{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T16:19:04Z","timestamp":1780503544975,"version":"3.54.1"},"reference-count":39,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2018,10,24]],"date-time":"2018-10-24T00:00:00Z","timestamp":1540339200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"National Multiple Sclerosis Society (NMSS)"},{"name":"Novartis Save Neuron Grant"},{"name":"Sydney Eye Hospital foundation grant"},{"DOI":"10.13039\/501100007811","name":"Sydney Medical School Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100007811","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2018,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>There is currently an urgent need for reliable clinical biomarkers of remyelination to be used in Phase 2 and Phase 3 clinical trials. Low contrast visual acuity (<jats:styled-content style=\"fixed-case\">LCVA<\/jats:styled-content>) has been suggested as a functional measure of the integrity of the visual pathway. Therefore, the aim of this study was to elucidate the potential contribution of axonal loss and demyelination to<jats:styled-content style=\"fixed-case\">LCVA<\/jats:styled-content>loss in<jats:styled-content style=\"fixed-case\">MS<\/jats:styled-content>patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>In this study, 50 consecutive relapsing remitting<jats:styled-content style=\"fixed-case\">MS<\/jats:styled-content>patients with a previous history of unilateral optic neuritis were enrolled. Using the linear regression model, we assessed the relative contribution of multifocal Visual Evoked Potentials (mf<jats:styled-content style=\"fixed-case\">VEP<\/jats:styled-content>) latency and Retinal Nerve Fiber Layer (<jats:styled-content style=\"fixed-case\">RNFL<\/jats:styled-content>) thickness to<jats:styled-content style=\"fixed-case\">LCVA<\/jats:styled-content>deficit.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Intereye asymmetry of mf<jats:styled-content style=\"fixed-case\">VEP<\/jats:styled-content>latency and<jats:styled-content style=\"fixed-case\">RNFL<\/jats:styled-content>thickness correlated significantly with intereye asymmetry of<jats:styled-content style=\"fixed-case\">LCVA<\/jats:styled-content>(<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001). A linear regression model demonstrated increased predictive power of<jats:styled-content style=\"fixed-case\">LCVA<\/jats:styled-content>when mf<jats:styled-content style=\"fixed-case\">VEP<\/jats:styled-content>latency and<jats:styled-content style=\"fixed-case\">RNFL<\/jats:styled-content>thinning were combined (reaching<jats:italic>R<\/jats:italic><jats:sup>2<\/jats:sup>\u00a0=\u00a00.67) and confirmed a higher predictive value of<jats:styled-content style=\"fixed-case\">RNFL<\/jats:styled-content>thinning compared to mf<jats:styled-content style=\"fixed-case\">VEP<\/jats:styled-content>latency delay for both contrast levels. However, elimination of subjects with severe axonal loss dramatically increased the relative contribution of mf<jats:styled-content style=\"fixed-case\">VEP<\/jats:styled-content>latency, with contribution of<jats:styled-content style=\"fixed-case\">RNFL<\/jats:styled-content>thickness losing significance for both 1.25% and 2.5%<jats:styled-content style=\"fixed-case\">LCVA<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>While retinal ganglion cell axonal loss is a superior predictor of<jats:styled-content style=\"fixed-case\">LCVA<\/jats:styled-content>, the degree of demyelination contributes significantly to worsening of<jats:styled-content style=\"fixed-case\">LCVA<\/jats:styled-content>, particularly when patients with severe axonal loss are excluded. These results support the feasibility of using<jats:styled-content style=\"fixed-case\">LCVA<\/jats:styled-content>as a functional biomarker in remyelination therapy trials, providing appropriate patient's selection criteria are implemented.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.659","type":"journal-article","created":{"date-parts":[[2018,10,25]],"date-time":"2018-10-25T06:49:48Z","timestamp":1540450188000},"page":"1505-1512","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Pathophysiological basis of low contrast visual acuity loss in multiple sclerosis"],"prefix":"10.1002","volume":"5","author":[{"given":"James D.","family":"Triplett","sequence":"first","affiliation":[{"name":"Concord Hospital Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Con","family":"Yiannikas","sequence":"additional","affiliation":[{"name":"Concord Hospital Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael H.","family":"Barnett","sequence":"additional","affiliation":[{"name":"Sydney Neuroimaging Analysis Centre Sydney New South Wales Australia"},{"name":"Brain and Mind Centre University of Sydney Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Parratt","sequence":"additional","affiliation":[{"name":"Royal North Shore Hospital Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua","family":"Barton","sequence":"additional","affiliation":[{"name":"Brain and Mind Centre University of Sydney Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart L.","family":"Graham","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Health Sciences Macquarie University Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuyi","family":"You","sequence":"additional","affiliation":[{"name":"Save Sight Institute University of Sydney Sydney Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Klistorner","sequence":"additional","affiliation":[{"name":"Sydney Neuroimaging Analysis Centre Sydney New South Wales Australia"},{"name":"Brain and Mind Centre University of Sydney Sydney New South Wales Australia"},{"name":"Faculty of Medicine and Health Sciences Macquarie University Sydney New South Wales Australia"},{"name":"Save Sight Institute University of Sydney Sydney Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,10,24]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199801293380502"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.60.8.1073"},{"key":"e_1_2_7_4_1","first-page":"527","article-title":"Progressive multiple sclerosis: from pathogenic mechanisms to treatment multiple sclerosis","volume":"140","author":"Correale J","year":"2017","journal-title":"Brain"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-65921-3_3"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.23493"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(16)30377-5"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)32346-2"},{"issue":"16","key":"e_1_2_7_9_1","doi-asserted-by":"crossref","first-page":"P3\u2010041","DOI":"10.1212\/WNL.86.16_supplement.P3.041","article-title":"Correlation of physical, cognitive and MRI measures with multifocal visual evoked potential using baseline data from the Anti\u2010LINGO\u20101 SYNERGY Trial in multiple sclerosis","volume":"86","author":"Cadavid D","year":"2016","journal-title":"Nerology"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)32346-2"},{"key":"e_1_2_7_11_1","first-page":"4032","article-title":"Tracking the recovery of local optic nerve function after optic neuritis: a multifocal VEP study","volume":"41","author":"Hood DC","year":"2000","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1177\/1352458508095731"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.06-0475"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1177\/1352458510371408"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2005.10.040"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.22005"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneurol.2007.10"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1177\/1352458511418630"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e31827b1a1c"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20575"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.22554"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000154521.40686.63"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.2008.165449"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1177\/1352458517690822"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2011.11.032"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2006.10.061"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneurol.2009.107"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2377-14-31"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1191\/1352458503ms935rr"},{"key":"e_1_2_7_30_1","first-page":"175","article-title":"Contrast sensitivity versus visual evoked potentials in multiple sclerosis","volume":"5","author":"Shandiz JH","year":"2010","journal-title":"J Ophthal Vis Res"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.22366"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0102546"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000002774"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.11-8732"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0034823"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1097\/00061198-200002000-00004"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2014-308189"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24030"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/0167-8760(91)90019-T"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1097\/WNO.0b013e318238937f"}],"container-title":["Annals of Clinical and Translational Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Facn3.659","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/acn3.659","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/acn3.659","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/acn3.659","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,11]],"date-time":"2024-07-11T19:13:36Z","timestamp":1720725216000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/acn3.659"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,10,24]]},"references-count":39,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2018,12]]}},"alternative-id":["10.1002\/acn3.659"],"URL":"https:\/\/doi.org\/10.1002\/acn3.659","archive":["Portico"],"relation":{},"ISSN":["2328-9503","2328-9503"],"issn-type":[{"value":"2328-9503","type":"print"},{"value":"2328-9503","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,10,24]]},"assertion":[{"value":"2018-08-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-09-02","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-10-24","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}