More details have emerged regarding a new clinical study led by the National Eye Institute (NEI), part of the National Institutes of Health. The study will follow 500 people over 5 years to learn more about the natural history of early-stage AMD. By using the latest technologies to visualize structures within the eye and measure their function, researchers hope to identify biomarkers of disease progression, well before it advances to late-stage disease and causes vision loss. 

"The findings will contribute to our understanding of the underlying biology driving the transition from early to late-stage disease so that therapies can be developed to halt its progression,” said the study’s lead investigator, Emily Y. Chew, MD, deputy clinical director at NEI and director of the NEI Division of Epidemiology and Clinical Applications. “Treatments that halt the disease at its early stage would have an enormous public health impact.”

Only about 10% to 20% of people with early AMD progress to late-stage disease within 5 years. It is difficult to predict who will progress, because AMD is a complex, multifactorial disease influenced by a combination of age, family history, genetic and health behavioral factors.

“We want to better leverage advances in genetics, imaging and visual functioning tests so we can look at early-stage disease with more granularity. There may be surrogate markers of an individual’s risk of developing late-stage disease long before the disease progresses,” Dr. Chew said.

The AMD Ryan Initiative Study (ARIS) will track the eye health of 200 people who have bilateral early AMD, defined by the presence of medium-size drusen, yellowish deposits that accumulate under the retina. In addition, ARIS will include 200 people with early, reticular pseudodrusen, a type of lesion that causes the retina to have a giraffe-like macular pattern. The composition and location of the reticular pseudodrusen differ from that of typical drusen. Some data suggest reticular pseudodrusen are associated with a higher than usual risk for progression to late disease, but more research is needed about this group. For comparison, the study will enroll 100 age-matched, drusen-free control participants.

All participants will undergo routine spectral domain optical coherence tomography (SD-OCT), which is sensitive enough to detect even small changes in the volume of drusen over time. In addition, visual function will be measured by dark-adapted fundus perimetry, a test that measures the sensitivity of light perception in specific parts of the retina after a person’s eyes have adapted to the dark. Another visual function test, dark adaption, is useful for evaluating night vision impairment. Researchers at each of the 20 ARIS study sites will track drusen volume changes as well as other findings on SD-OCT to see if they correspond to functional changes in visual acuity and dark adaptation.

Ideally, the investigators would like to complement their studies by analyzing the participants’ DNA to look for correlations between genes and AMD progression. In total, scientists have so far identified 52 independent genetic variants associated with AMD. Further research is needed to determine if and how these variants influence the development and progression of the disease.

The clinical study is funded by NEI, with study sites located throughout the United States, the United Kingdom, Australia, Germany, and Italy. The study is named after the late Stephen J. Ryan, MD, a widely recognized expert in retinal disease and president of the Doheny Eye Institute, an independent nonprofit institution supporting ophthalmic research, training, and clinical care.