January 01, 2017
11 min read

Dark adaptation test may detect AMD earlier than traditional technology

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Clinicians are beginning to recognize that dark adaptation testing may indicate a diagnosis of age-related macular degeneration in patients who have no other clinical signs.

The diagnostic testing device, AdaptDx (MacuLogix), has been shown in a clinical trial to identify patients at risk for vision loss who have no other detectable signs of AMD by using abnormal dark adaptation (DA) as a biomarker for disease.

The role of DA in AMD could be significant, “as research has found that the disease is three times more prevalent than glaucoma, with one out of eight adults over 60 years and one out of three over 75 years afflicted,” according to Greg Jackson, PhD, chief scientific officer, MacuLogix and creator of AdaptDx, in an interview with Primary Care Optometry News.

The Eye Diseases Prevalence research group published these statistics in 2004.

Glenn S. Corbin, OD, a private practitioner in Wyomissing, Pa., and Section of Optometry chief at Penn State Health St. Joseph Medical Center, received the first AdaptDx unit off the assembly line in the U.S. more than 2 years ago.

Glenn S. Corbin

“The idea of performing dark adaptation in practice was new to eye care,” Corbin told PCON. “I looked at the technology; the platform was similar to an autoperimeter, and I was intrigued by it.

“We are able to find people that would have normally been undiagnosed until a later stage of the disease,” he continued. “I would have never thought that a couple of drusen could indicate an early diagnosis of AMD. Now the technology tells me their dark adaptation is abnormal and they do have early signs of AMD.”

Based on this testing, Corbin can provide those with disease risk factors or a family history a much more accurate response, he said. Additionally, he can diagnose the disease at an earlier stage.

Glen S. Corbin, OD, said that dark adaptation testing has allowed him to identify patients with AMD who would have normally been undiagnosed until a later stage of the disease.

Image: Corbin GS

“We’ve learned of an entity called subclinical AMD, where a patient appears to have a healthy retina, and you cannot physically see drusen, but they may have a sheet of drusen underneath that is not clinically visible upon examination,” Corbin added.

He believes that every optometrist should test for DA in their practice.

“With the aging population, longer lifespans and increased visual demands that are much different than a generation or two ago, it’s critical to identify patients before they start losing vision,” Damon Dierker, OD, FAAO, of the Eye Surgeons of Indiana and adjunct faculty member at the Indiana University School of Optometry, said in an interview

Corbin added: “I screen patients as a precaution or if there’s a family history of AMD. Clinically, we may not observe AMD signs, but based on abnormal DA testing results, we can feel confident that they have the disease.”

AdaptDx is changing the timeline for AMD diagnosis, according to Leo P. Semes, OD, FAAO, former professor of optometry at the University of Alabama at Birmingham and a Primary Care Optometry News Editorial Board member.

Early research

Jackson spearheaded DA research during his graduate days in the mid-90s in the ophthalmology department of the University of Alabama at Birmingham. He was interested in why older adults had trouble with night vision, when their day vision was adequate.

“We found that older adults, many in fact, had normal retinal health through imaging by color stereo fundus photographs, but they had clinically abnormal dark adaptation, which meant terrible night vision. We couldn’t figure out why,” Jackson said.


Jackson and his colleagues began tracking these patients and discovering that 3 or 4 years later they would develop AMD.

He then began working with a colleague, Christine A. Curcio, PhD, at UAB, an expert in histopathology.

Curcio uncovered that as people age, deposits of cholesterol appear in the macula and are invisible to clinical imaging, he said.

“These deposits build up in the back of the eye and slow vitamin A in getting to the outer retina,” Jackson said.

Even before one has enough drusen for clinical detection, a patient can have a localized vitamin A deficiency in the outer retina. The first thing that happens is that night vision is impaired, he said.

Through DA, early AMD is identifiable up to 3 years earlier than using OCT or fundus photography, he said.

When dark adaptation is impaired, the retinal pigment epithelium is sick, creating sub-drusenoid deposits, which impairs the retinoid cycle, which slows DA, Jackson explained.

“So knowing that we have this very large impairment, knowing the why – we could put everything together,” he said.

In 2004, he set off on a mission to create a practical test to determine a patient’s DA. After spending 10 years refining the test, improving accuracy and testing for repeatability, AdaptDx was commercially available as of April 2014.

How it works

The test is simple to conduct, Jackson said, similar in operation to visual field testing and resembling it in size and complexity.

The device measures how fast a patient can go from day to night vision by measuring the speed of that adjustment, Jackson explained.

Greg Jackson

When the patient sits in front of the instrument he or she sees a single flash that is similar to the intensity of a cell phone camera flash and located outside the fovea so it is nonirritating, he said. The flash brings everyone to the same daylight retinal illumination.

After the flash, a stimulus light appears, and the patient pushes a button every time he or she sees the light, Jackson continued. The light gets progressively dimmer, and when a patient misses a stimulus, the light gets brighter. A rest break occurs in between each threshold measurement.

The AdaptDx interprets the data and calculates the rod intercept, Jackson explained. The faster the eyes adapt from light to dark, the better. If the testing takes more than 6.5 minutes, a patient is considered to have abnormal DA.

“Typically, measuring rod vision requires that a patient sit in the dark for 20 or 30 minutes before the test. AdaptDx doesn’t have that requirement,” Jackson said.

The test has 90% sensitivity and specificity, he said.

“The problem we face with AMD is that patients are not being diagnosed until they already have lost visual acuity,” Jackson added.

If a person develops choroidal neovascularization that is left to progress for 6 months, he or she loses an average of five lines of visual acuity, he said. If this patient was tested with AdaptDx and the abnormal DA was identified, those five lines of visual acuity could be saved.

“In 78% of patients that receive their first anti-VEGF injection, they are 20/50 or worse in the first affected eye. In nearly 40% that first eye is 20/200 or worse – so these patients have had the disease for years and were unaware,” Jackson explained, based on his research with colleagues.

Optometrists need to be aware when patients have early disease markers, and patients need to be aware of the disease to enhance compliance, he said.

“If we did just that, it would dramatically improve patient outcomes,” Jackson said.

Dierker agrees that practitioners should keep patient education at the forefront.

“Right now, we should be focusing on what we can do, like patient education and slowing vision loss. We should be telling our patients that they have risk for vision loss and identifying the risk at the earliest stages,” he said.


Biomarker for disease

The findings from a 2016 Ophthalmology (ALSTAR) study by Owsley and colleagues are some of the most well-known and cited on the topic of dark adaptation. Researchers found 62 participants with abnormal rod-intercepts from 325 adults 60 years and older. Those with abnormal rod-incepts, or delayed DA, were found to be twice as likely to show signs of AMD at follow-up, 3 years later.

“I think it’s quite significant with the results of the ALSTAR study that impaired dark adaptation has emerged as a biomarker and probably the first of its kind,” Semes said. “I like to think of it as a crystal ball.”

“Delayed rod-mediated DA in older adults with normal macular health is associated with incident early AMD 3 years later, and thus is a functional biomarker for early disease,” Owsley wrote. “The biological relevance of this test is high, because it assesses translocation of vitamin A derivatives across the retinal pigment epithelium and Bruch’s membrane, two tissues with prominent age- and AMD-related pathology,” she continued.

Historically, choroidal neovascularization in the second eye is avoided because the patient is already in the system and being observed, so it is found much quicker, Jackson said.

“We need to bring that awareness to the first eye,” he added.

“Patients come in complaining about their night vision, but their day vision is unaffected,” he continued. “They look normal, the cataract isn’t mature. You can now explain what the issue is; now we can find the reason.”

Prevention is more and more important, Jackson said, because an increased incidence of geographic atrophy is seen in patients on long-term anti-VEGFs.

“We can’t simply put patients on anti-VEGF therapy and maintain high visual function,” he said.

Renewed focus on AMD diagnosis, treatment

The first step is to evaluate the severity of the disease and put the patient on an appropriate visit schedule, Jackson explained. The disease will be monitored in the follow-up visits, and prompt anti-VEGF therapy can begin when indicated. The second step is to institute proper prevention strategies to lessen the chance of progression.

Damon Dierker

Dierker screens patients older than 50 years, those with a family history of AMD, cardiovascular disease and a history of smoking even if they have a normal macula. If they fail the screening test and have DA impairment, which likely represents subclinical macular degeneration, he intervenes with dietary recommendations, such as green, leafy vegetables and omega-3s (a minimum of 1,000 mg of EPA and DHA in triglyceride form), smoking cessation and nutritional supplements, he said.

He noted that he has not had the technology long enough to determine whether DA improves after intervention.

Patients could also simply have a few benign, age-related drusen and not be at risk for future vision loss, Dierker continued.

“The test helps sort through these patients, where early diagnosis can sometimes be difficult,” he said.

“We are thinking preventively in diabetes and glaucoma, but we need a renewed focus at the primary care level of macular degeneration,” Jackson added. “These patients are in OD practices, and many are unidentified.

“Routinely, even in practices that are sensitive to AMD, when they adopt our technology they find 20% to 30% of newly discovered AMD and subclinical AMD,” he continued. “Doctors are stunned when they find patients that they think are normal and realize they have this problem. They are very grateful for the technology.”

Corbin said he was surprised with how many of his patients had abnormal DA with no other clinical signs of AMD. And he was pleased with the repeatability of the test, which reinforced its accuracy.

“Some patients have a big difference between each of their eyes, so they would come back for a repeat test, and that difference would be consistent,” he explained.


Corbin said a normal DA test also eases the concern for patients who have drusen deposits. The normal test result indicates that the drusen is nonpathologic and they do not have AMD. In those with macular degeneration, the test alerts him to be more aggressive in properly managing those patients according to the current guidelines.

The process can also encourage patient compliance.

“Sometimes if you see things are changing within the eye or a patient’s vision, they are more willing to be compliant with our recommendations,” Dierker said.

Also, the financial return on the device was fairly quick, according to Corbin.

“There are some technologies where the reimbursement is so low, you’ll never see a return,” he explained. He says the average busy practice can receive a good return on the investment.

Corbin said he uses procedure code 92284 for dark adaptometry, which reimburses his practice $61 per test, unilateral or bilateral.

“We use diagnosis codes (ICD-10) for retinal drusen, macular degeneration, night blindness or abnormal dark adaptation, which is diagnosed when a patient undergoes a screening and fails, requiring a full DA test protocol,” he said.

“When a patient has abnormal dark adaptation, I’m going to see that patient twice a year with OCT testing, photography and electrodiagnostic imaging and start them on AREDS2 supplements. I’ll be counseling them on smoking cessation and diet and monitoring them more frequently,” Corbin continued.

Leo P. Semes

In the future, Semes anticipates a lower age threshold for routine AMD screening, with more research.

“If we looked at 40- to 50-year-olds with risk factors such as family history, occupational or recreational exposure to sunlight (especially if unprotected) or cigarette smoking, and impaired DA was demonstrated, we could consider interventions such as smoking cessation, protection from light exposure and dietary supplements,” he said.

“We are still working out how to use it to monitor disease,” Dierker added. “Some patients’ DA will get worse and their acuity and fundus exam will be unchanged. We are still working on those protocols. In general, we are testing DA every 6 to 12 months to monitor patients to determine whether or not they are getting worse.”

Future research

The National Eye Institute is currently recruiting participants for a 5-year clinical trial to evaluate the effectiveness of using a dark adaptation protocol to identify and monitor early to middle dry AMD. The principal investigator is Catherine A. Cukras, MD.

Ocular Surgery News reported on Cukras’ research at the Angiogenesis, Exudation and Degeneration meeting in February 2015.

“We can see that there’s an increase in average rod intercept time that increases monotonically with increasing AMD severity, with the eyes with reticular pseudodrusen having the highest mean rod intercept time,” she said.

Jackson cited research from Mark Pyfer, MD, at Wills Eye Hospital in Philadelphia, who is using DA to help determine which intraocular lens to place in cataract patients.

Others are looking at the effect of nutritional intervention on AMD and outcomes on DA, Jackson explained. Also, researchers are testing the effectiveness of next generation therapeutics with DA.

Earlier screening for AMD could be in the near future, with evolving guidelines in the next 5 to 10 years likely, according to Semes.

“We typically start screening clinically at age 50, which has been the traditional clinical cutoff and was the threshold for inclusion in the AREDS studies. With this new information, we may be lowering that age threshold.”

Semes is taking part in research studying DA in adults younger than 50 years, which could help shape future AMD screening guidelines.

Jackson suggests that his test is the “canary in the coal mine” for AMD.

“If the doctor and patient are unaware of the disease, the opportunities are missed to prevent vision loss,” he said. – by Abigail Sutton

Disclosures: Corbin is a speaker for MacuLogix. Dierker is on the speaker panel for MacuLogix and has served as an advisory board member for Genentech. Jackson is the cofounder and chief scientific officer of MacuLogix and invented the technology while at UAB. Semes is an advisor or on the speakers bureau for Alcon, Allergan, Bausch + Lomb, Genentech, MacuLogix, OptoVue, Shire and ZeaVision. He is a stock holder with HPO.