For the 13 million people in the United States alone who have untreatable vision loss as a result of age-related macular degeneration (AMD), hope is on the way in the form of a new diagnostic testing method which has the potential to identify people for treatment before visual impairment occurs. “This is an early warning system,” said Greg Jackson, PhD, assistant professor of ophthalmology at UAB. “The instrument will be able to detect the beginnings of macular degeneration earlier than any other clinical test that is currently available, and before an individual even notices any vision loss.” Jackson said the device resulted from 10 years of research. “Our initial research was focused on night vision problems experienced by older adults. We documented that the ability to adjust to darkness, a process called dark adaptation, declines with increasing age,” he said. The researchers became interested in AMD because some older adults performed much worse in the testing than their peers, Jackson added. “These individuals had no clinical signs of disease and every other aspect of their vision that we tested was normal. We followed a few of these people and found them to be diagnosed later with age-related macular degeneration, a fairly common retinal disease in adults over 50 years old,” he said. As a result of these observations, Jackson and his team studied the night vision of patients with AMD and found they had tremendous impairment of dark adaptation even in the earliest stages of the disease. One study showed that 86 percent of patients with AMD exhibited impaired dark adaptation while only 25 percent exhibited impaired contrast sensitivity or visual fields. None exhibited impaired acuity. “The impairment was so large that we came to believe it could be a useful clinical trial endpoint and diagnostic device,” Jackson said. The team’s ability to study these individuals was hampered by the fact that there was no commercially available dark adaptometer that was sensitive to the disease, and the research protocol required more than 60 minutes to characterize a patient’s dark adaptation, Jackson said. With the support of the National Institute on Aging and two local foundations — the International Retinal Research Foundation and the EyeSight Foundation of Alabama — the researchers translated the research apparatus and protocol into a clinically useful version. “We partnered with Apeliotus Technologies in Atlanta to build a new dark adaptometer called the AdaptDx,” Jackson said. “The AdaptDx greatly simplifies the process of measuring dark adaptation.” AdaptDx is a computer-automated machine, so the operator simply aligns the patient’s eye, and the machine and computer conduct the test which takes only 20 minutes, compared to the 60 minutes previously required. The patient’s task is to look at a dim red fixation light. “First a weak flash of light appears below the fixation light as the computer determines the least amount of light a person can detect at a given time,” Jackson said. “Over time, the patient will be able to see dimmer lights than at the beginning of the test.” Jackson added that about 20 measurements are needed to determine whether a person’s speed adjusting to the dark is normal. “A normal person requires about 12 minutes to complete the examination. Patients with the disease require more time,” he said. Upon completion of the test, the computer analyzes the data and classifies the person as having normal or abnormal dark adaptation. Apeliotus Technologies has constructed the first clinical versions of the device based on Jackson’s research prototype. The clinical version is being trialed at UAB, Johns Hopkins and Pennsylvania State University to validate the earlier research findings of Jackson and his research colleague, Cynthia Owsley, Ph.D., professor of ophthalmology at UAB. “The device is similar in size, operation and cost to the instruments routinely used for glaucoma screening,” said John Edwards, Chief Executive Office of Apeliotus Technologies. Apeliotus Technologies develops life science products based on university inventions and licenses high potential innovations from research universities throughout the Southeast. The company works with both targeted industry users and the inventors to transform innovations from academic concept to commercial reality. Edwards is excited about the possibilities for Jackson’s device. “Our grandparents worried about cataracts and our parents worried about glaucoma. Both are treatable now,” said Edwards. “The third great wave of eye disease is macular degeneration, and the only treatments available now are for the late stages of the disease after it is too late. Greg’s device can detect the disease while it is still treatable, so maybe our children won’t have to worry about macular degeneration.” Jackson said that currently the Food and Drug Administration only permits the use of moderate acuity loss or gross changes in the clinical appearance of the fundus as outcome measurements in clinical trials aimed at age-related macular degeneration. Neither of these outcomes is likely until later stages of the disease, he pointed out. “Long study durations required by acuity and fundus appearance to evaluate early disease interventions are economically unfeasible. Obviously, we would like to treat patients before substantial irreversible vision loss occurs,” Jackson said. “Thus, better clinical trial endpoints are needed, and we believe that dark adaptation is a much more sensitive indicator of the disease progression than either acuity or changes in fundus appearance. Used as an endpoint, treatment trials aimed at early disease are feasible.” Jackson said he expects the device will be available to physicians as a clinical tool within the next three years. “We envision patients over 50 years old having this screening test as part of their yearly examination,” he said. “The technology will enable companies to prove the efficacy of their treatments aimed at early AMD. If a patient exhibits the characteristic impairment of AMD, intervention would be indicated. The eye care provider can then objectively monitor the progression of the disease and the efficacy of the treatment regimen.” July 2007