{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T14:41:27Z","timestamp":1783521687063,"version":"3.55.0"},"reference-count":47,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2024,5,7]],"date-time":"2024-05-07T00:00:00Z","timestamp":1715040000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Systemic sclerosis is a complex autoimmune disease characterized by vasculopathy, fibrosis, and immune dysregulation. Ocular manifestations in these patients are increasingly recognized, suggesting potential correlations between systemic vascular abnormalities and ocular microvascular changes. Advancements in molecular immunology and imaging technology using ocular coherence tomography (OCT) have unveiled intricate pathways underlying possible disease pathogenesis. Understanding the interplay between retinal vascular abnormalities and molecular immunology parameters could provide insights into disease mechanisms and potential biomarkers. Purpose: The aim of this study was to investigate vascular abnormalities, detected with optical coherence tomography angiography (OCT-A), in systemic sclerosis patients and to find correlations between the severity of the disease detected with molecular immunology findings and OCT-A parameters. Methods: A group of 32 systemic sclerosis patients were compared with 9 healthy controls. Ganglion cell complex thickness (GCC), retina thickness of the fovea and parafovea, nerve fiber layer thickness (RNFL) and cup\/disc area ratio were investigated using OCT. Vessel density (VD) of the superficial (SCP) and deep capillary plexus (DCP) of the whole macular area and ETDRS grid, size of the foveal avascular zone (FAZ) and vessel density of the radial peripapillary capillary plexus (RPCP) were evaluated using OCT-A. Modified Rodnan skin score (mRSS), capillaroscopy and disease duration were used to stage disease severity. Results: There was a statistically significant reduction in retina thickness of the fovea and parafovea, VD of the whole DCP, VD of the SCP and DCP in ETDRS grid in the patient group compared to controls (p &lt; 0.001). The patients presented a significant enlargement of the FAZ (p 0.005). No significant correlation between OCT and OCT-A parameters and disease severity scores was found. Conclusions: OCT-A could represent a non-invasive tool to detect retinal microvascular damage in systemic sclerosis.<\/jats:p>","DOI":"10.3390\/jcm13102738","type":"journal-article","created":{"date-parts":[[2024,5,7]],"date-time":"2024-05-07T09:03:38Z","timestamp":1715072618000},"page":"2738","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Retinal Vascular Abnormalities and Clinical Parameters in Systemic Sclerosis"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7301-8362","authenticated-orcid":false,"given":"Rosario","family":"Foti","sequence":"first","affiliation":[{"name":"Rheumatology Unit, Policlinico San Marco Hospital, 95121 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0999-5545","authenticated-orcid":false,"given":"Marco","family":"Zeppieri","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University Hospital of Udine, 33100 Udine, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3074-4508","authenticated-orcid":false,"given":"Roberta","family":"Foti","sequence":"additional","affiliation":[{"name":"Rheumatology Unit, Policlinico San Marco Hospital, 95121 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Visalli","sequence":"additional","affiliation":[{"name":"Rheumatology Unit, Policlinico San Marco Hospital, 95121 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgio","family":"Amato","sequence":"additional","affiliation":[{"name":"Rheumatology Unit, Policlinico San Marco Hospital, 95121 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Amato","sequence":"additional","affiliation":[{"name":"Eye Clinic, Catania University, San Marco Hospital, Viale Carlo Azeglio Ciampi, 95121 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-0648-1040","authenticated-orcid":false,"given":"Edoardo","family":"Dammino","sequence":"additional","affiliation":[{"name":"Eye Clinic, Catania University, San Marco Hospital, Viale Carlo Azeglio Ciampi, 95121 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7938-876X","authenticated-orcid":false,"given":"Fabiana","family":"D\u2019Esposito","sequence":"additional","affiliation":[{"name":"Imperial College Ophthalmic Research Group (ICORG) Unit, Imperial College, London NW1 5QH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8424-0068","authenticated-orcid":false,"given":"Caterina","family":"Gagliano","sequence":"additional","affiliation":[{"name":"Eye Clinic, Catania University, San Marco Hospital, Viale Carlo Azeglio Ciampi, 95121 Catania, Italy"},{"name":"Department of Medicine and Surgery, University of Enna \u201cKore\u201d, Piazza dell\u2019Universit\u00e0, 94100 Enna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1685","DOI":"10.1016\/S0140-6736(17)30933-9","article-title":"Systemic sclerosis","volume":"390","author":"Denton","year":"2017","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1097\/BOR.0000000000000785","article-title":"Scleroderma epidemiology update","volume":"33","author":"Calderon","year":"2021","journal-title":"Curr. Opin. Rheum."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1007\/s00296-020-04720-3","article-title":"Incidence, prevalence and mortality of systemic sclerosis in Italy: A nationwide population-based study using administrative health data","volume":"41","author":"Ciaffi","year":"2021","journal-title":"Rheumatol. Int."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1007\/s12026-017-8926-y","article-title":"Pathogenesis of systemic sclerosis\u2014Current concept and emerging treatments","volume":"65","author":"Furue","year":"2017","journal-title":"Immunol. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1002\/kjm2.12505","article-title":"Pathophysiology of systemic sclerosis (scleroderma)","volume":"38","author":"Rosendahl","year":"2022","journal-title":"Kaohsiung J. Med. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/0167-5699(94)90021-3","article-title":"Interleukin 13, an interleukin 4-like cytokine that acts on monocytes and B cells, but not on T cells","volume":"15","author":"Zurawski","year":"1994","journal-title":"Immunol. Today"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1093\/intimm\/10.10.1421","article-title":"IL-4 and IL-13 specifically increase adhesion molecule and inflammatory cytokine expression in human lung fibroblasts","volume":"10","author":"Doucet","year":"1998","journal-title":"Int. Immunol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1038\/nrm3434","article-title":"TGF\u03b2 signalling in context","volume":"13","year":"2012","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1016\/j.immuni.2015.09.005","article-title":"Interleukin-4 receptor \u03b1 signaling in myeloid cells controls collagen fibril assembly in skin repair","volume":"43","author":"Knipper","year":"2015","journal-title":"Immunity"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"508","DOI":"10.3389\/fimmu.2014.00508","article-title":"Neutrophil-derived cytokines: Facts beyond expression","volume":"5","author":"Tecchio","year":"2014","journal-title":"Front. Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"eaam8458","DOI":"10.1126\/scitranslmed.aam8458","article-title":"Plasmacytoid dendritic cells promote systemic sclerosis with a key role for TLR8","volume":"10","author":"Tripodo","year":"2018","journal-title":"Sci. Transl. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"84","DOI":"10.5493\/wjem.v7.i3.84","article-title":"Treg\/Th17 cell balance and phytohaemagglutinin activation of T lymphocytes in peripheral blood of systemic sclerosis patients","volume":"7","author":"Krasimirova","year":"2017","journal-title":"World J. Exp. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2445","DOI":"10.1002\/1529-0131(200011)43:11<2445::AID-ANR11>3.0.CO;2-Q","article-title":"Skin thickness score as a predictor and correlate of outcome in systemic sclerosis","volume":"43","author":"Clements","year":"2000","journal-title":"Arthritis Rheum."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/s41232-016-0001-x","article-title":"Usefulness of nailfold videocapillaroscopy for systemic sclerosis","volume":"36","author":"Kubo","year":"2016","journal-title":"Inflamm. Regen."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"221","DOI":"10.5114\/reum.2019.87619","article-title":"Systemic sclerosis-multidisciplinary disease: Clinical features and treatment","volume":"57","author":"Sobolewski","year":"2019","journal-title":"Rheumatology"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"401","DOI":"10.5114\/reum.2020.102004","article-title":"Ocular manifestations in patients with systemic sclerosis","volume":"58","author":"Kozikowska","year":"2020","journal-title":"Rheumatology"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Gagliano, C., Visalli, E., Toro, M.D., Amato, R., Panta, G., Scollo, D., Scandura, G., Ficili, S., Amato, G., and Benenati, A. (2020). Dry Eye in Systemic Sclerosis Patients: Novel Methods to Monitor Disease Activity. Diagnostics, 10.","DOI":"10.3390\/diagnostics10060404"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1590\/S1807-59322011000300003","article-title":"Ocular findings in patients with systemic sclerosis","volume":"66","author":"Santhiago","year":"2011","journal-title":"Clinics"},{"key":"ref_19","first-page":"1","article-title":"A Wide Spectrum of Ocular Manifestations Signify Patients with Systemic Sclerosis","volume":"2","author":"Szucs","year":"2019","journal-title":"Ocul. Immunol. Inflamm."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Ren, H., Liu, L., Xiao, Y., Shi, Y., Zeng, Z., Ding, Y., Zou, P., and Xiao, R. (2023). Further insight into systemic sclerosis from the vasculopathy perspective. Biomed. Pharmacother., 166.","DOI":"10.1016\/j.biopha.2023.115282"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1136\/annrheumdis-2016-210229","article-title":"Endothelial-to-mesenchymal transition contributes to endothelial dysfunction and dermal fibrosis in systemic sclerosis","volume":"76","author":"Manetti","year":"2017","journal-title":"Ann. Rheum. Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.1080\/1744666X.2021.2000391","article-title":"The role of the Notch pathway in the pathogenesis of systemic sclerosis: Clinical implications","volume":"17","year":"2021","journal-title":"Expert. Rev. Clin. Immunol."},{"key":"ref_23","first-page":"141","article-title":"Role of IL-33\/ST2 signaling pathway in systemic sclerosis and other fibrotic diseases","volume":"37","author":"Xu","year":"2019","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.1016\/j.cell.2022.03.011","article-title":"LGR5 expressing skin fibroblasts define a major cellular hub perturbed in scleroderma","volume":"185","author":"Gur","year":"2022","journal-title":"Cell"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1097\/BOR.0000000000000959","article-title":"Pathogenesis of vasculopathy in systemic sclerosis and its contribution to fibrosis","volume":"35","author":"Kawaguchi","year":"2023","journal-title":"Curr. Opin. Rheumatol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1136\/ard.36.2.152","article-title":"Involvement of the eye in SLE and scleroderma","volume":"36","author":"Grennan","year":"1977","journal-title":"Ann. Rheum. Dis."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1136\/bjo.63.12.845","article-title":"Ocular involvement in scleroderma","volume":"63","author":"West","year":"1979","journal-title":"Br. J. Ophthalmol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1159\/000309083","article-title":"Bilateral central retinal vein occlusion in a patient with scleroderma","volume":"182","author":"Saari","year":"1981","journal-title":"Ophthalmologica"},{"key":"ref_29","first-page":"597","article-title":"Closure of the ventral artery of the retina in progressive scleroderma","volume":"171","author":"Berndt","year":"1977","journal-title":"Klin. Monatsbl. Augenheilkd."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1136\/ard.62.3.204","article-title":"Retinal findings in systemic sclerosis: A comparison with Nailfold capillaroscopic patterns","volume":"62","author":"Ushiyama","year":"2003","journal-title":"Ann. Rheum. Dis."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1007\/s10792-024-02950-z","article-title":"The effect of systemic sclerosis and its subtypes on ocular anterior and posterior segment parameters","volume":"44","author":"Tezcan","year":"2024","journal-title":"Int. Ophthalmol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1038\/s41433-019-0591-z","article-title":"Analysis of retinal and choroidal microvasculature in systemic sclerosis: An optical coherence tomography angiography study","volume":"34","year":"2020","journal-title":"Eye"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"104166","DOI":"10.1016\/j.mvr.2021.104166","article-title":"Evaluation of the direct effects on retinal and choroidal microvascularity of systemic scleroderma","volume":"136","author":"Ayan","year":"2021","journal-title":"Microvasc. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1080\/03009742.2019.1641616","article-title":"Evaluation of choroidal substructure perfusion in patients affected by systemic sclerosis: An optical coherence tomography angiography study","volume":"49","author":"Ranjbar","year":"2020","journal-title":"Scand. J. Rheumatol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1186\/s13023-020-01649-5","article-title":"Correlation of retinal and choroidal microvascular impairment in systemic sclerosis","volume":"16","author":"Rommel","year":"2021","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"10990","DOI":"10.1038\/s41598-022-14377-6","article-title":"Altered ocular microvasculature in patients with systemic sclerosis and very early disease of systemic sclerosis using optical coherence tomography angiography","volume":"12","author":"Mihailovic","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Erturk, A., Erogul, O., and Kasikci, M. (2023). Optical Coherence Tomography Angiography Is a Useful Tool for Distinguishing Primary Raynaud\u2019s Phenomenon from Systemic Sclerosis and\/or Very Early Disease of Systemic Sclerosis. Diagnostics, 13.","DOI":"10.3390\/diagnostics13152607"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"382","DOI":"10.4103\/idoj.IDOJ_264_19","article-title":"Nailfold Capillaroscopy and Retinal Findings in Patients with Systemic Sclerosis: Is There an Association?","volume":"11","author":"Jakhar","year":"2020","journal-title":"Indian Dermatol. Online J."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Lee, H.Y., Chen, J., Ying, P., Xu, S.H., Kang, M., Zou, J., Liao, X.L., Shi, W., Ling, Q., and Wang, Y.X. (2023). Investigation of altered retinal microvasculature in female patients with rheumatoid arthritis: Optical coherence tomography angiography detection. Biosci. Rep., 43.","DOI":"10.1042\/BSR20230045"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1080\/14397595.2020.1830740","article-title":"Evaluation of retinal vascularization by optical coherence tomography angiography (OCTA) in rheumatoid arthritis, and its relationship with disease activity","volume":"31","author":"Ayar","year":"2021","journal-title":"Mod. Rheumatol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2433","DOI":"10.1177\/11206721211035626","article-title":"OCT retinal angiography features in patients with rheumatoid arthritis: A pilot study","volume":"32","author":"Iacono","year":"2022","journal-title":"Eur. J. Ophthalmol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1007\/s10792-021-02100-9","article-title":"Evaluation of retinal microvascular structures by optical coherence tomography angiography in primary Sj\u00f6gren\u2019s syndrome","volume":"42","author":"Yener","year":"2022","journal-title":"Int. Ophthalmol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"853930","DOI":"10.3389\/fneur.2022.853930","article-title":"Optical Coherence Tomography Angiography Biomarkers of Retinal Thickness and Microvascular Alterations in Sjogren\u2019s Syndrome","volume":"13","author":"Liu","year":"2022","journal-title":"Front. Neurol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1007\/s10792-024-02970-9","article-title":"Choroidal, retinal, and optic nerve changes in rheumatoid arthritis and primary sjogren\u2019s syndrome patients: Compar\u0131son with each other and healthy subjects","volume":"44","author":"Kiyat","year":"2024","journal-title":"Int. Ophthalmol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1186\/s13023-023-02782-7","article-title":"Subclinical microvascular changes in ANCA-vasculitides: The role of optical coherence tomography angiography and nailfold capillaroscopy in the detection of disease-related damage","volume":"18","author":"Triggianese","year":"2023","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Mimier-Janczak, M., Kaczmarek, D., Janczak, D., and Kaczmarek, R. (2021). Optical Coherence Tomography Angiography as a New Tool for Evaluation of the Subclinical Retinal Involvement in Patients with Systemic Lupus Erythematosus-A Review. J. Clin. Med., 10.","DOI":"10.3390\/jcm10132887"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2111","DOI":"10.1007\/s10792-020-01388-3","article-title":"Optical coherence tomography angiography findings in systemic lupus erythematosus patients with no ocular disease","volume":"40","author":"Pichi","year":"2020","journal-title":"Int. Ophthalmol."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/13\/10\/2738\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:40:53Z","timestamp":1760107253000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/13\/10\/2738"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,7]]},"references-count":47,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2024,5]]}},"alternative-id":["jcm13102738"],"URL":"https:\/\/doi.org\/10.3390\/jcm13102738","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,7]]}}}