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Ronald Klein

Publications and source records attributed to Ronald Klein.

At least 145 records · Page 8Linked to original sources

Impact of current and past blood pressure on retinal arteriolar diameter in an older population.

OBJECTIVE: To examine the effects of current and past blood pressure on retinal arteriolar diameter in a general older population. DESIGN: Cross-sectional and longitudinal studies. SETTING: Population-based cohort study of older residents from an area west of Sydney, Australia. PARTICIPANTS: Two thousand three hundred and thirty-five individuals (n = 2335) (aged > or = 54 years) who attended the 5-year follow-up Blue Mountains Eye Study during 1997-99. MAIN OUTCOME MEASURES: A computer-assisted method measured vessel diameters from digitized right eye retinal photographs. The narrowest quintile of central retinal arteriolar equivalent or arteriole-to-venule ratio (AVR) defined generalized arteriolar narrowing. Blood pressure was measured using a mercury sphygmomanometer. RESULTS: After simultaneous adjustment for age, sex, body mass index, smoking and current or past blood pressure, elevated levels of both current and past blood pressure were associated with narrower retinal arterioles [Ptrend = 0.009 and 0.007 for current and past systolic blood pressure (SBP), respectively] and lower AVR [Ptrend = 0.001 and 0.0009 for current and past diastolic blood pressure (DBP), respectively]. Generalized arteriolar narrowing was associated with both current blood pressure [adjusted odds ratio (OR) 2.4, 95% confidence interval (CI) 1.5-3.8 for the highest versus lowest quintile of current DBP] and past blood pressure (adjusted OR 1.7, 95% CI 1.1-2.6, for the highest versus lowest quintile of past DBP). Hypertension duration or control status at baseline had no additional effect on arteriolar diameter after adjusting for current blood pressure. CONCLUSIONS: Our data document the independent effects of both current and past blood pressure on small vessel calibre in the retina, suggesting that retinal arteriolar narrowing may result from the cumulative effects of long-standing hypertension.

Aged↗

Screening for diabetic retinopathy using a digital non-mydriatic camera compared with standard 35-mm stereo colour transparencies.

PURPOSE: To investigate the use of a digital non-mydriatic camera for determining the ETDRS clinical level of diabetic retinopathy, and to evaluate its use in a screening setting to appropriately determine the need for referral to an ophthalmologist (ETDRS level > or = 35). METHODS: A total of 83 patients with diabetes were photographed with and without pharmacological pupil dilation at an ophthalmology department using a digital non-mydriatic camera, obtaining two sets of five non-stereoscopic, 45 degree field images of each eye. ETDRS seven standard field, 35-mm stereoscopic colour fundus photographs were also obtained. A subgroup of 59 patients was photographed at an optician's shop using the digital non-mydriatic camera without pupil dilation. RESULTS: There was substantial agreement between the clinical level of diabetic retinopathy assessed from the 35-mm photographs and the digital images: the ophthalmology department (kappa = 0.76) with pupil dilation and (kappa = 0.66) without pupil dilation, respectively, and at the optician's (kappa = 0.60 without pupil dilation). With respect to the need for referral to an ophthalmologist, there was almost perfect agreement in the ophthalmology department (kappa = 0.88) with pupil dilation and (kappa = 0.84) without pupil dilation, respectively, and those taken at the optician's (kappa = 0.87 without pupil dilation). CONCLUSION: A digital non-mydriatic camera may be used in a screening situation to appropriately determine the need for referral to an ophthalmologist (ETDRS level > or = 35).

Adult↗

Life-style correlates of tooth loss in an adult Midwestern population.

OBJECTIVES: To describe life-style correlates of tooth loss in a representative rural American population. METHODS: Information on tooth loss as well as past medical history and life-style factors was obtained in a well-defined cohort of 2,764 persons 53-96 years of age in Beaver Dam, WI (1998-2000). RESULTS: There were 1,992 (68.2%) persons missing some and 447 (15.3%) missing all of their teeth. In univariable analyses, age, cigarette smoking, heavy drinking, education, multivitamin use, and diabetes status were associated with tooth loss. Tooth loss was associated with poorer self-rated health and with difficulty eating solid food and inability to enjoy some food. In multivariable models age, education, smoking, heavy drinking, and diabetes were significantly associated with tooth loss. CONCLUSIONS: Tooth loss is common in older persons and is associated with many risk factors including education, smoking, and heavy drinking. It is possible that modifying these may influence risk of tooth loss.

Adult↗

Heritability of risk factors for primary open-angle glaucoma: the Beaver Dam Eye Study.

PURPOSE: To investigate the family aggregation and heritability of risk indicators of primary open-angle glaucoma. METHODS: During the baseline examination of the Beaver Dam Eye Study, standardized measurements of intraocular pressure were performed with a Goldmann applanation tonometer. Stereoscopic photographs of the optic discs were taken of both eyes of each study participant. The eyes were graded for the size of the optic disc and cup according to a standardized protocol, with graders masked to other subject characteristics. Family members who had participated in the examination phase were identified. RESULTS: Correlations in sibling pairs (n = 1136), parent-child pairs (n = 514), and cousin pairs (n = 1807) for intraocular pressure were 0.17, 0.18, and 0.12, respectively and were all statistically significant, whereas the spouse pair correlation was not. Correlations for sibling, parent-child, and avuncular pairs were higher for vertical optic disc, vertical optic cup, and vertical cup-to-disc ratio than for intraocular pressure. Heritability estimates were 0.36, 0.55, 0.57, and 0.48 for intraocular pressure, optic cup diameter, optic disc diameter, and cup-to-disc ratio, respectively. Correlations for the optic disc parameters were compatible with the amount of gene sharing in relative pairs of different degrees. CONCLUSIONS: Risk indicators of open-angle glaucoma correlate highly in families, and the patterns are consistent with the hypothesis of genetic determinants of these factors.

Adult↗

Location of lesions associated with age-related maculopathy over a 10-year period: the Beaver Dam Eye Study.

PURPOSE: To describe cumulative incidence and changes in retinal lesions associated with age-related maculopathy (ARM) by location over a 10-year period and to examine the relation of location of those lesions to progression of ARM. METHODS: Persons ranging in age from 43 to 84 years and living in Beaver Dam, Wisconsin, at the time of a census (1987-1988) were examined two to three times over a 10-year period (n = 3684). Drusen area, size, and type; retinal pigment epithelium depigmentation; increased pigment; geographic atrophy; and neovascular macular degeneration were determined in each of nine macular subfields: central, inner and outer superior, inner and outer nasal, inner and outer inferior, and inner and outer temporal by grading of stereoscopic color fundus photographs. Late ARM was defined as presence of either geographic atrophy or neovascular ARM. RESULTS: Lesions were more likely to change or develop in specific locations. Drusen area increased most in the central circle. Compared with other quadrants, drusen greater than 125 micro m in diameter and soft indistinct or reticular drusen were most likely to develop in the superior or temporal quadrants, whereas pigmentary abnormalities were most likely to occur in the nasal or superior quadrants. In general, large drusen, soft indistinct drusen, and pigmentary abnormalities were more likely to develop in the inner circle versus the central and outer circles. The quadrant location of early ARM lesions in 72 persons in whom late ARM developed was generally similar to that in persons who did not have late ARM. However, persons who had geographic atrophy were more likely to have large drusen in the inner circle than in the outer circle, while those who did not have late ARM were more likely to have large drusen in the outer circle. CONCLUSIONS: Lesions associated with early ARM were more likely to develop in specific locations in the macular area, and persons with lesions closer to the fovea may be related to a higher risk of development of late ARM. The quadrant location of early ARM lesions does not appear to add additional information to the risk of development of late ARM.

Adult↗

Prevalence and associations of epiretinal membranes in latinos: the Los Angeles Latino Eye Study.

PURPOSE: To determine age- and gender-specific prevalence and associations of epiretinal membranes (ERMs) in adult Latinos. METHODS: The Los Angeles Latino Eye Study (LALES) is a population-based study of eye disease among Latinos aged 40 or more years. Complete ophthalmic examinations included stereoscopic fundus photography. Masked photographic grading was used to identify and classify ERMs as cellophane macular reflex (CMR) without retinal folds or preretinal macular fibrosis (PMF) with folds. RESULTS: Of the 6142 persons examined at the clinic, 5982 (97%) had gradable retinal photographs. The mean age of the participants was 54.7 +/- 10.7 years; 58% were women. ERMs were present in 18.5% (95% confidence interval [CI]: 17.5%-19.5%) of the participants. Of the participants with ERMs, 19.9% had bilateral ERMs. The prevalence of ERMs increased from 10.1% in persons 40 to 49 years of age to 35.7% in those aged 70 to 79 years and was 22.5% in persons aged 80 years or more. The prevalence was similar in men and women. CMR was present in 16.3% (95% CI: 15.3%-17.2%) and PMF in 2.2% (95% CI: 1.9%-2.6%). Retinal folds involved the fovea in 11% of PMF cases. On average, eyes with central PMF had poorer visual acuity than did eyes without (P < 0.0002). Epiretinal membranes (ERMs) were present in 71% of eyes with macular holes. ERMs were also more common in individuals who had undergone cataract surgery (39.9%), those with proliferative diabetic retinopathy (25.7%), and those with any retinal disease (27.5%). CONCLUSIONS: ERMs occur frequently in Latinos, often bilaterally. The associations of ERMs with proliferative retinopathy, retinal lesions, macular holes, and cataract surgery were confirmed. Central PMF is associated with reduced visual acuity.

Adult↗

Impact of aging and age-related maculopathy on activation of the a-wave of the rod-mediated electroretinogram.

PURPOSE: To examine the impact of aging and age-related maculopathy (ARM) on the activation of phototransduction in rod photoreceptors by measuring the a-wave of the flash, full-field electroretinogram (ERG). METHODS: Enrollees consisted of older adults (> or = 60 years of age) in normal retinal health (n = 41) and those with early (n = 39) or late ARM (n = 7), in whom disease presence and severity were defined based on grading of stereoscopic color fundus photographs according to the Wisconsin Age-Related Maculopathy grading system. Young adults (ages 16-30 years; n = 27) were enrolled for comparison purposes. Previously established procedures were used to estimate the ERG response to two families of flash intensities. By computer subtraction of responses, the isolated rod response was identified. Each participant's ensemble rod responses were fit with the following equation to describe the response (R) as function of flash intensity (I), and time (t): R(I,t) = [1 - exp[-I x S x (t - td)2]] x RmP3, where S is sensitivity, td is the delay before onset of the a-wave, and Rm(P3) is the maximum amplitude. RESULTS: In analyses of older adults, there was no impact of early ARM presence or severity on log S, Rm(P3), or td after adjustment for age and intraocular lens presence. Differences between young and old normal subjects in log S, RmP3, and td disappeared when analyses were limited to older adults with intraocular lenses. CONCLUSIONS: When the light absorption of the aged lens is taken into account and reliable definitions of normal retinal aging and ARM are used, the activation of the a-wave as measured by the rod-mediated full-field ERG is not affected by early ARM, nor is it impacted by normal retinal aging.

Adolescent↗

Associations between the metabolic syndrome and retinal microvascular signs: the Atherosclerosis Risk In Communities study.

PURPOSE: To examine the cross-sectional relationship of the metabolic syndrome (hypertension, hyperglycemia, central obesity, and dyslipidemia) and retinal microvascular abnormalities in middle-aged men and women. METHODS: A population-based, cross-sectional study involving 11,265 persons aged 49 to 73 years who had retinal photography from 1993 through 1995. Photographs were graded for presence of retinal microvascular signs (microaneurysms, retinal hemorrhages, arteriovenous nicking, and focal arteriolar narrowing) according to a standardized protocol. To quantify retinal vessel diameters, photographs were digitized and individual arteriolar and venular diameters were measured and summarized. The metabolic syndrome was defined according to the Third Report of the National Cholesterol Education Program Adult Treatment Panel. RESULTS: After adjustment for age, gender, race, education, cigarette smoking and alcohol consumption, persons with the metabolic syndrome were more likely to have retinopathy (odds ratio [OR] 1.68, 95% confidence interval [CI], 1.45-1.96), arteriovenous nicking (OR 1.30, 95% CI, 1.16-1.45), focal arteriolar narrowing (OR 1.24, 95% CI, 1.10-1.38), generalized retinal arteriolar narrowing (OR 1.23, 95% CI, 1.12-1.35), and generalized retinal venular dilatation (OR 1.30, 95% CI, 1.18-1.48) than persons without the metabolic syndrome. Associations for arteriovenous nicking, focal arteriolar narrowing, generalized arteriolar narrowing, and venular dilatation were noted, even in people without diabetes or hypertension. CONCLUSIONS: These data suggest that the metabolic syndrome is associated with microvascular changes in the retina. This finding reflects, in part, the associations of individual syndrome components with retinal microvascular abnormalities.

Aged↗

Familial aggregation of retinal vessel caliber in the beaver dam eye study.

PURPOSE: To describe familial correlations of retinal vessel measurements. METHODS: A standardized examination and interview was administered to a population-based cohort of adults aged 43-86 years. Blood pressure was measured, and family relationships, current smoking status, and photographs of the retina were obtained. Computer-assisted grading was done to determine central retinal arteriole (CRAE) and venule equivalents (CRVE), and the arteriole-to-venule ratio (AVR) was computed. Familial correlations were calculated using FCOR in the SAGE software package. Analysis was done on the right eye measures for 871 sibling, 341 parent-child, 1362 cousin, 554 avuncular, and 887 spousal pairs. RESULTS: After adjustment for age, gender, mean arterial blood pressure, and current smoking status, the correlations (and 95% confidence interval) between siblings for the CRVE, CRAE, and AVR were 0.23 (0.16, 0.31), 0.20 (0.12, 0.28) and 0.13 (0.05, 0.20), respectively. Parent-child correlations were very similar, and the avuncular correlations were about half as great. The cousin correlations were about half the avuncular correlations. Spousal correlations of 0.03, 0.04, and 0.01 for CRVE, CRAE, and AVR, respectively, were not significantly different from 0. CONCLUSIONS: Retinal vessel equivalents were more highly correlated between relatives than between unrelated individuals. The relative magnitudes of these correlations were likely the result of shared genes. Because the vessel measurements have been shown to be predictive of cardiovascular and other systemic diseases, understanding the determinants of these familial relationships could have important health benefits.

Adult↗

Retinal vessel diameters and the incidence of gross proteinuria and renal insufficiency in people with type 1 diabetes.

Early retinal vessel caliber changes may predict risk of diabetic nephropathy. We examined the association of retinal vessel diameters and the incidence of gross proteinuria and renal insufficiency in a population-based cohort of people with type 1 diabetes (n = 557). Baseline retinal photographs were digitized, and diameters of individual retinal vessels were measured and summarized. Incident cases of gross proteinuria and renal insufficiency were identified over a 16-year period. Larger retinal venular diameter was associated with higher cumulative incidence of gross proteinuria (18.6, 25.4, 37.7, and 50.4%, comparing increasing venular diameter quartiles) and renal insufficiency (10.7, 15.5, 23.2, and 32.8%). After adjusting for age, sex, duration of diabetes, HbA(1c) levels, baseline retinopathy levels, and other factors, larger retinal venular diameter was associated with an increased risk of gross proteinuria (RR 1.53, 95% CI 1.19-1.97, comparing 4th vs. 1st to 3rd quartiles of venular diameter) and renal insufficiency (1.51, 1.05-2.17). Retinal arteriolar diameter was not associated with either gross proteinuria or renal insufficiency. We conclude that in individuals with type 1 diabetes, larger retinal venular diameter is independently associated with the long-term incidence of gross proteinuria and renal insufficiency and may provide additional predictive information regarding risk of nephropathy.

Adult↗

Diabetic retinopathy.

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Combined Modality Therapy↗

Familial aggregation of components of the multiple metabolic syndrome in the Framingham Heart and Offspring Cohorts: Genetic Analysis Workshop Problem 1.

BACKGROUND: The multiple metabolic syndrome is defined by a clustering of risk factors for cardiovascular disease. We sought to evaluate the familial correlations of the components of the syndrome using data from the Framingham Heart Study original and offspring cohorts as provided for the Genetic Analysis Workshop 13. Measures of plasma cholesterol (total and HDL), body mass index (BMI), and systolic blood pressure were used from selected calendar years of exams. Familial correlations were calculated using FCOR in S.A.G.E. RESULTS: The sibling correlations were relatively high for all measures and exams, from 0.17 for systolic blood pressure to 0.27 for HDL cholesterol. The parent-child correlations were very similar, except for systolic blood pressure. The avuncular correlations were much smaller and the cousin correlations were even smaller. For HDL cholesterol the avuncular correlation was half the sibling correlation and the cousin correlation was half that again. Spousal correlations ranged from 0.07 for systolic blood pressure to 0.34 for BMI. Correlations were somewhat lower from 1984 to 1987 examinations than from 1971 to 1975 examinations, except for spousal correlations for systolic blood pressure and BMI. CONCLUSION: The results of the family pair correlations are suggestive of genetic determinants of lipid levels and BMI. These components have been shown to be predictive of cardiovascular disease as well as diabetes. Genes in common with each of the components might also influence development of cardiovascular disease and diabetes, both complex diseases.

Adult↗

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.

Aged↗

Retinal vascular changes and 20-year incidence of lower extremity amputations in a cohort with diabetes.

OBJECTIVE: To examine the association of retinal vascular changes with the incidence of lower extremity amputations (LEAs) in a cohort with diabetes mellitus. METHODS: Baseline examinations were performed in a cohort of 996 persons with diabetes diagnosed before the age of 30 years and using insulin. History of LEA was obtained at baseline and at 4, 10, 14, and 20 years. The cumulative 20-year incidence of first LEA was calculated by the product-limit method in 906 persons with follow-up information. Retinal arterioles and venules were measured on digitized fundus photographs obtained at baseline by a standard protocol. Generalized arteriolar narrowing was defined as the lowest 25% of the arteriole-venule ratio. Measurements were obtained in at least one eye for 820 persons. Focal arteriolar narrowing and arteriovenous nicking were also determined from fundus photographs by a standard protocol. RESULTS: The 20-year cumulative incidence of LEAs was 9.9%. The unadjusted risk of undergoing a LEA was higher in persons with generalized arteriolar narrowing than in those without it (15.7% vs 5.7%; odds ratio [OR], 3.08; 95% confidence interval [CI], 1.60-4.68), and in persons with focal narrowing (33.1% vs 6.8%; OR, 5.59; 95% CI, 3.27-9.54). The results for arteriovenous nicking were not significant. With control for age, sex, levels of glycosylated hemoglobin, diastolic blood pressure, and history of ulcers of the feet, the relationships were attenuated but still statistically significant for both generalized narrowing (OR, 1.89; 95% CI, 1.06-3.35) and focal narrowing (OR, 3.56; 95% CI, 1.87-6.78). CONCLUSION: In persons with diabetes, generalized as well as focal retinal arteriolar narrowing may reflect damage to the microvasculature, which manifests itself elsewhere in the body as a need for LEAs.

Adult↗

Hypertensive retinal vessel wall signs in a general older population: the Blue Mountains Eye Study.

To describe cross-sectional relations between hypertension and retinal vessel wall signs in an older white population. These signs were defined from fundus photographs in 3654 Blue Mountains Eye Study participants > or =49 years of age. Focal arteriolar narrowing and arteriovenous nicking were graded through the use of standard protocol. Photographs were digitized to measure retinal vessel diameters. Average arteriolar diameter, summarized as central retinal arteriolar equivalent and arteriole-to-venule ratio, were used as indexes of generalized arteriolar narrowing. Blood pressure was measured with the use of a mercury sphygmomanometer. Hypertension was defined through the use of antihypertensive medications, systolic blood pressure > or =160 mm Hg, or diastolic blood pressure > or =95 mm Hg. Hypertension was categorized as controlled (using medication, normal blood pressure), uncontrolled (using medication, high blood pressure), or untreated (not using medication). Hypertensive subjects had higher prevalence of all retinal microvascular signs. After adjusting for age, gender, body mass index, and smoking, persons with controlled (18.2%), uncontrolled (13.8%), or untreated hypertension (13.8%) were significantly more likely than normotensive subjects (54.2%) to have (a) lower central retinal arteriolar equivalent: adjusted odds ratios 1.5, (95% CI, 1.1 to 1.9), 2.1 (1.6 to 2.7), and 2.1 (1.6 to 2.7), respectively, and lower arteriole-to-venule ratio: 1.3 (1.0 to 1.6), 1.4 (1.1 to 1.8), and 1.7 (1.3 to 2.2), respectively; (b) focal arteriolar narrowing: 1.3 (0.9 to 1.9), 2.2 (1.5 to 3.2), and 2.5 (1.8 to 3.6), respectively; and (c) arteriovenous nicking: 1.3 (0.9 to 1.8), 2.3 (1.6 to 3.2), and 1.9 (1.3 to 2.7), respectively. Our findings demonstrate a strong relation between presence and severity of hypertension and retinal microvascular structural changes.

Aged↗

A whole-genome screen of a quantitative trait of age-related maculopathy in sibships from the Beaver Dam Eye Study.

Age-related maculopathy (ARM) is a leading cause of visual impairment among the elderly in Western populations. To identify ARM-susceptibility loci, we genotyped a subset of subjects from the Beaver Dam (WI) Eye Study and performed a model-free genomewide linkage analysis for markers linked to a quantitative measure of ARM. We initially genotyped 345 autosomal markers in 325 individuals (N=263 sib pairs) from 102 pedigrees. Ten regions suggestive of linkage with ARM were observed on chromosomes 3, 5, 6, 12, 15, and 16. Prior to fine mapping, the most significant regions were an 18-cM region on chromosome 12, near D12S1300 (P=.0159); a region on chromosome 3, near D3S1763, with a P value of.0062; and a 6-cM region on chromosome 16, near D16S769, with a P value of.0086. After expanding our analysis to include 25 additional fine-mapping markers, we found that a 14-cM region on chromosome 12, near D12S346 (located at 106.89 cM), showed the strongest indication of linkage, with a P value of.004. Three other regions, on chromosomes 5, 6, and 15, that were nominally significant at P< or =.01 are also appropriate for fine mapping.

Adult↗

Birth cohort effect on prevalence of age-related maculopathy in the Beaver Dam Eye Study.

The number of people in the United States with age-related maculopathy is increasing in recent years because of increasing longevity. However, it is possible that a birth cohort effect, due to different levels of exposure to risk factors, may explain changes in the prevalence of age-related maculopathy by age. In this report, the authors utilize data from the population-based Beaver Dam Eye Study (1988-2000) to examine this possibility. They propose a strategy to handle issues of longitudinal measurements and risk factor adjustment for analyzing the birth cohort effect. Results from the analysis (after adjusting for known risk factors) showed an apparent independent birth cohort effect on age-related maculopathy. The authors also found a strong positive association between age-related maculopathy and age, when comparing participants from the same birth cohort. The birth cohort effect was the same across different age groups, except for early age-related maculopathy, where older age increased the association. Our findings demonstrate that the birth cohort effect is likely attributable to unmeasured risk factors for age-related maculopathy and limitations of risk factor measurements. Further study of possible unmeasured risk factors that cause the cohort effect may help us understand the etiology of the disease.

Adult↗