The Development of AMD in Participants with No or Small Drusen in the Age-Related Eye Disease Study (AREDS)
Year of Publication
Shih, GC; Nigam, D; Agron, E; Chew, EY; The Age-Related Eye Disease Study Research Group (AREDS)
Association for Research in Vision and Ophthalmology - ARVO
Ft. Lauderdale, FL
age-related macular degeneration; clinical (human) or epidemiologic studies; drusen; natural history
Purpose: The development of advanced age-related macular degeneration (AMD) is usually associated with large size drusen, increasing drusen area, and/or retinal pigmentary epithelial changes. However, participants with no drusen (AREDS Category 1) or small drusen (Category 2) enrolled in AREDS also progressed to various stages of AMD. The objective of this presentation is to discuss the incidence of bilateral large drusen and advanced AMD, defined as both neovascular (NV) and central geographic atrophy (CGA). Methods: Baseline and annual fundus photographs from AREDS Category 1 and 2 participants were evaluated for the progression of AMD features and the development of bilateral large drusen, CGA, or NV AMD. Additionally, potential risk factors (age, gender, smoking history, and body mass index) were evaluated for association with the development of more severe stages of AMD with multivariate logistic regression. Kaplan-Meier analyses of progression to advanced AMD and bilateral large drusen were performed. Results: Of the 1117 AREDS participants with no drusen (category 1) and 1062 with small drusen (category 2), 69 (6.1%) and 238 (22.4%) developed persistent large drusen in either eye, respectively, over 10 years of follow-up. 0.54% of category 1 patients and 0.66% of category 2 patients progressed to persistent NV. No category 1 patients developed CGA, while 1.22% of category 2 patients progressed to CGA over 10 years. Of those who progressed to advanced AMD, peripapillary atrophy was noted in 30.4% of category 1 patients and 20% of category 2 participants. 17.4% category 1 and 40% category 2 end-stage AMD patients demonstrated hyperpigmentary changes. No significant correlation was found between the development of advanced AMD and age, gender, smoking, or BMI. Conclusions: The natural history of category 1 and 2 patients’ eyes is characterized by an exceedingly low rate of progression to NV AMD and CGA. However, among eyes proceeding to advanced AMD, the progressive development of pigmentary changes and peripapillary atrophy was observed, particularly in those eyes that did not develop large drusen prior to development of advanced disease. This phenotype is distinctly different from the usual pathway of AMD progression through large drusen and pigmentary changes, and may signify unique susceptibilities and disease processes in Category 1 and 2 progressors. Genotyping will be conducted at a later date to determine the role of genetic susceptibility.