Why timing is everything in AMD

April 7, 2020



Anti-vascular endothelial growth factor (VEGF) treatment has undoubtedly revolutionized how ophthalmologists manage patients with wet age-related macular degeneration (AMD). Unfortunately, after more than a decade of the current anti-VEGF monotherapy treatment paradigm, we have plateaued.

Why have we leveled out? More importantly, how do we break through the plateau?

It's simple: Detect wet AMD earlier, before patients lose several lines of vision.  As physicians, we intuitively know that patients have better outcomes if we detect disease in its earliest stages. We know that the longer the disease goes undetected and undiagnosed, the larger the lesion will be and that more letters will be lost.

Multiple studies, including randomized clinical trials, have demonstrated that lesion size and visual acuity at the time of wet AMD diagnosis are two of the best predictors of visual outcomes following anti-VEGF treatments.1,2

Given what we know and what has been studied, early detection of wet AMD is an urgent matter that requires our focus. Our goal should not be the number of letters gained. Our goal should be maintaining functional vision in a higher proportion of our patients.  Gaining 2 or 3 lines is irrelevant if the patient is still unable to have functional independence-the ability to drive, read, watch television, see their grandkids-because this is the outcome that matters most to our patients.

What the numbers tell us

Decreasing the time between onset of disease and initiating anti-VEGF treatment the key to improving outcomes and maintaining functional vision. However, the reality is that too many patients are diagnosed late with poor baseline vision.

One analysis suggested that patients have wet AMD for 7.7 months prior to being treated with anti-VEGF monotherapy.3 The negative impact to visual acuity is devastating. Additionally. real-world data and clinical trials showed us that few newly diagnosed eyes were detected when visual acuity was 20/40 or better.

The AAO IRIS Registry (Intelligent Research in Sight) retrospective cohort study of more than 150,000 patients with neovascular AMD included nearly five years of data (January 2013 to June 2017). The study included eyes with a diagnosis of wet AMD (as designated by the first anti-VEGF injection) and a second anti-VEGF intravitreal injection in the study eye less than 45 days from the first. Eyes receiving anti-VEGF injections prior to the diagnosis of wet AMD were excluded.

The IRIS study reaffirms an alarming statistic-only a small percentage (34%) have vision of 20/40 or better when initiating anti-VEGF therapy.4 The mean visual acuity at diagnosis was 20/83, far from functional. Even under the careful management of a treating physician, the second eye fared only slightly better with a mean visual acuity of 20/79. Intermediate AMD often escapes detection until functional vision is lost.

The physician's role

Our current standard of care includes the Amsler grid, a self-administered and subjective vision test. This is an outdated and antiquated method yielding unreliable results.
We are capable of better and equipped with telemonitoring technologies to provide us with highly effective way to detect wet AMD earlier. Conducting a highly sensitive, objective test in the convenience of a patient's home is a reasonable and necessary option to preserve vision. Simply put, telemonitoring offers at-risk patients a viable alternative to daily office visits.

Several technologies currently exist. Mobile visual technology such as the FDA-cleared Paxos (DigiSight Technologies) and mVT App (Vital Art and Science LLC) offer a visual monitoring solution, and the ForeseeHome (Notal Vision) testing device has definitively proven efficacy in early disease detection.

The AREDS2 HOME Study compared outcomes between patients using the Amsler grid and the ForeseeHome device and Amsler grid. Ninety-four percent who converted to wet AMD maintained ≥20/40 compared with 64% of patients using other methods.5 The disparity in outcomes between ForeseeHome and the current standard of care was so significant that the Data Safety and Monitoring Committee terminated the study early so that all patients could have access to this sight-preserving technology. The ForeseeHome device is covered by Medicare for patients with 20/60 or better visual acuity and intermediate dry AMD.

What patients do we need to monitor more closely?

A simplified risk scoring system was developed by the AREDS Research Group that assigns one risk factor for the presence of one or more large drusen and one risk factor for the presence of any pigment abnormality. The risk factors are then summed across both eyes.6 Three risk factors represent a 25% risk of developing advanced AMD over five years, and four risk factors jumps to a 50% risk. Given, that these patients are at high risk for progressing to wet AMD, our immediate objective should be to monitor these patients more closely, with objective monitoring technologies.

For the sake of simplicity, the patients to whom you recommend an AREDS2-formulated vitamin are most likely candidates for intensive home monitoring. Many of these patients are Medicare patients and fortunately for them, ForeseeHome is covered as long as the patient has intermediate AMD and best-corrected visual acuity of 20/60 or better.  

Breaking through the plateau

Early detection and decreasing the time between detection, diagnosis, and treatment is critical to preserving independence and quality of life for our patients at risk for wet AMD. We know that patients who start with better vision have the best outcomes, and conversely, patients who start with poor vision end up with poor outcomes. As doctors, we can dramatically improve visual outcomes by identifying high-risk intermediate AMD patients and ensuring that they use an effective telemonitoring system. The difference can be life changing.

References:

1. Ying GS, Huang J,Maguire MG, et al; Comparison of Age-related Macular Degeneration Treatments Trials Research Group. Baseline predictors for one-year visual outcomes with ranibizumab or bevacizumab for neovascular age-related macular degeneration. Ophthalmology. 2013;120:122-129.
 2. Ying GS, Maguire MG, Daniel E, et al; Comparison of Age-Related Macular Degeneration Treatments Trials (CATT) Research Group. Association of baseline characteristics and early vision response with 2-year vision outcomes in the Comparison of AMD Treatment Trials (CATT). Ophthalmology. 2015;122:2523-2531.e1.
3. 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;131:335-340.
4. Rao P, Lum F, Wood K, Salman C, Burugapalli B, Hall R, Singh S, Parke DW 2nd, Williams GA. Real-World Vision in Age-Related Macular Degeneration Patients Treated with Single Anti-VEGF Drug Type for 1 Year in the IRIS Registry. Ophthalmology. 2017 Nov 13. pii: S0161-6420(17)31946-2. 
5. AREDS2-Home Study Research Group. Randomized Trial of a Home Monitoring System for Early Detection of choroidal neovascularization home monitoring of the eye (HOME) study. Ophthalmology. 2014;121:535-544.
6. Age-related Eye Disease Study Research Group. A simplified severity scale for age-related macular degeneration. Arch Ophthalmol. 2005;123:1570-1574.