{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:12:52Z","timestamp":1787029972660,"version":"build-2736575974"},"reference-count":54,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2021,12,8]],"date-time":"2021-12-08T00:00:00Z","timestamp":1638921600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Tomography"],"abstract":"<jats:p>Ocular abnormalities occur frequently in Friedreich\u2019s ataxia (FRDA), although visual symptoms are not always reported. We evaluated a cohort of patients with FRDA to characterise the clinical phenotype and optic nerve findings as detected with optical coherence tomography (OCT). A total of 48 patients from 42 unrelated families were recruited. Mean age at onset was 13.8 years (range 4\u201340), mean disease duration 19.5 years (range 5\u201343), mean disease severity as quantified with the Scale for the Assessment and Rating of Ataxia 22\/40 (range 4.5\u201338). All patients displayed variable ataxia and two-thirds had ocular abnormalities. Statistically significant thinning of average retinal nerve fibre layer (RNFL) and thinning in all but the temporal quadrant compared to controls was demonstrated on OCT. Significant RNFL and macular thinning was documented over time in 20 individuals. Disease severity and visual acuity were correlated with RNFL and macular thickness, but no association was found with disease duration. Our results highlight that FDRA is associated with subclinical optic neuropathy. This is the largest longitudinal study of OCT findings in FRDA to date, demonstrating progressive RNFL thickness decline, suggesting that RNFL thickness as measured by OCT has the potential to become a quantifiable biomarker for the evaluation of disease progression in FRDA.<\/jats:p>","DOI":"10.3390\/tomography7040076","type":"journal-article","created":{"date-parts":[[2021,12,13]],"date-time":"2021-12-13T03:14:29Z","timestamp":1639365269000},"page":"915-931","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Longitudinal Assessment Using Optical Coherence Tomography in Patients with Friedreich\u2019s Ataxia"],"prefix":"10.3390","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8944-4921","authenticated-orcid":false,"given":"Petya","family":"Bogdanova-Mihaylova","sequence":"first","affiliation":[{"name":"National Ataxia Clinic, Department of Neurology, Tallaght University Hospital, Tallaght, Dublin 24, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helena Maria","family":"Plapp","sequence":"additional","affiliation":[{"name":"School of Medicine, Trinity College Dublin, Dublin 2, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongying","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Medicine, Trinity College Dublin, Dublin 2, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Early","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Tallaght University Hospital, Dublin 24, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorraine","family":"Cassidy","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Tallaght University Hospital, Dublin 24, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard A.","family":"Walsh","sequence":"additional","affiliation":[{"name":"National Ataxia Clinic, Department of Neurology, Tallaght University Hospital, Tallaght, Dublin 24, Ireland"},{"name":"Dublin Neurological Institute at the Mater Hospital and University College Dublin, Dublin 7, Ireland"},{"name":"Academic Unit of Neurology, Trinity College Dublin, Dublin 2, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sin\u00e9ad M.","family":"Murphy","sequence":"additional","affiliation":[{"name":"National Ataxia Clinic, Department of Neurology, Tallaght University Hospital, Tallaght, Dublin 24, Ireland"},{"name":"Academic Unit of Neurology, Trinity College Dublin, Dublin 2, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1007\/s12311-019-01052-2","article-title":"The Classification of Autosomal Recessive Cerebellar Ataxias: A Consensus Statement from the Society for Research on the Cerebellum and Ataxias Task Force","volume":"18","author":"Beaudin","year":"2019","journal-title":"Cerebellum"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/s40673-017-0062-x","article-title":"Friedreich Ataxia: Current Status and Future Prospects","volume":"4","year":"2017","journal-title":"Cerebellum Ataxias"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1126\/science.271.5254.1423","article-title":"Friedreich\u2019s ataxia: Autosomal recessive disease caused by an intronic GAA triplet repeat expansion","volume":"271","author":"Campuzano","year":"1996","journal-title":"Science"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1002\/ana.24595","article-title":"Compound heterozygous FXN mutations and clinical outcome in friedreich ataxia","volume":"79","author":"Galea","year":"2016","journal-title":"Ann. Neurol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1001\/archneur.59.2.296","article-title":"Intrafamilial phenotypic variability in Friedreich ataxia associated with a G130V mutation in the FRDA gene","volume":"59","author":"McCabe","year":"2002","journal-title":"Arch. Neurol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/s00415-009-1002-3","article-title":"Friedreich ataxia: The clinical picture","volume":"256","author":"Pandolfo","year":"2009","journal-title":"J. Neurol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1111\/jnc.12317","article-title":"Clinical features of Friedreich\u2019s ataxia: Classical and atypical phenotypes","volume":"126","author":"Parkinson","year":"2013","journal-title":"J. Neurochem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1056\/NEJM199610173351601","article-title":"Clinical and genetic abnormalities in patients with Friedreich\u2019s ataxia","volume":"335","author":"Cossee","year":"1996","journal-title":"N. Engl. J. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1097\/NEN.0b013e31827e5762","article-title":"Friedreich ataxia: Neuropathology revised","volume":"72","author":"Koeppen","year":"2013","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1093\/brain\/104.3.589","article-title":"Friedreich\u2019s ataxia: A clinical and genetic study of 90 families with an analysis of early diagnostic criteria and intrafamilial clustering of clinical features","volume":"104","author":"Harding","year":"1981","journal-title":"Brain"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1007\/s11845-011-0744-y","article-title":"Friedreich\u2019s Ataxia: A review from a cardiology perspective","volume":"180","author":"Bourke","year":"2011","journal-title":"Ir. J. Med. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e917","DOI":"10.1212\/WNL.0000000000006121","article-title":"Nonataxia symptoms in Friedreich Ataxia: Report from the registry of the European Friedreich\u2019s Ataxia consortium for translational studies (EFACTS)","volume":"91","author":"Reetz","year":"2018","journal-title":"Neurology"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1093\/brain\/awm323","article-title":"Vestibular, saccadic and fixation abnormalities in genetically confirmed Friedreich ataxia","volume":"131","author":"Fahey","year":"2008","journal-title":"Brain"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1093\/brain\/awl309","article-title":"What clinical disorders tell us about the neural control of saccadic eye movements","volume":"130","author":"Ramat","year":"2007","journal-title":"Brain"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1001\/archneur.1983.04050060043006","article-title":"Eye movements in Friedreich\u2019s ataxia","volume":"40","author":"Furman","year":"1983","journal-title":"Arch. Neurol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2131","DOI":"10.1093\/brain\/120.12.2131","article-title":"Friedrcih\u2019s ataxia: Revision of the phenotype according to molecular genetics","volume":"120","author":"Amoiridis","year":"1997","journal-title":"Brain"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1093\/brain\/117.1.15","article-title":"Comparison of oculomotor findings in the progressive ataxia syndromes","volume":"117","author":"Moschner","year":"1994","journal-title":"Brain"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2362","DOI":"10.1007\/s00415-013-6978-z","article-title":"Analysis of the visual system in Friedreich ataxia","volume":"260","author":"Seyer","year":"2013","journal-title":"J. Neurol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1093\/brain\/awn269","article-title":"Visual system involvement in patients with Friedreich\u2019s ataxia","volume":"132","author":"Fortuna","year":"2009","journal-title":"Brain"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1038\/eye.2011.291","article-title":"Ophthalmic features of Friedreich\u2019s ataxia","volume":"26","author":"Noval","year":"2012","journal-title":"Eye"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1097\/WNO.0000000000000068","article-title":"Optical Coherence Tomography and Visual Field Findings in Patients With Friedreich Ataxia","volume":"34","author":"Parkinson","year":"2014","journal-title":"J. Neuro-Ophthalmol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Rojas, P., Ram\u00edrez, A.I., de Hoz, R., Cadena, M., Ferreras, A., Monsalve, B., Salobrar-Garc\u00eda, E., Mu\u00f1oz-Blanco, J.L., Urcelay-Segura, J.L., and Salazar, J.J. (2020). Ocular Involvement in Friedreich Ataxia Patients and Its Relationship with Neurological Disability, a Follow-Up Study. Diagnostics, 10.","DOI":"10.3390\/diagnostics10020075"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1093\/brain\/awy028","article-title":"Optical coherence tomography in autosomal recessive spastic ataxia of Charlevoix-Saguenay","volume":"141","author":"Parkinson","year":"2018","journal-title":"Brain"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1717","DOI":"10.1212\/01.wnl.0000219042.60538.92","article-title":"Scale for the assessment and rating of ataxia: Development of a new clinical scale","volume":"66","author":"Parkinson","year":"2006","journal-title":"Neurology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e23","DOI":"10.1093\/brain\/awz117","article-title":"Peripapillary retinal nerve fibre layer thickness in Friedreich\u2019s ataxia: A biomarker for trials?","volume":"142","author":"Parkinson","year":"2019","journal-title":"Brain"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Adhi, M., Aziz, S., Muhammad, K., and Adhi, M.I. (2012). Macular Thickness by Age and Gender in Healthy Eyes Using Spectral Domain Optical Coherence Tomography. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0037638"},{"key":"ref_27","unstructured":"(2011). Topcon 3D OCT Series. Normative Database-Summary, Topcon Medical Systems."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1016\/j.ophtha.2011.10.010","article-title":"Retinal nerve fiber layer imaging with spectral-domain optical coherence tomography: A prospective analysis of age-related loss","volume":"119","author":"Leung","year":"2012","journal-title":"Ophthalmology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3897","DOI":"10.1007\/s00415-021-10507-8","article-title":"Neurophysiological and ophthalmological findings of SPG7-related spastic ataxia: A phenotype study in an Irish cohort","volume":"268","author":"Chen","year":"2021","journal-title":"J. Neurol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1111\/jns.12348","article-title":"Clinical spectrum of AIFM1-associated disease in an Irish family, from mild neuropathy to severe cerebellar ataxia with colour blindness","volume":"24","author":"Alexander","year":"2019","journal-title":"J. Peripher. Nerv. Syst."},{"key":"ref_31","first-page":"e9","article-title":"Spastic ataxia associated with colour vision deficiency due to DDHD2 mutations","volume":"27","author":"Austin","year":"2020","journal-title":"Eur. J. Neurol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1111\/jns.12409","article-title":"Childhood onset demyelinating neuropathy with late onset ataxia due to mutation in SAMD9L","volume":"25","author":"Vaughan","year":"2020","journal-title":"J. Peripher. Nerv. Syst."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.preteyeres.2003.10.003","article-title":"Mitochondrial dysfunction as a cause of optic neuropathies","volume":"23","author":"Carelli","year":"2004","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"7608","DOI":"10.1167\/iovs.12-10452","article-title":"Mathematically modeling the involvement of axons in Leber\u2019s hereditary optic neuropathy","volume":"53","author":"Pan","year":"2012","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.preteyeres.2010.11.002","article-title":"Mitochondrial optic neuropathies\u2013disease mechanisms and therapeutic strategies","volume":"30","author":"Griffiths","year":"2011","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/j.survophthal.2009.10.002","article-title":"The Neuro-Ophthalmology of Mitochondrial Disease","volume":"55","author":"Fraser","year":"2010","journal-title":"Surv. Ophthalmol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1136\/bjo.83.2.231","article-title":"Histochemical localization of mitochondrial enzyme activity in human optic nerve and retina","volume":"83","author":"Andrews","year":"1999","journal-title":"Br. J. Ophthalmol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1016\/j.mehy.2004.10.021","article-title":"Optic neuropathies\u2013importance of spatial distribution of mitochondria as well as function","volume":"65","author":"Chinnery","year":"2005","journal-title":"Med. Hypotheses"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1016\/j.bbabio.2009.02.024","article-title":"Retinal ganglion cell neurodegeneration in mitochondrial inherited disorders","volume":"1787","author":"Carelli","year":"2009","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1038\/nrm1620","article-title":"Iron-sulphur cluster biogenesis and mitochondrial iron homeostasis","volume":"6","author":"Rouault","year":"2005","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1038\/ng1097-215","article-title":"Aconitase and mitochondrial iron-sulphur protein deficiency in Friedreich ataxia","volume":"17","author":"Rotig","year":"1997","journal-title":"Nat. Genet."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1719","DOI":"10.1212\/WNL.55.11.1719","article-title":"Oxidative stress in patients with Friedreich ataxia","volume":"55","author":"Schulz","year":"2000","journal-title":"Neurology"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"NS20180060","DOI":"10.1042\/NS20180060","article-title":"Role of frataxin protein deficiency and metabolic dysfunction in Friedreich ataxia, an autosomal recessive mitochondrial disease","volume":"2","author":"Clark","year":"2018","journal-title":"Neuronal Signal."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"R103","DOI":"10.1093\/hmg\/ddq165","article-title":"Understanding the molecular mechanisms of Friedreich\u2019s ataxia to develop therapeutic approaches","volume":"19","author":"Schmucker","year":"2010","journal-title":"Hum. Mol. Genet."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1582","DOI":"10.1001\/archopht.121.11.1582","article-title":"Pathophysiology of the optic neuropathy associated with Friedreich ataxia","volume":"121","author":"Alldredge","year":"2003","journal-title":"Arch. Ophthalmol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1002\/1531-8249(199902)45:2<200::AID-ANA10>3.0.CO;2-U","article-title":"Friedreich\u2019s ataxia: Point mutations and clinical presentation of compound heterozygotes","volume":"45","author":"Schmitt","year":"1999","journal-title":"Ann. Neurol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1159\/000116277","article-title":"Visual involvement in Friedreich\u2019s ataxia: pERG and VEP study","volume":"28","author":"Pinto","year":"1998","journal-title":"Eur. Neurol."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Stricker, S., Oberwahrenbrock, T., Zimmermann, H., Schroeter, J., Endres, M., Brandt, A.U., and Paul, F. (2011). Temporal retinal nerve fiber loss in patients with spinocerebellar ataxia type 1. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0023024"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1376","DOI":"10.1038\/eye.2013.201","article-title":"Optical coherence tomography findings in spinocerebellar ataxia-3","volume":"27","author":"Alvarez","year":"2013","journal-title":"Eye"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1186\/s13023-017-0725-y","article-title":"The progression rate of spinocerebellar ataxia type 2 changes with stage of disease","volume":"13","author":"Monte","year":"2018","journal-title":"Orphanet. J. Rare Dis."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1007\/s00415-010-5467-x","article-title":"A preliminary longitudinal study of the retinal nerve fiber layer in progressive multiple sclerosis","volume":"257","author":"Henderson","year":"2010","journal-title":"J. Neurol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2071","DOI":"10.1038\/eye.2008.363","article-title":"Comparison of time domain Stratus OCT and spectral domain SLO\/OCT for assessment of macular thickness and volume","volume":"23","author":"Forte","year":"2009","journal-title":"Eye"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"564627","DOI":"10.1155\/2012\/564627","article-title":"Time-Domain and Spectral-Domain Optical Coherence Tomography of Retinal Nerve Fiber Layer in MS Patients and Healthy Controls","volume":"2012","author":"Lange","year":"2012","journal-title":"J. Ophthalmol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"FSO398","DOI":"10.2144\/fsoa-2019-0026","article-title":"The current state of biomarker research for Friedreich\u2019s ataxia: A report from the 2018. FARA biomarker meeting","volume":"5","author":"Blair","year":"2019","journal-title":"Futur. Sci. OA"}],"container-title":["Tomography"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2379-139X\/7\/4\/76\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:43:16Z","timestamp":1760168596000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2379-139X\/7\/4\/76"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,8]]},"references-count":54,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["tomography7040076"],"URL":"https:\/\/doi.org\/10.3390\/tomography7040076","relation":{},"ISSN":["2379-139X"],"issn-type":[{"value":"2379-139X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,8]]}}}