Ben Young, MD
University of Michigan
AREDS/AREDS2 Collaboration: Past, Present and Future
Both Dr. Frederick Ferris and Dr. Emily Chew of the National Eye Institute were awarded the J. Donald M. Gass Lectureship Award at Retina Society. After a sweeping introduction by Dr. Dan Martin, Dr. Chew reviewed the past, present and future of the AREDS/AREDS2 collaboration that was led in collaboration with Dr. Ferris. First, she outlined the history of the AREDS trials. In 1992, Dr. Ferris determined that a longitudinal study was needed to properly study geographic atrophy (GA) in age-related macular degeneration (AMD). They combined this with an interventional study to study whether micronutrients could impact the development of advanced AMD, which ultimately became the AREDS trial which ran from 1992-2001, followed by AREDS2 from 2006-2012. Even after trial conclusion, they continued long term follow-up, including ten year results, which produced datasets that many research teams have benefited from to enhance our understanding of AMD. Further, both the AREDS and AREDS2 vitamin formulations were found to be effective in reducing the chance of developing advanced AMD. Dr. Chew showed that 10 year results confirmed that not only was AREDS2 superior because it did not increase the risk of lung cancer in smokers, but also that the lutein substitution actually outperformed beta-carotene in preventing advanced AMD.
Further, because of the detailed nutritional surveys taken of all AREDS/AREDS2 participants, they found other dietary factors that impacted progression to advanced AMD. For example, the mediterranean diet was protective against development of both GA and neovascular AMD. Specifically, higher fish intake was found to be protective against development of GA. In contrast, a higher whole fruit diet and MUFA:SFA intake, along with moderate alcohol and lower red meat intake, were found to slow the progression of existing GA.
Then, Dr. Chew described work her team is doing to better identify reticular pseudodrusen (RPD), which she has found is an independent risk factor for the development of GA. However, they are difficult to identify in standard color fundus photos. Her team trained a deep learning algorithm to identify RPD in fundus autofluoresence photos. Further, they were also able to use deep learning to identify drusen, pigmentary changes and geographic atrophy. In combination with patient demographics and genotypic information, they have now developed an application that can predict a patient’s chance of progression of disease. Their goal is to develop an FDA-approved AI-based device which can be used for both clinical care and clinical trials.
Lastly, Dr. Chew described what she sees as the future of AMD research, which is centered on “-Omics”, including metabolomics, proteomics, genomics, and transcriptomics. She hopes these techniques will help us understand why patient’s AMD progresses, and why the AREDS/AREDS2 supplements work. Her goal is to use this type of information to eventually develop a trial aimed at preventing the development of AMD in the future.