Macular Degeneration

What is Macular Degeneration?

Macular Degeneration is the leading cause of vision loss, affecting more than 10 million Americans – more than cataracts and glaucoma combined.

At present, Macular Degeneration is considered an incurable eye disease.

Macular Degeneration is caused by the deterioration of the central portion of the retina, the inside back layer of the eye that records the images we see and sends them via the optic nerve from the eye to the brain. The retina’s central portion, known as the macula, is responsible for focusing central vision in the eye, and it controls our ability to read, drive a car, recognize faces or colors, and see objects in fine detail.

One can compare the human eye to a camera. The macula is the central and most sensitive area of the so-called film. When it is working properly, the macula collects highly detailed images at the center of the field of vision and sends them up the optic nerve to the brain, which interprets them as sight.  When the cells of the macula deteriorate, images are not received correctly. In early stages, macular degeneration does not affect vision. Later, if the disease progresses, people experience wavy or blurred vision, and, if the condition continues to worsen, central vision may be completely lost. People with very advanced macular degeneration are considered legally blind. Even so, because the rest of the retina is still working, they retain their peripheral vision, which is not as clear as central vision.

Types of Macular Degeneration

There are two basic types of Macular Degeneration: “dry” and “wet”. Approximately 85% to 90% of the cases of Macular Degeneration are the “dry” (atrophic) type, while 10-15% are the “wet” (exudative) type.

Stages of Macular Degeneration

There are three stages of Age-related Macular Degeneration (AMD).

  • Early AMD – Most people do not experience vision loss in the early stage of AMD, which is why regular eye exams are important, particularly if you have more than one risk factor (see below). Early AMD is diagnosed by the presence of medium-sized drusen (yellow deposits beneath the retina).
  • Intermediate AMD – At this stage, there may be some vision loss, but there still may not be noticeable symptoms. A comprehensive eye exam with specific tests will look for larger drusen and/or pigment changes in the retina.
  • Late AMD – At this stage, vision loss has become noticeable.

Causes of AMD

The specific factors that cause macular degeneration are not conclusively known, and research into this little understood disease is limited by insufficient funding. At this point, what is known about age-related Macular Degeneration is that the causes are complex, but include both heredity and environment. Scientists are working to understand what causes the cells of the macula to deteriorate, seeking a macular degeneration treatment breakthrough. They know the causes are  not the same for Age-related Macular Degeneration as they are for Stargardt disease. Stargardt disease has a specific genetic cause in most cases, whereas AMD involves both genetic and environmental factors.

Risk Factors

The biggest risk factor for Macular Degeneration is age. Your risk increases as you age, and the disease is most likely to occur in those 55 and older. Other risk factors include:

  • Genetics – People with a family history of AMD are at a higher risk.
  • Race – Caucasians are more likely to develop the disease than African-Americans or Hispanics/Latinos.
  • Smoking – Smoking doubles the risk of AMD.

Treatment

There is currently no known cure for Macular Degeneration, but there are things you can do to reduce your risk and possibly slow the progression once you’ve been diagnosed. For example, one can pursue lifestyle changes like dieting, exercise, avoiding smoking, and protecting your eyes from ultraviolet light.

Treatment for Early Dry AMD

The treatment for early dry AMD is generally nutritional therapy, with a healthy diet high in antioxidants to support the cells of the macula.
If AMD is further advanced but still dry, supplements are prescribed, to add higher quantities of certain vitamins and minerals which may increase healthy pigments and support cell structure.

Treatments for Wet AMD: Laser Photocoagulation

Until recently the only available treatment to seal leaking blood vessels associated with wet AMD was with a laser. The earliest treatment was Laser Photocoagulation. Between 1979 and 1994, the Macular Photocoagulation Study Group conducted a number of clinical trials that enrolled patients with CNV lesions (Choroidal Neovascularization) in one or both eyes. Each affected eye was randomly assigned to either laser treatment or observation. For eligible eyes with CNV in extrafoveal, juxtafoveal and subfoveal locations, laser treatment reduced the risk of severe visual loss.

Laser photocoagulation was followed by Photodynamic Therapy (PDT) with Visudyne (a drug injected intravenously and used to help direct the laser to the affected area). Visudyne therapy is a two-step procedure that can be performed in a doctor’s office. First, Visudyne is injected intravenously into the patient’s arm. The drug is then activated by shining non-thermal laser light into the patient’s eye. Visudyne™ therapy involves the use of a specifically-designed laser that produces the low-level, non-thermal light required to activate the drug which results in a selective destruction of the unwanted leaking vessels. The procedure seals off leaking vessels while leaving healthy ones intact and is believed to be a major improvement over previous laser treatments. In one large clinical trial, photodynamic therapy with Visudyne photosensitizer delayed or prevented loss of vision during at least one year follow-up in patients with predominantly classic CNV lesions. Unfortunately, even the most successful treatments do not preclude reoccurrence, making multiple treatments likely. However, the rate of vision loss may be slowed down and some sight may be preserved. It is important to understand that this drug is not a cure. At best it preserves the status quo: It will not restore vision that has already been lost.

In sum, there are three major limitations of laser photocoagulation treatments. First, not more than 10-15% of CNV lesions are small enough and sufficiently delineated by fluorescent angiography to be eligible for laser treatment. Second, even if laser treatment is initially successful, there is at least 50% chance that leakage will recur during the next two years. Many such recurrences are amenable to additional treatment if detected early, which means that patients need careful monitoring after the first treatment. Finally, at least half of patients post-treatment with sufficiently well-circumscribed CNV lesions still have some leakage beneath the center of the fovea. Laser treatment leads to immediate reduction in central vision in these patients with leakages, but with sufficient follow-up, the extent of visual loss is less in laser treated eyes than in untreated eyes. Nevertheless, these existing laser therapies are limited in their effectiveness and may also lead to scarring of the macula and additional vision loss.

Because of the limitations of laser treatment, researchers and physicians are in search of macular degeneration treatment breakthroughs, in order to maintain vision for a longer period of time without repeated laser use. They are also looking for new therapies which would be effective for all types of wet AMD.

Treatments for Wet AMD: Anti-VEGF Therapy

VEGF is an acronym for vascular endothelial growth factor. Currently, the most common and effective clinical treatment for wet Age-related Macular Degeneration is anti-VEGF therapy – which is periodic intravitreal (into the eye) injection of a chemical called an “anti-VEGF.” In the normal life of the human body, VEGF is a healthy molecule which supports the growth of new blood vessels. In the case of macular health, though, VEGF is unhealthy. It promotes the growth of new, weak blood vessels in the choroid layer behind the retina, and those vessels leak blood, lipids, and serum into the retinal layers. The leakage (hemorrhaging) causes scarring in the retina and kills macular cells, including photoreceptor rods and cones.

An intraocular shot of an anti-VEGF drug inhibits the formation of new blood vessels behind the retina and may keep the retina free of leakage. An injection in the eye can be a disconcerting experience, and it may take several treatments to become accustomed to the procedure. However, the shot is usually not painful because the eye has been anesthetized. The procedure takes about fifteen minutes. Usually the appointment requires an hour. The effect lasts for a month or maybe more.

Researchers report high rates of success with anti-VEGF injections, including receding blood vessels behind the retina, a far slower progression of the disease, and, in some cases, moderate gains made in vision. In some parts of the world, anti-VEGF treatments have reduced the incidence of legal blindness by 50 percent. However, they have noted that injections of even small amounts of anti-VEGF drugs could — though research is inconclusive — have an effect on vascular function in the rest of the body. Strokes and hemorrhaging are two concerns, but because cardiovascular disease is already often associated with Age-related Macular Degeneration, any data available to date about strokes or hemorrhaging has been difficult to interpret.

Types of Anti-VEGF Drugs

Several anti-VEGF drugs are being developed to inhibit VEGF by trapping it or preventing it from binding with elements which will stimulate growth. Chemically synthesized short strands of RNA (nucleic acid) called “aptamers” prevent the binding of VEGF to its receptor. The various forms of anti-VEGF injections include ranibizumab (Lucentis, made by Genentech/Novartis), bevacizumab (off label Avastin from Genentech), and the recently Food and Drug Administration-approved aflibercept (Eylea/VEGF Trap-Eye from Regeneron/Bayer). Each of these chemicals works in a different way to inhibit blood vessel growth.

Side Effects of Intravetreal Injections

Side effects of intravetreal injections may include:

Serious eye infection that may include eye pain, light sensitivity, vision changes.

  • Increased eye pressure
  • Retinal detachment
  • Vitreous floaters

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