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ALSTAR Study Finds Answers in the Dark

The AdaptDx instrument was developed here at UAB by Cynthia Owsley, PhD, and a former colleague, Greg Jackson, PhD. Dr. Owsley says there was no computerized device available at the time that could measure dark adaptation, yet they saw a commercial and research need for such a device, so they developed one.
Cynthia Owsley, PhD, MSPH, is studying the functional and structural risk factors for early- onset age-related macular degeneration (AMD) through the ALSTAR Study. ALSTAR, the Alabama Study on Early Age-Related Macular Degeneration, is funded by the National Institutes of Health (NIH) and aims to identify those factors that are responsible for developing early-stage AMD.

AMD is the leading cause of severe vision loss and legal blindness in Americans age 60 and older, affecting up to 15 million people in the United States today and expected to grow to almost 200 million people worldwide by 2020. As the population ages, those numbers will only increase. AMD occurs when the central portion of the retina, known as the macula, deteriorates. The exact cause is unknown, and new treatments are desperately needed.

Dr. Owsley, the Nathan E. Miles Chair of Ophthalmology, vice chair of research administration, and director of the clinical research unit, says lots of information is known about the characteristics that put people at risk for intermediate AMD, or AMD that progresses to advanced stages, but the scientific community knows very little about why the disease develops in the first place. Most researchers focus on preventing end-stage AMD, as this causes severe blindness, but she prefers to focus on the root cause and is searching for what factors are responsible for the transition between normal aging and early AMD.

Biomarker Found

The initial ALSTAR study is complete, and Dr. Owsley and her team are analyzing data. So far, there has been a significant finding. Dr. Owsley was able to identify the first functional biomarker for early-onset AMD: slowed dark adaptation – the amount of time it takes a person to adjust to darkness after leaving bright daylight.

“Imagine you are walking around outside on a bright, sunny day,” Dr. Owsley says. “Then you step into a dark movie theater. We all have that brief moment where our eyes naturally adjust between the light and the dark, but for people with early-onset AMD, that period of time is extended past a normal threshold. For these people, it doesn’t just take seconds – it takes several minutes.”

This was measured in the study using a dark adaptometer instrument known as AdaptDx. Patients were given a bright flash of light, similar to a bright photoflash. The flash “photobleached” the photoreceptors temporarily, but as the receptors sat in the dark and recovered, Dr. Owsley was able to measure the rate of light sensitivity recovery over the next few minutes.

There are generally two types of photoreceptors in the eye: rods and cones. Cones are mostly responsible for seeing daylight, vision, and color, while rods specifically are used for seeing under dim illumination and at night. Rods are especially vulnerable to the aging process and the early degenerative changes in AMD. The more time it takes the rods to respond and take over, the slower the dark adaptation.

Over 600 patients were involved in the study. They were followed for three years, but the study took nearly seven years. Dr. Owsley and her colleague, Christine A. Curcio, PhD, a professor in the UAB Department of Ophthalmology, hope to soon move on to the next phase of the study, which calls for examining the structure-function relationships to better understand the disease’s progression over time. This should provide more information about how anatomical changes in the retina underlie slowed dark adaptation in AMD.

Dr. Owsley says this research will not only clarify what is going on in the initial phases of the disease, but it also will provide new tools for evaluating treatments to prevent AMD in older adults at higher risk for developing the disease.