{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T23:49:07Z","timestamp":1791676147865,"version":"4.3.4"},"reference-count":28,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T00:00:00Z","timestamp":1767830400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T00:00:00Z","timestamp":1767830400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Filling the Gap","award":["Filling the Gap"],"award-info":[{"award-number":["Filling the Gap"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Graefes Arch Clin Exp Ophthalmol"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>Hydroxychloroquine (HCQ) is a frequently used drug for a variety of rheumatological conditions. One significant adverse effect is HCQ retinopathy, which irreversibly affects the photoreceptor layer and retinal pigment epithelium, causing paracentral scotomas and potential visual loss. Retinal impairment is irreversible, even after termination of therapy. This study investigates the progression of the retinal destruction after drug cessation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Setting\/venue<\/jats:title>\n                    <jats:p>The study was performed at the Departments of Ophthalmology at Zurich University Hospital and Tel Aviv Sourasky Medical Center from January 2012 \u2013 December 2020.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In a multicenter retrospective observational design, we analyzed 25 lesions in 18 eyes of 11 patients with HCQ retinopathy. Patients were examined for retinal alterations using spectral-domain (SD) optical coherence tomography (OCT) scans (Heidelberg Engineering, Heidelberg Germany) at first diagnosis of HCQ retinopathy and at least one follow-up (minimum follow up 2 months duration, maximum follow up 5.5 years). Demographics and clinical aspects including age, ethnicity, therapy duration, indication, cumulative dosage, and follow-up interval were recorded. The lengths of the structural damage including ellipsoid zone defect and photoreceptor alterations were analyzed on OCT images.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Demographically, the average patient age was 53.0 years at time of enrollment. All patients were female. The cohort consisted of 54.5% non-Ashkenazi Caucasian and 18.2% Ashkenazi. Roughly half (54.5%) of the cohort held systemic lupus erythematosus (SLE) as a main diagnosis. The average daily dose of HCQ was 310\u00a0mg, with an average treatment duration of 15.6 years. Absolute increases in lesion size ranged from 7 to 552\u00a0\u03bcm (median change 99\u00a0\u03bcm). The average rate of progression in this cohort was 131.6\u00a0\u03bcm\/year in across all included eyes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our data elucidates the progression of HCQ-induced retinopathy in regard to SD-OCT detected structural changes of the retina after drug cessation. The study highlights the pivotal role of an early detection of retinopathy to reduce the potential risk of fovea-threatening progression as an irreversible side effect of the prevalent drug HCQ.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00417-025-07037-8","type":"journal-article","created":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T11:22:29Z","timestamp":1767871349000},"page":"975-982","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Progression of hydroxychloroquine-induced retinopathy after drug cessation"],"prefix":"10.1007","volume":"264","author":[{"given":"Richard B.","family":"Brown","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice M.","family":"Kitay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Driban","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dinah","family":"Zur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Kniestedt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Barthelmes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elham","family":"Sadeghi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jay K.","family":"Chhablani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3364-2232","authenticated-orcid":false,"given":"Mayss","family":"Al-Sheikh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,1,8]]},"reference":[{"issue":"3","key":"7037_CR1","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1080\/14740338.2017.1269168","volume":"16","author":"C Ponticelli","year":"2017","unstructured":"Ponticelli C, Moroni G (2017) Hydroxychloroquine in systemic lupus erythematosus (SLE). Expert Opin Drug Saf 16(3):411\u20139","journal-title":"Expert Opin Drug Saf"},{"key":"7037_CR2","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1007\/s12016-015-8469-8","volume":"49","author":"N Costedoat-Chalumeau","year":"2015","unstructured":"Costedoat-Chalumeau N, Dunogu\u00e9 B, Leroux G, Morel N, Jallouli M, Le Guern V et al (2015) A critical review of the effects of hydroxychloroquine and chloroquine on the eye. Clin Rev Allergy Immunol 49:317\u201326","journal-title":"Clin Rev Allergy Immunol"},{"issue":"8","key":"7037_CR3","doi-asserted-by":"publisher","first-page":"e12476","DOI":"10.15252\/emmm.202012476","volume":"12","author":"EL Nirk","year":"2020","unstructured":"Nirk EL, Reggiori F, Mauthe M (2020) Hydroxychloroquine in rheumatic autoimmune disorders and beyond. EMBO Mol Med 12(8):e12476","journal-title":"EMBO Mol Med"},{"issue":"6","key":"7037_CR4","doi-asserted-by":"publisher","first-page":"957","DOI":"10.1093\/rheumatology\/kev357","volume":"55","author":"HJ Ding","year":"2016","unstructured":"Ding HJ, Denniston AK, Rao VK, Gordon C (2016) Hydroxychloroquine-related retinal toxicity. Rheumatology 55(6):957\u2013967","journal-title":"Rheumatology"},{"key":"7037_CR5","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/8643174","author":"H Uslu","year":"2016","unstructured":"Uslu H, Gurler B, Yildirim A, Tatar MG, Aylin Kantarc\u0131 F, Goker H et al (2016) Effect of hydroxychloroquine on the retinal layers: a quantitative evaluation with spectral-domain optical coherence tomography. J Ophthalmol. https:\/\/doi.org\/10.1155\/2016\/8643174","journal-title":"J Ophthalmol"},{"key":"7037_CR6","doi-asserted-by":"crossref","unstructured":"Chen E, Brown DM, Benz MS, Fish RH, Wong TP, Kim RY et al (2010) Spectral domain optical coherence tomography as an effective screening test for hydroxychloroquine retinopathy (the flying saucer sign). Clin Ophthalmol. 1151\u20131158","DOI":"10.2147\/OPTH.S14257"},{"issue":"1","key":"7037_CR7","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1097\/IIO.0000000000000294","volume":"60","author":"M Dahrouj","year":"2020","unstructured":"Dahrouj M, Young L (2020) Hydroxychloroquine retinopathy in the era of advanced imaging modalities. Int Ophthalmol Clin 60(1):73\u201383","journal-title":"Int Ophthalmol Clin"},{"issue":"1","key":"7037_CR8","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1001\/archophthalmol.2010.321","volume":"129","author":"M Michaelides","year":"2011","unstructured":"Michaelides M, Stover NB, Francis PJ, Weleber RG (2011) Retinal toxicity associated with hydroxychloroquine and chloroquine: risk factors, screening, and progression despite cessation of therapy. Arch Ophthalmol 129(1):30\u201339","journal-title":"Arch Ophthalmol"},{"issue":"5","key":"7037_CR9","doi-asserted-by":"publisher","first-page":"1016","DOI":"10.1097\/IAE.0000000000002047","volume":"39","author":"SJ Ahn","year":"2019","unstructured":"Ahn SJ, Ryu SJ, Lim HW, Lee BR (2019) Toxic effects of hydroxychloroquine on the choroid: evidence from multimodal imaging. Retina 39(5):1016\u20131026","journal-title":"Retina"},{"issue":"6","key":"7037_CR10","doi-asserted-by":"publisher","first-page":"889","DOI":"10.1016\/j.ophtha.2020.10.029","volume":"128","author":"SJ Ahn","year":"2021","unstructured":"Ahn SJ, Seo EJ, Kim KE, Kim YJ, Lee BR, Kim JG et al (2021) Long-term progression of pericentral hydroxychloroquine retinopathy. Ophthalmology 128(6):889\u2013898","journal-title":"Ophthalmology"},{"issue":"6","key":"7037_CR11","doi-asserted-by":"publisher","first-page":"1386","DOI":"10.1016\/j.ophtha.2016.01.058","volume":"123","author":"MF Marmor","year":"2016","unstructured":"Marmor MF, Kellner U, Lai TY, Melles RB, Mieler WF (2016) Recommendations on screening for chloroquine and hydroxychloroquine retinopathy (2016 revision). Ophthalmology 123(6):1386\u20131394","journal-title":"Ophthalmology"},{"issue":"7","key":"7037_CR12","doi-asserted-by":"publisher","first-page":"1377","DOI":"10.1016\/S0161-6420(02)01168-5","volume":"109","author":"MF Marmor","year":"2002","unstructured":"Marmor MF, Carr RE, Easterbrook M, Farjo AA, Mieler WF (2002) Recommendations on screening for chloroquine and hydroxychloroquine retinopathy: a report by the American academy of ophthalmology. Ophthalmology 109(7):1377\u20131382","journal-title":"Ophthalmology"},{"issue":"7","key":"7037_CR13","doi-asserted-by":"publisher","first-page":"1321","DOI":"10.1016\/S0161-6420(03)00409-3","volume":"110","author":"I Mavrikakis","year":"2003","unstructured":"Mavrikakis I, Sfikakis PP, Mavrikakis E, Rougas K, Nikolaou A, Kostopoulos C et al (2003) The incidence of irreversible retinal toxicity in patients treated with hydroxychloroquine: a reappraisal. Ophthalmology 110(7):1321\u20136","journal-title":"Ophthalmology"},{"issue":"12","key":"7037_CR14","doi-asserted-by":"publisher","first-page":"1453","DOI":"10.1001\/jamaophthalmol.2014.3459","volume":"132","author":"RB Melles","year":"2014","unstructured":"Melles RB, Marmor MF (2014) The risk of toxic retinopathy in patients on long-term hydroxychloroquine therapy. JAMA Ophthalmol 132(12):1453\u20131460","journal-title":"JAMA Ophthalmol"},{"issue":"1","key":"7037_CR15","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s40942-016-0042-y","volume":"2","author":"DR Lally","year":"2016","unstructured":"Lally DR, Heier JS, Baumal C, Witkin AJ, Maler S, Shah CP et al (2016) Expanded spectral domain-OCT findings in the early detection of hydroxychloroquine retinopathy and changes following drug cessation. Int J Retina Vitreous 2(1):1\u201311","journal-title":"Int J Retina Vitreous"},{"issue":"3","key":"7037_CR16","doi-asserted-by":"publisher","first-page":"492","DOI":"10.1097\/IAE.0000000000002408","volume":"39","author":"BH Pham","year":"2019","unstructured":"Pham BH, Marmor MF (2019) Sequential changes in hydroxychloroquine retinopathy up to 20 years after stopping the drug: implications for mild versus severe toxicity. Retina 39(3):492\u2013501","journal-title":"Retina"},{"issue":"9","key":"7037_CR17","doi-asserted-by":"publisher","first-page":"1187","DOI":"10.1001\/jamaophthalmol.2013.4244","volume":"131","author":"M Mititelu","year":"2013","unstructured":"Mititelu M, Wong BJ, Brenner M, Bryar PJ, Jampol LM, Fawzi AA (2013) Progression of hydroxychloroquine toxic effects after drug therapy cessation: new evidence from multimodal imaging. JAMA Ophthalmol 131(9):1187\u20131197","journal-title":"JAMA Ophthalmol"},{"issue":"7","key":"7037_CR18","doi-asserted-by":"publisher","first-page":"1168","DOI":"10.1038\/s41433-018-0136-x","volume":"32","author":"IH Yusuf","year":"2018","unstructured":"Yusuf IH, Foot B, Galloway J, Ardern-Jones MR, Watson S-L, Yelf C et al (2018) The Royal college of ophthalmologists recommendations on screening for hydroxychloroquine and chloroquine users in the united kingdom: executive summary. Eye 32(7):1168\u20131173","journal-title":"Eye"},{"issue":"12","key":"7037_CR19","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1038\/s41584-018-0111-8","volume":"14","author":"A Jorge","year":"2018","unstructured":"Jorge A, Ung C, Young LH, Melles RB, Choi HK (2018) Hydroxychloroquine retinopathy\u2014implications of research advances for rheumatology care. Nat Rev Rheumatol 14(12):693\u2013703","journal-title":"Nat Rev Rheumatol"},{"key":"7037_CR20","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jaut.2018.11.001","volume":"96","author":"A Fava","year":"2019","unstructured":"Fava A, Petri M (2019) Systemic lupus erythematosus: diagnosis and clinical management. J Autoimmun 96:1\u201313","journal-title":"J Autoimmun"},{"key":"7037_CR21","doi-asserted-by":"publisher","DOI":"10.2147\/OPTH.S66527","author":"DJ Browning","year":"2014","unstructured":"Browning DJ, Lee C (2014) Relative sensitivity and specificity of 10\u2009\u2013\u20092 visual fields, multifocal electroretinography, and spectral domain optical coherence tomography in detecting hydroxychloroquine and chloroquine retinopathy. Clin Ophthalmol. https:\/\/doi.org\/10.2147\/OPTH.S66527","journal-title":"Clin Ophthalmol"},{"issue":"4","key":"7037_CR22","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1001\/archophthalmol.2011.371","volume":"130","author":"MF Marmor","year":"2012","unstructured":"Marmor MF (2012) Comparison of screening procedures in hydroxychloroquine toxicity. Arch Ophthalmol 130(4):461\u2013469","journal-title":"Arch Ophthalmol"},{"issue":"2","key":"7037_CR23","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1080\/17469899.2021.1851599","volume":"16","author":"PJ Murtagh","year":"2021","unstructured":"Murtagh PJ, Murphy ML, Smyth AC, McElnea EM, Fahy GT (2021) Improving ophthalmic screening for hydroxychloroquine associated retinopathy. Expert Rev Ophthalmol 16(2):133\u2013138","journal-title":"Expert Rev Ophthalmol"},{"key":"7037_CR24","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/ar2825","volume":"11","author":"JE Oliver","year":"2009","unstructured":"Oliver JE, Silman AJ (2009) Why are women predisposed to autoimmune rheumatic diseases? Arthritis Res Ther 11:1\u20139","journal-title":"Arthritis Res Ther"},{"issue":"8","key":"7037_CR25","doi-asserted-by":"publisher","first-page":"2176","DOI":"10.1002\/art.39194","volume":"67","author":"M Jallouli","year":"2015","unstructured":"Jallouli M, Galicier L, Zahr N, Aumaitre O, Frances C, Le Guern V et al (2015) Determinants of hydroxychloroquine blood concentration variations in systemic lupus erythematosus. Arthritis Rheumatol 67(8):2176\u201384","journal-title":"Arthritis Rheumatol"},{"key":"7037_CR26","doi-asserted-by":"publisher","first-page":"1853","DOI":"10.1007\/s10067-018-4116-0","volume":"37","author":"RB Melles","year":"2018","unstructured":"Melles RB, Jorge AM, Marmor MF, Zhang Y, Choi HK (2018) Sharp decline in hydroxychloroquine dosing\u2014analysis of 17,797 initiators from 2007 to 2016. Clin Rheumatol 37:1853\u20131859","journal-title":"Clin Rheumatol"},{"key":"7037_CR27","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1016\/j.ajo.2020.06.030","volume":"219","author":"DJ Browning","year":"2020","unstructured":"Browning DJ, Yokogawa N, Greenberg PB, Perlman E (2020) Rethinking the hydroxychloroquine dosing and retinopathy screening guidelines. Am J Ophthalmol 219:101\u2013106","journal-title":"Am J Ophthalmol"},{"key":"7037_CR28","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fmed.2022.1026934","volume":"9","author":"IH Yusuf","year":"2022","unstructured":"Yusuf IH, Charbel Issa P, Ahn SJ (2022) Novel imaging techniques for hydroxychloroquine retinopathy. Front Med 9:1\u201313","journal-title":"Front Med"}],"container-title":["Graefe's Archive for Clinical and Experimental Ophthalmology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00417-025-07037-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00417-025-07037-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00417-025-07037-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T23:05:48Z","timestamp":1791673548000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00417-025-07037-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,8]]},"references-count":28,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["7037"],"URL":"https:\/\/doi.org\/10.1007\/s00417-025-07037-8","relation":{},"ISSN":["0721-832X","1435-702X"],"issn-type":[{"value":"0721-832X","type":"print"},{"value":"1435-702X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,8]]},"assertion":[{"value":"22 May 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 October 2025","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 November 2025","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 January 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 October 2026","order":6,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Update","order":7,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"This article was originally published under the subscription model but it is now published under an Open Access license.","order":8,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Informed consent was obtained from all individual participants included in the study.","order":1,"name":"Ethics","label":"Informed consent","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All procedures performed in studies involving human participants were in accordance with the ethical standards of the Cantonal Ethics Committee Zurich (BASEC-Nr. 2018\u2009\u2212\u200901050) and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.","order":2,"name":"Ethics","label":"Ethical approval","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers\u2019 bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript.","order":3,"name":"Ethics","label":"Conflict of interest","group":{"name":"EthicsHeading","label":"Declarations"}}]}}