{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T13:36:03Z","timestamp":1791293763888,"version":"4.1.0"},"reference-count":38,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2016,7,15]],"date-time":"2016-07-15T00:00:00Z","timestamp":1468540800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,7,15]],"date-time":"2016-07-15T00:00:00Z","timestamp":1468540800000},"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>Recent developments in optical coherence tomography (OCT) systems for the cornea have limited resolution or acquisition speed. In this study we aim to evaluate the use of a \u2018micro-OCT\u2019 (\u03bcOCT ~1\u2009\u03bcm axial resolution) compared to existing imaging modalities using animal models of corneal endothelial disease. We used established cryoinjury and bullous keratopathy models in Sprague Dawley rats comparing <jats:italic>ex vivo<\/jats:italic> \u03bcOCT imaging in normal and diseased eyes to (1) histology; (2) <jats:italic>in vivo<\/jats:italic> confocal microscopy (IVCM); and (3) scanning electron microscopy (SEM). Qualitative and quantitative comparisons amongst imaging modalities were performed using mean endothelial cell circularity [(4\u03c0\u2009\u00d7\u2009Area)\/Perimeter<jats:sup>2<\/jats:sup>] with coefficient of variation (COV). We found that \u03bcOCT imaging was able to delineate endothelial cells (with nuclei), detect inflammatory cells and corneal layers with histology-like resolution, comparable to existing imaging modalities. The mean endothelial cell circularity score was 0.88\u2009\u00b1\u20090.03, 0.87\u2009\u00b1\u20090.04 and 0.88\u2009\u00b1\u20090.05 (P\u2009=\u20090.216) for the SEM, IVCM and \u03bcOCT respectively, with SEM producing homogenous endothelial cell images (COV\u2009=\u20090.028) compared to the IVCM (0.051) and \u03bcOCT (0.062). In summary, our preliminary study suggests that the \u03bcOCT may be useful for achieving non-contact, histology-like images of the cornea for endothelial cell evaluation, which requires further development for <jats:italic>in vivo<\/jats:italic> imaging.<\/jats:p>","DOI":"10.1038\/srep29769","type":"journal-article","created":{"date-parts":[[2016,7,15]],"date-time":"2016-07-15T09:56:27Z","timestamp":1468576587000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Evaluation of a Micro-Optical Coherence Tomography for the Corneal Endothelium in an Animal Model"],"prefix":"10.1038","volume":"6","author":[{"given":"Marcus","family":"Ang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aris","family":"Konstantopoulos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gwendoline","family":"Goh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hla M.","family":"Htoon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyi","family":"Seah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nyein Chan","family":"Lwin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyu","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Si","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linbo","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jodhbir S.","family":"Mehta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,7,15]]},"reference":[{"key":"BFsrep29769_CR1","first-page":"214","volume":"79","author":"JP Whitcher","year":"2001","unstructured":"Whitcher, J. P., Srinivasan, M. & Upadhyay, M. P. Corneal blindness: a global perspective. Bull World Health Organ 79, 214\u2013221 (2001).","journal-title":"Bull World Health Organ"},{"key":"BFsrep29769_CR2","doi-asserted-by":"publisher","first-page":"1133","DOI":"10.1038\/sj.eye.6701973","volume":"19","author":"A Foster","year":"2005","unstructured":"Foster, A. & Resnikoff, S. The impact of Vision 2020 on global blindness. Eye (Lond) 19, 1133\u20131135 (2005).","journal-title":"Eye (Lond)"},{"key":"BFsrep29769_CR3","doi-asserted-by":"publisher","first-page":"1749","DOI":"10.1016\/S0140-6736(12)60437-1","volume":"379","author":"DT Tan","year":"2012","unstructured":"Tan, D. T., Dart, J. K., Holland, E. J. & Kinoshita, S. Corneal transplantation. Lancet 379, 1749\u20131761 (2012).","journal-title":"Lancet"},{"key":"BFsrep29769_CR4","doi-asserted-by":"publisher","first-page":"2239","DOI":"10.1016\/j.ophtha.2012.06.012","volume":"119","author":"M Ang","year":"2012","unstructured":"Ang, M. et al. Endothelial cell loss and graft survival after Descemet\u2019s stripping automated endothelial keratoplasty and penetrating keratoplasty. Ophthalmology 119, 2239\u20132244 (2012).","journal-title":"Ophthalmology"},{"key":"BFsrep29769_CR5","doi-asserted-by":"publisher","first-page":"e741","DOI":"10.1016\/j.ajo.2009.05.028","volume":"148","author":"DC Han","year":"2009","unstructured":"Han, D. C., Mehta, J. S., Por, Y. M., Htoon, H. M. & Tan, D. T. Comparison of outcomes of lamellar keratoplasty and penetrating keratoplasty in keratoconus. Am J Ophthalmol 148, 744\u2013751 e741 (2009).","journal-title":"Am J Ophthalmol"},{"key":"BFsrep29769_CR6","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1016\/j.survophthal.2014.05.001","volume":"59","author":"A Rio-Cristobal","year":"2014","unstructured":"Rio-Cristobal, A. & Martin, R. Corneal assessment technologies: current status. Surv Ophthalmol 59, 599\u2013614 (2014).","journal-title":"Surv Ophthalmol"},{"key":"BFsrep29769_CR7","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1167\/iovs.11-8386","volume":"53","author":"M Ang","year":"2012","unstructured":"Ang, M. et al. Anterior segment optical coherence tomography study of the cornea and anterior segment in adult ethnic South Asian Indian eyes. Invest Ophthalmol Vis Sci. 53, 120\u2013125 (2012).","journal-title":"Invest Ophthalmol Vis Sci."},{"key":"BFsrep29769_CR8","doi-asserted-by":"publisher","first-page":"7738","DOI":"10.1167\/iovs.10-6925","volume":"52","author":"MJ Girard","year":"2011","unstructured":"Girard, M. J., Strouthidis, N. G., Ethier, C. R. & Mari, J. M. Shadow removal and contrast enhancement in optical coherence tomography images of the human optic nerve head. Invest Ophthalmol Vis Sci. 52, 7738\u20137748 (2011).","journal-title":"Invest Ophthalmol Vis Sci."},{"key":"BFsrep29769_CR9","doi-asserted-by":"publisher","first-page":"2238","DOI":"10.1167\/iovs.12-11327","volume":"54","author":"JM Mari","year":"2013","unstructured":"Mari, J. M., Strouthidis, N. G., Park, S. C. & Girard, M. J. Enhancement of lamina cribrosa visibility in optical coherence tomography images using adaptive compensation. Invest Ophthalmol Vis Sci. 54, 2238\u20132247 (2013).","journal-title":"Invest Ophthalmol Vis Sci."},{"key":"BFsrep29769_CR10","doi-asserted-by":"publisher","first-page":"e54473","DOI":"10.1371\/journal.pone.0054473","volume":"8","author":"L Liu","year":"2013","unstructured":"Liu, L. et al. Method for quantitative study of airway functional microanatomy using micro-optical coherence tomography. PloS one 8, e54473 (2013).","journal-title":"PloS one"},{"key":"BFsrep29769_CR11","doi-asserted-by":"publisher","first-page":"1010","DOI":"10.1038\/nm.2409","volume":"17","author":"L Liu","year":"2011","unstructured":"Liu, L. et al. Imaging the subcellular structure of human coronary atherosclerosis using micro-optical coherence tomography. Nature Medicine 17, 1010\u20131014 (2011).","journal-title":"Nature Medicine"},{"key":"BFsrep29769_CR12","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1165\/rcmb.2013-0499MA","volume":"51","author":"L Liu","year":"2014","unstructured":"Liu, L. et al. An autoregulatory mechanism governing mucociliary transport is sensitive to mucus load. American journal of respiratory cell and molecular biology 51, 485\u2013493 (2014).","journal-title":"American journal of respiratory cell and molecular biology"},{"key":"BFsrep29769_CR13","doi-asserted-by":"publisher","first-page":"e54473","DOI":"10.1371\/journal.pone.0054473","volume":"8","author":"L Liu","year":"2013","unstructured":"Liu, L. et al. Method for Quantitative Study of Airway Functional Microanatomy Using Micro-Optical Coherence Tomography. Plos One 8, e54473 (2013).","journal-title":"Plos One"},{"key":"BFsrep29769_CR14","doi-asserted-by":"publisher","first-page":"1010","DOI":"10.1038\/nm.2409","volume":"17","author":"L Liu","year":"2011","unstructured":"Liu, L. et al. Imaging the subcellular structure of human coronary atherosclerosis using micro-optical coherence tomography. Nat Med. 17, 1010\u20131014 (2011).","journal-title":"Nat Med."},{"key":"BFsrep29769_CR15","doi-asserted-by":"publisher","first-page":"6727","DOI":"10.1364\/OL.39.006727","volume":"39(23)","author":"D Cui","year":"2014","unstructured":"Cui, D., Liu, X. & Zhang, J. et al. Dual spectrometer system with spectral compounding for 1-\u00b5m optical coherence tomography in vivo. Opt. Lett. 39(23), 6727\u201330 (2014).","journal-title":"Opt. Lett."},{"key":"BFsrep29769_CR16","doi-asserted-by":"publisher","first-page":"26521","DOI":"10.1364\/OE.23.026521","volume":"23","author":"X Liu","year":"2015","unstructured":"Liu, X., Chen, S., Cui, D., Yu, X. & Liu, L. Spectral estimation optical coherence tomography for axial super-resolution. Optics Express 23, 26521\u201326532 (2015).","journal-title":"Optics Express"},{"key":"BFsrep29769_CR17","first-page":"1222","volume":"19","author":"SB Han","year":"2013","unstructured":"Han, S. B. et al. A mouse model of corneal endothelial decompensation using cryoinjury. Mol Vis 19, 1222\u20131230 (2013).","journal-title":"Mol Vis"},{"key":"BFsrep29769_CR18","first-page":"683","volume":"20","author":"L Bredow","year":"2014","unstructured":"Bredow, L., Schwartzkopff, J. & Reinhard, T. Regeneration of corneal endothelial cells following keratoplasty in rats with bullous keratopathy. Mol Vis. 20, 683\u2013690 (2014).","journal-title":"Mol Vis."},{"key":"BFsrep29769_CR19","doi-asserted-by":"crossref","unstructured":"Han, S. B. et al. Mice with a Targeted Disruption of Slc4a11 Model the Progressive Corneal Changes of Congenital Hereditary Endothelial Dystrophy. Invest Ophthalmol Vis Sci. (2013).","DOI":"10.1167\/iovs.13-12089"},{"key":"BFsrep29769_CR20","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1186\/1756-0500-6-176","volume":"6","author":"GS Peh","year":"2013","unstructured":"Peh, G. S. et al. Optimization of human corneal endothelial cell culture: density dependency of successful cultures in vitro. BMC Res Notes 6, 176 (2013).","journal-title":"BMC Res Notes"},{"key":"BFsrep29769_CR21","doi-asserted-by":"publisher","first-page":"682","DOI":"10.1016\/j.exer.2005.09.006","volume":"82","author":"DV Patel","year":"2006","unstructured":"Patel, D. V., Phua, Y. S. & McGhee, C. N. Clinical and microstructural analysis of patients with hyper-reflective corneal endothelial nuclei imaged by in vivo confocal microscopy. Exp Eye Res. 82, 682\u2013687 (2006).","journal-title":"Exp Eye Res."},{"key":"BFsrep29769_CR22","doi-asserted-by":"publisher","first-page":"1864","DOI":"10.1364\/OL.18.001864","volume":"18","author":"EA Swanson","year":"1993","unstructured":"Swanson, E. A. et al. In vivo retinal imaging by optical coherence tomography. Opt Lett 18, 1864\u20131866 (1993).","journal-title":"Opt Lett"},{"key":"BFsrep29769_CR23","doi-asserted-by":"publisher","first-page":"1740","DOI":"10.1016\/j.ophtha.2015.05.017","volume":"122","author":"M Ang","year":"2015","unstructured":"Ang, M. et al. Optical Coherence Tomography Angiography for Anterior Segment Vasculature Imaging. Ophthalmology 122, 1740\u20131747 (2015).","journal-title":"Ophthalmology"},{"key":"BFsrep29769_CR24","doi-asserted-by":"publisher","first-page":"616","DOI":"10.1136\/bjophthalmol-2015-307338","volume":"100(5)","author":"M Ang","year":"2016","unstructured":"Ang, M., Cai, Y., Shahipasand, S. et al. En face optical coherence tomography angiography for corneal neovascularisation. Br J Ophthalmol 100(5), 616\u201321 (2016).","journal-title":"Br J Ophthalmol"},{"key":"BFsrep29769_CR25","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1167\/tvst.4.3.3","volume":"4","author":"MJ Girard","year":"2015","unstructured":"Girard, M. J. et al. Enhancement of Corneal Visibility in Optical Coherence Tomography Images Using Corneal Adaptive Compensation. Transl Vis Sci Technol 4, 3 (2015).","journal-title":"Transl Vis Sci Technol"},{"key":"BFsrep29769_CR26","doi-asserted-by":"publisher","first-page":"502","DOI":"10.1038\/86589","volume":"7","author":"W Drexler","year":"2001","unstructured":"Drexler, W. et al. Ultrahigh-resolution ophthalmic optical coherence tomography. Nat Med. 7, 502\u2013507 (2001).","journal-title":"Nat Med."},{"key":"BFsrep29769_CR27","doi-asserted-by":"publisher","first-page":"1027","DOI":"10.1001\/archopht.125.8.1027","volume":"125","author":"V Christopoulos","year":"2007","unstructured":"Christopoulos, V. et al. In vivo corneal high-speed, ultra high-resolution optical coherence tomography. Arch Ophthalmol 125, 1027\u20131035 (2007).","journal-title":"Arch Ophthalmol"},{"key":"BFsrep29769_CR28","doi-asserted-by":"publisher","first-page":"e1221","DOI":"10.1016\/j.ajo.2014.08.024","volume":"158","author":"M Ang","year":"2014","unstructured":"Ang, M. et al. Endothelial keratoplasty after failed penetrating keratoplasty: an alternative to repeat penetrating keratoplasty. Am J Ophthalmol 158, 1221-1227 e1221 (2014).","journal-title":"Am J Ophthalmol"},{"key":"BFsrep29769_CR29","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1136\/bjophthalmol-2015-306837","volume":"100","author":"M Ang","year":"2016","unstructured":"Ang, M., Wilkins, M. R., Mehta, J. S. & Tan, D. Descemet membrane endothelial keratoplasty. Br J Ophthalmol 100, 15\u201321 (2016).","journal-title":"Br J Ophthalmol"},{"key":"BFsrep29769_CR30","doi-asserted-by":"publisher","first-page":"e262","DOI":"10.1016\/j.ajo.2013.03.020","volume":"156","author":"M Ang","year":"2013","unstructured":"Ang, M., Sng, C. C., Chee, S. P., Tan, D. T. & Mehta, J. S. Outcomes of corneal transplantation for irreversible corneal decompensation secondary to corneal endotheliitis in Asian eyes. Am J Ophthalmol 156, 260\u2013266 e262 (2013).","journal-title":"Am J Ophthalmol"},{"key":"BFsrep29769_CR31","doi-asserted-by":"publisher","first-page":"1361","DOI":"10.1038\/nbt892","volume":"21","author":"JG Fujimoto","year":"2003","unstructured":"Fujimoto, J. G. Optical coherence tomography for ultrahigh resolution in vivo imaging. Nature Biotechnology 21, 1361\u20131367 (2003).","journal-title":"Nature Biotechnology"},{"key":"BFsrep29769_CR32","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\u20134725 (2012).","journal-title":"Optics Express"},{"key":"BFsrep29769_CR33","doi-asserted-by":"publisher","first-page":"2450","DOI":"10.1364\/OL.31.002450","volume":"31","author":"RA Leitgeb","year":"2006","unstructured":"Leitgeb, R. A., Villiger, M., Bachmann, A. H., Steinmann, L. & Lasser, T. Extended focus depth for Fourier domain optical coherence microscopy. Opt. Lett. 31, 2450\u20132452 (2006).","journal-title":"Opt. Lett."},{"key":"BFsrep29769_CR34","doi-asserted-by":"publisher","first-page":"26956","DOI":"10.1364\/OE.22.026956","volume":"22","author":"X Yu","year":"2014","unstructured":"Yu, X. et al. Depth extension and sidelobe suppression in optical coherence tomography using pupil filters. Optics Express 22, 26956\u201326966 (2014).","journal-title":"Optics Express"},{"key":"BFsrep29769_CR35","doi-asserted-by":"publisher","first-page":"2375","DOI":"10.1364\/OL.32.002375","volume":"32","author":"L Liu","year":"2007","unstructured":"Liu, L., Liu, C., Howe, W. C., Sheppard, C. J. R. & Chen, N. Binary-phase spatial filter for real-time swept-source optical coherence microscopy. Optics Letters 32, 2375\u20132377 (2007).","journal-title":"Optics Letters"},{"key":"BFsrep29769_CR36","doi-asserted-by":"publisher","first-page":"957","DOI":"10.1364\/OPEX.13.000957","volume":"13","author":"M Sarunic","year":"2005","unstructured":"Sarunic, M., Choma, M. A., Yang, C. & Izatt, J. A. Instantaneous complex conjugate resolved spectral domain and swept-source OCT using 3x3 fiber couplers. Optics Express 13, 957\u2013967 (2005).","journal-title":"Optics Express"},{"key":"BFsrep29769_CR37","doi-asserted-by":"publisher","first-page":"041202","DOI":"10.1117\/1.2764461","volume":"12","author":"M Akiba","year":"2007","unstructured":"Akiba, M. et al. Ultrahigh-resolution imaging of human donor cornea using full-field optical coherence tomography. J Biomed Opt. 12, 041202 (2007).","journal-title":"J Biomed Opt."},{"key":"BFsrep29769_CR38","doi-asserted-by":"publisher","first-page":"5333","DOI":"10.1364\/OL.39.005333","volume":"39(18)","author":"DJ Fechtig","year":"2014","unstructured":"Fechtig, D. J., Schmoll, T., Grajciar, B. et al. Line-field parallel swept source interferometric imaging at up to 1 MHz. Opt. Lett. 39(18), 5333\u20136 (2014).","journal-title":"Opt. Lett."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep29769","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep29769.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep29769.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T19:38:23Z","timestamp":1672861103000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep29769"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,7,15]]},"references-count":38,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2016,9,30]]}},"alternative-id":["BFsrep29769"],"URL":"https:\/\/doi.org\/10.1038\/srep29769","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,7,15]]},"assertion":[{"value":"23 March 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 June 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 July 2016","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"29769"}}