Macular degeneration
Overview
 
Age-related macular degeneration (AMD) is a medical condition which usually affects older adults and results in a loss of vision in the center of the visual field (the macula
Macula
The macula or macula lutea is an oval-shaped highly pigmented yellow spot near the center of the retina of the human eye. It has a diameter of around 5 mm and is often histologically defined as having two or more layers of ganglion cells...

) because of damage to the retina
Retina
The vertebrate retina is a light-sensitive tissue lining the inner surface of the eye. The optics of the eye create an image of the visual world on the retina, which serves much the same function as the film in a camera. Light striking the retina initiates a cascade of chemical and electrical...

. It occurs in “dry” and “wet” forms. It is a major cause of blindness and visual impairment in older adults (>50 years). Macular degeneration can make it difficult or impossible to read or recognize faces, although enough peripheral vision remains to allow other activities of daily life.

Starting from the inside of the eye
Human eye
The human eye is an organ which reacts to light for several purposes. As a conscious sense organ, the eye allows vision. Rod and cone cells in the retina allow conscious light perception and vision including color differentiation and the perception of depth...

 and going towards the back, the three main layers at the back of the eye are the retina
Retina
The vertebrate retina is a light-sensitive tissue lining the inner surface of the eye. The optics of the eye create an image of the visual world on the retina, which serves much the same function as the film in a camera. Light striking the retina initiates a cascade of chemical and electrical...

, which contains the nerves; the choroid
Choroid
The choroid, also known as the choroidea or choroid coat, is the vascular layer of the eye, containing connective tissue, and lying between the retina and the sclera. The human choroid is thickest at the far extreme rear of the eye , while in the outlying areas it narrows to 0.1 mm...

, which contains the blood supply; and the sclera
Sclera
The sclera , also known as the white or white of the eye, is the opaque , fibrous, protective, outer layer of the eye containing collagen and elastic fiber. In the development of the embryo, the sclera is derived from the neural crest...

, which is the white of the eye.

The macula is the central area of the retina, which provides the most detailed central vision.

In the dry (nonexudative) form, cellular debris called drusen
Drusen
Drusen are tiny yellow or white accumulations of extracellular material that build up in Bruch's membrane of the eye. The presence of a few small drusen is normal with advancing age, and most people over 40 have some hard drusen...

 accumulate between the retina and the choroid, and the retina can become detached.
Encyclopedia
Age-related macular degeneration (AMD) is a medical condition which usually affects older adults and results in a loss of vision in the center of the visual field (the macula
Macula
The macula or macula lutea is an oval-shaped highly pigmented yellow spot near the center of the retina of the human eye. It has a diameter of around 5 mm and is often histologically defined as having two or more layers of ganglion cells...

) because of damage to the retina
Retina
The vertebrate retina is a light-sensitive tissue lining the inner surface of the eye. The optics of the eye create an image of the visual world on the retina, which serves much the same function as the film in a camera. Light striking the retina initiates a cascade of chemical and electrical...

. It occurs in “dry” and “wet” forms. It is a major cause of blindness and visual impairment in older adults (>50 years). Macular degeneration can make it difficult or impossible to read or recognize faces, although enough peripheral vision remains to allow other activities of daily life.

Starting from the inside of the eye
Human eye
The human eye is an organ which reacts to light for several purposes. As a conscious sense organ, the eye allows vision. Rod and cone cells in the retina allow conscious light perception and vision including color differentiation and the perception of depth...

 and going towards the back, the three main layers at the back of the eye are the retina
Retina
The vertebrate retina is a light-sensitive tissue lining the inner surface of the eye. The optics of the eye create an image of the visual world on the retina, which serves much the same function as the film in a camera. Light striking the retina initiates a cascade of chemical and electrical...

, which contains the nerves; the choroid
Choroid
The choroid, also known as the choroidea or choroid coat, is the vascular layer of the eye, containing connective tissue, and lying between the retina and the sclera. The human choroid is thickest at the far extreme rear of the eye , while in the outlying areas it narrows to 0.1 mm...

, which contains the blood supply; and the sclera
Sclera
The sclera , also known as the white or white of the eye, is the opaque , fibrous, protective, outer layer of the eye containing collagen and elastic fiber. In the development of the embryo, the sclera is derived from the neural crest...

, which is the white of the eye.

The macula is the central area of the retina, which provides the most detailed central vision.

In the dry (nonexudative) form, cellular debris called drusen
Drusen
Drusen are tiny yellow or white accumulations of extracellular material that build up in Bruch's membrane of the eye. The presence of a few small drusen is normal with advancing age, and most people over 40 have some hard drusen...

 accumulate between the retina and the choroid, and the retina can become detached. In the wet (exudative) form, which is more severe, blood vessels grow up from the choroid behind the retina, and the retina can also become detached. It can be treated with laser coagulation, and with medication that stops and sometimes reverses the growth of blood vessels.

Although some macular dystrophies affecting younger individuals are sometimes referred to as macular degeneration, the term generally refers to age-related macular degeneration (AMD or ARMD).

Age-related macular degeneration begins with characteristic yellow deposits (drusen
Drusen
Drusen are tiny yellow or white accumulations of extracellular material that build up in Bruch's membrane of the eye. The presence of a few small drusen is normal with advancing age, and most people over 40 have some hard drusen...

) in the macula, between the retinal pigment epithelium and the underlying choroid
Choroid
The choroid, also known as the choroidea or choroid coat, is the vascular layer of the eye, containing connective tissue, and lying between the retina and the sclera. The human choroid is thickest at the far extreme rear of the eye , while in the outlying areas it narrows to 0.1 mm...

. 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.

Classification

'Early' AMD is before some loss of vision. 'Advanced' AMD is after some loss of vision.

Dry AMD

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. No medical or surgical treatment is available for this condition, however vitamin supplements with high doses of antioxidants, lutein
Lutein
Lutein is a xanthophyll and one of 600 known naturally occurring carotenoids. Lutein is synthesized only by plants and like other xanthophylls is found in high quantities in green leafy vegetables such as spinach and kale...

 and zeaxanthin
Zeaxanthin
Zeaxanthin is one of the most common carotenoid alcohols found in nature. It is important in the xanthophyll cycle. Synthesized in plants & some micro-organisms, it is the pigment that gives paprika , corn, saffron, and many other plants & microbes their characteristic color.The name is derived...

, have been suggested by the National Eye Institute and others to slow the progression of dry macular degeneration and, in some patients, improve visual acuity.

Higher beta-Carotene
Beta-carotene
β-Carotene is a strongly-coloured red-orange pigment abundant in plants and fruits. It is an organic compound and chemically is classified as a hydrocarbon and specifically as a terpenoid , reflecting its derivation from isoprene units...

 intake was associated with an increased risk of AMD.

Wet AMD

Neovascular or exudative AMD, the “wet” form of advanced AMD, causes vision loss due to abnormal blood vessel growth (choroidal neovascularization
Choroidal neovascularization
Choroidal neovascularization is the creation of new blood vessels in the choroid layer of the eye. This is a common symptom of the degenerative maculopathy wet AMD .-Causes:...

) in the choriocapillaris
Choriocapillaris
The capillary lamina of choroid or choriocapillaris is a layer of capillaries that is immediately adjacent to Bruch's membrane in the choroid....

, through Bruch's membrane
Bruch's membrane
Bruch's membrane is the innermost layer of the choroid. It is also called the vitreous lamina, because of its glassy microscopic appearance.It is 2–4 μm thick.-Layers:Bruch's membrane consists of five layers :...

, 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.

Only about 10% of patients suffering from macular degeneration have the wet type.

Macular degeneration is not painful, and this may allow it to go unnoticed for some time.

Signs and symptoms

  • Drusen
    Drusen
    Drusen are tiny yellow or white accumulations of extracellular material that build up in Bruch's membrane of the eye. The presence of a few small drusen is normal with advancing age, and most people over 40 have some hard drusen...

  • Pigmentary alterations
  • Exudative changes: hemorrhages in the eye, 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.
  • Preferential hyperacuity perimetry
    Preferential hyperacuity perimetry
    Preferential hyperacuity perimetry is a psychophysical test used to identify and quantify visual abnormalities such as metamorphopsia and scotoma.-Background:...

     changes (for wet AMD)

  • Blurred vision: Those with nonexudative macular degeneration may be asymptomatic or notice a gradual loss of central vision, whereas those with exudative macular degeneration often notice a rapid onset of vision loss.
  • Central scotoma
    Scotoma
    A scotoma is an area of partial alteration in one's field of vision consisting of a partially diminished or entirely degenerated visual acuity which is surrounded by a field of normal - or relatively well-preserved - vision.Every normal mammalian eye has a scotoma in its field of vision, usually...

    s (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. Patients often first notice this when looking at mini-blinds in their home.
  • 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
  • A loss in contrast sensitivity
    Contrast (vision)
    Contrast is the difference in visual properties that makes an object distinguishable from other objects and the background. In visual perception of the real world, contrast is determined by the difference in the color and brightness of the object and other objects within the same field of view...

    .


Macular degeneration by itself will not lead to total blindness. For that matter, only a very small number of people with visual impairment are totally blind. In almost all cases, some vision remains. Other complicating conditions may possibly lead to such an acute condition (severe stroke or trauma, untreated glaucoma, etc.), but few macular degeneration patients experience total visual loss. The area of the macula comprises only about 2.1% of the retina, and the remaining 97.9% (the peripheral field) remains unaffected by the disease. Interestingly, even though the macula provides such a small fraction of the visual field, almost half of the visual cortex is devoted to processing macular information.

The loss of central vision profoundly affects visual functioning. It is not possible, for example, to read without central vision. Pictures that attempt to depict the central visual loss of macular degeneration with a black spot do not really do justice to the devastating 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 difficult to do.

There is a loss of contrast sensitivity, so that contours, shadows, and color vision are less vivid. The loss in contrast sensitivity can be quickly and easily measured by a contrast sensitivity test performed either at home or by an eye specialist.

Similar symptoms with a very different etiology and different treatment can be caused by Epiretinal membrane
Epiretinal membrane
Epiretinal membrane is a disease of the eye in response to changes in the vitreous humor or more rarely, diabetes. It is also called macular pucker. Sometimes, as a result of immune system response to protect the retina, cells converge in the macular area as the vitreous ages and pulls away in...

 or macular pucker or leaking blood vessels in the eye.

Causes and 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.
  • Family history: The lifetime risk of developing late-stage macular degeneration is 50% for people that have a relative with macular degeneration, versus 12% for people that do not have relatives with macular degeneration, a fourfold higher risk. Researchers from the University of Southampton
    University of Southampton
    The University of Southampton is a British public university located in the city of Southampton, England, a member of the Russell Group. The origins of the university can be dated back to the founding of the Hartley Institution in 1862 by Henry Robertson Hartley. In 1902, the Institution developed...

     reported October 7, 2008 that they had discovered six mutations of the gene SERPING1 that are associated with AMD. Mutations in this gene can also cause hereditary angioedema
    Hereditary angioedema
    Hereditary angioedema presents in the second to fourth decade, and is characterized by local swelling in subcutaneous tissues....

    .
  • Macular degeneration gene: The genes for the complement system
    Complement system
    The complement system helps or “complements” the ability of antibodies and phagocytic cells to clear pathogens from an organism. It is part of the immune system called the innate immune system that is not adaptable and does not change over the course of an individual's lifetime...

     proteins factor H
    Factor H
    Factor H is a member of the regulators of complement activation family and is a complement control protein. It is a large , soluble glycoprotein that circulates in human plasma...

     (CFH), factor B (CFB) and factor 3 (C3) 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 cofactor for cleavage of C3b to its inactive form, C3bi, and by weakening the activecomplex 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 recognise specific glycosaminoglycans. This change results in reduced ability of CFH to regulate complement on critical surfaces such as the specialised 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.
    The mitochondrial genome (mtDNA) in humans is contained on a single circular chromosome 16,569 basepairs around, and each mitochondrion contains 5 to 10 copies of the mitochondrial chromosome. There are several essential genes in mtDNA that are involved in replication and translation, along with some genes that are crucial for the machinery that converts metabolic energy into ATP. These include NADH dehydrogenase, cytochrome c oxidase, ubiquinol/cytochrome c oxidoreductase, and ATP synthase, as well as the genes for unique ribosomal RNA and transfer RNA particles that are required for translating these genes into proteins.
    There are specific diseases associated with mutations in some of these genes. Below is one of the affected genes and the disease that arises from its mutation.
    • Mutation of the ATP synthase gene: Retinitis pigmentosa
      Retinitis pigmentosa
      Retinitis pigmentosa is a group of genetic eye conditions that leads to incurable blindness. In the progression of symptoms for RP, night blindness generally precedes tunnel vision by years or even decades. Many people with RP do not become legally blind until their 40s or 50s and retain some...

       (RP) is a genetically linked dysfunction of the retina and is related to mutation of the adenosine triphosphate (ATP) synthase gene 615.1617

  • Stargardt's disease
    Stargardt's disease
    Stargardt disease, or fundus flavimaculatus, is an inherited juvenile macular degeneration that causes progressive vision loss usually to the point of legal blindness...

     (STGD, also known as juvenile macular degeneration) is an autosomal recessive retinal disorder characterized by a juvenile-onset macular dystrophy, alterations of the peripheral retina, and subretinal deposition of lipofuscin-like material. A gene encoding an ATP-binding cassette (ABC) transporter was mapped to the 2-cM (centiMorgan) interval at 1p13-p21 previously shown by linkage analysis to harbor the STGD gene. This gene, ABCR, is expressed exclusively and at high levels in the retina, in rod but not cone photoreceptors, as detected by in situ hybridization. Mutational analysis of ABCR in STGD families revealed a total of 19 different mutations including homozygous mutations in two families with consanguineous parentage. These data indicate that ABCR is the causal gene of STGD/FFM.

  • Drusen: CMSD studies indicate that drusen
    Drusen
    Drusen are tiny yellow or white accumulations of extracellular material that build up in Bruch's membrane of the eye. The presence of a few small drusen is normal with advancing age, and most people over 40 have some hard drusen...

     are similar in molecular composition to plaques and deposits in other age-related diseases such as Alzheimer's disease and atherosclerosis. While there is a tendency for drusen to be blamed for the progressive loss of vision, drusen deposits can be present in the retina without vision loss. Some patients with large deposits of drusen have normal visual acuity. If normal retinal reception and image transmission are sometimes possible in a retina when high concentrations of drusen are present, then, even if drusen can be implicated in the loss of visual function, there must be at least one other factor that accounts for the loss of vision.

  • Arg80Gly variant of the complement protein C3
    Complement system
    The complement system helps or “complements” the ability of antibodies and phagocytic cells to clear pathogens from an organism. It is part of the immune system called the innate immune system that is not adaptable and does not change over the course of an individual's lifetime...

    : Two independent studies published in the New England Journal of Medicine and Nature Genetics in 2007 showed that a certain common mutation in the C3 gene which is a central protein of the complement system
    Complement system
    The complement system helps or “complements” the ability of antibodies and phagocytic cells to clear pathogens from an organism. It is part of the immune system called the innate immune system that is not adaptable and does not change over the course of an individual's lifetime...

     is strongly associated with the occurrence of age-related macular degeneration. The authors of both papers 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
    Obesity
    Obesity is a medical condition in which excess body fat has accumulated to the extent that it may have an adverse effect on health, leading to reduced life expectancy and/or increased health problems...

    .

  • 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
    Food energy
    Food energy is the amount of energy obtained from food that is available through cellular respiration.Food energy is expressed in food calories or kilojoules...

     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 high-fat dairy products such as whole 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.

  • Oxidative stress: It has been proposed that age-related accumulation of low-molecular-weight, phototoxic, pro-oxidant
    Pro-oxidant
    Pro-oxidants are chemicals that induce oxidative stress, through either creating reactive oxygen species or inhibiting antioxidant systems. The oxidative stress produced by these chemicals can damage cells and tissues...

     melanin
    Melanin
    Melanin is a pigment that is ubiquitous in nature, being found in most organisms . In animals melanin pigments are derivatives of the amino acid tyrosine. The most common form of biological melanin is eumelanin, a brown-black polymer of dihydroxyindole carboxylic acids, and their reduced forms...

     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
    Lipofuscin
    Lipofuscin is the name given to finely granular yellow-brown pigment granules composed of lipid-containing residues of lysosomal digestion. It is considered one of the aging or "wear-and-tear" pigments, found in the liver, kidney, heart muscle, adrenals, nerve cells, and ganglion cells...

     formation - a classic sign associated with macular degeneration.

  • Fibulin-5 mutation: Rare forms of the disease are caused by geneic defects in fibulin-5, in an autosomal dominant manner. In 2004, Stone et al. performed a screen on 402 AMD patients and revealed a statistically significant correlation between mutations in Fibulin-5 and incidence of the disease. Furthermore, the point mutants were found in the calcium binding sites of the cbEGF domains of the protein. There is no structural basis for the effects of the mutations.

  • Race: Macular degeneration is more likely to be found in Caucasians than in people of African descent.

  • 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. Other research, however, has shown that high-energy visible light (HEV) may contribute to age-related macular degeneration.

  • Smoking: Smoking tobacco increases the risk of macular degeneration by two to three times that of someone who has never smoked, and may be the most important modifiable factor in its prevention. A review of previous studies found that "the literature review confirmed a strong association between current smoking and AMD. ... Cigarette smoking is likely to have toxic effects on the retina."

  • Deletion of CFHR3 and CFHR1: Deletion of the complement factor H-related genes CFHR3 and CFHR1 protects against age-related macular degeneration.

Genetic testing

A practical application of AMD-associated markers is in the prediction of progression of AMD from early stages of the disease to neovascularization.

Early work demonstrated that a family of immune mediators was plentiful in drusen
Drusen
Drusen are tiny yellow or white accumulations of extracellular material that build up in Bruch's membrane of the eye. The presence of a few small drusen is normal with advancing age, and most people over 40 have some hard drusen...

. complement factor H
Factor H
Factor H is a member of the regulators of complement activation family and is a complement control protein. It is a large , soluble glycoprotein that circulates in human plasma...

 (CFH) is an important inhibitor of this inflammatory cascade and a disease-associated polymorphism in the CFH gene strongly associates with AMD. Thus an AMD pathophysiological model of chronic low grade complement activation and inflammation in the macula has been advanced. Lending credibility to this has been the discovery of disease-associated genetic polymorphisms in other elements of the complement cascade including complement component 3 (C3).

The role of retinal oxidative stress
Oxidative stress
Oxidative stress represents an imbalance between the production and manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage...

 in the etiology
Etiology
Etiology is the study of causation, or origination. The word is derived from the Greek , aitiologia, "giving a reason for" ....

 of AMD by causing further inflammation of the macula
Macula
The macula or macula lutea is an oval-shaped highly pigmented yellow spot near the center of the retina of the human eye. It has a diameter of around 5 mm and is often histologically defined as having two or more layers of ganglion cells...

 is suggested by the enhanced rate of disease in smokers and those exposed to UV irradiation. Mitochondria
Mitochondrion
In cell biology, a mitochondrion is a membrane-enclosed organelle found in most eukaryotic cells. These organelles range from 0.5 to 1.0 micrometers in diameter...

 are a major source of oxygen free radicals that occur as a byproduct of energy metabolism. Mitochondrial gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...

 polymorphisms, such as that in the MT-ND2 molecule, predicts wet AMD.

A powerful predictor of AMD is found on chromosome 10q26 at LOC 387715. An insertion/deletion polymorphism at this site reduces expression of the ARMS2
ARMS2
Age-related maculopathy susceptibility protein 2, mitochondrial is a protein that in humans is encoded by the ARMS2 gene.-Further reading:...

 gene though destabilization of its mRNA through deletion of the polyadenylation
Polyadenylation
Polyadenylation is the addition of a poly tail to an RNA molecule. The poly tail consists of multiple adenosine monophosphates; in other words, it is a stretch of RNA that has only adenine bases. In eukaryotes, polyadenylation is part of the process that produces mature messenger RNA for translation...

 signal. ARMS2
ARMS2
Age-related maculopathy susceptibility protein 2, mitochondrial is a protein that in humans is encoded by the ARMS2 gene.-Further reading:...

 protein may localize to the mitochondria and participate in energy metabolism, though much remains to be discovered about its function.

Other gene markers of progression risk includes Tissue Inhibitor of Metalloproteinase 3 (TIMP3
TIMP3
Metalloproteinase inhibitor 3 is an protein that in humans is encoded by the TIMP3 gene.This gene belongs to the tissue inhibitor of metalloproteinases gene family. The proteins encoded by this gene family are inhibitors of the matrix metalloproteinases, a group of peptidases involved in...

) suggesting a role for intracellular matrix metabolism in AMD progression. Variations in cholesterol metabolising genes such as the hepatic lipase
Hepatic lipase
Hepatic lipase is a form of lipase. It is expressed in the liver and adrenal glands.One of the principal functions of hepatic lipase is to convert IDL to LDL.-Clinical significance:...

 (LIPC), cholesterol ester transferase (CETP), lipoprotein lipase
Lipoprotein lipase
Lipoprotein lipase is a member of the lipase gene family, which includes pancreatic lipase, hepatic lipase, and endothelial lipase. It is a water soluble enzyme that hydrolyzes triglycerides in lipoproteins, such as those found in chylomicrons and very low-density lipoproteins , into two free...

 (LPL) and the ABC-binding cassette A1 (ABCA1
ABCA1
ATP-binding cassette transporter ABCA1 , also known as the cholesterol efflux regulatory protein is a protein which in humans is encoded by the ABCA1 gene...

) correlate with disease progression, Early stigmata of disease, drusen, are rich in cholesterol, offering face validity to the results of genome wide association studies

Diagnosis

Fluorescein angiography
Fluorescein angiography
Intravenous Fluorescein angiography or fluorescent angiography is a technique for examining the circulation of the retina using the dye tracing method...

 allows for the identification and localization of abnormal vascular processes.
Optical coherence tomography
Optical coherence tomography
Optical coherence tomography is an optical signal acquisition and processing method. It captures micrometer-resolution, three-dimensional images from within optical scattering media . Optical coherence tomography is an interferometric technique, typically employing near-infrared light...

 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.

Management

Drugs approved for some variety of macular degeneration include : ranibizumab
Ranibizumab
Ranibizumab is a monoclonal antibody fragment derived from the same parent mouse antibody as bevacizumab . It is much smaller than the parent molecule and has been affinity matured to provide stronger binding to VEGF-A...

 (Lucentis) and Aflibercept
Aflibercept
Aflibercept is a fusion protein approved in the United States for the treatment of wet macular degeneration. It is under development for the treatment of cancer.It functions as an inhibitor of vascular endothelial growth factor...

 (for wet AMD).

Treatments for wet AMD

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
Vascular endothelial growth factor
Vascular endothelial growth factor is a signal protein produced by cells that stimulates vasculogenesis and angiogenesis. It is part of the system that restores the oxygen supply to tissues when blood circulation is inadequate....

) agents, can cause regression of the abnormal blood vessels and improvement of vision when injected directly into the vitreous humor of the eye. The injections have to be repeated on a monthly or bi-monthly basis. Examples of these agents include ranibizumab
Ranibizumab
Ranibizumab is a monoclonal antibody fragment derived from the same parent mouse antibody as bevacizumab . It is much smaller than the parent molecule and has been affinity matured to provide stronger binding to VEGF-A...

 (trade name Lucentis), bevacizumab
Bevacizumab
Bevacizumab is a drug that blocks angiogenesis, the growth of new blood vessels. It is commonly used to treat various cancers, including colorectal, lung, breast, kidney, and glioblastomas....

 (trade name Avastin, a close chemical relative of ranibizumab) and pegaptanib
Pegaptanib
Pegaptanib sodium injection is an anti-angiogenic medicine for the treatment of neovascular age-related macular degeneration . It was discovered by Gilead Sciences and licensed in 2000 to EyeTech Pharmaceuticals, now OSI Pharmaceuticals, for late stage development and marketing in the United...

 (trade name Macugen). In November 2011 the FDA approved aflibercept
Aflibercept
Aflibercept is a fusion protein approved in the United States for the treatment of wet macular degeneration. It is under development for the treatment of cancer.It functions as an inhibitor of vascular endothelial growth factor...

 (trade name Eylea) for treatment of wet AMD. Bevacizumab is not approved for intra-ocular use, but is approved for other systemic indications. Pegaptanib (Macugen) has benefits in neovascular AMD and has approval for such use. Worldwide, bevacizumab has been used extensively despite its "off label" status. The cost of ranibizumab (Lucentis) is approximately US$2000 per treatment while the cost of bevacizumab (Avastin) is approximately US$150 per treatment. Both drugs are made by Genentech
Genentech
Genentech Inc., or Genetic Engineering Technology, Inc., is a biotechnology corporation, founded in 1976 by venture capitalist Robert A. Swanson and biochemist Dr. Herbert Boyer. Trailing the founding of Cetus by five years, it was an important step in the evolution of the biotechnology industry...

. In the UK NICE
NICE
NICE may refer to:* National Independent Cadres and Elites in Iraq* National Institute for Coordinated Experiments, a fictional organisation in C.S...

 institute issued guidelines for the treatment of wet AMD in the NHS
National Health Service
The National Health Service is the shared name of three of the four publicly funded healthcare systems in the United Kingdom. They provide a comprehensive range of health services, the vast majority of which are free at the point of use to residents of the United Kingdom...

. NICE only approved use of ranibizumab (trade name Lucentis) for wet AMD in the NHS in England. NHS hospitals and Primary Care Trusts in England are required to follow NICE guidance.

Photodynamic therapy
Photodynamic therapy
Photodynamic therapy is used clinically to treat a wide range of medical conditions, including malignant cancers, and is recognised as a treatment strategy which is both minimally invasive and minimally toxic...

 has also been used to treat wet AMD.

Non-drug interventions

Some evidence supports a reduction in the risk of age-related macular degeneration with increasing intake of two carotenoids, lutein
Lutein
Lutein is a xanthophyll and one of 600 known naturally occurring carotenoids. Lutein is synthesized only by plants and like other xanthophylls is found in high quantities in green leafy vegetables such as spinach and kale...

 and zeaxanthin
Zeaxanthin
Zeaxanthin is one of the most common carotenoid alcohols found in nature. It is important in the xanthophyll cycle. Synthesized in plants & some micro-organisms, it is the pigment that gives paprika , corn, saffron, and many other plants & microbes their characteristic color.The name is derived...

,

Consuming omega-3 fatty acid
Omega-3 fatty acid
N−3 fatty acids are essential unsaturated fatty acids with a double bond starting after the third carbon atom from the end of the carbon chain....

s (docosahexaenoic acid
Docosahexaenoic acid
Docosahexaenoic acid is an omega-3 fatty acid that is a primary structural component of the human brain and retina. In chemical structure, DHA is a carboxylic acid with a 22-carbon chain and six cis double bonds; the first double bond is located at the third carbon from the omega end...

 and eicosapentaenoic acid
Eicosapentaenoic acid
Eicosapentaenoic acid is an omega-3 fatty acid. In physiological literature, it is given the name 20:5. It also has the trivial name timnodonic acid...

) has been correlated
Correlation
In statistics, dependence refers to any statistical relationship between two random variables or two sets of data. Correlation refers to any of a broad class of statistical relationships involving dependence....

 with a reduced progression of early ARMD, and in conjunction with low glycemic index
Glycemic index
The glycemic index, glycaemic index, or GI is a measure of the effects of carbohydrates on blood sugar levels. Carbohydrates that break down quickly during digestion and release glucose rapidly into the bloodstream have a high GI; carbohydrates that break down more slowly, releasing glucose more...

 foods, with reduced progression of advanced ARMD.

A Cochrane Database Review
Cochrane Library
The Cochrane Library is a collection of databases in medicine and other healthcare specialties provided by the Cochrane Collaboration and other organisations. At its core is the collection of Cochrane Reviews, a database of systematic reviews and meta-analyses which summarize and interpret the...

 of publications to 2007 found that the use of vitamin and mineral supplements, alone or in combination, by the general population had no effect on age-related macular degeneration, a finding echoed by another review. A 2006 Cochrane Review of the effects of vitamins and minerals on the slowing of ARMD found that positive results mainly came from a single large trial in the United States (the Age-Related Eye Disease Study
Age-Related Eye Disease Study
The Age-Related Eye Disease Study was a clinical trial sponsored by the National Eye Institute, one of the National Institutes of Health in the United States...

), with funding from the eye care product company Bausch & Lomb
Bausch & Lomb
Bausch & Lomb, an American company based in Rochester, New York, is one of the world's leading suppliers of eye health products, such as contact lenses and lens care products today. In addition to this main activity, in recent years the area of medical technology has been developed...

 who also manufactured the supplements used in the study, and questioned the generalization
Generalization
A generalization of a concept is an extension of the concept to less-specific criteria. It is a foundational element of logic and human reasoning. Generalizations posit the existence of a domain or set of elements, as well as one or more common characteristics shared by those elements. As such, it...

 of the data to any other populations with different nutritional status. The review also questioned the possible harm of such supplements, given the increased risk of lung cancer
Lung cancer
Lung cancer is a disease characterized by uncontrolled cell growth in tissues of the lung. If left untreated, this growth can spread beyond the lung in a process called metastasis into nearby tissue and, eventually, into other parts of the body. Most cancers that start in lung, known as primary...

 in smokers with high intakes of beta-carotene
Beta-carotene
β-Carotene is a strongly-coloured red-orange pigment abundant in plants and fruits. It is an organic compound and chemically is classified as a hydrocarbon and specifically as a terpenoid , reflecting its derivation from isoprene units...

, and the increased risk of heart failure in at-risk populations who consume high levels of vitamin E
Vitamin E
Vitamin E is used to refer to a group of fat-soluble compounds that include both tocopherols and tocotrienols. There are many different forms of vitamin E, of which γ-tocopherol is the most common in the North American diet. γ-Tocopherol can be found in corn oil, soybean oil, margarine and dressings...

 supplements.

Adaptive devices

Because peripheral vision is not affected, people with macular degeneration can learn to use their remaining vision to partially compensate. Assistance and resources are available in many countries and every state in the U.S. Classes for "independent living" are given and some technology can be obtained from a state department of rehabilitation.

Adaptive devices can help people read. These include magnifying glasses, special eyeglass lenses, computer screen readers, and TV systems that enlarge reading material.

Computer screen readers such as JAWS
JAWS (screen reader)
JAWS is a computer screen reader program in Microsoft Windows that allows blind and visually impaired users to read the screen either with a text-to-speech output or by a Refreshable Braille display....

 or Thunder
Thunder (assistive technology)
Thunder is a free screen reader for blind and visually impaired computer users. It can be used on the Windows operating system....

 work with standard Windows
Microsoft Windows
Microsoft Windows is a series of operating systems produced by Microsoft.Microsoft introduced an operating environment named Windows on November 20, 1985 as an add-on to MS-DOS in response to the growing interest in graphical user interfaces . Microsoft Windows came to dominate the world's personal...

 computers.

Video cameras can be fed into standard or special-purpose computer monitors, and the image can be zoomed in and magnified. These systems often include a movable table to move the written material.

Accessible publishing
Accessible publishing
Accessible publishing is an approach to publishing and reading whereby books and other texts aren't only available in one standard format. Other formats that have been developed to aid different people to read include varieties of larger fonts, specialised fonts for certain kinds of reading...

 provides larger fonts for printed books, patterns to make tracking easier, audiobooks and DAISY
DAISY Digital Talking Book
DAISY is a standard for digital talking books. DAISY books are typically used by people have "print disabilities," including blindness, impaired vision, dyslexia...

 books with both text and audio.

Text of internet articles can be copied and pasted into a word processing program, the font size increased. A white background can be difficult for a person with ARMD to read, so the background color can be changed to black, and the font color to white.

In Windows, this can be done with the key combination Left-alt Left-shift Print Screen.

In Mac OS X, this kind of visual inversion can be enabled systemwide via the Universal Access panel of System Preferences (located under the Apple menu at the extreme left of all menubars). Text-to-speech and other assistive options are also available there.

Amsler Grid Test

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
Amsler grid
The Amsler grid, used since 1945, is a grid of horizontal and vertical lines used to monitor a person's central visual field. The grid was developed by Marc Amsler, a Swiss ophthalmologist. It is a diagnostic tool that aids in the detection of visual disturbances caused by changes in the retina,...

 is, in essence, 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. See a video on how to use an Amsler grid here: and watch an animation showing the Amsler grid with macular degeneration here:

See also

  • Cherry-red spot
    Cherry-red spot
    A cherry-red spot is a finding in the macula of the eye in a variety of lipid storage disorders and in central retinal artery occlusion.It describes the appearance of a small circular choroid shape as seen through the fovea centralis....

  • Fuchs spot
    Fuchs spot
    The Fuchs spot or sometimes Forster-Fuchs' retinal spot is a degeneration of the macula in case of high myopia. It is named after the two persons who first described it: Ernst Fuchs who described a pigmented lesion in 1901 and Forster who described subretinal neovascularisation in 1862...

  • Micropsia
    Micropsia
    Micropsia is a condition affecting human visual perception in which objects are perceived to be smaller than they actually are. Micropsia can be caused by either optical distortion of images in the eye or by a neurological dysfunction. The condition of micropsia can be caused by more factors than...

  • Alta Eficacia Method
    Alta Eficacia Method
    Alta Eficacia Method certifies that the lenses bearing this accreditation of guarantee are fitted with a special filter that prevents violet light reaching the eye to protect against the appearance of avoidable blindness.. This lens was invented by the Spanish scientist Dr...

  • Video showing the effect of antiVEGF treatment on the retina.
  • Adeno associated virus and gene therapy of the human retina
    Adeno associated virus and gene therapy of the human retina
    Gene therapy is the use of genetic material inserted into a patient’s cell for the treatment of an inherited or acquired diseases. There are many medical conditions that are a result of mutation in patient’s gene...


External links

The source of this article is wikipedia, the free encyclopedia.  The text of this article is licensed under the GFDL.
 
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