{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T09:22:21Z","timestamp":1792574541178,"version":"4.5.0"},"reference-count":35,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,10,13]],"date-time":"2017-10-13T00:00:00Z","timestamp":1507852800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,10,13]],"date-time":"2017-10-13T00:00:00Z","timestamp":1507852800000},"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>Klinefelter Syndrome (KS), the most common chromosomal disorder in men (47,XXY), is associated with numerous comorbidities. Based on a number of isolated case reports, we performed the first systematic and comprehensive evaluation of eye health in KS patients with a focus on ocular structure and vascularization. Twenty-one KS patients and 26 male and 38 female controls underwent a variety of non-invasive examinations investigating ocular morphology (examination of retinal thickness, optic nerve head, and cornea) and function (visual field testing and quantification of ocular vessel density by optical coherence tomography angiography). In comparison to healthy controls, KS patients exhibited a smaller foveal avascular zone and a decreased retinal thickness due to a drastically thinner outer nuclear layer. The cornea of KS patients showed a decreased peripheral thickness and volume. In perimetry evaluation, KS patients required brighter stimuli and gave more irregular values. KS patients show an ocular phenotype including morphological and functional features, which is very likely caused by the supernumerary X chromosome. Thus, KS should not be limited to infertility, endocrine dysfunction, neurocognitive and psychosocial comorbidities. Defining an aberrant ocular morphology and function, awareness for possible eye problems should be raised.<\/jats:p>","DOI":"10.1038\/s41598-017-13528-4","type":"journal-article","created":{"date-parts":[[2017,10,9]],"date-time":"2017-10-09T10:31:16Z","timestamp":1507545076000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Aberrant ocular architecture and function in patients with Klinefelter syndrome"],"prefix":"10.1038","volume":"7","author":[{"given":"Cristin","family":"Brand","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Zitzmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Eter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine","family":"Kliesch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joachim","family":"Wistuba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maged","family":"Alnawaiseh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Heiduschka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,10,13]]},"reference":[{"key":"13528_CR1","doi-asserted-by":"publisher","first-page":"386","DOI":"10.1093\/molehr\/gaq019","volume":"16","author":"F Tuttelmann","year":"2010","unstructured":"Tuttelmann, F. & Gromoll, J. Novel genetic aspects of Klinefelter\u2019s syndrome. Mol. Hum. Reprod. \n                           16, 386\u2013395 (2010).","journal-title":"Mol. Hum. Reprod."},{"key":"13528_CR2","doi-asserted-by":"publisher","first-page":"807","DOI":"10.1111\/j.1651-2227.2011.02274.x","volume":"100","author":"A Bojesen","year":"2011","unstructured":"Bojesen, A. & Gravholt, C. H. Morbidity and mortality in Klinefelter syndrome (47,XXY). Acta Paediatr. \n                           100, 807\u2013813 (2011).","journal-title":"Acta Paediatr."},{"key":"13528_CR3","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1016\/S0140-6736(04)16678-6","volume":"364","author":"F Lanfranco","year":"2004","unstructured":"Lanfranco, F., Kamischke, A., Zitzmann, M. & Nieschlag, E. Klinefelter\u2019s syndrome. Lancet (London, England) \n                           364, 273\u201383 (2004).","journal-title":"Lancet (London, England)"},{"key":"13528_CR4","doi-asserted-by":"publisher","first-page":"R67","DOI":"10.1530\/EJE-12-0934","volume":"168","author":"L Aksglaede","year":"2013","unstructured":"Aksglaede, L. & Juul, A. Therapy of endocrine disease: Testicular function and fertility in men with Klinefelter syndrome: a review. Eur. J. Endocrinol. \n                           168, R67\u2013R76 (2013).","journal-title":"Eur. J. Endocrinol."},{"key":"13528_CR5","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1111\/andr.12208","volume":"4","author":"E Nieschlag","year":"2016","unstructured":"Nieschlag, E. et al. The Klinefelter syndrome: current management and research challenges. Andrology \n                           4, 545\u2013549 (2016).","journal-title":"Andrology"},{"key":"13528_CR6","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1159\/000477277","volume":"21","author":"J Wistuba","year":"2017","unstructured":"Wistuba, J., Brand, C., Zitzmann, M. & Damm, O. S. Genetics of Klinefelter Syndrome: Experimental Exploration. Genet. Hum. Infertil. \n                           21, 40\u201356 (2017).","journal-title":"Genet. Hum. Infertil."},{"key":"13528_CR7","doi-asserted-by":"publisher","first-page":"720","DOI":"10.1111\/j.1365-2605.2012.01269.x","volume":"35","author":"C Foresta","year":"2012","unstructured":"Foresta, C. et al. Reduced artery diameters in Klinefelter syndrome. Int. J. Androl. \n                           35, 720\u20135 (2012).","journal-title":"Int. J. Androl."},{"key":"13528_CR8","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1111\/j.2047-2927.2014.00190.x","volume":"2","author":"F T\u00fcttelmann","year":"2014","unstructured":"T\u00fcttelmann, F. et al. Intratesticular testosterone is increased in men with Klinefelter syndrome and may not be released into the bloodstream owing to altered testicular vascularization - a preliminary report. Andrology \n                           2, 275\u2013281 (2014).","journal-title":"Andrology"},{"key":"13528_CR9","doi-asserted-by":"publisher","first-page":"843","DOI":"10.1016\/j.ecl.2015.07.008","volume":"44","author":"SM Davis","year":"2015","unstructured":"Davis, S. M., Rogol, A. D. & Ross, J. L. Testis Development and Fertility Potential in Boys with Klinefelter Syndrome. Endocrinol. Metab. Clin. North Am. \n                           44, 843\u201365 (2015).","journal-title":"Endocrinol. Metab. Clin. North Am."},{"key":"13528_CR10","doi-asserted-by":"publisher","first-page":"472","DOI":"10.1111\/pace.12580","volume":"38","author":"IN J\u00f8rgensen","year":"2015","unstructured":"J\u00f8rgensen, I. N. et al. Short QTc Interval in Males with Klinefelter Syndrome-Influence of CAG Repeat Length, Body Composition, and Testosterone Replacement Therapy. Pacing Clin. Electrophysiol. \n                           38, 472\u2013482 (2015).","journal-title":"Pacing Clin. Electrophysiol."},{"key":"13528_CR11","doi-asserted-by":"publisher","first-page":"E518","DOI":"10.1210\/jc.2014-2780","volume":"100","author":"M Zitzmann","year":"2015","unstructured":"Zitzmann, M. et al. Gene Expression Patterns in Relation to the Clinical Phenotype in Klinefelter Syndrome. J. Clin. Endocrinol. Metab. \n                           100, E518\u2013E523 (2015).","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"13528_CR12","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1210\/jcem-2-11-615","volume":"2","author":"HF Klinefelter","year":"1942","unstructured":"Klinefelter, H. F., Reifenstein, E. C. & Albright, F. Syndrome Characterized by Gynecomastia, Aspermatogenesis without A-Leydigism, and Increased Excretion of Follicle-Stimulating Hormone1. J. Clin. Endocrinol. Metab. \n                           2, 615\u2013627 (1942).","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"13528_CR13","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1111\/j.1755-3768.1983.tb01425.x","volume":"61","author":"MA Wolkstein","year":"1983","unstructured":"Wolkstein, M. A., Atkin, A. K., Willner, J. P. & Mindel, J. S. Diffuse choroidal atrophy and Klinefelter syndrome. Acta Ophthalmol. \n                           61, 313\u201321 (1983).","journal-title":"Acta Ophthalmol."},{"key":"13528_CR14","doi-asserted-by":"crossref","first-page":"247","DOI":"10.3928\/0191-3913-20040701-17","volume":"41","author":"MB Boettger","year":"2004","unstructured":"Boettger, M. B., Kirchhof, K., Sergi, C., Sakmann, C. & Meyer, P. Colobomas of the iris and choroid and high signal intensity cerebral foci on T2-weighted magnetic resonance images in Klinefelter\u2019s syndrome. J. Pediatr. Ophthalmol. Strabismus \n                           41, 247\u20138 (2004).","journal-title":"J. Pediatr. Ophthalmol. Strabismus"},{"key":"13528_CR15","doi-asserted-by":"publisher","first-page":"64","DOI":"10.3928\/01913913-20110106-04","volume":"48","author":"S Verstraeten","year":"2011","unstructured":"Verstraeten, S., Jaenen, N., Spileers, W., de Ravel, T. & Casteels, I. Diffuse Choroidal Atrophy in a Boy with Klinefelter Syndrome. J. Pediatr. Ophthalmol. Strabismus \n                           48, 64\u201364 (2011).","journal-title":"J. Pediatr. Ophthalmol. Strabismus"},{"key":"13528_CR16","doi-asserted-by":"publisher","first-page":"232","DOI":"10.3109\/13816810.2012.670361","volume":"33","author":"AT Juhn","year":"2012","unstructured":"Juhn, A. T., Nabi, N. U. & Levin, A. V. Ocular anomalies in an infant with Klinefelter Syndrome. Ophthalmic Genet. \n                           33, 232\u2013234 (2012).","journal-title":"Ophthalmic Genet."},{"key":"13528_CR17","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1016\/j.oftal.2011.09.020","volume":"87","author":"MJ Muniesa Royo","year":"2012","unstructured":"Muniesa Royo, M. J., S\u00e1nchez P\u00e9rez, C. & Jurjo Campo, C. Glaucoma juvenil y foseta papilar con desprendimiento macular asociado a s\u00edndrome de Klinefelter. Arch. Soc. Esp. Oftalmol. \n                           87, 256\u2013259 (2012).","journal-title":"Arch. Soc. Esp. Oftalmol."},{"key":"13528_CR18","doi-asserted-by":"publisher","first-page":"e7","DOI":"10.1097\/IJG.0b013e31824477ef","volume":"22","author":"J Matlach","year":"2013","unstructured":"Matlach, J., Grehn, F. & Klink, T. Klinefelter Syndrome Associated With Goniodysgenesis. J. Glaucoma \n                           22, e7\u2013e8 (2013).","journal-title":"J. Glaucoma"},{"key":"13528_CR19","doi-asserted-by":"publisher","first-page":"420","DOI":"10.1159\/000442461","volume":"6","author":"K Tajiri","year":"2015","unstructured":"Tajiri, K. et al. Vitrectomy for Proliferative Diabetic Retinopathy Associated with Klinefelter Syndrome. Case Rep. Ophthalmol. \n                           6, 420\u2013426 (2015).","journal-title":"Case Rep. Ophthalmol."},{"key":"13528_CR20","doi-asserted-by":"crossref","unstructured":"Coscas, F. et al. Normative Data for Vascular Density in Superficial and Deep Capillary Plexuses of Healthy Adults Assessed by Optical Coherence Tomography Angiography. Invest. Ophthalmol. Vis. Sci. 57, OCT211-23 (2016).","DOI":"10.1167\/iovs.15-18793"},{"key":"13528_CR21","doi-asserted-by":"publisher","unstructured":"Alnawaiseh Brand, C., Lauermann, J. L. & Eter, N. Flow density measurements using optical coherence tomography angiography: Impact of age and gender. Ophthalmologe \n                           https:\/\/doi.org\/10.1007\/s00347-017-0539-2 (2017).","DOI":"10.1007\/s00347-017-0539-2"},{"key":"13528_CR22","doi-asserted-by":"publisher","first-page":"1409","DOI":"10.1016\/S0161-6420(99)00732-0","volume":"106","author":"HA Mintz-Hittner","year":"1999","unstructured":"Mintz-Hittner, H. A., Knight-Nanan, D. M., Satriano, D. R. & Kretzer, F. L. A small foveal avascular zone may be an historic mark of prematurity. Ophthalmology \n                           106, 1409\u20131413 (1999).","journal-title":"Ophthalmology"},{"key":"13528_CR23","first-page":"3442","volume":"35","author":"RF Gariano","year":"1994","unstructured":"Gariano, R. F., Iruela-Arispe, M. L. & Hendrickson, A. E. Vascular development in primate retina: comparison of laminar plexus formation in monkey and human. Invest. Ophthalmol. Vis. Sci. \n                           35, 3442\u201355 (1994).","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"13528_CR24","doi-asserted-by":"publisher","first-page":"549","DOI":"10.1016\/S0301-0082(97)00079-8","volume":"54","author":"JM Provis","year":"1998","unstructured":"Provis, J. M., Diaz, C. M. & Dreher, B. Ontogeny of the primate fovea: a central issue in retinal development. Prog. Neurobiol. \n                           54, 549\u201380 (1998).","journal-title":"Prog. Neurobiol."},{"key":"13528_CR25","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.126.4.507","volume":"126","author":"JM Provis","year":"2008","unstructured":"Provis, J. M. & Hendrickson, A. E. The Foveal Avascular Region of Developing Human Retina. Arch. Ophthalmol. \n                           126, 507 (2008).","journal-title":"Arch. Ophthalmol."},{"key":"13528_CR26","doi-asserted-by":"publisher","first-page":"3509","DOI":"10.1523\/JNEUROSCI.2790-13.2014","volume":"34","author":"DS Hong","year":"2014","unstructured":"Hong, D. S. et al. Influence of the X-Chromosome on Neuroanatomy: Evidence from Turner and Klinefelter Syndromes. J. Neurosci. \n                           34, 3509\u20133516 (2014).","journal-title":"J. Neurosci."},{"key":"13528_CR27","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1016\/j.nicl.2016.02.002","volume":"11","author":"M Wallentin","year":"2016","unstructured":"Wallentin, M. et al. Klinefelter syndrome has increased brain responses to auditory stimuli and motor output, but not to visual stimuli or Stroop adaptation. NeuroImage Clin. \n                           11, 239\u2013251 (2016).","journal-title":"NeuroImage Clin."},{"key":"13528_CR28","doi-asserted-by":"publisher","first-page":"142","DOI":"10.3928\/23258160-20160126-07","volume":"47","author":"D Gong","year":"2016","unstructured":"Gong, D. et al. The Influence of Age and Central Foveal Thickness on Foveal Zone Size in Healthy People. Ophthalmic Surgery, Lasers Imaging Retin. \n                           47, 142\u2013148 (2016).","journal-title":"Ophthalmic Surgery, Lasers Imaging Retin."},{"key":"13528_CR29","doi-asserted-by":"publisher","first-page":"830","DOI":"10.1016\/j.jcrs.2006.12.025","volume":"33","author":"R Khoramnia","year":"2007","unstructured":"Khoramnia, R., Rabsilber, T. M. & Auffarth, G. U. Central and peripheral pachymetry measurements according to age using the Pentacam rotating Scheimpflug camera. J. Cataract Refract. Surg. \n                           33, 830\u20136 (2007).","journal-title":"J. Cataract Refract. Surg."},{"key":"13528_CR30","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1097\/OPX.0b013e318196a737","volume":"86","author":"MA Miranda","year":"2009","unstructured":"Miranda, M. A., Radhakrishnan, H. & O\u2019Donnell, C. Repeatability of corneal thickness measured using an Oculus Pentacam. Optom. Vis. Sci. \n                           86, 266\u201372 (2009).","journal-title":"Optom. Vis. Sci."},{"key":"13528_CR31","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/j.clae.2011.07.004","volume":"35","author":"U Fares","year":"2012","unstructured":"Fares, U., Otri, A. M., Al-Aqaba, M. A. & Dua, H. S. Correlation of central and peripheral corneal thickness in healthy corneas. Contact Lens Anterior Eye \n                           35, 39\u201345 (2012).","journal-title":"Contact Lens Anterior Eye"},{"key":"13528_CR32","doi-asserted-by":"publisher","first-page":"358","DOI":"10.1097\/ICO.0000000000000711","volume":"35","author":"M Alnawaiseh","year":"2016","unstructured":"Alnawaiseh, M. et al. Corneal Densitometry, Central Corneal Thickness, and Corneal Central-to-Peripheral Thickness Ratio in Patients With Fuchs Endothelial Dystrophy. Cornea \n                           35, 358\u2013362 (2016).","journal-title":"Cornea"},{"key":"13528_CR33","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1530\/EJE-09-0768","volume":"162","author":"A Poplinski","year":"2010","unstructured":"Poplinski, A., Wieacker, P., Kliesch, S. & Gromoll, J. Severe XIST hypomethylation clearly distinguishes (SRY\u2009+\u2009) 46,XX-maleness from Klinefelter syndrome. Eur. J. Endocrinol. \n                           162, 169\u2013175 (2010).","journal-title":"Eur. J. Endocrinol."},{"key":"13528_CR34","doi-asserted-by":"publisher","first-page":"1435","DOI":"10.1016\/j.ophtha.2014.01.034","volume":"121","author":"Y Jia","year":"2014","unstructured":"Jia, Y. et al. Quantitative Optical Coherence Tomography Angiography of Choroidal Neovascularization in Age-Related Macular Degeneration. Ophthalmology \n                           121, 1435\u20131444 (2014).","journal-title":"Ophthalmology"},{"key":"13528_CR35","doi-asserted-by":"crossref","unstructured":"Ishibazawa, A. et al. Optical Coherence Tomography Angiography in Diabetic Retinopathy: A Prospective Pilot Study. Am. J. Ophthalmol. 160, 35\u201344.e1 (2015).","DOI":"10.1016\/j.ajo.2015.04.021"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-13528-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-13528-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-13528-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,23]],"date-time":"2022-12-23T12:00:59Z","timestamp":1671796859000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-13528-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,10,13]]},"references-count":35,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2017,12]]}},"alternative-id":["13528"],"URL":"https:\/\/doi.org\/10.1038\/s41598-017-13528-4","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,10,13]]},"assertion":[{"value":"9 June 2017","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 September 2017","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 October 2017","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"JW and MZ received public grants to conduct this study (German Research Foundation and Medical Faculty at Muenster University). The funders of the study had no role in the study design, data collection, data analysis or interpretation, writing of the report, or decision to submit the results for publication. The remaining authors have nothing to disclose.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"13130"}}