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| | {{Infobox_Disease |
| | | Name = {{PAGENAME}} |
| | | Image = Human eye cross-sectional view grayscale.png |
| | | Caption = Human [[eye]] cross-sectional view. Courtesy [[National Institutes of Health|NIH]] [[National Eye Institute]] |
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| {{Macular degeneration}} | | {{Macular degeneration}} |
| '''For patient information, click [[{{PAGENAME}} (patient information)|here]]''' | | '''For patient information, click [[{{PAGENAME}} (patient information)|here]].''' |
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| {{CMG}} | | {{CMG}} |
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| ==Overview== | | ==[[Macular degeneration overview|Overview]]== |
| '''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 | id = PMID 17021323}}</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).
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| [[Image:Human eye cross-sectional view grayscale.png|left|thumb|175px|Human [[eye]] cross-sectional view. Courtesy [[National Institutes of Health|NIH]] [[National Eye Institute]]]]
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| [[Image:Human eyesight two children and ball normal vision.jpg|center|thumb|220px|Normal vision. Courtesy [[National Institutes of Health|NIH]] [[National Eye Institute]]]] | | ==[[Macular degeneration classification|Classification]]== |
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| [[Image:Human eyesight two children and ball with age-related macular degeneration.jpg|left|thumb|220px|The same view with age-related macular deneneration.]] | | ==[[Macular degeneration pathophysiology|Pathophysiology]]== |
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| ==Age-related macular degeneration== | | ==[[Macular degeneration causes|Causes]]== |
| 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.
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| 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.
| | ==[[Macular degeneration differential diagnosis|Differentiating Macular Degeneration from other Diseases]]== |
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| [[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. | | ==[[Macular degeneration epidemiology and demographics|Epidemiology and Demographics]]== |
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| 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 US while the cost of Avastin is approximately $50. Fortunately, retinal specialists worldwide have together proven that Avastin is at least as effective and safe as Lucentis, at a fraction of the cost.
| | ==[[Macular degeneration risk factors|Risk Factors]]== |
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| ===Risk factors=== | | ==[[Macular degeneration natural history, complications and prognosis|Natural History, Complications and Prognosis]]== |
| *'''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}}
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| *'''Smoking:''' The only environmental exposure clearly associated with macular degeneration is [[tobacco smoking]].<ref>http://news.bbc.co.uk/2/hi/health/4217010.stm</ref> Exposure to cigarette smoke more than doubles the risk of macular degeneration.{{Fact|date=April 2007}}
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| *'''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 fourfold higher risk.{{Fact|date=March 2007}}
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| *'''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>
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| *'''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 | id = PMID 17634448 }}</ref> This authors consider their study to underscore the influence of the complement pathway in the pathogenesis of this disease.
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| *'''Hypertension''': Also known as [[high blood pressure]].
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| *'''Cardiovascular status''' - high cholesterol, [[obesity]].
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| *'''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<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>
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| *'''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>
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| *'''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>
| | ==Diagnosis== |
| *'''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.<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 | id = PMID 16361662}}</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 | id = PMID 16395131 }}</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 | id = PMID 15302349 }}</ref>
| | [[Macular degeneration history and symptoms|History and Symptoms]] | [[Macular degeneration physical examination|Physical Examination]] | [[Macular degeneration other imaging findings|Other Imaging Findings]] | [[Macular degeneration other diagnostic studies|Other Diagnostic Studies]] |
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| ===Signs=== | | ==Treatment== |
| *[[Drusen]]
| | [[Macular degeneration medical therapy|Medical Therapy]] | [[Macular degeneration surgery|Surgery]] | [[Macular degeneration primary prevention|Primary Prevention]] | [[Macular degeneration cost-effectiveness of therapy|Cost-Effectiveness of Therapy]] | [[Macular degeneration future or investigational therapies|Future or Investigational Therapies]] |
| *Pigmentary alterations
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| *Exudative changes: [[hemorrhages]] in the eye, hard exudates, subretinal/sub-RPE/intraretinal fluid
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| *Atrophy: incipient and geographic
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| *Visual acuity drastically decreasing (two levels or more) ex: 20/20 to 20/80.
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| ===Symptoms=== | | ==Case Studies== |
| [[Image:Amsler.jpg|thumb|220px|right|Image courtesy [http://www.agingeye.net/ AgingEye Times] ]] | | [[Macular degeneration case study one|Case #1]] |
| *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.
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| *Central scotomas (shadows or missing areas of vision)
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| *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.
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| *Trouble discerning colors; specifically dark ones from dark ones and light ones from light ones.
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| *Slow recovery of visual function after exposure to bright light
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| 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.
| | ==External Links== |
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| '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.
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| 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.
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| 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..
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| ===Diagnosis===
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| [[Fluorescein angiography]] allows for the identification and localization of abnormal vascular processes.
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| 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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| ===Prevention===
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| 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.
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| 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.
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| 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.
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| 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.") Several similar studies are currently being underway.
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| 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>
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| Studies are underway at Harvard, with the goal of reducing [[lipofuscin]] accumulation. <ref name=Harvard />
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| 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 eggs, spinach and other green vegetables) protect against [[blindness]] (macular degeneration), affecting 1.2 million 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 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>
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| ==Juvenile macular degeneration==
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| 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:
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| *[[Best's disease]]
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| *Doyne's honeycomb retinal dystrophy
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| *Sorsby's disease
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| *[[Stargardt's disease]]
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| The first genetic link to juvenile macular degeneration was discovered at the [[Cleveland Clinic]].
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| ==Impact==
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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.
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| 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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| ==References==
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| {{reflist|2}}
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| ==External links== | |
| *[http://www.nei.nih.gov/health/maculardegen/armd_facts.asp Age-related Macular Degeneration] Resource Guide from the National Eye Institute (NEI). | | *[http://www.nei.nih.gov/health/maculardegen/armd_facts.asp Age-related Macular Degeneration] Resource Guide from the National Eye Institute (NEI). |
| *[http://www.nei.nih.gov/amd/ Results from NEI's Age Related Eye Disease Study] showed that high levels of antioxidants and zinc significantly reduce the risk of advanced AMD and its associated vision loss. | | *[http://www.nei.nih.gov/amd/ Results from NEI's Age Related Eye Disease Study] showed that high levels of antioxidants and zinc significantly reduce the risk of advanced AMD and its associated vision loss. |
| *[http://www.mdsupport.org Macular Degeneration Support]
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| *[http://www.medrounds.org/protect-your-sight/ An open-access eBook on Macular Degeneration: Protect Your Sight - How to Save your Vision in the Epidemic of Age-Related Macular Degeneration] by James C. Folk, MD and Mark E. Wilkinson, OD - Published March 2006
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| *[http://www.ahaf.org/macular/about/maabout.htm Macular Degeneration Research]
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| *[http://www.amdreport.com Macular Degeneration 3000 word report] A Patients Guide to AMD
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| *[http://www.rheo.com/ Rheo.com |The RHEO procedure is a unique type of therapeutic apheresis that removes large molecules like cholesterol, fibrinogen and certain immunoglobulins from the blood.]
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| *[http://www.osnsupersite.com/ Home of Ocular Surgery News]
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| *[http://news.bbc.co.uk/2/hi/health/medical_notes/2042906.stm BBC News] — AMD from a European perspective
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| *[http://www.eyesight.org/ Macular Degeneration Foundation]
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| * {{cite web | title=Living with Macular Degeneration | url=http://health-net-now.blogspot.com/2007/04/macular-degeneration-living-with.html | publisher=NLM}} video
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| *[http://www.VisionSimulations.com/ VisionSimulations.com |What the world looks like to people with various diseases and conditions of the eye]
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| *[http://www.visivite.com/vitamin-supplements-for-maculardegeneration.html Why good food isn't enough - Powerful antioxidant vitamin supplements can halt the progression of dry macular degeneration of the eye and in some people even improve vision.]
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| *[http://www.armdcook.com/ ARMD Cook |Recipes using medical guidelines for the prevention and possible reversal of MD and ARMD]
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| *[http://www.mgh.harvard.edu/wellman/ Wellman Center for Photomedicine] at [[Massachusetts General Hospital]] and [[Harvard Medical School]] information on the use of [[photomedicine]] as treatment
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| *[http://www.amdcanada.com Age Related Macular Degeneration] amdcanada.com
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| *{{cite web |url=http://news.bbc.co.uk/2/hi/uk_news/scotland/glasgow_and_west/5168862.stm |title=Scientists seek to restore sight |accessmonthday= |accessyear= |author= |last= |first= |authorlink= |coauthors= |year= |month= |format= |work= |publisher=BBC News Scotland |pages= |language= |archiveurl= |archivedate=}}
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| *[http://news.bbc.co.uk/1/hi/health/6457427.stm BBC News, Friday, 16 March 2007]; Zinc could be key to eye disease
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| *[http://www.myvisiontest.com/ MyVisionTest] A free modern Amsler Grid test for macular degeneration
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| *[http://www.amdalliance.org AMD Alliance International]
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| | [[Category:Optometry]] |
| | [[Category:Ophthalmology]] |
| | [[Category:Pediatrics]] |
| | [[Category:Gerontology]] |
| | [[Category:Disease]] |
| [[Category:Aging-associated diseases]] | | [[Category:Aging-associated diseases]] |
| [[Category:Blindness]] | | [[Category:Blindness]] |
| [[Category:Disease]]
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| [[Category:Ophthalmology]]
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| [[Category:Primary care]]
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