The COVID pandemic negatively impacted visual acuity (VA) in diseases traditionally reliant on in-person office visits, such as anti-VEGF treatment discontinuity among neovascular AMD (nAMD) patients. Furthermore, population health data collected from UK retina specialist practices showed a drop in VA from 61.5 to 57.2 letters during 8-16 weeks of delayed treatment, January to March 2020. In patients with 16 weeks delay, the drop in VA was even worse, from 56.3 to 50.5 during the same period of time.¹ Missed appointments and hesitancy to see an eye-care provider despite symptoms likely contributed to the negative impact of the pandemic on patients’ vision.

Even pre-pandemic, we failed to ideally monitor patients at risk for sudden conversion to nAMD. In an analysis of AAO IRIS Registry data, Ho et al showed that only 34% of newly converted nAMD eyes have a VA of 20/40 or better — functional vision.² The same real-world data set revealed that eyes presenting with less than 20/40 VA did not reach a mean of 20/40 VA at 1 or 2 years under anti-VEGF therapy.

As retina specialists, we assume that fellow eyes of nAMD patients fare better because of frequent office visits. However, IRIS Registry data disproved this perception. Similar to the first eye diagnosed with nAMD, only about one third (34%) of fellow eyes presented with VA of at least 20/40, limiting the ability to regain and maintain functional vision through long-term treatment.

The gap in care between office visits calls for better monitoring than patient self-reported changes in vision observed with, at best, the Amsler grid test. Partnerships with remote monitoring service providers may well fill that gap, supporting our ability to detect disease early and begin treatment. In particular, a new at-home OCT service offers retinal specialists invaluable assistance in monitoring.

DIGITAL HEALTH SERVICES AS COMANAGEMENT PARTNERS

Monitoring centers that deploy to homes tele-connected, patient-operated devices with objective visual function tests can be strong partners in the co-management of patients at risk for vision loss. Preferential hyperacuity perimetry (PHP) combined with artificial intelligence-based daily test data analysis has shown itself an effective tool to identify the conversion to nAMD earlier than standard of care.

In 2021, we were part of a team of researchers who examined patient data housed in the Notal Vision Diagnostic Clinic, medical provider of the PHP-based ForeseeHome AMD Monitoring Program.³ Our retrospective review included patients whose VA was at least 20/60 at the time the ForeseeHome platform was prescribed. Patients in the study were monitored for disease progression by both the device and by in-person examination, conducted routinely or when symptoms presented.

Among patients who fit the enrollment criteria, 306 converted to nAMD in that study; 109 had at least 20/40 VA at baseline, 81% of whom retained at least 20/40 VA when disease activity was detected. Given the aforementioned findings from the IRIS Registry study that baseline 20/40 VA at the time of disease detection is the cutoff for maintaining 20/40 VA after 1 or 2 years of therapy, it is noteworthy that 81% of new nAMD patients with at least 20/40 VA whose disease was detected after adding at-home testing to their monitoring regimen were able to initiate therapy before their VA dipped below the cutoff point.

These positive findings are a stark contrast to the aforementioned 34% in the IRIS registry, which reflect the inferior performance of standard of care that is typically limited to the use of an Amsler grid.

HOW IT WORKS

A successful remote monitoring solution relies on both technology and patient engagement. Monitoring centers staffed by certified ophthalmic professionals partner with physician offices and engage patients remotely. Following receipt of a prescription, such centers contact the patient over the phone, provide the testing device, educate the patient about AMD, teach them how to use the device, monitor test compliance and provide compliance coaching as needed.

For the referring clinicians, the monitoring center analyzes test data and provides reports and alert notifications. The remote patient engagement the provider offers can help reduce valuable chair time in the office.

Clinical decision-making during routine and alert-driven office visits can benefit from the online review of remote test data. Functional abnormalities seen on home-based visual field maps support the review of in-office OCT and OCT angiography images. The consideration of the amount and/or complexity of data to be reviewed and analyzed in the Current Procedural Terminology (CPT) 2021 Evaluation and Management (E/M) Services Guidelines speaks to the value recognition of remote patient data for the clinical decision-making process.

NEW TO U.S. MARKETS

One promising remote monitoring solution is the Home OCT (Notal Vision, Figure 1), an investigational patient-operated spectral domain OCT system. It operates like other such remote monitoring systems, contacting the patient, providing the testing device, educating the patient about AMD and device operation, etc.

Images from patient self-operated OCT devices and tracked changes in disease activity are expected to add a new dimension to the management of patients with exudative retinal diseases. Patients’ daily self-imaging will give us new insights in disease dynamics and treatment response. To make large amounts of image data manageable for clinicians, artificial intelligence-based image analysis algorithms are needed to identify and quantify actionable biomarkers, such as fluid volume in the intra- and subretinal space. Online review of temporal fluid volume trajectories will allow treating physicians to set specific alert thresholds that providers of such monitoring services will identify and inform the physician when the criteria have been met.

The physician-led utilization of remote OCT data will enable new proactive highly personalized treatment regimes. We will be able to perform intravitreal injections responding to each individual eye’s level of disease activity in an agile fashion. Patients with good treatment response may benefit from extended retreatment intervals over the safety net of Home OCT. Fluid alerts in eyes with early recurrence will prompt remote review of OCT images, potential office visits for further diagnostic testing and decisions to treat.

Such treatment paradigms will potentially reduce fluid exposure to the retina, reduce the burden that office visits and treatments create for patients and caregivers and hopefully promote better adherence to and persistence with intravitreal anti-VEGF therapy.

NIP NONADHERENCE IN THE BUD

A review of the data demonstrates how critical it is to keep nAMD patients from falling into nonadherence. In a recent systematic literature review, we found that nonadherence occurred early, with up to 50% of patients stopping anti-VEGF treatment by 24 months.⁴ Lower baseline vision, poor response to treatment and worse final VA were associated with higher rates of nonadherence, again highlighting the need for early disease detection. Nonadherence to treatment or monitoring appointments was high, with variable rates depending on how strictly this was defined (32% to 95%). Social factors play a significant role for most patients, with many citing a lack of caretakers to take them to appointments (25.9%).

One report examined whether patients on a PRN regimen who performed their monitoring visit at a local clinic with telemedicine capabilities had better treatment adherence and increased injections compared to patients who had both monitoring and injections at the same tertiary reference center. The outcomes suggested that the telemedicine group had greater treatment adherence, with a significantly higher number of monitoring visits (telemedicine group 22.8 visits vs. control group 18.4 visits, P < 0.001) and a greater number of injections (telemedicine group 13.9 injections vs control group 11.1 injections, P = 0.02) over the total monitoring period.⁵

These findings support the positive impact on treatment adherence and persistence we should expect from the introduction of home OCT monitoring services.

DEMONSTRATED EFFICACY

We recently evaluated the Home OCT on 69 study participants with nAMD with regard to image quality and usability.⁶ The artificial-intelligence-based algorithm (Notal OCT Analyzer [NOA], Notal Vision) was used to identify, quantify and map intra- and subretinal fluids.

Successful imaging with the Home OCT was performed in all patients and in 93% of the enrolled eyes. The positive percent agreement and negative percent agreement for detection of fluid, intraretinal fluid and subretinal fluid in at least one of three consecutive home OCT images was 97%/95%, 96%/94% and 100%/98%, respectively, when compared to commercial in-office OCT systems. Additionally, 95% of patients rated it “easy” to operate the device and scanned their own eyes without assistance.

In a prospective observational longitudinal pilot study, we followed four individuals (mean age 73.8 years) with nAMD undergoing anti-VEGF therapy in routine clinical practice with daily home OCT.⁷ The macular cube scans were automatically uploaded to the secure cloud of the monitoring provider. They underwent evaluation separately by the NOA and human expert graders for fluid presence, segmentation and volume. Of 240 self-imaging attempts initiated, 211 (87.9%) were successfully completed. Of these, 97.6% had satisfactory quality. For fluid presence, the NOA agreed with human grading in 94.7% of cases. For agreement between NOA and human fluid volume measurements, the correlation coefficient was 0.996 and mean absolute difference was 1.5 nl (vs 0.995 and 1.2 nl, respectively, for inter-human agreement).

Graphical plots of daily fluid volume revealed a wide variation in the dynamics of fluid exudation and treatment response. Metrics describing these dynamics may become important disease biomarkers in the future and inform decisions about retreatment, switch in drugs or selection of emerging sustained-release or gene therapeutic options. A bilateral nAMD case illustrates the difference in retinal fluid exposure between the eyes of an 85-year-old subject on a treat-and-extend regimen (Figure 2).

NEW COMPLEXITY, BILLING OPPORTUNITIES

Reliance on the performance of device technology, cloud connectivity, data analytics and partnerships with remote monitoring providers clearly requires reliable integration of image, data and alert notification review through web portals into the clinic workflow. Regulatory oversight is critical as well. In addition to the clinical benefits for patients, the publication of dedicated CPT codes for reporting of patient-initiated remote retinal OCT scans in January 2020 gives prescribing retina specialists the opportunity to bill for review, interpretation and report of data and analyses from remote diagnostic surveillance center every 30 days (CPT code 0606T).

For practices engaging in remote monitoring, physicians will be responsible for setting eye-specific time intervals or fluid volume-based notification criteria to prompt their data review. The use of remote data sources will add complexity to the clinical decision-making process and should be documented by the physician who prescribed the service. The Home OCT provider will support patient compliance and should inform the referring physician if monitoring is not occurring in cases where a patient lapses self-imaging for a period of time or a technical device or connectivity problem prevents acquisition and access to data.

CONCLUSION

With several longitudinal home OCT studies currently under way in the United States, we are at the brink of a new paradigm for more precise disease management.

Reminiscent of the coinciding introduction about 15 years ago of spectral domain OCT devices and effective anti-VEGF agents, tele-connected home OCT, especially combined with more durable treatment solutions, offers the potential to improve treatment outcomes and lower the burden for both patients and caregivers. OM

REFERENCES

1. Stone LG, Grinton ME, Talks JS. Delayed follow-up of medical retina patients due to COVID-19: Impact on disease activity and visual acuity. Graefes Arch Clin Exp Ophthalmol. 2021;259:1773-1780. Epub May 11, 2021.
2. 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;51:633-639.
3. 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;10:1355.
4. Mali O, Mitchell P, Finger RP. Nonadherence or nonpersistence to intravitreal injection therapy for neovascular age-related macular degeneration: A mixed-methods systematic review. Ophthalmology. 2021;128: 234–247.
5. Heimes B, Gunnemann F, Ziegler M, et al. Compliance of age related macular degeneration patients undergoing anti-VEGF therapy: analysis and suggestions for improvement. Ophthalmologe. 2016;113:925–932.
6. Nahen K, Benyamini G, Loewenstein A. Evaluation of a self-imaging SD-OCT system for remote monitoring of patients with neovascular age-related macular degeneration. Klin Monbl Augenheilkd. 2020;237:1410-1418.
7. Keenan TD, Goldstein M, Goldberg D, et al. Prospective longitudinal pilot study: daily self-imaging with patient-operated home OCT. Ophthalmol Sci (in press).

About the Authors

Anat Loewenstein, MD, MHA, is director of the Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.

Michael J. Elman, MD, is president, Elman Retina Group, P.A., Baltimore, Md., and assistant professor of ophthalmology at the Johns Hopkins University School of Medicine.

Disclosures: Dr. Loewenstein reports relationships with Allergan, Beyeonics, Beyer, Notal Vision, Novartis, Roche and Web MD. Dr. Elman reports relationships with Alimera, Apellis Pharmaceuticals, Clover Therapeutics, Emmes Corp., Jaeb Center for Health Research, Kodiak Sciences, Neurotech Pharmaceuticals, NGM Biopharmaceuticals, Notal Vision, Novartis and Opthea.