Macular degeneration

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Macular degeneration is a medical condition predominantly found in elderly adults in which the center of the inner lining of the eye, known as the macula area of the retina, suffers thinning, atrophy, and in some cases bleeding. This can result in loss of central vision, which entails inability to see fine details, to read, or to recognize faces. 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 years.^[1] Although some macular dystrophies that affect younger individuals are sometimes referred to as macular degeneration, the term generally refers to age-related macular degeneration (AMD or ARMD).

Macular degeneration should be differentiated from other causes of distorted vision with a very different etiology and different treatment such as epiretinal membrane or macular pucker or leaking blood vessels in the eye.

Macular degeneration, in its advanced forms, 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.

Fluorescein angiography allows for the identification and localization of abnormal vascular processes. Optical coherence tomography is now used by most ophthalmologists in the diagnosis and the followup evaluation of the response to treatment by using either Avastin or Lucentis which are injected into the vitreous of the eye at various intervals.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Age-related macular degeneration begins with characteristic yellow deposits in the macula (central area of the retina which provides detailed central vision) called drusen between the retinal pigment epithelium and the underlying choroid. Most people with these early changes (referred to as age-related maculopathy) have good vision. People with drusen can go on to develop advanced AMD. The risk is considerably higher when the drusen are large and numerous and associated with disturbance in the pigmented cell layer under the macula. Recent research suggests that large and soft drusen are related to elevated cholesterol deposits and may respond to cholesterol lowering agents or the Rheo Procedure.

Advanced AMD, which is responsible for profound vision loss, has two forms: dry and wet. Central geographic atrophy, the dry form of advanced AMD, results from atrophy to the retinal pigment epithelial layer below the retina, which causes vision loss through loss of photoreceptors (rods and cones) in the central part of the eye. While no treatment is available for this condition, vitamin supplements with high doses of antioxidants, lutein and zeaxanthin, have been demonstrated by the National Eye Institute and others to slow the progression of dry macular degeneration and in some patients, improve visual acuity.

Neovascular or exudative AMD, the wet form of advanced AMD, causes vision loss due to abnormal blood vessel growth in the choriocapillaries, through Bruch’s membrane, ultimately leading to blood and protein leakage below the macula. Bleeding, leaking, and scarring from these blood vessels eventually cause irreversible damage to the photoreceptors and rapid vision loss if left untreated.

Until recently, no effective treatments were known for wet macular degeneration. However, new drugs, called anti-angiogenics or anti-VEGF (anti-Vascular Endothelial Growth Factor) agents, when injected directly into the vitreous humor of the eye using a small, painless needle, can cause regression of the abnormal blood vessels and improvement of vision. The injections frequently have to be repeated on a monthly or bi-monthly basis. Examples of these agents include Lucentis, Avastin, and Macugen. Only Lucentis and Macugen are FDA approved as of April 2007. Macugen has been found to have only minimal benefits in neovascular AMD and is no longer used. Worldwide, Avastin has been used extensively, with excellent results, despite its “off label” status. Genentech, the maker of both Avastin and Lucentis, has been hoping to promote the use of Lucentis due to the potential for much higher revenues. The cost of Lucentis is approximately 2000 USD while the cost of Avastin is approximately 50 USD. Fortunately, retinal specialists worldwide have together proven that Avastin is at least as effective and safe as Lucentis, at a fraction of the cost.

Juvenile macular degeneration is not a term in standard usage at this time. The preferred term for conditions that affect the macula in younger individuals related to genetics is macular dystrophy. Examples of these include:

• Best’s disease
• Doyne’s honeycomb retinal dystrophy
• Sorsby’s disease
• Stargardt’s disease

The first genetic link to juvenile macular degeneration was discovered at the Cleveland Clinic.

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Macular degeneration should be differentiated from other causes of distorted vision with a very different etiology and different treatment such as epiretinal membrane or macular pucker or leaking blood vessels in the eye.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

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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.

Macular degeneration is more likely to be found in whites than in blacks.^[1][2]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

• Smoking: The only environmental exposure clearly associated with macular degeneration is tobacco smoking. Exposure to cigarette smoke more than doubles the risk of macular degeneration.
• Family history: The lifetime risk of developing late-stage macular degeneration is 50% for people who have a relative with macular degeneration v/s 12% for people who do not have relatives with macular degeneration, i.e. a fourfold higher risk.
• Macular degeneration gene: The genes for the complement system proteins factor H (CFH) and factor B (CFB) have been determined to be strongly associated with a person’s risk for developing macular degeneration. CFH is involved in inhibiting the inflammatory response mediated via C3b (and the alternative pathway of complement) both by acting as a co-factor for cleavage of C3b to its inactive form, C3bi, and by weakening the active complex that forms between C3b and factor B. C-reactive protein and polyanionic surface markers such as glycosaminoglycans normally enhance the ability of factor H to inhibit complement. But the mutation in CFH (Tyr402His) reduces the affinity of CFH for CRP and probably also alters the ability of factor H to recognize specific glycosaminoglycans. This change results in reduced ability of CFH to regulate complement on critical surfaces such as the specialized membrane at the back of the eye and leads to increased inflammatory response within the macula. In two 2006 studies at Yale Department of Epidemiology and Public Health and the Department of Ophthalmology and Visual Sciences, Moran Eye Center at the University of Utah School of Medicine, another gene that has implications for the disease, called HTRA1 (encoding a secreted serine protease), was identified.^[1][2]
• Arg80Gly Variant of the Complement Protein C3: A genetic study published in the New England Journal of Medicine in 2007 showed that a certain, common mutation in the C3 gene which is a central protein of the complement system is strongly associated with the occurrence of age-related macular degeneration.^[3] This authors consider their study to underscore the influence of the complement pathway in the pathogenesis of this disease.
• Hypertension: Also known as high blood pressure.
• Cardiovascular status: High cholesterol, obesity.
• High fat intake: It 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^[4] (at least twice weekly), rather than red meats, and eating any type of nuts may help macular degeneration patients.
• 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 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.^[5][6]
• 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.^[7] High energy visible light (HEV) has been implicated as a cause of age-related macular degeneration.^[8][9]

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Macular degeneration, in its advanced forms, 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.

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