{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T14:58:46Z","timestamp":1789570726466,"version":"build-2803163510"},"reference-count":25,"publisher":"Springer Science and Business Media LLC","issue":"8","license":[{"start":{"date-parts":[[2019,3,28]],"date-time":"2019-03-28T00:00:00Z","timestamp":1553731200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Eye"],"published-print":{"date-parts":[[2019,8]]},"DOI":"10.1038\/s41433-019-0406-2","type":"journal-article","created":{"date-parts":[[2019,3,28]],"date-time":"2019-03-28T08:03:34Z","timestamp":1553760214000},"page":"1271-1279","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["A pilot study of fluorescence lifetime imaging ophthalmoscopy in preclinical Alzheimer\u2019s disease"],"prefix":"10.1038","volume":"33","author":[{"given":"SriniVas R.","family":"Sadda","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2815-5031","authenticated-orcid":false,"given":"Enrico","family":"Borrelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenying","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adel","family":"Ebraheem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1275-5729","authenticated-orcid":false,"given":"Kenneth M.","family":"Marion","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Harrington","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soonil","family":"Kwon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,3,28]]},"reference":[{"key":"406_CR1","unstructured":"Prince PM, Ali G, Ali G. World Alzheimer Report 2015. The global impact of dementia. London: Alzheimers Disease International; 2015."},{"key":"406_CR2","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1016\/j.jalz.2011.03.005","volume":"7","author":"GM McKhann","year":"2011","unstructured":"McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack CR Jr, Kawas CH, et al. The diagnosis of dementia due to Alzheimer\u2019s disease: recommendations from the National Institute on Aging-Alzheimer\u2019s Association workgroups on diagnostic guidelines for Alzheimer\u2019s disease. Alzheimers Dement. 2011;7:263\u20139.","journal-title":"Alzheimers Dement"},{"key":"406_CR3","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1016\/S1474-4422(13)70044-9","volume":"12","author":"VL Villemagne","year":"2013","unstructured":"Villemagne VL, Burnham S, Bourgeat P, Brown B, Ellis KA, Salvado O, et al. Amyloid \u03b2 deposition, neurodegeneration and cognitive decline in sporadic Alzheimer\u2019s disease: a prospective cohort study. Lancet Neurol. 2013;12:357\u201367.","journal-title":"Lancet Neurol"},{"key":"406_CR4","doi-asserted-by":"publisher","first-page":"454","DOI":"10.1016\/j.jalz.2015.09.005","volume":"12","author":"YY Lim","year":"2016","unstructured":"Lim YY, Maruff P, Getter C, Snyder PJ. Discloure of PET amyloid imaging results: a preliminary study of safety and tolerability. Alzheimers Dement. 2016;12:454\u20138.","journal-title":"Alzheimers Dement"},{"key":"406_CR5","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1056\/NEJM198608213150804","volume":"315","author":"DR Hinton","year":"1986","unstructured":"Hinton DR, Sadun AA, Blanks JC, Miller CA. Optic nerve degeneration in Alzheimer\u2019s disease. N Eng J Med. 1986;315:485\u20137.","journal-title":"N Eng J Med"},{"key":"406_CR6","first-page":"144","volume":"1","author":"GT Feke","year":"2015","unstructured":"Feke GT, Hyman BT, Stern RA, Pasquale LR. Retinal blood flow in mild cognitive impairment and Alzheimer\u2019s disease. Alzheimers Dement. 2015;1:144\u201351.","journal-title":"Alzheimers Dement"},{"key":"406_CR7","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1111\/aos.12374","volume":"92","author":"MP Bambo","year":"2014","unstructured":"Bambo MP, Garcia-Martin E, Pinilla J, Herrero R, Satue M, Otin S, et al. Detection of retinal nerve fiber layer degeneration in patients with Alzheimer\u2019s disease using optical coherence tomography: searching new biomarkers. Acta Ophthalmol. 2014;92:581\u20132.","journal-title":"Acta Ophthalmol"},{"key":"406_CR8","doi-asserted-by":"publisher","first-page":"S204","DOI":"10.1016\/j.neuroimage.2010.06.020","volume":"54","author":"M Koronyo-Hamaoui","year":"2011","unstructured":"Koronyo-Hamaoui M, Koronyo Y, Ljubimov AV, Miller CA, Ko MK, Black KL, et al. Identification of amyloid plaques in retinas from Alzheimer\u2019s patients and noninvasive in vivo optical imaging of retinal plaques in a mouse model. Neuroimage. 2011;54:S204\u201317.","journal-title":"Neuroimage"},{"key":"406_CR9","doi-asserted-by":"publisher","first-page":"1214","DOI":"10.1117\/1.1806833","volume":"9","author":"D Schweitzer","year":"2004","unstructured":"Schweitzer D, Hammer M, Schwietzer F, Schweitzer F, Jentsch S, Birckner E, et al. In vivo measurement of time-resolved autofluorescence at the human fundus. J Biomed Opt. 2004;9:1214\u201322.","journal-title":"J Biomed Opt"},{"key":"406_CR10","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1002\/jemt.20427","volume":"70","author":"D Schweitzer","year":"2007","unstructured":"Schweitzer D, Schenke S, Hammer M, Schweitzer F, Jentsch S, Birckner E, et al. Towards metabolic mapping of the human retina. Microsc Res Technol. 2007;70:410\u20139.","journal-title":"Microsc Res Technol"},{"key":"406_CR11","doi-asserted-by":"publisher","first-page":"2106","DOI":"10.1167\/iovs.13-13627","volume":"55","author":"C Dysli","year":"2014","unstructured":"Dysli C, Quellec G, Abegg M, Menke MN, Wolf-Schnurrbusch U, Kowal J, et al. Quantitative analysis of fluorescence lifetime measurements of the macula using the fluorescence liftime imaging ophthalmoscope in healthy subjects. Invest Ophthalmol Vis Sci. 2014;55:2106\u201313.","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"406_CR12","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1016\/j.preteyeres.2017.06.005","volume":"60","author":"C Dysli","year":"2017","unstructured":"Dysli C, Wolf S, Berezin MY, Sauer L, Hammer M, Zinkernagel MS. Fluorescence lifetime imaging ophthalmoscopy. Prog Retin Eye Res. 2017;60:120\u201343.","journal-title":"Prog Retin Eye Res"},{"key":"406_CR13","doi-asserted-by":"publisher","first-page":"61106","DOI":"10.1117\/1.JBO.20.6.061106","volume":"20","author":"D Schweitzer","year":"2015","unstructured":"Schweitzer D, Deutsch L, Klemm M, Jentsch S, Hammer M, Peters S, et al. Fluorescence lifetime imaging ophthalmoscopy in type 2 diabetic patients who have no signs of diabetic retinopathy. J Biomed Opt. 2015;20:61106.","journal-title":"J Biomed Opt"},{"key":"406_CR14","doi-asserted-by":"publisher","first-page":"e241","DOI":"10.1111\/aos.12609","volume":"93","author":"S Jentsch","year":"2015","unstructured":"Jentsch S, Schweitzer D, Schmidtke KU, Peters S, Dawczynski J, B\u00e4r KJ, et al. Retinal fluorescence lifetime imaging ophthalmoscopy measures depend on the severity of Alzheimer\u2019s disease. Acta Ophthalmol. 2015;93:e241\u20137.","journal-title":"Acta Ophthalmol"},{"key":"406_CR15","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1136\/bjophthalmol-2017-310476","volume":"102","author":"M Bulut","year":"2018","unstructured":"Bulut M, Kurtulu\u015f F, G\u00f6zkaya O, Erol MK, Cengiz A, Ak\u0131dan M, et al. Evaluation of optical coherence tomography angiographic findings in Alzheimer\u2019s type dementia. Br J Ophthalmol. 2018;102:233\u20137.","journal-title":"Br J Ophthalmol"},{"key":"406_CR16","doi-asserted-by":"publisher","first-page":"993","DOI":"10.1136\/bjophthalmol-2016-309017","volume":"101","author":"S McGrory","year":"2017","unstructured":"McGrory S, Taylor AM, Kirin M, Corley J, Pattie A, Cox SR, et al. Retinal microvascular network geometry and cognitive abilities in community-dwelling older people: The Lothian Birth Cohort 1936 study. Br J Ophthalmol. 2017;101:993\u20138.","journal-title":"Br J Ophthalmol"},{"key":"406_CR17","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1186\/s13195-017-0239-9","volume":"9","author":"SM Golzan","year":"2017","unstructured":"Golzan SM, Goozee K, Georgevsky D, Avolio A, Chatterjee P, Shen K, et al. Retinal vascular and structural changes are associated with amyloid burden in the elderly: ophthalmic biomarkers of preclinical Alzheimer\u2019s disease. Alzheimers Res Ther. 2017;9:13.","journal-title":"Alzheimers Res Ther"},{"key":"406_CR18","doi-asserted-by":"publisher","first-page":"362","DOI":"10.1167\/iovs.15-18904","volume":"57","author":"AY Kim","year":"2016","unstructured":"Kim AY, Chu Z, Shahidzadeh A, Wang RK, Puliafito CA, Kashani AH. Quantifying microvascular density and morphology in diabetic retinopathy using spectral-domain optical coherence tomography angiography. Invest Ophthalmol Vis Sci. 2016;57:362\u201370.","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"406_CR19","doi-asserted-by":"publisher","first-page":"944","DOI":"10.1016\/j.ophtha.2017.02.006","volume":"124","author":"A Uji","year":"2017","unstructured":"Uji A, Balasubramanian S, Lei J, Baghdasaryan E, Al-Sheikh M, Sadda SR. Impact of multiple en face image averaging on quantitative assessment from optical coherence tomography angiography images. Ophthalmology. 2017;124:944\u201352.","journal-title":"Ophthalmology"},{"key":"406_CR20","doi-asserted-by":"publisher","first-page":"2034","DOI":"10.1212\/WNL.0b013e31823b9c5e","volume":"77","author":"GD Rabinovici","year":"2011","unstructured":"Rabinovici GD, Rosen HJ, Alkalay A, Kornak J, Furst AJ, Agarwal N, et al. Amyloid vs FDG-PET in the differential diagnosis of AD and FTLD. Neurology. 2011;77:2034\u201342.","journal-title":"Neurology"},{"key":"406_CR21","first-page":"718","volume":"36","author":"FC Delori","year":"1995","unstructured":"Delori FC, Dorey KC, Staurenghi G, Arend O, Goger DG, Weiter JJ. In vivo fluorescence of the ocular fundus exhibits retinal pigment epithelium lipofusin characteristics. Invest Ophthalmol Vis Sci. 1995;36:718\u201329.","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"406_CR22","doi-asserted-by":"publisher","first-page":"1629","DOI":"10.1001\/archopht.116.12.1629","volume":"116","author":"T Ishibashi","year":"1998","unstructured":"Ishibashi T, Murata T, Hanagai M, Nagai R, Horiuchi S, Lopez PF, et al. Advanced glycation end products in age related macular degeneration. Arch Ophthalmol. 1998;116:1629\u201332.","journal-title":"Arch Ophthalmol"},{"key":"406_CR23","doi-asserted-by":"publisher","first-page":"2479","DOI":"10.1167\/iovs.15-18381","volume":"57","author":"C Dysli","year":"2016","unstructured":"Dysli C, Wolf S, Zinkernagel MS. autofluorescence lifetimes in geographic atrophy in patients with age-related macular degeneration. Invest Ophthalmol Vis Sci. 2016;57:2479\u201387.","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"406_CR24","doi-asserted-by":"publisher","first-page":"5953","DOI":"10.1167\/iovs.13-12046","volume":"54","author":"E Marziani","year":"2013","unstructured":"Marziani E, Pomati S, Ramolfo P, Cigada M, Giani A, Mariani C, et al. Evaluation of retinal nerve fiber layer and ganglion cell layer thickness in Alzheimer\u2019s disease using spectral-domain optical coherence tomography. Invest Ophthalmol Vis Sci. 2013;54:5953\u20138.","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"406_CR25","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/j.neulet.2010.06.006","volume":"480","author":"Y Lu","year":"2010","unstructured":"Lu Y, Li Z, Zhang X,\u00a0Ming B, Jia J, Wang R, et al. Retinal nerve fiber layer structure abnormalities in early Alzheimer\u2019s disease: evidence in optical coherence tomography. Neurosci Lett. 2010;480:69\u201372.","journal-title":"Neurosci Lett"}],"container-title":["Eye"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/s41433-019-0406-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/s41433-019-0406-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/s41433-019-0406-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,20]],"date-time":"2023-05-20T21:06:50Z","timestamp":1684616810000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41433-019-0406-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,3,28]]},"references-count":25,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2019,8]]}},"alternative-id":["406"],"URL":"https:\/\/doi.org\/10.1038\/s41433-019-0406-2","relation":{},"ISSN":["0950-222X","1476-5454"],"issn-type":[{"value":"0950-222X","type":"print"},{"value":"1476-5454","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,3,28]]},"assertion":[{"value":"18 December 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 February 2019","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 February 2019","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 March 2019","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"SRS is a consultant for and receives research support from Optos and Carl Zeiss Meditec, and serves as a consultant for Centervue, and has access to research instruments provided by Heidelberg Engineering, Topcon Medical Systems, Optos, Carl Zeiss Meditec, Nidek, and Centervue. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The other authors declare that they have no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}