{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T18:47:02Z","timestamp":1740163622700,"version":"3.37.3"},"reference-count":36,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,6,28]],"date-time":"2019-06-28T00:00:00Z","timestamp":1561680000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2019,6,28]],"date-time":"2019-06-28T00:00:00Z","timestamp":1561680000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The cold pressor test (CPT) induces a cardiovascular response, which may affect ocular blood flow and neuronal function. This study assessed whether optical coherence tomography angiography (OCT-A) can be used to evaluate CPT-induced changes in healthy eyes and in eyes with primary open-angle glaucoma (POAG). Twenty-two healthy subjects and 23 subjects with POAG and retinal fibre layer defects in only one hemifield were included in this study. The CPT was performed by submerging a subject\u2019s hand in cold water (0\u20134\u2009\u00b0C) for 1\u2009minute. The results showed that baseline peripapillary and macular vessel density (VD) measurements were significantly lower in subjects with POAG than in controls (all P\u2009&lt;\u20090.05). Post-CPT VD measurements did not significantly differ from baseline in either healthy or glaucomatous eyes. Additionally, CPT-induced changes in VD did not differ among normal eyes, damaged and undamaged glaucomatous hemifields. Changes in VD were also not significantly influenced by self-reported history of cold extremities. In conclusion, the CPT does not induce significant VD changes, as measured by OCT-A, in the peripapillary or macular areas of either healthy eyes or eyes with POAG. The VD, an all-or-nothing flow measure, may not be sensitive enough for evaluating cold-induced ocular haemodynamic changes.<\/jats:p>","DOI":"10.1038\/s41598-019-45386-7","type":"journal-article","created":{"date-parts":[[2019,6,28]],"date-time":"2019-06-28T10:03:14Z","timestamp":1561716194000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Effect of cold provocation on vessel density in eyes with primary open angle glaucoma: An optical coherence tomography angiography study"],"prefix":"10.1038","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3509-525X","authenticated-orcid":false,"given":"Wei-Yi","family":"Chou","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catherine Jui-Ling","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mei-Ju","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shih-Hwa","family":"Chiou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei-Ta","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu-Chieh","family":"Ko","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2019,6,28]]},"reference":[{"key":"45386_CR1","doi-asserted-by":"publisher","first-page":"e0162229","DOI":"10.1371\/journal.pone.0162229","volume":"11","author":"RR Bourne","year":"2016","unstructured":"Bourne, R. R. et al. Number of people blind or visually impaired by glaucoma worldwide and in world regions 1990\u20132010: a meta-analysis. PLoS One. 11, e0162229 (2016).","journal-title":"PLoS One."},{"key":"45386_CR2","doi-asserted-by":"publisher","first-page":"1268","DOI":"10.1001\/archopht.120.10.1268","volume":"120","author":"A Heijl","year":"2002","unstructured":"Heijl, A. et al. Reduction of Intraocular Pressure and Glaucoma Progression: Results From the Early Manifest Glaucoma Trial. Archives of Ophthalmology. 120, 1268\u20131279 (2002).","journal-title":"Archives of Ophthalmology."},{"key":"45386_CR3","doi-asserted-by":"publisher","first-page":"1690","DOI":"10.1016\/S0161-6420(84)34091-X","volume":"91","author":"JE Grunwald","year":"1984","unstructured":"Grunwald, J. E., Riva, C. E., Stone, R. A., Keates, E. U. & Petrig, B. L. Retinal autoregulation in open-angle glaucoma. Ophthalmology. 91, 1690\u20134 (1984).","journal-title":"Ophthalmology."},{"key":"45386_CR4","doi-asserted-by":"publisher","first-page":"809","DOI":"10.1136\/bjo.83.7.809","volume":"83","author":"DW Evans","year":"1999","unstructured":"Evans, D. W., Harris, A., Garrett, M., Chung, H. S. & Kagemann, L. Glaucoma patients demonstrate faulty autoregulation of ocular blood flow during posture change. Br J Ophthalmol. 83, 809\u201313 (1999).","journal-title":"Br J Ophthalmol."},{"key":"45386_CR5","doi-asserted-by":"publisher","first-page":"3546","DOI":"10.1167\/iovs.04-0290","volume":"45","author":"D Gherghel","year":"2004","unstructured":"Gherghel, D., Hosking, S. L. & Cunliffe, I. A. Abnormal systemic and ocular vascular response to temperature provocation in primary open-angle glaucoma patients: a case for autonomic failure? Invest Ophthalmol Vis Sci. 45, 3546\u201354 (2004).","journal-title":"Invest Ophthalmol Vis Sci."},{"key":"45386_CR6","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1097\/ICU.0000000000000245","volume":"27","author":"LR Pasquale","year":"2016","unstructured":"Pasquale, L. R. Vascular and autonomic dysregulation in primary open-angle glaucoma. Curr Opin Ophthalmol. 27, 94\u2013101 (2016).","journal-title":"Curr Opin Ophthalmol."},{"key":"45386_CR7","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1016\/j.survophthal.2015.10.004","volume":"61","author":"D Prada","year":"2016","unstructured":"Prada, D. et al. Autoregulation and neurovascular coupling in the optic nerve head. Surv Ophthalmol. 61, 164\u201386 (2016).","journal-title":"Surv Ophthalmol."},{"key":"45386_CR8","first-page":"1710","volume":"40","author":"E Henry","year":"1999","unstructured":"Henry, E., Newby, D. E., Webb, D. J. & O\u2019Brien, C. Peripheral Endothelial Dysfunction in Normal Pressure Glaucoma. Invest Ophthalmol Vis Sci. 40, 1710\u20131714 (1999).","journal-title":"Invest Ophthalmol Vis Sci."},{"key":"45386_CR9","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1111\/j.1755-3768.2009.01573.x","volume":"88","author":"GP Fadini","year":"2010","unstructured":"Fadini, G. P. et al. Reduced endothelial progenitor cells and brachial artery flow-mediated dilation as evidence of endothelial dysfunction in ocular hypertension and primary open-angle glaucoma. Acta Ophthalmol. 88, 135\u201341 (2010).","journal-title":"Acta Ophthalmol."},{"key":"45386_CR10","doi-asserted-by":"publisher","first-page":"7021","DOI":"10.1167\/iovs.15-17860","volume":"56","author":"LR Pasquale","year":"2015","unstructured":"Pasquale, L. R. et al. Nailfold Capillary Abnormalities in Primary Open-Angle Glaucoma: A Multisite StudyNailfold Capillary Abnormalities in Glaucoma. Invest Ophthalmol Vis Sci. 56, 7021\u20137028 (2015).","journal-title":"Invest Ophthalmol Vis Sci."},{"key":"45386_CR11","doi-asserted-by":"publisher","first-page":"2565","DOI":"10.1167\/iovs.02-0913","volume":"44","author":"MT Nicolela","year":"2003","unstructured":"Nicolela, M. T. et al. Effects of cold-induced vasospasm in glaucoma: the role of endothelin-1. Invest Ophthalmol Vis Sci. 44, 2565\u201372 (2003).","journal-title":"Invest Ophthalmol Vis Sci."},{"key":"45386_CR12","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1007\/BF02181185","volume":"226","author":"U Guthauser","year":"1988","unstructured":"Guthauser, U., Flammer, J. & Mahler, F. The relationship between digital and ocular vasospasm. Graefes Arch Clin Exp Ophthalmol. 226, 224\u20136 (1988).","journal-title":"Graefes Arch Clin Exp Ophthalmol."},{"key":"45386_CR13","doi-asserted-by":"publisher","first-page":"1573","DOI":"10.1167\/iovs.02-0521","volume":"44","author":"K Gugleta","year":"2003","unstructured":"Gugleta, K. et al. Choroidal vascular reaction to hand-grip stress in subjects with vasospasm and its relevance in glaucoma. Invest Ophthalmol Vis Sci. 44, 1573\u201380 (2003).","journal-title":"Invest Ophthalmol Vis Sci."},{"key":"45386_CR14","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1016\/S0161-6420(96)30703-3","volume":"103","author":"A Sawada","year":"1996","unstructured":"Sawada, A., Kitazawa, Y., Yamamoto, T., Okabe, I. & Ichien, K. Prevention of visual field defect progression with brovincamine in eyes with normal-tension glaucoma. Ophthalmology. 103, 283\u20138 (1996).","journal-title":"Ophthalmology."},{"key":"45386_CR15","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1016\/0002-9149(65)90007-X","volume":"16","author":"MA Greene","year":"1965","unstructured":"Greene, M. A., Boltax, A. J., Lustig, G. A. & Rogow, E. Circulatory dynamics during the cold pressor test. Am J Cardiol. 16, 54\u201360 (1965).","journal-title":"Am J Cardiol."},{"key":"45386_CR16","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/S0002-8703(36)90370-8","volume":"11","author":"EA Hines","year":"1936","unstructured":"Hines, E. A. & Brown, G. E. The cold pressor test for measuring the reactibility of the blood pressure: Data concerning 571 normal and hypertensive subjects. American Heart Journal. 11, 1\u20139 (1936).","journal-title":"American Heart Journal."},{"issue":"Suppl 7","key":"45386_CR17","doi-asserted-by":"publisher","first-page":"S91","DOI":"10.1093\/aje\/kws294","volume":"176","author":"Q Zhao","year":"2012","unstructured":"Zhao, Q. et al. Reproducibility of blood pressure response to the cold pressor test: the GenSalt Study. Am J Epidemiol. 176(Suppl 7), S91\u20138 (2012).","journal-title":"Am J Epidemiol."},{"key":"45386_CR18","doi-asserted-by":"publisher","first-page":"1132","DOI":"10.1093\/ajh\/hpt075","volume":"26","author":"M Zhang","year":"2013","unstructured":"Zhang, M. et al. Factors associated with blood pressure response to the cold pressor test: the GenSalt Study. Am J Hypertens. 26, 1132\u20139 (2013).","journal-title":"Am J Hypertens."},{"key":"45386_CR19","doi-asserted-by":"publisher","first-page":"e0172538","DOI":"10.1371\/journal.pone.0172538","volume":"12","author":"A AlBadri","year":"2017","unstructured":"AlBadri, A. et al. Acetylcholine versus cold pressor testing for evaluation of coronary endothelial function. PLoS One. 12, e0172538 (2017).","journal-title":"PLoS One."},{"key":"45386_CR20","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1111\/j.1748-1716.1989.tb08760.x","volume":"137","author":"J Fagius","year":"1989","unstructured":"Fagius, J., Karhuvaara, S. & Sundlof, G. The cold pressor test: effects on sympathetic nerve activity in human muscle and skin nerve fascicles. Acta Physiol Scand. 137, 325\u201334 (1989).","journal-title":"Acta Physiol Scand."},{"key":"45386_CR21","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1007\/BF02291228","volume":"6","author":"A Stancak","year":"1996","unstructured":"Stancak, A., Yamamotova, A., Kulls, I. P. & Sekyra, I. V. Cardiovascular adjustments and pain during repeated cold pressor test. Clin Auton Res. 6, 83\u20139 (1996).","journal-title":"Clin Auton Res."},{"key":"45386_CR22","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1038\/nrrheum.2014.195","volume":"11","author":"NA Flavahan","year":"2015","unstructured":"Flavahan, N. A. A vascular mechanistic approach to understanding Raynaud phenomenon. Nat Rev Rheumatol. 11, 146\u201358 (2015).","journal-title":"Nat Rev Rheumatol."},{"key":"45386_CR23","doi-asserted-by":"publisher","first-page":"851","DOI":"10.1097\/IJG.0000000000000768","volume":"26","author":"PIC Manalastas","year":"2017","unstructured":"Manalastas, P. I. C. et al. Reproducibility of Optical Coherence Tomography Angiography Macular and Optic Nerve Head Vascular Density in Glaucoma and Healthy Eyes. J Glaucoma. 26, 851\u2013859 (2017).","journal-title":"J Glaucoma."},{"key":"45386_CR24","doi-asserted-by":"publisher","first-page":"e0184948","DOI":"10.1371\/journal.pone.0184948","volume":"12","author":"J Choi","year":"2017","unstructured":"Choi, J. et al. Quantitative optical coherence tomography angiography of macular vascular structure and foveal avascular zone in glaucoma. PLoS One. 12, e0184948 (2017).","journal-title":"PLoS One."},{"key":"45386_CR25","doi-asserted-by":"publisher","first-page":"OCT451","DOI":"10.1167\/iovs.15-18944","volume":"57","author":"A Yarmohammadi","year":"2016","unstructured":"Yarmohammadi, A. et al. Optical coherence tomography angiography vessel density in healthy, glaucoma suspect, and glaucoma eyes. Invest Ophthalmol Vis Sci. 57, OCT451\u20139 (2016).","journal-title":"Invest Ophthalmol Vis Sci."},{"key":"45386_CR26","doi-asserted-by":"publisher","first-page":"3287","DOI":"10.1167\/iovs.15-16655","volume":"56","author":"AD Pechauer","year":"2015","unstructured":"Pechauer, A. D. et al. Optical coherence tomography angiography of peripapillary retinal blood flow response to hyperoxia. Invest Ophthalmol Vis Sci. 56, 3287\u201391 (2015).","journal-title":"Invest Ophthalmol Vis Sci."},{"key":"45386_CR27","doi-asserted-by":"publisher","first-page":"e7","DOI":"10.1097\/IJG.0000000000000527","volume":"26","author":"G Hollo","year":"2017","unstructured":"Hollo, G. Influence of large intraocular pressure reduction on peripapillary OCT vessel density in ocular hypertensive and glaucoma eyes. J Glaucoma. 26, e7\u201310 (2017).","journal-title":"J Glaucoma."},{"key":"45386_CR28","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/j.ajo.2016.08.030","volume":"171","author":"HL Rao","year":"2016","unstructured":"Rao, H. L. et al. Regional comparisons of optical coherence tomography angiography vessel density in primary open-angle glaucoma. Am J Ophthalmol. 171, 75\u201383 (2016).","journal-title":"Am J Ophthalmol."},{"key":"45386_CR29","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1007\/BF00919643","volume":"231","author":"P Rojanapongpun","year":"1993","unstructured":"Rojanapongpun, P. & Drance, S. M. The response of blood flow velocity in the ophthalmic artery and blood flow of the finger to warm and cold stimuli in glaucomatous patients. Graefes Arch Clin Exp Ophthalmol. 231, 375\u20137 (1993).","journal-title":"Graefes Arch Clin Exp Ophthalmol."},{"key":"45386_CR30","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.preteyeres.2017.11.003","volume":"64","author":"RF Spaide","year":"2018","unstructured":"Spaide, R. F., Fujimoto, J. G., Waheed, N. K., Sadda, S. R. & Staurenghi, G. Optical coherence tomography angiography. Prog Retin Eye Res. 64, 1\u201355 (2018).","journal-title":"Prog Retin Eye Res."},{"key":"45386_CR31","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1016\/S1350-9462(00)00028-8","volume":"20","author":"J Flammer","year":"2001","unstructured":"Flammer, J., Pache, M. & Resink, T. Vasospasm, its role in the pathogenesis of diseases with particular reference to the eye. Prog Retin Eye Res. 20, 319\u201349 (2001).","journal-title":"Prog Retin Eye Res."},{"key":"45386_CR32","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1177\/112067211002000119","volume":"20","author":"M Mozaffarieh","year":"2010","unstructured":"Mozaffarieh, M., Osusky, R., Schotzau, A. & Flammer, J. Relationship between optic nerve head and finger blood flow. Eur J Ophthalmol. 20, 136\u201341 (2010).","journal-title":"Eur J Ophthalmol."},{"key":"45386_CR33","doi-asserted-by":"publisher","first-page":"246","DOI":"10.1167\/iovs.15-18287","volume":"57","author":"SG Gadde","year":"2016","unstructured":"Gadde, S. G. et al. Quantification of vessel density in retinal optical coherence tomography angiography images using local fractal dimension. Invest Ophthalmol Vis Sci. 57, 246\u201352 (2016).","journal-title":"Invest Ophthalmol Vis Sci."},{"key":"45386_CR34","doi-asserted-by":"publisher","first-page":"2509","DOI":"10.1016\/j.ophtha.2016.09.002","volume":"123","author":"MH Suh","year":"2016","unstructured":"Suh, M. H. et al. Deep Retinal Layer Microvasculature Dropout Detected by the Optical Coherence Tomography Angiography in Glaucoma. Ophthalmology. 123, 2509\u20132518 (2016).","journal-title":"Ophthalmology."},{"key":"45386_CR35","doi-asserted-by":"publisher","first-page":"2498","DOI":"10.1016\/j.ophtha.2016.08.041","volume":"123","author":"A Yarmohammadi","year":"2016","unstructured":"Yarmohammadi, A. et al. Relationship between Optical Coherence Tomography Angiography Vessel Density and Severity of Visual Field Loss in Glaucoma. Ophthalmology. 123, 2498\u20132508 (2016).","journal-title":"Ophthalmology."},{"key":"45386_CR36","doi-asserted-by":"publisher","first-page":"4710","DOI":"10.1364\/OE.20.004710","volume":"20","author":"Y Jia","year":"2012","unstructured":"Jia, Y. et al. Split-spectrum amplitude-decorrelation angiography with optical coherence tomography. Optics Express. 20, 4710\u201325 (2012).","journal-title":"Optics Express."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-45386-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-45386-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-45386-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,17]],"date-time":"2022-12-17T10:52:21Z","timestamp":1671274341000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-45386-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,6,28]]},"references-count":36,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2019,12]]}},"alternative-id":["45386"],"URL":"https:\/\/doi.org\/10.1038\/s41598-019-45386-7","relation":{},"ISSN":["2045-2322"],"issn-type":[{"type":"electronic","value":"2045-2322"}],"subject":[],"published":{"date-parts":[[2019,6,28]]},"assertion":[{"value":"5 January 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 May 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 June 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"9384"}}