{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,8]],"date-time":"2026-08-08T05:44:16Z","timestamp":1786167856246,"version":"build-2736575974"},"reference-count":34,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T00:00:00Z","timestamp":1774656000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T00:00:00Z","timestamp":1774656000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Grant by National Hospital Organization for young investigators","award":["R4-NHO-PI-03"],"award-info":[{"award-number":["R4-NHO-PI-03"]}]},{"name":"National Hospital Organization Network Research Fund","award":["H30-NHO-Sensory Organs-03"],"award-info":[{"award-number":["H30-NHO-Sensory Organs-03"]}]},{"name":"Grants from the Japan Society for the Promotion of Science","award":["JSPS"],"award-info":[{"award-number":["JSPS"]}]},{"name":"Grants from the Japan Society for the Promotion of Science","award":["2 1 K 0 9 7 1 2"],"award-info":[{"award-number":["2 1 K 0 9 7 1 2"]}]},{"name":"Research Committee on the Epidemiology of Intractable Diseases of Retinochoroidal and Optic Nerve Atrophy from Ministry of Health, Labour and Welfare of Japan","award":["23FC1043"],"award-info":[{"award-number":["23FC1043"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Jpn J Ophthalmol"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>To investigate the long-term longitudinal changes of the retinal morphology and visual function in patients with fundus albipunctatus (FA).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Study design<\/jats:title>\n                    <jats:p>Retrospective observational study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Seventeen Japanese patients with FA who had pathogenic variants of the\n                      <jats:italic>RDH5<\/jats:italic>\n                      gene were studied in a multicenter retrospective study.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The baseline ages ranged from 3 to 61 years, and the patients were followed longitudinally for 3 to 21 years. The relative size of the flecks\/dots decreased throughout the course of the disease; rapidly in the first and second decades of life and slowly thereafter. The flecks\/dots in the OCT images were seen as hyperreflective flat deposits on the retinal pigment epithelium in the first decade of life, and as hyperreflective pile-like formations that extended to the ellipsoid zone (EZ) of the photoreceptors after the second decade of life. At later ages, the EZ in the mid-peripheral retina was not present due to photoreceptor atrophy. The Goldmann visual fields had a peripheral constriction in 7 of 11 cases that developed during the course of the disease process.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The long-term longitudinal observations of the morphological changes of the retina and visual fields revealed that FA is a slowly progressive retinal dystrophy with atrophy of the peripheral photoreceptors in older patients. These findings will be very important information for the patients when providing genetic counseling.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s10384-026-01337-0","type":"journal-article","created":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T05:14:18Z","timestamp":1774674858000},"page":"852-866","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Longitudinal evaluation of peripheral photoreceptor atrophy in fundus albipunctatus"],"prefix":"10.1007","volume":"70","author":[{"given":"Takuhiro","family":"Hayakawa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kei","family":"Mizobuchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takaaki","family":"Hayashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taro","family":"Kominami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koji M","family":"Nishiguchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinji","family":"Ueno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuki","family":"Kuniyoshi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mineo","family":"Kondo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Iwata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaoru","family":"Fujinami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazushige","family":"Tsunoda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,28]]},"reference":[{"key":"1337_CR1","first-page":"185","volume":"121","author":"A Franceschetti","year":"1951","unstructured":"Franceschetti A, Chome-Bercioux N. [Fundus albipunctatus with hemeralopia of 49 years\u2019 duration]. Ophthalmologica. 1951;121:185\u201393 (in German).","journal-title":"Ophthalmologica"},{"key":"1337_CR2","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1007\/BF01569200","volume":"43","author":"MF Marmor","year":"1977","unstructured":"Marmor MF. Fundus albipunctatus: a clinical study of the fundus lesions, the physiologic deficit, and the vitamin A metabolism. Doc Ophthalmol. 1977;43:277\u2013302.","journal-title":"Doc Ophthalmol"},{"key":"1337_CR3","first-page":"41","volume":"5","author":"F Gonzalez-Fernandez","year":"1999","unstructured":"Gonzalez-Fernandez F, Kurz D, Bao Y, Newman S, Conway BP, Young JE, et al. 11-cis retinol dehydrogenase mutations as a major cause of the congenital night-blindness disorder known as fundus albipunctatus. Mol vis. 1999;5:41.","journal-title":"Mol vis"},{"key":"1337_CR4","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1038\/9707","volume":"22","author":"H Yamamoto","year":"1999","unstructured":"Yamamoto H, Simon A, Eriksson U, Harris E, Berson EL, Dryja TP. Mutations in the gene encoding 11-cis retinol dehydrogenase cause delayed dark adaptation and fundus albipunctatus. Nat Genet. 1999;22:188\u201391.","journal-title":"Nat Genet"},{"key":"1337_CR5","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1136\/bjo.76.6.375","volume":"76","author":"Y Miyake","year":"1992","unstructured":"Miyake Y, Shiroyama N, Sugita S, Horiguchi M, Yagasaki K. Fundus albipunctatus associated with cone dystrophy. Br J Ophthalmol. 1992;76:375\u20139.","journal-title":"Br J Ophthalmol"},{"key":"1337_CR6","first-page":"3925","volume":"41","author":"M Nakamura","year":"2000","unstructured":"Nakamura M, Hotta Y, Tanikawa A, Terasaki H, Miyake Y. A high association with cone dystrophy in fundus albipunctatus caused by mutations of the RDH5 gene. Invest Ophthalmol Vis Sci. 2000;41:3925\u201332.","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"1337_CR7","doi-asserted-by":"publisher","first-page":"917","DOI":"10.1016\/S0002-9394(02)02290-0","volume":"135","author":"K Hotta","year":"2003","unstructured":"Hotta K, Nakamura M, Kondo M, Ito S, Terasaki H, Miyake Y, et al. Macular dystrophy in a Japanese family with fundus albipunctatus. Am J Ophthalmol. 2003;135:917\u20139.","journal-title":"Am J Ophthalmol"},{"key":"1337_CR8","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.61.3.53","volume":"61","author":"S Katagiri","year":"2020","unstructured":"Katagiri S, Hayashi T, Nakamura M, Mizobuchi K, Gekka T, Komori S, et al. RDH5-related fundus albipunctatus in a large Japanese cohort. Invest Ophthalmol Vis Sci. 2020;61:53.","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"1337_CR9","doi-asserted-by":"publisher","first-page":"2251","DOI":"10.1002\/humu.24492","volume":"43","author":"A Suga","year":"2022","unstructured":"Suga A, Yoshitake K, Minematsu N, Tsunoda K, Fujinami K, Miyake Y, et al. Genetic characterization of 1210 Japanese pedigrees with inherited retinal diseases by whole-exome sequencing. Hum Mutat. 2022;43:2251\u201364.","journal-title":"Hum Mutat"},{"key":"1337_CR10","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1007\/s10633-022-09872-0","volume":"144","author":"AG Robson","year":"2022","unstructured":"Robson AG, Frishman LJ, Grigg J, Hamilton R, Jeffrey BG, Kondo M, et al. ISCEV Standard for full-field clinical electroretinography (2022 update). Doc Ophthalmol. 2022;144:165\u201377.","journal-title":"Doc Ophthalmol"},{"key":"1337_CR11","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1111\/j.1600-0420.2005.00575.x","volume":"84","author":"T Hayashi","year":"2006","unstructured":"Hayashi T, Goto-Omoto S, Takeuchi T, Gekka T, Ueoka Y, Kitahara K. Compound heterozygous RDH5 mutations in familial fleck retina with night blindness. Acta Ophthalmol Scand. 2006;84:254\u20138.","journal-title":"Acta Ophthalmol Scand"},{"key":"1337_CR12","doi-asserted-by":"publisher","first-page":"500","DOI":"10.1080\/13816810.2018.1466338","volume":"39","author":"D Kubota","year":"2018","unstructured":"Kubota D, Gocho K, Kikuchi S, Akeo K, Miura M, Yamaki K, et al. CEP250 mutations associated with mild cone-rod dystrophy and sensorineural hearing loss in a Japanese family. Ophthalmic Genet. 2018;39:500\u20137.","journal-title":"Ophthalmic Genet"},{"key":"1337_CR13","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1016\/j.ajo.2023.06.013","volume":"254","author":"K Mizobuchi","year":"2023","unstructured":"Mizobuchi K, Hayashi T, Ueno S, Kondo M, Terasaki H, Aoki T, et al. One-year outcomes of oral treatment with alga capsules containing low levels of 9-cis-\u03b2-carotene in RDH5-related fundus albipunctatus. Am J Ophthalmol. 2023;254:193\u2013202.","journal-title":"Am J Ophthalmol"},{"key":"1337_CR14","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1016\/S0161-6420(90)32577-0","volume":"97","author":"MF Marmor","year":"1990","unstructured":"Marmor MF. Long-term follow-up of the physiologic abnormalities and fundus changes in fundus albipunctatus. Ophthalmology. 1990;97:380\u20134.","journal-title":"Ophthalmology"},{"key":"1337_CR15","doi-asserted-by":"publisher","first-page":"1480","DOI":"10.1167\/iovs.04-0638","volume":"46","author":"Y Niwa","year":"2005","unstructured":"Niwa Y, Kondo M, Ueno S, Nakamura M, Terasaki H, Miyake Y. Cone and rod dysfunction in fundus albipunctatus with RDH5 mutation: an electrophysiological study. Invest Ophthalmol Vis Sci. 2005;46:1480\u20135.","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"1337_CR16","doi-asserted-by":"publisher","first-page":"703","DOI":"10.1001\/archophthalmol.2009.87","volume":"127","author":"G Querques","year":"2009","unstructured":"Querques G, Carrillo P, Querques L, Bux AV, Del Curatolo MV, Delle Noci N. High-definition optical coherence tomographic visualization of photoreceptor layer and retinal flecks in fundus albipunctatus associated with cone dystrophy. Arch Ophthalmol. 2009;127:703\u20136.","journal-title":"Arch Ophthalmol"},{"key":"1337_CR17","doi-asserted-by":"publisher","first-page":"1704","DOI":"10.1097\/IAE.0b013e3181dc050a","volume":"30","author":"P Schatz","year":"2010","unstructured":"Schatz P, Preising M, Lorenz B, Sander B, Larsen M, Eckstein C, et al. Lack of autofluorescence in fundus albipunctatus associated with mutations in RDH5. Retina. 2010;30:1704\u201313.","journal-title":"Retina"},{"key":"1337_CR18","doi-asserted-by":"publisher","first-page":"1661","DOI":"10.1016\/j.ophtha.2010.12.031","volume":"118","author":"PI Sergouniotis","year":"2011","unstructured":"Sergouniotis PI, Sohn EH, Li Z, McBain VA, Wright GA, Moore AT, et al. Phenotypic variability in RDH5 retinopathy (Fundus Albipunctatus). Ophthalmology. 2011;118:1661\u201370.","journal-title":"Ophthalmology"},{"key":"1337_CR19","doi-asserted-by":"publisher","first-page":"69","DOI":"10.2147\/EB.S23208","volume":"3","author":"E Zaharova","year":"2011","unstructured":"Zaharova E, Sherman J. The use of SD-OCT in the differential diagnosis of dots, spots and other white retinal lesions. Eye brain. 2011;3:69\u201380.","journal-title":"Eye brain"},{"key":"1337_CR20","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1007\/s10633-012-9336-z","volume":"125","author":"NK Wang","year":"2012","unstructured":"Wang NK, Chuang LH, Lai CC, Chou CL, Chu HY, Yeung L, et al. Multimodal fundus imaging in fundus albipunctatus with RDH5 mutation: a newly identified compound heterozygous mutation and review of the literature. Doc Ophthalmol. 2012;125:51\u201362.","journal-title":"Doc Ophthalmol"},{"key":"1337_CR21","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.62.7.15","volume":"62","author":"JR Sparrow","year":"2021","unstructured":"Sparrow JR, Parmann R, Tsang SH, Allikmets R, Chang S, Jauregui R. Shared features in retinal disorders with involvement of retinal pigment epithelium. Invest Ophthalmol Vis Sci. 2021;62:15.","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"1337_CR22","doi-asserted-by":"publisher","first-page":"1364","DOI":"10.1097\/IAE.0000000000003466","volume":"42","author":"H Newman","year":"2022","unstructured":"Newman H, Perlman I, Pras E, Rozenberg A, Ben-Yosef T, Iovino C, et al. The target sign: a near infrared feature and multimodal imaging in a pluri-ethnic cohort with RDH5-related fundus albipunctatus. Retina. 2022;42:1364\u20139.","journal-title":"Retina"},{"key":"1337_CR23","doi-asserted-by":"publisher","first-page":"618","DOI":"10.1097\/IAE.0000000000002657","volume":"40","author":"L Chen","year":"2020","unstructured":"Chen L, Messinger JD, Zhang Y, Spaide RF, Freund KB, Curcio CA. Subretinal drusenoid deposit in age-related macular degeneration: histologic insights into initiation, progression to atrophy, and imaging. Retina. 2020;40:618\u201331.","journal-title":"Retina"},{"key":"1337_CR24","doi-asserted-by":"publisher","first-page":"888","DOI":"10.1016\/j.ophtha.2010.09.005","volume":"118","author":"P Schatz","year":"2011","unstructured":"Schatz P, Preising M, Lorenz B, Sander B, Larsen M, Rosenberg T. Fundus albipunctatus associated with compound heterozygous mutations in RPE65. Ophthalmology. 2011;118:888\u201394.","journal-title":"Ophthalmology"},{"key":"1337_CR25","doi-asserted-by":"publisher","first-page":"1899","DOI":"10.1016\/j.ophtha.2012.02.037","volume":"119","author":"KW Littink","year":"2012","unstructured":"Littink KW, van Genderen MM, van Schooneveld MJ, Visser L, Riemslag FC, Keunen JE, et al. A homozygous frameshift mutation in LRAT causes retinitis punctata albescens. Ophthalmology. 2012;119:1899\u2013906.","journal-title":"Ophthalmology"},{"key":"1337_CR26","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1007\/s10633-013-9403-0","volume":"127","author":"TS Aleman","year":"2013","unstructured":"Aleman TS, Garrity ST, Brucker AJ. Retinal structure in vitamin A deficiency as explored with multimodal imaging. Doc Ophthalmol. 2013;127:239\u201343.","journal-title":"Doc Ophthalmol"},{"key":"1337_CR27","doi-asserted-by":"publisher","first-page":"1489","DOI":"10.1038\/s41433-022-02137-9","volume":"37","author":"MP Breazzano","year":"2023","unstructured":"Breazzano MP, Oh JK, Batson SA, Kucherich JA, Karani R, Rohrmann CM, et al. Vitamin A deficiency and the retinal \u201cdouble carrot\u201d sign with optical coherence tomography. Eye (London). 2023;37:1489\u201395.","journal-title":"Eye (London)."},{"key":"1337_CR28","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1016\/j.ophtha.2009.07.014","volume":"117","author":"SA Zweifel","year":"2010","unstructured":"Zweifel SA, Spaide RF, Curcio CA, Malek G, Imamura Y. Reticular pseudodrusen are subretinal drusenoid deposits. Ophthalmology. 2010;117:303\u201312 e1.","journal-title":"Ophthalmology"},{"key":"1337_CR29","doi-asserted-by":"publisher","first-page":"1005","DOI":"10.1016\/j.ajo.2014.01.025","volume":"157","author":"M Suzuki","year":"2014","unstructured":"Suzuki M, Sato T, Spaide RF. Pseudodrusen subtypes as delineated by multimodal imaging of the fundus. Am J Ophthalmol. 2014;157:1005\u201312.","journal-title":"Am J Ophthalmol"},{"key":"1337_CR30","doi-asserted-by":"publisher","first-page":"2053","DOI":"10.1016\/j.ophtha.2015.06.023","volume":"122","author":"J Flamendorf","year":"2015","unstructured":"Flamendorf J, Agron E, Wong WT, Thompson D, Wiley HE, Doss EL, et al. Impairments in dark adaptation are associated with age-related macular degeneration severity and reticular pseudodrusen. Ophthalmology. 2015;122:2053\u201362.","journal-title":"Ophthalmology"},{"key":"1337_CR31","doi-asserted-by":"publisher","first-page":"2911","DOI":"10.1167\/iovs.13-13409","volume":"55","author":"M Fleckenstein","year":"2014","unstructured":"Fleckenstein M, Schmitz-Valckenberg S, Lindner M, Bezatis A, Becker E, Fimmers R, et al. The \u201cdiffuse-trickling\u201d fundus autofluorescence phenotype in geographic atrophy. Invest Ophthalmol Vis Sci. 2014;55:2911\u201320.","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"1337_CR32","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1007\/s10633-019-09705-7","volume":"139","author":"K Tsunoda","year":"2019","unstructured":"Tsunoda K, Fujinami K, Yoshitake K, Iwata T. Late-onset night blindness with peripheral flecks accompanied by progressive trickle-like macular degeneration. Doc Ophthalmol. 2019;139:171\u201384.","journal-title":"Doc Ophthalmol"},{"key":"1337_CR33","doi-asserted-by":"publisher","first-page":"4275","DOI":"10.1128\/MCB.20.12.4275-4287.2000","volume":"20","author":"CA Driessen","year":"2000","unstructured":"Driessen CA, Winkens HJ, Hoffmann K, Kuhlmann LD, Janssen BP, Van Vugt AH, et al. Disruption of the 11-cis-retinol dehydrogenase gene leads to accumulation of cis-retinols and cis-retinyl esters. Mol Cell Biol. 2000;20:4275\u201387.","journal-title":"Mol Cell Biol"},{"key":"1337_CR34","doi-asserted-by":"publisher","first-page":"1585","DOI":"10.1016\/j.ophtha.2004.01.033","volume":"111","author":"B Lorenz","year":"2004","unstructured":"Lorenz B, Wabbels B, Wegscheider E, Hamel CP, Drexler W, Preising MN. Lack of fundus autofluorescence to 488 nanometers from childhood on in patients with early-onset severe retinal dystrophy associated with mutations in RPE65. Ophthalmology. 2004;111:1585\u201394.","journal-title":"Ophthalmology"}],"container-title":["Japanese Journal of Ophthalmology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10384-026-01337-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10384-026-01337-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10384-026-01337-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,8]],"date-time":"2026-08-08T05:23:09Z","timestamp":1786166589000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10384-026-01337-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,28]]},"references-count":34,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["1337"],"URL":"https:\/\/doi.org\/10.1007\/s10384-026-01337-0","relation":{},"ISSN":["0021-5155","1613-2246"],"issn-type":[{"value":"0021-5155","type":"print"},{"value":"1613-2246","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,28]]},"assertion":[{"value":"6 October 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 January 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 March 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"T. Hayakawa, None; K. Mizobuchi, None; T. Hayashi, None; T. Kominami, None; K. M. Nishiguchi, None; S. Ueno, None; K. Kuniyoshi, None; M. Kondo, None; T. Iwata, None; K. Fujinami, None; K. Tsunoda, None.","order":1,"name":"Ethics","label":"Conflicts of interest","group":{"name":"EthicsHeading","label":"Declarations"}}]}}