{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T12:04:52Z","timestamp":1756382692980,"version":"3.37.3"},"reference-count":12,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2021,11,11]],"date-time":"2021-11-11T00:00:00Z","timestamp":1636588800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,11,11]],"date-time":"2021-11-11T00:00:00Z","timestamp":1636588800000},"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":["Doc Ophthalmol"],"published-print":{"date-parts":[[2022,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Purpose<\/jats:title>\n                <jats:p>Multifocal electroretinogram (mfERG) shows great utility as a screening tool to detect early hydroxychloroquine (HCQ) retinopathy, but its widespread use is limited by the lack of accessibility and long test duration. In this study, we evaluated a novel concentric 5-ring mfERG stimulus to provide a simplified and rapid protocol for screening HCQ toxicity.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Patients referred for HCQ retinopathy screening were consented to this observational cross-sectional study. Patients with amblyopia, high refractive error (more than 8 diopters), other retinal diseases precluding appropriate evaluation or history of retinal surgery were excluded. The data were collected from patients undergoing HCQ screening at a single center from July 2019 to March 2020. Patients were tested with the new concentric 5-ring mfERG stimulus, standard 61-hexagon mfERG stimulus, spectral domain optical coherence tomography and automated 10-2 visual fields. For the main outcome, the 5-ring mfERG was compared to 61-hexagon stimulus to determine the time-to-test completion and assess the association between ring (R1\u2013R5) amplitude and ring ratio compared against cumulative dose, dose by real body weight and duration of therapy using Pearson correlation.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>In total, 52 patients (104 eyes; 5 males and 47 females) were recruited with a mean age of 59\u00a0years (range 23\u201385\u00a0years). The 5-ring protocol was markedly quicker to perform (1.3\u2009\u00b1\u20090.2\u00a0min; mean (SD)) compared to the 61-hexagon protocol (5.2\u2009\u00b1\u20090.6\u00a0min), <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001; <jats:italic>n<\/jats:italic>\u2009=\u200910 patients. The new R2\/R5 ring ratio showed a moderate correlation with daily dose (<jats:italic>r<\/jats:italic>\u2009=\u2009\u2212\u20090.640), cumulative dose (<jats:italic>r<\/jats:italic>\u2009=\u2009\u2212\u20090.581) and duration of therapy (<jats:italic>r<\/jats:italic>\u2009=\u2009\u2212\u20090.417). Similar correlations were observed with the new R2\/R4 ring ratio which were not significantly different from the new R2\/R5 correlation coefficients. The new R2\/R5 ring ratio demonstrated a stronger correlation with daily (<jats:italic>p<\/jats:italic>\u2009=\u20090.002) and cumulative dose (<jats:italic>p<\/jats:italic>\u2009=\u20090.0001) compared to the 61-hexagon stimulus.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>In this exploratory study, our novel 5-ring mfERG protocol significantly shortened data acquisition time while providing comparable results to the standard 61-hexagon stimulus for detecting HCQ-induced electrophysiological changes that are correlated with HCQ dosages and treatment duration. Our protocol has the potential to be more clinically practical by simplifying routine screening.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s10633-021-09858-4","type":"journal-article","created":{"date-parts":[[2021,11,11]],"date-time":"2021-11-11T08:02:45Z","timestamp":1636617765000},"page":"117-124","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A novel 5-ring multifocal electroretinography stimulus for detecting hydroxychloroquine retinal toxicity"],"prefix":"10.1007","volume":"144","author":[{"given":"Adrian","family":"Tsang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0877-5631","authenticated-orcid":false,"given":"Pushpinder","family":"Kanda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chloe","family":"Gottlieb","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gianni","family":"Virgili","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lynca","family":"Kantungane","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stuart","family":"Coupland","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,11,11]]},"reference":[{"key":"9858_CR1","doi-asserted-by":"publisher","first-page":"653","DOI":"10.1007\/s40261-018-0656-y","volume":"38","author":"D Plantone","year":"2018","unstructured":"Plantone D, Koudriavtseva T (2018) Current and future use of chloroquine and hydroxychloroquine in infectious, immune, neoplastic, and neurological diseases: a mini-review. Clin Drug Investig 38:653\u2013671. https:\/\/doi.org\/10.1007\/s40261-018-0656-y","journal-title":"Clin Drug Investig"},{"key":"9858_CR2","doi-asserted-by":"publisher","first-page":"5214751","DOI":"10.1155\/2020\/5214751","volume":"2020","author":"DZ Wondafrash","year":"2020","unstructured":"Wondafrash DZ, Desalegn TZ, Yimer EM, Tsige AG, Adamu BA, Zewdie KA (2020) Potential effect of hydroxychloroquine in diabetes mellitus: a systematic review on preclinical and clinical trial studies. J Diabetes Res 2020:5214751. https:\/\/doi.org\/10.1155\/2020\/5214751","journal-title":"J Diabetes Res"},{"key":"9858_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 123:1386\u20131394. https:\/\/doi.org\/10.1016\/j.ophtha.2016.01.058","journal-title":"Ophthalmology"},{"key":"9858_CR4","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 132:1453\u20131460. https:\/\/doi.org\/10.1001\/jamaophthalmol.2014.3459","journal-title":"JAMA Ophthalmol"},{"key":"9858_CR5","doi-asserted-by":"publisher","first-page":"875","DOI":"10.1007\/s00347-007-1560-7","volume":"104","author":"K Ruther","year":"2007","unstructured":"Ruther K, Foerster J, Berndt S, Schroeter J (2007) Chloroquine\/hydroxychloroquine: Variability of retinotoxic cumulative doses. Ophthalmologe 104:875\u2013879. https:\/\/doi.org\/10.1007\/s00347-007-1560-7","journal-title":"Ophthalmologe"},{"key":"9858_CR6","doi-asserted-by":"publisher","first-page":"1105","DOI":"10.1001\/jamaophthalmol.2014.1099","volume":"132","author":"MF Marmor","year":"2014","unstructured":"Marmor MF, Hu J (2014) Effect of disease stage on progression of hydroxychloroquine retinopathy. JAMA Ophthalmol 132:1105\u20131112. https:\/\/doi.org\/10.1001\/jamaophthalmol.2014.1099","journal-title":"JAMA Ophthalmol"},{"key":"9858_CR7","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1136\/bjophthalmol-2013-303897","volume":"98","author":"S Kellner","year":"2014","unstructured":"Kellner S, Weinitz S, Farmand G, Kellner U (2014) Cystoid macular oedema and epiretinal membrane formation during progression of chloroquine retinopathy after drug cessation. Br J Ophthalmol 98:200\u2013206. https:\/\/doi.org\/10.1136\/bjophthalmol-2013-303897","journal-title":"Br J Ophthalmol"},{"issue":"1239\u201351","key":"9858_CR8","doi-asserted-by":"publisher","first-page":"e4","DOI":"10.1016\/j.ophtha.2015.02.011","volume":"122","author":"AC Tsang","year":"2015","unstructured":"Tsang AC, Ahmadi Pirshahid S, Virgili G, Gottlieb CC, Hamilton J, Coupland SG (2015) Hydroxychloroquine and chloroquine retinopathy: A systematic review evaluating the multifocal electroretinogram as a screening test. Ophthalmology 122(1239\u201351):e4. https:\/\/doi.org\/10.1016\/j.ophtha.2015.02.011","journal-title":"Ophthalmology"},{"key":"9858_CR9","doi-asserted-by":"publisher","first-page":"1257","DOI":"10.1016\/j.ophtha.2013.12.002","volume":"121","author":"MF Marmor","year":"2014","unstructured":"Marmor MF, Melles RB (2014) Disparity between visual fields and optical coherence tomography in hydroxychloroquine retinopathy. 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Am J Ophthalmol 143:801\u2013809. https:\/\/doi.org\/10.1016\/j.ajo.2006.12.042","journal-title":"Am J Ophthalmol"},{"key":"9858_CR12","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1007\/s10633-014-9474-6","volume":"130","author":"VC Greenstein","year":"2015","unstructured":"Greenstein VC, Amaro-Quireza L, Abraham ES, Ramachandran R, Tsang SH, Hood DC (2015) A comparison of structural and functional changes in patients screened for hydroxychloroquine retinopathy. Doc Ophthalmol 130:13\u201323. https:\/\/doi.org\/10.1007\/s10633-014-9474-6","journal-title":"Doc Ophthalmol"}],"container-title":["Documenta Ophthalmologica"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10633-021-09858-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10633-021-09858-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10633-021-09858-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,22]],"date-time":"2022-04-22T16:05:53Z","timestamp":1650643553000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10633-021-09858-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,11]]},"references-count":12,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2022,4]]}},"alternative-id":["9858"],"URL":"https:\/\/doi.org\/10.1007\/s10633-021-09858-4","relation":{},"ISSN":["0012-4486","1573-2622"],"issn-type":[{"type":"print","value":"0012-4486"},{"type":"electronic","value":"1573-2622"}],"subject":[],"published":{"date-parts":[[2021,11,11]]},"assertion":[{"value":"14 April 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 October 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 November 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":"All authors declare that there is no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"All procedures performed in this study were approved and performed in accordance with the ethical standards of the Ottawa Health Science Network Research Ethics Board. This study adhered to the tenets of the Declaration of Helsinki.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Statement of human rights"}},{"value":"Not applicable.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Statement on the welfare of animals"}},{"value":"All procedures performed in this study were approved by the Ottawa Health Science Network Research Ethics Board. This study adhered to the tenets of the Declaration of Helsinki.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"Informed consent was obtained from all patients participating in this study as approved by the Ottawa Health Science Network Research Ethics Board.","order":6,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}}]}}