{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T22:58:37Z","timestamp":1783033117944,"version":"3.54.6"},"reference-count":99,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2023,8,30]],"date-time":"2023-08-30T00:00:00Z","timestamp":1693353600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Neurofibromatosis type 1 (NF1) is a rare inherited neurocutaneous disorder with a major impact on the skin, nervous system and eyes. The ocular diagnostic hallmarks of this disease include iris Lisch nodules, ocular and eyelid neurofibromas, eyelid caf\u00e9-au-lait spots and optic pathway gliomas (OPGs). In the last years, new manifestations have been identified in the ocular district in NF1 including choroidal abnormalities (CAs), hyperpigmented spots (HSs) and retinal vascular abnormalities (RVAs). Recent advances in multi-modality imaging in ophthalmology have allowed for the improved characterization of these clinical signs. Accordingly, CAs, easily detectable as bright patchy nodules on near-infrared imaging, have recently been added to the revised diagnostic criteria for NF1 due to their high specificity and sensitivity. Furthermore, subclinical alterations of the visual pathways, regardless of the presence of OPGs, have been recently described in NF1, with a primary role of neurofibromin in the myelination process. In this paper, we reviewed the latest progress in the understanding of choroidal and retinal abnormalities in NF1 patients. The clinical significance of the recently revised diagnostic criteria for NF1 is discussed along with new updates in molecular diagnosis. New insights into NF1-related neuro-ophthalmic manifestations are also provided based on electrophysiological and optical coherence tomography (OCT) studies.<\/jats:p>","DOI":"10.3390\/ijms241713481","type":"journal-article","created":{"date-parts":[[2023,8,30]],"date-time":"2023-08-30T10:30:52Z","timestamp":1693391452000},"page":"13481","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Insights into Novel Choroidal and Retinal Clinical Signs in Neurofibromatosis Type 1"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6274-015X","authenticated-orcid":false,"given":"Fabiana","family":"Mallone","sequence":"first","affiliation":[{"name":"Department of Sense Organs, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5366-882X","authenticated-orcid":false,"given":"Ludovico","family":"Alisi","sequence":"additional","affiliation":[{"name":"Department of Sense Organs, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Lucchino","sequence":"additional","affiliation":[{"name":"Department of Sense Organs, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerio","family":"Di Martino","sequence":"additional","affiliation":[{"name":"Department of Sense Organs, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5512-0849","authenticated-orcid":false,"given":"Marcella","family":"Nebbioso","sequence":"additional","affiliation":[{"name":"Department of Sense Organs, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Armentano","sequence":"additional","affiliation":[{"name":"Department of Sense Organs, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8974-991X","authenticated-orcid":false,"given":"Alessandro","family":"Lambiase","sequence":"additional","affiliation":[{"name":"Department of Sense Organs, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonietta","family":"Moramarco","sequence":"additional","affiliation":[{"name":"Department of Sense Organs, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1097\/GIM.0b013e3181bf15e3","article-title":"Clinical and genetic aspects of neurofibromatosis 1","volume":"12","author":"Jett","year":"2010","journal-title":"Genet. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1080\/08820530701745223","article-title":"Neurofibromatosis type I: Genetics and clinical manifestations","volume":"23","author":"Savar","year":"2008","journal-title":"Semin. Ophthalmol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1097\/ICU.0b013e3283570127","article-title":"Type I neurofibromatosis: A geno-oculo-dermatologic update","volume":"23","author":"Schnur","year":"2012","journal-title":"Curr. Opin. Ophthalmol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1001\/archderm.141.1.71","article-title":"Prevalence of neurofibromatosis 1 in German children at elementary school enrollment","volume":"141","author":"Lammert","year":"2005","journal-title":"Arch. Dermatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/0896-6273(93)90324-K","article-title":"The neurofibromatosis type 1 gene and its protein product, neurofibromin","volume":"10","author":"Gutmann","year":"1993","journal-title":"Neuron"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1111\/j.1365-2133.1994.tb06893.x","article-title":"What is segmental neurofibromatosis?","volume":"130","author":"MOSS","year":"1994","journal-title":"Br. J. Dermatol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1016\/j.survophthal.2017.10.007","article-title":"Ophthalmic manifestations in neurofibromatosis type 1","volume":"63","author":"Kinori","year":"2018","journal-title":"Surv. Ophthalmol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1506","DOI":"10.1038\/s41436-021-01170-5","article-title":"Revised diagnostic criteria for neurofibromatosis type 1 and Legius syndrome: An international consensus recommendation","volume":"23","author":"Legius","year":"2021","journal-title":"Genet. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1186\/s13023-022-02369-8","article-title":"An update on choroidal abnormalities and retinal microvascular changes in neurofibromatosis type 1","volume":"17","author":"Mallone","year":"2022","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1001\/archopht.1965.00970030698019","article-title":"Nerve Fibrils in Ovoid Bodies: With Neurofibromatosis of the Choroid","volume":"73","author":"Wolter","year":"1965","journal-title":"Arch. Ophthalmol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/0002-9394(85)90376-9","article-title":"Neurofibromatosis of the choroid","volume":"99","author":"Klein","year":"1985","journal-title":"Am. J. Ophthalmol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1939","DOI":"10.1001\/archopht.1982.01030040919010","article-title":"Ovoid Bodies in Choroidal Neurofibromatosis","volume":"100","author":"Kurosawa","year":"1982","journal-title":"Arch. Ophthalmol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1016\/S0140-6736(00)02716-1","article-title":"Frequency of choroidal abnormalities in neurofibromatosis type 1","volume":"356","author":"Yasunari","year":"2000","journal-title":"Lancet"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/j.ophtha.2011.07.046","article-title":"Choroidal abnormalities detected by near-infrared reflectance imaging as a new diagnostic criterion for neurofibromatosis 1","volume":"119","author":"Viola","year":"2012","journal-title":"Ophthalmology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/0042-6989(95)00100-E","article-title":"Infrared imaging of sub-retinal structures in the human ocular fundus","volume":"36","author":"Elsner","year":"1996","journal-title":"Vision Res."},{"key":"ref_16","first-page":"1191","article-title":"Near-infrared fundus autofluorescence-visualized melanin in the choroidal abnormalities of neurofibromatosis type 1","volume":"6","author":"Miyakoshi","year":"2012","journal-title":"Clin. Ophthalmol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1007\/s00417-005-1184-z","article-title":"Quantification and anatomic distribution of choroidal abnormalities in patients with type I neurofibromatosis","volume":"243","author":"Nakakura","year":"2005","journal-title":"Graefe\u2019s Arch. Clin. Exp. Ophthalmol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1136\/bjophthalmol-2014-306062","article-title":"Morphologic and vasculature features of the choroid and associated choroid-retinal thickness alterations in neurofibromatosis type 1","volume":"99","author":"Abdolrahimzadeh","year":"2015","journal-title":"Br. J. Ophthalmol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"586","DOI":"10.4103\/ijo.IJO_1095_17","article-title":"Multimodal imaging of choroidal nodules in neurofibromatosis type-1","volume":"66","author":"Kumar","year":"2018","journal-title":"Indian J. Ophthalmol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1789","DOI":"10.1007\/s00417-018-4028-3","article-title":"SD-OCT in NIR modality to diagnose retinal microvascular abnormalities in neurofibromatosis type 1","volume":"256","author":"Moramarco","year":"2018","journal-title":"Graefe\u2019s Arch. Clin. Exp. Ophthalmol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e667","DOI":"10.1111\/aos.12750","article-title":"Choroidal abnormalities in neurofibromatosis type 1 detected by near-infrared reflectance imaging in paediatric population","volume":"93","author":"Vagge","year":"2015","journal-title":"Acta Ophthalmol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"6748","DOI":"10.1167\/iovs.12-10123","article-title":"Cytokines and chemokines in the vitreous fluid of eyes with uveal melanoma","volume":"53","author":"Bronkhorst","year":"2012","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1167\/tvst.11.2.10","article-title":"Prevalence of Choroidal Abnormalities and Lisch Nodules in Children Meeting Clinical and Molecular Diagnosis of Neurofibromatosis Type 1","volume":"11","author":"Pimentel","year":"2022","journal-title":"Transl. Vis. Sci. Technol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"204","DOI":"10.3928\/01913913-20140513-02","article-title":"Frequency of choroidal abnormalities in pediatric patients with neurofibromatosis type 1","volume":"51","author":"Goktas","year":"2014","journal-title":"J. Pediatr. Ophthalmol. Strabismus"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"165","DOI":"10.2147\/OPTH.S56327","article-title":"Correlations between choroidal abnormalities, Lisch nodules, and age in patients with neurofibromatosis type 1","volume":"8","author":"Makino","year":"2014","journal-title":"Clin. Ophthalmol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1111\/ceo.13936","article-title":"Long-term follow-up of choroidal abnormalities in children with neurofibromatosis type 1","volume":"49","author":"Manassero","year":"2021","journal-title":"Clin. Experiment. Ophthalmol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1080\/13816810.2021.1881977","article-title":"The presence and progression of choroidal neurofibromas in a predominantly pediatric population with neurofibromatosis type-1","volume":"42","author":"Chilibeck","year":"2021","journal-title":"Ophthalmic Genet."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Cosmo, E., Frizziero, L., Miglionico, G., De Biasi, C.S., Bruno, M., Trevisson, E., Gabbiato, I., Midena, G., and Parrozzani, R. (2022). Choroidal Abnormalities in Pediatric NF1: A Cohort Natural History Study. Cancers, 14.","DOI":"10.3390\/cancers14061423"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1097\/01.icu.0000193070.32369.37","article-title":"Optic-nerve gliomas, chiasmal gliomas and neurofibromatosis type 1","volume":"17","author":"Sylvester","year":"2006","journal-title":"Curr. Opin. Ophthalmol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1186\/s13023-021-01773-w","article-title":"Hyperpigmented spots at fundus examination: A new ocular sign in Neurofibromatosis Type I","volume":"16","author":"Moramarco","year":"2021","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1007\/s00417-017-3870-z","article-title":"Near-infrared imaging: An in vivo, non-invasive diagnostic tool in neurofibromatosis type 1","volume":"256","author":"Moramarco","year":"2018","journal-title":"Graefe\u2019s Arch. Clin. Exp. Ophthalmol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"(1988). Neurofibromatosis: Conference Statement. Arch Neurol., 45, 575\u2013578.","DOI":"10.1001\/archneur.1988.00520290115023"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1001\/jama.1997.03550010065042","article-title":"The diagnostic evaluation and multidisciplinary management of neurofibromatosis 1 and neurofibromatosis 2","volume":"278","author":"Gutmann","year":"1997","journal-title":"Jama"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Tamura, R. (2021). Current Understanding of Neurofibromatosis Type 1, 2, and Schwannomatosis. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22115850"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1007\/s00439-021-02410-z","article-title":"Challenges in the diagnosis of neurofibromatosis type 1 (NF1) in young children facilitated by means of revised diagnostic criteria including genetic testing for pathogenic NF1 gene variants","volume":"141","author":"Cooper","year":"2022","journal-title":"Hum. Genet."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1002\/humu.23929","article-title":"Clinical spectrum of individuals with pathogenic NF1 missense variants affecting p.Met1149, p.Arg1276, and p.Lys1423: Genotype-phenotype study in neurofibromatosis type 1","volume":"41","author":"Koczkowska","year":"2020","journal-title":"Hum. Mutat."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"S91","DOI":"10.1212\/WNL.0000000000012436","article-title":"Genotype-Phenotype Correlations in Neurofibromatosis and Their Potential Clinical Use","volume":"97","author":"Bettegowda","year":"2021","journal-title":"Neurology"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.ajhg.2017.12.001","article-title":"Genotype-Phenotype Correlation in NF1: Evidence for a More Severe Phenotype Associated with Missense Mutations Affecting NF1 Codons 844-848","volume":"102","author":"Koczkowska","year":"2018","journal-title":"Am. J. Hum. Genet."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2285","DOI":"10.1007\/s00381-020-04771-8","article-title":"Genetic basis of neurofibromatosis type 1 and related conditions, including mosaicism","volume":"36","author":"Legius","year":"2020","journal-title":"Childs. Nerv. Syst."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1002\/ajmg.a.36313","article-title":"Novel association of neurofibromatosis type 1-causing mutations in families with neurofibromatosis-Noonan syndrome","volume":"164A","author":"Ekvall","year":"2014","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1111\/cge.14040","article-title":"Clinical variability of neurofibromatosis 1: A modifying role of cooccurring PTPN11 variants and atypical brain MRI findings","volume":"100","author":"Rosano","year":"2021","journal-title":"Clin. Genet."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1136\/jmg.28.11.752","article-title":"Watson syndrome: Is it a subtype of type 1 neurofibromatosis?","volume":"28","author":"Allanson","year":"1991","journal-title":"J. Med. Genet."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1007\/s10048-011-0278-5","article-title":"Familial spinal neurofibromatosis due to a multiexonic NF1 gene deletion","volume":"12","author":"Pizzuti","year":"2011","journal-title":"Neurogenetics"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1111\/j.1399-0004.2009.01292.x","article-title":"Multiple spinal ganglioneuromas in a patient harboring a pathogenic NF1 mutation","volume":"77","author":"Bacci","year":"2010","journal-title":"Clin. Genet."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e582","DOI":"10.1212\/NXG.0000000000000582","article-title":"Familial Lipomas without Classic Neurofibromatosis-1 Caused by a Missense Germline NF1 Mutation","volume":"7","author":"Ramirez","year":"2021","journal-title":"Neurol. Genet."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1002\/(SICI)1096-8628(19991008)86:4<328::AID-AJMG6>3.0.CO;2-O","article-title":"Recurrent NF1 gene mutation in a patient with oligosymptomatic neurofibromatosis type 1 (NF1)","volume":"86","author":"Buske","year":"1999","journal-title":"Am. J. Med. Genet."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1136\/jmg.32.4.316","article-title":"Encephalocraniocutaneous lipomatosis with a mutation in the NF1 gene","volume":"32","author":"Legius","year":"1995","journal-title":"J. Med. Genet."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1002\/1098-1004(200006)15:6<541::AID-HUMU6>3.0.CO;2-N","article-title":"Exhaustive mutation analysis of the NF1 gene allows identification of 95% of mutations and reveals a high frequency of unusual splicing defects","volume":"15","author":"Messiaen","year":"2000","journal-title":"Hum. Mutat."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1002\/gcc.20289","article-title":"Spectrum of single- and multiexon NF1 copy number changes in a cohort of 1,100 unselected NF1 patients","volume":"45","author":"Wimmer","year":"2006","journal-title":"Genes Chromosom. Cancer"},{"key":"ref_50","first-page":"271","article-title":"Neurofibromatosis type 1 associated with systemic vasculopathy","volume":"8","author":"Amorosi","year":"1998","journal-title":"Eur. J. Dermatol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1016\/j.jvs.2007.03.055","article-title":"Vascular abnormalities in patients with neurofibromatosis syndrome type I: Clinical spectrum, management, and results","volume":"46","author":"Oderich","year":"2007","journal-title":"J. Vasc. Surg."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2148","DOI":"10.1161\/CIRCULATIONAHA.107.707752","article-title":"NF1 regulates a Ras-dependent vascular smooth muscle proliferative injury response","volume":"116","author":"Xu","year":"2007","journal-title":"Circulation"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Bajaj, A., Li, Q.F., Zheng, Q., and Pumiglia, K. (2012). Loss of NF1 expression in human endothelial cells promotes autonomous proliferation and altered vascular morphogenesis. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0049222"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1007\/s10456-004-6643-3","article-title":"Targeting neovascular pericytes in neurofibromatosis type 1","volume":"7","author":"Ozerdem","year":"2004","journal-title":"Angiogenesis"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1590","DOI":"10.1136\/bjophthalmol-2018-313002","article-title":"Retinal microvascular abnormalities in neurofibromatosis type 1","volume":"103","author":"Moramarco","year":"2019","journal-title":"Br. J. Ophthalmol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1136\/bjo.86.3.282","article-title":"Corkscrew retinal vessels in neurofibromatosis type 1: Report of 12 cases","volume":"86","author":"Ramella","year":"2002","journal-title":"Br. J. Ophthalmol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1097\/IAE.0000000000001578","article-title":"Retinal vascular abnormalities in a large cohort of patients affected by neurofibromatosis type: 1 a study using optical coherence tomography angiography","volume":"38","author":"Parrozzani","year":"2018","journal-title":"Retina"},{"key":"ref_58","first-page":"E4","article-title":"A characteristic type of retinal microvascular abnormalities in a patient with Neurofibromatosis type 1","volume":"170","author":"Moramarco","year":"2019","journal-title":"Clin. Ter."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Abdolrahimzadeh, S., Felli, L., Piraino, D.C., Mollo, R., Calvieri, S., and Recupero, S.M. (2014). Retinal microvascular abnormalities overlying choroidal nodules in neurofibromatosis type 1. BMC Ophthalmol., 14.","DOI":"10.1186\/1471-2415-14-146"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2589","DOI":"10.1097\/IAE.0000000000003234","article-title":"Retinal vascular abnormalities in children with neurofibromatosis type 1","volume":"41","author":"Abitbol","year":"2021","journal-title":"Retina"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1097\/00041327-200312000-00008","article-title":"Retinal vascular abnormalities in neurofibromatosis type 1","volume":"23","author":"Karadimas","year":"2003","journal-title":"J. Neuroophthalmol."},{"key":"ref_62","first-page":"604191","article-title":"Retinal microvascular abnormalities in neurofibromatosis type 1 associated with congenital retinal macrovessels","volume":"2013","author":"Makino","year":"2013","journal-title":"Case Rep. Ophthalmol. Med."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1097\/IAE.0000000000002962","article-title":"Retinal vascular abnormalities related to neurofibromatosis type 1: Natural History and Classification by Optical Coherence Tomography Angiography in 473 Patients","volume":"41","author":"Parrozzani","year":"2021","journal-title":"Retina"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"E35","DOI":"10.1097\/IAE.0000000000003532","article-title":"Correspondence","volume":"42","author":"Lucchino","year":"2022","journal-title":"Retina"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"12865","DOI":"10.1038\/s41598-020-69852-9","article-title":"Congenital abnormalities of the retinal vasculature in neurofibromatosis type I","volume":"10","author":"Chun","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1186\/1824-7288-40-59","article-title":"Moyamoya syndrome and neurofibromatosis type 1","volume":"40","author":"Vargiami","year":"2014","journal-title":"Ital. J. Pediatr."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1226","DOI":"10.1056\/NEJMra0804622","article-title":"Moyamoya Disease and Moyamoya Syndrome","volume":"360","author":"Scott","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1111\/j.1468-1331.2007.01819.x","article-title":"Anterior ischemic optic neuropathy in moyamoya disease: A first case report","volume":"14","author":"Chen","year":"2007","journal-title":"Eur. J. Neurol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1016\/S0039-6257(96)82016-9","article-title":"Ocular ischemic syndrome in a child with moyamoya disease and neurofibromatosis","volume":"40","author":"Barrall","year":"1996","journal-title":"Surv. Ophthalmol."},{"key":"ref_70","first-page":"123","article-title":"Moyamoya disease with central retinal vein occlusion. Case report","volume":"1","author":"Slamovits","year":"1981","journal-title":"J. Clin. Neuroophthalmol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1159\/000310428","article-title":"Sudden blindness in the fourth month of pregnancy led to diagnosis of moyamoya disease","volume":"207","author":"Ushimura","year":"1993","journal-title":"Ophthalmologica"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"417","DOI":"10.3171\/2012.12.PEDS12281","article-title":"Moyamoya syndrome associated with neurofibromatosis Type 1: Perioperative and long-term outcome after surgical revascularization","volume":"11","author":"Koss","year":"2013","journal-title":"J. Neurosurg. Pediatr."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"S162","DOI":"10.1016\/S0303-8467(97)00054-1","article-title":"Familial occurrence of moyamoya disease","volume":"99","author":"Yamauchi","year":"1997","journal-title":"Clin. Neurol. Neurosurg."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1016\/j.jocn.2014.05.046","article-title":"Clinical characteristics and long-term outcomes of moyamoya syndrome associated with neurofibromatosis type 1","volume":"22","author":"Han","year":"2015","journal-title":"J. Clin. Neurosci."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1001\/jamaophthalmol.2013.2902","article-title":"Ophthalmic artery ischemic syndrome associated with neurofibromatosis and moyamoya syndrome","volume":"131","author":"Witmer","year":"2013","journal-title":"JAMA Ophthalmol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1159\/000469702","article-title":"Optical Coherence Tomography Angiography of Retinal Microvascular Changes Overlying Choroidal Nodules in Neurofibromatosis Type 1","volume":"8","author":"Cassiman","year":"2017","journal-title":"Case Rep. Ophthalmol."},{"key":"ref_77","first-page":"NP91","article-title":"Optical coherence tomography angiography of choroidal nodules in neurofibromatosis type-1: A case series","volume":"32","year":"2021","journal-title":"Eur. J. Ophthalmol."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Vagge, A., Corazza, P., Desideri, L.F., Camicione, P., Agosto, G., Vagge, R., Grazia, C.M., Carnevali, A., Giannaccare, G., and Nicol\u00f2, M. (2021). Ocular biometric parameters changes and choroidal vascular abnormalities in patients with neurofibromatosis type 1 evaluated by OCT-A. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0251098"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"189.e1","DOI":"10.1016\/j.jaapos.2022.05.005","article-title":"Quantitative OCT angiography of the retinal and choroidal vascular circulation in pediatric patients with neurofibromatosis type 1","volume":"26","author":"Atesoglu","year":"2022","journal-title":"J. Am. Assoc. Pediatr. Ophthalmol. Strabismus"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/0887-8994(94)90043-4","article-title":"Optic gliomas in neurofibromatosis type 1: Role of visual evoked potentials","volume":"10","author":"North","year":"1994","journal-title":"Pediatr. Neurol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1007\/s10633-013-9399-5","article-title":"Role of visual evoked potentials in the assessment and management of optic pathway gliomas in children","volume":"127","author":"Spileers","year":"2013","journal-title":"Doc. Ophthalmol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1177\/1120672120906989","article-title":"Role of visual evoked potentials and optical coherence tomography in the screening for optic pathway gliomas in patients with neurofibromatosis type I","volume":"31","author":"Vagge","year":"2021","journal-title":"Eur. J. Ophthalmol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1097\/NEN.0b013e3181a3240b","article-title":"Optic nerve dysfunction in a mouse model of neurofibromatosis-1 optic glioma","volume":"68","author":"Hegedus","year":"2009","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"2469","DOI":"10.1167\/iovs.14-16235","article-title":"Functional loss of the inner retina in childhood optic gliomas detected by photopic negative response","volume":"56","author":"Abed","year":"2015","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1023\/A:1012271206258","article-title":"Electro-oculogram in patients with neurofibromatosis type 1","volume":"103","author":"Zajaczek","year":"2001","journal-title":"Doc. Ophthalmol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1186\/1897-4287-2-4-193","article-title":"Supernormal Electro-Oculograms in Patients with Neurofibromatosis Type 1","volume":"2","author":"Sych","year":"2004","journal-title":"Hered. Cancer Clin. Pract."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1167\/iovs.63.4.6","article-title":"Function of the Retinal Pigment Epithelium in Patients with Neurofibromatosis Type 1","volume":"63","author":"Touze","year":"2022","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1023\/A:1015719803719","article-title":"Visual evoked potentials in children with neurofibromatosis type 1","volume":"105","author":"Iannaccone","year":"2002","journal-title":"Doc. Ophthalmol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1111\/j.1749-6632.1999.tb08583.x","article-title":"Neurofibromin, the neurofibromatosis type 1 RaS-GAP, is required for appropriate P0 expression and myelination","volume":"883","author":"Rosenbaum","year":"1999","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"119","DOI":"10.2147\/EB.S255184","article-title":"Neurofibromatosis type 1: Ocular electrophysiological and perimetric anomalies","volume":"12","author":"Nebbioso","year":"2020","journal-title":"Eye Brain"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"773","DOI":"10.18240\/ijo.2022.05.13","article-title":"Neuroretinal dysfunction in patients affected by neurofibromatosis type 1","volume":"15","author":"Moramarco","year":"2022","journal-title":"Int. J. Ophthalmol."},{"key":"ref_92","first-page":"79","article-title":"Cone-rod retinal dystrophy in a patient with neurofibromatosis type 1","volume":"28","author":"Kylstra","year":"1993","journal-title":"Can. J. Ophthalmol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"34","DOI":"10.3109\/13816810.2011.592178","article-title":"Cone-rod dystrophy associated with amelogenesis imperfecta in a child with neurofibromatosis type 1","volume":"33","author":"Zobor","year":"2012","journal-title":"Ophthalmic Genet."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1093\/hmg\/6.4.597","article-title":"Localisation of a gene for dominant cone-rod dystrophy (CORD6) to chromosome 17p","volume":"6","author":"Kelsell","year":"1997","journal-title":"Hum. Mol. Genet."},{"key":"ref_95","first-page":"543","article-title":"Retinitis pigmentosa: An unusual ocular manifestation in a patient with neurofibromatosis type 1","volume":"152","author":"Miraglia","year":"2017","journal-title":"G. Ital. Dermatol. Venereol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1007\/s10792-006-9002-0","article-title":"Unusual macular lesions in a patient with neurofibromatosis type-1","volume":"26","author":"McLoone","year":"2005","journal-title":"Int. Ophthalmol."},{"key":"ref_97","first-page":"99","article-title":"Consanguineous marriage and morbi-mortality, short literature review based on an exceptional association: Usher syndrome and Von Recklinghausen neurofibromatosis","volume":"23","year":"2016","journal-title":"Pan Afr. Med. J."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1402","DOI":"10.1167\/iovs.13-13119","article-title":"Ganglion cell layer-inner plexiform layer thickness and vision loss in young children with optic pathway gliomas","volume":"55","author":"Gu","year":"2014","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1097\/IAE.0000000000000650","article-title":"Spectral domain optical coherence tomography evidence of retinal nerve fiber layer and ganglion cell loss in adult patients with neurofibromatosis type 1","volume":"36","author":"Abdolrahimzadeh","year":"2016","journal-title":"Retina"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/17\/13481\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:43:22Z","timestamp":1760129002000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/17\/13481"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,30]]},"references-count":99,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2023,9]]}},"alternative-id":["ijms241713481"],"URL":"https:\/\/doi.org\/10.3390\/ijms241713481","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,30]]}}}