{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T17:35:59Z","timestamp":1791567359746,"version":"4.3.4"},"reference-count":108,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,6,22]],"date-time":"2021-06-22T00:00:00Z","timestamp":1624320000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>The term amyloidosis describes a group of rare diseases caused by protein conformation abnormalities resulting in extracellular deposition and accumulation of insoluble fibrillar aggregates. So far, 36 amyloid precursor proteins have been identified, and each one is responsible for a specific disease entity. Transthyretin amyloidosis (ATTRv) is one of the most common forms of systemic and ocular amyloidosis, due to the deposition of transthyretin (TTR), which is a transport protein mainly synthesized in the liver but also in the retinal pigment epithelial cells. ATTRv amyloidosis may be misdiagnosed with several other conditions, resulting in a significant diagnostic delay. Gelsolin and keratoepithelin are other proteins that, when mutated, are responsible for a systemic amyloid disease with significant ocular manifestations that not infrequently appear before systemic involvement. The main signs of ocular amyloid deposition are in the cornea, irido-corneal angle and vitreous, causing complications related to vasculopathy and neuropathy at the local level. This review aims at describing the main biochemical, histopathological and clinical features of systemic amyloidosis associated with eye involvement, with particular emphasis on the inherited forms. We discuss currently available treatments, focusing on ocular involvement and specific ophthalmologic management and highlighting the importance of a prompt treatment for the potential sight-threatening complications derived from amyloid deposition in ocular tissues.<\/jats:p>","DOI":"10.3390\/genes12070955","type":"journal-article","created":{"date-parts":[[2021,6,22]],"date-time":"2021-06-22T13:02:10Z","timestamp":1624366930000},"page":"955","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":72,"title":["Ocular Involvement in Hereditary Amyloidosis"],"prefix":"10.3390","volume":"12","author":[{"given":"Angelo Maria","family":"Minnella","sequence":"first","affiliation":[{"name":"Dipartimento Universitario Testa-Collo Rgani di Senso, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"},{"name":"UOC Oculistica, Fondazione Policlinico Universitario A. Gemelli-IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Rissotto","sequence":"additional","affiliation":[{"name":"Eye Clinic, San Paolo Hospital, University of Milan, 20142 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Antoniazzi","sequence":"additional","affiliation":[{"name":"Institute of Ophthalmolgy, IRCCS Fondazione Policlinico San Matteo, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Di Girolamo","sequence":"additional","affiliation":[{"name":"Former Director \u201cPresidio Ambulatoriale per le Amiloidosi Sistemiche\u201d Fatebenefratelli \u201cSan Giovanni Calibita\u201d Hospital, 00135 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7539-505X","authenticated-orcid":false,"given":"Marco","family":"Luigetti","sequence":"additional","affiliation":[{"name":"Fondazione Policlinico A. Gemelli IRCCS. UOC Neurologia, 00168 Rome, Italy"},{"name":"Dipartimento di Neuroscienze, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3754-7486","authenticated-orcid":false,"given":"Martina","family":"Maceroni","sequence":"additional","affiliation":[{"name":"Dipartimento Universitario Testa-Collo Rgani di Senso, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7578-7563","authenticated-orcid":false,"given":"Daniela","family":"Bacherini","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Psychology, Drug Research and Child Health, Eye Clinic, University of Florence, 50139 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benedetto","family":"Falsini","sequence":"additional","affiliation":[{"name":"Dipartimento Universitario Testa-Collo Rgani di Senso, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"},{"name":"UOC Oculistica, Fondazione Policlinico Universitario A. Gemelli-IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stanislao","family":"Rizzo","sequence":"additional","affiliation":[{"name":"Dipartimento Universitario Testa-Collo Rgani di Senso, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"},{"name":"UOC Oculistica, Fondazione Policlinico Universitario A. Gemelli-IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Obici","sequence":"additional","affiliation":[{"name":"Amyloidosis Research and Treatment Centre, IRCCS Fondazione Policlinico San Matteo, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.ajo.2017.09.001","article-title":"Ocular Manifestations of Familial Transthyretin Amyloidosis","volume":"183","author":"Reynolds","year":"2017","journal-title":"Am. J. Ophthalmol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2239","DOI":"10.1182\/blood-2014-11-609883","article-title":"A practical approach to the diagnosis of systemic amyloidoses","volume":"125","author":"Verga","year":"2015","journal-title":"Blood"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1014","DOI":"10.1016\/j.ophtha.2017.03.011","article-title":"Vitreous Amyloidosis: Ocular, Systemic, and Genetic Insights","volume":"124","author":"Venkatesh","year":"2017","journal-title":"Ophthalmology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1006\/jsbi.2000.4221","article-title":"Review: History of the Amyloid Fibril","volume":"130","author":"Sipe","year":"2000","journal-title":"J. Struct. Biol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1038\/1831202a0","article-title":"Electron Microscopic Observations on a Fibrous Component in Amyloid of Diverse Origins","volume":"183","author":"Cohen","year":"1959","journal-title":"Nature"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1080\/13506129.2020.1835263","article-title":"Amyloid nomenclature 2020: Update and recommendations by the International Society of Amyloidosis (ISA) nomenclature committee","volume":"27","author":"Benson","year":"2020","journal-title":"Amyloid"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.ajo.2017.10.038","article-title":"Ocular Manifestations of Familial Transthyretin Amyloidosis","volume":"186","author":"Tripathy","year":"2018","journal-title":"Am. J. Ophthalmol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/2047-9158-3-19","article-title":"Recent advances in transthyretin amyloidosis therapy","volume":"3","author":"Ueda","year":"2014","journal-title":"Transl. Neurodegener."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1093\/eurheartj\/ehs123","article-title":"Disease profile and differential diagnosis of hereditary transthyretin-related amyloidosis with exclusively cardiac phenotype: An Italian perspective","volume":"34","author":"Rapezzi","year":"2013","journal-title":"Eur. Heart J."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1337","DOI":"10.15252\/emmm.201505357","article-title":"A novel mechano-enzymatic cleavage mechanism underlies transthyretin amyloidogenesis","volume":"7","author":"Marcoux","year":"2015","journal-title":"EMBO Mol Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2319","DOI":"10.1021\/acs.biochem.0c00079","article-title":"Disruption of the CD Loop by Enzymatic Cleavage Promotes the Formation of Toxic Transthyretin Oligomers through a Common Transthyretin Misfolding Pathway","volume":"59","author":"Dasari","year":"2020","journal-title":"Biochemistry"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1097\/YCO.0b013e3283523db6","article-title":"Recent progress in the understanding and treatment of nonepileptic seizures","volume":"25","author":"Reuber","year":"2012","journal-title":"Curr. Opin. Psychiatry"},{"key":"ref_13","first-page":"13506129","article-title":"No ocular involvement in familial amyloidotic polyneuropathy ATTR V30M domino liver recipients","volume":"19","author":"Matos","year":"2012","journal-title":"Transpl. Int."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"183","DOI":"10.3109\/13506120209114820","article-title":"Amyloid deposition in ocular tissues of patients with familial amyloidotic polyneuropathy (FAP)","volume":"9","author":"Haraoka","year":"2002","journal-title":"Amyloid"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1835","DOI":"10.1021\/bi00173a029","article-title":"Synthesis and secretion of retinol-binding protein and transthyretin by cultured retinal pigment epithelium","volume":"33","author":"Ong","year":"1994","journal-title":"Biochemistry"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.1515\/CCLM.2002.210","article-title":"The Evolution of Transthyretin Synthesis in the Choroid Plexus","volume":"40","author":"Schreiber","year":"2002","journal-title":"Clin. Chem. Lab. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"11910","DOI":"10.1007\/s11910-013-0435-3","article-title":"FAP Neuropathy and Emerging Treatments","volume":"14","author":"Adams","year":"2014","journal-title":"Curr. Neurol. Neurosci. Rep."},{"key":"ref_18","unstructured":"Leung, N., Nasr, S.H., and Sethi, S. (2012). How I diagnose amyloidosis. Blood."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1001\/archophthalmol.2009.390","article-title":"Impact of Liver Transplantation on Transthyretin-Related Ocular Amyloidosis in Japanese Patients","volume":"128","author":"Hara","year":"2010","journal-title":"Arch. Ophthalmol."},{"key":"ref_20","first-page":"307","article-title":"Vitrectomy for vitreous amyloidosis","volume":"4","author":"You","year":"2011","journal-title":"Int. J. Ophthalmol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1080\/13506129.2016.1276055","article-title":"Marked biochemical difference in amyloid proportion between intra- and extraocular tissues in a liver-transplanted patient with hereditary ATTR amyloidosis","volume":"24","author":"Yoshinaga","year":"2017","journal-title":"Amyloid"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"931","DOI":"10.7326\/0003-4819-135-10-200111200-00026","article-title":"Ocular amyloid involvement after liver transplantation for polyneuropathy","volume":"135","author":"Ando","year":"2001","journal-title":"Ann. Intern. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"266","DOI":"10.3109\/13506120009146440","article-title":"Vitreous amyloidosis after liver transplantation in patients with familial amyloid polyneuropathy: Ocular synthesis of mutant transthyretin","volume":"7","author":"Saraiva","year":"2000","journal-title":"Amyloid"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"136","DOI":"10.3109\/13506129.2016.1165197","article-title":"Biochemical characterization of vitreous amyloid formed after liver transplantation","volume":"23","author":"Liepnieks","year":"2016","journal-title":"Amyloid"},{"key":"ref_25","first-page":"1","article-title":"Ocular Manifestations and Therapeutic Options in Patients with Familial Amyloid Polyneuropathy: A Systematic Review","volume":"2015","author":"Martins","year":"2015","journal-title":"BioMed Res. Int."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1016\/j.ophtha.2009.07.042","article-title":"Novel Therapy for Transthyretin\u2013related Ocular Amyloidosis: A Pilot Study of Retinal Laser Photocoagulation","volume":"117","author":"Kawaji","year":"2010","journal-title":"Ophthalmology"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1111\/j.1600-0420.2007.01098.x","article-title":"Ocular manifestations in liver transplant recipients with familial amyloid polyneuropathy","volume":"86","author":"Sandgren","year":"2008","journal-title":"Acta Ophthalmol."},{"key":"ref_28","first-page":"117","article-title":"Ophthalmological manifestations in hereditary transthyretin (ATTR V30M) carriers: A review of 513 cases","volume":"22","author":"Malheiro","year":"2014","journal-title":"Amyloid"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1136\/bjo.81.4.295","article-title":"Ocular manifestations of familial amyloidotic polyneuropathy type I: Long term follow up","volume":"81","author":"Ando","year":"1997","journal-title":"Br. J. Ophthalmol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.ajo.2018.05.023","article-title":"Angiographic Signatures of the Predominant Form of Familial Transthyretin Amyloidosis (Val30Met Mutation)","volume":"192","author":"Rousseau","year":"2018","journal-title":"Am. J. Ophthalmol."},{"key":"ref_31","first-page":"31","article-title":"Impact of liver transplantation on the natural history of oculopathy in Portuguese patients with transthyretin (V30M) amyloidosis","volume":"22","author":"Malheiro","year":"2014","journal-title":"Amyloid"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"E2403","DOI":"10.1002\/humu.22619","article-title":"Online Registry for Mutations in Hereditary Amyloidosis Including Nomenclature Recommendations","volume":"35","author":"Rowczenio","year":"2014","journal-title":"Hum. Mutat."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1136\/jmg.29.12.888","article-title":"A new mutant transthyretin (Arg 10) associated with familial amyloid polyneuropathy","volume":"29","author":"Uemichi","year":"1992","journal-title":"J. Med. Genet."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"268","DOI":"10.3109\/13506120209114105","article-title":"A new transthyretin variant Leu55Gln in a patient with systemic amyloidosis","volume":"9","author":"Yazaki","year":"2002","journal-title":"Amyloid"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"114","DOI":"10.3109\/13506129909007311","article-title":"A new transthyretin variant (Ser23Asn) associated with familial amyloidosis in a Portuguese patient","volume":"6","author":"Connors","year":"1999","journal-title":"Amyloid"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"28","DOI":"10.3109\/13816810.2011.599356","article-title":"Vitreous amyloidosis in two large mainland Chinese kindreds resulting from transthyretin variant Lys35Thr and Leu55Arg","volume":"33","author":"Long","year":"2012","journal-title":"Ophthalmic Genet."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1080\/13816810.2016.1232413","article-title":"Elderly onset vitreous opacities as the initial manifestation in hereditary transthyretin (ATTR Val30Met) carriers","volume":"38","author":"Ishida","year":"2017","journal-title":"Ophthalmic Genet."},{"key":"ref_38","first-page":"353","article-title":"Transthyretin Pro55, a variant associated with early-onset, aggressive, diffuse amyloidosis with cardiac and neurologic involvement","volume":"89","author":"Jacobson","year":"1992","journal-title":"Qual. Life Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1016\/j.humpath.2013.10.037","article-title":"The pathologic spectrum of oculoleptomeningeal amyloidosis with Val30Gly transthyretin gene mutation in a postmortem case","volume":"45","author":"Martin","year":"2014","journal-title":"Hum. Pathol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1016\/S0006-291X(05)81304-X","article-title":"New mutant gene (transthyretin Arg 58) in cases with hereditary polyneuropathy detected by non-isotope method of single-strand conformation polymorphism analysis","volume":"180","author":"Saeki","year":"1991","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1775","DOI":"10.1110\/ps.0349703","article-title":"Identification ofS-sulfonation andS-thiolation of a novel transthyretin Phe33Cys variant from a patient diagnosed with familial transthyretin amyloidosis","volume":"12","author":"Lim","year":"2003","journal-title":"Protein Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.1001\/archneur.56.9.1152","article-title":"Oculoleptomeningeal Amyloidosis Associated With a New Transthyretin Variant Ser64","volume":"56","author":"Uemichi","year":"1999","journal-title":"Arch. Neurol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/S0006-291X(88)81208-7","article-title":"Restriction fragment analysis confirms the position 33 mutation in transthyretin from an Israeli patient (SKO) with familial amyloidotic polyneuropathy","volume":"153","author":"Jacobson","year":"1988","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"317","DOI":"10.3129\/i09-023","article-title":"Oculoleptomeningeal amyloidosis in 3 individuals with the transthyretin variant Tyr69His","volume":"44","author":"Schweitzer","year":"2009","journal-title":"Can. J. Ophthalmol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"201","DOI":"10.3109\/13506129.2012.724035","article-title":"Familial amyloid polyneuropathy associated with the novel transthyretin variant Arg34Gly","volume":"19","author":"Hawkins","year":"2012","journal-title":"Amyloid"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2094","DOI":"10.1212\/WNL.42.11.2094","article-title":"Familial amyloidotic polyneuropathy presenting with carpal tunnel syndrome and a new transthyretin mutation, asparagine 70","volume":"42","author":"Izumoto","year":"1992","journal-title":"Neurology"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1002\/humu.1380020516","article-title":"Transthyretin ALA 71: A new transthyretin variant in a Spanish family with familial amyloidotic polyneuropathy","volume":"2","author":"Almeida","year":"1993","journal-title":"Hum. Mutat."},{"key":"ref_48","first-page":"979","article-title":"Proline at position 36: A new transthyretin mutation associated with familial amyloidotic polyneuropathy","volume":"48","author":"Jones","year":"1991","journal-title":"Am. J. Hum. Genet."},{"key":"ref_49","first-page":"13","article-title":"Identification of a TTR gene mutation in a family with hereditary vitreous amyloidosis","volume":"29","author":"Xie","year":"2012","journal-title":"Zhonghua Yi Xue Yi Chuan Xue Za Zhi"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"263","DOI":"10.3109\/13506120209114104","article-title":"Transthyretin amyloidosis associated with a novel variant (Trp41Leu) presenting with vitreous opacities","volume":"9","author":"Yazaki","year":"2002","journal-title":"Amyloid"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1016\/S0161-6420(92)31949-9","article-title":"A new transthyretin mutation associated with amyloidotic vitreous opacities. Asparagine for isoleucine at position 84","volume":"99","author":"Skinner","year":"1992","journal-title":"Ophthalmology"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"S39","DOI":"10.3233\/JND-150091","article-title":"Transthyretin-Related Familial Amyloid Polyneuropathy (TTR-FAP): A Single-Center Experience in Sicily, an Italian Endemic Area","volume":"2","author":"Mazzeo","year":"2015","journal-title":"J. Neuromuscul. Dis."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1172\/JCI112675","article-title":"Characterization of a transthyretin (prealbumin) variant associated with familial amyloidotic polyneuropathy type II (Indiana\/Swiss)","volume":"78","author":"Dwulet","year":"1986","journal-title":"J. Clin. Investig."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1136\/jnnp.2006.093500","article-title":"A novel amyloidogenic transthyretin variant, Gly53Ala, associated with intermittent headaches and ataxia","volume":"78","author":"Douglass","year":"2007","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"282","DOI":"10.3109\/13506129909007341","article-title":"Usefulness of MALDI\/TOF mass spectrometry of immunoprecipitated serum variant transthyretin in the diagnosis of familial amyloid polyneuropathy","volume":"6","author":"Tachibana","year":"1999","journal-title":"Amyloid"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1093\/brain\/118.4.849","article-title":"Transthyretin gene analysis in European patients with suspected familial amyloid polyneuropathy","volume":"118","author":"Reilly","year":"1995","journal-title":"Brain"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/0006-291X(90)91445-X","article-title":"A novel variant of transthyretin (Tyr114 to Cys) deduced from the nucleotide sequences of gene fragments from familial amyloidotic polyneuropathy in Japanese sibling cases","volume":"169","author":"Ueno","year":"1990","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1212\/WNL.53.3.637","article-title":"An aggressive familial amyloidotic polyneuropathy caused by a new variant transthyretin Lys 54","volume":"53","author":"Togashi","year":"1999","journal-title":"Neurology"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"54","DOI":"10.3109\/13506129908993288","article-title":"A new amyloidogenic transthyretin variant (Val122Ala) found in a compound heterozygous patient","volume":"6","author":"Connors","year":"1999","journal-title":"Amyloid"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-020-62559-x","article-title":"Small gauge vitrectomy for vitreous amyloidosis and subsequent management of secondary glaucoma in patients with hereditary transthyretin amyloidosis","volume":"10","author":"Kakihara","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.1097\/IAE.0b013e318203c0c2","article-title":"Recurrence of vitreous amyloidosis and need of surgical reintervention in Portuguese patients with familial amyloidosis ATTR V30M","volume":"31","author":"Matos","year":"2011","journal-title":"Retina"},{"key":"ref_62","unstructured":"Ferreira, N.N., Dias, D.A.C., Carvalho, R.P.A., and Coelho, M.T.P.M. (2017). Re-Intervention in De Novo Vitreous Opacities After Pars Plana Vitrectomy in Familial Amyloidotic Polyneuropathy TTR Val30Met Portuguese Patients. Retin Cases Brief Rep., 1\u20136."},{"key":"ref_63","first-page":"5423027","article-title":"A Case of Conjunctival Amyloidosis with Repeated Subconjunctival Hemorrhage","volume":"2017","author":"Ando","year":"2017","journal-title":"Case Rep. Ophthalmol. Med."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"e230370","DOI":"10.1136\/bcr-2019-230370","article-title":"Yellow subconjunctival deposits","volume":"12","author":"Zloto","year":"2019","journal-title":"BMJ Case Rep."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1080\/13506129.2019.1594760","article-title":"Conjunctival lymphangiectasia: A novel ocular manifestation of hereditary transthyretin amyloidosis","volume":"26","author":"Hayek","year":"2019","journal-title":"Amyloid"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1136\/bjophthalmol-2019-315381","article-title":"Conjunctival lymphangiectasia as a biomarker of severe systemic disease in Ser77Tyr hereditary transthyretin amyloidosis","volume":"104","author":"Bunod","year":"2020","journal-title":"Br. J. Ophthalmol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1001\/jamaophthalmol.2016.1889","article-title":"Potential Role of In Vivo Confocal Microscopy for Imaging Corneal Nerves in Transthyretin Familial Amyloid Polyneuropathy","volume":"134","author":"Rousseau","year":"2016","journal-title":"JAMA Ophthalmol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1138","DOI":"10.2337\/dc14-2422","article-title":"Small Nerve Fiber Quantification in the Diagnosis of Diabetic Sensorimotor Polyneuropathy: Comparing Corneal Confocal Microscopy With Intraepidermal Nerve Fiber Density","volume":"38","author":"Chen","year":"2015","journal-title":"Diabetes Care"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"976","DOI":"10.1002\/mus.21383","article-title":"Corneal confocal microscopy: A novel noninvasive means to diagnose neuropathy in patients with fabry disease","volume":"40","author":"Tavakoli","year":"2009","journal-title":"Muscle Nerve"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1002\/mus.23377","article-title":"Corneal confocal microscopy detects small-fiber neuropathy in Charcot-Marie-Tooth disease type 1A patients","volume":"46","author":"Tavakoli","year":"2012","journal-title":"Muscle Nerve"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"92","DOI":"10.3109\/13506129.2011.576719","article-title":"Anticipation of presbyopia in Portuguese familial amyloidosis ATTR V30M","volume":"18","author":"Matos","year":"2011","journal-title":"Amyloid"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Kakihara, S., Hirano, T., Matsuda, Y., Takano, D., Imai, A., Miyahara, T., and Murata, T. (2021). Deposits on Retinal Surface Seen on OCT in Ocular Amyloidosis. Ophthalmol. Retin., 2468.","DOI":"10.1016\/j.oret.2020.12.028"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1080\/13506129.2020.1827381","article-title":"Subclinical retinal angiopathy associated with hereditary transthyretin amyloidosis\u2013Assessed with optical coherence tomography angiography","volume":"28","author":"Marques","year":"2021","journal-title":"Amyloid"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1097\/IAE.0000000000002961","article-title":"Association between Choroidal Characteristics and Systemic Severity in Amyloidosis","volume":"41","author":"Mano","year":"2021","journal-title":"Retina"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Marques, J.H., Malheiro, L., Malheiro, J., Oliveira, L., Men\u00e9res, M.J., and Beir\u00e3o, J.M. (2021). Pupillometry: An objective test to assess endocular hereditary transthyretin amyloidosis. Eur. J. Ophthalmol., 18.","DOI":"10.1177\/1120672121997294"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/S0039-6257(95)80025-5","article-title":"Ocular amyloidosis, with special reference to thehereditary forms with vitreous involvement","volume":"40","author":"Sandgren","year":"1995","journal-title":"Surv. Ophthalmol."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Dermarkarian, C.R., Bhatt, A., Ch\u00e9vez-Barrios, P., and Allen, R.C. (2021). Bilateral acquired nasolacrimal duct obstruction secondary to amyloidosis in a 15-year-old. J. Am. Assoc. Pediatr. Ophthalmol. Strabismus, 1091.","DOI":"10.1016\/j.jaapos.2020.11.011"},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Chean, C.S., Sovani, V., Boden, A., and Knapp, C. (2020). Lacrimal gland extranodal marginal zone B-cell lymphoma in the presence of amyloidosis. Orbit.","DOI":"10.1080\/01676830.2020.1852578"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.ajo.2018.05.032","article-title":"Ocular Adnexal Amyloidosis: A Mass Spectrometric Analysis","volume":"193","author":"Blandford","year":"2018","journal-title":"Am. J. Ophthalmol."},{"key":"ref_80","first-page":"148","article-title":"Orbital and peri-orbital amyloidosis: A report of four cases","volume":"38","author":"Bahamondes","year":"2018","journal-title":"Orbit"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.jaapos.2019.11.003","article-title":"Isolated orbital amyloidosis causing internal and external ophthalmoplegia","volume":"24","author":"Dodd","year":"2020","journal-title":"J. Am. Assoc. Pediatr. Ophthalmol. Strabismus"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1080\/01676830.2019.1594988","article-title":"Ocular amyloid: Adnexal and systemic involvement","volume":"39","author":"Kang","year":"2019","journal-title":"Orbit"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1080\/01676830.2019.1594980","article-title":"Orbital AL amyloid","volume":"39","author":"Chan","year":"2019","journal-title":"Orbit"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"976","DOI":"10.1007\/s00415-017-8708-4","article-title":"Transthyretin familial amyloid polyneuropathy: An update","volume":"265","year":"2018","journal-title":"J. Neurol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1080\/13506129.2016.1191458","article-title":"Suppressing transthyretin production in mice, monkeys and humans using 2nd-Generation antisense oligonucleotides","volume":"23","author":"Ackermann","year":"2016","journal-title":"Amyloid"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1864","DOI":"10.1073\/pnas.0910603106","article-title":"Lipid-like materials for low-dose, in vivo gene silencing","volume":"107","author":"Love","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1056\/NEJMoa1208760","article-title":"Safety and Efficacy of RNAi Therapy for Transthyretin Amyloidosis","volume":"369","author":"Coelho","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1056\/NEJMoa1805689","article-title":"Tafamidis Treatment for Patients with Transthyretin Amyloid Cardiomyopathy","volume":"379","author":"Maurer","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"2658","DOI":"10.1001\/jama.2013.283815","article-title":"Diflunisal Trial Consortium. Repurposing diflunisal for familial amyloid polyneuropathy: A randomized clinical trial","volume":"310","author":"Berk","year":"2013","journal-title":"JAMA"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"55","DOI":"10.3109\/13506129809007291","article-title":"Gelsolin-related familial amyloidosis, Finnish type (FAF), and its variants found worldwide","volume":"5","author":"Kiuru","year":"1998","journal-title":"Amyloid"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"282","DOI":"10.3109\/10409238.2012.661401","article-title":"Gelsolin amyloidosis: Genetics, biochemistry, pathology and possible strategies for therapeutic intervention","volume":"47","author":"Solomon","year":"2012","journal-title":"Crit. Rev. Biochem. Mol. Biol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"506","DOI":"10.3109\/07853890.2015.1075063","article-title":"Natural course of Finnish gelsolin amyloidosis","volume":"47","author":"Nikoskinen","year":"2015","journal-title":"Ann. Med."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Potr\u010d, M., Volk, M., de Rosa, M., Pi\u017eem, J., Teran, N., Jakli\u010d, H., Maver, A., Drnov\u0161ek-Olup, B., Bollati, M., and Vogelnik, K. (2021). Clinical and Histopathological Features of Gelsolin Amyloidosis Associated with a Novel GSN Variant p.Glu580Lys. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22031084"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1016\/B978-0-444-52902-2.00039-4","article-title":"Chapter 39\u2013Hereditary Gelsolin Amyloidosis","volume":"Volume 115","author":"Said","year":"2013","journal-title":"Peripheral Nerve Disorders"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1016\/0888-7543(92)90183-S","article-title":"Homozygosity for the Asn187 gelsolin mutation in Finnish-type familial amyloidosis is associated with severe renal disease","volume":"13","author":"Maury","year":"1992","journal-title":"Genomics"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1053\/j.ajkd.2012.07.016","article-title":"Renal Amyloidosis Associated With a Novel Sequence Variant of Gelsolin","volume":"61","author":"Sethi","year":"2013","journal-title":"Am. J. Kidney Dis."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"110","DOI":"10.3109\/13506129.2014.891502","article-title":"Novel gelsolin variant as the cause of nephrotic syndrome and renal amyloidosis in a large kindred","volume":"21","author":"Efebera","year":"2014","journal-title":"Amyloid"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1111\/j.1755-3768.2009.01686.x","article-title":"Lattice corneal dystrophy, gelsolin type (Meretoja\u2019s syndrome)","volume":"87","author":"Carrwik","year":"2009","journal-title":"Acta Ophthalmol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/j.febslet.2006.12.019","article-title":"Identification of an amyloidogenic region on keratoepithelin via synthetic peptides","volume":"581","author":"Yuan","year":"2006","journal-title":"FEBS Lett."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1007\/s00417-005-0153-x","article-title":"Keratoepithelin in secondary corneal amyloidosis","volume":"244","author":"Suesskind","year":"2005","journal-title":"Graefe\u2019s Arch. Clin. Exp. Ophthalmol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1080\/08820538.2019.1687738","article-title":"Amyloidosis and Ocular Involvement: An Overview","volume":"35","author":"Dammacco","year":"2020","journal-title":"Semin. Ophthalmol."},{"key":"ref_102","first-page":"31","article-title":"Familial subepithelial corneal amyloidosis (gelatinous drop-like corneal dystrophy): Exclusion of linkage to lactoferrin gene","volume":"4","author":"Klintworth","year":"1998","journal-title":"Mol. Vis."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1159\/000324079","article-title":"Clinical and basic aspects of gelatinous drop-like corneal dystrophy","volume":"48","author":"Kawasaki","year":"2011","journal-title":"Dev. Ophthalmol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"67","DOI":"10.3109\/13506129.2014.983222","article-title":"Clinico-histopathological and biochemical analyses of corneal amyloidosis in gelatinous drop-like corneal dystrophy","volume":"22","author":"Tasaki","year":"2014","journal-title":"Amyloid"},{"key":"ref_105","first-page":"2756","article-title":"Familial subepithelial corneal amyloidosis--a lactoferrin-related amyloidosis","volume":"38","author":"Klintworth","year":"1997","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1111\/ceo.12149","article-title":"Corneal dystrophies and genetics in the International Committee for Classification of Corneal Dystrophies era: A review","volume":"42","author":"Vincent","year":"2014","journal-title":"Clin. Exp. Ophthalmol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1166","DOI":"10.1016\/j.ophtha.2012.11.047","article-title":"Classification of Secondary Corneal Amyloidosis and Involvement of Lactoferrin","volume":"120","author":"Hirano","year":"2013","journal-title":"Ophthalmology"},{"key":"ref_108","first-page":"2115","article-title":"Findings of secondary corneal amyloidosis with ultrahigh-resolution optical coherence tomography","volume":"8","author":"Osakabe","year":"2014","journal-title":"Clin. Ophthalmol."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/12\/7\/955\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:21:09Z","timestamp":1760163669000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/12\/7\/955"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,22]]},"references-count":108,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2021,7]]}},"alternative-id":["genes12070955"],"URL":"https:\/\/doi.org\/10.3390\/genes12070955","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,22]]}}}