February has a few well-known associations. A lot of people think of Valentine’s Day, with all its pink hearts and chocolates. Many more know it as Black History Month in the United States and Canada or LGBTQ Month in the United Kingdom. Probably not so many think of it as National Cherry Month or National Bird-Feeding Month, which it also is. You can fit a lot into one month!
Another designation that’s not as commonly known is that February is also AMD Awareness Month — and age-related macular degeneration (AMD) is a condition that could always do with a bit more public education. As the leading cause of blindness among people aged 60 and over, it is vitally important to increase patient awareness of the need for regular check-ups in order to detect and begin treating the incurable (and progressive) condition as early as possible.
Within the eye care profession, AMD’s dangers are well known. For those already aware of the condition, this month presents an opportunity to look at some of the new developments seen in treating this disease from the past year.
Micronutrient Treatments: Take Your Vitamins!
Writing last August in the New England Journal of Medicine1, Dr. Rajendra Apte noted that one of the best tools available to combat AMD is micronutrient supplementation. Citing the Age-Related Eye Disease Studies (AREDS & AREDS2) conducted some years ago, Dr. Apte said that these supplements showed substantial efficacy in slowing the effects of intermediate AMD.
The supplements prescribed in this study were vitamin C, zinc, vitamin E and copper, along with beta carotene (AREDS) or lutein and zeaxanthin (AREDS2). Though the micronutrients in this formulation are commonly available over-the-counter, they have shown to have benefits to AMD sufferers, while presenting no significant drawbacks.
While the findings of these studies are significant, Dr. Apte points out that they are limited in their applicability to those with intermediate-stage AMD. Studies have not shown conclusively that the formulation has any effect in patients without AMD, nor that it prevents progression among advanced-stage patients or those with only small drusen in either eye.
New Clinical Results in Gene Therapy
While numerous gene therapies for AMD have been undergoing preclinical and clinical testing over the course of the past several years, recently there have been several exciting developments that have brought these closer to widespread application.
Gene therapies work by addressing protein deficiencies in protein chains in the body’s tissue, in this case, the macula. They are typically administered as a one-time injection at the site of the deficiency. These injections effectively create a biofactory that produces anti-VEGF protein.
There are a lot of ongoing clinical trials about new genetic therapies which are often a hot topic of discussion among experts.
One of these trials, OPTIC, uses the gene therapy ADVM-022.2 Developed by Adverum Biotechnologies (California, USA), this is injected in the macula, and releases aflibercept within the eye. Recent results have shown that following ADVM-022 injection, there was an 85 to 96% reduction in annualized injection frequency of aflibercept as a result of the genetic therapy.
Another study conducted by Regenxbio (Maryland, USA) evaluated the use of RGX-314, which produces ranibizumab following either subretinal or suprachoroidal delivery.3 This study, conducted in five cohorts of AMD sufferers, has demonstrated a significant reduction in anti-VEGF treatment burden, with reduction by more than 80% in cohort five.
Both of these treatments aim to reduce, or even potentially replace, the need for regular injections of the treatment being produced. In addition to Luxturna (Spark Therapeutics Inc., Pennsylvania, USA) — which is already FDA approved — these two viable gene therapies aim to give doctors many more treatment options for combatting AMD.
FDA Approved Implants
While the advances of gene therapy provide one avenue for reducing the need for injection treatments of AMD in the future, another technology has taken a different approach. And unlike the aforementioned therapies still undergoing trials, this treatment option is now available for public use.
On October 22, 2021, the FDA approved Susvimo™, a ranibizumab delivery system developed by Roche (Basel, Switzerland). This ocular implant, or port delivery system, is a device placed within the eye that delivers regular doses of ranibizumab automatically, without the need for regular injections.
Port delivery systems have long been a subject of speculative interest and clinical trials in the world of ophthalmology, and it is promising news indeed for doctors and patients alike. While these implants still require an office visit for refilling and maintenance two or more times a year, they nonetheless represent a significant reduction in patient visits and injections.
Prevention is Still the Best Bet
These recent developments represent substantial breakthroughs in the management of AMD. But at the same time, they remain just that: merely management. No treatment exists today to reverse the progression of AMD.
To that end, we return to Dr. Apte, who notes that a strong correlation has been shown between the onset of AMD and two major factors: smoking and high blood pressure. As the former of these is manageable as a lifestyle choice, as well as a danger to myriad other areas of patient health, Dr. Apte advocates for smoking cessation counseling. While this is surely the case in all fields of medicine, it often escapes patients’ notice that smoking may not just harm their lungs and their heart, but could potentially rob them of their eyesight as well.
High blood pressure can also be managed in various ways. The first of these is through the patient’s diet. Pharmacological treatments are also available for patients with chronic blood pressure conditions. Reduction in these two potentially contributing factors can lead to reduced risk for AMD overall.
Along with reducing risk factors, early detection remains key for treatment as early as possible. The great leaps forward allow for slowing AMD’s progression, often to a very substantial degree. Regular testing is the best method for this, and can only be achieved through increased patient awareness of AMD.
References
- Apte RS. Age-Related Macular Degeneration. N Engl J Med. 2021;385(6):539-547.
- Grishanin R, Vuillemenot B, Sharma P, et al. Preclinical Evaluation of ADVM-022, a Novel Gene Therapy Approach to Treating Wet Age-Related Macular Degeneration. Mol Ther. 2019; 27(1): 118–129.
- Ding KD, Lorenc VE, Chen D, et al. AAV8-vectored suprachoroidal gene transfer produces widespread ocular transgene expression. J Clin Invest. 2019;129(11):4901–4911.
