{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T16:23:25Z","timestamp":1787502205532,"version":"build-2736575974"},"reference-count":51,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2020,4,28]],"date-time":"2020-04-28T00:00:00Z","timestamp":1588032000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01NS082347"],"award-info":[{"award-number":["R01NS082347"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000890","name":"National Multiple Sclerosis Society","doi-asserted-by":"publisher","award":["FP\u20101607\u201024999"],"award-info":[{"award-number":["FP\u20101607\u201024999"]}],"id":[{"id":"10.13039\/100000890","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000890","name":"National Multiple Sclerosis Society","doi-asserted-by":"publisher","award":["RG\u20101606\u201008768"],"award-info":[{"award-number":["RG\u20101606\u201008768"]}],"id":[{"id":"10.13039\/100000890","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000890","name":"National Multiple Sclerosis Society","doi-asserted-by":"publisher","award":["TR 3760\u2010A\u20103"],"award-info":[{"award-number":["TR 3760\u2010A\u20103"]}],"id":[{"id":"10.13039\/100000890","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014842","name":"Race to Erase MS","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014842","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2020,6]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Therapeutic development in progressive multiple sclerosis (PMS) has been hampered by a lack of reliable biomarkers to monitor neurodegeneration. Optical coherence tomography (OCT)\u2010derived retinal measures have been proposed as promising biomarkers to fulfill this role. However, it is unclear whether retinal atrophy persists in PMS, exceeds normal aging, or can be distinguished from relapsing\u2013remitting multiple sclerosis (RRMS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>178 RRMS, 186 PMS, and 66 control participants were followed with serial OCT for a median follow\u2010up of 3.7\u2009years.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The estimated proportion of peripapillary retinal nerve fiber layer (pRNFL) and macular ganglion cell + inner plexiform layer (GCIPL) thinning in multiple sclerosis (MS) attributable to normal aging increased from 42.7% and 16.7% respectively at age 25\u2009years, to 83.7% and 81.1% at age 65\u2009years. However, independent of age, PMS was associated with faster pRNFL (\u22120.34\u2009\u00b1\u20090.09%\/yr,\n                      <jats:italic>p<\/jats:italic>\n                      &lt;\u20090.001) and GCIPL (\u22120.27\u2009\u00b1\u20090.07%\/yr,\n                      <jats:italic>p<\/jats:italic>\n                      &lt;\u20090.001) thinning, as compared to RRMS. In both MS and controls, higher baseline age was associated with faster inner nuclear layer (INL) and outer nuclear layer (ONL) thinning. INL and ONL thinning were independently faster in PMS, as compared to controls (INL:\u22120.09\u2009\u00b1\u20090.04%\/yr,\n                      <jats:italic>p<\/jats:italic>\n                      =\u20090.03; ONL:\u22120.12\u2009\u00b1\u20090.06%\/yr,\n                      <jats:italic>p<\/jats:italic>\n                      =\u20090.04), and RRMS (INL:\u22120.10\u2009\u00b1\u20090.04%\/yr,\n                      <jats:italic>p<\/jats:italic>\n                      =\u20090.01; ONL:\u22120.13\u2009\u00b1\u20090.05%\/yr,\n                      <jats:italic>p<\/jats:italic>\n                      =\u20090.01), whereas they were similar in RRMS and controls. Unlike RRMS, disease\u2010modifying therapies (DMTs) did not impact rates of retinal layer atrophy in PMS.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>\n                      PMS is associated with faster retinal atrophy independent of age. INL and ONL measures may be novel biomarkers of neurodegeneration in PMS that appear to be unaffected by conventional DMTs. The effects of aging on rates of retinal layer atrophy should be considered in clinical trials incorporating OCT outcomes.\n                      <jats:bold>ANN NEUROL 2020;87:885\u2013896<\/jats:bold>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ana.25738","type":"journal-article","created":{"date-parts":[[2020,4,13]],"date-time":"2020-04-13T22:23:46Z","timestamp":1586816626000},"page":"885-896","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":87,"title":["Progressive Multiple Sclerosis Is Associated with Faster and Specific Retinal Layer Atrophy"],"prefix":"10.1002","volume":"87","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8812-1637","authenticated-orcid":false,"given":"Elias S.","family":"Sotirchos","sequence":"first","affiliation":[{"name":"Department of Neurology Johns Hopkins University School of Medicine  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5265-3404","authenticated-orcid":false,"given":"Natalia","family":"Gonzalez Caldito","sequence":"additional","affiliation":[{"name":"Department of Neurology Johns Hopkins University School of Medicine  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0419-233X","authenticated-orcid":false,"given":"Angeliki","family":"Filippatou","sequence":"additional","affiliation":[{"name":"Department of Neurology Johns Hopkins University School of Medicine  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn C.","family":"Fitzgerald","sequence":"additional","affiliation":[{"name":"Department of Neurology Johns Hopkins University School of Medicine  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olwen C.","family":"Murphy","sequence":"additional","affiliation":[{"name":"Department of Neurology Johns Hopkins University School of Medicine  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3306-0988","authenticated-orcid":false,"given":"Jeffrey","family":"Lambe","sequence":"additional","affiliation":[{"name":"Department of Neurology Johns Hopkins University School of Medicine  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Neurology Johns Hopkins University School of Medicine  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Button","sequence":"additional","affiliation":[{"name":"Department of Neurology Johns Hopkins University School of Medicine  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther","family":"Ogbuokiri","sequence":"additional","affiliation":[{"name":"Department of Neurology Johns Hopkins University School of Medicine  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ciprian M.","family":"Crainiceanu","sequence":"additional","affiliation":[{"name":"Department of Biostatistics Johns Hopkins University  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerry L.","family":"Prince","sequence":"additional","affiliation":[{"name":"Department of Electrical and Computer Engineering Johns Hopkins University  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter A.","family":"Calabresi","sequence":"additional","affiliation":[{"name":"Department of Neurology Johns Hopkins University School of Medicine  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiv","family":"Saidha","sequence":"additional","affiliation":[{"name":"Department of Neurology Johns Hopkins University School of Medicine  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"International Multiple Sclerosis Visual System (IMSVISUAL) Consortium","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,4,28]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1401483"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(14)70256-X"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(09)70043-2"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(14)70264-9"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1177\/1352458517753722"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1080\/14737175.2019.1559051"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e31827b1a1c"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24487"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000003582"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(12)70213-2"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/aww219"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awq346"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awq080"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000294876.49861.dc"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0036847"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1177\/1352458512439237"},{"key":"e_1_2_8_18_1","first-page":"530305","article-title":"Retinal damage in multiple sclerosis disease subtypes measured by high\u2010resolution optical coherence tomography","volume":"2012","author":"Oberwahrenbrock T","year":"2012","journal-title":"Mult Scler Int"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-016-8127-y"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20703"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.1032"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0034823"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1177\/1352458510371640"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1177\/1352458514538110"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1364\/BOE.4.001133"},{"key":"e_1_2_8_26_1","first-page":"136295","article-title":"Applying an open\u2010source segmentation algorithm to different OCT devices in multiple sclerosis patients and healthy controls: implications for clinical trials","volume":"2015","author":"Bhargava P","year":"2015","journal-title":"Mult Scler Int"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/aws098"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000002774"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.clinpsy.032408.153550"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/gln024"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1214\/aos\/1176344136"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1086\/230638"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.2307\/2533554"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0895-4356(00)00314-0"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1177\/1352458515590646"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(17)30278-8"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000260064.77700.fd"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40263-014-0140-z"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2011.10.010"},{"key":"e_1_2_8_40_1","first-page":"1","article-title":"Longitudinal and cross\u2010sectional analyses of age effects on retinal nerve fiber layer and ganglion cell complex thickness by Fourier\u2010domain OCT","volume":"5","author":"Zhang X","year":"2016","journal-title":"Transl Vis Sci Technol"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0194169"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000161871.83614.BB"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3252-09.2009"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2019.05.010"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1212\/NXI.0000000000000616"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjophth-2016-000003"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000000560"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21867"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1606468"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(18)30069-3"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)30475-6"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)30426-4"}],"container-title":["Annals of Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fana.25738","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ana.25738","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ana.25738","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ana.25738","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,6]],"date-time":"2023-09-06T05:08:30Z","timestamp":1693976910000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ana.25738"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,28]]},"references-count":51,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2020,6]]}},"alternative-id":["10.1002\/ana.25738"],"URL":"https:\/\/doi.org\/10.1002\/ana.25738","archive":["Portico"],"relation":{},"ISSN":["0364-5134","1531-8249"],"issn-type":[{"value":"0364-5134","type":"print"},{"value":"1531-8249","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,4,28]]},"assertion":[{"value":"2019-07-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-04-01","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-04-28","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}