{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T15:58:33Z","timestamp":1753891113260,"version":"3.41.2"},"reference-count":19,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,8,19]],"date-time":"2024-08-19T00:00:00Z","timestamp":1724025600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Objectives<\/jats:title><jats:p>The pathophysiology of multiple sclerosis (MS) involves inflammatory neurodegeneration in the brainstem, cerebellum, and retina. The clinical relevance of oculomotor involvement in MS, however, remains uncertain.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this cross-sectional study, we evaluated heterophoria as a (sub)clinical tool in 54 MS patients and 55 age-matched healthy controls (HCs). We quantified heterophoria in prism diopters for distance and near range with orthoptic examination. Our primary outcome was high degrees of horizontal heterophoria (HDHH) defined as measurements beyond \u00b12 standard deviations from the mean prism diopter of heterophoria of our HCs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>More than one-third (37%, n=20\/54) of MS patients but only 11% (n=6\/55) of HCs were classified as HDHH [distance, MS=9% (n=5\/54) versus HC=6% (n=3\/55); near, MS=19% (n=10\/54) versus HC=5% (n=3\/55)]. Our MS patients presented more combined vertical and horizontal deviations at near range [MS 19% (n=10\/54) versus for HC 7% (n=4\/55)]. We observed the combination of HDHH both at distance and at near testing in 9% (n=5\/54) of MS patients but not at all in HCs (n=0\/55).<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Despite the high prevalence of heterophoria, HDHH may be an additional (sub)clinical tool of subclinical involvement in MS. Thus, orthoptic examination may be an additional tool to improve MS diagnostic procedures.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2024.1431394","type":"journal-article","created":{"date-parts":[[2024,8,19]],"date-time":"2024-08-19T04:20:11Z","timestamp":1724041211000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Heterophoria in multiple sclerosis patients: a proof of principle cross-sectional study"],"prefix":"10.3389","volume":"15","author":[{"given":"Jonas","family":"Graf","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Margit","family":"Weise","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tanja","family":"Guthoff","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carolin","family":"Balloff","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcia","family":"Gasis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heike","family":"Link","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sebastian","family":"K\u00fcchlin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wolf","family":"Lagr\u00e8ze","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sven G.","family":"Meuth","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Orhan","family":"Aktas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philipp","family":"Albrecht","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2024,8,19]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/13803395.2014.983465","article-title":"Speedy eye movements in multiple sclerosis: association with performance on visual and nonvisual cognitive tests","volume":"37","author":"Roberg","year":"2015","journal-title":"J Clin Exp Neuropsychol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1007\/s12311-016-0831-8","article-title":"Cerebellar assessment in early multiple sclerosis","volume":"16","author":"Moroso","year":"2017","journal-title":"Cerebellum"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1177\/1352458512439237","article-title":"Degeneration of retinal layers in multiple sclerosis subtypes quantified by optical coherence tomography","volume":"18","author":"Albrecht","year":"2012","journal-title":"Mult Scler"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(16)00068-5","article-title":"Retinal thickness measured with optical coherence tomography and risk of disability worsening in multiple sclerosis: a cohort study","volume":"15","author":"Martinez-Lapiscina","year":"2016","journal-title":"Lancet Neurol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"39","DOI":"10.2147\/OPTO.S286862","article-title":"Binocular vision in patients with multiple sclerosis","volume":"13","author":"Gil-Casas","year":"2021","journal-title":"Clin Optom (Auckl)"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1177\/112067210201200312","article-title":"Divergence insufficiency and demyelinating disorder","volume":"12","author":"Reche Sainz","year":"2002","journal-title":"Eur J Ophthalmol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1111\/j.1475-1313.1987.tb01016.x","article-title":"The orthophorization of heterophoria","volume":"7","author":"Dowley","year":"1987","journal-title":"Ophthal Physiol Opt"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1111\/j.1475-1313.1997.tb00094.x","article-title":"Epidemiology of strabismus","volume":"17","author":"Stidwill","year":"1997","journal-title":"Ophthal Physiol Opt"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1111\/aos.12476","article-title":"Ophthalmological findings in 10-year-old full-term children\u2013a population-based study","volume":"93","author":"Larsson","year":"2015","journal-title":"Acta Ophthalmol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.61.2.217","article-title":"Infratentorial lesions predict long-term disability in patients with initial findings suggestive of multiple sclerosis","volume":"61","author":"Minneboo","year":"2004","journal-title":"Arch Neurol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3988\/jcn.2019.15.2.228","article-title":"Conjugate Eye Deviation in Unilateral Lateral Medullary Infarction","volume":"15","author":"Teufel","year":"2019","journal-title":"J Clin Neurol (Seoul Korea)"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3109\/08820538809063825","article-title":"Ophthalmic manifestations of multiple sclerosis","volume":"3","author":"Arnold","year":"1988","journal-title":"Semin Ophthalmol"},{"key":"B13","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1007\/BF02162972","article-title":"Untersuchungen \u00fcber die bei der multiplen Herdsklerose vorkommenden Augenst\u00f6rungen","volume":"21","author":"Uhthoff","year":"1890","journal-title":"Archiv f Psychiatr"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.55.9.747","article-title":"The ocular manifestations of multiple sclerosis. 1. Abnormalities of the afferent visual system","volume":"55","author":"McDonald","year":"1992","journal-title":"J neurol neurosurg Psychiatry"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.55.10.863","article-title":"The ocular manifestations of multiple sclerosis. 2. Abnormalities of eye movements","volume":"55","author":"Barnes","year":"1992","journal-title":"J neurol neurosurg Psychiatry"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.2147\/OPTH.S6383","article-title":"Eye disorders in patients with multiple sclerosis: natural history and management","volume":"4","author":"Graves","year":"2010","journal-title":"Clin Ophthalmol (Auckland N.Z.)"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1097\/01.opx.0000214316.50270.24","article-title":"Comparison of subjective heterophoria testing with a phoropter and trial frame","volume":"83","author":"Casillas Casillas","year":"2006","journal-title":"Optom Vis Sci"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06250-x","article-title":"Locus for severity implicates CNS resilience in progression of multiple sclerosis","volume":"619","year":"2023","journal-title":"Nature"},{"key":"B19","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1586\/ern.13.18","article-title":"Evaluation of brainstem involvement in multiple sclerosis","volume":"13","author":"Habek","year":"2013","journal-title":"Expert Rev Neurother"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2024.1431394\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,19]],"date-time":"2024-08-19T04:20:14Z","timestamp":1724041214000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2024.1431394\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,19]]},"references-count":19,"alternative-id":["10.3389\/fimmu.2024.1431394"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2024.1431394","relation":{},"ISSN":["1664-3224"],"issn-type":[{"type":"electronic","value":"1664-3224"}],"subject":[],"published":{"date-parts":[[2024,8,19]]},"article-number":"1431394"}}