{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T08:23:55Z","timestamp":1791015835034,"version":"4.1.0"},"reference-count":181,"publisher":"Wiley","license":[{"start":{"date-parts":[[2018,7,30]],"date-time":"2018-07-30T00:00:00Z","timestamp":1532908800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Ophthalmology"],"published-print":{"date-parts":[[2018,7,30]]},"abstract":"<jats:p>Dementia, including Alzheimer\u2019s disease (AD), is a major disorder, leading to several ocular manifestations amongst the elderly population. These visual disorders may be due to retinal nerve degenerative changes, including nerve fibre layer thinning, degeneration of retinal ganglion cells, and changes to vascular parameters. There is no cure for Alzheimer\u2019s, but medicines can slow down the development of many of the classic symptoms, such as loss of memory and communication skills, mood swings, and depression. The disease diagnosis is difficult, and it is only possible through PET scans of the brain, detecting evidence of the accumulation of amyloid and tau. PET is expensive and invasive, requiring the injection of radioactive tracers, which bind with these proteins and glow during scanning. Recently, scientists developed promising eye-scan techniques that may detect Alzheimer\u2019s disease at its earliest stage, before major symptoms appear, leading to improved management of the disease symptoms. In this review, we are discussing the visual abnormalities of Alzheimer\u2019s and other neurodegenerative diseases, focused on ocular functional-visual-structural biomarkers, retinal pathology, and potential novel diagnostic tools.<\/jats:p>","DOI":"10.1155\/2018\/8538573","type":"journal-article","created":{"date-parts":[[2018,7,30]],"date-time":"2018-07-30T19:31:47Z","timestamp":1532979107000},"page":"1-12","source":"Crossref","is-referenced-by-count":74,"title":["Ocular Manifestations of Alzheimer\u2019s and Other Neurodegenerative Diseases: The Prospect of the Eye as a Tool for the Early Diagnosis of Alzheimer\u2019s Disease"],"prefix":"10.1155","volume":"2018","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4906-9546","authenticated-orcid":true,"given":"Pade","family":"Colligris","sequence":"first","affiliation":[{"name":"Universidad Alfonso X, Madrid, Spain"},{"name":"Ocupharm Diagnostics SL, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Jesus","family":"Perez de Lara","sequence":"additional","affiliation":[{"name":"Ocupharm Diagnostics SL, Madrid, Spain"},{"name":"Universidad Complutense de Madrid, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6907-3636","authenticated-orcid":true,"given":"Basilio","family":"Colligris","sequence":"additional","affiliation":[{"name":"Ocupharm Diagnostics SL, Madrid, Spain"},{"name":"Universidad Complutense de Madrid, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9191-7679","authenticated-orcid":true,"given":"Jesus","family":"Pintor","sequence":"additional","affiliation":[{"name":"Ocupharm Diagnostics SL, Madrid, Spain"},{"name":"Universidad Complutense de Madrid, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","reference":[{"key":"1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2013.02.003"},{"key":"2","doi-asserted-by":"publisher","DOI":"10.1056\/nejmra0909142"},{"key":"3","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.322.7300.1447"},{"key":"4","doi-asserted-by":"publisher","DOI":"10.3233\/jad-2009-1022"},{"key":"5","doi-asserted-by":"publisher","DOI":"10.1212\/wnl.0b013e3181f4d7f8"},{"key":"6","doi-asserted-by":"publisher","DOI":"10.1111\/ene.13374"},{"key":"7","first-page":"613","volume":"24","year":"2017","journal-title":"European Journal of Neurology"},{"key":"8","doi-asserted-by":"publisher","DOI":"10.1097\/wad.0000000000000172"},{"key":"9","doi-asserted-by":"publisher","DOI":"10.1002\/syn.21990"},{"key":"10","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a006296"},{"key":"11","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2013.10.008"},{"key":"12","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2015.12.023"},{"key":"13","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2017.4198"},{"key":"14","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1002270"},{"key":"15","doi-asserted-by":"publisher","DOI":"10.1186\/alzrt269"},{"key":"16","doi-asserted-by":"publisher","DOI":"10.1586\/14737175.8.11.1703"},{"key":"17","doi-asserted-by":"publisher","DOI":"10.1016\/j.jfma.2015.04.001"},{"key":"18","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2018.02.035"},{"key":"19","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2017.12.015"},{"key":"20","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.09.172"},{"key":"21","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2013.04.005"},{"key":"22","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.h3029"},{"key":"23","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.03.005"},{"key":"24","doi-asserted-by":"publisher","DOI":"10.1016\/s1474-4422(10)70306-9"},{"key":"25","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(15)01124-1"},{"key":"26","volume-title":"Structural basis of the cognitive alterations in Alzheimer disease","year":"1994"},{"key":"27","doi-asserted-by":"publisher","DOI":"10.1016\/s0962-8924(98)01368-3"},{"key":"28","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2000.tb05561.x"},{"key":"29","doi-asserted-by":"publisher","DOI":"10.3233\/jad-2002-4313"},{"key":"30","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2009.090159"},{"key":"31","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddq160"},{"key":"32","first-page":"403","volume":"15","year":"2016","journal-title":"EXCLI Journal"},{"key":"33","year":"2013"},{"key":"34","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2010.06.020"},{"key":"35","doi-asserted-by":"publisher","DOI":"10.1159\/000335154"},{"key":"36","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2016.00267"},{"key":"37","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24548"},{"key":"38","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.93621"},{"key":"39","doi-asserted-by":"publisher","DOI":"10.1097\/wnr.0b013e3283497334"},{"key":"40","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.13-12888"},{"key":"41","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-017-0199-3"},{"key":"42","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.19886"},{"key":"43","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2018.03.017"},{"issue":"1","key":"44","first-page":"3","volume":"1","year":"2014","journal-title":"International Journal of Ophthalmic and Pathology"},{"key":"45","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-016-1613-6"},{"key":"46","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2017.00701"},{"key":"47","doi-asserted-by":"publisher","DOI":"10.3233\/jad-179932"},{"key":"48","doi-asserted-by":"publisher","DOI":"10.2174\/1567205015666180123122637"},{"issue":"3","key":"49","first-page":"145","volume":"2","year":"2013","journal-title":"American Journal of Neurodegenerative Disease"},{"key":"50","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.195"},{"key":"51","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.323"},{"key":"52","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2017.00166"},{"key":"53","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2013.12.024"},{"key":"54","doi-asserted-by":"publisher","DOI":"10.1111\/ceo.12872"},{"key":"55","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-biochem-061516-045115"},{"key":"56","doi-asserted-by":"publisher","DOI":"10.1096\/fj.07-099671"},{"key":"57","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(03)12981-9"},{"key":"58","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.med.57.121304.131243"},{"key":"59","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2016.04.059"},{"key":"60","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.17-21776"},{"issue":"2","key":"61","first-page":"222","volume":"32","year":"2006","journal-title":"Neuropathology and Applied Neurobiology"},{"key":"62","doi-asserted-by":"publisher","DOI":"10.1159\/000178756"},{"key":"63","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropsychologia.2008.02.008"},{"key":"64","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awp068"},{"key":"65","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24182"},{"key":"66","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.192203399"},{"key":"67","volume":"43","year":"2002","journal-title":"Investigative Ophthalmology and Visual Science"},{"key":"68","doi-asserted-by":"publisher","DOI":"10.1007\/s10384-004-0156-x"},{"key":"69","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.06-1249"},{"key":"70","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0703707104"},{"key":"71","doi-asserted-by":"publisher","DOI":"10.2174\/1570159x16666171206144045"},{"key":"72","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-12858-7"},{"key":"73","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-7407-8_7"},{"key":"74","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.23862"},{"key":"75","doi-asserted-by":"publisher","DOI":"10.1186\/s12987-015-0012-z"},{"key":"76","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-015-1581-6"},{"key":"77","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/5123148"},{"key":"78","doi-asserted-by":"publisher","DOI":"10.1111\/ceo.12915"},{"key":"79","doi-asserted-by":"publisher","DOI":"10.2741\/e794"},{"issue":"5","key":"80","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1007\/s10571-017-0572-3","volume":"38","year":"2018","journal-title":"Cellular and Molecular Neurobiology"},{"key":"81","doi-asserted-by":"publisher","DOI":"10.2174\/1567205013666160603003800"},{"key":"82","doi-asserted-by":"publisher","DOI":"10.3906\/sag-1406-135"},{"key":"83","doi-asserted-by":"publisher","DOI":"10.1016\/j.jagp.2015.06.005"},{"key":"84","doi-asserted-by":"publisher","DOI":"10.1002\/1873-3468.12093"},{"key":"85","doi-asserted-by":"publisher","DOI":"10.1056\/nejm198608213150804"},{"key":"86","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(89)90653-7"},{"key":"87","doi-asserted-by":"publisher","DOI":"10.1016\/s0161-6420(90)32621-0"},{"key":"88","doi-asserted-by":"publisher","DOI":"10.1016\/0197-4580(96)00009-7"},{"key":"89","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0420.1996.tb00090.x"},{"key":"90","doi-asserted-by":"publisher","DOI":"10.1016\/0197-4580(96)00010-3"},{"key":"91","doi-asserted-by":"publisher","DOI":"10.1097\/01.wno.0000204645.56873.26"},{"key":"92","doi-asserted-by":"publisher","DOI":"10.1016\/s0002-9394(01)01196-5"},{"key":"93","doi-asserted-by":"publisher","DOI":"10.1016\/s1388-2457(01)00620-4"},{"key":"94","doi-asserted-by":"publisher","DOI":"10.31524\/bkkmedj.2015.09.017"},{"key":"95","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2014.04.012"},{"key":"96","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2017.00747"},{"key":"97","doi-asserted-by":"publisher","DOI":"10.3233\/jad-150457"},{"key":"98","doi-asserted-by":"publisher","DOI":"10.1096\/fj.14-255489"},{"key":"99","doi-asserted-by":"publisher","DOI":"10.1007\/s00592-017-0970-5"},{"key":"100","doi-asserted-by":"publisher","DOI":"10.2337\/db17-0382"},{"key":"101","doi-asserted-by":"publisher","DOI":"10.1111\/aos.12658"},{"key":"102","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.16-20104"},{"key":"103","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.16-19838"},{"key":"104","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2017.00093"},{"key":"105","doi-asserted-by":"publisher","DOI":"10.1017\/s0007114515004687"},{"key":"106","doi-asserted-by":"publisher","DOI":"10.4103\/1673-5374.230303"},{"key":"107","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.08-1849"},{"key":"108","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.08-2384"},{"key":"109","doi-asserted-by":"publisher","DOI":"10.1007\/s11357-011-9260-2"},{"key":"110","doi-asserted-by":"publisher","DOI":"10.1006\/exnr.1995.1104"},{"key":"111","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2017.00214"},{"key":"112","doi-asserted-by":"publisher","DOI":"10.1038\/eye.2014.169"},{"key":"113","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2013.06.001"},{"key":"114","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.15-17908"},{"key":"115","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4017"},{"key":"116","doi-asserted-by":"publisher","DOI":"10.1021\/cn500242z"},{"key":"117","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.15-17406"},{"key":"118","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0053547"},{"key":"119","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2013.01.006"},{"key":"120","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2013.06.026"},{"key":"121","doi-asserted-by":"publisher","DOI":"10.1111\/bpa.12070"},{"key":"122","doi-asserted-by":"publisher","DOI":"10.1016\/s1474-4422(11)70072-2"},{"key":"123","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2011.2"},{"key":"124","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2013.00062"},{"key":"125","doi-asserted-by":"publisher","DOI":"10.1016\/j.dadm.2015.03.001"},{"key":"126","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0153830"},{"key":"127","doi-asserted-by":"publisher","DOI":"10.1016\/j.dadm.2017.10.005"},{"key":"128","doi-asserted-by":"publisher","DOI":"10.1038\/tp.2012.150"},{"key":"129","doi-asserted-by":"publisher","DOI":"10.1097\/wno.0000000000000580"},{"key":"130","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-13349-5"},{"key":"131","doi-asserted-by":"publisher","DOI":"10.1136\/bjophthalmol-2017-310476"},{"key":"132","doi-asserted-by":"publisher","DOI":"10.1001\/jamaophthalmol.2016.2507"},{"key":"133","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.16-20598"},{"key":"134","doi-asserted-by":"publisher","DOI":"10.1038\/srep43477"},{"key":"135","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2018.04.002"},{"key":"136","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0158000"},{"key":"137","doi-asserted-by":"publisher","DOI":"10.3109\/02713683.2014.930154"},{"key":"138","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2008.11.007"},{"key":"139","doi-asserted-by":"publisher","DOI":"10.1016\/s0166-2236(00)02031-2"},{"key":"140","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2007.05341.x"},{"key":"141","doi-asserted-by":"publisher","DOI":"10.1007\/s00417-009-1060-3"},{"key":"142","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2015.04.013"},{"key":"143","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.06-1029"},{"key":"144","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2016.07.006"},{"key":"145","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0134750"},{"key":"146","doi-asserted-by":"publisher","DOI":"10.1212\/wnl.35.8.1089"},{"key":"147","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410240409"},{"key":"148","doi-asserted-by":"publisher","DOI":"10.1016\/s1474-4422(15)70016-5"},{"key":"149","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2018.02.015"},{"key":"150","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(91)90490-k"},{"key":"151","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2004.05.017"},{"key":"152","doi-asserted-by":"publisher","DOI":"10.1016\/j.dadm.2015.01.004"},{"key":"153","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.1991.01080020045040"},{"key":"154","doi-asserted-by":"publisher","DOI":"10.1016\/j.clineuro.2011.02.014"},{"key":"155","doi-asserted-by":"publisher","DOI":"10.1016\/j.clineuro.2015.02.016"},{"key":"156","doi-asserted-by":"publisher","DOI":"10.3760\/cma.j.issn.0412-4081.2017.04.016"},{"key":"157","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/826503"},{"key":"158","doi-asserted-by":"publisher","DOI":"10.3233\/jad-161078"},{"key":"159","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.03.003"},{"key":"160","doi-asserted-by":"publisher","DOI":"10.1097\/wad.0000000000000176"},{"key":"161","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.12-9619"},{"key":"162","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.13-12245"},{"key":"163","doi-asserted-by":"publisher","DOI":"10.5301\/ejo.2010.2108"},{"key":"164","doi-asserted-by":"publisher","DOI":"10.1097\/00006324-199110000-00006"},{"key":"165","doi-asserted-by":"publisher","DOI":"10.1038\/eye.2017.23"},{"key":"166","doi-asserted-by":"publisher","DOI":"10.1016\/j.pscychresns.2008.11.002"},{"key":"167","doi-asserted-by":"publisher","DOI":"10.1002\/1099-1166(200007)15:7<614::aid-gps153>3.0.co;2-0"},{"key":"168","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awn064"},{"key":"169","doi-asserted-by":"publisher","DOI":"10.1093\/geronj\/49.2.p52"},{"key":"170","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/121.12.2259"},{"key":"171","doi-asserted-by":"publisher","DOI":"10.1016\/0197-4580(93)90105-k"},{"key":"172","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.2015.0254"},{"key":"173","doi-asserted-by":"publisher","DOI":"10.1093\/arclin\/15.7.561"},{"key":"174","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2016.4966"},{"key":"175","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2017.00162"},{"key":"176","doi-asserted-by":"publisher","DOI":"10.1038\/emm.2014.121"},{"issue":"6","key":"177","first-page":"473","volume":"13","year":"2001","journal-title":"Aging"},{"key":"178","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.1996.01100130322017"},{"key":"179","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0010659"},{"key":"180","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2008.05613.x"},{"key":"181","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinorgbio.2015.07.009"}],"container-title":["Journal of Ophthalmology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/downloads.hindawi.com\/journals\/joph\/2018\/8538573.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/joph\/2018\/8538573.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/joph\/2018\/8538573.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2018,7,30]],"date-time":"2018-07-30T19:31:51Z","timestamp":1532979111000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.hindawi.com\/journals\/joph\/2018\/8538573\/"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,7,30]]},"references-count":181,"alternative-id":["8538573","8538573"],"URL":"https:\/\/doi.org\/10.1155\/2018\/8538573","relation":{},"ISSN":["2090-004X","2090-0058"],"issn-type":[{"value":"2090-004X","type":"print"},{"value":"2090-0058","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,7,30]]}}}