Macular degeneration

File:Eye disease simulation, normal vision.jpg

File:Eye disease simulation, age-related macular degeneration.jpg

Early or intermediate AMD may be asymptomatic, or it may present with blurred or decreased vision in one or both eyes. This may manifest initially as difficulty with reading or driving (especially in poorly lit areas). Other symptoms of AMD include distortion of vision and blind spots (especially in and around the central visual field).

Other signs and symptoms of macular degeneration include:

• Distorted vision in the form of metamorphopsia, in which a grid of straight lines appears wavy and parts of the grid may appear blank: Patients often first notice this when looking at things like miniblinds in their home or telephone poles while driving. There may also be central scotomas, shadows, or missing areas of vision.{{citation needed|date=September 2024}}
• Slow recovery of visual function after exposure to bright light (photostress test){{citation needed|date=September 2024}}
• Visual acuity drastically decreasing (two levels or more), e.g.: 20/20 to 20/80{{cite web |title=Nandhana Eye Hospital |url=https://nandhanaeyehospital.com/Treatment/amd.html |access-date=19 May 2023 |website=nandhanaeyehospital.com}}
• Blurred vision: Those with nonexudative (dry) macular degeneration may be asymptomatic or notice a gradual loss of central vision, whereas those with exudative (wet) macular degeneration often notice a rapid onset of vision loss (often caused by leakage and bleeding of abnormal blood vessels).{{citation needed|date=September 2024}}
• Trouble discerning colors, specifically dark ones from dark ones and light ones from light ones{{citation needed|date=September 2024}}
• A loss in contrast sensitivity{{citation needed|date=September 2024}}
• Formed visual hallucinations and flashing lights have also been associated with severe visual loss secondary to wet AMD{{cite news|url=https://www.aao.org/preferred-practice-pattern/age-related-macular-degeneration-ppp-2015|title=Age-Related Macular Degeneration PPP – Updated 2015|date=29 January 2015|work=American Academy of Ophthalmology|access-date=13 November 2018|archive-date=13 November 2018|archive-url=https://web.archive.org/web/20181113210456/https://www.aao.org/preferred-practice-pattern/age-related-macular-degeneration-ppp-2015|url-status=dead}}

Macular degeneration by itself will not lead to total blindness. For that matter, only a small number of people with visual impairment are blind. In almost all cases, some vision remains, mainly peripheral. Other complicating conditions may lead to such an acute condition (severe stroke or trauma, untreated glaucoma, etc.), but few macular degeneration patients experience total visual loss.{{cite journal |first=DL |last=Roberts |date=September 2006 |title=The First Year – Age Related Macular Degeneration |journal=Marlowe & Company |page=100}}

The area of the macula constitutes only about 2.1% of the retina, and the remaining 97.9% (the peripheral field) remains unaffected by the disease. 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.{{cite journal |first=DL |last=Roberts |date=September 2006 |title=The First Year – Age Related Macular Degeneration |journal=Marlowe & Company |page=20}}

In addition, people with dry macular degeneration often do not experience any symptoms but can experience gradual onset of blurry vision in one or both eyes.{{cite journal | vauthors = Cunningham J | title = Recognizing age-related macular degeneration in primary care | journal = JAAPA | volume = 30 | issue = 3 | pages = 18–22 | date = March 2017 | pmid = 28151737 | doi = 10.1097/01.jaa.0000512227.85313.05 | s2cid = 205396269 }}{{cite journal | vauthors = Lim LS, Mitchell P, Seddon JM, Holz FG, Wong TY | title = Age-related macular degeneration | journal = The Lancet | volume = 379 | issue = 9827 | pages = 1728–38 | date = May 2012 | pmid = 22559899 | doi = 10.1016/S0140-6736(12)60282-7 | s2cid = 25049931 }} People with wet macular degeneration may experience acute onset of visual symptoms.

The pathogenesis of age-related macular degeneration (AMD) is intricately linked to gene-environment interactions.{{cite journal | vauthors = Karmoker JR, Bounds SE, Cai J | title = Aryl hydrocarbon receptor (AhR)-mediated immune responses to degeneration of the retinal pigment epithelium | journal = Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease | volume = 1870 | issue = 7 | pages = 167351 | date = July 2024 | pmid = 39004382 | pmc = 11330344 | doi = 10.1016/j.bbadis.2024.167351 | pmc-embargo-date = October 1, 2025 }} Key risk factors are age, race/ethnicity, smoking, and family history.{{cite journal|last1=Tzoumas|first1=Nikolaos|last2=Hallam|first2=Dean|last3=Harris|first3=Claire L.|last4=Lako|first4=Majlinda|last5=Kavanagh|first5=David|last6=Steel|first6=David H.W.|date=November 2020|title=Revisiting the role of factor H in age-related macular degeneration: Insights from complement-mediated renal disease and rare genetic variants|url=https://doi.org/10.1016/j.survophthal.2020.10.008|journal=Survey of Ophthalmology|volume=66|issue=2|pages=378–401|doi=10.1016/j.survophthal.2020.10.008|pmid=33157112|s2cid=226274874|issn=0039-6257|url-access=subscription}} Advanced age is the strongest predictor of AMD, particularly over 50.{{cite journal | vauthors = Deangelis MM, Silveira AC, Carr EA, Kim IK | title = Genetics of age-related macular degeneration: current concepts, future directions | journal = Seminars in Ophthalmology | volume = 26 | issue = 3 | pages = 77–93 | date = May 2011 | pmid = 21609220 | pmc = 4242505 | doi = 10.3109/08820538.2011.577129 }}

File:AMD by race and age from National Eye Institute data.jpg

As illustrated by the Figure in this section, derived from data presented by the National Eye Institute of the United States,{{cite web|url=https://www.nei.nih.gov/learn-about-eye-health/eye-health-data-and-statistics/age-related-macular-degeneration-amd-data-and-statistics/age-related-macular-degeneration-amd-tables|title=Age-Related Macular Degeneration (AMD) Tables |website=National Eye Institute}} among those over 80 years of age, White individuals are more than 6-fold more likely to develop AMD than Black or Hispanic individuals. Thus, white background is a major risk factor for AMD.{{citation needed|date=September 2024}}

In Caucasian (white) skin, there is a specific group of polymorphic genes (with single nucleotide alterations) that encode for enzymes and transcription factors responsible for the early steps (including the first step, formation of L-DOPA from the amino acid tyrosine) of the melanin synthesis pathway. Many of these enzymes and transcription factors are reviewed by Markiewicz and Idowu.{{cite journal |vauthors=Markiewicz E, Idowu OC |title=Melanogenic Difference Consideration in Ethnic Skin Type: A Balance Approach Between Skin Brightening Applications and Beneficial Sun Exposure |journal=Clin Cosmet Investig Dermatol |volume=13 |issue= |pages=215–232 |date=2020 |pmid=32210602 |pmc=7069578 |doi=10.2147/CCID.S245043 |url= |doi-access=free }} Also, as reviewed by Sturm et al.{{cite journal |vauthors=Sturm RA, Teasdale RD, Box NF |title=Human pigmentation genes: identification, structure and consequences of polymorphic variation |journal=Gene |volume=277 |issue=1–2 |pages=49–62 |date=October 2001 |pmid=11602344 |doi=10.1016/s0378-1119(01)00694-1 |url=}} "increasing intracellular concentrations of either tyrosine or L-DOPA both increase melanogenesis" or formation of the black pigment melanin. Thus there appears to be an association between reduced L-DOPA production and white skin. As suggested by the Figure and information in this section, reduced L-DOPA, resulting in white skin, appears to be associated with an increased risk of macular degeneration for white individuals over the age of 80.{{citation needed|date=September 2024}}

• Smoking: Smoking tobacco increases the risk of AMD 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 "a strong association between current smoking and AMD. ... Cigarette smoking is likely to have toxic effects on the retina."{{cite journal | vauthors = Thornton J, Edwards R, Mitchell P, Harrison RA, Buchan I, Kelly SP | title = Smoking and age-related macular degeneration: a review of association | journal = Eye | volume = 19 | issue = 9 | pages = 935–44 | date = September 2005 | pmid = 16151432 | doi = 10.1038/sj.eye.6701978 | doi-access = free }}
• Hypertension (high blood pressure): In the ALIENOR study 2013, early and late AMD were not significantly associated with systolic or diastolic blood pressure (BP), hypertension, or use of antihypertensive medications, but elevated pulse pressure [(PP) systolic BP minus diastolic BP] was significantly associated with an increased risk of late AMD.{{cite journal | vauthors = Cougnard-Grégoire A, Delyfer MN, Korobelnik JF, Rougier MB, Malet F, Le Goff M, Dartigues JF, Colin J, Barberger-Gateau P, Delcourt C | title = Long-term blood pressure and age-related macular degeneration: the ALIENOR study | journal = Investigative Ophthalmology & Visual Science | volume = 54 | issue = 3 | pages = 1905–12 | date = March 2013 | pmid = 23404120 | doi = 10.1167/iovs.12-10192 | doi-access = free }}
• Atherosclerosis{{cite journal | vauthors = García-Layana A, Cabrera-López F, García-Arumí J, Arias-Barquet L, Ruiz-Moreno JM | title = Early and intermediate age-related macular degeneration: update and clinical review | journal = Clinical Interventions in Aging | volume = 12 | pages = 1579–87 | date = October 2017 | pmid = 29042759 | pmc = 5633280 | doi = 10.2147/cia.s142685 | doi-access = free }}
• High cholesterol: Elevated cholesterol may increase the risk of AMD{{cite journal | vauthors = Dasari B, Prasanthi JR, Marwarha G, Singh BB, Ghribi O | title = Cholesterol-enriched diet causes age-related macular degeneration-like pathology in rabbit retina | journal = BMC Ophthalmology | volume = 11 | pages = 22 | date = August 2011 | pmid = 21851605 | pmc = 3170645 | doi = 10.1186/1471-2415-11-22 | doi-access = free }}{{cite journal |last1=Burgess |first1=Stephen |last2=Davey Smith |first2=George |title=Mendelian Randomization Implicates High-Density Lipoprotein Cholesterol–Associated Mechanisms in Etiology of Age-Related Macular Degeneration |journal=Ophthalmology |date=August 2017 |volume=124 |issue=8 |pages=1165–1174 |doi=10.1016/j.ophtha.2017.03.042 |pmid=28456421 |pmc=5526457 }}
• Obesity: Abdominal obesity is a risk factor, especially among men{{cite journal | vauthors = Adams MK, Simpson JA, Aung KZ, Makeyeva GA, Giles GG, English DR, Hopper J, Guymer RH, Baird PN, Robman LD | title = Abdominal obesity and age-related macular degeneration | journal = American Journal of Epidemiology | volume = 173 | issue = 11 | pages = 1246–55 | date = June 2011 | pmid = 21422060 | doi = 10.1093/aje/kwr005 | doi-access = free }}
• Fat intake: Consuming high amounts of certain fats, including saturated fats, trans fats, and omega-6 fatty acids, likely contributes to AMD, while monounsaturated fats are potentially protective.{{cite journal | vauthors = Parekh N, Voland RP, Moeller SM, Blodi BA, Ritenbaugh C, Chappell RJ, Wallace RB, Mares JA | title = Association between dietary fat intake and age-related macular degeneration in the Carotenoids in Age-Related Eye Disease Study (CAREDS): an ancillary study of the Women's Health Initiative | journal = Archives of Ophthalmology | volume = 127 | issue = 11 | pages = 1483–93 | date = November 2009 | pmid = 19901214 | pmc = 3144752 | doi = 10.1001/archophthalmol.2009.130 }} In particular, omega-3 fatty acids may decrease the risk of AMD.{{cite journal | vauthors = SanGiovanni JP, Chew EY, Clemons TE, Davis MD, Ferris FL, Gensler GR, Kurinij N, Lindblad AS, Milton RC, Seddon JM, Sperduto RD | title = The relationship of dietary lipid intake and age-related macular degeneration in a case-control study: AREDS Report No. 20 | journal = Archives of Ophthalmology | volume = 125 | issue = 5 | pages = 671–79 | date = May 2007 | pmid = 17502507 | doi = 10.1001/archopht.125.5.671 | doi-access = free }}
• Exposure to UV light from sunlight may be associated with an increased risk of developing AMD, although evidence for this is weaker than for other causes.{{cite journal | vauthors = Arunkumar R, Calvo CM, Conrady CD, Bernstein PS | title = What do we know about the macular pigment in AMD: the past, the present, and the future | journal = Eye | volume = 32 | issue = 5 | pages = 992–1004 | date = May 2018 | pmid = 29576617 | pmc = 5944649 | doi = 10.1038/s41433-018-0044-0 }}
• There is no evidence to support the claim that exposure to digital screens contributes to the risk of macular degeneration.{{cite web | title=Are Computer Glasses Worth It? | website=American Academy of Ophthalmology | date=27 April 2017 | url=https://www.aao.org/eye-health/tips-prevention/are-computer-glasses-worth-it | access-date=2 February 2020}}

AMD is a highly heritable condition. Recurrence ratios for siblings of an affected individual are three- to six-fold higher than in the general population.{{cite journal | vauthors = Maller J, George S, Purcell S, Fagerness J, Altshuler D, Daly MJ, Seddon JM | title = Common variation in three genes, including a noncoding variant in CFH, strongly influences risk of age-related macular degeneration | journal = Nature Genetics | volume = 38 | issue = 9 | pages = 1055–59 | date = September 2006 | pmid = 16936732 | doi = 10.1038/ng1873 | s2cid = 15830119 }} Genetic linkage analysis has identified 5 sets of gene variants at three locations on different chromosomes (1, 6 and 10) as explaining at least 50% of the risk.{{cite journal | last1=Schmitz-Valckenberg | first1=Steffen | last2=Fleckenstein | first2=Monika | last3=Zouache | first3=Moussa A. | last4=Pfau | first4=Maximilian | last5=Pappas | first5=Christian | last6=Hageman | first6=Jill L. | last7=Agrón | first7=Elvira | last8=Malley | first8=Claire | last9=Keenan | first9=Tiarnan D. L. | last10=Chew | first10=Emily Y. | last11=Hageman | first11=Gregory S. | title=Progression of Age-Related Macular Degeneration and Homozygous Risk at Chromosome 1 or 10 | journal=JAMA Ophthalmology | date=3 February 2022 | volume=140 | issue=3 | pages=252–260 | doi=10.1001/jamaophthalmol.2021.6072 | url=https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2788507 | access-date=3 February 2022 | pmid=35113155 | pmc=8814975 }} These genes have roles regulating the immune response, inflammatory processes and homeostasis of the retina. Variants of these genes give rise to different kinds of dysfunction in these processes. Over time, this results in the accumulation of intracellular and extracellular metabolic debris. This can cause scarring of the retina or breakdown of its vascularization.{{cite web |date=10 June 2022 |title=Understanding Wet AMD |url=https://www.everydayhealth.com/hs/managing-wet-amd/understanding/ |access-date=19 May 2023 |website=EverydayHealth.com |language=en}}

The list of genetic variations associated with AMD includes complement factors, apolipoprotein E, fibroblast growth factor 2, DNA excision repair protein, and age-related maculopathy susceptibility protein 2.{{cite journal|last1=Tong|first1=Yao|last2=Wang|first2=Shusheng|date=2020|title=Not All Stressors Are Equal: Mechanism of Stressors on RPE Cell Degeneration|journal=Frontiers in Cell and Developmental Biology|volume=8|pages=591067|doi=10.3389/fcell.2020.591067|issn=2296-634X|pmc=7710875|pmid=33330470|doi-access=free}}

Although genetic testing can lead to the identification of genetic variation that can predispose to AMD, the complex pathogenesis of the condition prevents the use of these tests in routine practice. Nevertheless, they can be useful in selecting patients for clinical trials and analyzing their response to treatment. The three loci where identified gene variants are found are designated:

• Complement Factor H (CFH) on chromosome 1 at location 1q31.3{{cite journal | vauthors = Edwards AO, Ritter R, Abel KJ, Manning A, Panhuysen C, Farrer LA | title = Complement factor H polymorphism and age-related macular degeneration | journal = Science | volume = 308 | issue = 5720 | pages = 421–24 | date = April 2005 | pmid = 15761121 | doi = 10.1126/science.1110189 | bibcode = 2005Sci...308..421E | s2cid = 31337096 | doi-access = free }}
• HTRA serine peptidase 1/Age Related Maculopathy Susceptibility 2 (HTRA1/ARMS2) on chromosome 10 at location 10q26
• Complement Factor B/Complement Component 2 (CFB/CC2) on chromosome 6 at 6p21.3{{citation needed|date=September 2024}}

• Polymorphisms in genes for complement system proteins: Variation in the genes for the complement system proteins factor H (CFH), factor B (CFB) and factor 3 (C3), among others, are strongly associated with a person's risk for developing AMD. CFH is involved in inhibiting the inflammatory response. The mutation in CFH (Y402H) results in reduced ability of the protein to localise to and protect tissues such as the retina from complement overactivation. Absence of the complement factor H-related genes R3 and R1 protects against AMD.{{cite journal | vauthors = Hughes AE, Orr N, Esfandiary H, Diaz-Torres M, Goodship T, Chakravarthy U | title = A common CFH haplotype, with deletion of CFHR1 and CFHR3, is associated with lower risk of age-related macular degeneration | journal = Nature Genetics | volume = 38 | issue = 10 | pages = 1173–77 | date = October 2006 | pmid = 16998489 | doi = 10.1038/ng1890 | s2cid = 21178921 }}{{cite journal | vauthors = Fritsche LG, Lauer N, Hartmann A, Stippa S, Keilhauer CN, Oppermann M, Pandey MK, Köhl J, Zipfel PF, Weber BH, Skerka C | title = An imbalance of human complement regulatory proteins CFHR1, CFHR3 and factor H influences risk for age-related macular degeneration (AMD) | journal = Human Molecular Genetics | volume = 19 | issue = 23 | pages = 4694–704 | date = December 2010 | pmid = 20843825 | doi = 10.1093/hmg/ddq399 | doi-access = free }} Two independent studies in 2007 showed a certain common mutation Arg80Gly in the C3 gene, which is a central protein of the complement system, is strongly associated with the occurrence of AMD.{{cite journal | vauthors = Maller JB, Fagerness JA, Reynolds RC, Neale BM, Daly MJ, Seddon JM | title = Variation in complement factor 3 is associated with risk of age-related macular degeneration | journal = Nature Genetics | volume = 39 | issue = 10 | pages = 1200–01 | date = October 2007 | pmid = 17767156 | doi = 10.1038/ng2131 | s2cid = 8595223 }} The authors of both papers consider their study to underscore the influence of the complement pathway in the pathogenesis of this disease.
• In two 2006 studies, another gene that has implications for the disease, called HTRA1 (encoding a secreted serine protease), was identified.{{cite journal | vauthors = 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 | title = A variant of the HTRA1 gene increases susceptibility to age-related macular degeneration | journal = Science | volume = 314 | issue = 5801 | pages = 992–93 | date = November 2006 | pmid = 17053109 | doi = 10.1126/science.1133811 | bibcode = 2006Sci...314..992Y | s2cid = 19577378 | doi-access = free }}{{cite journal | vauthors = 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 | title = HTRA1 promoter polymorphism in wet age-related macular degeneration | journal = Science | volume = 314 | issue = 5801 | pages = 989–92 | date = November 2006 | pmid = 17053108 | doi = 10.1126/science.1133807 | bibcode = 2006Sci...314..989D | s2cid = 85725181 }}
• Six mutations of the gene SERPING1 (Serpin Peptidase Inhibitor, Clade G (C1 Inhibitor), Member 1) are associated with AMD. Mutations in this gene can also cause hereditary angioedema.{{cite news|last=Hirschler |first=Ben |title=Gene discovery may help hunt for blindness cure |publisher=Reuters |date=7 October 2008 |url=https://news.yahoo.com/s/nm/20081007/sc_nm/us_blindness_gene |access-date=7 October 2008 |url-status=dead |archive-url=https://web.archive.org/web/20081011202634/http://news.yahoo.com/s/nm/20081007/sc_nm/us_blindness_gene |archive-date=11 October 2008 }}
• Fibulin-5 mutation: Rare forms of the disease are caused by genetic defects in fibulin-5, in an autosomal dominant manner. In 2004, Stone et al. performed a screening on 402 AMD patients and revealed a statistically significant correlation between mutations in fibulin-5 and the incidence of the disease.{{citation needed|date=September 2024}}
• Mitochondrial-related gene polymorphisms such as that in the MT-ND2 molecule, predicts wet AMD.{{cite journal | vauthors = Udar N, Atilano SR, Memarzadeh M, Boyer DS, Chwa M, Lu S, Maguen B, Langberg J, Coskun P, Wallace DC, Nesburn AB, Khatibi N, Hertzog D, Le K, Hwang D, Kenney MC | title = Mitochondrial DNA haplogroups associated with age-related macular degeneration | journal = Investigative Ophthalmology & Visual Science | volume = 50 | issue = 6 | pages = 2966–74 | date = June 2009 | pmid = 19151382 | doi = 10.1167/iovs.08-2646 | doi-access = free }}{{cite journal | vauthors = Canter JA, Olson LM, Spencer K, Schnetz-Boutaud N, Anderson B, Hauser MA, Schmidt S, Postel EA, Agarwal A, Pericak-Vance MA, Sternberg P, Haines JL | title = Mitochondrial DNA polymorphism A4917G is independently associated with age-related macular degeneration | journal = PLOS ONE | volume = 3 | issue = 5 | pages = e2091 | date = May 2008 | pmid = 18461138 | pmc = 2330085 | doi = 10.1371/journal.pone.0002091 | editor1-last = Nicholas Weedon | editor1-first = Michael | bibcode = 2008PLoSO...3.2091C | doi-access = free }} {{open access}}

File:Human eye cross-sectional view grayscale.png cross-sectional view]]

The pathogenesis of age-related macular degeneration is not fully understood, although some theories have been put forward, including oxidative stress, mitochondrial dysfunction, and inflammatory processes.{{citation needed|date=September 2024}}

The imbalance between the production of damaged cellular components and degradation leads to the accumulation of harmful products, for example, intracellular lipofuscin and extracellular drusen. Incipient atrophy is demarcated by areas of retinal pigment epithelium (RPE) thinning or depigmentation that precedes geographic atrophy in the early stages of AMD. In advanced stages of AMD, atrophy of the RPE (geographic atrophy) and/or development of new blood vessels (neovascularization) result in the death of photoreceptors and central vision loss.{{citation needed|date=September 2024}}

In the dry (nonexudative) form, drusen accumulate between the retina and the choroid, causing atrophy and scarring to the retina. In the wet (exudative) form, which is more severe, blood vessels grow up from the choroid (neovascularization) behind the retina which can leak exudate and fluid and also cause hemorrhaging.{{citation needed|date=September 2024}}

Early work demonstrated a family of immune mediators was plentiful in drusen.{{cite journal | vauthors = Mullins RF, Russell SR, Anderson DH, Hageman GS | title = Drusen associated with aging and age-related macular degeneration contain proteins common to extracellular deposits associated with atherosclerosis, elastosis, amyloidosis, and dense deposit disease | journal = FASEB Journal | volume = 14 | issue = 7 | pages = 835–46 | date = May 2000 | pmid = 10783137 | doi = 10.1096/fasebj.14.7.835 | doi-access = free | s2cid = 24601453 }} Complement factor H (CFH) is an important inhibitor of this inflammatory cascade, and a disease-associated polymorphism in the CFH gene strongly associates with AMD.{{cite journal | vauthors = Hageman GS, Anderson DH, Johnson LV, Hancox LS, Taiber AJ, Hardisty LI, Hageman JL, Stockman HA, Borchardt JD, Gehrs KM, Smith RJ, Silvestri G, Russell SR, Klaver CC, Barbazetto I, Chang S, Yannuzzi LA, Barile GR, Merriam JC, Smith RT, Olsh AK, Bergeron J, Zernant J, Merriam JE, Gold B, Dean M, Allikmets R | title = A common haplotype in the complement regulatory gene factor H (HF1/CFH) predisposes individuals to age-related macular degeneration | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 102 | issue = 20 | pages = 7227–32 | date = May 2005 | pmid = 15870199 | pmc = 1088171 | doi = 10.1073/pnas.0501536102 | doi-access = free }}{{cite journal | vauthors = Chen LJ, Liu DT, Tam PO, Chan WM, Liu K, Chong KK, Lam DS, Pang CP | title = Association of complement factor H polymorphisms with exudative age-related macular degeneration | journal = Molecular Vision | volume = 12 | pages = 1536–42 | date = December 2006 | pmid = 17167412 }}{{cite journal | vauthors = Despriet DD, Klaver CC, Witteman JC, Bergen AA, Kardys I, de Maat MP, Boekhoorn SS, Vingerling JR, Hofman A, Oostra BA, Uitterlinden AG, Stijnen T, van Duijn CM, de Jong PT | title = Complement factor H polymorphism, complement activators, and risk of age-related macular degeneration | journal = JAMA | volume = 296 | issue = 3 | pages = 301–09 | date = July 2006 | pmid = 16849663 | doi = 10.1001/jama.296.3.301 | doi-access = free | hdl = 1765/63640 | hdl-access = free }}{{cite journal | vauthors = Li M, Atmaca-Sonmez P, Othman M, Branham KE, Khanna R, Wade MS, Li Y, Liang L, Zareparsi S, Swaroop A, Abecasis GR | title = CFH haplotypes without the Y402H coding variant show strong association with susceptibility to age-related macular degeneration | journal = Nature Genetics | volume = 38 | issue = 9 | pages = 1049–54 | date = September 2006 | pmid = 16936733 | pmc = 1941700 | doi = 10.1038/ng1871 }}{{cite journal | vauthors = Haines JL, Hauser MA, Schmidt S, Scott WK, Olson LM, Gallins P, Spencer KL, Kwan SY, Noureddine M, Gilbert JR, Schnetz-Boutaud N, Agarwal A, Postel EA, Pericak-Vance MA | title = Complement factor H variant increases the risk of age-related macular degeneration | journal = Science | volume = 308 | issue = 5720 | pages = 419–21 | date = April 2005 | pmid = 15761120 | doi = 10.1126/science.1110359 | bibcode = 2005Sci...308..419H | s2cid = 32716116 | doi-access = free }} Thus an AMD pathophysiological model of chronic low grade complement activation and inflammation in the macula has been advanced.{{cite book |doi=10.1007/978-1-4419-5635-4_10 |pmid=20711712 |chapter=A Targeted Inhibitor of the Complement Alternative Pathway Reduces RPE Injury and Angiogenesis in Models of Age-Related Macular Degeneration |title=Inflammation and Retinal Disease: Complement Biology and Pathology |volume=703 |pages=137–49 |series=Advances in Experimental Medicine and Biology |year=2010 |last1=Rohrer |first1=Bärbel |last2=Long |first2=Qin |last3=Coughlin |first3=Beth |last4=Renner |first4=Brandon |last5=Huang |first5=Yuxiang |last6=Kunchithapautham |first6=Kannan |last7=Ferreira |first7=Viviana P. |last8=Pangburn |first8=Michael K. |last9=Gilkeson |first9=Gary S. |last10=Thurman |first10=Joshua M. |last11=Tomlinson |first11=Stephen |last12=Holers |first12=V. Michael |isbn=978-1-4419-5634-7 }}{{cite journal | vauthors = Kunchithapautham K, Rohrer B | title = Sublytic membrane-attack-complex (MAC) activation alters regulated rather than constitutive vascular endothelial growth factor (VEGF) secretion in retinal pigment epithelium monolayers | journal = The Journal of Biological Chemistry | volume = 286 | issue = 27 | pages = 23717–24 | date = July 2011 | pmid = 21566137 | pmc = 3129152 | doi = 10.1074/jbc.M110.214593 | doi-access = free }} 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).{{cite journal |last1=Yates |first1=John R.W. |last2=Sepp |first2=Tiina |last3=Matharu |first3=Baljinder K. |last4=Khan |first4=Jane C. |last5=Thurlby |first5=Deborah A. |last6=Shahid |first6=Humma |last7=Clayton |first7=David G. |last8=Hayward |first8=Caroline |last9=Morgan |first9=Joanne |last10=Wright |first10=Alan F. |last11=Armbrecht |first11=Ana Maria |last12=Dhillon |first12=Baljean |last13=Deary |first13=Ian J. |last14=Redmond |first14=Elizabeth |last15=Bird |first15=Alan C. |last16=Moore |first16=Anthony T. |last17=Genetic Factors in AMD Study |first17=Group. |title=Complement C3 Variant and the Risk of Age-Related Macular Degeneration |journal=New England Journal of Medicine |date=9 August 2007 |volume=357 |issue=6 |pages=553–61 |doi=10.1056/NEJMoa072618 |pmid=17634448 |url=https://discovery.ucl.ac.uk/id/eprint/7361/ |doi-access=free }}

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 gene through destabilization of its mRNA through deletion of the polyadenylation signal.{{cite journal | vauthors = Fritsche LG, Loenhardt T, Janssen A, Fisher SA, Rivera A, Keilhauer CN, Weber BH | title = Age-related macular degeneration is associated with an unstable ARMS2 (LOC387715) mRNA | journal = Nature Genetics | volume = 40 | issue = 7 | pages = 892–96 | date = July 2008 | pmid = 18511946 | doi = 10.1038/ng.170 | s2cid = 205344383 }} ARMS2 protein may localize to the mitochondria and participate in energy metabolism, though much remains to be discovered about its function.{{citation needed|date=September 2024}}

Other gene markers of progression risk includes tissue inhibitor of metalloproteinase 3 (TIMP3), suggesting a role for extracellular matrix metabolism in AMD progression.{{cite journal | vauthors = Chen W, Stambolian D, Edwards AO, Branham KE, Othman M, Jakobsdottir J, Tosakulwong N, Pericak-Vance MA, Campochiaro PA, Klein ML, Tan PL, Conley YP, Kanda A, Kopplin L, Li Y, Augustaitis KJ, Karoukis AJ, Scott WK, Agarwal A, Kovach JL, Schwartz SG, Postel EA, Brooks M, Baratz KH, Brown WL, Brucker AJ, Orlin A, Brown G, Ho A, Regillo C, Donoso L, Tian L, Kaderli B, Hadley D, Hagstrom SA, Peachey NS, Klein R, Klein BE, Gotoh N, Yamashiro K, Ferris Iii F, Fagerness JA, Reynolds R, Farrer LA, Kim IK, Miller JW, Cortón M, Carracedo A, Sanchez-Salorio M, Pugh EW, Doheny KF, Brion M, Deangelis MM, Weeks DE, Zack DJ, Chew EY, Heckenlively JR, Yoshimura N, Iyengar SK, Francis PJ, Katsanis N, Seddon JM, Haines JL, Gorin MB, Abecasis GR, Swaroop A | title = Genetic variants near TIMP3 and high-density lipoprotein-associated loci influence susceptibility to age-related macular degeneration | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 107 | issue = 16 | pages = 7401–06 | date = April 2010 | pmid = 20385819 | pmc = 2867722 | doi = 10.1073/pnas.0912702107 | bibcode = 2010PNAS..107.7401C | doi-access = free }} Variations in cholesterol metabolising genes such as the hepatic lipase, cholesterol ester transferase, lipoprotein lipase and the ATP-binding cassette A1 correlate with disease progression. The early stigmata of the disease, drusen, are rich in cholesterol, offering face validity to the results of genome-wide association studies.{{cite journal | vauthors = Neale BM, Fagerness J, Reynolds R, Sobrin L, Parker M, Raychaudhuri S, Tan PL, Oh EC, Merriam JE, Souied E, Bernstein PS, Li B, Frederick JM, Zhang K, Brantley MA, Lee AY, Zack DJ, Campochiaro B, Campochiaro P, Ripke S, Smith RT, Barile GR, Katsanis N, Allikmets R, Daly MJ, Seddon JM | title = Genome-wide association study of advanced age-related macular degeneration identifies a role of the hepatic lipase gene (LIPC) | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 107 | issue = 16 | pages = 7395–400 | date = April 2010 | pmid = 20385826 | pmc = 2867697 | doi = 10.1073/pnas.0912019107 | bibcode = 2010PNAS..107.7395N | doi-access = free }}

In AMD there is a progressive accumulation of characteristic yellow deposits, called drusen (buildup of extracellular proteins and lipids), in the macula (a part of the retina), between the retinal pigment epithelium and the underlying choroid. This accumulation is believed to damage the retina over time. Amyloid beta, which builds up in Alzheimer's disease brains, is one of the proteins that accumulate in AMD, which is a reason why AMD is sometimes called "Alzheimer's of the eye" or "Alzheimer's of the retina".{{cite journal | vauthors = Ratnayaka JA, Serpell LC, Lotery AJ | title = Dementia of the eye: the role of amyloid beta in retinal degeneration | journal = Eye | volume = 29 | issue = 8 | pages = 1013–26 | date = August 2015 | pmid = 26088679 | pmc = 4541342 | doi = 10.1038/eye.2015.100 }} AMD can be divided into 3 stages: early, intermediate, and late, based partially on the extent (size and number) of drusen.

AMD-like pathology begins with small yellow deposits (drusen) in the macula, between the retinal pigment epithelium and the underlying choroid. Most people with these early changes (referred to as age-related maculopathy) still have good vision. People with drusen may or may not develop AMD. The majority of people over age 60 have drusen with no adverse effects. The risk of developing symptoms is higher when the drusen are large and numerous, and associated with the disturbance in the pigmented cell layer under the macula. Large and soft drusen are thought to be related to elevated cholesterol deposits.{{citation needed|date=September 2024}}

Early AMD is diagnosed based on the presence of medium-sized drusen, which is about the width of an average human hair. It is usually asymptomatic.

Intermediate AMD is diagnosed by large drusen and/or any retinal pigment abnormalities. Intermediate AMD may cause some vision loss, but, like early AMD, it is usually asymptomatic.{{cite journal | vauthors = Ferris FL, Wilkinson CP, Bird A, Chakravarthy U, Chew E, Csaky K, Sadda SR | title = Clinical classification of age-related macular degeneration | journal = Ophthalmology | volume = 120 | issue = 4 | pages = 844–51 | date = April 2013 | pmid = 23332590 | doi = 10.1016/j.ophtha.2012.10.036 | pmc = 11551519 }}

Recently, subgroups of intermediate AMD have been identified, which have a very high risk of progression toward late AMD. This subgroup (depending on the precise definitions) is termed nascent GA and/or iRORA (incomplete retinal pigment epithelium and outer retinal atrophy).{{cite journal |vauthors=Wu Z, Luu CD, Hodgson LA, Caruso E, Tindill N, Aung KZ, McGuinness MB, Makeyeva G, Chen FK, Chakravarthy U, Arnold JJ, Heriot WJ, Durkin SR, Guymer RH |title=Prospective Longitudinal Evaluation of Nascent Geographic Atrophy in Age-Related Macular Degeneration |journal=Ophthalmol Retina |volume=4 |issue=6 |pages=568–575 |date=June 2020 |pmid=32088159 |doi=10.1016/j.oret.2019.12.011 |s2cid=211263484 |url=|doi-access=free }}{{cite journal |vauthors=Wu Z, Pfau M, Blodi BA, Holz FG, Jaffe GJ, Liakopoulos S, Sadda SR, Staurenghi G, Bjelopera E, Brown T, Chang P, Choong J, Corradetti G, Corvi F, Domalpally A, Hurtenbach C, Nittala MG, Olson A, Pak JW, Pappe J, Saßmannshausen M, Skalak C, Thiele S, Guymer RH, Schmitz-Valckenberg S |title=OCT Signs of Early Atrophy in Age-Related Macular Degeneration: Interreader Agreement: Classification of Atrophy Meetings Report 6 |journal=Ophthalmol Retina |volume= 6|issue= 1|pages= 4–14|date=March 2021 |pmid=33766801 |doi=10.1016/j.oret.2021.03.008| issn=2468-6530 |url=|doi-access=free }} These 'high-risk' subgroups of intermediate AMD can be used to inform patients of their prognosis. In addition, these can be applied in clinical trials as endpoints.{{citation needed|date=September 2024}}

In late AMD, enough retinal damage occurs that, in addition to drusen, people will also begin to experience symptomatic central vision loss. The damage can either be the development of atrophy or the onset of neovascular disease. Late AMD is further divided into two subtypes based on the types of damage: Geographic atrophy and Wet AMD (also called Neovascular AMD).

Dry AMD (also called nonexudative AMD) is a broad designation, encompassing all forms of AMD that are not neovascular (wet AMD). This includes early and intermediate forms of AMD, as well as the advanced form of dry AMD known as geographic atrophy. Dry AMD patients tend to have minimal symptoms in the earlier stages; visual function loss occurs more often if the condition advances to geographic atrophy. Dry AMD accounts for 80–90% of cases and usually progresses slowly. In 10–20% of people, dry AMD progresses to the wet type.{{citation needed|date=September 2024}}

{{main|Geographic atrophy}}

Geographic atrophy (also called atrophic AMD) is an advanced form of AMD in which progressive and irreversible loss of retinal cells leads to a loss of visual function. Multiple layers make up the retina, and in geographic atrophy, three specific layers undergo atrophy: the choriocapillaris, retinal pigment epithelium, and the overlying photoreceptors.{{citation needed|date=September 2024}}

The three layers that undergo atrophy in geographic atrophy are all adjacent to each other. The photoreceptors are the most superficial and they are the cells that are responsible for converting energy from the light from the outside world, into an electrical signal to be sent to the brain. There are several functions of the retinal pigment epithelium. One of the main functions of the retinal pigment epithelium is to minimize oxidative stress. It does so by absorbing light and thus preventing it from getting to the underlying layers. The layers underlying the retinal pigment epithelium are very vascularized so they have very high oxygen tension. Thus, if light were to get to those layers, many free radicals would form and cause damage to nearby tissues. The deepest layer that undergoes atrophy in geographic atrophy is called the choriocappilaris. It is a capillary network that provides nutrients to the retinal pigment epithelium.{{citation needed|date=September 2024}}

The pathophysiology of geographic atrophy is still uncertain. Some studies questioned whether it was due to a deficient retinal pigment epithelium, leading to increased oxidative stress.{{cite journal |last1=X. Shaw |first1=Peter |last2=Stiles |first2=Travis |last3=Douglas |first3=Christopher |last4=Ho |first4=Daisy |last5=Fan |first5=Wei |last6=Du |first6=Hongjun |last7=Xiao |first7=Xu |title=Oxidative stress, innate immunity, and age-related macular degeneration |journal=AIMS Molecular Science |date=2016 |volume=3 |issue=2 |pages=196–221 |doi=10.3934/molsci.2016.2.196 |pmid=27239555 |pmc=4882104 }} Other studies have looked for inflammatory causes of damage.{{cite journal |last1=Kauppinen |first1=Anu |last2=Paterno |first2=Jussi J. |last3=Blasiak |first3=Janusz |last4=Salminen |first4=Antero |last5=Kaarniranta |first5=Kai |title=Inflammation and its role in age-related macular degeneration |journal=Cellular and Molecular Life Sciences |date=6 February 2016 |volume=73 |issue=9 |pages=1765–86 |doi=10.1007/s00018-016-2147-8 |pmid=26852158 |pmc=4819943 }} Thus far, the medical community is still not certain. Recent studies have begun to look at each layer individually. They found that decreased blood flow in the choriocapillaris precedes atrophy of the retinal pigment epithelium and the overlying photoreceptors.{{cite journal |last1=Thulliez |first1=Marie |last2=Zhang |first2=Qinqin |last3=Shi |first3=Yingying |last4=Zhou |first4=Hao |last5=Chu |first5=Zhongdi |last6=de Sisternes |first6=Luis |last7=Durbin |first7=Mary K. |last8=Feuer |first8=William |last9=Gregori |first9=Giovanni |last10=Wang |first10=Ruikang K. |last11=Rosenfeld |first11=Philip J. |title=Correlations between Choriocapillaris Flow Deficits around Geographic Atrophy and Enlargement Rates Based on Swept-Source OCT Imaging |journal=Ophthalmology Retina |date=June 2019 |volume=3 |issue=6 |pages=478–88 |doi=10.1016/j.oret.2019.01.024 |pmid=31174669 |s2cid=86851083 |pmc=11402513 }} Since the choriocapillaris is a vascular layer, this may be used as an argument for why geographic atrophy could be a disease due to decreased blood flow.{{citation needed|date=September 2024}}

Neovascular or exudative AMD, the "wet" form of advanced AMD, causes vision loss due to abnormal blood vessel growth (choroidal neovascularization) in the choriocapillaris, through Bruch's membrane. It is usually, but not always, preceded by the dry form of AMD. The proliferation of abnormal blood vessels in the retina is stimulated by vascular endothelial growth factor (VEGF). Because these blood vessels are abnormal, they are also more fragile than typical blood vessels, which ultimately leads 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.

File:Opthalmology AMD Super Resolution Cremer.png

Diagnosis of age-related macular degeneration depends on signs in the macula, not necessarily vision. Early diagnosis of AMD can prevent further visual deterioration and potentially improve vision.{{cite book|url=https://www.ncbi.nlm.nih.gov/books/NBK481428/|title=Age-related macular degeneration: diagnosis and management|last=National Guideline Alliance (UK)|date=2018|publisher=National Institute for Health and Care Excellence (UK)|isbn=978-1473127876|series=National Institute for Health and Care Excellence: Clinical Guidelines|location=London|pmid=29400919}}

Diagnosis of dry (or early stage) AMD may include the following clinical examinations as well as procedures and tests:

• The transition from dry to wet AMD can happen rapidly, and if it is left untreated can lead to legal blindness in as little as six months. To prevent this from occurring and to initiate preventive strategies earlier in the disease process, dark adaptation testing may be performed. A dark adaptometer can detect subclinical AMD at least three years earlier than it is clinically evident.{{cite journal | vauthors = Owsley C, McGwin G, Clark ME, Jackson GR, Callahan MA, Kline LB, Witherspoon CD, Curcio CA | title = Delayed Rod-Mediated Dark Adaptation Is a Functional Biomarker for Incident Early Age-Related Macular Degeneration | journal = Ophthalmology | volume = 123 | issue = 2 | pages = 344–51 | date = February 2016 | pmid = 26522707 | pmc = 4724453 | doi = 10.1016/j.ophtha.2015.09.041 }}
• There is a loss of contrast sensitivity, so that contours, shadows, and color vision are less vivid. The loss of contrast sensitivity can be quickly and easily measured by a contrast sensitivity test like Pelli Robson performed either at home or by an eye specialist.{{citation needed|date=September 2024}}
• When viewing an Amsler grid, some straight lines appear wavy and some patches appear blank{{cite web |title=Amsler grid |url=https://myhealth.alberta.ca:443/Health/Pages/conditions.aspx?hwid=hw173885 |access-date=19 May 2023 |website=myhealth.alberta.ca |language=en-US}}
• When viewing a Snellen chart, at least 2 lines decline{{citation needed|date=September 2024}}
• In dry macular degeneration, which occurs in 85–90 percent of AMD cases, drusen spots can be seen in Fundus photography{{citation needed|date=September 2024}}
• Using an electroretinogram, points in the macula with a weak or absent response compared to a normal eye may be found{{citation needed|date=September 2024}}
• Farnsworth-Munsell 100 hue test and Maximum Color Contrast Sensitivity test (MCCS) for assessing color acuity and color contrast sensitivity
• Optical coherence tomography is now used by most ophthalmologists in the diagnosis and the follow-up evaluation of the response to treatment with antiangiogenic drugs.{{citation needed|date=September 2024}}

Diagnosis of wet (or late-stage) AMD may include the following in addition to the above tests:

• Preferential hyperacuity perimetry changes (for wet AMD). Preferential hyperacuity perimetry is a test that detects drastic changes in vision and involves the macula being stimulated with distorted patterns of dots and the patient identification of where in the visual field this occurs.{{cite journal | vauthors = Faes L, Bodmer NS, Bachmann LM, Thiel MA, Schmid MK | title = Diagnostic accuracy of the Amsler grid and the preferential hyperacuity perimetry in the screening of patients with age-related macular degeneration: systematic review and meta-analysis | journal = Eye | volume = 28 | issue = 7 | pages = 788–96 | date = July 2014 | pmid = 24788016 | pmc = 4094801 | doi = 10.1038/eye.2014.104 }}
• In wet macular degeneration, angiography can visualize the leakage of the bloodstream behind the macula. Fluorescein angiography allows for the identification and localization of abnormal vascular processes.

• Pigmentary changes in the retina – In addition to the pigmented cells in the iris (the colored part of the eye), there are pigmented cells beneath the retina. As these cells break down and release their pigment, dark clumps of released pigment and later, areas that are less pigmented may appear{{citation needed|date=September 2024}}
• Exudative changes: hemorrhages in the eye, hard exudates, subretinal/sub-RPE/intraretinal fluid{{citation needed|date=September 2024}}
• Drusen, tiny accumulations of extracellular material that build up on the retina. 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.{{citation needed|date=September 2024}}

Treatment of AMD varies depending on the category of the disease at the time of diagnosis. In general, treatment is aimed at slowing down the progression of AMD.Bishop P. Age-related macular degeneration. BMJ Best Practice. 2018. As of 2018, there are no treatments to reverse the effects of AMD. As of 2024, there are two drugs to dissolve the drusen in dry AMD, see below. Early-stage and intermediate-stage AMD is managed by modifying known risk factors such as smoking cessation, management of hypertension and atherosclerosis, and making dietary modifications. For intermediate-stage AMD, management also includes antioxidant and mineral supplementation. Advanced-stage AMD is managed based on the presence of choroidal neovascularization (CNV): dry AMD (no CNV present) or wet AMD (CNV present). No effective treatments exist for dry AMD. The CNV present in wet AMD is managed with vascular endothelial growth factor (VEGF) inhibitors.{{cite journal | vauthors = Sarwar S, Clearfield E, Soliman MK, Sadiq MA, Baldwin AJ, Hanout M, Agarwal A, Sepah YJ, Do DV, Nguyen QD | title = Aflibercept for neovascular age-related macular degeneration | journal = The Cochrane Database of Systematic Reviews | volume = 2016 | pages = CD011346 | date = February 2016 | issue = 2 | pmid = 26857947 | pmc = 5030844 | doi = 10.1002/14651858.cd011346.pub2 }}{{cite journal | vauthors = Lawrenson JG, Evans JR | title = Omega 3 fatty acids for preventing or slowing the progression of age-related macular degeneration | journal = The Cochrane Database of Systematic Reviews | issue = 4 | pages = CD010015 | date = April 2015 | volume = 2015 | pmid = 25856365 | doi = 10.1002/14651858.cd010015.pub3 | pmc = 7087473 | url = http://openaccess.city.ac.uk/8613/1/CD010015.pdf }} Daily use of an Amsler grid or other home visual monitoring tools can be used to monitor for development of distorted vision, which may be a sign of disease progression.

Dietary supplements may be suggested for people with AMD, to reduce damage to the cells in the retina with antioxidants. The formulations commonly suggested are known as AREDS. The specific vitamins and minerals in AREDS-1 are vitamin C (500 mg), zinc (80 mg), vitamin E (400 IU), copper (2 mg) and beta-carotene (15 mg). In the AREDS-2 formulation, lutein (10 mg) and zeaxanthin (2 mg) replaced beta-carotene due to the risk of lung cancer in smokers taking beta-carotene. There is some evidence to indicate that people with bilateral early or intermediate AMD, or intermediate AMD in one eye and advanced AMD in the other eye may benefit from vitamin and mineral supplementation. AREDS supplementation may help slow the progression to more severe forms of AMD and there is some evidence of improved visual acuity at 5 years. There is no evidence that micronutrient supplementation prevents AMD progression in those with severe disease or prevents disease onset in those without AMD.

With regards to AREDS-1 compared with AREDS-2 formulations, there is only weak evidence comparing the effectiveness of each formulation and the effectiveness of lutein and zeaxanthin as a replacement in the AREDS-2 formulation.

{{Further|topic=the investigational new drug|Tinlarebant}}

Pegcetacoplan (Syfovre){{cite web | title=Syfovre- pegcetacoplan injection, solution | website=DailyMed | date=23 February 2023 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b4434e61-9ec9-4e0e-bd60-45aaa0a87e64 | access-date=6 June 2023}}{{cite press release |title=FDA Approves Syfovre (pegcetacoplan injection) as the First and Only Treatment for Geographic Atrophy (GA), a Leading Cause of Blindness |publisher=Apellis Pharmaceuticals |via=GlobeNewswire |date=17 February 2023 |url=https://www.globenewswire.com/news-release/2023/02/17/2610967/0/en/FDA-Approves-SYFOVRE-pegcetacoplan-injection-as-the-First-and-Only-Treatment-for-Geographic-Atrophy-GA-a-Leading-Cause-of-Blindness.html |access-date=18 February 2023 |archive-date=17 February 2023 |archive-url=https://web.archive.org/web/20230217233556/https://www.globenewswire.com/news-release/2023/02/17/2610967/0/en/FDA-Approves-SYFOVRE-pegcetacoplan-injection-as-the-First-and-Only-Treatment-for-Geographic-Atrophy-GA-a-Leading-Cause-of-Blindness.html |url-status=live}} and avacincaptad pegol (Izervay){{cite web | title=Novel Drug Approvals for 2023 | website=U.S. Food and Drug Administration (FDA) | date=18 August 2023 | url=https://www.fda.gov/drugs/novel-drug-approvals-fda/novel-drug-approvals-2023 | access-date=25 August 2023}}{{cite press release | title=Iveric Bio Receives U.S. FDA Approval for Izervay (avacincaptad pegol intravitreal solution), a New Treatment for Geographic Atrophy | publisher=Astellas Pharma Inc. | via=PR Newswire | date=4 August 2023 | url=https://www.prnewswire.com/news-releases/iveric-bio-receives-us-fda-approval-for-izervay-avacincaptad-pegol-intravitreal-solution-a-new-treatment-for-geographic-atrophy-301894042.html | access-date=25 August 2023}} are approved for medical use in the United States. In 2023 it was reported that the aging pigment lipofuscin can be broken down with the help of melanin and drugs through a newly discovered mechanism.Lyu Y, Tschulakow AV, Wang K, Brash DE, Schraermeyer U. Chemiexcitation and melanin in photoreceptor disc turnover and prevention of macular degeneration. Proc Natl Acad Sci U S A. 2023;120(20):e2216935120. The pigment lipofuscin plays a central role in the development of dry AMD and Stargardt's disease. The clinical development of this mechanism, which has the potential to clear Bruch's membrane and reduce the formation of drusen, is in preparation.{{citation needed|date=September 2024}}

Ranibizumab, aflibercept, brolucizumab, and faricimab are approved VEGF inhibitors for the treatment of CNV in wet AMD.{{cite journal |last1=Nguyen |first1=Quan Dong |title=Brolucizumab: Evolution through Preclinical and Clinical Studies and the Implications for the Management of Neovascular Age-Related Macular Degeneration |journal= Ophthalmology|year=2020 |volume=127 |issue=7 |pages=963–76 |doi=10.1016/j.ophtha.2019.12.031 |pmid=32107066 |doi-access=free }} All three drugs are administered via intravitreal injection, meaning they are injected directly into the eye. Bevacizumab is another VEGF inhibitor that has been shown to have similar efficacy and safety as the previous two drugs, however, is not currently indicated for AMD. AMD can also be treated with laser coagulation therapy.{{cite journal | vauthors = Virgili G, Bini A | title = Laser photocoagulation for neovascular age-related macular degeneration | journal = The Cochrane Database of Systematic Reviews | issue = 3 | pages = CD004763 | date = July 2007 | pmid = 17636773 | doi = 10.1002/14651858.cd004763.pub2 }}

A randomized control trial found that bevacizumab and ranibizumab had similar efficacy, and reported no significant increase in adverse events with bevacizumab.{{cite journal | vauthors = Chakravarthy U, Harding SP, Rogers CA, Downes SM, Lotery AJ, Culliford LA, Reeves BC | title = Alternative treatments to inhibit VEGF in age-related choroidal neovascularisation: 2-year findings of the IVAN randomised controlled trial | journal = The Lancet | volume = 382 | issue = 9900 | pages = 1258–67 | date = October 2013 | pmid = 23870813 | doi = 10.1016/S0140-6736(13)61501-9 | doi-access = free }} A 2014 Cochrane review found that the systemic safety of bevacizumab and ranibizumab are similar when used to treat neovascular AMD, except for gastrointestinal disorders.{{cite journal | vauthors = Moja L, Lucenteforte E, Kwag KH, Bertele V, Campomori A, Chakravarthy U, D'Amico R, Dickersin K, Kodjikian L, Lindsley K, Loke Y, Maguire M, Martin DF, Mugelli A, Mühlbauer B, Püntmann I, Reeves B, Rogers C, Schmucker C, Subramanian ML, Virgili G | editor1-first = Lorenzo | editor1-last = Moja | title = Systemic safety of bevacizumab versus ranibizumab for neovascular age-related macular degeneration | journal = The Cochrane Database of Systematic Reviews | volume = 9 | issue = 9 | pages = CD011230 | date = September 2014 | pmid = 25220133 | pmc = 4262120 | doi = 10.1002/14651858.CD011230.pub2 | hdl = 2434/273140 }} Bevacizumab, however, is not FDA-approved for the treatment of macular degeneration. A controversy in the UK involved the off-label use of cheaper bevacizumab over the approved, but expensive, ranibizumab.{{cite news |last1=Copley |first1=Caroline |first2=Ben |last2=Hirschler |date=24 April 2012 |title=Novartis challenges UK Avastin use in eye disease |work=Reuters |url=https://www.reuters.com/article/us-novartis-britain-idUSBRE83N0GM20120424 |url-status=live |archive-url=https://web.archive.org/web/20130522203804/https://www.reuters.com/article/2012/04/24/us-novartis-britain-idUSBRE83N0GM20120424 |archive-date=22 May 2013 }} Ranibizumab is a smaller fragment, Fab fragment, of the parent bevacizumab molecule specifically designed for eye injections.{{cite journal|last1=Heidary|first1=Fatemeh|last2=Hitam|first2=Wan Hazabbah Wan|last3=Ngah|first3=Nor Fariza|last4=George|first4=Tara Mary|last5=Hashim|first5=Hanizasurana|last6=Shatriah|first6=Ismail|date=2011|title=Intravitreal Ranibizumab for Choroidal Neovascularization in Best's Vitelliform Macular Dystrophy in a 6-Year-Old Boy|url=https://journals.healio.com/doi/abs/10.3928/01913913-20110308-02|journal=Journal of Pediatric Ophthalmology & Strabismus|language=en|volume=48|issue=6|pages=e19-22|doi=10.3928/01913913-20110308-02|pmid=21417187|issn=0191-3913|url-access=subscription}} Other approved antiangiogenic drugs for the treatment of neovascular AMD include pegaptanib{{cite web |title=FDA Approves New Drug Treatment for Age-Related Macular Degeneration |url=https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2004/ucm108385.htm |website=FDA.gov |publisher=U.S. Food and Drug Administration |url-status=dead |archive-url=https://web.archive.org/web/20151120020217/https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2004/ucm108385.htm |archive-date=20 November 2015 }} and aflibercept.{{cite web|url=https://www.medpagetoday.com/ophthalmology/generalophthalmology/29811|archiveurl=https://web.archive.org/web/20130528151430/http://www.medpagetoday.com/Ophthalmology/GeneralOphthalmology/29811|url-status=dead|title=FDA Approves Eylea for Macular Degeneration|date=19 November 2011|archivedate=28 May 2013|website=www.medpagetoday.com}}

These anti-VEGF agents may be administered monthly or adaptively. For adaptive anti-VEGF treatment, two approaches are conventionally applied. In the case of pro re nata, the patient comes at fixed intervals, but treatment is only administered if an activity is detected (i.e., the presence of fluid). In the case of treat-and-extend, the patients always receive treatment, but the interval to the next visit is extended if the lesion is inactive.{{cite journal |vauthors=Okada M, Kandasamy R, Chong EW, McGuiness M, Guymer RH |title=The Treat-and-Extend Injection Regimen Versus Alternate Dosing Strategies in Age-related Macular Degeneration: A Systematic Review and Meta-analysis |journal=Am J Ophthalmol |volume=192 |issue= |pages=184–197 |date=August 2018 |pmid=29885297 |doi=10.1016/j.ajo.2018.05.026 |s2cid=47012435 |url=}}

Recently, researchers have started to apply AI algorithms to predict the future need for treatment.{{cite journal |vauthors=Pfau M, Sahu S, Rupnow RA, Romond K, Millet D, Holz FG, Schmitz-Valckenberg S, Fleckenstein M, Lim JI, de Sisternes L, Leng T, Rubin DL, Hallak JA |title=Probabilistic Forecasting of Anti-VEGF Treatment Frequency in Neovascular Age-Related Macular Degeneration |journal=Transl Vis Sci Technol |volume=10 |issue=7 |pages=30 |date=June 2021 |pmid=34185055 |pmc=8254013 |doi=10.1167/tvst.10.7.30 |url=}}{{cite journal |vauthors=Vogl WD, Waldstein SM, Gerendas BS, Schlegl T, Langs G, Schmidt-Erfurth U |title=Analyzing and Predicting Visual Acuity Outcomes of Anti-VEGF Therapy by a Longitudinal Mixed Effects Model of Imaging and Clinical Data |journal=Invest Ophthalmol Vis Sci |volume=58 |issue=10 |pages=4173–4181 |date=August 2017 |pmid=28837729 |doi=10.1167/iovs.17-21878 |url=|doi-access=free }}{{cite journal |vauthors=Gallardo M, Munk MR, Kurmann T, De Zanet S, Mosinska A, Karagoz IK, Zinkernagel MS, Wolf S, Sznitman R |title=Machine Learning Can Predict Anti-VEGF Treatment Demand in a Treat-and-Extend Regimen for Patients with Neovascular AMD, DME, and RVO Associated Macular Edema |journal=Ophthalmol Retina |volume=5 |issue=7 |pages=604–624 |date=July 2021 |pmid=33971352 |doi=10.1016/j.oret.2021.05.002 |url=|doi-access=free }}

The American Academy of Ophthalmology practice guidelines do not recommend laser coagulation therapy for macular degeneration, but state that it may be useful in people with new blood vessels in the choroid outside of the fovea who do not respond to drug treatment.{{cite web|title=Age-Related Macular Degeneration PPP – Updated 2015|url=http://www.aao.org/preferred-practice-pattern/age-related-macular-degeneration-ppp-2015|publisher=American Academy of Ophthalmology Preferred Practice Pattern|access-date=22 October 2016|date=29 January 2015|url-status=live|archive-url=https://web.archive.org/web/20161021033327/http://www.aao.org/preferred-practice-pattern/age-related-macular-degeneration-ppp-2015|archive-date=21 October 2016}}{{cite journal | vauthors = Lindsley K, Li T, Ssemanda E, Virgili G, Dickersin K | title = Interventions for Age-Related Macular Degeneration: Are Practice Guidelines Based on Systematic Reviews? | journal = Ophthalmology | volume = 123 | issue = 4 | pages = 884–97 | date = April 2016 | pmid = 26804762 | pmc = 4808456 | doi = 10.1016/j.ophtha.2015.12.004 }} There is strong evidence that laser coagulation will result in the disappearance of drusen but does not affect choroidal neovascularisation.{{cite journal | vauthors = Virgili G, Michelessi M, Parodi MB, Bacherini D, Evans JR | title = Laser treatment of drusen to prevent progression to advanced age-related macular degeneration | journal = The Cochrane Database of Systematic Reviews | volume = 2015 | issue = 10 | pages = CD006537 | date = October 2015 | pmid = 26493180 | pmc = 4733883 | doi = 10.1002/14651858.CD006537.pub3 }} A 2007 Cochrane review found that laser photocoagulation of new blood vessels in the choroid outside of the fovea is an effective and economical method, but that the benefits are limited for vessels next to or below the fovea.{{cite journal | vauthors = Virgili G, Bini A | title = Laser photocoagulation for neovascular age-related macular degeneration | journal = The Cochrane Database of Systematic Reviews | issue = 3 | pages = CD004763 | date = July 2007 | pmid = 17636773 | doi = 10.1002/14651858.CD004763.pub2 }}

Photodynamic therapy has also been used to treat wet AMD.{{cite journal |journal=Health Technology Assessment |year=2003 |volume=7 |issue=9 |pages=v–vi, 1–98 |title=Clinical effectiveness and cost-utility of photodynamic therapy for wet age-related macular degeneration: a systematic review and economic evaluation |doi=10.3310/hta7090 |pmid=12709292 |author=Meads C|doi-access=free }} The drug verteporfin is administered intravenously; light of a certain wavelength is then applied to the abnormal blood vessels. This activates the verteporfin destroying the vessels.

Cataract surgery could improve visual outcomes for people with AMD, though there have been concerns about surgery increasing the progression of AMD. A randomized controlled trial found that people who underwent immediate cataract surgery (within two weeks) had improved visual acuity and better quality of life outcomes than those who underwent delayed cataract surgery (6 months).{{cite journal | vauthors = Casparis H, Lindsley K, Kuo IC, Sikder S, Bressler NM | title = Surgery for cataracts in people with age-related macular degeneration | journal = The Cochrane Database of Systematic Reviews | volume = 2017 | pages = CD006757 | date = February 2017 | issue = 2 | pmid = 28206671 | pmc = 3480178 | doi = 10.1002/14651858.CD006757.pub4 }}

Radiotherapy has been proposed as a treatment for wet AMD but the evidence to support the use of modern stereotactic radiotherapy combined with anti-VEGF is currently uncertain and is awaiting the results of ongoing studies.{{cite journal|last1=Evans|first1=Jennifer R|last2=Igwe|first2=Chinedu|last3=Jackson|first3=Timothy L|last4=Chong|first4=Victor|date=26 August 2020|title=Radiotherapy for neovascular age-related macular degeneration|url=https://doi.org/10.1002/14651858.CD004004.pub4|journal=Cochrane Database of Systematic Reviews|volume=2020|issue=8|pages=CD004004|doi=10.1002/14651858.cd004004.pub4|pmid=32844399|pmc=8812340|s2cid=221326233|issn=1465-1858}}

Nucleoside reverse transcription inhibitors like they are used in anti-HIV therapy were associated with a reduced risk of developing atrophic macular degeneration. This is because Alu elements undergo L1 (protein)-mediated reverse transcription in the cytoplasm resulting in DNA synthesis. First clinical trials are being prepared as of January 2021.{{cite journal |last1=Fukuda |first1=Shinichi |last2=Varshney |first2=Akhil |last3=Fowler |first3=Benjamin J. |last4=Wang |first4=Shao-bin |last5=Narendran |first5=Siddharth |last6=Ambati |first6=Kameshwari |last7=Yasuma |first7=Tetsuhiro |last8=Magagnoli |first8=Joseph |last9=Leung |first9=Hannah |last10=Hirahara |first10=Shuichiro |last11=Nagasaka |first11=Yosuke |date=9 February 2021 |title=Cytoplasmic synthesis of endogenous Alu complementary DNA via reverse transcription and implications in age-related macular degeneration |journal=Proceedings of the National Academy of Sciences |language=en |volume=118 |issue=6 |pages=e2022751118 |doi=10.1073/pnas.2022751118 |issn=0027-8424 |pmid=33526699|pmc=8017980 |bibcode=2021PNAS..11822751F |s2cid=231761522 |doi-access=free }}

File:Josef Tal & Computer Screen.jpg, an Israeli composer who was affected by macular degeneration, checks a manuscript using a CCTV desktop unit.]]

Because peripheral vision is not affected, persons with macular degeneration can learn to use their remaining vision to partially compensate.{{cite web |url=http://www.mdsupport.org/lvrehab.html |title=Low Vision Rehabilitation Delivery Model |publisher=Mdsupport.org |access-date=11 January 2011 |url-status=dead |archive-url=https://web.archive.org/web/20101107045042/http://www.mdsupport.org/lvrehab.html |archive-date=7 November 2010 }} Assistance and resources are available in many countries and every state in the U.S.{{cite web |url=http://www.mdsupport.org/resource_index.html |title=Agencies, Centers, Organizations, & Societies |publisher=Mdsupport.org |date=1 September 2005 |access-date=11 January 2011 |url-status=dead |archive-url=https://web.archive.org/web/20110611142648/http://www.mdsupport.org/resource_index.html |archive-date=11 June 2011 }} 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, electronic glasses, and TV systems that enlarge the reading material.

Computer screen readers such as JAWS or Thunder work with standard Windows computers.

Also, Apple devices provide a wide range of features (voice-over, screen readers, Braille, etc.).

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 provides larger fonts for printed books, patterns to make tracking easier, audiobooks and DAISY books with both text and audio.

File:Macular degeneration and other (sense organ diseases) world map - DALY - WHO2004.svg for macular degeneration and other (sense organ diseases) per 100,000 inhabitants in 2004{{cite web |url=https://www.who.int/healthinfo/global_burden_disease/estimates_country/en/index.html |title=WHO Disease and injury country estimates |year=2009 |work=World Health Organization |access-date=11 November 2009 |url-status=live |archive-url=https://web.archive.org/web/20091111101009/http://www.who.int/healthinfo/global_burden_disease/estimates_country/en/index.html |archive-date=11 November 2009 }}{{Div col|small=yes|colwidth=10em}}

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The prevalence of any age-related macular degeneration is higher in Europeans than in Asians and Africans.{{cite journal | vauthors = Wong WL, Su X, Li X, Cheung CM, Klein R, Cheng CY, Wong TY | title = Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis | journal = The Lancet. Global Health | volume = 2 | issue = 2 | pages = e106–16 | date = February 2014 | pmid = 25104651 | doi = 10.1016/S2214-109X(13)70145-1 | doi-access = free }} There is no difference in prevalence between Asians and Africans. The incidence of age-related macular degeneration and its associated features increases with age and is low in people <55 years of age.{{cite web |url=https://bestpractice.bmj.com/topics/en-us/554 |title=Age-related macular degeneration - Symptoms, diagnosis and treatment |website=BMJ Best Practice |access-date=13 November 2018}} Smoking is the strongest modifiable risk factor.{{cite journal | vauthors = Velilla S, García-Medina JJ, García-Layana A, Dolz-Marco R, Pons-Vázquez S, Pinazo-Durán MD, Gómez-Ulla F, Arévalo JF, Díaz-Llopis M, Gallego-Pinazo R | title = Smoking and age-related macular degeneration: review and update | journal = Journal of Ophthalmology | volume = 2013 | pages = 895147 | date = 2013 | pmid = 24368940 | pmc = 3866712 | doi = 10.1155/2013/895147 | doi-access = free }} As of 2008, age-related macular degeneration accounts for more than 54% of all vision loss in the white population in the US.{{cite journal|last1=Coleman|first1=Hanna R|last2=Chan|first2=Chi-Chao|last3=Ferris|first3=Frederick L|last4=Chew|first4=Emily Y|date=November 2008|title=Age-related macular degeneration|journal=The Lancet|language=en|volume=372|issue=9652|pages=1835–45|doi=10.1016/S0140-6736(08)61759-6|pmid=19027484|issn=0140-6736|pmc=2603424}} An estimated 8 million Americans are affected with early age-related macular degeneration, of whom over 1 million will develop advanced age-related macular degeneration within the next 5 years. In the UK, age-related macular degeneration is the cause of blindness in almost 42% of those who go blind aged 65–74 years, almost two-thirds of those aged 75–84 years, and almost three-quarters of those aged 85 years or older.

Studies indicate drusen associated with AMD are similar in molecular composition to amyloid beta (Aβ) plaques and deposits in other age-related diseases such as Alzheimer's disease and atherosclerosis. This suggests that similar pathways may be involved in the etiologies of AMD and other age-related diseases.{{cite journal | vauthors = Mullins RF, Russell SR, Anderson DH, Hageman GS | title = Drusen associated with aging and age-related macular degeneration contain proteins common to extracellular deposits associated with atherosclerosis, elastosis, amyloidosis, and dense deposit disease | journal = FASEB Journal | volume = 14 | issue = 7 | pages = 835–46 | date = May 2000 | pmid = 10783137 | display-authors = et al | doi = 10.1096/fasebj.14.7.835 | doi-access = free | s2cid = 24601453 }}

Genetic testing can help identify whether a patient with AMD is at a greater risk of developing the condition and can inform disease progression. Genetic testing can also allow researchers to identify whether patients are more or less likely to respond to treatments, such anti-VEGF medication or complement inhibitors.{{cite web|title=EYE-RISK - EYE-RISK|url=http://www.eyerisk.eu/|access-date=15 May 2021|website=www.eyerisk.eu}} However, there remain several challenges to using predictive tools which incorporate genetic variation in clinical practice. As well as our limited understanding of the way that different genetic variants and environmental factors interact to influence AMD risk, the single nucleotide polymorphisms that are common in the population have small effects on individual patients with AMD. Therefore, there is increasing interest in understanding the functional consequences of rare mutations, which often have more pronounced effects. Genetic testing to guide clinical management is not currently recommended.

CRISPR-Cas9 genome editing may be used to treat wet age-related macular degeneration caused by VEGFA. Scientists described an approach in which engineered lentiviruses are injected into the affected anatomical regions for transient editing that could reduce the area of choroidal neovascularization by 63% without inducing undesired off-target edits or anti-Cas9 immune responses.{{cite journal |title=Transient editing catches the eye |journal=Nature Biomedical Engineering |page=127|language=en |doi=10.1038/s41551-021-00695-z |date=February 2021|volume=5 |issue=2 |pmid=33580230 | format = Editorial |doi-access=free }}{{cite journal |last1=Ling |first1=Sikai |last2=Yang |first2=Shiqi |last3=Hu |first3=Xinde |last4=Yin |first4=Di |last5=Dai |first5=Yao |last6=Qian |first6=Xiaoqing |last7=Wang |first7=Dawei |last8=Pan |first8=Xiaoyong |last9=Hong |first9=Jiaxu |last10=Sun |first10=Xiaodong |last11=Yang |first11=Hui |last12=Paludan |first12=Soren Riis |last13=Cai |first13=Yujia |title=Lentiviral delivery of co-packaged Cas9 mRNA and a Vegfa -targeting guide RNA prevents wet age-related macular degeneration in mice |journal=Nature Biomedical Engineering |date=February 2021 |volume=5 |issue=2 |pages=144–56 |doi=10.1038/s41551-020-00656-y |pmid=33398131 |s2cid=230508724 |url=https://www.nature.com/articles/s41551-020-00656-y |access-date=7 March 2021 |language=en |issn=2157-846X|url-access=subscription }}

File:Retinal pigment epithelium.jpg

The retinal pigment epithelium (RPE) (see diagram) has an essential role in the eye. It secretes a large variety of factors including at least 22 proteins important in maintaining the structure, function and micro-environments on the two sides of the RPE.{{cite journal |vauthors=Kay P, Yang YC, Paraoan L |title=Directional protein secretion by the retinal pigment epithelium: roles in retinal health and the development of age-related macular degeneration |journal=J Cell Mol Med |volume=17 |issue=7 |pages=833–43 |date=July 2013 |pmid=23663427 |pmc=3822888 |doi=10.1111/jcmm.12070 |url=}} (The two sides of the RPE include the choroid side, where blood vessels form and bring nourishment to the eye, and the photoreceptor side, with rods and cones that receive light signals.) In particular, the RPE secretes vascular endothelial growth factor (VEGF) at its basement membrane, with the VEGF reaching the choriocapillaris to maintain proper blood vessel formation in the choroid region.

Many factors, including genetic factors, hypoxia, oxidative stress, and inflammatory stressors, may cause pathologic over-production of VEGF by the RPE. This over-production causes excess blood vessel formation in the choroid region (the choriocapillaris), which is a major cause of wet AMD.{{cite journal |vauthors=Penn JS, Madan A, Caldwell RB, Bartoli M, Caldwell RW, Hartnett ME |title=Vascular endothelial growth factor in eye disease |journal=Prog Retin Eye Res |volume=27 |issue=4 |pages=331–71 |date=July 2008 |pmid=18653375 |pmc=3682685 |doi=10.1016/j.preteyeres.2008.05.001 |url=}}

It was recently discovered that the aging pigment lipofuscin can be broken down with the help of melanin and drugs through a newly discovered mechanism (chemical excitation). The pigment lipofuscin plays a central role in the development of dry AMD and geographic atrophy. This breakdown can be supported by medication. This discovery can be translated into the development of a therapy to treat dry AMD.

Research is exploring if artificial intelligence can help in predicting wet AMD early enough to make prevention possible. A study tested an AI model for predicting whether people with wet AMD in one eye would develop it in the other within six months. Compared to doctors and optometrists the AI model predicted the development more accurately.{{cite journal |date=6 November 2020 |title=Artificial intelligence can predict the development of a leading cause of blindness |url=https://evidence.nihr.ac.uk/alert/artificial-intelligence-predicts-development-of-wet-amd/ |journal=NIHR Evidence |type=Plain English summary |language=en |publisher=National Institute for Health and Care Research |doi=10.3310/alert_42401|s2cid=243121774 |url-access=subscription }}{{cite journal |last1=Yim |first1=Jason |last2=Chopra |first2=Reena |last3=Spitz |first3=Terry |last4=Winkens |first4=Jim |last5=Obika |first5=Annette |last6=Kelly |first6=Christopher |last7=Askham |first7=Harry |last8=Lukic |first8=Marko |last9=Huemer |first9=Josef |last10=Fasler |first10=Katrin |last11=Moraes |first11=Gabriella |last12=Meyer |first12=Clemens |last13=Wilson |first13=Marc |last14=Dixon |first14=Jonathan |last15=Hughes |first15=Cian |date=18 May 2020 |title=Predicting conversion to wet age-related macular degeneration using deep learning |url=http://www.nature.com/articles/s41591-020-0867-7 |journal=Nature Medicine |language=en |volume=26 |issue=6 |pages=892–899 |doi=10.1038/s41591-020-0867-7 |pmid=32424211 |s2cid=218682821 |issn=1078-8956}}

There are a few other (rare) kinds of macular degeneration with similar symptoms but unrelated in etiology to Wet or Dry age-related macular degeneration. They are all genetic disorders that may occur in childhood or middle age.

• Vitelliform macular dystrophy
• Sorsby's fundus dystrophy is an autosomal dominant, retinal disease characterized by sudden acuity loss resulting from untreatable submacular neovascularisation
• Stargardt's disease (juvenile macular degeneration, STGD) is an autosomal recessive retinal disorder characterized by juvenile-onset macular dystrophy, alterations of the peripheral retina, and subretinal deposition of lipofuscin-like material.

Similar symptoms with a very different etiology and different treatment can be caused by epiretinal membrane or macular pucker or any other condition affecting the macula, such as central serous retinopathy.

• Judi Dench"[https://www.theguardian.com/culture/2014/feb/23/judi-dench-failing-eyesight Judi Dench 'can't read any more due to failing eyesight] {{webarchive|url=https://web.archive.org/web/20161019155627/https://www.theguardian.com/culture/2014/feb/23/judi-dench-failing-eyesight |date=2016-10-19 }}", The Guardian, 23 February 2014
• Joan Plowright"[https://www.telegraph.co.uk/culture/theatre/theatre-news/10825654/Joan-Plowright-bows-out-to-a-standing-ovation.html Joan bows out to a standing ovation] {{webarchive|url=https://web.archive.org/web/20160420064158/http://www.telegraph.co.uk/culture/theatre/theatre-news/10825654/Joan-Plowright-bows-out-to-a-standing-ovation.html |date=2016-04-20 }}", The Guardian, 13 May 2014
• Peter Sallis"[http://www.macularsociety.org/How-we-help/About-us/Who-we-are/Patrons Patrons of the Macular Society] {{webarchive|url=https://web.archive.org/web/20130208035759/http://www.macularsociety.org/how-we-help/About-us/Who-we-are/Patrons |date=2013-02-08 }}", Macular Society. (notable for doing the voice of Wallace from Wallace and Gromit until 2012)

{{Portal|Medicine}}

• Ophthalmology
• Macula of retina
• Visual impairment
• Gene therapy for color blindness
• Gene therapy of the human retina
• Stem cell therapy for macular degeneration
• epiretinal membrane = macular pucker

{{Reflist}}

{{Spoken Wikipedia|Macular_degeneration.ogg|date=19 July 2005}}

{{Medical resources

| ICD10 = {{ICD10|H|35|3|h|30}}

| ICD9 = {{ICD9|362.50}}

| DiseasesDB = 11948

| eMedicineSubj = article

| eMedicineTopic = 1223154

| MedlinePlus = 001000

| MeshID = D008268

}}

{{Eye pathology}}

{{Authority control}}

{{DEFAULTSORT:Macular Degeneration}}

Category:Disorders of choroid and retina

Category:Senescence

Category:Wikipedia medicine articles ready to translate

Category:Wikipedia neurology articles ready to translate

Category:Visual disturbances and blindness