{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T20:24:31Z","timestamp":1792873471376,"version":"4.5.0"},"reference-count":47,"publisher":"American Society for Clinical Investigation","issue":"2","license":[{"start":{"date-parts":[[2019,3,19]],"date-time":"2019-03-19T00:00:00Z","timestamp":1552953600000},"content-version":"vor","delay-in-days":54,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,1,24]]},"abstract":"<jats:p>\n                    <jats:bold>BACKGROUND.<\/jats:bold>\n                    Oculocutaneous albinism (OCA) results in reduced melanin synthesis, skin hypopigmentation, increased risk of UV-induced malignancy, and developmental eye abnormalities affecting vision. No treatments exist. We have shown that oral nitisinone increases ocular and fur pigmentation in a mouse model of one form of albinism, OCA-1B, due to hypomorphic mutations in the\n                    <jats:italic>Tyrosinase<\/jats:italic>\n                    gene.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>METHODS.<\/jats:bold>\n                    In this open-label pilot study, 5 adult patients with OCA-1B established baseline measurements of iris, skin, and hair pigmentation and were treated over 12 months with 2 mg\/d oral nitisinone. Changes in pigmentation and visual function were evaluated at 3-month intervals.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>RESULTS.<\/jats:bold>\n                    The mean change in iris transillumination, a marker of melanin, from baseline was 1.0 \u00b1 1.54 points, representing no change. The method of iris transillumination grading showed a high intergrader reliability (intraclass correlation coefficient \u2265 0.88 at each visit). The number of letters read (visual acuity) improved significantly at month 12 for both eyes (right eye, OD, mean 4.2 [95% CI, 0.3, 8.1],\n                    <jats:italic>P<\/jats:italic>\n                    = 0.04) and left eye (OS, 5 [1.0, 9.1],\n                    <jats:italic>P<\/jats:italic>\n                    = 0.003). Skin pigmentation on the inner bicep increased (M index increase = 1.72 [0.03, 3.41],\n                    <jats:italic>P<\/jats:italic>\n                    = 0.047). Finally, hair pigmentation increased by both reflectometry (M index [17.3 {4.4, 30.2},\n                    <jats:italic>P<\/jats:italic>\n                    = 0.01]) and biochemically.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>CONCLUSION.<\/jats:bold>\n                    Nitisinone did not result in an increase in iris melanin content but may increase hair and skin pigmentation in patients with OCA-1B. The iris transillumination grading scale used in this study proved robust, with potential for use in future clinical trials.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>TRIAL REGISTRATION.<\/jats:bold>\n                    ClinicalTrials.gov NCT01838655.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>FUNDING.<\/jats:bold>\n                    Intramural program of the National Eye Institute.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.124387","type":"journal-article","created":{"date-parts":[[2019,1,23]],"date-time":"2019-01-23T11:01:58Z","timestamp":1548241318000},"source":"Crossref","is-referenced-by-count":32,"title":["One-year pilot study on the effects of nitisinone on melanin in patients with OCA-1B"],"prefix":"10.1172","volume":"4","author":[{"given":"David R.","family":"Adams","sequence":"first","affiliation":[{"name":"National Human Genome Research Institute, NIH, Department of Health and Human Services, Bethesda, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Supriya","family":"Menezes","sequence":"additional","affiliation":[{"name":"Emmes, Rockville, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramon","family":"Jauregui","sequence":"additional","affiliation":[{"name":"National Eye Institute and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zaheer M.","family":"Valivullah","sequence":"additional","affiliation":[{"name":"National Human Genome Research Institute, NIH, Department of Health and Human Services, Bethesda, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8557-5756","authenticated-orcid":true,"given":"Bradley","family":"Power","sequence":"additional","affiliation":[{"name":"National Human Genome Research Institute, NIH, Department of Health and Human Services, Bethesda, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Abraham","sequence":"additional","affiliation":[{"name":"Emmes, Rockville, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brett G.","family":"Jeffrey","sequence":"additional","affiliation":[{"name":"National Eye Institute and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angel","family":"Garced","sequence":"additional","affiliation":[{"name":"National Eye Institute and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramakrishna P.","family":"Alur","sequence":"additional","affiliation":[{"name":"National Eye Institute and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denise","family":"Cunningham","sequence":"additional","affiliation":[{"name":"National Eye Institute and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edythe","family":"Wiggs","sequence":"additional","affiliation":[{"name":"National Institute of Neurological Disease and Stroke, NIH, Department of Health and Human Services, Bethesda, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa A.","family":"Merideth","sequence":"additional","affiliation":[{"name":"National Human Genome Research Institute, NIH, Department of Health and Human Services, Bethesda, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei-Wen","family":"Chiang","sequence":"additional","affiliation":[{"name":"Molecular Vision Laboratory, Hillsboro, Oregon, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanna","family":"Bernstein","sequence":"additional","affiliation":[{"name":"Nutrition Department, NIH Clinical Center, Bethesda, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shosuke","family":"Ito","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Fujita Health University School of Health Sciences, Toyoake, Aichi, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1748-9001","authenticated-orcid":true,"given":"Kazumasa","family":"Wakamatsu","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Fujita Health University School of Health Sciences, Toyoake, Aichi, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rhona M.","family":"Jack","sequence":"additional","affiliation":[{"name":"Seattle Children\u2019s Hospital, Department of Pathology & Laboratory Medicine, Seattle, Washington, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendy J.","family":"Introne","sequence":"additional","affiliation":[{"name":"National Human Genome Research Institute, NIH, Department of Health and Human Services, Bethesda, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William A.","family":"Gahl","sequence":"additional","affiliation":[{"name":"National Human Genome Research Institute, NIH, Department of Health and Human Services, Bethesda, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian P.","family":"Brooks","sequence":"additional","affiliation":[{"name":"National Eye Institute and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2019,1,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1111\/pcmr.12167"},{"key":"B2","doi-asserted-by":"crossref","DOI":"10.1186\/1750-1172-2-43","article-title":"Oculocutaneous albinism","volume":"2","author":"Gr\u00f8nskov","year":"2007","journal-title":"Orphanet J Rare Dis"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22315"},{"key":"B4","doi-asserted-by":"crossref","DOI":"10.1155\/2014\/905472","article-title":"Mutational analysis of oculocutaneous albinism: a compact review","volume":"2014","author":"Kamaraj","year":"2014","journal-title":"Biomed Res Int"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2008.109"},{"key":"B6","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.04543","article-title":"An intracellular anion channel critical for pigmentation","volume":"3","author":"Bellono","year":"2014","journal-title":"Elife"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0129273"},{"issue":"Pt 2","key":"B8","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1042\/bj3550259","article-title":"The molecular basis of oculocutaneous albinism type 1 (OCA1): sorting failure and degradation of mutant tyrosinases results in a lack of pigmentation","volume":"355","author":"Toyofuku","year":"2001","journal-title":"Biochem J"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1111\/j.1751-1097.2007.00226.x"},{"key":"B10","doi-asserted-by":"crossref","DOI":"10.1155\/2015\/167847","article-title":"Oculocutaneous albinism and squamous cell carcinoma of the skin of the head and neck in sub-Saharan Africa","volume":"2015","author":"Lekalakala","year":"2015","journal-title":"J Skin Cancer"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/0190-9622(95)90352-6"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-3083.2012.04633.x"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.visres.2010.02.003"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1046\/j.1460-9568.2003.02929.x"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1097\/OPX.0b013e3181a5254c"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.13-13217"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1001\/archophthalmol.2008.550"},{"key":"B18","first-page":"1095","article-title":"Vision in albinism","volume":"94","author":"Summers","year":"1996","journal-title":"Trans Am Ophthalmol Soc"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1001\/archophthalmol.2012.2270"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/S0161-6420(84)34247-6"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1172\/JCI59372"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.2147\/TACG.S113310"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2011.04.016"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1080\/13816810.2017.1342134"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0084494"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpsychires.2010.10.008"},{"issue":"2","key":"B27","first-page":"145","article-title":"Retinal pigment epithelial lipofuscin and melanin and choroidal melanin in human eyes","volume":"27","author":"Weiter","year":"1986","journal-title":"Invest Ophthalmol Vis Sci"},{"issue":"Pt3b","key":"B28","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1038\/eye.1998.137","article-title":"The retinal pigment epithelium as a developmental regulator of the neural retina","volume":"12","author":"Jeffery","year":"1998","journal-title":"Eye (Lond)"},{"key":"B29","doi-asserted-by":"crossref","DOI":"10.1186\/1749-8104-9-11","article-title":"Delayed neurogenesis leads to altered specification of ventrotemporal retinal ganglion cells in albino mice","volume":"9","author":"Bhansali","year":"2014","journal-title":"Neural Dev"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1002\/dneu.22473"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2006.03657.x"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.0060236"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1111\/ceo.12325"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1038\/ng0694-176"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1093\/inthealth\/ihv039"},{"issue":"5","key":"B36","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1111\/j.1365-2133.1975.tb03116.x","article-title":"Albinism in Nigeria. A clinical and social study","volume":"92","author":"Okoro","year":"1975","journal-title":"Br J Dermatol"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1007\/s10038-007-0181-y"},{"issue":"6","key":"B38","first-page":"1320","article-title":"Frequent intragenic deletion of the P gene in Tanzanian patients with type II oculocutaneous albinism (OCA2)","volume":"56","author":"Spritz","year":"1995","journal-title":"Am J Hum Genet"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9394(02)01825-1"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0749.2002.02042.x"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1016\/S0161-6420(88)33152-0"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1111\/j.1755-148X.2011.00864.x"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0749.2002.02009.x"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-4347(99)00199-1"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1046\/j.0306-5251.2001.01421.x"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1037\/0033-2909.86.2.420"},{"key":"B47","unstructured":"Mangione CM. Version 2000: The National Eye Institute 25-Item Visual Function Questionnaire (VFQ-25). National Eye Institute Web site. https:\/\/www.nei.nih.gov\/sites\/default\/files\/nei-pdfs\/manual_cm2000.pdf Accessed December 19, 2018"}],"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/insight.jci.org\/articles\/view\/124387\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T12:35:07Z","timestamp":1779194107000},"score":1,"resource":{"primary":{"URL":"https:\/\/insight.jci.org\/articles\/view\/124387"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,1,24]]},"references-count":47,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2019,1,24]]},"published-print":{"date-parts":[[2019,1,24]]}},"alternative-id":["10.1172\/jci.insight.124387"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.124387","relation":{},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,1,24]]},"article-number":"e124387"}}