AMD is the leading cause of irreversible blindness in older adults, and ophthalmology professor Cynthia Owsley, PhD, MSPH, lead investigator, and her colleagues have been working for years to determine some of the functional indications of the disease. “The challenge has been that while there has been a lot of progress in developing treatments for end-stage AMD, we don’t have any prevention strategies or treatments you can take early in the progression of the disease,” she says. “When we were studying AMD patients, we noticed that they had problems seeing at night and under reduced illumination. We discovered in the late 1990s that they had delayed dark adaptation (DA). When these people walked into a dark room, it took them longer to adjust to the darkness than it would a person who didn’t have the disease. At that time, we hypothesized that this might be the precursor to AMD, a functional bio-marker for the emergence of the earliest form of the disease. And the rest is history.”
The device the scientists have used to measure DA was designed by Owsley and colleague Greg Jackson and was built at UAB in 2005. The machine was designed to detect AMD four years before clinical signs of the disease are evident. UAB partnered with Apeliotus Technologies to develop the diagnostic device which could, one day, be found in any ophthalmologist’s or optometrist’s office.
“At that point in time, there was no testing instrument in our ophthalmology clinic that could test DA except a device that was developed decades ago, and it was not automated or computerized. If we were going to suggest that DA could be a risk for AMD, we had to develop our own technology to test that theory,” Owsley says. “The whole process, from our original exploration of DA as a risk factor for AMD to the commercialization process of developing instruments that could be placed in clinics, was largely funded by the National Institute on Aging which is part of the National Institutes of Health (NIH). The NIH has continued to fund my research so that I could determine if DA abnormality comes before the disease, which we now have confirmed.”
While treatment for AMD is available, it is not applicable until later stages of the disease when vision problems are already severe. The researchers are focusing on understanding AMD’s early stages in hopes that will lead to earlier treatments and, ultimately, prevention. Owsley and fellow UAB scientists Christine Curcio, PhD and Gerald McGwin, MS, PhD conducted the Alabama Study on Early Age-Related Macular Degeneration (ALSTAR). The study was designed to address the question of whether rod-mediated DA impairment in older adults in normal macular health as measured at baseline is associated with incident development of AMD three years later.
“In AMD, the macula is abnormal and already has started to degenerate, but everybody we enrolled at the baseline part of the study was in good macula health. We found that about 25 percent of them had abnormal DA even though they presumably had normal macula. We followed those people for three years and found that those with abnormal DA were two times more likely to have AMD three years later,” Owsley says. “With that finding, we identified abnormal DA as a functional biomarker for this disease. It also is a risk factor for AMD if you have this characteristic, because you are more likely to get the disease down the road than somebody who doesn’t have it.”
Owsley is optimistic about ongoing research for AMD, because this is the first functional vision problem that has been tied to an increased risk for early disease. “In ophthalmology research, this is a significant finding. In early AMD, acuity isn’t hampered, your visual field -- your peripheral vision – is also normal,” she says. “Now, when people come to us with difficulty seeing in the dark, this test can be performed to see if they have DA impairment. It also has potential as a functional biomarker that can to lead us to studies evaluating new treatments for prevention or for stopping progression in early stages of the disease.”
So far, the team’s research has focused on DA and delays in people who are in normal macular health who may be moving into the early stages of the disease. “We’d also like to track changes in rod-mediated DA in the more advanced stages of the disease, what is called intermediate AMD and advanced AMD. The impact of these later stages of disease on DA are largely unknown,” Owsley says. “We need to do more work to understand the natural history of DA and how it changes over years in older adults who are just getting the disease.”
Owsley and her colleagues have published these recent findings and are putting together a new grant proposal to the NIH for continuation of the research to examine some of the underlying structural, biomedical and physiological mechanisms of the disease so they can better understand how everything fits together in the development of AMD.
“We realize that this was an essential finding in our journey to better understand AMD, and it will enable us to move forward in our understanding of night vision problems in individuals with AMD. This discovery had to happen for us to move forward,” Owsley says. “This is something we have been working on for a long time, and it is gratifying to finally have the finding we were hypothesizing all along.”
