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This was a cross-sectional study including patients with AMD (early, intermediate, and late) and control subjects older than 50 years without any vitreoretinal disease. Fasting blood samples were collected and used for metabolomic profiling with ultra-performance liquid chromatography\u2013mass spectrometry (LC-MS). Patients were also tested with the AdaptDx (MacuLogix, Middletown, PA, USA) DA extended protocol (20 min). Two measures of dark adaptation were calculated and used: rod-intercept time (RIT) and area under the dark adaptation curve (AUDAC). Associations between dark adaption and metabolite levels were tested using multilevel mixed-effects linear modelling, adjusting for age, gender, body mass index (BMI), smoking, race, AMD stage, and Age-Related Eye Disease Study (AREDS) formulation supplementation. We included a total of 71 subjects: 53 with AMD (13 early AMD, 31 intermediate AMD, and 9 late AMD) and 18 controls. Our results revealed that fatty acid-related lipids and amino acids related to glutamate and leucine, isoleucine and valine metabolism were associated with RIT (p &lt; 0.01). Similar results were found when AUDAC was used as the outcome. Fatty acid-related lipids and amino acids are associated with DA, thus suggesting that oxidative stress and mitochondrial dysfunction likely play a role in AMD and visual impairment in this condition.<\/jats:p>","DOI":"10.3390\/metabo11030183","type":"journal-article","created":{"date-parts":[[2021,3,21]],"date-time":"2021-03-21T23:47:41Z","timestamp":1616370461000},"page":"183","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Association of Human Plasma Metabolomics with Delayed Dark Adaptation in Age-Related Macular Degeneration"],"prefix":"10.3390","volume":"11","author":[{"given":"Kevin M.","family":"Mendez","sequence":"first","affiliation":[{"name":"Retina Service, Massachusetts Eye and Ear, Harvard Medical School, 243 Charles Street, Boston, MA 02114, USA"},{"name":"Channing Division of Network Medicine, Department of Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0706-5021","authenticated-orcid":false,"given":"Janice","family":"Kim","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"In\u00eas","family":"La\u00edns","sequence":"additional","affiliation":[{"name":"Retina Service, Massachusetts Eye and Ear, Harvard Medical School, 243 Charles Street, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Archana","family":"Nigalye","sequence":"additional","affiliation":[{"name":"Retina Service, Massachusetts Eye and Ear, Harvard Medical School, 243 Charles Street, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raviv","family":"Katz","sequence":"additional","affiliation":[{"name":"Retina Service, Massachusetts Eye and Ear, Harvard Medical School, 243 Charles Street, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shrinivas","family":"Pundik","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Schepens Eye Research Institute of Massachusetts Eye &amp; Ear, Harvard Medical School, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivana K.","family":"Kim","sequence":"additional","affiliation":[{"name":"Retina Service, Massachusetts Eye and Ear, Harvard Medical School, 243 Charles Street, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liming","family":"Liang","sequence":"additional","affiliation":[{"name":"Program in Genetic Epidemiology and Statistical Genetics, Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02114, USA"},{"name":"Department of Biostatistics, Harvard T.H. 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