Published in Retina
The Evolving World of AMD Diagnosis and Treatment
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5 min read
In this session from Eyes On 2023, Michael Singer, MD, reviews recent studies and innovations in treating age-related macular degeneration (AMD).
Dry age-related macular degeneration (AMD) is by far the most common form of macular degeneration, and it's the type with the least amount of treatment options currently available. Essentially, all there is for treatment are AREDs vitamins.
The original AREDs1 contained 15mg of beta-carotene, which was associated with lung cancer in smokers, so it was removed from the AREDs2 formula. AREDs2 also added lutein and zeaxanthin, which showed a 20% percent reduction in AMD progression.
New therapies are on the horizon to slow the progression of dry AMD, particularly geographic atrophy. Several clinical trials are currently in progress, such as the Apellis-Derby, Oaks, Gather 1, and Gather 2, all studying new medications that will block inflammatory components to slow geographic atrophy.
These clinical trials released 24-month studies showing promising results, which have been submitted for FDA review. If approved, this would be the first therapy for geographic atrophy and the first therapy for dry macular degeneration beyond vitamins.
There are a number of therapies available for wet macular degeneration, and those numbers continue to grow. Lucentis was the first anti-VEGF therapy to be approved for up to 2 years and showed a significant improvement in both clinical trials.
There are currently five FDA-approved injections for the treatment of wet AMD, all are forms of anti-vascular endothelial growth factor (VEGF) that are just slightly different molecules in different concentrations.
The CATT study, sponsored by the National Eye Institute, compared Lucentis to Avastin in both monthly and as-needed applications. The study found at the 2-year point that there was no statistical difference in visual improvement between the two injections; however, monthly injections, regardless of which medications were used, were markedly superior to as-needed injections, and patients who were switched to as-needed from monthly showed a decrease in vision.
When those patients were evaluated 5 years after the clinical trial ended, it was found that they had lost all progress and were worse off than their starting point. This is attributed to the fact that these patients received fewer injections, and with fewer injections comes less improvement in therapies. There was no long-term benefit to the study.
What has been found over all of the wet macular degeneration trials is that the more you shoot, the better you get. Intraocular inflammation remains a concern with all these injections, though it must be noted that these cases remain relatively low in studies.
A recent study compared 2mg doses of Eylea every 8 weeks with a much higher concentration of 8mg every 12 to 16 weeks, and what was found was that all patients did well, regardless of which category they were in. This study suggests that higher doses given less often could be equally effective. Even more encouraging is that at the 1-year mark, patients who received those higher doses at longer intervals maintained visual benefits and were able to continue only receiving injections every 12 weeks or longer.
A port delivery system for anti-VEGF was approved in 2022. The port is a surgically implanted pump that diffuses over time. Unlike injections which supply medication in monthly intervals, the pump offers a slow continuous supply of medication, similar to an insulin pump.
Compared to traditional monthly injections, the port was found to be equivalent to monthly injections, with 98% of people not needing a rescue injection for over 6 months. Patients were found at the 2-year mark to have comparable vision and a greatly reduced treatment burden.
Gene therapy is an option that could potentially last even longer than both the port delivery system and high-dose Eylea injections. Currently, two major companies are working on gene therapies, conducting studies on hard-to-treat patients who have received many injections for wet AMD.
The patients in the clinical study who received injections, followed by gene therapy, required little to no rescue injections in the 12 months following treatment and lowered their need for injections from an average of ten times a year to less than one injection in a 12-month period.
In addition to the benefits of adding gene therapy, these studies also focused on the concentration of dose and found patients who received higher concentrations had improved results in their long-term visual acuity.
This is a very exciting time to be involved in the retina because the future of treating macular degeneration treatment is bright. Multiple pathways exist to evaluate and treat retinal disease, with more being added every year.
Improving traditional anti-VEGF molecules, adding sustained delivery, inhibiting new mechanisms of action, and gene therapies all provide a better visual future for patients with wet and dry macular degeneration.