Macular degeneration
895033
224817950
2008-07-10T15:33:21Z
71.131.33.212
/* Age-related macular degeneration */
{{DiseaseDisorder infobox |
Name = Macular degeneration |
ICD10 = {{ICD10|H|35|3|h|30}} |
ICD9 = {{ICD9|362.50}} |
MeshID = D008268
}}
{{Spoken Wikipedia|Macular_degeneration.ogg|2005-07-19}}
[[Image:Human eye cross-sectional view grayscale.png|right|thumb|175px|Human [[eye]] cross-sectional view. Courtesy [[National Institutes of Health|NIH]] [[National Eye Institute]]]]
[[Image:Human eyesight two children and ball normal vision.jpg|right|thumb|220px|Normal vision (B&W). Courtesy [[National Institutes of Health|NIH]] [[National Eye Institute]]]]
[[Image:Human eyesight two children and ball with age-related macular degeneration.jpg|right|thumb|220px|The same view with age-related macular degeneration (B&W).]]
'''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.<ref>{{cite journal | author = de Jong PT | title = Age-related macular degeneration | journal = N Engl J Med.| volume = 355 | issue = 14 | pages = 1474–1485| year = 2006 | pmid = 17021323 | doi = 10.1056/NEJMra062326}}</ref> 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).
==Age-related macular degeneration==
Age-related macular degeneration begins with characteristic yellow deposits in the macula (central area of the retina which provides detailed central vision, called fovea) 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 despite its "[[off label]]" status. The cost of Lucentis is approximately $2000 US per treatment while the cost of Avastin is approximately $150 per treatment. Lucentis is a close chemical relative of Avastin. Both drugs are made by Genentech.
===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.{{Fact|date=March 2007}}
*'''Family history:''' The lifetime risk of developing late-stage macular degeneration is 50% for people who have a relative with macular degeneration versus 12% for people who do not have relatives with macular degeneration; a fourfold higher risk.{{Fact|date=March 2007}}
*'''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 cofactor 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 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. <ref>Yang Z, Camp NJ, Sun H, Tong Z, Gibbs D, Cameron DJ, Chen H, Zhao Y, Pearson E, Li X, Chien J, Dewan A, Harmon J, Bernstein PS, Shridhar V, Zabriskie NA, Hoh J, Howes K, Zhang K. "A variant of the HTRA1 gene increases susceptibility to age-related macular degeneration." ''Science.'' 2006 Nov 10;314(5801):992-3. PMID 17053109.</ref><ref>Dewan A, Liu M, Hartman S, Zhang SS, Liu DT, Zhao C, Tam PO, Chan WM, Lam DS, Snyder M, Barnstable C, Pang CP, Hoh J. "A variant of the HTRA1 gene increases susceptibility to age-related macular degeneration". Science. 2006 Nov 10;314(5801):989-92. PMID 17053108 </ref>
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 which arises from its mutation.
Mutation of the ATP synthase gene:
Retinitis Pigmentosa (RP) is a genetically linked dysfunction of the retina and is related to mutation of the Adenesine Tri-Phosphate (ATP) Synthase Gene 615.1617
'''Stargardt’s disease''' (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 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, however, 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, which indicates there must be at least one other factor that accounts for the loss of vision. Retinitis Pigmentosa (RP) is a genetically linked dysfunction of the retina and is related to mutation of the ATP Synthase Gene 63.
*'''Arg80Gly variant of the [[complement system| 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.<ref>{{cite journal | author = Yates JR, Sepp T, Matharu BK, Khan JC, Thurlby DA, Shahid H, Clayton DG, Hayward C, Morgan J, Wright AF, Armbrecht AM, Dhillon B, Deary IJ, Redmond E, Bird AC, Moore AT | title = Complement C3 Variant and the Risk of Age-Related Macular Degeneration | journal = N Engl J Med.| volume = 357 | issue = 6| pages = 553–561 | year = 2007 | pmid = 17634448 | doi = 10.1056/NEJMoa072618}}</ref> The 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''' 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 high-fat dairy products such as whole milk, cheese, and butter. Eating more cold-water fish<ref name='areds20'> {{cite web|url=http://archopht.ama-assn.org/cgi/content/short/125/5/671 |title=The Relationship of Dietary Lipid Intake and Age-Related Macular Degeneration in a Case-Control Study |last=John Paul SanGiovanni, ScD; Emily Y. Chew, MD; Traci E. Clemons, PhD; Matthew D. Davis, MD; Frederick L. Ferris III, MD; Gary R. Gensler, MS; Natalie Kurinij, PhD; Anne S. Lindblad, PhD; Roy C. Milton, PhD; Johanna M. Seddon, MD; and Robert D. Sperduto, MD |date=May 5, 2007 |work=Archives of Ophthamology }}</ref> (at least twice weekly), rather than red meats, and eating any type of nuts may help macular degeneration patients.<ref>[http://www.agingeye.net/maculardegen/maculardegeninformation.php Macular degeneration Types and Risk Factors]</ref>
*'''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.<ref>"Melanin aggregation and polymerization: possible implications in age related macular degeneration." ''Ophthalmic Research'', 2005; volume 37: pages 136-141. </ref><ref name=Harvard>John Lacey, "[http://www.eurekalert.org/pub_releases/2006-05/hms-hms052306.php Harvard Medical signs agreement with Merck to develop potential therapy for macular degeneration]", 23-May-2006</ref>
*'''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 whites than in blacks.<ref>Age-Related Eye Disease Study Research Group. "Risk factors associated with age-related macular degeneration. A case-control study in the age-related eye disease study: Age-Related Eye Disease Study Report Number 3." ''Ophthalmology.'' 2000 Dec;107(12):2224-32. PMID 11097601.</ref><ref>Clemons TE, Milton RC, Klein R, Seddon JM, Ferris FL 3rd; Age-Related Eye Disease Study Research Group. "Risk factors for the incidence of Advanced Age-Related Macular Degeneration in the Age-Related Eye Disease Study (AREDS) AREDS report no. 19." ''Ophthalmology.'' 2005 Apr;112(4):533-9. PMID 15808240.</ref>
*'''Exposure to sunlight''' especially [[Blue-light hazard|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.<ref>{{cite journal | first = JC | last = Khan | coauthors = Shahid H, Thurlby DA, Bradley M, Clayton DG, Moore AT, Bird AC, Yates JR, Genetic Factors in AMD Study | year = 2006 | month = Jan | title = Age related macular degeneration and sun exposure, iris colour, and skin sensitivity to sunlight | journal = The British Journal of Ophthalmology | volume = 90 | issue = 1 | pages = 29–32 | pmid = 16361662 | accessdate = 2006-10-23 | doi = 10.1136/bjo.2005.073825}}</ref> [[High-energy visible light]] (HEV) has been implicated as a cause of age-related macular degeneration.<ref>{{cite journal | first = C | last = Glazer-Hockstein | coauthors = Dunaief JL | year = 2006 | month = Jan | title = Could blue light-blocking lenses decrease the risk of age-related macular degeneration? | journal = Retina | volume = 26 | issue = 1 | pages = 1–4 | pmid = 16395131 | accessdate = 2006-10-23 | doi = 10.1097/00006982-200601000-00001}}</ref><ref>{{cite journal | first = TH | last = Margrain | coauthors = Boulton M, Marshall J, Sliney DH | year = 2004 | month = Sep | title = Do blue light filters confer protection against age-related macular degeneration? | journal = Progress in Retinal and Eye Research | volume = 23 | issue = 5 | pages = 523–31 | pmid = 15302349 | accessdate = 2006-10-23 | doi = 10.1016/j.preteyeres.2004.05.001}}</ref><ref>{{cite journal | first = D | last = Roberts | year = 2005 | month = Sep | title = Artificial Lighting and the Blue Light Hazard | journal = Macular Degeneration Support Online Library | volume = http://www.mdsupport.org/library/hazard.html#blue}}</ref>
===Signs===
*[[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.
===Symptoms===
<!-- Deleted image removed: [[Image:Amsler.jpg|thumb|220px|right|Image courtesy Eyescience.com ]] -->
*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. 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
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. See a VIDEO on HOW-TO-USE-AN-AMSLER-GRID Here: [http://www.eyescience.com/videos/index.php?id=102]
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.<ref>{{cite journal | first = DL | last = Roberts | year = 2006 | month = Sep | title = The First Year--Age Related Macular Degeneration | journal = (Marlowe & Company) | pages = 100}}</ref> The area of the macula comprises about 5% of the retina and is responsible for about 35% of the visual field. The remaining 65% (the peripheral field) remains unaffected by the disease.<ref>{{cite journal | first = DL | last = Roberts | year = 2006 | month = Sep | title = The First Year--Age Related Macular Degeneration | journal = (Marlowe & Company) | pages = 20}}</ref>
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 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 surprisingly difficult to do.
Similar symptoms with a very different etiology and different treatment can be caused by [[Epiretinal membrane]] or [[macular pucker]]or leaking blood vessels in the eye..
===Diagnosis===
[[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.
===Prevention===
The [[Age-Related Eye Disease Study]] showed that a combination of high-dose [[beta-carotene]], [[vitamin C]], [[vitamin E]], and [[zinc]] can reduce the risk of developing advanced AMD by about 25 percent in those patients who have earlier but significant forms of the disease. This is the only proven intervention to decrease the risk of advanced AMD at this time. A follow up study, Age-Related Eye Disease Study 2 to study the potential benefits of lutein, zeaxanthine, and fish oil, is currently underway.
Anecortave acetate, (Retanne), is an anti-angiogenic drug that is given as an injection behind the eye (avoiding an injection directly into the eye) that is currently being studied as a potential way of reducing the risk of neovascular (or wet) AMD in high-risk patients.
Research started in 2005 has shown that intravitreal injection of Avastin (bevacizumab) can improve vision and slow down the macular degeneration. This therapy is currently being used in various centres around the world. Avastin is an immunoligic drug that prevents neovascularization. Hence it may also be effective in diabetic retinopathy. Avastin was initially used for the treatment of colorectal cancer.
A study by a neuroretinologist in the late 80's suggested that microcurrent stimulation of acupuncture points for the eye had positive effects in slowing and even stopping progression of the disease{{Fact|date=August 2007}}. This study was based on Ngok Cheng's research on the increased amounts of ATP levels in living tissue after being stimulated with microcurrent. ("The Effects of Electric Currents on ATP Generation, Protein Synthesis, and Membrane Transport in Rat Skin.")<ref>http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=AbstractPlus&list_uids=7140077</ref Several similar studies are currently underway.
In initial clinical trials in 2004, nearly 92% of patients showed significant improvement using micro-acupuncture.<ref>[http://www.acupuncturehealth.net/articles/nat_clin_studies.php Acupuncture & Macular Degeneration - National Clinical Studies, by Andy Rosenfarb<!-- Bot generated title -->]</ref>
Recent studies suggest that [[statin]]s, a family of drugs used for reducing [[cholesterol]] levels, may be effective in prevention of AMD, and in slowing its progression.<ref>http://bjo.bmjjournals.com/cgi/content/full/882/161</ref>
Studies are underway at [[Harvard]], with the goal of reducing [[lipofuscin]] accumulation. <ref name=Harvard />
On September 10, 2007, in a 6-year study, [[researchers]], led by John Paul SanGiovanni of the [[National Eye Institute]], [[Maryland]] found that [[Lutein]] and [[zeaxanthin]] ([[nutrients]] in [[Egg (biology)|eggs]], [[spinach]] and other [[green]] [[vegetables]]) protect against [[blindness]] (macular degeneration), affecting 1.2 million [[United States|Americans]], mostly after age 65. Lutein and zeaxanthin reduce the risk of [[AMD]] ([[journal]] [[Archives of Ophthalmology]]). Foods considered good sources of the nutrients also include [[kale]], [[turnip]] [[Leaf vegetable|greens]], [[collard]] greens, [[romaine lettuce]], [[broccoli]], [[zucchini]], [[corn]], [[garden]] [[peas]] and [[Brussels sprouts]].<ref>[http://news.yahoo.com/s/nm/20070910/hl_nm/eyesight_nutrients_dc;_ylt=AhJwo077jBEbQvMoRIMIxV2s0NUE Yahoo.com, Study finds spinach, eggs ward off cause of blindness]</ref>
==Juvenile macular degeneration==
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]].
==Impact==
Macular degeneration, in its advanced forms, can result in [[Blindness#Legal blindness|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 (screen reader)|JAWS]] for [[Microsoft Windows|Windows]], can give the blind person access to word processing, spreadsheet, financial, and e-mail programs.
==References==
{{reflist|2}}
==External links==
* {{DMOZ|Health/Conditions_and_Diseases/Eye_Disorders/Retina/Macular_Degeneration/}}
* [http://www.myvisiontest.com/ MyVisionTest] A free modern Amsler Grid test for macular degeneration
* [http://www.amdsupport.ca/ Age Related Macular Degeneration Support]
* [http://www.webmd.com/eye-health/macular-degeneration/news/20080317/robo-gene-fights-macular-degeneration 'Robo' Gene Fights Macular Degeneration]
[http://maculardoctor.com Microcurrent treatment]
{{Eye pathology}}
[[Category:Aging-associated diseases]]
[[Category:Blindness]]
[[Category:Diseases]]
[[Category:Ophthalmology]]
[[ca:Degeneració macular per edat]]
[[de:Makuladegeneration]]
[[es:Degeneración macular asociada a la edad]]
[[fr:Syndrome maculaire]]
[[it:Degenerazione maculare]]
[[he:ניוון מקולרי]]
[[nl:Maculadegeneratie]]
[[ja:加齢黄斑変性]]
[[pl:Zwyrodnienie plamki żółtej]]
[[pt:Degeneração macular]]