What innovations will meet the challenges of undertreating retinal disease?
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Telemedicine and home monitoring
Clinical trials have clearly laid out treatment protocols, usually with monthly treatment intervals, and the subjects tend to be compliant and motivated for the study visits. In the real world, life gets in the way.
Treatment burden, such as the distance needed to travel, transportation, time, cost, illnesses, physician access and now the fear of COVID-19, may all contribute to undertreatment. How can we improve on this? One method I propose is early disease detection and personalized treatment intervals through telemedicine with home monitoring.
Studies have shown that we cannot precisely predict when intermediate age-related macular degeneration converts to wet AMD or when fluid recurs after a treatment injection. With home monitoring, patients can be monitored frequently, even daily, in the convenience of their home. The alerts can be set at an individualized threshold level, customized for each eye, and the patient can come to the office as soon as the conversion to wet AMD is detected or fluid buildup beyond the threshold level occurs. This will allow not only more timely detection of disease change, resulting in less vision loss, but also the office visits will be based on the needs of the individual patient, when the examination and treatment are truly needed.
We already have telemedicine with home monitoring services available in the form of Foresee Home (Notal Vision Diagnostic Clinic) for detection of conversion to wet AMD. With the advent of home OCT in the future, we will be able to optimize therapeutic agents and treatment intervals for patients with wet AMD initially and then hopefully for other retinal conditions. Home monitoring via telemedicine will become increasingly important as we move toward longer-duration agents because not all patients will respond to the treatments in the same manner. Given that retina is heavily image based, this and other types of imaging are ideally suited for telemedicine. The COVID-19 pandemic has shown the benefits of telemedicine and home monitoring, and we should continue to explore partnering with remote diagnostic clinics for the benefit of our patients, minimizing treatment burden and undertreatment while optimizing and personalizing care.
Judy E. Kim, MD, is an OSN Retina/Vitreous Board Member and professor of ophthalmology at Medical College of Wisconsin.
Long-acting therapeutics
The burden of repeated treatment, every 4 or 6 weeks, is too much to bear in the long term, for patients, providers and our health care systems. Real-world studies have demonstrated that patients receive fewer injections as compared with patients in randomized clinical trials and that undertreatment is associated with suboptimal visual and anatomic outcomes. Options that allow patients to be treated successfully with less frequent dosing are the key innovation we need to prevent undertreatment and to provide adequate care to the steadily growing number of patients with retinal diseases managed with repeated intravitreal injections.
New options currently on the horizon include novel anti-VEGF pharmaceuticals, such as KSI-301 (Kodiak Sciences); mechanically, it is similar to the classic anti-VEGFs, but it is based on a novel antibody biopolymer conjugate (ABC) platform engineered specifically for increased durability.
Another approach is gene therapy. RGX-314 (Regenxbio) and ADVM-022 (Adverum Biotechnologies) have shown promising results in early phase human trials focused to date on neovascular age-related macular degeneration. They hold the promise of a one-time treatment to create an intraocular biofactory to produce an anti-VEGF agent inside the eye.
A third promising option is a surgical approach, such as the Port Delivery System (PDS, Genentech), which has shown positive efficacy results in the phase 3 Archway study. Safety signals related to the surgical procedure and the presence of a device in the eye wall were reported and are important to consider in relation to the risk-benefit ratio of ongoing repeated intravitreal injections.
Finally, there are new drugs that include additional targets beyond VEGF-A. The most promising currently is faricimab (Genentech), a molecule that blocks Ang-2 as well as VEGF-A. Data from the YOSEMITE and RHINE as well as the TENAYA and LUCERNE phase 3 clinical trials have shown potential to extend the treatment interval up to 16 weeks for diabetic macular edema and wet AMD, respectively. Other in-human trials also appear to offer improved outcomes beyond anti-VEGF-A monotherapies, including tyrosine kinase inhibitors, medications that inhibit the kallikrein cascade and OPT-302 (Opthea), which inhibits the activity of VEGF-C and VEGF-D.
I believe some of these approaches, and hopefully most of these options, will help us achieve sustained exudative retinal disease control with decreased treatment burden, leading to better long-term outcomes for patients.
Charles C. Wykoff, MD, PhD, is from Retina Consultants of Texas and Blanton Eye Institute at Houston Methodist.
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