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Markers of inflammation, oxidative stress, and endothelial dysfunction and the 20-year cumulative incidence of early age-related macular degeneration: the Beaver Dam Eye Study.

ABSTRACT: 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-? 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-?m 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-? 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-? 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.

SUBMITTER: Klein R

PROVIDER: S-EPMC4076038 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

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Markers of inflammation, oxidative stress, and endothelial dysfunction and the 20-year cumulative incidence of early age-related macular degeneration: the Beaver Dam Eye Study.

Klein Ronald R Myers Chelsea E CE Cruickshanks Karen J KJ Gangnon Ronald E RE Danforth Lorraine G LG Sivakumaran Theru A TA Iyengar Sudha K SK Tsai Michael Y MY Klein Barbara E K BE

JAMA ophthalmology 20140401 4

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 partic ...[more]

PMID: 24481424

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Project description:PurposeTo describe visual impairment (VI) over a 20-year period and its associations with age-related eye diseases and socioeconomic factors in the Beaver Dam Eye Study.DesignPopulation-based cohort study.ParticipantsFour thousand nine hundred twenty-six persons 43 to 86 years of age participated in the baseline examination phase from 1988 through 1990, and 3721, 2962, 2375, and 1913 persons participated in follow-up examinations each spaced 5 years apart from 1993 through 1995, 1998 through 2000, 2003 through 2005, and 2008 through 2010, respectively.MethodsBest-corrected visual acuity after refraction, assessed by the Early Treatment Diabetic Retinopathy Study protocol.Main outcome measuresIncidence of VI, defined as best-corrected visual acuity of poorer than 20/40 in the better eye in persons with one or both eyes 20/40 or better at the beginning of a 5-year interval, and incidence of severe VI, defined as best-corrected visual acuity of 20/200 or worse in the better eye in persons with one or both eyes better than 20/200 at the beginning of a 5-year interval.ResultsOverall incidence of VI between examinations (5-year interval) was 1.4% (varying from 0.1% in persons 50-54 years of age to 14.6% in those 85 years of age and older), whereas for severe VI it was 0.4% (varying from 0.0% in persons 50-54 years of age to 6.9% in those ? 85 years of age). The incidence of VI decreased for each (2003-2005 to 2008-2010; odds ratio fourth interval vs. first interval, 0.53; 95% confidence interval, 0.32-0.87; P = 0.01 period after adjustment for age, from the first 5-year interval between examinations (1988-1990 to 1993-1995) to the fourth and most recent 5-year interval ). This period effect was no longer significant after adjustment for age-related macular degeneration. Age-related macular degeneration remained the leading cause of incident severe VI (54% of eyes with incident severe VI, which was as low as 40% and as high as 57% for specific visits), with no evidence of a trend across visits. The overall frequency of VI correctable with new refraction was 38% of all eyes with VI.ConclusionsThese data provide population-based estimates that show a high (15%) 5-year incidence of VI in persons 85 years of age and older. Age-related macular degeneration remained the leading cause of severe VI in this population over the 20 years of the study.Financial disclosure(s)The author(s) have no proprietary or commercial interest in any materials discussed in this article.

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.

Project description:ObjectiveTo describe how retinal venular diameter changes over time for an individual and to examine differences in these changes among people with different risk profiles.DesignPopulation-based cohort study.ParticipantsA total of 4600 persons aged 43 to 86 years from the Beaver Dam Eye Study (BDES) who participated in at least 1 examination and had venular diameter measured in the right eye.MethodsData from 4 examinations during a 15-year period were analyzed. Retinal venular diameter was measured from photographs at each examination by computer-assisted methods and summarized as the central retinal venular equivalent (CRVE). Associations of risk factors with concurrent CRVE measurements and changes in CRVE over time were determined using multivariate analyses.Main outcome measuresCentral retinal venular equivalent.ResultsThe CRVE tended to narrow with age. Mean CRVE was approximately 5 ?m smaller (225 vs. 230 ?m) for the average 70-year-old compared with the average 50-year-old, and was approximately 13 ?m smaller (217 vs. 230 ?m) for the average 85-year-old compared with the average 50-year-old. Male sex (beta estimate [?] = 5.24; 95% confidence interval [CI], 3.58-6.90), history of current cigarette smoking (? = 9.38; 95% CI, 8.26-10.49), and higher white blood cell (WBC) count (per 1000/?L: ? = 0.95; 95% CI, 0.74-1.16) were independently associated with larger concurrent CRVE, whereas higher mean arterial blood pressure (per 5 mmHg: ? = -0.36; 95% CI, -0.50 to -0.23) and higher serum high-density lipoprotein (HDL) cholesterol (per 10 mg/dl: ? = 0.89; 95% CI, -1.15 to -0.63) were independently associated with smaller concurrent CRVE. History of cardiovascular disease (CVD) (? = -0.16; 95% CI, -0.26 to -0.06) and presence of chronic kidney disease (CKD) (? = -0.20; 95% CI, -0.34 to -0.05) were associated with a greater decrease in CRVE over time.ConclusionsThese data show that retinal venular diameter tends to narrow with age; concurrent venular diameter is independently associated with sex, blood pressure, serum HDL cholesterol, WBC count, and history of current cigarette smoking; and change in CRVE is independently associated with a history of CVD and presence of CKD. The different independent effects of these interrelated factors on CRVE highlight the complex relationship between CRVE and systemic diseases and conditions and the difficulty in determining specific causes of change in CRVE over time.Financial disclosure(s)The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Project description:ImportanceSince the advent of optical coherence tomography angiography (OCT-A), nonexudative neovascularization has been described in the fellow eyes of unilateral exudative age-related macular degeneration (AMD). However, there is limited literature describing the natural course and optimal management of these lesions.ObjectiveTo determine the incidence of fellow eye involvement in patients presenting with unilateral typical AMD or polypoidal choroidal vasculopathy and to evaluate the patterns of OCT-A changes within 6 months before the onset of exudative changes, especially focusing on nonexudative neovascularization.Design, setting, and participantsData for this study were taken from a prospective, observational cohort study involving Asian patients with exudative AMD in the Asian AMD Phenotyping Study between October 2015 and March 2016. Analyses began in June 2017. Only patients who had gradable OCT-A and indocyanine green angiography (ICGA) scans of the fellow eye at baseline and follow-up at least 6 months apart were included for the analysis. The contralateral eye was evaluated for presence of nonexudative neovascularization based on multimodal imaging, which included ICGA, spectral domain optical coherence tomography, and OCT-A.Main outcomes and measuresThe difference between the incidence of those with nonexudative choroidal neovascularization and those without as analyzed using log-rank test and qualitative analysis of OCT-A images.ResultsWe included 95 fellow eyes of 95 patients who presented with unilateral exudative AMD with a mean (SD) age of 68.6 (8.6) years. Nonexudative neovascularization was present in 18 eyes (19%) (8 [22.9%] and 10 [19.0%] fellow eyes with typical AMD and polypoidal choroidal vasculopathy, respectively; 8 [44.4%] on OCT-A; 5 [27.8%] on ICGA; and 5 [27.8%] on both OCT-A and ICGA). Development of exudative changes was noted in 6 fellow eyes (6.3%). Four eyes developed exudation from previously noted nonexudative neovascularization, and 2 eyes arose exudative changes from de novo. The probability of developing exudation within 6 months was significantly higher in eyes with baseline nonexudative neovascularization (0.087; 95% CI, 0.0033-0.210) compared with eyes without (0.010; 95% CI, 0.0026-0.041) (P = .008). In all eyes whose OCT-A images were available immediately before the onset of exudative changes, there was an increase in the size of network vessels compared with baseline.Conclusions and relevanceThe presence of nonexudative neovascularization may predispose to the development of exudative changes.

Dataset Information

Markers of inflammation, oxidative stress, and endothelial dysfunction and the 20-year cumulative incidence of early age-related macular degeneration: the Beaver Dam Eye Study.

Publications

Markers of inflammation, oxidative stress, and endothelial dysfunction and the 20-year cumulative incidence of early age-related macular degeneration: the Beaver Dam Eye Study.

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