Macular degeneration, also known as age-related macular degeneration (ARMD), is a degenerative disease of the macula, a part of the retina. Vision loss begins with central vision, which mainly affects reading, but it can later spread into peripheral vision, and can lead to profound visual disability if not treated.
There are two types of ARMD: dry (nonexudative) and wet (exudative). The term wet refers to leakage of fluid and blood from abnormal vessels below the retina (neovascularization). Vision loss can occur from both nonexudative and exudative ARMD; however, the latter is rapidly progressive and largely treatable.
Signs and symptoms
Though ARMD has often been attributed to aging, many patients develop changes as soon as the fifth decade, especially if there is a family history. While early ARMD has no symptoms, more advanced ARMD has patterns of blind spots called scotomas, distortion called metamorphopsia, and varying degrees of vision loss. Very often, these changes affect the quality of vision, most commonly reading vision, and is often manifested as missing words or words jumping.
An eye-care professional will see drusen, or yellow spots under the retina, and/or areas of retinal damage in nonexudative ARMD, or leakage of fluid or blood in exudative ARMD. He or she will then commonly refer the person to a retinal physician.
The retinal specialist might then use advanced imaging techniques, such as fluorescein angiography or indocyanine green imaging, in which dyes are injected into the vein for visualization of damage, and/or optical coherent tomography (OCT) angiography, a new technique that allows for visualization of damage without the dye injection. The presence of early or intermediate ARMD can be monitored for progress. This process can take years and then abruptly cause severe vision loss if unrecognized. To paraphrase Ernest Hemingway, vision loss from ARMD occurs, “in two ways … gradually and then suddenly.”
The process that causes nonexudative ARMD to become exudative ARMD is unclear, but large clinical trials strongly suggest that taking a collection of over-the-counter vitamins called AREDS and AREDS2 can slow this progression. These contain slightly different combinations of vitamins, and your eye-care professional will suggest which version is better for you.
The treatment of moderate to severe nonexudative ARMD has been elusive, but recent FDA approvals of two new drugs are encouraging. They include pegcetacoplan (Syfovre) and avacincaptad pegol intravitreal solution (Izervay).
The treatment of exudative ARMD comes from groundbreaking research to suppress abnormal vessel growth in solid cancers. In exudative ARMD, neovascularization grows in the tissue below the retina (the choroid) in response to an unknown injury or stimulus. This process is mediated by a chemical called a cytokine, specifically vascular endothelial growth factor (VEGF). While VEGF naturally repairs damaged blood vessels in patients with a heart attack or stroke, it promotes abnormal neovascularization in exudative ARMD.
Injecting drugs that block the production of VEGF by the diseased choroid has been found to lead to visual improvement and/or stability in a large majority of patients.
There are four anti-VEGF drugs that are the standard of care:
- Ranibizumab (Lucentis) and aflibercept (Eylea) have been used for more than 10 years and are FDA approved.
- Bevacizumab (Avastin) is not FDA approved for ophthalmic use (it is for cancer), but it is widely used due to its affordability.
- A new entry, faricimab (Vabysmo) is now FDA approved and is becoming more commonly used due to its longevity and the need for fewer injections.
Originally, patients were given anti-VEGF injections monthly, but research has shown that some patients can be treated with fewer injections. We now know that every patient, and every eye, has different requirements for treatment. The goal is to reduce the number of treatments and have the best clinical effect. The use of anti-VEGF drug therapy is an ongoing process that may continue for years. The treating ophthalmologist must monitor the response to treatment by testing visual acuity and OCT imaging. Treatment that is not working has to be modified, either by increasing the frequency of injections or by changing the drug. Faricimab (Vabysmo) represents a new class of drugs as it suppresses two specific cytokines simultaneously.
Another treatment option is photodynamic therapy (PDT), which was largely abandoned after the start of the anti-VEGF era but is again being investigated in combination with anti-VEGF agents.
Even though patients can progress from nonexudative to exudative stages, the nonexudative changes continue in a slowly progressive manner. Despite successful resolution of neovascularization and leakage with anti-VEGF drugs, vision loss may still ensue over time. The next challenge for treatment will be integrating intraocular injections for both nonexudative and exudative ARMD together in a successful protocol.
Treating exudative ARMD with anti-VEGF drugs can help most people maintain or improve vision. The challenges in the future involve the mitigation of treatment burden, improved treatment response, and the successful treatment of nonexudative ARMD.
The vision loss from ARMD is largely limited to the inability to read or drive, but the risk of severe vision loss is increased by the use of an anticoagulant drug. Despite this risk, it is imperative that a patient consult their primary care or specialist doctor on the discontinuance of anticoagulation, as this could cause serious consequences such as heart attack or stroke.
Patients with family histories of ARMD may display imaging biomarkers, or measurable findings on imaging techniques, that may predict future progression. It is also clear that genetic predisposition increases the risk of developing ARMD and can predict future progression into the exudative form. Genetic tests are commercially available but not entirely definitive on their own. Patients with a strong family history should be followed by eye care professionals and have OCTs done routinely as early as age 40 or 50.
ARMD vs. Cataracts
Cataracts, or the clouding of a normal clear ocular lens, is a common cause of vision loss in the aging eye. It is essential to differentiate between the cataracts and ARMD because they have different treatments. Cataracts generally cause blurred vision, especially at night, and are easily removed with surgery. ARMD, on the other hand, causes changes in the quality of vision, with scotomas and metamorphopsia.