Age-Related Macular Degeneration (AMD)

Age-related macular degeneration (AMD)

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Age-Related Macular Degeneration (AMD) is a deterioration of the macula, the central area of the retina,  that can cause substantial central visual loss but almost never total blindness. AMD is the leading cause of significant visual acuity loss in seniors and dramatically increases with age. There are 2 types of AMD: non-neovascular or dry AMD; and neovascular or wet AMD.

Handout Age-related Macular Degeneration
AMD can cause central visual defects, distortion or blurring

The retina is a thin layer of light sensitive nerve tissue lining the inner wall of the eye. When light is focused onto the retina, the images are converted into electrical signals that are carried from the eye to the brain by the trunk line of the optic nerve. The visual portion of the brain interprets these as images. The macula is the specialized portion of the central retina packed with cone photoreceptors and is the only part of the retina capable of fine vision and reading. Imaging can visualize most of the layers of the retina that are only a few hundred microns thick in the center.

The Retina Layers

Dry Age-Related Macular Degeneration (Dry AMD)

Dry AMD usually starts with discolored yellowish spots on the retina, called drusen analogous to blotchy skin. Dry AMD typically slowly progresses over years with pigment changes and then progress to a confluent spot of pigment loss called geographic atrophy (GA) with a missing, or central blind spot.

Drusen precursors of Dry AMD
Drusen precursors of Dry AMD
Intermediate dry AMD with more drusen and pigmentary change in the central macula.
Intermediate dry AMD with more drusen and pigmentary change in the central macula.

Wet Age-Related Macular Degeneration (exudative or neovascular) AMD

In contrast, wet (exudative or neovascular) AMD involves fluid or blood leaking from an abnormal blood vessel that grows from the choroid layer of blood vessels under the retina. As it progresses, it leaks under or within the retina causing thicken.  Subsequently, the abnormal choroidal neovascular membrane bleeds and then scar tissue forms with irreversible loss of central vision.

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[photo/caption] Intermediate Wet AMD

Early Wet AMD. Choroidal neovascularization
Early Wet AMD. Choroidal neovascularization
Advanced Wet AMD with Disciform scar
Advanced Wet AMD with Disciform scar

Age-Related Macular Degeneration (AMD) Symptoms

The macula is responsible for the fine central vision for tasks such as reading small print and is subject to over 50 other conditions. In early stages, AMD (and other macular problems) may have no symptoms at all. The dry type of macular degeneration usually progresses very slowly with fewer symptoms that slowly progress over a period of decade. The wet type can progress suddenly with distortion and progressive central visual loss that, without treatment, usually causes loss of most of the central vision within 6 months or a year at most. Macular degeneration symptoms include:

  • Distortion (warping) of straight lines such as a venetian blind
  • Faded colors
  • Loss of central vision with difficulty reading and seeing faces
  • Dark, blurry areas in the center of vision

 

Advanced AMD causes loss of the central vision. Courtesy NEI-NIH.
Advanced AMD causes loss of the central vision. Courtesy NEI-NIH.
Amsler grid showing different effects from macular degeneration on vision

Amsler Grid Test for AMD

An Amsler grid is an excellent tool for monitoring the macula. The test is performed one eye at a time with glasses used for reading. Symptoms of a macular problem are noted in about 90% of cases but not always.

AMD RISK FACTORS

  • Age—the strongest risk factor
  • Family history of AMD
  • Caucasian race
  • Cigarette smoking

Possible AMD risk factors:

  • Female gender
  • High blood pressure
  • Higher level of education
  • High cholesterol
  • Light iris color
  • Sunlight exposure
  • Far-sightedness
  • Low dietary fish intake
  • Cardiovascular (heart) disease
  • Use of more than 2 full aspirins daily

Diagnostic testing

When symptoms or exam findings are noted on clinical exam, additional testing may be performed including imaging to determine the presence or absence of a leak, an abnormal blood vessel or to identify other causes of the macular disease. Disease features related to AMD may be found in the retina and in the layers beneath it. According to these abnormal findings, AMD is classified as dry or wet.

An AMD diagnosis is confirmed with specialized imaging, including:

  • Optical coherence tomography (OCT). This non-invasive imaging technique uses a low power laser light to create a 3-dimensional image of your retina that shows leakage within or under the retina.
  • Fundus autofluoresce. This imaging technique uses a blue light to illuminate the retina. Special filters allow the reflected light to be captured often identifying areas of dry macular degeneration
  • Fluorescein angiography (FA). This imaging technique utilizes a teaspoon of a yellow vegetable dye called fluorescein that is injected into a vein in the arm. A low power laser imaging instrument records the circulation in the retina and choroid in the back of the eye. The dye is excreted rapidly in the urine and can be used in most patients with renal disease. This test can be very useful in diagnosing a number of retinal disorders.
  • Indocyanine green angiography (ICG). This diagnostic procedure  uses a green dye to illuminate blood flow in the choroid, which is a layer of blood vessels located under the retina where the abnormal neovascular membranes usually originate.

Other tests helpful for evaluating both dry and wet AMD include:

  • Color photographs to document the number and location of drusen, the presence or absence of pigment, blood or discoloration and the extent of the area involved. The digital pictures are useful for following the disease for progression and response to treatment.
  • Visual fields.  Blind spots  near the center of the vision may be identified with testing of the central visual field. These defects may cause problems with reading even when the vision is 20/20.
  • Color vision may be affected by macular degeneration.

ICG diagnostic procedure
ICG diagnostic procedure
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Intravitreal injections (c)2016 James M Maisel
Intravitreal Injection (c)2016 James M Maisel

Treatment and prognosis for Dry AMD

No treatment can prevent visual loss for patients with geographic atrophy (GA), the advanced form of dry AMD but there are at least 2 encouraging drug treatments under Stage III Clinical trials. However, the Age-Related Eye Disease Studies (AREDS), conducted on 5000 patients by the National Eye Institute, have found that a nutritional supplement formula may delay and prevent intermediate dry AMD from progressing to the advanced form. The AREDS 2 supplement formula, which is widely available over the counter, contains:

  • Vitamin C
  • Lutein
  • Vitamin E
  • Zeaxanthin
  • Zinc (with Copper)

Higher doses of these supplements are not more effective and may interfere with other medications or cause side effects and are not recommended. Vitamin E doses over 400 units daily are associated with other medical problems. Taking Zinc without Copper may cause anemia and there are studies regarding stomach problems and possibly early Alzheimer’s with high doses of Zinc. Keeping active, eating healthy, avoiding smoking are thought to be beneficial. Although patients with either form of AMD can experience a severe decrease in visual acuity, they will almost never be completely blind.

Treatment and prognosis for Wet AMD

Prior to 2006, most patients with neovascular or wet AMD could not benefit from, or failed to respond to thermal laser or photodynamic therapy (Visudyne PDT) and lost central vision.

Since 2006, wet-AMD treatment has been revolutionized stemming from a Nobel Prize winning discovery of vascular endothelial growth factors (VEGF), a family of compounds in the body. VEGF regulates the growth of abnormal new blood vessels in the eye—known as neovascularization—that can lead to wet AMD. Anti-VEGF drugs have been developed to help stop neovascularization and preserve vision for AMD patients.

There are currently 3 anti-VEGF drugs:

  • Avastin® (bevacizumab®) non-FDA approved off-label usage
  • Lucentis® (ranibizumab®) FDA approved for neovascular AMD
  • Eylea® (aflibercept®)  FDA approved for neovascular AMD

Wet AMD cannot be cured, but its progression may be blocked with the use of intravitreal (in-the-eye) anti-VEGF injections. Local anesthetic eye drops are given before the injections to numb the eye and minimize discomfort and the treatment is quickly performed in the office. While controversy exists over the frequency and treatment regimens, most data suggests that regular suppressive treatments, on a monthly to bimonthly basis, allow 90% of patients to maintain vision for at least 2 years and about ? show significant visual improvement. The medication washes out of the eye within weeks and without regular treatment the vessels often recur and eventually cause bleeding and irreversible scarring. When patients who did well with regular injections for 2 years were only treated an average of 4 times a year, over half lose their reading vision by five years. Many patients at the Retina Group of New York have received treatments for 10 years  and have maintained their vision, especially when treated on a regular basis. Fewer than 1 % of patients experience any of the more serious complications of the injections such as retinal detachment, bleeding, cataract progression or infection.

How the Eye Works and AMD
EyeSmart -  American Academy of Ophthalmology