{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:38:44Z","timestamp":1787027924880,"version":"build-2736575974"},"reference-count":39,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,12,12]],"date-time":"2022-12-12T00:00:00Z","timestamp":1670803200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Friedreich\u2019s ataxia (FRDA) is a rare autosomal recessive neurodegenerative disorder due to the homozygous pathological expansion of guanine-adenine-adenine (GAA) triplet repeats in the first intron of the FXN gene, which encodes for the mitochondrial protein frataxin. In the visual system, the typical manifestations are ocular motility abnormality, optic neuropathy, and retinopathy. Despite the evidence of ophthalmological impairment in FRDA patients, there is a lack of information about the morpho-functional condition of the retina and of the optic pathways in healthy heterozygous carriers of Friedreich\u2019s ataxia (C-FRDA). Ten C-FRDA subjects (providing 20 eyes) and thirty-five Controls (providing 70 eyes) underwent a complete neurological and ophthalmological examination comprehensive of functional (full-field Electroretinogram (ffERG), multifocal Electroretinogram (mfERG), Visual Evoked Potential (VEP), and Pattern Reversal Electroretinogram (PERG)) and morphological assessments (Optical Coherence Tomography, OCT) of the retina, macula, retinal ganglion cells, and visual pathways. The groups\u2019 data were compared using a two-sample t-test. Pearson\u2019s test was used to investigate the morpho-functional correlations. Statistically significant differences (p &lt; 0.01) between C-FRDA and Control eyes for the values of the following parameters were found: ffERG b-wave amplitude, mfERG Response Amplitude Densities, PERG P50 implicit time and P50-N95 amplitude, VEP P100 implicit time, Retinal Nerve Fiber Layer (RNFL) Overall, and Nasal thickness. The values of the OCT macular volume were not statistically different (p &gt; 0.01) between the two Groups. Therefore, our data suggest that, in C-FRDA, a dysfunction of retinal elements without morphological macular impairment may occur. In addition, a morphological impairment of RNFL associated with an abnormal neural conduction along the visual pathways can be also detected.<\/jats:p>","DOI":"10.3390\/diagnostics12123135","type":"journal-article","created":{"date-parts":[[2022,12,13]],"date-time":"2022-12-13T02:59:01Z","timestamp":1670900341000},"page":"3135","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Retinal and Visual Pathways Involvement in Carriers of Friedreich\u2019s Ataxia"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5563-1243","authenticated-orcid":false,"given":"Lucia","family":"Ziccardi","sequence":"first","affiliation":[{"name":"IRCCS\u2014Fondazione Bietti, Via Livenza 1, 00198 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucilla","family":"Barbano","sequence":"additional","affiliation":[{"name":"IRCCS\u2014Fondazione Bietti, Via Livenza 1, 00198 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5200-6071","authenticated-orcid":false,"given":"Giulio","family":"Antonelli","sequence":"additional","affiliation":[{"name":"IRCCS\u2014Fondazione Bietti, Via Livenza 1, 00198 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9720-1065","authenticated-orcid":false,"given":"Ettore","family":"Cioffi","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences and Biotechnologies, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Di Renzo","sequence":"additional","affiliation":[{"name":"IRCCS\u2014Fondazione Bietti, Via Livenza 1, 00198 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"Gioiosa","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences and Biotechnologies, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Marcotulli","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences and Biotechnologies, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3724-2391","authenticated-orcid":false,"given":"Andrzej","family":"Grzybowski","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of Warmia and Mazury, Micha\u0142a Oczapowskiego 2, 10455 Olsztyn, Poland"},{"name":"Institute for Research in Ophthalmology, Foundation for Ophthalmology Development, Mickiewicza 24\/3B, 60-836 Pozna\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Casali","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences and Biotechnologies, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"Parisi","sequence":"additional","affiliation":[{"name":"IRCCS\u2014Fondazione Bietti, Via Livenza 1, 00198 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,12]]},"reference":[{"key":"ref_1","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_2","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_3","doi-asserted-by":"crossref","first-page":"1709","DOI":"10.1126\/science.276.5319.1709","article-title":"Regulation of Mitochondrial Iron Accumulation by Yfh1p, a Putative Homolog of Frataxin","volume":"276","author":"Babcock","year":"1997","journal-title":"Science"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1042\/BJ20111574","article-title":"Inactivation of mitochondrial aspartate aminotransferase contributes to the respiratory deficit of yeast frataxin-deficient cells","volume":"441","author":"Sliwa","year":"2012","journal-title":"Biochem. J."},{"key":"ref_5","first-page":"41","article-title":"Friedreich Ataxia: Current status and future prospects","volume":"4","year":"2017","journal-title":"Cerebellum Ataxias"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1771","DOI":"10.1093\/hmg\/6.11.1771","article-title":"Frataxin is Reduced in Friedreich Ataxia Patients and is Associated with Mitochondrial Membranes","volume":"6","author":"Campuzano","year":"1997","journal-title":"Hum. Mol. Genet."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Rojas, P., De Hoz, R., Cadena, M., Salobrar-Garc\u00eda, E., Fern\u00e1ndez-Albarral, J., L\u00f3pez-Cuenca, I., Elvira-Hurtado, L., Urcelay-Segura, J., Salazar, J., and Ram\u00edrez, J. (2021). Neuro-Ophthalmological Findings in Friedreich\u2019s Ataxia. J. Pers. Med., 11.","DOI":"10.3390\/jpm11080708"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1016\/S0002-9394(14)77738-4","article-title":"Square Wave Jerks in Friedreich\u2019s Ataxia","volume":"85","author":"Dale","year":"1978","journal-title":"Am. J. Ophthalmol."},{"key":"ref_9","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_10","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_11","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":"2008","journal-title":"Brain"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1038\/eye.2011.291","article-title":"Ophthalmic features of Friedreich ataxia","volume":"26","author":"Noval","year":"2011","journal-title":"Eye"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1001\/archopht.125.2.273","article-title":"Catastrophic Visual Loss in a Patient With Friedreich Ataxia","volume":"125","author":"Porter","year":"2007","journal-title":"Arch. Ophthalmol."},{"key":"ref_14","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":"1988","journal-title":"Eur. Neurol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1093\/brain\/103.2.413","article-title":"The Incidence and Nature of Visual Pathway Involvement in Friedreich\u2019s Ataxia","volume":"103","author":"Carroll","year":"1980","journal-title":"Brain"},{"key":"ref_16","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","year":"2014","journal-title":"J. Neuro-Ophthalmol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1038\/nrneurol.2014.79","article-title":"Ophthalmic manifestations of inherited neurodegenerative disorders","volume":"10","author":"Kersten","year":"2014","journal-title":"Nat. Rev. Neurol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1604","DOI":"10.2337\/diabetes.49.9.1604","article-title":"Heterozygous expansion of the GAA tract of the X25\/frataxin gene is associated with insulin resistance in humans","volume":"49","author":"Hebinck","year":"2000","journal-title":"Diabetes"},{"key":"ref_19","first-page":"1191","article-title":"Early and localized retinal dysfunction in patients with type 1 diabetes mellitus studied by multifocal electroretinogram","volume":"55","author":"Ziccardi","year":"2018","journal-title":"Geol. Rundsch."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/j.neucli.2019.04.002","article-title":"Pattern electroretinography and retinal changes in patients with diabetes mellitus type 2","volume":"49","author":"Mermeklieva","year":"2019","journal-title":"Neurophysiol. Clin."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1002\/dmrr.177","article-title":"Visual electrophysiological responses in persons with type 1 diabetes","volume":"17","author":"Parisi","year":"2001","journal-title":"Diabetes\/Metab. Res. Rev."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"473","DOI":"10.2337\/diacare.11.6.473","article-title":"Early Detection of Neurological Involvement in IDDM and NIDDM: Multimodal Evoked Potentials Versus Metabolic Control","volume":"11","author":"Pozzessere","year":"1988","journal-title":"Diabetes Care"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1007\/s10633-022-09872-0","article-title":"ISCEV Standard for full-field clinical electroretinography (2022 update)","volume":"144","author":"Robson","year":"2022","journal-title":"Doc. Ophthalmol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1007\/s10633-020-09812-w","article-title":"ISCEV standard for clinical multifocal electroretinography (mfERG) (2021 update)","volume":"142","author":"Hoffmann","year":"2021","journal-title":"Doc. Ophthalmol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1167\/iovs.61.5.11","article-title":"Macular Functional and Morphological Changes in Intermediate Age-Related Maculopathy","volume":"61","author":"Parisi","year":"2020","journal-title":"Investig. Opthalmol. Vis. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"6893","DOI":"10.1167\/iovs.13-12894","article-title":"Retinal Function and Neural Conduction Along the Visual Pathways in Affected and Unaffected Carriers With Leber\u2019s Hereditary Optic Neuropathy","volume":"54","author":"Ziccardi","year":"2013","journal-title":"Investig. Opthalmol. Vis. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1111\/j.1468-1331.2008.02200.x","article-title":"Electrophysiological assessment of visual function in patients with non-arteritic ischaemic optic neuropathy","volume":"15","author":"Parisi","year":"2008","journal-title":"Eur. J. Neurol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1016\/j.ophtha.2019.02.018","article-title":"Functional Changes of Retinal Ganglion Cells and Visual Pathways in Patients with Chronic Leber\u2019s Hereditary Optic Neuropathy during One Year of Follow-up","volume":"126","author":"Parisi","year":"2019","journal-title":"Ophthalmology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1007\/s10633-009-9195-4","article-title":"Vaegan ISCEV standard for clinical visual evoked potentials (2009 update)","volume":"120","author":"Odom","year":"2009","journal-title":"Doc. Ophthalmol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1097\/00004691-198401000-00003","article-title":"Evoked Potential Techniques in the Evaluation of Visual Function*","volume":"1","author":"Celesia","year":"1984","journal-title":"J. Clin. Neurophysiol."},{"key":"ref_31","first-page":"490","article-title":"The ERG in response to alternating gratings in patients with diseases of the peripheral visual pathway","volume":"21","author":"Fiorentini","year":"1981","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2303","DOI":"10.1212\/WNL.0000000000002774","article-title":"The APOSTEL recommendations for reporting quantitative optical coherence tomography studies","volume":"86","author":"Balk","year":"2016","journal-title":"Neurology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1007\/s00417-020-05023-w","article-title":"Correlations between visual morphological, electrophysiological, and acuity changes in chronic non-arteritic ischemic optic neuropathy","volume":"259","author":"Barbano","year":"2021","journal-title":"Graefes. Arch. Clin. Exp. Ophthalmol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1080\/13816810701537440","article-title":"Retinal Dysfunction in Carriers of Bardet-Biedl Syndrome","volume":"28","author":"Kim","year":"2007","journal-title":"Ophthalmic Genet."},{"key":"ref_35","first-page":"141","article-title":"Characterization of the retinal pigment epithelium in Friedreich ataxia","volume":"4","author":"Crombie","year":"2015","journal-title":"Biochem. Biophys. Rep."},{"key":"ref_36","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 (BBA)\u2014Bioenerg."},{"key":"ref_37","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_38","doi-asserted-by":"crossref","first-page":"710","DOI":"10.3389\/fneur.2017.00710","article-title":"Patterns of Retinal Ganglion Cell Damage in Neurodegenerative Disorders: Parvocellular vs Magnocellular Degeneration in Optical Coherence Tomography Studies","volume":"8","author":"Carelli","year":"2017","journal-title":"Front. Neurol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1017\/S0317167100043407","article-title":"An Electroretinal and Visual Evoked Potential Study in Friedreich\u2019s Ataxia","volume":"8","author":"Kirkham","year":"1981","journal-title":"Can. J. Neurol. Sci."}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/12\/12\/3135\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:40:02Z","timestamp":1760146802000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/12\/12\/3135"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,12]]},"references-count":39,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["diagnostics12123135"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics12123135","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,12]]}}}