{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T23:39:56Z","timestamp":1779147596881,"version":"3.51.4"},"reference-count":16,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,4,7]],"date-time":"2021-04-07T00:00:00Z","timestamp":1617753600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,4,7]],"date-time":"2021-04-07T00:00:00Z","timestamp":1617753600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001700","name":"Japanese Ministry of Education, Science, Sports and Culture","doi-asserted-by":"crossref","award":["#20K18394"],"award-info":[{"award-number":["#20K18394"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001700","name":"Japanese Ministry of Education, Science, Sports and Culture","doi-asserted-by":"crossref","award":["#26462668"],"award-info":[{"award-number":["#26462668"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100007572","name":"Akaeda Medical Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007572","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Ophthalmol"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Chronic ocular graft-versus-host disease (oGVHD) is an ocular comorbidity of graft-versus-host disease (GVHD) that usually occurs concurrently with systemic manifestations. Failure to detect and treat oGVHD in its early stages may lead to progression of ocular signs and symptoms leading to oGVHD that is refractory to conventional treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case presentation<\/jats:title>\n                    <jats:p>We report the clinical course of a 19-year-old male and a 59-year-old female with severe and progressive chronic oGVHD without concurrent systemic signs of chronic graft-versus-host disease (cGVHD). Although their systemic conditions had been stable, both suffered from severe oGVHD and were referred to our clinic. Both cases exhibited marked improvement in conjunctival inflammation and fibrotic changes after amniotic membrane transplantation (AMT). Both cases underwent keratoplasty eventually to stabilize ocular surface conditions and to improve visual function.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We reported the clinical outcomes of 2 cases of chronic oGVHD without concurrent systemic comorbidities that were treated with AMT. The clinician should be aware that cGVHD may persist in target organs even in the absence of concurrent systemic comorbidities following seemingly successful systemic treatment. A multidisciplinary team approach is essential in the early detection and therapeutic intervention for chronic oGVHD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12886-021-01925-3","type":"journal-article","created":{"date-parts":[[2021,4,7]],"date-time":"2021-04-07T10:03:26Z","timestamp":1617789806000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Two case reports of continued progression of chronic ocular graft-versus-host disease without concurrent systemic comorbidities treated by amniotic membrane transplantation"],"prefix":"10.1186","volume":"21","author":[{"given":"Hideto","family":"Ikarashi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0188-1255","authenticated-orcid":false,"given":"Naohiko","family":"Aketa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eisuke","family":"Shimizu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoji","family":"Takano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tetsuya","family":"Kawakita","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuichi","family":"Uchino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yukihiro","family":"Matsumoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junko","family":"Ogawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuo","family":"Tsubota","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoko","family":"Ogawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,4,7]]},"reference":[{"issue":"2","key":"1925_CR1","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1097\/ICO.0000000000001109","volume":"36","author":"Y Rapoport","year":"2017","unstructured":"Rapoport Y, Freeman T, Koyama T, Engelhardt BG, Jagasia M, Savani BN, et al. Validation of international chronic ocular graft-versus-host disease (GVHD) group diagnostic criteria as a chronic ocular GVHD-specific metric. Cornea. 2017;36(2):258\u201363. https:\/\/doi.org\/10.1097\/ICO.0000000000001109.","journal-title":"Cornea"},{"issue":"5","key":"1925_CR2","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1055\/s-0035-1545836","volume":"232","author":"T Dietrich-Ntoukas","year":"2015","unstructured":"Dietrich-Ntoukas T. Clinical signs of ocular graft-versus-host disease. Klin Monatsbl Augenheilkd. 2015;232(5):647\u201351. https:\/\/doi.org\/10.1055\/s-0035-1545836.","journal-title":"Klin Monatsbl Augenheilkd"},{"issue":"10","key":"1925_CR3","doi-asserted-by":"publisher","first-page":"1125","DOI":"10.1136\/bjo.83.10.1125","volume":"83","author":"Y Ogawa","year":"1999","unstructured":"Ogawa Y, Okamoto S, Wakui M, Watanabe R, Yamada M, Yoshino M, et al. Dry eye after haematopoietic stem cell transplantation. Br J Ophthalmol. 1999;83(10):1125\u201330. https:\/\/doi.org\/10.1136\/bjo.83.10.1125.","journal-title":"Br J Ophthalmol"},{"issue":"3","key":"1925_CR4","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1016\/j.survophthal.2012.08.004","volume":"58","author":"H Shikari","year":"2013","unstructured":"Shikari H, Antin JH, Dana R. Ocular graft-versus-host disease: a review. Surv Ophthalmol. 2013;58(3):233\u201351. https:\/\/doi.org\/10.1016\/j.survophthal.2012.08.004.","journal-title":"Surv Ophthalmol"},{"issue":"3","key":"1925_CR5","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1016\/j.bbmt.2014.12.001","volume":"21","author":"MH Jagasia","year":"2015","unstructured":"Jagasia MH, Greinix HT, Arora M, Williams KM, Wolff D, Cowen EW, et al. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. the 2014 diagnosis and staging working group report. Biol Blood Marrow Transplant. 2015;21(3):389\u2013401.e381. https:\/\/doi.org\/10.1016\/j.bbmt.2014.12.001.","journal-title":"Biol Blood Marrow Transplant"},{"issue":"5","key":"1925_CR6","doi-asserted-by":"crossref","first-page":"428","DOI":"10.3928\/1542-8877-19980501-12","volume":"29","author":"H Fujishima","year":"1998","unstructured":"Fujishima H, Shimazaki J, Shinozaki N, Tsubota K. Trabeculectomy with the use of amniotic membrane for uncontrollable glaucoma. Ophthalmic Surg Lasers. 1998;29(5):428\u201331.","journal-title":"Ophthalmic Surg Lasers"},{"issue":"7","key":"1925_CR7","doi-asserted-by":"publisher","first-page":"723","DOI":"10.1097\/01.ico.0000126319.28390.f0","volume":"23","author":"Y Takano","year":"2004","unstructured":"Takano Y, Fukagawa K, Miyake-Kashima M, Tanaka M, Asano-Kato N, Dogru M, et al. Dramatic healing of an allergic corneal ulcer persistent for 6 months by amniotic membrane patching in a patient with atopic keratoconjunctivitis: a case report. Cornea. 2004;23(7):723\u20135. https:\/\/doi.org\/10.1097\/01.ico.0000126319.28390.f0.","journal-title":"Cornea"},{"issue":"3","key":"1925_CR8","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1002\/(SICI)1097-4652(199906)179:3<325::AID-JCP10>3.0.CO;2-X","volume":"179","author":"SC Tseng","year":"1999","unstructured":"Tseng SC, Li DQ, Ma X. Suppression of transforming growth factor-beta isoforms, TGF-beta receptor type II, and myofibroblast differentiation in cultured human corneal and limbal fibroblasts by amniotic membrane matrix. J Cell Physiol. 1999;179(3):325\u201335. https:\/\/doi.org\/10.1002\/(SICI)1097-4652(199906)179:3<325::AID-JCP10>3.0.CO;2-X.","journal-title":"J Cell Physiol"},{"issue":"1","key":"1925_CR9","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/S0002-9394(14)71962-2","volume":"122","author":"K Tsubota","year":"1996","unstructured":"Tsubota K, Satake Y, Ohyama M, et al. Surgical reconstruction of the ocular surface in advanced ocular cicatricial pemphigoid and Stevens-Johnson syndrome. Am J Ophthalmol. 1996;122(1):38\u201352. https:\/\/doi.org\/10.1016\/S0002-9394(14)71962-2.","journal-title":"Am J Ophthalmol"},{"issue":"5","key":"1925_CR10","doi-asserted-by":"publisher","first-page":"975","DOI":"10.1016\/S0161-6420(00)00026-9","volume":"107","author":"SG Honavar","year":"2000","unstructured":"Honavar SG, Bansal AK, Sangwan VS, Rao GN. Amniotic membrane transplantation for ocular surface reconstruction in Stevens-Johnson syndrome. Ophthalmology. 2000;107(5):975\u20139. https:\/\/doi.org\/10.1016\/S0161-6420(00)00026-9.","journal-title":"Ophthalmology"},{"issue":"2","key":"1925_CR11","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1177\/112067210101100215","volume":"11","author":"C Peris-Martinez","year":"2001","unstructured":"Peris-Martinez C, Menezo JL, Diaz-Llopis M, et al. Multilayer amniotic membrane transplantation in severe ocular graft versus host disease. Eur J Ophthalmol. 2001;11(2):183\u20136. https:\/\/doi.org\/10.1177\/112067210101100215.","journal-title":"Eur J Ophthalmol"},{"issue":"4","key":"1925_CR12","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1016\/s0929-6646(09)60125-x","volume":"105","author":"PT Yeh","year":"2006","unstructured":"Yeh PT, Hou YC, Lin WC, Wang IJ, Hu FR. Recurrent corneal perforation and acute calcareous corneal degeneration in chronic graft-versus-host disease. J Formos Med Assoc. 2006;105(4):334\u20139. https:\/\/doi.org\/10.1016\/s0929-6646(09)60125-x.","journal-title":"J Formos Med Assoc"},{"key":"1925_CR13","doi-asserted-by":"publisher","first-page":"ORSFh1","DOI":"10.1167\/iovs.15-17637","volume":"57","author":"SC Tseng","year":"2016","unstructured":"Tseng SC. HC-HA\/PTX3 purified from amniotic membrane as novel regenerative matrix: insight into relationship between inflammation and regeneration. Invest Ophthalmol Vis Sci. 2016;57:ORSFh1\u20138.","journal-title":"Invest Ophthalmol Vis Sci"},{"issue":"1","key":"1925_CR14","doi-asserted-by":"publisher","first-page":"42195","DOI":"10.1038\/srep42195","volume":"7","author":"Y Ogawa","year":"2017","unstructured":"Ogawa Y, He H, Mukai S, Imada T, Nakamura S, Su CW, et al. Heavy chain-hyaluronan\/pentraxin 3 from amniotic membrane suppresses inflammation and scarring in murine lacrimal gland and conjunctiva of chronic graft-versus-host disease. Sci Rep. 2017;7(1):42195. https:\/\/doi.org\/10.1038\/srep42195.","journal-title":"Sci Rep"},{"issue":"1","key":"1925_CR15","doi-asserted-by":"publisher","first-page":"10720","DOI":"10.1038\/s41598-017-10237-w","volume":"7","author":"J He","year":"2017","unstructured":"He J, Ogawa Y, Mukai S, Saijo-Ban Y, Kamoi M, Uchino M, et al. In vivo confocal microscopy evaluation of ocular surface in ocular chronic graft-versus-host disease. Sci Rep. 2017 Sep;7(1):10720. https:\/\/doi.org\/10.1038\/s41598-017-10237-w.","journal-title":"Sci Rep"},{"key":"1925_CR16","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1016\/j.ajo.2017.09.029","volume":"184","author":"N Aketa","year":"2017","unstructured":"Aketa N, Yamaguchi T, Asato T, Yagi-Yaguchi Y, Suzuki T, Higa K, et al. Elevated aqueous cytokine levels in eyes with ocular surface diseases. Am J Ophthalmol. 2017;184:42\u201351. https:\/\/doi.org\/10.1016\/j.ajo.2017.09.029.","journal-title":"Am J Ophthalmol"}],"container-title":["BMC Ophthalmology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12886-021-01925-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s12886-021-01925-3\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12886-021-01925-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,5,1]],"date-time":"2021-05-01T04:27:47Z","timestamp":1619843267000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcophthalmol.biomedcentral.com\/articles\/10.1186\/s12886-021-01925-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,7]]},"references-count":16,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["1925"],"URL":"https:\/\/doi.org\/10.1186\/s12886-021-01925-3","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-47594\/v1","asserted-by":"object"}]},"ISSN":["1471-2415"],"issn-type":[{"value":"1471-2415","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,7]]},"assertion":[{"value":"10 September 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 March 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 April 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The Ethical Committee at Keio University School of Medicine approved this study (No. 20170350).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Written informed consent was obtained from the patients for publication of this Case Report and any accompanying images and videos. A copy of the written consent is available for review by the Editor of this journal.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"Not applicable.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"164"}}