Purpose
To describe 20-year progression rates for participants with early and intermediate age related macular degeneration (AMD).
Methods
We observed a subset of participants from the Age-Related Eye Disease Study (AREDS) for an additional 15 years, either through enrollment in the AREDS2 (n = 112) or through a follow-up protocol at the National Eye Institute (NEI), in Bethesda, MD (n = 121). Of the original AREDS participants followed at the NEI clinic, 62 participants were excluded from analysis due to insufficient follow-up (less than 10 years) or the development of an ocular condition which precluded grading of AMD severity. A total of 171 participants (342 eyes) aged 55 to 77 years with either no AMD or AMD of varying severity were followed for a median duration of 18.0 years (range: 11.8 - 21.7 years). Eyes were evaluated for progression to later stages of AMD, notably, neovascular AMD and central geographic atrophy, using annual color fundus photographs graded according to a 9-step AMD severity scale previously validated in AREDS. Best-corrected visual acuity was measured at each annual clinic visit.
Results
Fifty-six percent of participants were women, 92% were white, and median age at baseline was 65 years. In eyes with early AMD changes, step 1-3, (n = 179), 13.97% developed advanced AMD by the end of follow-up. In eyes with moderate AMD changes, step 4-6, (n = 108) and step 7-9, (n = 34), 45.37% and 58.82%, respectively, developed late AMD. Thirty percent of the 118 eyes initially labeled as step 1 (total drusen area < 125 µm and no pigmentary changes), remained at this exact grade. Median visual acuity from baseline to the end of follow-up changed from 20/20 to 20/25 among step 1-3 eyes and from 20/20 to 20/40 in step 4-6 eyes.
Conclusions
The natural history of early and intermediate AMD over the very long term (>10 years) has not been previously described. Eyes with either no or early AMD changes show low rates of progression to late AMD, while a significantly larger proportion of eyes with intermediate AMD progressed to either geographic atrophy or neovascular AMD. These results demonstrate that AMD pathology, once definitively present, tends to progress continuously with time over the long term.