JAMA Ophthalmology Journal Club Slides: AMD in the Age-Related Eye Disease Study

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JAMA Ophthalmology Journal Club Slides:AMD in the Age-Related Eye Disease Study

Chew EY, Clemons TE, Agrón E, et al; Age-Related Eye Disease Study Research Group. Ten-year follow-up of age-related macular degeneration in the Age-Related Eye Disease Study: AREDS report No. 36. JAMA Ophthalmol. Published online January 2, 2014. doi:10.1001/jamaophthalmol.2013.6636.


Introduction

• Importance

– Providing long-term follow-up of the natural history of age-related macular degeneration (AMD) and associated risk factors will facilitate future epidemiologic studies and clinical trials.

• Objective

– To describe 10-year progression rates to intermediate or advanced AMD in the Age-Related Eye Disease Study (AREDS).


• Study Design– AREDS was a multicentered randomized clinical trial of nutrients for the treatment

of AMD from 1992 to 2001. Participants were then followed up as an epidemiologic study for an additional 5 years.

• Participants– 4757 men and women aged 55-80 years were enrolled at 11 clinical sites of

medical retinal practices for the clinical trial; 3549 of the 4203 surviving participants in 2001 were followed up for another 5 years in an observational study.

• Data Analysis– Cox proportional hazards regression model to compute probabilities of

progression to advanced AMD, stratified by baseline drusen; life-table method to estimate the rates of progression to large drusen and advanced AMD in 10 years.

Methods


• The risk of progression to advanced AMD increased with increasing age (P = .01) and severity of drusen.

• Women (P = .005) and current smokers (P < .001) were at increased risk of neovascular AMD. In the oldest participants with the most severe AMD status at baseline, the risks of developing neovascular AMD and central geographic atrophy by 10 years were 48.1% and 26.0%, respectively.

• Progression to large drusen increased with increasing severity of drusen at baseline, with 70.9% of participants with bilateral medium drusen progressing to large drusen and 13.8% to advanced AMD in 10 years.

• Median visual acuity at 10 years in eyes that had large drusen at baseline but never developed advanced AMD was 20/25; eyes that developed advanced AMD had a median visual acuity of 20/200.

Results


Results

Life-Table Estimates of Developing Large Drusen (n = 2248)


Life‐Table Estimates of Advanced AMD in Eyes That Developed Large Drusen and Retinal Pigment Epithelial Abnormalities During the Study With

Absence (A) or Presence (B) of Advanced AMD in Fellow Eye

Results

A B


Life‐Table Estimates of Advanced AMD in Participants With Bilateral Large Drusen at Baseline, Without (A) or With (B)

Retinal Pigment Epithelial (RPE) Abnormalities

A B

Results


Life‐Table Estimates of Advanced AMD in Eyes With Fellow Eyes Without (A) or With (B) Advanced AMD

A B

Results


Results

Development of Neovascularization in Eyes With Geographic Atrophy, Stratified by Presence of Neovascular AMD in Fellow Eye


Results

Median Visual Acuity in Eyes That Progressed to Advanced AMD

20/25

20/200


• The following factors increased the risk of progression to advanced AMD: increasing severity of drusen at baseline, presence of large drusen within 1 disc diameter of fovea, presence of bilateral medium drusen, presence of advanced AMD in the fellow eye, and presence of large drusen with AMD RPE abnormalities.

• Increasing age is associated with neovascular and geographic atrophy.

• Female sex and current smoking increase the risk of progression to neovascular AMD.

• Long-term visual acuity loss is relentless once advanced AMD develops.

• Median visual acuity at 10 years in eyes that had large drusen but never developed advanced AMD was 20/25; eyes that developed advanced AMD had a median visual acuity of 20/200.

Comment


• Strengths

– Low rate of loss to follow-up, 2.4% during the clinical trial and 3.7% during the observational phase.

– Standardized centralized grading of AMD.

• Limitation

– Not a population-based cohort. The participants are highly educated and well nourished, typical of clinical trial volunteers. Also, participants who were at higher risk of progression were less likely to participate in the extended follow-up.

Comment


• These clinic-based data provide important information for investigators who are interested in designing controlled clinical trials or epidemiologic studies of AMD in clinic-based populations.

Conclusions


• If you have questions, please contact the corresponding author:

– Emily Y. Chew, MD, Division of Epidemiology and Clinical Applications, National Eye Institute, National Institutes of Health, 10 Center Dr, MSC 1204, Bldg 10, CRC Room 3-2531, Bethesda, MD 20892 ([email protected]).

Funding/Support

• This study is supported by the intramural program funds and contract NOI-EY-0-2127 from the National Eye Institute, National Institutes of Health, Department of Health and Human Services.

Conflict of Interest Disclosures

• None reported.

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JAMA Ophthalmology Journal Club Slides: AMD in the Age-Related Eye Disease Study