Here, then, is that story.The Problem
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. 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 a precursor to the wet form. However, as shown in the accompanying table, about 9 million people in the U.S. have either intermediate or advanced dry AMD, and 15%-20% 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.
Table 1.– AMD Cases in the U.S. by Type and Stage in 2007, based on estimates by Market Scope, made from NEI and NIH data developed in 2000. Ophthalmic Market Perspectives
, Market Scope
, June 2008.A Possible Solution
As also noted in the table above, there are no
people in the early wet AMD classification. This is because the 220,000 or so people transitioning from the advanced dry state into the wet are not detected until their disease has progressed into the intermediate stage, with fairly large lesions in their retinas and significant visual acuity loss.
If the changes in retinal health of a patient at high risk of transitioning from advanced dry AMD into early wet AMD could be detected early enough and treated with current anti-VEGF drugs (Lucentis and/or Avastin), visual loss could be held to a minimum. This is the promise of this new device developed by Notal Vision.The Company and Its Products
Notal Vision was founded in Tel Aviv, Israel in 2000 by two ophthalmologists, Drs. Barak Azmon and Yair Alster. Along with other research scientists, they were determined to reduce vision loss associated with AMD. Working with leading experts in the field, this team of medical professionals and scientists developed a new technology for monitoring AMD. This new technology, the Forsee Preferential Hyperacuity Perimetry (PHP) visual field analyzer was developed and tested. In clinical trials conducted by the company, the Foresee PHP provided excellent detection of choroidal neovascularization (CNV), demonstrating 82% sensitivity and 88% specificity. The technology also has the potential to detect other visual distortion conditions due to macular disturbances, such as pigment epithelial detachment, histoplasmosis, epiretinal membranes and central serous retinopathy. The Forsee PHP obtained FDA 510 (k) marketing approval to detect the formation of drusen associated with dry AMD, and to monitor for the conversion into the wet stage of AMD in April 2005.
The clinically-based professional version of the PHP was sold to Reichert Ophthalmic Instruments in November 2009, so that the company could fully invest its time and resources in the home-based PHP device.
About 500 of the professional model Reichert PHPs are now providing eye care professionals around the world with valuable clinical data for monitoring patients with AMD, while the home-based device, the ForseeHome AMD Monitor has just received FDA marketing approval (December 2009) and is in the process of being launched commercially.
As noted below, the management team is composed of several ophthalmologists and other professionals with years of experience in the ophthalmic sales and marketing fields.The Management Team
Barak Azmon, MD – Co-founder and CEO. Dr. Azmon formerly worked at the Ophthalmology Department of the Tel Aviv Sourasky Medical Center. Prior to founding Notal he founded and managed an educational company.
Yair Alster, MD – Co-founder and Medical advisor to the company. Dr. Alster is the former head of the Ophthalmology Outpatient Clinic at the Tel Aviv Sourasky Medical Center, and has worked as a clinician and researcher in the field of retinal diseases.
John Moore, President – Mr. Moore has over 30 years of industry experience. He was formerly the CEO of Laser Diagnostic Technology (LDT), a $30 Million Ophthalmic Company which was acquired by Zeiss in October 2004. Prior to leading LDT Mr. Moore held senior positions in Alcon, $2.5 Billion Pharmaceutical corporation, Zeiss - $2 Billion multinational company with its primary business in optics, medical and semiconductor products, and Coherent, the largest U.S. Laser Manufacturer.
Gidi Benyamini, Executive VP – Prior to joining Notal VisionTM, Mr. Benyamini was VP of Engineering and Manufacturing at LaserComm, a telecommunications company based in Dallas, Texas. Prior to that he held various managerial positions at Scitex.
Garrett O’Connell, VP Sales and Marketing – Mr. O’Connell has over 19 years of management and sales experience in the eye care industry. Mr. O’Connell previously served as Director of Business Development with Sightpath Medical. Prior to that, he served as Director of Sales with Laser Diagnostic Technologies, Central Regional Manager with Optos, as well as past sales positions with Zeiss Humphrey, and Storz Instrument Co/Baush & Lomb Surgical. He holds a BS in Business Administration with a major in Marketing from St. Louis University .
Hadar Levy, VP Business Development and CFO -- Mr. Levy has over 13 years experience in accounting and finance. Prior to joining Notal Vision, Levy was the Finance Manager of GE Healthcare Technologies in Israel. Prior to that he spent several years in the US, working for Deloitte in both the medical and hi tech fields. He holds an MBA degree from the Faculty of law & Business Administration in BarIlan University and is also a CPA.
Muki Rapp, Ph.D. VP Research and Development -- Prior to joining Notal Vision, Dr. Rapp worked as a senior SW engineer in several start-up companies. He holds Ph.D. and M.Sc. in Neuroscience and B.Sc. in Computer Science from the Hebrew University of Jerusalem.
Miri Sani, VP of Clinical and Regulatory Affairs -- Prior to joining Notal Vision, Mrs. Sani worked in several Start-up companies in the cardiovascular and gynecological fields. She also worked as a regulatory and clinical consultant for Start-up Companies from the early stage to FDA and CE clearance.The Product
The ForeseeHome AMD Monitor is the first telemedicine ophthalmic device approved by the FDA for linking patients and doctors between eye exams, for ongoing monitoring of wet age-related macular degeneration. This telemedicine-based home monitoring system, based on the Forsee PHP technology, gives doctors access to valuable patient data through a secure online connection, allowing frequent and personalized monitoring of patients at risk of vision loss from the devastating effects of wet AMD.(Editors Note: Telemedicine or connected care is one of the “disruptive innovations” that are altering patient encounters in medicine, according to a recent article in Review of Ophthalmology, February 2010, pg 51.)
The personal home monitor is not intended to diagnose eye disease, but rather to track changes in the characterization of central and paracentral metamorphopsia (visual distortion) in patients with age-related macular degeneration, as an aid in monitoring progression of disease factors causing metamorphopsia including but not limited to choroidal neovascularization (CNV). It is intended to be used in the home environment for patients with stable fixation.
The appropriate type of patients for using this device are those diagnosed by their physician with intermediate or advanced dry AMD as defined by the Age related Eye Disease Study (AREDS)
, National Eye Institute.(1)
The Foresee Home device will not be useful in patients who have unstable fixation.
The effectiveness of the device has not been evaluated in AMD patients:
o Who have any co-existing retinal or choroidal disease
o Who have significant media opacity precluding a clear view of the macula
o Who have previous surgical or laser treatment within the macular area, or
o Who have a recent non-macular ocular surgery.Product Features:
The ForseeHome is designed to be user friendly, from unpacking and installation to test monitoring and usage. It uses a projection screen that is viewed through an un-occluded ocular. The patient uses a mouse pointer to identify the disturbance pattern projected in the viewer and guides the disturbance pattern back to a central fixation point, to initiate each subsequent presentation. The test takes three to four minutes per eye.Device in use at homeA typical test, showing the patient moving the test spot back to center.
After each test sequence, the results are automatically transmitted via a telephone linkage to a data monitoring center. The test results are evaluated by computers at the monitoring center and compared previous results (including a baseline initial test result). If a change is detected that surpasses the built-in algorithms, the monitoring center issues an urgent notification to the patient’s physician so that he/she can call in the patient for further examination and/or treatment.
The ForeseeHome collects data in three phases:(2)• Phase 1.
During the first several days of testing, the results are used to establish a baseline reading.• Phase 2.
Consistent retesting performance is used to statistically strengthen the baseline. If, however, there is a change in performance during this period (the next three weeks), the data-monitoring center will be alerted.• Phase 3.
The third phase is termed the “usage period.” During this ongoing phase, any statistically significant change in the pattern of the test results relative to the first two phases will generate an alert. Once the data-monitoring center is alerted, the clinic associated with the patient is notified so that an emergency follow-up visit can be scheduled with the treating clinician.The ForeseeHome Device
* Field tested ergonomics and human factors driven design
* Simple plug and play operation
* Automatic eye detection
* Closed hood and head sensors to control for ambient light and distance from display
* Mouse operatedThe ForeseeHome Test
* Built-in interactive self tutorial designed for elderly patients
* Short (~ 3 minutes per eye)
* Sensitive and specific test based on PHP technology
* Test reliability module
* Test performed by patient at least 3x per weekForeseeHome Analysis
* State-of-the-art machine learning classification techniques
* Establishment of a baseline pattern of tests
* Exclusion of patients unable to establish a baseline
* Spatiotemporal abnormality mapsForeseeHome Telemedicine
* Call center assistance with initial installation
* Call center intervention when compliance falls below requested minimum
* Privileged on-line access to patient's information according to role (eye care professional, data monitoring center, administrator, patient).
* Accessible web report that includes daily test results, trend analysis, spatial maps of interest, frequency of usageTest Results
The ForeseeHome has been evaluated in contrast to Amsler grid (AG) testing as a home monitoring device, and has demonstrated significantly greater sensitivity than the Amsler Grid among patients with CNV and intermediate AMD.
In a study that evaluated frequency of ForeseeHome usage,(3) 15 subjects with AMD were followed for seven months, and were told only to use the device at their convenience at home, as frequently as possible. The subjects elected to use the device an average of 3.7 ± 1.7 times/week. Half of the subjects were “organized,” using the ForeseeHome at regular intervals (4.9 ±1.4 times/week). The other half of the subjects tended to use the device more spontaneously (2.1± 0.8 times/week).5 Testing several times per week is recommended to monitor for early changes in vision, particularly in active CNV cases.
(The company now believes that patients should be instructed to use the device at a minimum of three times a week, and preferably at approximately the same time of day each time it is used.)
In a recent study(4) to evaluate the ability of the home device to discriminate between choroidal neovascularization (CNV) (wet stage) and non-neovascular (dry) intermediate age related macular degeneration (AMD) patients, the home device had good sensitivity and specificity in discriminating between newly diagnosed CNV and intermediate non-neovascular AMD patients. A secondary objective was to determine if sensitivity dependent on lesion characteristics.
In 66 CNV and 65 intermediate AMD eyes, sensitivity and specificity were both 0.85. In the retrospective part (34 CNV and 43 intermediate AMD), sensitivity and specificity were 0.85. In the prospective part (32 CNV and 22 intermediate AMD), sensitivity and specificity were 0.84 and 0.86 respectively.
This study concluded that the at-home device had good sensitivity and specificity in discriminating between newly diagnosed CNV and intermediate AMD patients. Sensitivity was not dependent on lesion characteristics.Commercial Development
With the recent FDA marketing approval, the company plans a controlled rollout over the coming months. Initially, Notal Vision will work with twenty large U.S. retinal specialist practices to identify those of its patients at high risk to convert from intermediate- or late-stage dry AMD into early-stage wet AMD. The physicians will write a prescription for the selected patients who, upon filling the Rx (and paying the up-front fee), will be mailed a device and instructions for its use. In this way, the company expects to have 300 to 400 devices in use by this summer.
Pricing has yet to be determined, but it is anticipated that there will be a one-time up-front payment and a monthly continuing fee. Part of the payments will go back to the referring physician.
It is yet unclear if Medicare or private insurance plans will pay for these diagnostic devices.(In the article on “disruptive innovations’ referred to above, in regards to telemedicine being used by Johns Hopkins for monitoring diabetic retinopathy, Dr. Zimmer-Galler, an associate professor, discussing the “reimbursement glitch” said, “We don’t really have specific codes that fall under teleophthalmology or ocular health, so it’s hard to get insurance companies and even Medicare to cover this.” However, he went on to say that professional organizations are working to develop new codes. The American Telemedicine Association, for one, has issued guidelines (for DR monitoring). And, other applications will not be far behind.)
In addition to the rollout described above, the company has been invited by the National Eye Institute (NEI/NIH), the sponsors of the AREDS2 clinical trial to provide 500 home devices, to be given to an ancillary cohort of patients participating in the trials. Half of 1000 patients will be given the Notal devices for evaluation, while the rest will be evaluated using the Amsler Grid.The Potential for the Product
This device meets an unmet need, that of detecting wet AMD in its very earliest stages, before significant vision loss has occurred.
By working with retinal physicians to identify those of their patients that are at high risk to transition from advanced stage dry AMD into early stage wet AMD, the company hopes to place its ForeseeHome monitor in the hands of those at-risk patients and track progression of the disease to detect the very earliest signs of CNV. In this way, the physician will be able to treat the patient’s disease before significant visual acuity has been lost and, hopefully, maintaining “good” vision.
Using the numbers from the table shown at the beginning of this writeup, the immediate market for the device is in the order of 800,000 people, give or take a few that cannot fixate. And, with about 200,000 people being diagnosed with AMD each year, as well as a portion of the intermediate dry AMD group that progress into the advanced stage, the potential for saving vision with this device is huge!
I also believe that this device will find use in both the intermediate and advanced wet AMD groups, to monitor progression of their disease between anti-VEGF treatments and between doctor appointments, to detect changes that should lead to an immediate doctor visit and/or treatment. Another very large group of potential users.References:
1. Age-Related Eye Disease Study Research Group. A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta caroteen, and zinc for age-related macular degeneration and vision loss: AREDS report no. 8. Arch Ophthalmol 2001; 119: 1417-1436.
2. Samantha Slotnik, OD. Portable and At-Home Tech for AMD – An Update on Portable and at-home diagnostic instruments that can be used to monitor the onset and progression of AMD. Review of Optometry, February 17, 2010.
3. Loewenstein A, Ferencz JR, Yeshurun I, et al. Comparison between the ForeseeHome perimeter and the Amsler gird, in patients with Age Related Macular Degeneration. Poster presented at American Society of Retinal Specialists (ASRS). Maui, Hawaii, October 11-15, 2008.
4. Loewenstein A, Ferencz JR, Lang Y, Yeshurun I, Pollack A, Siegal R, Lifshitz T, Karp J , Roth D, Bronner G, Brown J, Mansour S, Friedman S,Michels M,Johnston R, Rapp M, Havilio M, Rafaeli O, Manor Y. Towards earlier detection of CNV secondary to AMD: multicenter evaluation of a preferential hyperacuity perimeter designed as a home device . Retina. 2010, In press.Recommended For Further Reading:
1. Das R, Shi Y, Silvestri G, Chakravarthy U. Distortion maps from preferential hyperacuity perimetry are helpful in monitoring functional response to Lucentis therapy. Retina. 2009 29(7):1013-8.
2. Lowenstein A, Lang Y. Frequency of usage of the ForeseeHome, a home perimeter for early detection of choroidal neovascularization. European Society of Retinal Specialists, Nice, France: May 15, 2009.
3. Anderson C, Pahk P, Blaha GR, Spindel GP, Alster Y, Rafaeli O, Marx JL. Preferential Hyperacuity Perimetry to detect hydroxychloroquine retinal toxicity. Retina. 2009 29(8):1188-92.
4. Loewenstein A, Ferencz JR, Yeshurun I, et al. Comparison between the ForeseeHome perimeter and the Amsler gird, in patients with Age Related Macular Degeneration. Poster presented at American Society of Retinal Specialists (ASRS). Maui, Hawaii, October 11-15, 2008.
5. Loewenstein A. The significance of early detection of age-related macular degeneration: Richard & Hinda Rosenthal Foundation lecture, The Macula Society 29th annual meeting. Retina 2007;27:873-8.
6. Alster Y, Bressler NM, Bressler SB et al. Preferential Hyperacuity Perimeter (PreView PHP) for detecting choroidal neovascularization study. Ophthalmology 2005;112:1758-65.
7. Goldstein M, Loewenstein A, Barak A et al. Results of a multicenter clinical trial to evaluate the preferential hyperacuity perimeter for detection of age-related macular degeneration. Retina 2005;25:296-303.
8. Loewenstein A, Malach R, Goldstein M et al. Replacing the Amsler grid: a new method for monitoring patients with age-related macular degeneration. Ophthalmology 2003;110:966-70.