Skin Intrinsic Fluorescence and Age-Related Macular Degeneration: The Beaver Dam Eye Study.
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ABSTRACT:
SUBMITTER: Klein R
PROVIDER: S-EPMC5742994 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:We tested the hypothesis that large areas of small hard drusen (diameter <63 μm) and intermediate drusen (diameter 63-124 μm) are associated with the incidence of age-related macular degeneration (AMD). Eyes of 3344 older adults with at least 2 consecutive visits spaced 5 years apart over a 20-year period were included. A 6-level severity scale including no drusen, 4 levels of increasing area (from minimal [<2596 μm(2)] to large [>9086 μm(2)]) of only small hard drusen, and intermediate drusen was used. The 5-year incidence of AMD was 3% in eyes at the start of the interval with no, minimal, small, and moderate areas of only small drusen and 5% and 25% for eyes with large area of only small drusen and intermediate drusen, respectively. Compared to eyes with a moderate area of small drusen, the odds ratio (OR) of developing AMD in eyes with a large area of only small drusen was 1.8 (P<.001). Compared to eyes with large area of only small drusen, eyes with intermediate drusen had an OR of 5.5 (P<0.001) of developing AMD. Our results are consistent with our hypothesis that large areas of only small drusen are associated with the incidence of AMD.
| S-EPMC4402933 | biostudies-literature
Project description:To examine the association of vasodilator and antihypertensive medication use with the incidence of age-related macular degeneration (AMD).Longitudinal population-based study.Persons 43 to 86 years of age living in Beaver Dam, Wisconsin, from 1988 through 1990.Examinations were performed every 5 years over a 20-year period. There were 9676 total person-visits over the course of the study. Status of AMD was determined from grading retinal photographs.Incidence of AMD.The 5-year incidence of early AMD over the 20-year period was 8.4%; for late AMD, it was 1.4%; for pure geographic atrophy (GA), it was 0.6%; for exudative AMD, it was 0.9%; and for progression of AMD, it was 24.9%. While adjusting for age, gender, and other factors, using a vasodilator (hazard ratio [HR], 1.72; 95% confidence interval [CI], 1.25-2.38), particularly oral nitroglycerin (HR, 1.81; 95% CI, 1.14-2.90), was associated with an increased risk of early AMD. Using an oral ?-blocker was associated with an increased hazard of incident exudative AMD (HR, 1.71; 95% CI, 1.04-2.82), but not pure GA (HR, 0.51; 95% CI, 0.20-1.29) or progression of AMD (HR, 0.92; 95% CI, 0.67-1.28) over the 20-year period.Use of vasodilators is associated with a 72% increase in the hazard of incidence of early AMD, and use of oral ?-blockers is associated with a 71% increase in the hazard of incident exudative AMD. If these findings are replicated, it may have implications for care of older adults because vasodilators and oral ?-blockers are drugs that are used commonly by older persons.
| S-EPMC4122609 | biostudies-literature
Project description:To examine the association of current cigarette smoking and pack-years smoked with the incidence and progression of age-related macular degeneration (AMD) and to examine the interactions of current smoking and pack-years smoked with complement factor H (CFH, rs1061170) and age-related maculopathy susceptibility 2 (ARMS2, rs10490924) genotype.A longitudinal population-based study of AMD in a representative American community. Examinations were performed every 5 years over a 20-year period.A total of 4439 participants in the population-based Beaver Dam Eye Study (BDES).Age-related macular degeneration status was determined from grading retinal photographs. Multi-state models were used to model the relationship of current smoking and pack-years smoked and interactions with CFH and ARMS2 with the incidence and progression of AMD over the entire age range.Incidence and progression of AMD over a 20-year period and interactions between current smoking and pack-years smoked with CFH and ARMS2 genotype.The incidence of early AMD over the 20-year period was 24.4%, and the incidence of late AMD was 4.5%. Current smoking was associated with an increased risk of transitioning from minimal to moderate early AMD. A greater number of pack-years smoked was associated with an increased risk of transitioning from no AMD to minimal early AMD and from severe early AMD to late AMD. Current smoking and a greater number of pack-years smoked were associated with an increased risk of death. There were no statistically significant multiplicative interactions between current smoking or pack-years smoked and CFH or ARMS2 genotype.Current smoking and a greater number of pack-years smoked increase the risk of the progression of AMD. This has important health care implications because smoking is a modifiable behavior.
| S-EPMC4177947 | biostudies-literature
Project description:ObjectiveTo examine the associations of cataract and cataract surgery with early and late age-related macular degeneration (AMD) over a 20-year interval.DesignLongitudinal population-based study of age-related eye diseases.ParticipantsBeaver Dam Eye Study participants.MethodsPersons aged 43 to 86 years participated in the baseline examination in 1988-1990. Participants were followed up at 5-year intervals after the baseline examination. Examinations consisted of ocular examination with lens and fundus photography, medical history, measurements of blood pressure, height, and weight. Values of risk variables were updated, and incidences of early and late AMD were calculated for each 5-year interval. Odds ratios were computed using discrete linear logistic regression modeling with generalized estimating equation methods to account for correlation between the eyes and multiple intervals.Main outcome measuresAge-related macular degeneration.ResultsAfter adjusting for age and sex, neither cataract nor cataract surgery was associated with increased odds for developing early AMD. Further adjusting for high-risk gene alleles (CFH and ARMS2) and other possible risk factors did not materially affect the odds ratio (OR). However, cataract surgery was associated with incidence of late AMD (OR 1.93; 95% confidence interval [CI], 1.28-2.90). This OR was not materially altered by further adjusting for high-risk alleles (CFH Y402H, ARMS2) or other risk factors. The OR for late AMD was higher for cataract surgery performed 5 or more years prior compared with less than 5 years prior.ConclusionsThese data strongly support the past findings of an association of cataract surgery with late AMD independent of other risk factors, including high-risk genetic status, and suggest the importance of considering these findings when counseling patients regarding cataract surgery. These findings should provide further impetus for the search for measures to prevent or delay the development of age-related cataract.
| S-EPMC3411928 | biostudies-literature
Project description:ObjectiveTo describe the relationships of risk alleles in complement factor H (CFH, rs1061170) and age-related maculopathy susceptibility 2 (ARMS2, rs10490924) to the incidence and progression of age-related macular degeneration (AMD) during a 20-year period.MethodsThere were 4282 persons aged 43 to 86 years at the baseline examination in 1988-1990 enrolled in a population-based cohort study who participated in at least 1 examination spaced 5 years apart during a 20-year period and had gradable fundus photographs for AMD and genotype information on CFH and ARMS2. Low, intermediate, and high genetic risk for AMD was defined by the presence of 0 to 1, 2, or 3 to 4 risk alleles for CFH and ARMS2, respectively. Multistate models were used to estimate the progression of AMD throughout the entire age range.ResultsThere were 2820 (66%), 1129 (26%), and 333 persons (8%) with low, intermediate, and high genetic risk for AMD, respectively. The 5-year incidences of early and late AMD were 9.1% and 1.6%, respectively, and increased with age but did not differ significantly by sex. Using the multistate model, of persons aged 45 years with no AMD in the low, intermediate, and high AMD genetic risk groups, 33.0%, 39.9%, and 46.5%, respectively, were estimated to develop early AMD, and 1.4%, 5.2%, and 15.3% were estimated to develop late AMD by age 80 years.ConclusionsThese population-based data provide estimates of the long-term risk of the incidence and progression of AMD and its lesions by age and genetic risk alleles for CFH and ARMS2. They also show that when early AMD is present, knowing the phenotype contributes more to risk assessment than knowing the genetic risk based on these 2 AMD genes.
| S-EPMC3602927 | biostudies-literature
Project description:IMPORTANCE Modifying levels of factors associated with age-related macular degeneration (AMD) may decrease the risk for visual impairment in older persons. OBJECTIVE To examine the relationships of markers of inflammation, oxidative stress, and endothelial dysfunction to the 20-year cumulative incidence of early AMD. DESIGN, SETTING, AND PARTICIPANTS This longitudinal population-based cohort study involved a random sample of 975 persons in the Beaver Dam Eye Study without signs of AMD who participated in the baseline examination in 1988-1990 and up to 4 follow-up examinations in 1993-1995, 1998-2000, 2003-2005, and 2008-2010. EXPOSURES Serum markers of inflammation (high-sensitivity C-reactive protein, tumor necrosis factor-α receptor 2, interleukin-6, and white blood cell count), oxidative stress (8-isoprostane and total carbonyl content), and endothelial dysfunction (soluble vascular cell adhesion molecule-1 and soluble intercellular adhesion molecule-1) were measured. Interactions with complement factor H (rs1061170), age-related maculopathy susceptibility 2 (rs10490924), complement component 3 (rs2230199), and complement component 2/complement factor B (rs4151667) were examined using multiplicative models. Age-related macular degeneration was assessed from fundus photographs. MAIN OUTCOMES AND MEASURES Early AMD defined by the presence of any size drusen and the presence of pigmentary abnormalities or by the presence of large-sized drusen (≥125-μm diameter) in the absence of late AMD. RESULTS The 20-year cumulative incidence of early AMD was 23.0%. Adjusting for age, sex, and other risk factors, high-sensitivity C-reactive protein (odds ratio comparing fourth with first quartile, 2.18; P = .005), tumor necrosis factor-α receptor 2 (odds ratio, 1.78; P = .04), and interleukin-6 (odds ratio, 1.78; P = .03) were associated with the incidence of early AMD. Increased incidence of early AMD was associated with soluble vascular cell adhesion molecule-1 (odds ratio per SD on the logarithmic scale, 1.21; P = .04). CONCLUSIONS AND RELEVANCE We found modest evidence of relationships of serum high-sensitivity C-reactive protein, tumor necrosis factor-α receptor 2, interleukin-6, and soluble vascular cell adhesion molecule-1 to the 20-year cumulative incidence of early AMD independent of age, smoking status, and other factors. It is not known whether these associations represent a cause and effect relationship or whether other unknown confounders accounted for the findings. Even if inflammatory processes are a cause of early AMD, it is not known whether interventions that reduce systemic inflammatory processes will reduce the incidence of early AMD.
| S-EPMC4076038 | biostudies-literature
Project description:PurposeTo report the natural history of untreated neovascular age-related macular degeneration (nAMD) regarding subsequent macular atrophy.DesignProspective cohort within a randomized, controlled trial of oral micronutrient supplements.ParticipantsAge-Related Eye Disease Study (AREDS) participants (55-80 years) who demonstrated nAMD during follow-up (1992-2005), prior to anti-vascular endothelial growth factor (VEGF) therapy.MethodsColor fundus photographs were collected at annual study visits and graded centrally for late age-related macular degeneration (AMD). Incident macular atrophy after nAMD was examined by Kaplan-Meier analysis and proportional hazards regression.Main outcome measuresIncident macular atrophy after nAMD.ResultsOf the 4757 AREDS participants, 708 eyes (627 participants) demonstrated nAMD during follow-up and were eligible. The cumulative risks of incident macular atrophy after untreated nAMD were 9.6% (standard error, 1.2%), 31.4% (standard error, 2.2%), 43.1% (standard error, 2.6%), and 61.5% (standard error, 4.3%) at 2, 5, 7, and 10 years, respectively. This corresponded to a linear risk of 6.5% per year. The cumulative risk of central involvement was 30.4% (standard error, 3.2%), 43.4% (standard error, 3.8%), and 57.0% (standard error, 4.8%) at first appearance of atrophy, 2 years, and 5 years, respectively. Geographic atrophy (GA) in the fellow eye was associated with increased risk of macular atrophy (hazard ratio [HR], 1.70; 95% confidence interval [CI], 1.17-2.49; P = 0.006). However, higher 52-single nucleotide polymorphism AMD genetic risk score was not associated with increased risk of macular atrophy (HR, 1.03; 95% CI, 0.90-1.17; P = 0.67). Similarly, no significant differences were observed according to SNPs at CFH, ARMS2, or C3.ConclusionsThe rate of incident macular atrophy after untreated nAMD is relatively high, increasing linearly over time and affecting half of eyes by 8 years. Hence, factors other than anti-VEGF therapy are involved in atrophy development, including natural progression to GA. Comparison with studies of treated nAMD suggests it may not be necessary to invoke a large effect of anti-VEGF therapy on inciting macular atrophy, although a contribution remains possible. Central involvement is present in one third of eyes at the outset (similar to pure GA) and increases linearly to half at 3 years.
| S-EPMC7246151 | biostudies-literature
Project description:PurposeThis work aims to determine whether previously defined genotype risk groups interact with Age-Related Eye Disease Study formulation (AREDS-F) use in progression to neovascular age-related macular degeneration (nvAMD).MethodsWe conducted a case-only study of 265 nvAMD patients. Patients were anonymously genotyped at the complement factor H and age-related maculopathy susceptibility 2 loci and segregated into genotype groups (GTGs) defined by specific combinations of risk alleles. Physicians, who were blind to patients' GTGs, obtained patients' AREDS-F use history. The facility performing genetic analysis was blind to the AREDS-F use history. We used logistic analysis to estimate the interaction coefficient between AREDS-F use and GTG 2 vs GTG 3 in a general-population model.ResultsThe odds ratio of numbers of patients reporting prior AREDS-F use to nonuse for GTG 2 vs GTG 3 was 4.18 (P = .001). Logistic regression, correcting for nongenetic risk factors, gave an estimate of the β for interaction of AREDS-F with genotype of 1.57 (P = .001). This estimates a corrected odds ratio associated with the effect of interaction of 4.81 between those in GTG 2 compared with those in GTG 3.ConclusionsOur data indicate an interaction between GTGs and AREDS-F use that is consistent in size and direction with previously published reports, which had found that using AREDS-F supplements significantly increases the risk of nvAMD for some users and significantly protects other users.
| S-EPMC9976046 | biostudies-literature
Project description:Age-related cataracts are one of the leading causes of visual impairment and blindness among the elderly worldwide. Among age-related cataracts, cortical opacities rank as the second most common type; however, little is known about their molecular pathogenesis or genetics. To identify susceptibility loci for cortical cataracts, we genotyped a subset of families (102 families; n = 224 sib pairs) from the Beaver Dam Eye Study and performed a model-free genome-wide linkage analysis for markers linked to a quantitative measure of cortical opacity. We obtained evidence for linkage at marker D1S1622 on chromosome 1p35 (P < 0.0002) and at marker D6S1053 on 6q12 (P < 0.00008) in the initial scan. Five additional regions on 1q31, 2p24, 2q11, 4q28, and 15q13 that are suggestive of linkage (P < or = 0.01 or logarithm of the likelihood ratio > or = 1.18) were observed. The region on chromosomes 6p12-q12 was selected for fine mapping, and the intermarker distance was reduced to 3 cM by adding 11 markers in the interval between D6S1017 and D6S1021. After fine mapping, significant evidence of linkage remained on chromosome 6p12-q12 at D6S1053 (P < 0.00005). The current genome scan for age-related cortical cataracts may lead to identification of novel genes, because few regions identified in the current scan have previously been implicated in congenital or age-related cataracts.
| S-EPMC521942 | biostudies-literature
Project description: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.
| S-EPMC1180302 | biostudies-literature