The ForeseeHome AMD Monitoring Program (Notal Vision) is the first ophthalmic FDA-cleared, home-based patient monitoring system to become available that is supported by robust clinical evidence. As shown in the AREDS2 The Home Monitoring of the Eye (HOME) study, ForeseeHome enables earlier detection of progression from dry age-related macular degeneration (AMD) to wet AMD by detecting changes in metamorphopsia.¹ When physicians prescribe the ForeseeHome program, intermediate AMD patients can self-test at home, allowing their physician to monitor the progression of their disease between office visits. It is recommended that patients test their vision with the preferential hyperacuity perimeter several times a week. Their test results are automatically sent to a data-monitoring center. When a statistically significant change in testing is detected, the doctor is notified so an office visit can be scheduled. In addition, the doctor receives monthly reports and can view patient data online at any time.

This is an important development for retina specialists and our patients because detecting wet AMD early gives us the opportunity to obtain the best treatment outcomes. We know this because analyses from landmark studies have identified baseline characteristics that predict vision outcomes. The two baseline characteristics associated most consistently with vision outcomes are visual acuity (VA) and size of the choroidal neovascularization (CNV) (Figure 1).

Figure 1. The two baseline characteristics associated most consistently with vision outcomes in wet AMD are visual acuity and size of the CNV lesion.

Consider, for example, the CATT study, which compared the effectiveness of Avastin (bevacizumab, Genentech) and Lucentis (ranibizumab, Genentech) for the treatment of wet AMD. As with most AMD studies, CATT used mean change in vision as an outcome measure.

When we look at the results of a cohort study within CATT,² we see, at 1 year, patients with 20/100 to 20/160 baseline VA gained an average of 11.9 letters, while patients with 20/25 to 20/40 baseline VA gained an average of 3.3 letters. The eyes that gained the most vision were the eyes that had worse VA at baseline. However, we know that a ceiling effect is at work. In other words, patients with poorer vision have more to gain; whereas, patients with better vision have less room for improvement. That said, it is important to understand that what this and other analyses show is that it is still baseline VA that determines the outcome, not in terms of mean vision change, but rather in terms of what level of vision patients ultimately achieve.

In the CATT cohort study, the average vision at 1 year among patients with worse baseline VA was 59 letters (20/63) compared with three lines better, 76 letters (20/32) among those with better baseline VA (Figure 2). As the CATT Study Group stated in its paper, “The detection of CNV before there is a large loss of vision remains important even in the era of highly effective treatment.”

Figure 2. A cohort study within CATT showed baseline VA to be a predictor of vision outcomes at 1 year, independent of mean vision change.

Lesion size is another baseline characteristic that has been shown in studies to predict vision outcomes in wet AMD. In the cohort study within CATT, patients who started the study with CNV lesions ≤1 disc area had mean VA of 20/40 at 1 year, while at the same point those with baseline CNV lesions >4 disc areas had mean VA of 20/50 or worse. Patients with smaller lesions, presumably younger lesions, ended up with better vision, suggesting that smaller lesions are predictive of better ultimate outcomes (Figure 3).

Figure 3. A cohort study within CATT showed baseline size of the CNV lesion to be a predictor of vision outcomes at 1 year.

What these two key baseline characteristics — visual acuity and lesion size — have in common is that they are both associated with early detection. The earlier we can detect the development of CNV, the more likely the lesion will be small and the visual acuity will be good, which gives patients the best chance of achieving good vision after treatment.

Room for Improvement in Early Detection

In addition to the link between vision outcomes and baseline lesion size and VA, the wealth of data we now have from AMD clinical trials has revealed other useful insights that point to a need to improve our rate of early detection. Contrary to what we might think, only a limited number of eyes with CNV are diagnosed early. Several studies^2-7 have illustrated this (Figure 4). For example, in one of the most recent studies, known as the Wills Eye treat and extend study, only 14% of patients with CNV were diagnosed when their VA was 20/40 or better.⁷

Figure 4. Studies show there is room for improvement in the early detection of CNV.

Studies have also shown that progression of AMD is unpredictable and patient-specific. For example, in reviewing the pathophysiology of AMD, Birch and Liang noted that we have no way to tell from the characteristics of dry AMD when it might progress to wet AMD.⁸ We all experience this in our practices. We see patients who have CNV as soon as 1 week after we last saw them, at which time there was no hint of it. Furthermore, while it is unusual today, studies in the past were more likely to include sham arms, which allowed analyses of disease progression in untreated eyes.

In a study by Vander and colleagues, based on consecutive fluorescein angiograms fewer than 120 days apart, the daily growth rate of subretinal neovascularization in eyes that had not been treated ranged from 0 to 74 microns.⁹ The authors also reported that it was not possible to reliably predict the growth rate, and slow growth in one eye did not preclude faster growth in the fellow eye. In another evaluation of untreated eyes, Liu and colleagues found the main determinant of CNV lesion enlargement to be the duration of exudative disease.¹⁰

In several other studies, researchers have come to the same conclusion regarding the interval between onset of wet AMD and treatment: the shorter, the better. Oliver-Fernandez and colleagues showed that delay in assessment and treatment of new-onset wet AMD was associated with a higher risk of visual loss.¹¹ In their prospective pilot study, the median time between initial diagnosis and referral assessment and treatment of patients who presented with newly diagnosed subfoveal CNV was 28 days. By that median time point, 44% of patients had experienced some degree of vision reduction. Among those 44%, 15% lost greater than three lines of distance VA.

Retrospectively, Rauch and colleagues evaluated whether the time between initial symptoms and treatment of wet AMD had an effect on vision outcomes. They assigned patients to one of three groups based on the duration of their visual symptoms prior to treatment (Group I: <1 month; Group II: 1 to 6 months; and Group III: >6 months). Duration of visual symptoms <1 month before treatment was associated with a better post-treatment visual outcome.¹²

Similarly, Canan and colleagues evaluated the effects of treatment with anti-VEGF therapy in patients with wet AMD. They found that shorter duration of disease, as measured by the subjective duration of visual symptoms, was associated with better visual outcomes after treatment.¹³

A Means for Achieving Earlier Detection of CNV

Taking this body of research into account, it is clear that earlier detection of the development of CNV in our AMD patients optimizes their visual outcomes. When diagnosed and treated early, patients maintain better visual acuity and, it follows, a better quality of life. Today, for the first time, we have a means that can help to achieve this goal. We can prescribe the ForeseeHome AMD Monitoring Program, which uses telemonitoring to alert us when changes in testing indicate a conversion from dry to wet AMD.

While patient tele-monitoring is new to ophthalmology, it is well established in other medical specialties. For example, patients who have sleep apnea or diabetes and those at risk for atrial fibrillation can use home-based technologies to monitor their conditions and stay connected to their doctors.

The ForeseeHome system puts our AMD patients on the same footing as the 78 million people around the world who by 2020 are expected to have more control over their health through the use of home-based medical technologies.¹⁴ ■

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.

3. Olsen TW, Feng X, Kasper TJ, Rath PP, Steuer ER. Fluorescein angiographic lesion type frequency in neovascular age-related macular degeneration. Ophthalmology. 2004;111(2):250-255.

4. Acharya N, Lois N, Townend J, Zaher S, Gallagher M, Gavin M. Socio-economic deprivation and visual acuity at presentation in exudative age-related macular degeneration. Br J Ophthalmol. 2009;93(5):627-629.

5. Fong DS, Custis P, Howes J, Hsu JW. Intravitreal bevacizumab and ranibizumab for age-related macular degeneration: a multicenter, retrospective study. Ophthalmology. 2010;117(2):298-302.

6. IVAN Study Investigators, Chakravarthy U, Harding SP, Rogers CA, et al. Ranibizumab versus bevacizumab to treat neovascular age-related macular degeneration: one-year findings from the IVAN randomized trial. Ophthalmology. 2012;119(7):1399-1411. [Erratum in Ophthalmology. 2012 Aug;119(8):1508 and Ophthalmology. 2013 Sep;120(9):1719.]

7. Shienbaum G, Gupta OP, Fecarotta C, Patel AH, Kaiser RS, Regillo CD. Bevacizumab for neovascular age-related macular degeneration using a treat-and-extend regimen: clinical and economic impact. Am J Ophthalmol. 2012;153(3):468-473.

8. Birch DG, Liang FQ. Age-related macular degeneration: a target for nanotechnology derived medicines. Int J Nanomedicine. 2007;2(1):65-77.

9. Vander JF, Morgan CM, Schatz H. Growth rate of subretinal neovascularization in age-related macular degeneration. Ophthalmology. 1989;96(9):1422-1426.

10. Liu TY, Shah AR, Del Priore LV. Progression of lesion size in untreated eyes with exudative age-related macular degeneration: a meta-analysis using Lineweaver-Burk plots. JAMA Ophthalmol. 2013;131(3):335-340.

11. Oliver-Fernandez A, Bakal J, Segal S, Shah GK, Dugar A, Sharma S. Progression of visual loss and time between initial assessment and treatment of wet age-related macular degeneration. Can J Ophthalmol. 2005;40(3):313-319.

12. Rauch R, Weingessel B, Maca SM, Vecsei-Marlovits PV. Time to first treatment: The significance of early treatment of exudative age-related macular degeneration. Retina. 2012;32(7):1260-1264.

13. Canan H, Sizmaz S, Altan-Yaycioglu R, Saritürk C, Yilmaz G. Visual outcome of intravitreal ranibizumab for exudative age-related macular degeneration: timing and prognosis. Clin Interv Aging. 2014;9:141-145.

14. Tractica. More than 78 million consumers will utilize home health technologies by 2020. Available at: https://www.tractica.com/newsroom/press-releases/more-than-78-million-consumers-will-utilize-home-health-technologies-by-2020/; last accessed Oct. 11, 2016.

Dr. Heier is co-president and director of retina research at Ophthalmic Consultants of Boston. He is a consultant for Genentech, Notal Vision, and Regeneron.