{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T13:21:33Z","timestamp":1762867293424,"version":"3.37.3"},"reference-count":18,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,11,9]],"date-time":"2017-11-09T00:00:00Z","timestamp":1510185600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2017,11,9]],"date-time":"2017-11-09T00:00:00Z","timestamp":1510185600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1054712"],"award-info":[{"award-number":["APP1054712"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001108","name":"The Ophthalmic Research Institute of Australia","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001108","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Doc Ophthalmol"],"published-print":{"date-parts":[[2018,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Purpose<\/jats:title>\n            <jats:p>To characterize the ultrastructural and functional correlates of hydroxychloroquine (HCQ)-induced subclinical bull\u2019s eye lesion seen on near-infrared reflectance (NIR) imaging.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>An asymptomatic 54-year-old male taking HCQ presented with paracentral ring-like scotoma, abnormal multifocal electroretinography (mfERG) and preserved ellipsoid zone on optical coherence tomography (OCT). Dense raster OCT was performed to create <jats:italic>en face<\/jats:italic> reflectivity maps of the interdigitation zone. Macular Integrity Assessment (MAIA) microperimetry and mfERG findings were compared with NIR imaging, <jats:italic>en face<\/jats:italic> OCT, retinal thickness profiles and wave-guiding cone density maps derived from flood-illumination adaptive optics (AO) retinal photography.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>The bull\u2019s eye lesion is an oval annular zone of increased reflectivity on NIR with an outer diameter of 1450\u00a0\u00b5m. This region corresponds exactly to an area of preserved interdigitation zone reflectivity in <jats:italic>en face<\/jats:italic> OCT images and of normal cone density on AO imaging. Immediately surrounding the bull\u2019s eye lesion is an annular zone (3\u00b0\u201312\u00b0 eccentricity) of depressed retinal sensitivity on MAIA and reduced amplitude density on mfERG. Wave-guiding cone density at 2\u00b0 temporal was 25,400 per mm<jats:sup>2<\/jats:sup>. This declined rapidly to 12,900 and 1200 per mm<jats:sup>2<\/jats:sup> at 3\u00b0 and 4\u00b0.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>Multimodal imaging illustrated pathology in the area surrounding the NIR bull\u2019s eye, characterized by reduced reflectance, wave-guiding cone density and retinal function. Further studies are required to investigate whether the bull\u2019s eye on NIR imaging and <jats:italic>en face<\/jats:italic> OCT is prominent or consistent enough for diagnostic use.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1007\/s10633-017-9615-9","type":"journal-article","created":{"date-parts":[[2017,11,9]],"date-time":"2017-11-09T09:02:54Z","timestamp":1510218174000},"page":"57-68","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Perifoveal interdigitation zone loss in hydroxychloroquine toxicity leads to subclinical bull\u2019s eye lesion appearance on near-infrared reflectance imaging"],"prefix":"10.1007","volume":"136","author":[{"given":"Avenell L.","family":"Chew","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danuta M.","family":"Sampson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Enid","family":"Chelva","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jane C.","family":"Khan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fred K.","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2017,11,9]]},"reference":[{"key":"9615_CR1","doi-asserted-by":"publisher","first-page":"521","DOI":"10.2147\/OPTH.S76963","volume":"9","author":"KL Wong","year":"2015","unstructured":"Wong KL, Pautler SE, Browning DJ (2015) Near-infrared reflectance bull\u2019s eye maculopathy as an early indication of hydroxychloroquine toxicity. Clin Ophthalmol 9:521\u2013525","journal-title":"Clin Ophthalmol"},{"key":"9615_CR2","first-page":"28","volume":"107","author":"KE Stepien","year":"2009","unstructured":"Stepien KE, Han DP, Schell J, Godara P, Rha J, Carroll J (2009) Spectral-domain optical coherence tomography and adaptive optics may detect hydroxychloroquine retinal toxicity before symptomatic vision loss. Trans Am Ophthalmol Soc 107:28\u201333","journal-title":"Trans Am Ophthalmol Soc"},{"key":"9615_CR3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s10633-011-9296-8","volume":"124","author":"DC Hood","year":"2012","unstructured":"Hood DC, Bach M, Brigell M, Keating D, Kondo M, Lyons JS, Marmor MF, McCulloch DL, Palmowski-Wolfe AM (2012) International society for clinical electrophysiology of vision. ISCEV standard for clinical multifocal electroretinography (mfERG) (2011 edition). Doc Ophthalmol 124:1\u201313","journal-title":"Doc Ophthalmol"},{"key":"9615_CR4","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1002\/jemt.20393","volume":"70","author":"P Th\u00e9venaz","year":"2007","unstructured":"Th\u00e9venaz P, Unser M (2007) User-friendly semiautomated assembly of accurate image mosaics in microscopy. Microsc Res Tech 70:135\u2013146","journal-title":"Microsc Res Tech"},{"key":"9615_CR5","doi-asserted-by":"publisher","first-page":"482","DOI":"10.1076\/clin.12.4.482.7241","volume":"12","author":"JR Crawford","year":"1998","unstructured":"Crawford JR, Howell DC (1998) Comparing an individual\u2019s test score against norms derived from small samples. Clin Neuropsychol 12:482\u2013486","journal-title":"Clin Neuropsychol"},{"key":"9615_CR6","volume-title":"Biometry: the principles and practice of statistics in biological research","author":"RR Sokal","year":"1995","unstructured":"Sokal RR, Rohlf FJ (1995) Biometry: the principles and practice of statistics in biological research. W.H. Freeman, New York"},{"key":"9615_CR7","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. Ophthalmology 121:1257\u20131262","journal-title":"Ophthalmology"},{"issue":"118\u2013123","key":"9615_CR8","first-page":"e1","volume":"159","author":"J Jacob","year":"2015","unstructured":"Jacob J, Paques M, Krivosic V, Dupas B, Couturier A, Kulcsar C, Tadayoni R, Massin P, Gaudric A (2015) Meaning of visualizing retinal cone mosaic on adaptive optics images. Am J Ophthalmol 159(118\u2013123):e1","journal-title":"Am J Ophthalmol"},{"key":"9615_CR9","doi-asserted-by":"publisher","first-page":"472","DOI":"10.1136\/bjo.2005.082487","volume":"90","author":"AG Robson","year":"2006","unstructured":"Robson AG, Saihan Z, Jenkins SA, Fitzke FW, Bird AC, Webster AR, Holder GE (2006) Functional characterisation and serial imaging of abnormal fundus autofluorescence in patients with retinitis pigmentosa and normal visual acuity. Br J Ophthalmol 90:472\u2013479","journal-title":"Br J Ophthalmol"},{"key":"9615_CR10","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1016\/j.ophtha.2010.11.017","volume":"118","author":"MF Marmor","year":"2011","unstructured":"Marmor MF, Kellner U, Lai TYY, Lyons JS, Mieler WF (2011) Revised recommendations on screening for chloroquine and hydroxychloroquine retinopathy. Ophthalmology 118:415\u2013422","journal-title":"Ophthalmology"},{"key":"9615_CR11","doi-asserted-by":"publisher","first-page":"4244","DOI":"10.1167\/iovs.14-14542","volume":"55","author":"D Scoles","year":"2014","unstructured":"Scoles D, Sulai YN, Langlo CS, Fishman GA, Curcio CA, Carroll J, Dubra A (2014) In vivo imaging of human cone photoreceptor inner segments. Invest Ophthalmol Vis Sci 55:4244\u20134251","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"9615_CR12","doi-asserted-by":"publisher","first-page":"1488","DOI":"10.1038\/eye.2014.229","volume":"28","author":"S Dabir","year":"2014","unstructured":"Dabir S, Mangalesh S, Kumar KA, Kummelil MK, Sinha Roy A, Shetty R (2014) Variations in the cone packing density with eccentricity in emmetropes. Eye 28:1488\u20131493","journal-title":"Eye"},{"key":"9615_CR13","doi-asserted-by":"publisher","first-page":"356","DOI":"10.1016\/j.ophtha.2014.07.056","volume":"122","author":"C Cukras","year":"2015","unstructured":"Cukras C, Huynh N, Vitale S, Wong WT, Ferris FL, Sieving PA (2015) Subjective and objective screening tests for hydroxychloroquine toxicity. Ophthalmology 122:356\u2013366","journal-title":"Ophthalmology"},{"key":"9615_CR14","doi-asserted-by":"publisher","first-page":"5751","DOI":"10.1167\/iovs.15-16954","volume":"56","author":"S Feng","year":"2015","unstructured":"Feng S, Gale MJ, Fay JD, Faridi A, Titus HE, Garg AK, Michaels KV, Erker LR, Peters D, Smith TB, Pennesi ME (2015) Assessment of different sampling methods for measuring and representing macular cone density using flood-illuminated adaptive optics. Invest Ophthalmol Vis Sci 56:5751\u20135763","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"9615_CR15","doi-asserted-by":"publisher","first-page":"4676","DOI":"10.1364\/BOE.6.004676","volume":"6","author":"DM Bukowska","year":"2015","unstructured":"Bukowska DM, Chew AL, Huynh E, Kashani I, Wan SL, Wan PM, Chen FK (2015) Semi-automated identification of cones in the human retina using circle Hough transform. Biomed Opt Express 6:4676\u20134693","journal-title":"Biomed Opt Express"},{"key":"9615_CR16","doi-asserted-by":"publisher","first-page":"7043","DOI":"10.1167\/iovs.15-17022","volume":"56","author":"C Miloudi","year":"2015","unstructured":"Miloudi C, Rossant F, Bloch I, Chaumette C, Leseigneur A, Sahel J-A, Meimon S, Mrejen S, Paques M (2015) The negative cone mosaic: a new manifestation of the optical Stiles\u2013Crawford effect in normal eyes. Invest Ophthalmol Vis Sci 56:7043\u20137050","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"9615_CR17","doi-asserted-by":"publisher","first-page":"2593","DOI":"10.1097\/IAE.0000000000000666","volume":"35","author":"MJ Heiferman","year":"2015","unstructured":"Heiferman MJ, Fernandes JK, Munk M, Mirza RG, Jampol LM, Fawzi AA (2015) Reticular pseudodrusen on infrared imaging are topographically distinct from subretinal drusenoid deposits on en face optical coherence tomography. Retina 35:2593\u20132603","journal-title":"Retina"},{"key":"9615_CR18","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 130:461\u2013469","journal-title":"Arch Ophthalmol"}],"container-title":["Documenta Ophthalmologica"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10633-017-9615-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10633-017-9615-9\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10633-017-9615-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,2]],"date-time":"2021-09-02T21:34:21Z","timestamp":1630618461000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10633-017-9615-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,11,9]]},"references-count":18,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2018,2]]}},"alternative-id":["9615"],"URL":"https:\/\/doi.org\/10.1007\/s10633-017-9615-9","relation":{},"ISSN":["0012-4486","1573-2622"],"issn-type":[{"type":"print","value":"0012-4486"},{"type":"electronic","value":"1573-2622"}],"subject":[],"published":{"date-parts":[[2017,11,9]]},"assertion":[{"value":"13 December 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 September 2017","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 November 2017","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"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":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of interest"}},{"value":"All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and\/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Informed consent was obtained from all individual participants included in the study.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}},{"value":"All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee (Sir Charles Gairdner Hospital Human Research Ethics Committee) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Statement of human rights"}},{"value":"This article does not contain any studies with animals performed by any of the authors.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Statement on the welfare of animals"}}]}}