{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T23:46:28Z","timestamp":1790034388899,"version":"4.0.1"},"reference-count":23,"publisher":"Springer Science and Business Media LLC","issue":"11","license":[{"start":{"date-parts":[[2024,6,5]],"date-time":"2024-06-05T00:00:00Z","timestamp":1717545600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,6,5]],"date-time":"2024-06-05T00:00:00Z","timestamp":1717545600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"University of Health Sciences"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Graefes Arch Clin Exp Ophthalmol"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Purpose<\/jats:title>\n                <jats:p>To evaluate the reflectivities of the retinal pigment epithelium (RPE), ellipsoid zone (EZ), and external limiting membrane (ELM) in the central fovea, perifoveal, and parafoveal regions with Optical Coherence Tomography (OCT) and the change in choroid vascular index (CVI) in patients using hydroxychloroquine (HCQ).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Sixty-one patients underwent HCQ treatment; age and sex-matched 44 control group subjects were included in the study. The RPE, EZ, and ELM reflectivities were measured with the ImageJ program at 5 points, and CVI was calculated.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>RPE, EZ, and ELM reflectivities in the central fovea were higher in the HCQ group than in the control group (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001, <jats:italic>p<\/jats:italic>\u2009=\u20090.013, <jats:italic>p<\/jats:italic>\u2009=\u20090.022). In the HCQ group, there was a decrease in RPE reflectivities in the temporal, nasal parafovea, and nasal perifovea (<jats:italic>p<\/jats:italic>\u2009=\u20090.001, <jats:italic>p<\/jats:italic>\u2009=\u20090.03, <jats:italic>p<\/jats:italic>\u2009=\u2009&lt;\u20090.001). EZ and ELM reflectivity in the nasal parafovea and nasal perifovea was lower in the patient group than in the control group (<jats:italic>p<\/jats:italic>\u2009=\u20090.007, <jats:italic>p<\/jats:italic>\u2009=\u20090.005, <jats:italic>p<\/jats:italic>\u2009=\u20090.009, <jats:italic>p<\/jats:italic>\u2009=\u20090.001). In the HCQ group, all absolute para and perifoveal reflectivities relative to the fovea decreased significantly more than in the control group (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>In patients who underwent HCQ treatment, there is a decrease in the reflectivities of the para and perifoveal RPE, EZ, and ELM compared to the fovea. This decrease is more pronounced than the decrease in reflectivity in the para and perifoveal regions compared to the fovea in people who do not use HCQ. This situation can be considered as a sign of toxicity that is a precursor to overt maculopathy.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00417-024-06532-8","type":"journal-article","created":{"date-parts":[[2024,6,5]],"date-time":"2024-06-05T09:02:05Z","timestamp":1717578125000},"page":"3543-3552","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Decreased peri-parafoveal RPE, EZ and ELM intensity: A novel predictive biomarker for hydroxychloroquine retinal toxicity"],"prefix":"10.1007","volume":"262","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2378-8462","authenticated-orcid":false,"given":"Aysun","family":"Yucel Gencoglu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7173-8617","authenticated-orcid":false,"given":"Abdullah","family":"A\u011f\u0131n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1621-9448","authenticated-orcid":false,"given":"Dilan","family":"Colak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6841-3969","authenticated-orcid":false,"given":"Yasemin","family":"Un","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8520-0073","authenticated-orcid":false,"given":"Yucel","family":"Ozturk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,6,5]]},"reference":[{"issue":"1","key":"6532_CR1","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1097\/iae.0000000000003638","volume":"43","author":"S Halouani","year":"2023","unstructured":"Halouani S, Le HM, Querques G, Borrelli E, Sacconi R, Battista M et al (2023) Choroidal Vascularity Index in hydroxychloroquine Toxic Retinopathy: a quantitative comparative analysis using enhanced depth imaging in spectral domain Optical Coherence Tomography. Retina 43(1):94\u2013101. https:\/\/doi.org\/10.1097\/iae.0000000000003638","journal-title":"Retina"},{"issue":"1","key":"6532_CR2","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. Archives Ophthalmol (Chicago Ill: 1960) 129(1):30\u201339. https:\/\/doi.org\/10.1001\/archophthalmol.2010.321","journal-title":"Archives Ophthalmol (Chicago Ill: 1960)"},{"issue":"6","key":"6532_CR3","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. https:\/\/doi.org\/10.1016\/j.ophtha.2016.01.058","journal-title":"Ophthalmology"},{"key":"6532_CR4","doi-asserted-by":"publisher","unstructured":"Rosenbaum JT, Costenbader KH, Desmarais J, Ginzler EM, Fett N, Goodman SM et al (2021) American College of Rheumatology, American Academy of Dermatology, Rheumatologic Dermatology Society, and American Academy of Ophthalmology 2020 Joint Statement on Hydroxychloroquine Use with respect to retinal toxicity. Arthritis Rheumatol 73(6):908\u2013911. https:\/\/doi.org\/10.1002\/art.41683","DOI":"10.1002\/art.41683"},{"issue":"1","key":"6532_CR5","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1038\/s41433-020-1038-2","volume":"35","author":"E Marshall","year":"2021","unstructured":"Marshall E, Robertson M, Kam S, Penwarden A, Riga P, Davies N (2021) Prevalence of hydroxychloroquine retinopathy using 2018 Royal College of ophthalmologists diagnostic criteria. Eye (Lond) 35(1):343\u2013348. https:\/\/doi.org\/10.1038\/s41433-020-1038-2","journal-title":"Eye (Lond)"},{"issue":"7","key":"6532_CR6","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. https:\/\/doi.org\/10.1016\/s0161-6420(02)01168-5","journal-title":"Ophthalmology"},{"issue":"12","key":"6532_CR7","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. https:\/\/doi.org\/10.1001\/jamaophthalmol.2014.3459","journal-title":"JAMA Ophthalmol"},{"key":"6532_CR8","doi-asserted-by":"publisher","unstructured":"Jallouli M, Galicier L, Zahr N, Auma\u00eetre O, Franc\u00e8s C, Le Guern V et al (2015) Determinants of hydroxychloroquine blood concentration variations in systemic lupus erythematosus. Arthritis Rheumatol 67(8):2176\u02132184. https:\/\/doi.org\/10.1002\/art.39194","DOI":"10.1002\/art.39194"},{"issue":"1","key":"6532_CR9","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1136\/bjophthalmol-2018-312363","volume":"103","author":"O Ugwuegbu","year":"2019","unstructured":"Ugwuegbu O, Uchida A, Singh RP, Beven L, Hu M, Kaiser S et al (2019) Quantitative assessment of outer retinal layers and ellipsoid zone mapping in hydroxychloroquine retinopathy. Br J Ophthalmol 103(1):3\u20137. https:\/\/doi.org\/10.1136\/bjophthalmol-2018-312363","journal-title":"Br J Ophthalmol"},{"key":"6532_CR10","doi-asserted-by":"publisher","first-page":"21090","DOI":"10.1038\/srep21090","volume":"6","author":"R Agrawal","year":"2016","unstructured":"Agrawal R, Gupta P, Tan KA, Cheung CM, Wong TY, Cheng CY (2016) Choroidal vascularity index as a measure of vascular status of the choroid: measurements in healthy eyes from a population-based study. Sci Rep 6:21090. https:\/\/doi.org\/10.1038\/srep21090","journal-title":"Sci Rep"},{"issue":"7","key":"6532_CR11","doi-asserted-by":"publisher","first-page":"1187","DOI":"10.1007\/s00296-021-05023-x","volume":"42","author":"A A\u011f\u0131n","year":"2022","unstructured":"A\u011f\u0131n A, Kaday\u0131f\u00e7\u0131lar S, Baytaro\u011flu A, Delikta\u015f \u00d6, Demir S, Sa\u011f E et al (2022) Assessment of systemic and ocular inflammation in juvenile idiopathic arthritis via choroidal vascularity index. Rheumatol Int 42(7):1187\u20131196. https:\/\/doi.org\/10.1007\/s00296-021-05023-x","journal-title":"Rheumatol Int"},{"issue":"2","key":"6532_CR12","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1097\/iae.0000000000003305","volume":"42","author":"R Sacconi","year":"2022","unstructured":"Sacconi R, Battista M, Borrelli E, Senni C, Tombolini B, Grosso D et al (2022) Choroidal vascularity index is associated with geographic atrophy progression. Retina 42(2):381\u2013387. https:\/\/doi.org\/10.1097\/iae.0000000000003305","journal-title":"Retina (Philadelphia Pa)"},{"issue":"6","key":"6532_CR13","doi-asserted-by":"publisher","first-page":"3893","DOI":"10.1167\/iovs.14-14447","volume":"55","author":"S Sonoda","year":"2014","unstructured":"Sonoda S, Sakamoto T, Yamashita T, Shirasawa M, Uchino E, Terasaki H et al (2014) Choroidal structure in normal eyes and after photodynamic therapy determined by binarization of optical coherence tomographic images. Invest Ophthalmol Vis Sci 55(6):3893\u20133899. https:\/\/doi.org\/10.1167\/iovs.14-14447","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"6532_CR14","doi-asserted-by":"publisher","first-page":"18","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 2:18. https:\/\/doi.org\/10.1186\/s40942-016-0042-y","journal-title":"Int J Retina Vitreous"},{"issue":"11","key":"6532_CR15","doi-asserted-by":"publisher","first-page":"1600","DOI":"10.1136\/bjophthalmol-2018-313350","volume":"103","author":"ST Garrity","year":"2019","unstructured":"Garrity ST, Jung JY, Zambrowski O, Pichi F, Su D, Arya M et al (2019) Early hydroxychloroquine retinopathy: optical coherence tomography abnormalities preceding Humphrey visual field defects. Br J Ophthalmol 103(11):1600\u20131604. https:\/\/doi.org\/10.1136\/bjophthalmol-2018-313350","journal-title":"Br J Ophthalmol"},{"issue":"3","key":"6532_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. https:\/\/doi.org\/10.1097\/IAE.0000000000002408","journal-title":"Retina"},{"issue":"10","key":"6532_CR17","doi-asserted-by":"publisher","first-page":"1941","DOI":"10.1097\/IAE.0000000000001036","volume":"36","author":"YS Modi","year":"2016","unstructured":"Modi YS, Au A, Parikh VS, Ehlers JP, Schachat AP, Singh RP (2016) Volumetric single-layer inner retinal analysis in patients with Hydroxychloroquine Toxicity. Retina 36(10):1941\u20131950. https:\/\/doi.org\/10.1097\/IAE.0000000000001036","journal-title":"Retina"},{"issue":"12","key":"6532_CR18","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1167\/iovs.62.12.28","volume":"62","author":"E Borrelli","year":"2021","unstructured":"Borrelli E, Battista M, Cascavilla ML, Vigano C, Borghesan F, Nicolini N et al (2021) Impact of structural changes on multifocal Electroretinography in patients with Use of Hydroxychloroquine. Invest Ophthalmol Vis Sci 62(12):28. https:\/\/doi.org\/10.1167\/iovs.62.12.28","journal-title":"Invest Ophthalmol Vis Sci"},{"issue":"3","key":"6532_CR19","doi-asserted-by":"publisher","first-page":"1506","DOI":"10.1167\/iovs.11-9231","volume":"53","author":"T Murakami","year":"2012","unstructured":"Murakami T, Nishijima K, Akagi T, Uji A, Horii T, Ueda-Arakawa N et al (2012) Optical coherence tomographic reflectivity of photoreceptors beneath cystoid spaces in diabetic macular edema. Invest Ophthalmol Vis Sci 53(3):1506\u20131511. https:\/\/doi.org\/10.1167\/iovs.11-9231","journal-title":"Invest Ophthalmol Vis Sci"},{"issue":"13","key":"6532_CR20","doi-asserted-by":"publisher","first-page":"9703","DOI":"10.1167\/iovs.11-8650","volume":"52","author":"DC Hood","year":"2011","unstructured":"Hood DC, Zhang X, Ramachandran R, Talamini CL, Raza A, Greenberg JP et al (2011) The inner segment\/outer segment border seen on optical coherence tomography is less intense in patients with diminished cone function. Invest Ophthalmol Vis Sci 52(13):9703\u20139709. https:\/\/doi.org\/10.1167\/iovs.11-8650","journal-title":"Invest Ophthalmol Vis Sci"},{"issue":"5","key":"6532_CR21","doi-asserted-by":"publisher","first-page":"283","DOI":"10.4274\/tjo.galenos.2020.21456","volume":"50","author":"B Yilmaz Tugan","year":"2020","unstructured":"Yilmaz Tugan B, Karabas L, Yenihayat F, Subasi S, Kesim E, Ozkan B (2020) Correlation of visual recovery and increased Ellipsoid Zone Reflectivity after successful macular hole surgery. Turk J Ophthalmol 50(5):283\u2013287. https:\/\/doi.org\/10.4274\/tjo.galenos.2020.21456","journal-title":"Turk J Ophthalmol"},{"issue":"9","key":"6532_CR22","doi-asserted-by":"publisher","first-page":"1126","DOI":"10.1038\/eye.2014.147","volume":"28","author":"I Toprak","year":"2014","unstructured":"Toprak I, Yaylali V, Yildirim C (2014) Decreased photoreceptor inner segment\/outer segment junction reflectivity in patients with idiopathic epimacular membrane. Eye (Lond) 28(9):1126\u20131130. https:\/\/doi.org\/10.1038\/eye.2014.147","journal-title":"Eye (Lond)"},{"key":"6532_CR23","doi-asserted-by":"publisher","DOI":"10.1038\/s41433-023-02747-x","author":"N Hasan","year":"2024","unstructured":"Hasan N, Driban M, Mohammed AR, Schwarz S, Yoosuf S, Barthelmes D et al (2024) Effects of hydroxychloroquine therapy on choroidal volume and choroidal vascularity index. Eye (Lond) 38(3):620\u2013624. https:\/\/doi.org\/10.1038\/s41433-023-02747-x","journal-title":"Eye (Lond)"}],"container-title":["Graefe's Archive for Clinical and Experimental Ophthalmology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00417-024-06532-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00417-024-06532-8\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00417-024-06532-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,23]],"date-time":"2024-11-23T13:02:45Z","timestamp":1732366965000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00417-024-06532-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,5]]},"references-count":23,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2024,11]]}},"alternative-id":["6532"],"URL":"https:\/\/doi.org\/10.1007\/s00417-024-06532-8","relation":{},"ISSN":["0721-832X","1435-702X"],"issn-type":[{"value":"0721-832X","type":"print"},{"value":"1435-702X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,5]]},"assertion":[{"value":"2 February 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 May 2024","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 May 2024","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 June 2024","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study protocol was approved by Haydarpasa Numune Training and Research Hospital Clinical Research Ethics Committee (HNEAH-KAEK 2023\/KK\/101).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Informed consent was waived due to the retrospective nature of this study.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}},{"value":"The authors declare that they have no conflict of interest.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}