{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T04:32:30Z","timestamp":1787632350854,"version":"build-2736575974"},"reference-count":29,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"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>\n          <jats:p>This single-center, retrospective study analyzed the development of macular neovascularization (MNV) in patients with chronic central serous chorioretinopathy (CSCR) during a treatment-free follow-up period and the factors associated with its development. In total, 236 patients (280 eyes, 149 males and 87 females, mean age 55.3\u2009\u00b1\u200913.9 years) with treatment-na\u00efve CSCR with no MNV detected on multimodal imaging who were observed for &gt;\u20096 months were assessed. The association between age, sex, the presence of MNV, central choroidal thickness (CCT), the presence of the double-layer sign (DLS), and the cumulative duration of the persistence of serous retinal detachment (SRD) was also analyzed to determine the visual outcome before the onset of MNV. Twenty-eight (10%) eyes developed MNV over a mean follow-up period of 48.3\u2009\u00b1\u200943.3 months. The persistence of SRD for \u2265\u20096 months (<jats:italic>p<\/jats:italic>\u2009=\u20090.003) and presence of DLS measuring\u2009\u2265\u20091000\u00a0\u03bcm in length and &lt;\u2009100\u00a0\u03bcm in height (<jats:italic>p<\/jats:italic>\u2009=\u20090.040) exhibited significant associations with the development of MNV. Furthermore, the persistence of SRD for \u2265\u20096 months showed a significant association with logMAR visual acuity loss of \u2265\u20090.3 (<jats:italic>p<\/jats:italic>\u2009=\u20090.0009). Thus, the persistence of SRD for \u2265\u20096 months and numerically defined DLS were identified as predictors for the development of MNV in patients with CSCR.<\/jats:p>","DOI":"10.1038\/s41598-025-17499-9","type":"journal-article","created":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T22:12:08Z","timestamp":1756764728000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Predictive factors for the development of macular neovascularization in chronic central serous chorioretinopathy"],"prefix":"10.1038","volume":"15","author":[{"given":"Marie","family":"Kitano","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuichiro","family":"Aoki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kohdai","family":"Kitamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryo","family":"Terao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuya","family":"Inoue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryo","family":"Obata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiko","family":"Azuma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,9,1]]},"reference":[{"key":"17499_CR1","doi-asserted-by":"publisher","first-page":"100865","DOI":"10.1016\/j.preteyeres.2020.100865","volume":"79","author":"R Kaye","year":"2020","unstructured":"Kaye, R. et al. Central serous chorioretinopathy: an update on risk factors, pathophysiology and imaging modalities. Prog Retin Eye Res. 79, 100865 (2020).","journal-title":"Prog Retin Eye Res."},{"key":"17499_CR2","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1016\/j.preteyeres.2015.05.003","volume":"48","author":"A Daruich","year":"2015","unstructured":"Daruich, A. et al. Central serous chorioretinopathy: recent findings and new physiopathology hypothesis. Prog Retin Eye Res. 48, 82\u2013118 (2015).","journal-title":"Prog Retin Eye Res."},{"key":"17499_CR3","doi-asserted-by":"publisher","first-page":"128","DOI":"10.3928\/23258160-20160126-05","volume":"47","author":"TE De Carlo","year":"2016","unstructured":"De Carlo, T. E. et al. Vascularization of irregular retinal pigment epithelial detachments in chronic central serous chorioretinopathy evaluated with OCT angiography. Ophthalmic Surg. Lasers Imaging Retina. 47, 128\u2013133 (2016).","journal-title":"Ophthalmic Surg. Lasers Imaging Retina"},{"key":"17499_CR4","doi-asserted-by":"publisher","first-page":"2489","DOI":"10.1097\/IAE.0000000000000655","volume":"35","author":"J Chhablani","year":"2015","unstructured":"Chhablani, J. et al. Outcomes of treatment of choroidal neovascularization associated with central serous chorioretinopathy with intravitreal antiangiogenic agents. Retina 35, 2489\u20132497 (2015).","journal-title":"Retina"},{"key":"17499_CR5","doi-asserted-by":"publisher","first-page":"101236","DOI":"10.1016\/j.preteyeres.2024.101236","volume":"101","author":"HMA Feenstra","year":"2024","unstructured":"Feenstra, H. M. A. et al. Central serous chorioretinopathy: an evidence-based treatment guideline. Prog Retin Eye Res. 101, 101236 (2024).","journal-title":"Prog Retin Eye Res."},{"key":"17499_CR6","doi-asserted-by":"publisher","first-page":"101843","DOI":"10.1016\/j.ajoc.2023.101843","volume":"30","author":"PC Staropoli","year":"2023","unstructured":"Staropoli, P. C., Iyer, P., Gregori, G., Rosenfeld, P. J. & Flynn, H. W. Identification of macular neovascularization in central serous chorioretinopathy using swept-source OCT angiography. Am. J. Ophthalmol. Case Rep. 30, 101843 (2023).","journal-title":"Am. J. Ophthalmol. Case Rep."},{"key":"17499_CR7","first-page":"680","volume":"128","author":"Japanese Ophthalmological Society","year":"2024","unstructured":"Japanese Ophthalmological Society. Guidelines for the management of neovascular age-related macular degeneration. Jpn J. Ophthalmol. 128, 680\u2013698 (2024).","journal-title":"Jpn J. Ophthalmol."},{"key":"17499_CR8","doi-asserted-by":"publisher","first-page":"21876","DOI":"10.1038\/s41598-023-49153-7","volume":"13","author":"K Azuma","year":"2023","unstructured":"Azuma, K. et al. Long-term visual outcomes in pachychoroid spectrum diseases and its associating factors of eyes with chronic central serous chorioretinopathy. Sci. Rep. 13, 21876 (2023).","journal-title":"Sci. Rep."},{"key":"17499_CR9","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1016\/j.ajo.2018.06.009","volume":"193","author":"C Shiragami","year":"2018","unstructured":"Shiragami, C. et al. Clinical features of central serous chorioretinopathy with type 1 choroidal neovascularization. Am. J. Ophthalmol. 193, 80\u201386 (2018).","journal-title":"Am. J. Ophthalmol."},{"key":"17499_CR10","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1007\/s40123-021-00336-3","volume":"10","author":"A Arrigo","year":"2021","unstructured":"Arrigo, A. et al. Structural OCT parameters associated with treatment response and macular neovascularization onset in central serous chorioretinopathy. Ophthalmol. Ther. 10, 289\u2013298 (2021).","journal-title":"Ophthalmol. Ther."},{"key":"17499_CR11","doi-asserted-by":"publisher","first-page":"1934","DOI":"10.3390\/jcm9061934","volume":"9","author":"AM Hagag","year":"2020","unstructured":"Hagag, A. M. et al. Multimodal imaging in the management of choroidal neovascularization secondary to central serous chorioretinopathy. J. Clin. Med. 9, 1934 (2020).","journal-title":"J. Clin. Med."},{"key":"17499_CR12","doi-asserted-by":"publisher","first-page":"488","DOI":"10.5301\/ejo.5000036","volume":"22","author":"J Pikkel","year":"2012","unstructured":"Pikkel, J. & Rumelt, S. Intravitreal bevacizumab for choroidal neovascularization secondary to laser photocoagulation for central serous chorioretinopathy. Eur. J. Ophthalmol. 22, 488\u2013491 (2012).","journal-title":"Eur. J. Ophthalmol."},{"key":"17499_CR13","doi-asserted-by":"publisher","first-page":"901","DOI":"10.1097\/IAE.0000000000000804","volume":"36","author":"J Chhablani","year":"2016","unstructured":"Chhablani, J. et al. Antiangiogenics in choroidal neovascularization associated with laser in central serous chorioretinopathy. Retina 36, 901\u2013908 (2016).","journal-title":"Retina"},{"key":"17499_CR14","doi-asserted-by":"publisher","first-page":"733","DOI":"10.1038\/s41433-020-01390-0","volume":"36","author":"Y Wang","year":"2022","unstructured":"Wang, Y. et al. Small dome-shaped pigment epithelium detachment in polypoidal choroidal vasculopathy: an under-recognized sign of polypoidal lesions on optical coherence tomography? Eye (Lond). 36, 733\u2013741 (2022).","journal-title":"Eye (Lond)"},{"key":"17499_CR15","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1016\/j.ajo.2021.10.021","volume":"236","author":"AM Hagag","year":"2022","unstructured":"Hagag, A. M., Rasheed, R., Chandra, S., Jeffery, G. & Sivaprasad, S. The diagnostic accuracy of double-layer sign in detection of macular neovascularization secondary to central serous chorioretinopathy. Am. J. Ophthalmol. 236, 271\u2013280 (2022).","journal-title":"Am. J. Ophthalmol."},{"key":"17499_CR16","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1097\/01.iae.0000249386.63482.05","volume":"27","author":"T Sato","year":"2007","unstructured":"Sato, T., Kishi, S., Watanabe, G., Matsumoto, H. & Mukai, R. Tomographic features of branching vascular networks in polypoidal choroidal vasculopathy. Retina 27, 589\u2013594 (2007).","journal-title":"Retina"},{"key":"17499_CR17","doi-asserted-by":"publisher","first-page":"6274","DOI":"10.3390\/jcm11216274","volume":"11","author":"M Sasaki","year":"2022","unstructured":"Sasaki, M., Kawasaki, R. & Yanagi, Y. Early stages of age-related macular degeneration: racial\/ethnic differences and proposal of a new classification incorporating emerging concept of choroidal pathology. J. Clin. Med. 11, 6274 (2022).","journal-title":"J. Clin. Med."},{"key":"17499_CR18","doi-asserted-by":"publisher","first-page":"e000976","DOI":"10.1136\/bmjophth-2022-000976","volume":"7","author":"X Zhou","year":"2022","unstructured":"Zhou, X. et al. Risk factors and characteristics of central serous chorioretinopathy with later development of macular neovascularisation detected on OCT angiography: A retrospective multicentre observational study. BMJ Open. Ophthalmol. 7, e000976 (2022).","journal-title":"BMJ Open. Ophthalmol."},{"key":"17499_CR19","doi-asserted-by":"publisher","first-page":"899","DOI":"10.1001\/jamaophthalmol.2015.1320","volume":"133","author":"MA Bonini Filho","year":"2015","unstructured":"Bonini Filho, M. A. et al. Association of choroidal neovascularization and central serous chorioretinopathy with optical coherence tomography angiography. JAMA Ophthalmol. 133, 899\u2013906 (2015).","journal-title":"JAMA Ophthalmol."},{"key":"17499_CR20","doi-asserted-by":"publisher","first-page":"e26980","DOI":"10.1097\/MD.0000000000026980","volume":"100","author":"RY Kim","year":"2021","unstructured":"Kim, R. Y. et al. Clinical course after the onset of choroidal neovascularization in eyes with central serous chorioretinopathy. Med. (Baltim). 100, e26980 (2021).","journal-title":"Med. (Baltim)"},{"key":"17499_CR21","doi-asserted-by":"publisher","first-page":"576","DOI":"10.1016\/j.ophtha.2018.12.048","volume":"126","author":"S Mrejen","year":"2019","unstructured":"Mrejen, S. et al. Long-term visual outcomes and causes of vision loss in chronic central serous chorioretinopathy. Ophthalmology 126, 576\u2013588 (2019).","journal-title":"Ophthalmology"},{"key":"17499_CR22","doi-asserted-by":"publisher","first-page":"3927","DOI":"10.1038\/s41598-019-40406-y","volume":"9","author":"GI Lee","year":"2019","unstructured":"Lee, G. I. et al. Risk factors and outcomes of choroidal neovascularization secondary to central serous chorioretinopathy. Sci. Rep. 9, 3927 (2019).","journal-title":"Sci. Rep."},{"key":"17499_CR23","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1016\/j.ophtha.2019.11.007","volume":"127","author":"C Narita","year":"2020","unstructured":"Narita, C. et al. Structural OCT signs suggestive of subclinical nonexudative macular neovascularization in eyes with large Drusen. Ophthalmology 127, 637\u2013647 (2020).","journal-title":"Ophthalmology"},{"key":"17499_CR24","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1016\/j.oret.2023.10.006","volume":"8","author":"L Csincsik","year":"2024","unstructured":"Csincsik, L. et al. The double layer sign is highly predictive of progression to exudation in Age-Related macular degeneration. Ophthalmol. Retina. 8, 234\u2013245 (2024).","journal-title":"Ophthalmol. Retina"},{"key":"17499_CR25","doi-asserted-by":"publisher","first-page":"1829","DOI":"10.1097\/IAE.0b013e3182680a66","volume":"32","author":"AT Fung","year":"2012","unstructured":"Fung, A. T., Yannuzzi, L. A. & Freund, K. B. Type 1 (sub-retinal pigmentepithelial) neovascularization in central serous chorioretinopathy masquerading as neovascular age-related macular degeneration. Retina 32, 1829\u20131837 (2012).","journal-title":"Retina"},{"key":"17499_CR26","doi-asserted-by":"publisher","first-page":"848","DOI":"10.1136\/bjophthalmol-2014-306018","volume":"99","author":"JD Pitcher 3rd","year":"2015","unstructured":"Pitcher, J. D. 3rd, Witkin, A. J., DeCroos, F. C. & Ho, A. C. A prospective pilot study of intravitreal Aflibercept for the treatment of chronic central serous chorioretinopathy: the CONTAIN study. Br. J. Ophthalmol. 99, 848\u2013852 (2015).","journal-title":"Br. J. Ophthalmol."},{"key":"17499_CR27","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1016\/j.ajo.2025.04.005","volume":"276","author":"P Viggiano","year":"2025","unstructured":"Viggiano, P. et al. Choroidal layer analysis under flat irregular pigment epithelial detachments in central serous chorioretinopathy. Am. J. Ophthalmol. 276, 210\u2013217 (2025).","journal-title":"Am. J. Ophthalmol."},{"key":"17499_CR28","doi-asserted-by":"crossref","unstructured":"Viggiano, P. et al. Pachychoroid disease spectrum: how multimodal imaging and OCT angiography have improved our knowledge. Prog. Retin. Eye Res. 107, 101372 (2025).","DOI":"10.1016\/j.preteyeres.2025.101372"},{"key":"17499_CR29","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1097\/00006982-200202000-00004","volume":"22","author":"RH Loo","year":"2002","unstructured":"Loo, R. H. et al. Factors associated with reduced visual acuity during long-term follow-up of patients with idiopathic central serous chorioretinopathy. Retina 22, 19\u201324 (2002).","journal-title":"Retina"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-17499-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-17499-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-17499-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T01:55:55Z","timestamp":1757469355000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-17499-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,1]]},"references-count":29,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["17499"],"URL":"https:\/\/doi.org\/10.1038\/s41598-025-17499-9","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,1]]},"assertion":[{"value":"13 March 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 August 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 September 2025","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 authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"The study was conducted in accordance with the tenets of the Declaration of Helsinki and approved by the ethics committee of the Coordinating Center of the University of Tokyo. All patients provided written informed consent before participating in the study.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}}],"article-number":"32250"}}