with a similar duration of diabetes had a lower prevalence of PDR independently of glycosylated hemoglobin level, blood pressure level, and presence of proteinuria. CONCLUSIONS These data show relatively high 25-year cumulative rates of progression of DR and incidence of PDR. The lower risk of prevalent PDR in more recently diagnosed persons possibly reflects improvement in care over the period of the study.

Changes in visual acuity in a population : The beaver dam eye study

PURPOSE To describe the change in visual acuity over a 5-year period in persons participating in a large population-based study. METHODS Best-corrected visual acuity was measured, after refraction, with logMAR charts using a modification of the Early Treatment Diabetic Retinopathy Study protocol in 3684 persons living in Beaver Dam, Wisconsin, who ranged in age from 43 to 86 years at the time of a baseline examination from 1988 to 1990, and at a follow-up examination from 1993 to 1995. RESULTS The change in the number of letters read correctly over the 5-year period varied from 0.4 +/- 4.9 (mean +/- standard deviation) in people between 43 and 54 years of age to -5.2 +/- 15.4 in people 75 years of age or older at baseline. Over the 5-year period, vision became impaired (20/40 or worse in the better eye) in 2.9% of the population and severely impaired (20/200 or worse in the better eye) in 0.3%. The visual angle doubled in 1.7% of the population, and 2.4% had improved vision. People 75 years of age or older at baseline were 12.5 times (95% confidence interval [Cl], 8.6-18.2; P < 0.001) more likely to have impaired vision, 9.7 times (95% Cl, 5.9-16.0; P < 0.001) more likely to have doubling of the visual angle, and 78 times more likely (95% Cl, 9.9-614.1; P < 0.001) to have severe visual impairment than people younger than 75 years of age at baseline. People 75 years of age or older who were living in nursing homes or group homes were 3.8 times more likely to have impaired vision, 3.3 times more likely to have severely impaired vision, and 5.7 times more likely to have a doubling of the visual angle than those not residing in a nursing home or a group home. CONCLUSION These data provide precise population-based estimates of incidence of visual loss over a wide spectrum of ages and show that decreased visual acuity in people 75 years of age is a common finding, especially in those who are in nursing homes or group homes.

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.

The Wisconsin Epidemiologic Study of Diabetic Retinopathy XXIII. The Twenty-Five-Year Incidence of Macular Edema in Persons with Type 1 Diabetes

OBJECTIVE To examine the 25-year cumulative incidence of macular edema (ME) and its relation to various risk factors. DESIGN Population-based study. PARTICIPANTS A total of 955 insulin-taking persons living in an 11-county area in southern Wisconsin with type 1 diabetes diagnosed before age 30 years who participated in baseline examinations (1980-1982) and at least 1 of 4 follow-up (4-, 10-, 14-, and 25-year) examinations (n=891) or died before the first follow-up examination (n=64). METHODS Stereoscopic color fundus photographs were graded using the modified Airlie House classification and the Early Treatment Diabetic Retinopathy Study retinopathy severity scheme. Competing risk of death was included in statistical models. MAIN OUTCOME MEASURES Incidence of ME and clinically significant ME (CSME). RESULTS The 25-year cumulative incidence was 29% for ME and 17% for CSME. Annualized incidences of ME were 2.3%, 2.1%, 2.3%, and 0.9% in the first, second, third, and fourth follow-up periods of the study, respectively. In univariate analyses, the incidence of ME was associated with male sex, more severe diabetic retinopathy, higher glycosylated hemoglobin, proteinuria, higher systolic and diastolic blood pressure, and more pack-years of smoking. Multivariate analyses showed that the incidence of ME was related to higher baseline glycosylated hemoglobin (hazard ratio [HR] per 1% 1.17; 95% confidence interval [CI], 1.10-1.25; P<0.001) and higher systolic blood pressure (HR per 10 mmHg 1.15; 95% CI, 1.04-1.26; P=0.004) and marginally to proteinuria (HR 1.43; 95% CI, 0.99-2.08; P=0.06). CONCLUSIONS These data show that relatively high 25-year cumulative rates of incidence of ME were related to glycemia and blood pressure. The lower risk of incident ME in the last period of the study may reflect recent improvement in care.

Refractive errors, intraocular pressure, and glaucoma in a white population.

OBJECTIVE To examine the relation of refractive errors to glaucoma and intraocular pressure (IOP) in a defined white population. DESIGN Population-based cross-sectional and follow-up study. PARTICIPANTS Persons aged 43 to 86 years living in Beaver Dam, Wisconsin (n = 4926). METHODS All participants received a standardized assessment of refraction, IOP, and glaucoma at baseline (1988-1990), with IOP remeasured 5 years later (1993-1995). Refraction was defined at baseline as follows: myopia as spherical equivalent of -1.00 diopters (D) or less, emmetropia as -0.75 to +0.75 D, and hyperopia as +1.00 D or more. MAIN OUTCOME MEASURES Relation of baseline refraction to prevalent glaucoma (defined from IOP, optic disc, and visual field criteria) and incident ocular hypertension (defined as IOP more than 21 mmHg at the 5-year examination in eyes with IOP of 21 mmHg or less at baseline). RESULTS A myopic refraction was correlated with increasing IOP at baseline (P < 0.001). After controlling for age and gender, persons with myopia were 60% more likely to have prevalent glaucoma than those with emmetropia (odds ratio [OR], 1.6; 95% confidence interval [CI], 1.1, 2.3). In contrast, controlling for age, gender, and baseline IOP, persons with hyperopia were 40% more likely to have incident ocular hypertension than those who were emmetropic at baseline (OR, 1.4; 95% CI, 1.0, 2.0). Myopia was not related to incident ocular hypertension. CONCLUSIONS In these population-based data, there was a cross-sectional association of myopia with higher IOP and prevalent glaucoma. Similar associations have been found in previous studies. Hyperopia may be associated with 5-year risk of ocular hypertension, a finding that needs further investigation.

Diabetes, cardiovascular disease, selected cardiovascular disease risk factors, and the 5-year incidence of age-related cataract and progression of lens opacities: the Beaver Dam Eye Study.

PURPOSE To describe the relationships of diabetes mellitus, cardiovascular disease, and selected cardiovascular disease risk factors to cumulative incidence of age-related cataract and to progression of lens opacities over a 5-year interval. METHODS A follow-up examination of the Beaver Dam Eye Study cohort was performed 5 years after the baseline evaluation. Ages at the census prior to baseline ranged from 43 to 84 years of age. Protocols for examination, lens photography, and grading were the same for both examinations. RESULTS Age at baseline was the most significant characteristic associated with incidence of nuclear, cortical, and posterior subcapsular cataract in those without diabetes (P < .001) for all cataracts. The positive association of age with cataract was found for nuclear and cortical cataract in the worse eye (P < or = .04) but not posterior subcapsular cataract in those with diabetes. Progression of nuclear sclerosis was common, occurring in about 70% of subjects when considering either eye. Incident cortical and posterior subcapsular cataracts (P < or = .001 for worse eye for each lesion) and progression of cortical and posterior subcapsular opacities were more common in those with diabetes (P < or = .001 for either eye for each lesion). Increased glycated hemoglobin level was associated with increased risk of nuclear and cortical cataracts in those with diabetes. Relationships of risk factors to posterior subcapsular cataracts, especially among those with diabetes, were often in the expected direction but lacked significance possibly due to small samples. CONCLUSIONS Diabetes mellitus is associated with incidence over 5 years of cortical and posterior subcapsular cataract and with progression of more minor cortical and posterior subcapsular lens opacities. These changes may be related to level of glycemia. Cardiovascular disease and its risk factors have little effect on incidence of any age-related cataract.

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.

Dissection of Genomewide-Scan Data in Extended Families Reveals a Major Locus and Oligogenic Susceptibility for Age-Related Macular Degeneration

To examine the genetic basis of age-related macular degeneration (ARMD), a degenerative disease of the retinal pigment epithelium and neurosensory retina, we conducted a genomewide scan in 34 extended families (297 individuals, 349 sib pairs) ascertained through index cases with neovascular disease or geographic atrophy. Family and medical history was obtained from index cases and family members. Fundus photographs were taken of all participating family members, and these were graded for severity by use of a quantitative scale. Model-free linkage analysis was performed, and tests of heterogeneity and epistasis were conducted. We have evidence of a major locus on chromosome 15q (GATA50C03 multipoint P=1.98x10-7; empirical P< or =1.0x10-5; single-point P=3.6x10-7). This locus was present as a weak linkage signal in our previous genome scan for ARMD, in the Beaver Dam Eye Study sample (D15S659, multipoint P=.047), but is otherwise novel. In this genome scan, we observed a total of 13 regions on 11 chromosomes (1q31, 2p21, 4p16, 5q34, 9p24, 9q31, 10q26, 12q13, 12q23, 15q21, 16p12, 18p11, and 20q13), with a nominal multipoint significance level of P< or =.01 or LOD > or =1.18. Family-by-family analysis of the data, performed using model-free linkage methods, suggests that there is evidence of heterogeneity in these families. For example, a single family (family 460) individually shows linkage evidence at 8 loci, at the level of P<.0001. We conducted tests for heterogeneity, which suggest that ARMD susceptibility loci on chromosomes 9p24, 10q26, and 15q21 are not present in all families. We tested for mutations in linked families and examined SNPs in two candidate genes, hemicentin-1 and EFEMP1, in subsamples (145 and 189 sib pairs, respectively) of the data. Mutations were not observed in any of the 11 exons of EFEMP1 nor in exon 104 of hemicentin-1. The SNP analysis for hemicentin-1 on 1q31 suggests that variants within or in very close proximity to this gene cause ARMD pathogenesis. In summary, we have evidence for a major ARMD locus on 15q21, which, coupled with numerous other loci segregating in these families, suggests complex oligogenic patterns of inheritance for ARMD.

Changes in visual acuity in a population over a 10-year period : The Beaver Dam Eye Study.

PURPOSE To describe the change in visual acuity in a 10-year period. DESIGN Population-based cohort study. PARTICIPANTS Included 3684 persons 43 to 86 years of age at the time of a baseline examination in 1988 to 1990, living in Beaver Dam, Wisconsin, at a follow-up examination in 1993 to 1995 and/or 1998 to 2000. METHODS Best-corrected visual acuity was measured, after refraction, with logarithm of the minimum angle of resolution charts using a modification of the Early Treatment Diabetic Retinopathy Study protocol. MAIN OUTCOMES MEASURES Doubling of the visual angle and incidence of visual impairment. RESULTS The change in the mean number of letters read correctly over the 10-year period varied in the right eye from -0.9 (standard deviation [SD] = 5.5) and in the left eye from -1.2 (SD = 6.6) in people between 43 and 54 years of age to -11.0 (SD = 20.0) in the right eye and -12.6 (SD = 20.4) in the left eye in people 75 years of age or older (n = 184) at baseline. Over the 10-year period, 5.9% of the population had impaired vision (20/40 or worse in the better eye) develop, 0.8% had severe visual impairment (20/200 or worse in the better eye) develop, 4.8% had doubling of the visual angle, and 3.9% had improved vision. People who were 75 years of age or older at baseline were 15.0 times (95% confidence interval [CI], 10.9-20.6; P < 0.001) as likely to have impaired vision develop, 9.3 times (95% CI, 6.5-13.3; P < 0.001) as likely to have doubling of the visual angle, and 19.8 times as likely (95% CI, 8.4-46.4; P < or = 0.001) to have severe visual impairment develop than people younger than 75 years of age at baseline. For the 82 persons 75 years of age or older, currently residing in a nursing or group home at follow-up, they were 2.6 times (95% CI, 1.45-4.52) as likely to have impaired vision develop, 1.6 times (95% CI, 0.47-5.62) as likely to have severely impaired vision develop, and 3.6 times (95% CI, 1.96-6.78) as likely to have had a doubling of the visual angle than those not residing in a nursing or group home at follow-up. CONCLUSIONS These data provide precise population-based estimates of the 10-year incidence of loss of vision over a wide spectrum of ages and show that decreased visual acuity in people 75 years of age after 10 years is a common finding, especially in those who are admitted to nursing or group homes.

Incidence of Age-Related Cataract over a 15-Year Interval The Beaver Dam Eye Study

OBJECTIVE To describe the long-term incidence of nuclear cataract, cortical cataract, and posterior subcapsular cataract (PSC) and to evaluate age and cohort effects on these rates. DESIGN Population-based study. PARTICIPANTS Members of the Beaver Dam Eye Study cohort. METHODS Subjects were seen in study offices for examinations (slit lamp, checking for occludable angles, dilation of pupils, lens photographs, measurement of blood pressures, and study interview). MAIN OUTCOME MEASURES Lens photographs were taken with specially modified cameras that have been maintained over the course of all study examinations. Photographs were graded according to standard protocols that have been continued throughout all the examinations. RESULTS Cumulative incidence of nuclear cataract was 29.7% (95% confidence interval [CI], 28.0-31.4); cortical cataract, 22.9% (95% CI, 21.3-24.5); PSC, 8.4% (95% CI, 7.4-9.4); and cataract surgery, 17.7% (95% CI, 16.4-19.0). The cumulative incidence increased with age and was greater for women after accounting for competing events. The relationship between age and incidence of cataracts was quadratic for nuclear cataract, cubic for cortical cataract, and linear for PSC. For persons with similar ages at time of examination, those in more recent birth cohorts were less likely to have any type of prevalent cataract; the effect was significant for nuclear cataract and for cataract surgery, and the effect persisted after controlling for relevant confounders. There were apparent cohort effects on cataract incidence. CONCLUSIONS Age-adjusted incidence of all cataract types increased with increasing age, although the age effect was not linear for all 3 types. More recent birth cohorts are relatively protected relative to persons born earlier. Further follow-up is needed to verify the trends we report here and to determine whether cohort effects on 10-year incidence are significant.