The next chapter of the anti-VEGF era in retina practice is that of extended-duration treatment, which allows patients and providers to increase the interval between anti-VEGF injections without sacrificing a treatment’s efficacy. Extended duration strategies initially manifested with the widespread adoption of treat-and-extend (TAE) dosing regimens, which have been shown in real-world patients to be effective at reducing treatment burden without sacrificing the efficacy of anti-VEGF agents.¹ Retina specialists were quick to adopt dosing regimens that are not fixed, and only 1% of retina specialists report using fixed dosing in patients with neovascular age-related macular degeneration (nAMD) regardless of disease response to therapy.² Still, anti-VEGF agents were not designed as extended-release or highly durable therapies, and a significant number of patients are unable to move beyond fixed monthly dosing.

Recent approvals by the US Food and Drug Administration of 2 new therapies that were specifically engineered to allow extended durations of treatment — the Port Delivery System with ranibizumab (Susvimo; Genentech) and faricimab (Vabysmo; Genentech/Roche) — give retina specialists new tools for reducing treatment burden in patients with nAMD. Interest in using these drugs appears to be enthusiastic. In 2022, 37% of retina specialists reported that they planned to implant Susvimo in 1% to 10% of their patients,³ and 64% of retina specialists said that faricimab’s most attractive quality was its enhanced durability.³

In the shadow of this progress, however, lives an uncomfortable truth: patients with unilateral nAMD whose fellow eyes are monitored for progression from intermediate AMD to nAMD during injection visits are at increased risk of experiencing undetected disease progression because more durable treatments lead to a reduced number of office visits. The timing of nAMD detection is key for this patient population. In a 2020 retrospective analysis of the IRIS Registry, Ho et al found that if anti-VEGF therapy for nAMD is initiated when a patient’s visual acuity (VA) is at least 20/40, then that patient is likely to maintain at least 20/40 vision after 1 and 2 years of treatment.⁴ Conversely, patients whose VA is worse than 20/40 at the time of first anti-VEGF treatment were significantly less likely to reach VA better than 20/40 at 1 or 2 years.⁴

Because fellow eyes’ visual function often determines the quality of life for patients with unilateral nAMD, preservation of vision in these eyes is of paramount importance. But how can patients enjoy the benefits of more durable therapies and TAE regimens without increasing the risk of undetected conversion to nAMD in their fellow eye? The answer is to use proven and reliable home-based monitoring to detect conversion from dry to nAMD. One method that has proven effective in a number of large-scale studies is the ForeseeHome AMD Monitoring Program (Notal Vision Monitoring Center).

PROTECTING PATIENTS’ FELLOW EYES WITH REMOTE MONITORING

Clinicians who wish to closely monitor progression to nAMD in patients with intermediate AMD may refer patients to the Notal Vision Monitoring Center for monitoring between office visits with the ForeseeHome program. The Medicare-covered program manages all aspects of the patient’s remote monitoring on behalf of the referring clinician, including verifying benefits and insurance, providing disease and program education, shipping the home-based device, and monitoring for compliance.

Patients are encouraged to test daily with the AI-enabled device. The monitoring center is notified if a patient’s routine home testing results have deviated from their baseline. Results are reviewed by in-house ophthalmologists before the provider’s office is alerted so they may determine the best course of action for the patient, which often includes a follow-up examination with diagnostic imaging to identify potential conversion to nAMD.

For now, many patients who have been implanted with Susvimo are still regularly appearing in the clinic for careful follow-up, regardless of whether a refill-exchange or a supplemental anti-VEGF injection are administered. As patients demonstrate consistent and predictable responses to Susvimo therapy, many retina specialists expect to see them less frequently. In the phase 3 ARCHWAY study, patients received refill-exchanges every 24 weeks. If this pattern proves to be similar to real-world practice, that means patients may only be examined in-office twice each year — a far drop-off from the 4-week to 12-week intervals patients were used to prior to Susvimo’s approval. Similarly, many faricimab patients complying with treatment recommendations will experience significantly fewer in-office visits each year thanks to the drug’s enhanced durability.

Use of ForeseeHome remote monitoring in these patient populations may enable clinicians to regularly monitor their patients’ fellow-eye status, thereby mitigating any concerns linked to fewer office visits. In doing so, clinicians allow patients to experience the benefits of the latest treatment options while reducing the secondary risks of those modalities.

THE LATEST DATA

As we learn more about risk assessment for fellow-eye conversion in patients with unilateral nAMD, and as we better understand the risks of late treatment in converted eyes, we can more deeply appreciate the value of regular monitoring. Data in the literature are useful in this regard.

The ALOFT study was a retrospective review of 3,334 eyes in 2,123 patients with bilateral dry AMD or unilateral nAMD with fellow-eye dry AMD who used the ForeseeHome monitoring service from 2010 to 2020.⁵ Eyes converted to nAMD at an annual rate of 2.72%. The real-world rates of detection in ALOFT were similar to those found in the HOME study, which was the randomized controlled trial that assessed the ForeseeHome device.^6,7 Data from ALOFT and HOME point to the clinical utility of ForeseeHome use: among patients who use the device, approximately half of patients who convert to nAMD from intermediate AMD had their disease detected by the device before a further drop in vision occurs.

Researchers in ALOFT theorized that eyes with intermediate AMD referencing fellow-eye nAMD would experience higher rates of detection via in-person examination given that these eyes were more likely to be examined during clinical visits. However, they found that the ratio of conversion detection via symptom-based or routine exams was not significantly different among eyes with or without fellow-eye nAMD, and that nearly half of patients with fellow-eye nAMD benefited from ForeseeHome device conversion detection.⁵ In short, a significant percentage of patients (47%) who underwent routine in-person evaluation still benefited from use of the ForeseeHome, underscoring the value of home monitoring.

Further analysis of the ALOFT data revealed that 29% of patients received a false positive (FP) alert from the ForeseeHome device in the 10-year study. Among those with FP alerts and fellow-eye nAMD, 22% reported eventual conversion in the eye that triggered the FP within 12 months and 43% within 24 months.⁸ The rate of eventual nAMD conversion in eyes with bilateral intermediate AMD and an FP alert was 6% and 10% with a 12-month and 24-month period, respectively. Compared to natural history data a ForeseeHome FP alert predicts a 2-fold higher risk of conversion.

In a sense, the term “false positive” in this instance is a misnomer, because the ForeseeHome AI algorithm may have in fact detected preclinical nAMD, nonexudative macular neovascularization (neMNV), or slight metamorphopsia secondary to RPE elevation, which puts the eye at an elevated risk of conversion. With that in mind, the term “nonexudative alert” may be more accurate. See the Sidebar for comment about billing and coding for patients whose visits are triggered by FPs.

Given that patients with nonexudative alerts on the ForeseeHome device may eventually progress from intermediate AMD to nAMD — particularly if they have fellow-eye nAMD — it may be prudent to flag these patients for more frequent office visits. Use of OCT angiography (OCTA) to characterize quiescent neovascularization (NV) has been published in the literature,^9,10 and OCTA may be a useful platform for evaluating patients with possible preclinical nAMD. Narita et al explained how OCTA and spectral-domain OCT may be used to detect shallow, irregular RPE elevation (SIRE) in patients with large drusen and concluded that eyes with SIRE signs were at increased risk of having subclinical nonexudative macular neovascularization (Table 1).¹¹

Patients with a high risk of conversion to exudative AMD as detected by ForeseeHome or imaging evaluation may be good candidates for enrollment in trials evaluating the safety and efficacy of prophylactic treatments for AMD. One such study, a phase 2 study evaluating iptacopan (LNP023; Novartis), has been recruiting patients with unilateral nAMD and fellow eyes (ie, study eyes) at risk for progression based on structural findings on OCT.¹²

KEEPING CLOSE WATCH OVER PATIENTS

For some retina specialists, it may have appeared that increased risk of undetected nAMD conversion in unilateral nAMD patients was the cost of using extended-duration treatments such as Susvimo or more durable therapies such as faricimab. As illustrated here, however, that is not the case as long as a patient is comanaged with a remote monitoring service provider and continues to undergo fellow-eye examinations whenever the patient visits the clinic. In the quest to keep a close watch over our patients, retina specialists can do patients the service of providing comfortable, affordable, and effective care by recommending a digital home monitoring program for conversion to nAMD. RP

REFERENCES

1. Wykoff CC, Croft DE, Brown DM, et al; TREX-AMD Study Group. Prospective trial of treat-and-extend versus monthly dosing for neovascular age-related macular degeneration: TREX-AMD 1-year results. Ophthalmology. 2015;122(12):2514-2522. doi:10.1016/j.ophtha.2015.08.009
2. Stone TW, Hahn P, Raef S, eds. ASRS 2019 Preferences and Trends Membership Survey. Chicago, IL. American Society of Retina Specialists; 2019.
3. Hahn P, ed. ASRS 2022 Preferences and Trends Membership Survey. Chicago, IL. American Society of Retina Specialists; 2022.
4. Ho AC, Kleinman DM, Lum FC, et al. Baseline visual acuity at wet AMD diagnosis predicts long-term vision outcomes: an analysis of the IRIS registry. Ophthalmic Surg Lasers Imaging Retina. 2020;51(11):633-639. doi: 10.3928/23258160-20201104-05
5. Mathai M, Reddy S, Elman MJ, et al; ALOFT Study Group. Analysis of the long-term visual outcomes of ForeseeHome remote telemonitoring. the ALOFT study. Ophthalmol Retina. Published online ahead of print April 26, 2022. doi: 10.1016/j.oret.2022.04.016
6. Chew EY, Clemons TE, Harrington M, et al; ARDS2-HOME Study Research Group. Effectiveness of different monitoring modalities in the detection of neovascular age-related macular degeneration: the HOME study, report number 3. Retina. 2016;36(8):1542-1547. doi: 10.1097/IAE.0000000000000940
7. Fleckenstein M, Schmitz-Valckenberg S, Adrion C, et al. Progression of age-related geographic atrophy: role of the fellow eye. Invest Ophthalmol Vis Sci. 2011;52:6552-6557. doi:10.1167/iovs.11-7298
8. Ho AC, Schechet SA, Mathai M, et al; ALOFT Study Group. The predictive value of false positive ForeseeHome alerts in the ALOFT study. Accepted for publication by Ophthalmology Retina.
9. Carnevali A, Cicinelli MV, Capuano V, et al. Optical coherence tomography angiography: a useful tool for diagnosis of treatment-naïve quiescent choroidal neovascularization. Am J Ophthalmol. 2016;169;189-198. doi:10.1016/j.ajo.2016.06.042
10. Carnevali A, Sacconi R, Querques L, et al. Natural history of treatment-naïve quiescent choroidal neovascularization in age-related macular degeneration using OCT angiography. Ophthalmol Retina. 2018;2(9):922-930. doi: 10.1016/j.oret.2018.02.002
11. Narita C, Wu Z, Rosenfeld, PJ, et al. Structural OCT signs suggestive of subclinical nonexudative macular neovascularization in eyes with large drusen. Ophthalmology. 2020;127(5):637-647. doi: 10.1016/j.ophtha.2019.11.007
12. A masked, placebo-controlled study to assess iptacopan in age-related macular degeneration. ClinicalTrials.gov identifier: NCT05230537. Accessed September 23, 2022. https://clinicaltrials.gov/ct2/show/NCT05230537 .