AMD Clinical Insights is a monthly e-newsletter that provides the optometrist with concise updates and valuable clinical information on age-related macular degeneration (AMD) that apply to everyday practice.

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September 2021

The Fellow Eye in nAMD

Patients with unilateral neovascular AMD (nAMD) have a significant risk for progression to macular neovascularization in the fellow (better) eye.1,2 (Figure 1). A recent real-world study found a significant rate of fellow eye conversion (from dry to nAMD) within a three-year window after onset of nAMD in the first eye.3 During this study, 38% of fellow eyes of 8,522 patients converted to nAMD. Median time to conversion in the second eye was 672 days.3
As discussed in the July issue of AMD Clinical Insights, the fellow eye should be monitored at frequent, regular intervals to detect signs of progression. Multiple studies have shown that the best predictor of final visual outcome in a nAMD diagnosis is the baseline acuity at presentation.4 Evidence from electronic medical record studies of patients with nAMD treated with anti-VEGF agents shows that second eyes with generally good visual acuity at diagnosis maintain better function over 3 years compared to first eyes that commenced treatment with (on average) lower levels of acuity.5
Several strategies are used to monitor for the onset of nAMD in the fellow eyes. When patients are followed in-office, VA, fundus examination and OCT/OCT-angiography are commonly used to monitor the fellow eye.6 Patients may be provided with an Amsler chart for self-testing in between visits. Visual change such as perceived distortion of the grid can signify the onset of nAMD. Unfortunately, self-reporting of change in visual function and Amsler testing have been shown to have poor sensitivity and only moderate specificity.7
While frequent monitoring of fellow eyes would be optimal, bringing a large, older population into clinics for evaluation of visual and anatomic changes can be difficult for both the patient and caregivers, particularly given current safety concerns related to the COVID-19 pandemic. One possible solution to address these difficulties is at-home self–monitoring using technology superior to Amsler testing. The AREDS2-HOME study8 evaluated one home self-monitoring strategy that included the ForeseeHome AMD monitoring system (Notal Vision, Inc., Manassas, VA, USA). 
The system uses preferential hyperacuity perimetry (PHP) to detect minute differences in the relative spatial localization of two or more objects. The AREDS2-HOME study randomized subjects to either a device arm that included the home monitoring system (in addition to standard care) or to a control arm that included standard care alone. The findings showed that a significantly higher percentage of patients were able to maintain a VA of 20/40 or better after using the strategy that included home monitoring to help identify conversion to nAMD in its early stages.8
In an effort to duplicate the AREDS2-HOME study results, investigators conducted a real-world performance evaluation of the same home telemonitoring system.9 In total, 8991 patients performed 3,200,999 tests at a frequency of 5.6 ± 3.2 times/week. The 306 eyes that converted from intermediate non-neovascular AMD to nAMD over the study period (a 2.7% annual rate) were included in the analyses. 
There was a median (interquartile range) change of −3.0 (0.0–(−10.0)) letters among converted eyes. 81% maintained a VA ≥ 20/40 at the time of conversion, while 69% of the conversion detections were triggered by system alerts. This real-world performance of an at-home testing strategy was similar to that reported for the device arm of the AREDS2-HOME study.9 The authors concluded that the home telemonitoring system can markedly increase early detection of conversion to nAMD. 
These clinical research findings suggest that the inclusion of the home monitoring program in an overall management strategy allows early detection of the majority of disease conversions, thereby providing an effective safety net for patient vision. There are some caveats. First, the system must be able to establish a reliable “negative” baseline PHP measurement. Secondly, the patient must commit to continuous, frequent use of the home device. Finally, upon the system’s detection of probable conversion, the patient must promptly be examined in-office to confirm the early presence of macular neovascularization. 
For many AMD patients, the disease can feel like a loss of control. An accurate method of home monitoring empowers both patient and provider.
Figure 1
Figure 1. An 81-year-old white male with bilateral glaucoma and unilateral nAMD (OS). The OD has intermediate dry AMD.
Key Clinical Takeaways
  • Fellow eyes of patients with unilateral neovascular AMD (nAMD) have a significant risk for progression to macular neovascularization. 
  • In studies of the efficacy of anti-VEGF agents, the best predictor of final visual outcome was baseline acuity at presentation. 
  • Patient self-reporting of change in visual function and Amsler testing have been shown to have poor sensitivity and only moderate specificity.
  • A home telemonitoring system can markedly increase early detection of conversion to nAMD.

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  1. Clemons TE, Milton RC, Klein R, et al. Age-Related Eye Disease Study Research Group. Risk factors for the incidence of Advanced Age- Related Macular Degeneration in the Age-Related Eye Disease Study (AREDS) AREDS report no. 19. Ophthalmology. 2005;112(4):533-9.
  2. Chakravarthy U, Bailey CC, Scanlon PH, McKibbin M, Khan RS, Mahmood S, Downey L, Dhingra N, Brand C, Brittain CJ, Willis JR, Venerus A, Muthutantri A, Cantrell RA. Progression from Early/Intermediate to Advanced Forms of Age-Related Macular Degeneration in a Large UK Cohort: Rates and Risk Factors. Ophthalmol Retina. 2020 Jul;4(7):662-672. doi: 10.1016/j.oret.2020.01.012. Epub 2020 Jan 25. PMID: 32144084.
  3. Starr M, Xu D, Patel LG, et al. Characteristics of Fellow Eye Conversion to Neovascular Age-Related Macular Degeneration in Patients with Unilateral Neovascular Disease. Presented during the ASRS 2020 Virtual Annual Meeting, July 24-26, 2020.
  4. Phan LT, Broadhead GK, Hong TH, Chang AA. Predictors of Visual Acuity After Treatment of Neovascular Age-Related Macular Degeneration - Current Perspectives. Clin Ophthalmol. 2021;15:3351-3367. Published 2021 Aug 11. doi:10.2147/OPTH.S205147
  5. Zarranz-Ventura J, Liew G, Johnston RL, et al. United Kingdom Age-Related Macular Degeneration Electronic Medical Records Users Group. The neovascular age-related macular degeneration database: report 2: incidence, management, and visual outcomes of second treated eyes. Ophthalmology. 2014;121(10):1966-75.
  6. Fletcher DC, Schuchard RA Visual function in patients with choroidal neovascularization resulting from age-related macular degeneration: the importance of looking beyond visual acuity. Optom Vis Sci. 2006; 83(3):178-89.
  7. Sivaprasad S, Banister K, Azuara-Blanco A, Goulao B, Cook JA, Hogg R, Scotland G, Heimann H, Lotery A, Ghanchi F, Gale R, Menon G, Downey L, Hopkins N, Scanlon P, Burton B, Ramsay C, Chakravarthy U, Diagnostic accuracy of monitoring tests of fellow eyes in patients with unilateral neovascular age related macular degeneration (EDNA study)., Ophthalmology (2021), doi:
  8. Alexander J Brucker, AREDS II -HOME STUDY; The Home Monitoring of the Eye (HOME) Study: Potential implication of Findings on Management of Intermediate AMD Patients. Invest Ophthalmol Vis Sci 2014;55(13):3067.
  9. Ho AC, Heier JS, Holekamp NM, et al. Real-World Performance of a Self-Operated Home Monitoring System for Early Detection of Neovascular Age-Related Macular Degeneration. J Clin Med. 2021;10(7):1355. Published 2021 Mar 25. doi:10.3390/jcm10071355
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