I follow The Massachusetts Eye and Ear Infirmary (MEEI) on Twitter, and late last month I noticed a message looking for candidates to participate in a trial using the Apeliotus AdaptDx to detect the early stages of AMD. This was the first I had heard about either this company or the device, and my natural curiosity compelled me to look further into both.
All I could find online was a document from 2008, describing the startup of this company out of Atlanta. I did not know the president, John Edwards, but I was quite familiar with one of the company’s advisors, Steve Martin (former CEO of CibaVision). So, I reached out to both and John agreed that I was one of the good guys, and that he could work with me to bring this writeup, about what he and his company were doing, to you.
History of the Company
This is the story of how an entrepreneur started a company, Apeliotus Technologies, with the express goal to seek out medical technologies residing within universities in the South East, for evaluation towards the possibility of licensing them for possible commercialization.
John Edwards, previously on the management teams of three successful university spin-off companies, started Apeliotus in 2003, to address the “development gap” that exists between academic innovations from research universities in the South East. His idea is to spend between three to five years and up to $3 million validating both the technology and its potential market value, and if he finds a technology meeting his criteria, launch a dedicated spin-off venture for commercialization or licensing to an established industry company or partner.
That is how he came across the technology under development by Dr. Gregory Jackson, then at the University of Alabama at Birmingham (UAB). Dr. Jackson is a psychophysicist specializing in vision and the effects of aging on vision. He stumbled upon the concept that some seniors had good dark adaptation – the quick response from, for example being blinded by a camera’s flash (photobleaching) and then re-adapting to seeing normally again, while some seniors took a much longer time to re-adapt. In fact, he found an anomaly in those seniors who had the early and later stages of age-related macular degeneration and those who did not.
Seniors with AMD had much slower re-adaption times than seniors who did not show signs of AMD.
Edwards & Jackson licensed the ideas and intellectual property from UAB in March 2004, and started the spin-off company Apeliotus Vision Science. (With Dr. Jackson moving to Pennsylvania State University in 2008, the company is now headquartered in Hershey, PA.)
The company has applied for and won three Small Business Innovation Research (SBIR) grants and three Foundation Grants amounting to about $1.5 million, in order to fund the building of prototypes of its AdaptDx diagnostic devices, and to run the clinical trials necessary to gain FDA approval of the device. An additional $1 million in venture capital funds has been obtained from Life Sciences Greenhouse and Ben Franklin Technology Partners.
The company has applied for a 510(k) as a Class I device, based on its initial clinical trials on a small number of patients, and expects to receive that approval by the end of this year or early in 2011.
An additional clinical trial of up to 200 people, for final validation, is currently underway at three independent sites including Mass Eye & Ear Institute in Boston; the Wilmer Eye Institute at Johns Hopkins University in Baltimore; and at the Hershey Eye Center at Penn State University in Hershey. Results are expected to be available by the second half of next year. If the results follow those obtained to date – with 90% sensitivity and 100% specificity, the company hopes to begin marketing its AdaptDx diagnostic device during next year's fourth quarter.
Blindness due to the onset of age-related macular degeneration (AMD) is the leading visual problem among those over the age of 65 in the United States and the world. It affects over 30 million people worldwide, including one in six over age 65 and one in three over age 75. In the U.S., there are currently over 18 million people with the disease. Fortunately, only about 10% are afflicted with the “wet” form, which causes blindness, while about 90% have the “dry” form, which is generally a precursor to the wet form. However, as shown in the accompanying table, about 8 million people in the U.S. have intermediate dry AMD, and 15%-20% of them will progress into wet AMD within about 5 years. In 2007, it was estimated by Market Scope, based on NEI/NIH data, that 1.4 million Americans had advanced wet AMD (CNV or choroidal neovascularization) and, without intervention and treatment, could lose significant vision or become blind. With the aging of the population and people living longer, these numbers will only increase.
Unfortunately, there is no effective diagnostic for the early detection of the dry form of AMD to allow intervention before the conversion to the wet form of the disease and the onset of significant vision loss.
A Possible Solution
Apeliotus Vision Science has developed a simple diagnostic device for the detection of the early to advanced stages of dry age-related macular degeneration. It is called the AdaptDx.
A commercial prototype of the AdaptDx is shown in Figure 1. It is based on a functional test of dark adaptation (the transition from being light-adapted to being dark-adapted). Specifically, the AdaptDx measures the rate of recovery of scotopic sensitivity, or dark vision, after photobleaching. Patients are exposed to a standard camera flash and then asked to indicate when they can detect a progressively dimmer spot of light presented as a randomly timed flash at the edge of the macula. Testing is completely non-invasive, and can be performed by an unskilled operator in ≤ 10 minutes with a minimum of patient burden.
Physiological Basis of AMD
AMD is related to a breakdown of the retinal pigment epithelium (RPE)/Bruch’s membrane complex in the retina, and measurement of dark adaptation is essentially a bioassay of the health of this membrane complex. During the AMD disease course, the RPE/Bruch’s function deteriorates, hampering nutrient and oxygen transport to the photoreceptors. As a side effect, the photoreceptors exhibit impaired dark adaptation because they require these nutrients for replenishment of photopigments and clearance of opsin, a group of light sensitive proteins found in the photoreceptors -- to regain dark vision sensitivity after light exposure. Consequently, impaired dark adaptation is a hallmark of early AMD.
Figure 2 compares recovery of dark vision following photobleaching for a normal older adult, an early-stage AMD patient and a late-stage AMD patient. The time for recovery to a benchmark sensitivity (the “rod intercept”) is used as a diagnostic parameter. There is a marked deterioration of dark adaptation speed as the disease progresses. Indeed, studies at UAB have shown that dark adaptation is impaired up to four years before AMD is clinically evident.
Proof-of-concept for the AdaptDx has been validated in replicate studies at University of Alabama at Birmingham (UAB) and Penn State University (PSU). The UAB study (N=26) compared two cohorts of old adults: 17 having early-to-late AMD and 9 having normal retinas (as determined by fundus photography grading). Diagnostic sensitivity and specificity were 88% (two false negatives) and 100% (no false positives). The effect size was extremely large, with mean recovery time for AMD patients twice that of normal older adults. Furthermore, the degree of impairment tracked disease severity. The PSU study (N=47) compared 33 AMD patients with 14 normal older adults. Diagnostic sensitivity and specificity were 91% (three false negatives) and 100% (no false positives), and mean recovery time for AMD patients was again twice that of normal old adults. In a separate study of 40 normal adults and AMD patients, test-retest reliability was shown to be very high (intraclass correlation of 0.95). As previously noted, a final validation study is ongoing at MEEI, Johns Hopkins, and PSU. It is comparing 140 patients having early-to-advanced AMD with 60 normal older adults. The study is scheduled to be completed by the end of 2010.
The AdaptDx has tremendous potential as a tool for AMD screening by optometrists and ophthalmologists. Glaucoma screening, which is routine practice, provides a direct precedent. Visual field testing using instruments such as the Humphrey perimeter is the standard for glaucoma screening. Although dark adaptometers and visual field perimeters measure completely different disease states, they are very similar in size, operation and cost. Both are psychophysical tests. Both take between 5 and 20 minutes depending on whether an initial screening test (for baseline evaluation) or a full diagnostic analysis is being performed. Both have reimbursements between $60 and $80 per test. The only difference is that, unlike glaucoma, everyone over age 50 years of age is at risk for AMD. Consequently, there is a larger need for AMD screening.
Early identification of dry AMD enables a growing array of options to delay or limit vision loss. First, the Age-Related Eye Disease Study (AREDS) demonstrated that anti-oxidant supplements such as Ocuvite PerserVision (Bausch & Lomb) and I-CAPS (Alcon Labs) can delay or even halt the progression from dry AMD, where vision loss is minimal, to wet AMD, where vision loss is severe.
Second, Lucentis and Avastin (Genentech) are FDA-approved drugs that can halt – and in some cases reverse -- the vision loss associated with wet AMD, if caught in its very early stages. However, there is a direct correlation between the effectiveness of these drugs and beginning treatment as soon as possible after conversion from dry to wet AMD. Identification of AMD while it is still in the mid to late dry stage will allow physicians to monitor progression toward wet AMD and begin treatment with Lucentis or Avastin at the earliest possible time.
Editors Note: I have done an extensive writeup on another device that can be used by patients in the advanced stages of dry AMD to monitor their progression to the very earliest stages of the wet form of the disease. This device, produced by Notal Vision , can be prescribed by a retinal physician to be used at home by the patient in the advanced stage of dry AMD. If used as directed (three times a week), it will detect the changeover and send a warning to a call center that then informs the patient’s doctor to call him/her into his office for treatment with one of the anti-VEGF drugs (Lucentis or Avastin) to ward off significant vision loss before it can occur. This device would be a perfect compliment to the AdaptDx.)
Finally, there are at least a dozen therapeutics in development for direct treatment of dry AMD, including fenretinide (Sirion Therapeutics), OT-551 (Othera Pharmaceuticals), compstatin/POT-4 (Potentia Pharmaceuticals), ACU-4429 (Acucela) and anti-CFH (Optherion). Apeliotus Vision Science is collaborating with several of these companies on the use of dark adaption to identify likely responders and track treatment progress.
(Editors Note: I have also posted a complete look at all of the new drugs under development for treating the dry form of AMD. Please see AMD Update 6 .)
The Centers for Medicare and Medicaid Services (CMS) and private insurers such as BlueCross/BlueShield already offer generous reimbursements for dark adaptation testing (CPT Code 92284). For example, the 2008 CMS reimbursement for dark adaptation (w/interpretation and report) was $69 in Atlanta, GA. This compares with $79 for fundus photography (w/interpretation and report) and $67 for an intermediate visual field examination. Based on the similar operating and cost characteristics for glaucoma screening via visual field examination (which is a profit center in optometry and general ophthalmology practices), AMD screening via dark adaptation should also be commercially attractive.
However, even without reimbursement there are compelling patient care and economic incentives for dark adaptation testing.
1. Elevated Examination – Patients with a documented eye condition merit greater scrutiny during an office visit and more frequent office visits. Routine screening of all patients over age 50 would identify a significant number of individuals with otherwise undetected dry AMD. These patients would then be eligible for comprehensive examinations vs. the basic examinations that would otherwise be given (and eligible for the commensurately higher reimbursement). Furthermore, they could be encouraged to schedule semi-annual visits to monitor their condition rather than the annual or even less frequent visits that might be appropriate in the absence of an AMD diagnosis.
2. Patient Recruitment – Unfortunately, most people only visit an optometrist or ophthalmologist when they are in need of a new eye glass prescription or they have a dramatic change in vision. In regions with a large number of senior citizens, almost all of whom either know or have heard about someone with AMD, offering free AMD screening would be a strong inducement for individuals to schedule an office visit and result in physicians building larger practices.
With the aging of the population, as the average person lives to an older age, the need for screening and detecting AMD, a normal aging occurrence, before it can cause significant vision loss becomes an ever important function for the medical community.
The development and marketing of a device such as the AdaptDx by Apeliotus Vision Science appears to be on track for accomplishing such a function. It, along with the device from Notal Vision, can become important diagnostic tools in the armamentarium of ophthalmic practitioners.
For further information about Apeliotus (and some of the other innovations they are pursuing) or about Apeliotus Vision Science and its AdaptDx, John Edwards can be contacted in Atlanta at email@example.com or by phone at (404) 875 9561. Dr. Gregory Jackson can be reached at Apeliotus Vision Science in Hersehy, PA at firstname.lastname@example.org , or (917) 531-6774.