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Cigarette smoking and the natural history of age-related macular degeneration: the Beaver Dam Eye Study.

ABSTRACT: 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.

SUBMITTER: Myers CE

PROVIDER: S-EPMC4177947 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

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Cigarette smoking and the natural history of age-related macular degeneration: the Beaver Dam Eye Study.

Myers Chelsea E CE Klein Barbara E K BE Gangnon Ronald R Sivakumaran Theru A TA Iyengar Sudha K SK Klein Ronald R

Ophthalmology 20140620 10

<h4>Purpose</h4>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.<h4>Design</h4>A longitudinal population-based study of AMD in a representative American community. Examinations were performed every 5 year ...[more]

PMID: 24953792

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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: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.

Project description:PurposeTo investigate the natural history and genetic associations of drusenoid pigment epithelial detachment (DPED) associated with age-related macular degeneration (AMD).DesignRetrospective analysis of a prospective cohort study.ParticipantsOf the 4203 Age-Related Eye Disease Study 2 (AREDS2) participants, 391 eyes (325 participants) had DPED without late AMD at the time of DPED detection. Genetic analyses included 120 white AREDS2 participants and 145 Age-Related Eye Disease Study (AREDS) participants with DPED.MethodsBaseline and annual stereoscopic fundus photographs were graded centrally to detect DPED, a well-defined yellow elevated mound of confluent drusen ≥433 μm in diameter, and to evaluate progression rates to late AMD: geographic atrophy (GA) and neovascular (NV)-AMD. Five single nucleotide polymorphisms (CFH [rs10611670], C3 [rs2230199], CFI [rs10033900], C2/CFB [rs114254831], ARMS2 [rs10490924]) and genetic risk score (GRS) group were investigated for association with DPED development. Kaplan-Meier analyses and multivariable proportional hazard regressions were performed.Main outcome measuresProgression rates to late AMD and decrease of ≥3 lines in visual acuity (VA) from the time of DPED detection; association of rate of DPED development with genotype.ResultsMean (standard deviation [SD]) follow-up time from DPED detection was 4.7 (0.9) years. DPED was associated with increased risk of progression to late AMD (hazard ratio [HR], 2.36; 95% confidence interval [CI], 1.98-2.82; P < 0.001); 67% of eyes progressed to late AMD 5 years after DPED detection. Drusenoid pigment epithelial detachment was associated with increased risk of ≥3 lines of VA loss (HR, 3.08; CI, 2.41-3.93; P < 0.001) with 46% of eyes experiencing vision loss at 5 years (with or without progression to late AMD). ARMS2 risk alleles (1 vs. 0: HR, 2.72, CI, 1.58-4.70; 2 vs. 0: HR, 3.16, CI, 1.60-6.21, P < 0.001) and increasing GRS group (4 vs. 1) (HR, 12.17, CI, 3.66-40.45, P < 0.001) were significantly associated with DPED development in AREDS. There were no significant genetic results in AREDS2.ConclusionsThis study replicates the results of previous natural history studies of eyes with DPED including the high rates of progression to late AMD and vision loss (regardless of progression to late AMD). The genetic associations are consistent with genes associated with AMD progression.

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.

Dataset Information

Cigarette smoking and the natural history of age-related macular degeneration: the Beaver Dam Eye Study.

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Cigarette smoking and the natural history of age-related macular degeneration: the Beaver Dam Eye Study.

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