Retina Treatment Beyond Protocol
CHICAGO — Optimal treatment of retinal diseases hinges on better understanding in three primary areas, said an expert panel at OIS@ASRS 2019: the disease mechanisms involved; individual patient differences; and the timing of injections.
A fourth point involves treatment yet to be developed: A safe, effective, long-term delivery system for anti-VEGF agents. Panel moderator Robert Avery, MD, California Retina Consultants, asked his peers why they thought such an advance was unavailable.
Baruch Kupperman, MD, PhD, professor and chair of ophthalmology at Gavin Herbert Eye Institute, University of California, Irvine, said manufacturing processes tend to denature the larger proteins used for anti-VEGF therapy. “It’s hard to put large biologic molecules into a drug-delivery system,” he said. One company working on this problem, he continued, is Re-Vana Therapeutics, with its 2, sustained release drug-loading platforms.
Finding the “Sweet Spot” for Injections
Dr. Avery also brought up timing of injections. Jay Duker, MD, director, New England Eye Center and co-founder of Hemera Biosciences, said some practitioners were concerned by the long-term, sustained-release nature of steroid implants. Dr. Kupperman pointed out that there is a “sweet spot” for drug delivery. “Generically,” he said, “you want something in the 6- to 12-month range for most conditions and most drugs.”
“The duration you want may also depend on the disease,” said Dr. Duker. “What’s the consequence of the drug running out? If a patient has DME [diabetic macular edema] or RVO [retinal vein occlusion], having a little macular edema may not be harmful. For AMD [age-related macular edema], you want continuous therapy—a longer-acting drug with an overlap between injections would be preferred.”
Decreasing Visual Acuity
Dr. Avery asked the panel to address why visual acuity (VA) drops over time. “Why does this happen?” he asked. “Is it lack of compliance? Or are there other pathways involved?”
Dr. Duker responded that multiple factors may be involved in decreased VA. “We’ve seen with many therapies that real-world compliance doesn’t match what’s done in clinical trials.”
One important variable, Dr. Duker noted, relates to individual differences between patients. “Some patients are big VEGF ‘makers,’” he said, “and they may need frequent injections or they’ll lose vision.” In the long term, many patients seem to develop geographic atrophy, Dr. Duker said, for which there is no known effective treatment.
David Boyer, MD, Retina-Vitreous Associates Medical Group in Southern California, pointed out differences between the disease states being treated. Longer-acting systems, like those being investigated by Graybug Vision and Kodiak, as well as gene therapy, could produce better outcomes.
Dr. Kupperman suggested that ongoing anti-VEGF therapy could contribute to development of geographic atrophy. “It’s a source of debate,” he said. “We are looking for nerve-protecting therapy.”
The Future of Adjunctive Treatments
The topic of adjunctive treatments arose, specifically whether Genentech’s investigational port delivery system for ranibizumab would devalue the adjunctives if the delivery system could suppress VEGF for a year.
Not likely, said Dr. Boyer. “If therapy lasts 6 months or a year, you’ll still have patients with breakthroughs,” said Dr. Boyer. “It’s an individualized problem. You can’t look at a patient on Day 1 necessarily and say, ‘You’ll need injections every 3 months for the rest of your life,’ or see another patient and say, ‘You’ll need injections every 6 weeks or every 4 weeks.’ We find a happy medium when we start treating patients and see how they respond.”
Adjunctive therapies will always be needed, because they treat different pathways, the panel agreed. Dr. Kupperman added that “We’re encouraging companies to continue to develop new therapeutic pathways.”
Added Dr. Boyer, “With diabetes, there’s a lot more room for additional treatment of inflammation. With AMD, it’s a VEGF-dominated disease.”
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