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Pace of eye disease over two years predicts long-term outcome

Finding could shorten clinical trials for age-related macular degeneration
May 18, 2020
Fundus photograph of age-related macular degeneration showing drusen.

Progression along an age-related macular degeneration (AMD) severity scale over two years predicts the likelihood of developing late-stage disease five years later, according to a new report from researchers at the National Eye Institute (NEI). This finding held true for both ‘wet’ and ‘dry’ types of AMD. The report suggests that studies of future AMD therapies could use this scale to shorten clinical trials by years. The findings were reported online in JAMA Ophthalmology on April 9. NEI is part of the National Institutes of Health.

“In this study, we’ve shown that if you progress two or three steps on our severity scale in two years, you’re more likely to end up with vision loss years later,” said Emily Chew, M.D., chief of the Division of Epidemiology and Clinical Application at NEI and senior author on the study. “This is especially important for the early stage of macular degeneration, where there’s very little vision change.”

AMD is a degenerative disease of the retina, the light-sensing tissue at the back of the eye. The disease comes in two forms: wet AMD, also called neovascular AMD, and dry AMD, also called geographic atrophy. In early stages of both forms, vision loss is uncommon, and signs of retinal damage are apparent only through clinical evaluation. Vision loss typically occurs during late stages of AMD. While there are treatments for wet AMD that can slow vision loss, there are no treatments currently available for dry AMD.

The researchers analyzed data from the Age-Related Eye Disease Study (AREDS) and AREDS2, which were randomized clinical trials testing the effect of dietary supplements on AMD and cataract. Participants’ disease was assessed with a specialized severity scale based on changes in the retina. The researchers examined photos taken during clinical exams and evaluated changes to pigment in the retina and changes in deposits beneath the retina called drusen, hallmark features of AMD. The study’s severity scale has more steps than the scores generally used in clinical practice, providing researchers a more nuanced picture of participants’ progression over time. AREDS researchers photographed and evaluated participants’ retinas annually for at least 5 years. AREDS enrolled 4757 participants, 3868 of whom did not yet have late AMD. AREDS2 included 4203 participants with intermediate to late AMD, 2718 of whom did not have late AMD in either eye at the start of the trial.

According to the latest report, participants who had increased at least two steps along the trial’s 9-step severity scale within the first two years of the study had a significantly greater risk of progressing to late AMD five years later, and that likelihood was even greater for those who had increased at least three steps along the scale. These two-step and three-step scale increases were also associated with a higher chance of vision loss five years later.

The researchers applied similar analyses to data from AREDS2. Because sufficient long-term data was not available for AREDS2, the team evaluated 3-year, rather than 5-year, outcomes in those who increased at least two steps (or 3 steps) along the severity scale within the first two years of the study. Results from the AREDS2 data were similar to those from AREDS.

“This study shows that use of the AREDS severity scale can substantially shorten the duration of clinical trials directed at reducing the progression of early AMD,” said Susan Vitale, Ph.D., lead author of the study. “You can reduce the duration and cost of such studies, and hopefully bring treatments to people who need them earlier.”

The AREDS scale is primarily based on color retinal photographs, but in the intervening years, many new imaging technologies have become available, said Chew. Going forward, the investigators plan to incorporate data from newer imaging methods such as other types of retinal photography and optical coherence tomography, she said. They also plan to use artificial intelligence to analyze data from these techniques and help refine this specialized AMD progression scale.


Reference: Vitale S, Agrón E, et al. “Association of 2-year progression along the AREDS AMD scale and development of late age-related macular degeneration or loss of visual acuity.” JAMA Ophthalmol. Apr 9, 2020. doi:10.1001/jamaophthalmol.2020.0824 

The study was completed in part at the NIH Clinical Center. The study was funded through the NEI’s intramural program and contract NOI-EY-0-2127. AREDS and AREDS2 follow-up can be found at with clinical trials identifier NCT00594672.




NEI leads the federal government’s research on the visual system and eye diseases. NEI supports basic and clinical science programs to develop sight-saving treatments and address special needs of people with vision loss. For more information, visit

About the National Institutes of Health (NIH): NIH, the nation’s medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit

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Lesley Earl