{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T08:58:47Z","timestamp":1782550727786,"version":"3.54.5"},"reference-count":40,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2023,10,22]],"date-time":"2023-10-22T00:00:00Z","timestamp":1697932800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Slovenian Research Agency"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Most Leber hereditary optic neuropathy (LHON) cases are bilateral and sequential; however, there are rare unilateral examples, or those in which the delay of onset of vision loss between one and the other eye is longer. In the case of presumed childhood amblyopia in one eye, vision loss in the good eye may be the only symptom of bilateral disease, which was unnoticed in the previously amblyopic eye, or a preexisting episode of LHON in the \u201camblyopic\u201d eye. The clinical decision in such cases may be difficult and suggestive of other forms of atypical optic neuropathy until confirmed by genetic testing. Case series: We present three genetically confirmed (MT-ND1:m.3700G&gt;A, MT-ND6:m14484 T&gt;C, and MT-ND4:m.11778G&gt;A) patients with subacute vision loss in the previously good eye, with the other eye believed to be amblyopic from childhood and their features different from what would be expected in true amblyopia. In all, electrophysiology testing showed a bilaterally reduced amplitude of PERG with low VEP P100 wave amplitudes and prolonged peak time in both eyes, also unusual for amblyopia. During follow-up, the pallor of the optic discs progressed in all eyes. Significant thinning of the peripapillary retinal nerve fiber layer (pRNFL; retinal nerve fiber layer around the optic disc) and ganglion cell complex (GCC) in the macular region was present. All three patients had a peculiar history. The first patient was treated for presumed hyperopic amblyopia that did not improve since childhood, experienced visual loss in the good eye at the age of 17, and was negative for the three typical LHON mutations. Extended testing confirmed an atypical pathogenic variant MT-ND1:m.3700G&gt;A in homoplasmy. The second patient with presumed strabismic amblyopia had an unusual presentation of vision loss only at the age of 61, and after the exclusion of other causes, a typical MT-ND4:m.11778G&gt;A pathogenic variant was found in homoplasmy. The third case was peculiar as he had presumed strabismic amblyopia since childhood and had some degree of disc pallor in the amblyopic eye upon presenting with loss of vision in the good eye at the age of 21, and a typical pathogenic variant m14484 T&gt;C, p.Met64Val was subsequently confirmed. However, one year after disease onset, he started to experience significant spontaneous functional improvement in the non-amblyopic up to 1.0 Snellen whilst improvement in the presumed amblyopic eye was modest, suggesting preexisting amblyopia. This interestingly extensive improvement was carefully followed by electrophysiology as well as visual acuity and fields. Conclusions: This report shows three different scenarios of presentation of LHON in patients with presumed uniocular amblyopia from childhood. In such cases, the diagnosis may be difficult, and detailed structural and functional evaluation of the optic nerve head is necessary to assess whether an earlier LHON episode was misdiagnosed as amblyopia or whether LHON presented bilaterally on both eyes whilst only being noticed in the previously good eye.<\/jats:p>","DOI":"10.3390\/jcm12206669","type":"journal-article","created":{"date-parts":[[2023,10,22]],"date-time":"2023-10-22T07:02:53Z","timestamp":1697958173000},"page":"6669","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Leber Hereditary Optic Neuropathy (LHON) in Patients with Presumed Childhood Monocular Amblyopia"],"prefix":"10.3390","volume":"12","author":[{"given":"Sanja","family":"Petrovic Pajic","sequence":"first","affiliation":[{"name":"Eye Hospital, University Medical Centre Ljubljana, Grablovi\u010deva 46, 1000 Ljubljana, Slovenia"},{"name":"Clinic for Eye Diseases, University Clinical Centre of Serbia, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Fakin","sequence":"additional","affiliation":[{"name":"Eye Hospital, University Medical Centre Ljubljana, Grablovi\u010deva 46, 1000 Ljubljana, Slovenia"},{"name":"Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maja","family":"Sustar Habjan","sequence":"additional","affiliation":[{"name":"Eye Hospital, University Medical Centre Ljubljana, Grablovi\u010deva 46, 1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-0053-2309","authenticated-orcid":false,"given":"Martina","family":"Jarc-Vidmar","sequence":"additional","affiliation":[{"name":"Eye Hospital, University Medical Centre Ljubljana, Grablovi\u010deva 46, 1000 Ljubljana, Slovenia"},{"name":"Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6878-8904","authenticated-orcid":false,"given":"Marko","family":"Hawlina","sequence":"additional","affiliation":[{"name":"Eye Hospital, University Medical Centre Ljubljana, Grablovi\u010deva 46, 1000 Ljubljana, Slovenia"},{"name":"Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1136\/jmg.2007.054270","article-title":"Inherited Mitochondrial Optic Neuropathies","volume":"46","author":"Griffiths","year":"2008","journal-title":"J. Med. Genet."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1016\/j.ajo.2005.03.017","article-title":"Hereditary Optic Neuropathies: From the Mitochondria to the Optic Nerve","volume":"140","author":"Newman","year":"2005","journal-title":"Am. J. Ophthalmol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1111\/j.1442-9071.2007.01628.x","article-title":"Clinical Case Notes: Woman with Atypical Unilateral Leber\u2019s Hereditary Optic Neuropathy with Visual Improvement","volume":"35","author":"Sugisaka","year":"2007","journal-title":"Clin. Exp. Ophthalmol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1007\/s10384-004-0140-5","article-title":"Unilateral Manifestation of Leber\u2019s Hereditary Optic Neuropathy After Blunt Ocular Trauma","volume":"49","author":"Nagai","year":"2005","journal-title":"Jpn. J. Ophthalmol."},{"key":"ref_5","first-page":"1208","article-title":"Segregation Patterns and Heteroplasmy Prevalence in Leber\u2019s Hereditary Optic Neuropathy","volume":"42","author":"Jacobi","year":"2001","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1177\/112067210201200615","article-title":"Ladies with Leber\u2019s Hereditary Optic Neuropathy: An Atypical Disease","volume":"12","author":"Dandekar","year":"2002","journal-title":"Eur. J. Ophthalmol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1093\/brain\/awt343","article-title":"Efficient Mitochondrial Biogenesis Drives Incomplete Penetrance in Leber\u2019s Hereditary Optic Neuropathy","volume":"137","author":"Giordano","year":"2014","journal-title":"Brain"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1167\/iovs.13-13365","article-title":"Retinal Ganglion Cell Dysfunction in Asymptomatic G11778A: Leber Hereditary Optic Neuropathy","volume":"55","author":"Guy","year":"2014","journal-title":"Investig. Opthalmol. Vis. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1038\/sj.eye.6701388","article-title":"Late Onset of Leber\u2019s Hereditary Optic Neuropathy Precipitated by Anaemia","volume":"18","author":"Goyal","year":"2004","journal-title":"Eye"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1505","DOI":"10.1136\/bjophthalmol-2016-310072","article-title":"Childhood-Onset Leber Hereditary Optic Neuropathy","volume":"101","author":"Majander","year":"2017","journal-title":"Br. J. Ophthalmol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.ajo.2022.12.014","article-title":"Childhood-Onset Leber Hereditary Optic Neuropathy\u2014Clinical and Prognostic Insights","volume":"249","author":"Barboni","year":"2023","journal-title":"Am. J. Ophthalmol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1097\/WNO.0000000000000346","article-title":"Atypical Leber Hereditary Optic Neuropathy: 18 Year Interval Between Eyes","volume":"36","author":"Ohden","year":"2016","journal-title":"J. Neuroophthalmol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1016\/S0161-6420(96)30665-9","article-title":"Ophthalmologic Findings in Leber Hereditary Optic Neuropathy, with Special Reference to mtDNA Mutations","volume":"103","author":"Nikoskelainen","year":"1996","journal-title":"Ophthalmology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"5303","DOI":"10.1167\/iovs.06-0520","article-title":"Leber\u2019s Hereditary Optic Neuropathy with Childhood Onset","volume":"47","author":"Barboni","year":"2006","journal-title":"Investig. Opthalmol. Vis. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2283","DOI":"10.1007\/s00417-020-04757-x","article-title":"Genotypic and Phenotypic Characteristics of Korean Children with Childhood-Onset Leber\u2019s Hereditary Optic Neuropathy","volume":"258","author":"Ahn","year":"2020","journal-title":"Graefes Arch. Clin. Exp. Ophthalmol."},{"key":"ref_16","first-page":"15","article-title":"Evidence for a Metabolic Trigger for Leber\u2019s Hereditary Optic Neuropathy. A Case Report","volume":"12","author":"DuBois","year":"1992","journal-title":"J. Clin. Neuroophthalmol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1001\/archneur.1993.00540050022009","article-title":"Atypical Leber\u2019s Hereditary Optic Neuropathy With Molecular Confirmation","volume":"50","author":"Weiner","year":"1993","journal-title":"Arch. Neurol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1542\/peds.91.5.988","article-title":"Leber\u2019s Hereditary Optic Neuropathy as a Cause of Severe Visual Loss in Childhood","volume":"91","author":"Moorman","year":"1993","journal-title":"Pediatrics"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1007\/s004170050301","article-title":"A Pedigree of Leber\u2019s Hereditary Optic Neuropathy with Visual Loss in Childhood, Primarily in Girls","volume":"237","author":"Thieme","year":"1999","journal-title":"Graefes Arch. Clin. Exp. Ophthalmol."},{"key":"ref_20","first-page":"1063","article-title":"Childhood Leber hereditary optic neuropathy. A case of a 6-year-old girl with loss of vision","volume":"26","author":"Balayre","year":"2003","journal-title":"J. Fr. Ophtalmol."},{"key":"ref_21","first-page":"1704","article-title":"Amblyopia: A Multidisciplinary Approach. Proctor Lecture","volume":"26","year":"1985","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"BIO300","DOI":"10.1167\/iovs.17-21773","article-title":"The Photopic Negative Response: An Objective Measure of Retinal Ganglion Cell Function in Patients With Leber\u2019s Hereditary Optic Neuropathy","volume":"58","author":"Karanjia","year":"2017","journal-title":"Investig. Opthalmol. Vis. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e963","DOI":"10.1111\/aos.14659","article-title":"A Novel Excel Sheet Conversion Tool from Snellen Fraction to LogMAR Including \u2018Counting Fingers\u2019, \u2018Hand Movement\u2019, \u2018Light Perception\u2019 and \u2018No Light Perception\u2019 and Focused Review of Literature of Low Visual Acuity Reference Values","volume":"99","author":"Moussa","year":"2021","journal-title":"Acta Ophthalmol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1016\/S0161-6420(89)32814-4","article-title":"Detection of Diabetic Macular Edema","volume":"96","author":"Kinyoun","year":"1989","journal-title":"Ophthalmology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1016\/S0161-6420(98)93601-6","article-title":"Topography of Diabetic Macular Edema with Optical Coherence Tomography","volume":"105","author":"Hee","year":"1998","journal-title":"Ophthalmology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1097\/WNO.0000000000001820","article-title":"Leber Hereditary Optic Neuropathy in a Family of Carriers of MT-ND5 m.13042G>T (A236S) Novel Variant","volume":"43","author":"Brecelj","year":"2023","journal-title":"J. Neuroophthalmol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1038\/ng.806","article-title":"A Framework for Variation Discovery and Genotyping Using Next-Generation DNA Sequencing Data","volume":"43","author":"DePristo","year":"2011","journal-title":"Nat. Genet."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1016\/S0006-291X(02)00672-1","article-title":"Sequence Analysis of the Complete Mitochondrial Genome in Patients with Leber\u2019s Hereditary Optic Neuropathy Lacking the Three Most Common Pathogenic DNA Mutations","volume":"295","author":"Fauser","year":"2002","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1111\/j.1528-1157.1992.tb01765.x","article-title":"Facial Asymmetry in Partial Epilepsies","volume":"33","author":"Tinuper","year":"1992","journal-title":"Epilepsia"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1097\/00041327-199509000-00012","article-title":"Vasculature and Morphometry of the Optic Canal and Intracanalicular Optic Nerve","volume":"15","author":"Chou","year":"1995","journal-title":"J. Neuro-Ophthalmol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"12","DOI":"10.3928\/0191-3913-19820101-05","article-title":"Observations in Sensory Heterotropia","volume":"19","author":"Sidikaro","year":"1982","journal-title":"J. Pediatr. Ophthalmol. Strabismus"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.visres.2017.01.004","article-title":"Interocular Suppression in Children with Deprivation Amblyopia","volume":"133","author":"Hamm","year":"2017","journal-title":"Vis. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1779","DOI":"10.1167\/iovs.16-20964","article-title":"Unilateral Amblyopia Affects Two Eyes: Fellow Eye Deficits in Amblyopia","volume":"58","author":"Meier","year":"2017","journal-title":"Investig. Opthalmol. Vis. Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/S0161-6420(78)35650-5","article-title":"Electrophysiologic Aspects of Amblyopia","volume":"85","author":"Lawwill","year":"1978","journal-title":"Ophthalmology"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Black, J., Lun, V., Phillips, G., and Thompson, B. (2011). Colour Vision in Adult Amblyopia. Acta Ophthalmol., 89.","DOI":"10.1111\/j.1755-3768.2011.465.x"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"21","DOI":"10.4103\/PAJO.PAJO_4_20","article-title":"Evaluation of Visual Function in Patients with Cataract, Amblyopia, Optic Neuritis, and Retinopathies","volume":"2","author":"Espinosa","year":"2020","journal-title":"Pan-Am. J. Ophthalmol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"28","DOI":"10.4274\/tjo.54289","article-title":"Retina and Optic Disc Characteristics in Amblyopic and Non-Amblyopic Eyes of Patients with Myopic or Hyperopic Anisometropia","volume":"47","author":"Ekim","year":"2017","journal-title":"T\u00fcrk Oftalmol. Derg."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2224","DOI":"10.1167\/iovs.03-0297","article-title":"Retinal Nerve Fiber Layer Thickness in Unilateral Amblyopia","volume":"45","author":"Yen","year":"2004","journal-title":"Investig. Opthalmol. Vis. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2444","DOI":"10.1167\/iovs.10-5550","article-title":"A Prospective Study of Macular Thickness in Amblyopic Children with Unilateral High Myopia","volume":"52","author":"Pang","year":"2011","journal-title":"Investig. Opthalmol. Vis. Sci."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Petrovic Pajic, S., Lapajne, L., Vratanar, B., Fakin, A., Jarc-Vidmar, M., Sustar Habjan, M., Volk, M., Maver, A., Peterlin, B., and Hawlina, M. (2022). The Relative Preservation of the Central Retinal Layers in Leber Hereditary Optic Neuropathy. J. Clin. Med., 11.","DOI":"10.3390\/jcm11206045"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/12\/20\/6669\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:09:47Z","timestamp":1760130587000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/12\/20\/6669"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,22]]},"references-count":40,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2023,10]]}},"alternative-id":["jcm12206669"],"URL":"https:\/\/doi.org\/10.3390\/jcm12206669","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,22]]}}}