The ForeseeHome AMD Monitoring Program (Notal Vision) derives its ability to detect the progression of dry age-related macular degeneration (AMD) to wet AMD, often before patients experience symptoms, from a patented technology called preferential hyperacuity perimetry (PHP). PHP measures hyperacuity, also known as Vernier acuity. Like Snellen visual acuity, hyperacuity reflects the eye’s ability to see fine detail, but it is a much more sensitive test. Hyperacuity is a measure of the eye’s capability to perceive minute differences in the relative spatial location of two objects. Therefore, it is approximately 10 times more sensitive than Snellen visual acuity. In the fovea, hyperacuity ability is in the range of 3 to 6 seconds of arc, whereas Snellen visual acuity ability is in the range of 30 to 60 seconds of arc. In addition, Snellen acuity is age- and blur-dependent, while hyperacuity is not as affected by age and is insensitive to a certain degree of blur.

How Patients Monitor Their Vision at Home

The ForeseeHome AMD Monitoring Program can be prescribed for any patient who has intermediate AMD provided he or she has a Snellen visual acuity of 20/60 or better and the cognitive and physical ability to use the ForeseeHome AMD monitor. The monitor is a closed viewer that presents the PHP testing for one eye at a time. The test takes approximately 3 minutes per eye. The patient puts his or her head up to the viewer, and infrared sensors in the sides of the viewer ensure the test doesn’t begin until the head is correctly positioned.

During the test, a series of stimuli appear on the screen. Each stimulus is presented as a line consisting of dots. Most of the dots are arranged along a linear axis, but some are misaligned, creating a bump in the line (Figure 1). The patient uses a mouse to move a cursor and click on the bump. The patient sets the pace of the stimuli appearing. A new stimulus won’t appear until the patient moves the cursor back to a center dot. The dots and lines are artificial distortions that simulate the type of distortion caused by choroidal neovascularization (CNV). Where a pathologic distortion exists, one that’s caused by CNV, it competes with the artificial distortion. According to the principal of preferential selection, or preferential looking, the patient will choose one distortion over the other based on its size (Figure 2). Therefore, if CNV causes the patient to see a bump in a line that appears greater than the bump in the artificial distortion, the patient will click on the physiologic distortion. The size of the artificial distortions is tailored to the patient’s performance in the first test session. As a check, a line with no distortion occasionally appears.

Figure 1. Patients prescribed the ForeseeHome AMD Monitoring Program test their hyperacuity by clicking on the “wave” or “bump” they see in a series of visual stimuli.

Figure 2. Hyperacuity can be used to detect CNV because pathological visual distortions, such as those caused by CNV, will compete with the artificial visual distortions introduced by the test. Based on the principle of preferential looking, the patient perceives the greater of the two. Pathological > artificial = possible CNV. In this illustration: 1) when a large artificial distortion (AD) is presented away from a CNV lesion, the patient is expected to identify the AD; 2) when a large AD is presented over a CNV lesion, the patient is expected to identify the AD; 3) when a small AD is presented over a CNV lesion, the patient is expected to identify the pathological distortion.

Sample Test Report

A. Patient and Usage Information

B. Date Selector
Enables the physician to select a specific testing period to view

C. Eye Selector
Physician selects left or right to view a report for that eye

D. Test Score Graph
Represents how the patient’s test results compare to the normative database. The shaded green section represents the baseline calculation period. Each bar along the bottom of the graph represents a test (blue if the test was reliable, grey if the test was unreliable). The solid green line [1] that runs horizontally across the graph represents the threshold point relative to the normative database. If the height of the blue test bar is below the solid green line, the test results are within normal limits; if the height of the blue test bar is above the solid green line, the test results are outside normal limits. The P values at the left of the test score graph indicate the probability percentage of normal subjects who would be expected to have such results. Normal subjects are defined as those who do not have wet AMD.

E. Trend Score Graph
A built-in standard statistical tool, the Statistical Change Detector, calculates a trend score [2], which reflects changes from baseline behavior. If the trend score exceeds the test score change threshold [3], it means a statistically significant change, represented by a red dot [4], was identified.

F. Metamorphopsia and Scotoma Maps
These maps provide a graphic representation of metamorphopsia and scotoma associated with the test results and can be overlaid onto FA and OCT images to denote areas of AMD progression. The scales to the right of the maps indicate the corresponding extent of metamorphopsia and scotoma. It is common for normal eyes to have minimal amounts of metamorphopsia and scotoma and a minimal amount of variability over time.

Reports and Alerts of Vision Changes

Within the first few weeks a patient uses the ForeseeHome AMD monitor, a baseline reference score and map are generated. After each test, the results, which are compared to a normative database as well as the patient’s own baseline, are automatically sent to the Notal Vision Data Monitoring Center. Physicians receive monthly reports and can view patient data online at any time. (See “Sample Test Report,” above.) When a statistically significant change in test patterns is detected, the Data Monitoring Center alerts the prescribing physician’s clinic so a prompt examination for the patient can be scheduled. Alerts can be sent simultaneously to the patient if the physician consents. If the patient also receives the alert, he or she is asked to contact the prescribing physician as soon as possible.

I usually recommend that my ForeseeHome patients test themselves every other day, and I give permission for them to receive alerts. That way, if I am out of the office when a change in vision is detected, they can call to make an appointment to see one of my partners.

It is important to understand that one abnormal test result doesn’t trigger an alert. We are all very familiar with the fact that our patients’ vision may fluctuate even if they haven’t developed CNV. When we test Snellen visual acuity in the office, it may have dropped a line or even two lines due to an unrelated factor, such as how tired they are or a medication they’re taking. The same type of minor variability is common when patients test with ForeseeHome PHP, and the algorithm used accommodates for it. Therefore, it’s possible for a single test result to fall outside normal limits while the comprehensive results are still considered normal. A series of consecutive tests measuring outside normal limits is required before an alert is issued to signal statistically significant change.

Evaluation of PHP in the HOME Study

The Home Monitoring of the Eye (HOME) study, a collaborative effort put forth by the investigators in the AREDS2 trial, clearly showed that home monitoring with ForeseeHome PHP plus standard care is capable of detecting the conversion of dry to wet AMD earlier than standard care alone. An unprecedented number of patients for a medical device study — 1,520 at 44 centers — were enrolled. They were randomized to either using the PHP home monitoring device along with receiving standard care (763) or receiving standard care alone (757). The overall intent-to-treat (ITT) group was further categorized into two cohorts, per protocol 1 (PP1, patients using the device at time of CNV detection, regardless of adherence) and per protocol 2 (PP2, patients who met the minimum use criteria of two tests per week in the study eye before the CNV event). Standard care was defined by the investigator and may have included use of the Amsler grid. Inclusion criteria were one druse 125 µm or larger, Snellen visual acuity of 20/60 or better, and no CNV, scarring, or geographic atrophy in the study eye(s) at the outset of the trial. Mean baseline vision was 20/25, and mean age was 72. When the PHP triggered an alert or a patient reported metamorphopsia at a standard care scheduled office visit, best-corrected visual acuity was measured and biomicroscopy, OCT, and fluorescein angiography were performed. If the physician determined active CNV was present, the patient met the primary endpoint. The study’s primary outcome measure was change in visual acuity from baseline to the time of incident CNV.

Interestingly, as a result of earlier detection, CNV events accumulated faster in the PHP plus standard care group than they did in the standard care alone group. At 6 months, 51 CNV events occurred in the PHP plus standard care group vs. 31 in the standard care group. On the primary outcome measure, by the time CNV was detected in the standard care alone group, a median of nine letters of vision had been lost (Figure 3). The median vision lost by the time of CNV detection in the ITT, PP1 and PP2 groups was four letters, three letters, and three letters, respectively.

Figure 3. In the HOME study, by the time CNV was diagnosed in the standard care only group, a median nine letters of vision had been lost. The median number of letters lost in the PHP plus standard care groups was at least five letters less.

On a secondary outcome — proportion of patients who had maintained visual acuity of 20/40 or better at the time of CNV detection — monitoring with PHP also outperformed standard care. Only 62% of patients in the standard care group achieved this outcome vs. 87% in the ITT PHP group, 91% in the PHP PP1 group, and 94% in the PHP PP2 group (Figure 4). Additionally, lesions in the ForeseeHome arm were a mean of 0.23 disc area (DA) compared to a mean of 0.7 DA in the control arm, approximately 3 times smaller at CNV diagnosis for the ForeseeHome arm.

Figure 4. In the HOME study, significantly more patients who used PHP monitoring maintained visual acuity of 20/40 or better at the time of CNV detection compared with those who did not use PHP.

As we know, having vision as good as 20/40 when wet AMD is diagnosed is very important for patients. In multiple randomized clinical trials, including CATT,² patients who were 20/40 or better at diagnosis achieved better vision outcomes following anti-VEGF therapy than patients who started anti-VEGF therapy with visual acuity below 20/40. Maintaining 20/40 vision is also important to patients because they need that level of visual acuity to legally drive.

HOME also evaluated the sensitivity and specificity of self-monitoring with PHP as secondary outcomes. PHP was the modality that led to detection of CNV in the highest proportion of patients, and, as the device was used more often, the likelihood that it was the “first-to-alert” modality increased. The specificity of any new test is certainly important to us, because we don’t want to be dealing with large numbers of false positives. During the study, 79% of patients never had a false positive PHP test result. The annual rate of false alerts was 0.24 per year. In other words, we should expect that one false alert may occur in one patient over the course of 4.2 years of continual testing for that patient.

Confidence in Patient Self-monitoring with PHP

I suspect that the favorable results obtained in the HOME study aren’t surprising to those of us who treat patients with AMD. On one hand, we frequently see patients who are asymptomatic yet are found to have active CNV. When they’re diagnosed at an early stage, while their visual acuity is still good, they tend to respond well to treatment. On the other hand, we also see patients who report symptoms, such as metamorphopsia for “only a day or so,” but testing reveals advanced CNV, an indication that patients’ ability to perceive vision changes on their own isn’t very good.

In contrast, the ForeseeHome AMD Monitoring Program has proven to be very effective for early detection. In fact, enrollment for the HOME study was complete in November 2012, but by April 2013, the data and safety monitoring committee unanimously recommended early termination of the study because members were confident it had met its primary objective of demonstrating that eyes at high risk of progression to neovascular AMD can be identified with better levels of vision, i.e., earlier, when they’re detected by home monitoring with PHP compared with standard methods. ■

References

1. AREDS2-HOME Study Research Group, Chew EY, Clemons TE, Bressler SB, et al. Randomized trial of a home monitoring system for early detection of choroidal neovascularization - home monitoring of the eye (HOME) study. Ophthalmology. 2014;121(2):535-544.

2. Ying GS, Huang J, Maguire MG, et al. Baseline predictors for one-year visual outcomes with ranibizumab or bevacizumab for neovascular age-related macular degeneration. Ophthalmology. 2013;120(1):122-129.

Dr. Boyer is a senior partner with Retina-Vitreous Associates Medical Group in Beverly Hills, Calif. He is a consultant for Genentech, Notal Vision, and Regeneron.