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Recently, a technique for non-invasive assessment of the retinal microvasculature called optical coherence tomography angiography (OCTA) was introduced. We investigated retinal microvasculature alterations in participants with relapsing\u2013remitting MS (RRMS) without history of optic neuritis (ON) and compared them to a healthy control group. The study was performed in a prospective, case\u2013control design, including 58 participants (n\u2009=\u2009100 eyes) with RRMS without ON and 78 age- and sex-matched control participants (n\u2009=\u2009136 eyes). OCTA images of the superficial capillary plexus (SCP), deep capillary plexus (DCP) and choriocapillaris (CC) were obtained using a commercial OCTA system (Zeiss Cirrus HD-5000 Spectral-Domain OCT with AngioPlex OCTA, Carl Zeiss Meditec, Dublin, CA). The outcome variables were perfusion density (PD) and foveal avascular zone (FAZ) features (area and circularity) in both the SCP and DCP, and flow deficit in the CC. MS group had on average higher intraocular pressure (IOP) than controls (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001). After adjusting for confounders, MS participants showed significantly increased PD in SCP (<jats:italic>P<\/jats:italic>\u2009=\u20090.003) and decreased PD in DCP (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001) as compared to controls. A significant difference was still noted when large vessels (LV) in the SCP were removed from the PD calculation (<jats:italic>P<\/jats:italic>\u2009=\u20090.004). Deep FAZ was significantly larger (<jats:italic>P<\/jats:italic>\u2009=\u20090.005) and less circular (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001) in the eyes of MS participants compared to the control ones. Neither LV, PD or FAZ features in the SCP, nor flow deficits in the CC showed any statistically significant differences between the MS group and control group (<jats:italic>P<\/jats:italic>\u2009&gt;\u20090.186). Our study indicates that there are microvascular changes in the macular parafoveal retina of RRMS patients without ON, showing increased PD in SCP and decreased PD in DCP. Further studies with a larger cohort of MS patients and MRI correlations are necessary to validate retinal microvascular changes as imaging biomarkers for diagnosis and screening of MS.<\/jats:p>","DOI":"10.1038\/s41598-022-17344-3","type":"journal-article","created":{"date-parts":[[2022,8,3]],"date-time":"2022-08-03T19:07:57Z","timestamp":1659553677000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Microvascular changes in the macular and parafoveal areas of multiple sclerosis patients without optic neuritis"],"prefix":"10.1038","volume":"12","author":[{"given":"Mihai","family":"Bostan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline","family":"Chua","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yin Ci","family":"Sim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingyao","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inna","family":"Bujor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Damon","family":"Wong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerhard","family":"Garh\u00f6fer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Tiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leopold","family":"Schmetterer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alina","family":"Popa-Cherecheanu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,8,3]]},"reference":[{"key":"17344_CR1","doi-asserted-by":"publisher","first-page":"752","DOI":"10.1097\/WCO.0000000000000622","volume":"31","author":"J Oh","year":"2018","unstructured":"Oh, J., Vidal-Jordana, A. & Montalban, X. 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