{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T02:03:07Z","timestamp":1790128987002,"version":"4.0.1"},"reference-count":46,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2021,5,7]],"date-time":"2021-05-07T00:00:00Z","timestamp":1620345600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Purpose<\/jats:title>\n<jats:p>Agonistic \u03b22-adrenergic receptor autoantibodies (\u03b22-agAAb) have been observed in sera of patients with ocular hypertension and open-angle glaucoma (OAG). They target the \u03b22-receptors on trabecular meshwork, ciliary body and pericytes (Junemann et al. 2018; Hohberger et al. 2019). In addition to their influence on the intraocular pressure, an association to retinal microcirculation is discussed. This study aimed to investigate foveal avascular zone (FAZ) characteristics by en face OCT angiography (OCT-A) in glaucoma suspects and its relationship to \u03b22-agAAb status in patients with OAG.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Material and methods<\/jats:title>\n<jats:p>Thirty-four patients (28 OAG, 6 glaucoma suspects) underwent standardized, clinical examination including sensory testing as white-on-white perimetry (Octopus G1, mean defect, MD) and structural measures as retinal nerve fibre layer (RNFL) thickness, neuroretinal rim width (BMO-MRW), retinal ganglion cell layer (RGCL) thickness, and inner nuclear layer (INL) thickness with high-resolution OCT. FAZ characteristics were measured by OCT-A scans of superficial vascular plexus (SVP), intermediate capillary plexus (ICP), and deep capillary plexus (DCP). FAZ-R was calculated (area FAZ (SVP)\/area FAZ (ICP)). Using cardiomyocyte bioassays we analysed serum samples for the presence of \u03b22-agAAb.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>(I) Total mean FAZ area [mm<jats:sup>2<\/jats:sup>]: 0.34\u00b10.16 (SVP), 0.24\u00b10.12 (ICP), and 0.49\u00b10.24 (DCP); mean FAZ-R 1.58\u00b10.94. No correlation was seen for FAZ-R with MD, RNFL, BMO-MRW, RGCL thickness and INL thickness (p&gt;0.05). (II) \u00df2-agAAb have been observed in 91% patients and showed no correlation with MD, RNFL, BMO-MRW, RGCL thickness and INL thickness (p&gt;0.05). (III) FAZ-R correlated significantly with the \u03b22-agAAb-induced increase of the beat rate of cardiomyocyte (p = 0.028).<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>FAZ characteristics did not correlate with any glaucoma associated functional and morphometric follow-up parameter in the present cohort. However, level of \u03b22-agAAb showed a significantly correlation with FAZ-ratio. We conclude that \u03b22-agAAb might be a novel biomarker in glaucoma pathogenesis showing association to FAZ-ratio with OCT-A.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0249202","type":"journal-article","created":{"date-parts":[[2021,5,7]],"date-time":"2021-05-07T20:06:41Z","timestamp":1620418001000},"page":"e0249202","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":11,"title":["Agonistic autoantibodies against \u00df2-adrenergic receptor influence retinal microcirculation in glaucoma suspects and 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I. Morphometric intrapapillary characteristics","volume":"226","author":"JB Jonas","year":"1988","journal-title":"Graefe\u2019s archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie"},{"issue":"8\u20139","key":"pone.0249202.ref019","first-page":"S634","article-title":"Effects of the serum gamma globulin fraction of patients with allergic asthma and dilated cardiomyopathy on chronotropic beta adrenoceptor function in cultured neonatal rat heart myocytes","volume":"46","author":"G Wallukat","year":"1987","journal-title":"Biomedica biochimica acta"},{"key":"pone.0249202.ref020","volume-title":"OCT angiography: Measurement of retinal macular microvasculature with Spectralis II OCT angiography reliability and reproducibility ARVO Imaging Conference","author":"HB Hosari S","year":"2019"},{"issue":"1","key":"pone.0249202.ref021","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1109\/TSMC.1979.4310076","article-title":"A threshold selection method from gray-level histograms","volume":"9","author":"N Otsu","year":"1979","journal-title":"IEEE transactions on systems, man, and cybernetics"},{"key":"pone.0249202.ref022","volume-title":"Multiscale vessel enhancement filtering","author":"F Alejandro","year":"1998"},{"issue":"3","key":"pone.0249202.ref023","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1007\/s000590050017","article-title":"Autoantibodies against the beta- and muscarinic receptors in cardiomyopathy","volume":"25","author":"G Wallukat","year":"2000","journal-title":"Herz"},{"issue":"10","key":"pone.0249202.ref024","doi-asserted-by":"crossref","first-page":"1419","DOI":"10.1172\/JCI200420149","article-title":"Direct evidence for a beta(1)-adrenergic receptor-directed autoimmune attack as a cause of idiopathic dilated 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mapping at various retinal layers in healthy and normal tension glaucoma eyes","volume":"255","author":"JW Shin","year":"2017","journal-title":"Graefe\u2019s Archive for Clinical and Experimental Ophthalmology"},{"issue":"11","key":"pone.0249202.ref028","doi-asserted-by":"crossref","first-page":"2039","DOI":"10.1097\/IAE.0000000000001077","article-title":"Characterization of the middle capillary plexus using optical coherence tomography angiography in healthy and diabetic eyes","volume":"36","author":"JJ Park","year":"2016","journal-title":"Retina (Philadelphia, Pa)"},{"issue":"4","key":"pone.0249202.ref029","doi-asserted-by":"crossref","first-page":"4710","DOI":"10.1364\/OE.20.004710","article-title":"Split-spectrum amplitude-decorrelation angiography with optical coherence tomography","volume":"20","author":"Y Jia","year":"2012","journal-title":"Optics express"},{"key":"pone.0249202.ref030","volume-title":"Multiscale vessel enhancement filtering1998","author":"AF Frangi"},{"issue":"7","key":"pone.0249202.ref031","doi-asserted-by":"crossref","first-page":"e0219164","DOI":"10.1371\/journal.pone.0219164","article-title":"Reduced vessel density in the superficial and deep plexuses in diabetic retinopathy is associated with structural changes in corresponding retinal layers","volume":"14","author":"C Lavia","year":"2019","journal-title":"PloS one"},{"key":"pone.0249202.ref032","article-title":"Early Detection of Microvascular Changes in Patients with Diabetes Mellitus without and with Diabetic Retinopathy: Comparison between Different Swept-Source OCT-A Instruments","author":"S Vujosevic","year":"2019","journal-title":"J Diabetes Res"},{"issue":"4","key":"pone.0249202.ref033","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1080\/08820538.2019.1620797","article-title":"Optical Coherence Tomography Angiography: Review of Current Technical Aspects and Applications in Chorioretinal Disease","volume":"34","author":"JC Wang","year":"2019","journal-title":"Seminars in ophthalmology"},{"issue":"7","key":"pone.0249202.ref034","doi-asserted-by":"crossref","first-page":"1435","DOI":"10.1016\/j.ophtha.2014.01.034","article-title":"Quantitative optical coherence tomography angiography of choroidal neovascularization in age-related macular degeneration","volume":"121","author":"Y Jia","year":"2014","journal-title":"Ophthalmology"},{"key":"pone.0249202.ref035","article-title":"Evaluation of vascular changes in intermediate uveitis and retinal vasculitis using swept-source wide-field optical coherence tomography angiography","author":"M Tian","year":"2018","journal-title":"The British journal of ophthalmology"},{"key":"pone.0249202.ref036","article-title":"Optical Coherence Tomography Angiography and Glaucoma: A Brief Review","author":"S Moghimi","year":"2019","journal-title":"Asia-Pacific journal of ophthalmology"},{"issue":"4","key":"pone.0249202.ref037","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1080\/08820538.2019.1620807","article-title":"A Review of OCT Angiography in Glaucoma","volume":"34","author":"AC Werner","year":"2019","journal-title":"Seminars in ophthalmology"},{"issue":"9","key":"pone.0249202.ref038","doi-asserted-by":"crossref","first-page":"OCT451","DOI":"10.1167\/iovs.15-18944","article-title":"Optical Coherence Tomography Angiography Vessel Density in Healthy, Glaucoma Suspect, and Glaucoma Eyes","volume":"57","author":"A Yarmohammadi","year":"2016","journal-title":"Investigative ophthalmology & visual science"},{"issue":"6","key":"pone.0249202.ref039","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1097\/IJG.0000000000001242","article-title":"Quantitative Analysis of Retinal and Choroidal Vascular Parameters in Patients With Low Tension Glaucoma","volume":"28","author":"TC Tepelus","year":"2019","journal-title":"Journal of glaucoma"},{"key":"pone.0249202.ref040","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.ajo.2018.03.026","article-title":"Inter-eye Asymmetry of Optical Coherence Tomography Angiography Vessel Density in Bilateral Glaucoma, Glaucoma Suspect, and Healthy Eyes","volume":"190","author":"H Hou","year":"2018","journal-title":"American journal of ophthalmology"},{"issue":"13","key":"pone.0249202.ref041","first-page":"532","article-title":"Agonistic \u03b22-AdrenergicReceptor Autoantibodies in Ocular Hypertension and Open-Angle Glaucoma","volume":"55","author":"HM Hohberger B","year":"2014","journal-title":"Invest Ophthalmol Vis Sci"},{"issue":"2\u20133","key":"pone.0249202.ref042","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.vph.2008.06.001","article-title":"Beta-adrenoceptor-mediated vasodilation of retinal blood vessels is reduced in streptozotocin-induced diabetic rats","volume":"49","author":"T Nakazawa","year":"2008","journal-title":"Vascular 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