Elsevier

Ophthalmology

Volume 112, Issue 4, April 2005, Pages 533-539.e1
Ophthalmology

Original article
Risk Factors for the Incidence of Advanced Age-Related Macular Degeneration in the Age-Related Eye Disease Study (AREDS): AREDS report no. 19

https://doi.org/10.1016/j.ophtha.2004.10.047Get rights and content

Purpose

To describe the association of demographic, behavioral, medical, and nonretinal ocular factors with the incidence of neovascular age-related macular degeneration (AMD) and central geographic atrophy (CGA) in the Age-Related Eye Disease Study (AREDS), a randomized trial of antioxidants and zinc supplementation prophylaxis for development of advanced AMD.

Design

Clinic-based prospective cohort study.

Participants

Of individuals with early or intermediate AMD at baseline with a median follow-up of 6.3 years, 788 were at risk of developing advanced AMD in one eye (the fellow eye had advanced AMD), and 2506 were at risk in both eyes.

Methods

The incidence of neovascular AMD and CGA was assessed from stereoscopic color fundus photographs taken at baseline and at annual visits beginning at year 2.

Main Outcome Measures

Neovascular AMD was defined as photocoagulation for choroidal neovascularization, or photographic documentation at the reading center of any of the following: nondrusenoid retinal pigment epithelial detachment, serous or hemorrhagic retinal detachment, hemorrhage under the retina or the retinal pigment epithelium, and subretinal fibrosis. Central geographic atrophy was defined as geographic atrophy involving the center of the macula.

Results

In multivariable models, in persons at risk of advanced AMD in both eyes, while controlling for age, gender, and AREDS treatment group, the following variables were statistically significantly associated with the incidence of neovascular AMD: race (odds ratio [OR], white vs. black, 6.77; 95% confidence interval [CI], 1.24–36.9) and larger amount smoked (OR, >10 vs. ≤10 pack-years [a pack-year is an average of 1 pack of cigarette smoked per day for a year], 1.55; 95% CI, 1.15–2.09). The following were statistically significantly associated with the incidence of CGA: less education (OR, high school graduate or less vs. college graduate, 1.75; 95% CI, 1.10–2.78), greater body mass index (BMI) (OR, obese vs. nonobese, 1.93; 95% CI, 1.25–2.65), larger amount smoked (OR, >10 pack-years vs. ≤10 pack-years, 1.82; 95% CI, 1.25–2.65), and antacid use (OR, 0.29; 95% CI, 0.09–0.91). In persons at risk of developing advanced AMD in one eye, the incidence of neovascular AMD was associated with diabetes (OR, 1.88; 95% CI, 1.07–3.31), and the incidence of CGA was associated with use of antiinflammatory medications (OR, 0.22; 95% CI, 0.08–0.59).

Conclusions

Results suggest that, among persons with early or intermediate AMD, smoking and BMI are modifiable factors associated with progression to advanced AMD, and suggest other associations (e.g., use of antacids and antiinflammatory medications) that warrant further study.

This article contains additional online-only material available at http://www.ophsource.org/periodicals/ophtha.

Section snippets

Study Population

Details of the study design and methods, presented elsewhere,18 are briefly summarized here. Eleven retinal specialty clinics enrolled 4757 participants in the AREDS from 1992 through 1998. Participants were 55 to 80 years old at enrollment and had best-corrected visual acuity (BCVA) of 20/32 or better in at least one eye (the study eye[s]). Media had to be sufficiently clear to obtain adequate quality stereoscopic fundus photographs of the macula in all study eyes. Visual acuity (VA) was

Results

In Table 1, baseline risk factors are categorized for the bilateral drusen participants and the participants with unilateral advanced AMD. For the 2506 participants in the bilateral drusen group, the mean age was 68.5 years (standard deviation [SD], 5.0). For the 788 participants with unilateral advanced AMD, the mean age was 70.3 years (SD, 5.2). Mean follow-up time for all participants was 6.3 years. More females than males participated, and they were predominantly (96%–98%) white. Relative

Discussion

Results of these analyses provide information regarding associations of demographic, behavioral, medical, and non-AMD ocular factors with the incidence of neovascular AMD and central GA among participants with preexisting signs of AMD. Strengths include the standardized protocols for obtaining data, standardized definitions for risk exposure, photographic assessment of the outcomes and retinal risk categories, the large size of the cohort (n = 3394) at risk for these conditions, and the

References (52)

  • G.S. Hageman et al.

    An integrated hypothesis that considers drusen as biomarkers of immune-mediated processes at the RPE-Bruch's membrane interface in aging and age-related macular degeneration

    Prog Retin Eye Res

    (2001)
  • R. Klein et al.

    Diabetes, hyperglycemia, and age-related maculopathyThe Beaver Dam Eye Study

    Ophthalmology

    (1992)
  • S.C. Tomany et al.

    Risk factors for incident age-related macular degenerationPooled findings from 3 continents

    Ophthalmology

    (2004)
  • K.K. Snow et al.

    Association between reproductive and hormonal factors and age-related maculopathy in postmenopausal women

    Am J Ophthalmol

    (2002)
  • Age-Related Eye Disease Study Research Group. Potential public health impact of Age-Related Eye Disease Study results....
  • R. Klein

    Epidemiology

  • J. Seddon

    Epidemiology of age-related macular degeneration

  • A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age-related macular degeneration and vision loss: AREDS report no

    8. Arch Ophthalmol

    (2001)
  • J.M. Seddon et al.

    A prospective study of cigarette smoking and age-related macular degeneration in women

    JAMA

    (1996)
  • W.G. Christen et al.

    A prospective study of cigarette smoking and risk of age-related macular degeneration in men

    JAMA

    (1996)
  • R. Klein et al.

    Ten-year incidence of age-related maculopathy and smoking and drinking: the Beaver Dam Eye Study

    Am J Epidemiol

    (2002)
  • Risk factors associated with age-related macular degeneration: a case-control study in the Age-Related Eye Disease StudyAge-Related Eye Disease Study report number 3

    Ophthalmology

    (2000)
  • R. van Leeuwen et al.

    Blood pressure, atherosclerosis, and the incidence of age-related maculopathy: the Rotterdam Study

    Invest Ophthalmol Vis Sci

    (2003)
  • J.M. Seddon et al.

    Progression of age-related macular degeneration: association with body mass index, waist circumference, and waist-hip ratio

    Arch Ophthalmol

    (2003)
  • J.A. Mares-Perlman et al.

    Dietary fat and age-related maculopathy

    Arch Ophthalmol

    (1995)
  • J.M. Seddon et al.

    Dietary fat and risk for advanced age-related macular degeneration

    Arch Ophthalmol

    (2001)
  • Cited by (543)

    View all citing articles on Scopus

    Manuscript no. 240543.

    The study was supported by contracts from the National Eye Institute, Bethesda, Maryland.

    The writing team and the members of the AREDS Research Group have no relevant financial interest in the article.

    Writing team: Traci E. Clemons, PhD (The EMMES Corporation, Rockville, Maryland), Roy C. Milton, PhD (The EMMES Corporation), Ronald Klein, MD (University of Wisconsin, Madison, Wisconsin), Johanna M. Seddon, MD (Massachusetts Eye and Ear Infirmary, Boston, Massachusetts), Frederick L. Ferris III, MD (National Eye Institute, Bethesda, Maryland).

    E-mail: [email protected].

    Reprint requests to AREDS Coordinating Center, The EMMES Corporation, 701 North Washington Street, Suite 700, Rockville, MD 20850-1707. E-mail: [email protected].

    A complete list of the AREDS Research Group is found in Ref. 52.

    View full text