1. Copyright restrictions may apply 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.

2. Copyright restrictions may apply 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).

3. Copyright restrictions may apply 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

4. Copyright restrictions may apply 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

5. Copyright restrictions may apply Results Life-Table Estimates of Developing Large Drusen (n = 2248)

6. Copyright restrictions may apply 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

7. Copyright restrictions may apply 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

8. Copyright restrictions may apply Life ‐ Table Estimates of Advanced AMD in Eyes With Fellow Eyes Without (A) or With (B) Advanced AMD AB Results

9. Copyright restrictions may apply Results Development of Neovascularization in Eyes With Geographic Atrophy, Stratified by Presence of Neovascular AMD in Fellow Eye

10. Copyright restrictions may apply Results Median Visual Acuity in Eyes That Progressed to Advanced AMD 20/25 20/200

11. Copyright restrictions may apply 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

12. Copyright restrictions may apply 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

13. Copyright restrictions may apply 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

14. Copyright restrictions may apply 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 (echew@nei.nih.gov). 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. Contact Information