Article: Macular degeneration

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Human eye cross-sectional view. Courtesy NIH National Eye Institute

Normal vision. Courtesy NIH National Eye Institute

The same view with age-related macular deneneration.

Macular degeneration is a medical condition where the light sensing cells in the macula malfunction and over time cease to work. According to the American Academy of Ophthalmology, it is the leading cause of central vision loss (blindness) in the United States today for those over the age of fifty. There are two basic types of the disease: Standard Macular Degeneration (MD) and Age Related Macular Degeneration (ARMD), with ARMD being the most common form of the condition. Macular degeneration that is not age related is most commonly caused by an inherited condition. These forms are sometimes called Juvenile macular degeneration (JMD). In macular degeneration the final form results in missing or blurred vision in the central, reading part of vision. The outer, peripheral part of the vision remains intact.

Age related macular degeneration

ARMD is further divided into a "dry," or nonexudative, form and a "wet," or exudative, form. Eighty five to ninety percent of cases are categorized as "dry" macular degeneration where fatty tissue, known as drusen, will slowly build up behind the retina. Ten to fifteen percent of cases involve the growth of abnormal blood vessels under the retina. These cases are called "wet" macular degeneration due to the leakage of blood and other fluid from behind the retina into the eye. Wet macular degeneration usually begins as the dry form. If allowed to continue without treatment it will completely destroy the macula. Medical, photodynamic, laser photocoagulation and laser treatment of wet macular degeneration are available.

Risk factors

• Aging: Approximately 10% of patients 66 to 74 years of age will have findings of macular degeneration. The prevalence increases to 30% in patients 75 to 85 years of age.
• Smoking: The only environmental exposure clearly associated with macular degeneration is tobacco smoking [1].
• Family history: The lifetime risk of developing late-stage macular degeneration is 50% for people who have a relative with macular degeneration vs. 12% for people who do not have relatives with macular degeneration, i.e. a four fold higher risk.
• Macular Degeneration Gene: Complement factor H (CFH) and complement factor B (CFB) genes have been determined to be strongly associated with a person's risk for developing macular degeneration. It is not yet clear what initiates the immune response against retina, although this might involve a humoral immune response.
• Hypertension: Also known as high blood pressure.
• Cardiovascular Risk Factors - high cholesterol, obesity.
• High fat intake is associated with an increased risk of macular degeneration in both women and men. Fat provides about 42 % of the food energy in the average American diet. A diet that derives closer to 20-25 % of total food energy from fat is probably healthier. Reducing fat intake to this level means cutting down greatly on consumption of red meats and dairy products such as milk, cheese, and butter. Eating more cold-water fish (at least twice weekly), rather than red meats and eating any type of nuts may help macular degeneration patients.(Reference: Macular degeneration Types and Risk Factors.
• Oxidative stress: It has been proposed that age related accumulation of low molecular weight, phototoxic, pro-oxidant melanin oligomers within lysosomes in the retinal pigment epithelium (RPE) may be partly responsible for decreasing the digestive rate of photoreceptor outer rod segments (POS) by the RPE. A decrease in the digestive rate of POS has been shown to be associated with lipofuscin formation - a classic sign associated with macular degeneration. (Reference: Ophthalmic Research, 2005; volume 37: pages 136-141. "Melanin aggregation and polymerization: possible implications in age related macular degeneration")
• Race Macular degeneration is more likely to be found in whites than in blacks[2][3].
• Exposure to sunlight especially blue light. There is conflicting evidence as to whether exposure to sunlight contributes to the development of macular degeneration. A recent study in the British Journal of Ophthalmology on 446 subjects found that it does not^[1]. High energy visible light (HEV) has been implicated as a cause of age-related macular degeneration^[2][3].

Signs

• Drusen
• Pigmentary alterations
• Exudative changes: hemorrhages, hard exudates, subretinal/sub-RPE/intraretinal fluid
• Atrophy: incipient and geographic
• Visual acuity drastically decreasing (two levels or more) ex: 20/20 to 20/80.

Symptoms

Image courtesy [http://www.agingeye.net/ AgingEye Times

• Blurred vision: Those with nonexudative macular degeneration may by asymptomatic or notice a gradual loss of central vision, whereas those with exudative macular degeneration often notice a rapid onset of vision loss.
• Central scotomas (shadows or missing areas of vision)
• Distorted vision (i.e. metamorphopsia) - A grid of straight lines appears wavy and parts of the grid may appear blank.
• Trouble discerning colors; specifically dark ones from dark ones and light ones from light ones.
• Slow recovery of visual function after exposure to bright light

The Amsler Grid Test is one of the simplest and most effective methods for patients to monitor the health of the macula. The Amsler Grid is essentially a pattern of intersecting lines (identical to graph paper) with a black dot in the middle. The central black dot is used for fixation (a place for the eye to stare at). With normal vision, all lines surrounding the black dot will look straight and evenly spaced with no missing or odd looking areas when fixating on the grid's central black dot. When there is disease affecting the macula, as in macular degeneration, the lines can look bent, distorted and/or missing.

The traditional Amsler grid test is a black and white pattern that may miss early defects (references at www.ixm.us). Since treatment and vision preservation in macular degeneration is facilitated by early detection of the disease, a more sensitive blue-on-yellow Amsler grid test pattern has recently been introduced (IXMUS Home Test).

'Vision loss' or 'blindness' in macular degeneration refers to the loss of 'central vision' only. The peripheral vision is preserved. Blindness in macular degeneration does not mean 'inability to see light' and even with far advanced macular degeneration, the peripheral retina allows for useful vision.

The loss of central vision profoundly affects visual functioning. It is not possible, for example, to read without central vision. Pictures which attempt to depict the central visual loss of macular degeneration with a black spot do not really do justice to the devasting nature of the visual loss. This can be demonstrated by printing letters 6 inches high on a piece of paper and attempting to identify them while looking straight ahead and holding the paper slightly to the side. Most people find this surprisingly difficult to do.

Diagnosis

Fluorescein angiography allows for the identification and localization of abnormal vascular processes.

Treatment

During the early stages of the disease, the neural layers of the retina remain relatively unaffected. This fact makes it a possible target for treatment with a retinal prosthesis, which are currently under development. Recently, the drug Lucentis has been cleared by the FDA for use in the treatment of AMD. Lucentis has been shown to not only halt the progession of the disease, but also works to reverse its effects-- and over time improve the patient's vision.

Prevention

Research on prevention of AMD

Several macular degeneration clinical trials are currently underway. The most promising approach is the anti-angiogenesis treatment for wet macular degeneration. Different anti-angiogenesis strategies that block VEGF-mediated choroidal neovascularization are being evaluated in clinical trials. Drugs currently approved for wet macular degeneration include: pegaptanib (Macugen). Drugs under investigation include: ranibizumab (Lucentis), anecortave (Retaane), bevacizumab (Avastin), squalamine (Evizon) and siRNA. Second generation antisense oligonucleotides iCo-007 targeting the Raf-1 kinase are also under investigation as a target for broad inhibition of multiple pro-angiogenic signals. The most promising of these treatments, ranibizumab (Lucentis), is the 1st drug tested that has shown significant improvement in visual acuity in multiple phase III trials. Radiation therapy (brachytherapy) and rheopheresis are also being evaluated for wet macular degeneration[4].

Recent studies suggest that statins, a family of drugs used for reducing cholesterol levels, may be effective in prevention of AMD, and in slowing its progression[5].

The Age-Related Eye Disease Study concluded that high levels of antioxidants and zinc can reduce some people's risk of developing advanced AMD by about 25 percent. In 2006 AREDS II is under way to study the effects of Genistein (a derivative in Soyabeans).

Juvenile macular degeneration

"Macular degeneration" is a descriptive term for any condition which leads to loss of function of the light sensitive cells at the center of the retina. Several rare hereditary conditions can lead to macular degeneration in children and adolescents. These include:

• Autosomal dominant hemorrhagic macular dystrophy
• Best's disease
• Doyne's honeycomb retinal dystrophy
• Sorsby's disease
• Stargardt's disease

Impact

Macular degeneration, especially the more aggressive wet form, can result in legal blindness, resulting in a loss of driving privileges and an inability to read all but very large type. Perhaps the most grievous loss is the inability to see faces clearly or at all.

Some of these losses can be offset by the use of adaptive devices. A closed-circuit television reader can make reading possible, and specialized screen-reading computer software, e.g., Jaws for Windows, can give the blind person access to word processing, spreadsheet, financial, and e-mail access.

Notes

See also

• Lutein
• Zeaxanthin