{ "abstract": "Objective\n\nCase Record Survey (CRS)-2 was an international, multicenter, retrospective study designed to characterize the natural history of vision loss and spontaneous recovery in patients with Leber hereditary optic neuropathy (LHON).Methods\n\nCase records of idebenone treatment-naïve patients aged ≥12 years, with mitochondrial DNA (mtDNA) variants m.3460G>A, m.11778G>A or m.14484 T>C, onset of symptoms (OoS) after 1999, and ≥2 visual acuity (VA) assessments within 5 years of OoS were analyzed. Disease phases were subacute/dynamic (≤1 year) or chronic (>1 year from OoS). Separate analyses were performed for eyes with VA assessments within 12 or 24±3 months from baseline (first VA assessment after OoS in each eye). Outcomes included: spontaneous clinically relevant recovery (sCRR; improvement from off-chart to ≤1.6 logMAR, or ≥0.2 logMAR if on-chart), sCR stabilization (sCRS; maintenance of VA <1.0 logMAR), sCR benefit (sCRB; eyes with a sCRR and/or sCRS), and sCR worsening (sCRW; worsening to off-chart, or loss of ≥0.2 logMAR if on-chart). The primary endpoint was the proportion of subacute/dynamic eyes 12 months from baseline with sCRB.Results\n\nOf 402 eligible eyes, 385 were subacute/dynamic at baseline, with 96 included in the 12-month analysis. Most patients were male (79.9%), with the m.11778G>A variant (71.7%). The primary endpoint was observed in 20.8% (n=20/96) of eyes. Spontaneous visual outcomes varied by disease phase, mtDNA variant, sex, and age at OoS.Conclusions\n\nCRS-2 provides insights into LHON natural history and suggests the disease course may be more dynamic than previously reported, with spontaneous VA changes occurring well into the chronic phase.Trial registration\n\nClinicalTrials.gov NCT02796274, May 2016.", "abstract_shown": true, "affiliations": [ "Department of Medical Genetics, Poznan University of Medical Sciences, 60-806, Poznan, Poland.", "GENESIS - Centers for Medical Genetics, 60-529, Poznan, Poland.", "Department of Neuro-Ophthalmology, The Rotterdam Eye Hospital (OZR), 3011 BH, Rotterdam, The Netherlands.", "The Rotterdam Ophthalmologic Institute (ROI), 3011 BH, Rotterdam, The Netherlands.", "Department of Ophthalmology & Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium.", "Department of Head & Skin, Ghent University, Ghent, Belgium.", "Centre de Référence des Maladies Neurogénétiques, Département de Neurologie, CHU d'Angers, Angers, France.", "MitoLab Team, UMR CNRS 6015 - INSERM U1083, Institut MitoVasc, SFR ICAT, Université Angers, Angers, France.", "University Eye Clinic Maastricht, Maastricht University Medical Center, Maastricht, Netherlands.", "CHU Sart Tilman, Liege, Belgium.", "Department of Ophthalmology, Justus-Liebig-University and Universitätsklinikum Giessen and Marburg GmbH, Giessen Campus, Giessen, Germany.", "Eye Department, Cardiff & Vale University Health Board, University Hospital of Wales, Cardiff, UK.", "School of Vision Science, Cardiff University, Cardiff, UK.", "Department of Ophthalmology, University Hospital, LMU Munich, Munich, Germany.", "Moorfields Eye Hospital NHS Foundation Trust, London, UK.", "National Hospital of Neurology and Neurosurgery, University College London Hospitals, London, UK.", "Institute of Ophthalmology, University College London, London, UK.", "Chiesi Farmaceutici SpA, Parma, Emilia-Romagna, Italy.", "Magda Joana Silva Lda, Porto, Portugal.", "IRCCS Istituto di Scienze Neurologiche di Bologna, Programma di Neurogenetica, Bologna, Italy.", "Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.", "John van Geest Centre for Brain Repair and MRC Mitochondrial Biology Unit, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.", "Cambridge Eye Unit, Addenbrooke's Hospital, Cambridge University Hospitals, Cambridge, UK.", "Department of Neurology, Friedrich-Baur-Institute, LMU University Hospital, LMU Medizin, Ludwig-Maximilians-Universität (LMU) München, 80336, Munich, Germany. Thomas.Klopstock@med.uni-muenchen.de.", "German Center for Neurodegenerative Diseases (DZNE), 81377, Munich, Germany. Thomas.Klopstock@med.uni-muenchen.de." ], "article_type": "research article", "arxiv": null, "author_total": 15, "authors": [ { "affs": [ 0, 1 ], "name": "Maciej R Krawczynski" }, { "affs": [ 2, 3 ], "name": "Judith van Everdingen" }, { "affs": [ 4, 5 ], "name": "Bart P Leroy" }, { "affs": [ 6, 7 ], "name": "Christophe Verny" }, { "affs": [ 8 ], "name": "Nöel J C Bauer" }, { "affs": [ 9 ], "name": "Cécile Andris" }, { "affs": [ 10 ], "name": "Birgit Lorenz" }, { "affs": [ 11, 12 ], "name": "Marcela Votruba" }, { "affs": [ 13 ], "name": "Claudia Priglinger" }, { "affs": [ 14, 15, 16 ], "name": "Neringa Jurkute" }, { "affs": [ 17 ], "name": "Xavier Llòria" }, { "affs": [ 18 ], "name": "Magda Silva" }, { "affs": [ 19, 20 ], "name": "Valerio Carelli" }, { "affs": [ 14, 21, 22, 16 ], "name": "Patrick Yu-Wai-Man" }, { "affs": [ 23, 24 ], "name": "Thomas Klopstock", "orcid": "0000-0003-2805-4652" } ], "bibtex": "https://research.draconitic.com/paper/a02knnyd1cmjc.bib", "cited_by": 0, "doi": "10.1007/s00415-026-14181-6", "fulltext_url": "https://europepmc.org/articles/PMC13719768", "id": "a02knnyd1cmjc", "issns": [ "0340-5354", "1432-1459" ], "landing_url": "https://europepmc.org/article/MED/42955336", "language": "eng", "licence": "CC-BY", "licence_label": "CC BY", "licence_source": "article", "licence_url": "https://creativecommons.org/licenses/by/4.0/", "metadata_licence": null, "native_subjects": [ [ "heading", "Original Communication" ], [ "openalex", "2731|Glaucoma and retinal disorders" ] ], "openalex": "W7224543179", "pdf_url": "https://europepmc.org/articles/PMC13719768?pdf=render", "pmcid": "PMC13719768", "pmid": "42955336", "published": "2026-10-28", "publisher": null, "ris": "https://research.draconitic.com/paper/a02knnyd1cmjc.ris", "sources": [ { "first_seen": "2026-11-01T00:20:36Z", "native_id": "MED:42955336", "source": "europepmc", "url": "https://europepmc.org/article/MED/42955336" }, { "first_seen": "2026-11-02T12:23:40Z", "native_id": "PMC13719768", "source": "pmc", "url": "https://doi.org/10.1007/s00415-026-14181-6" } ], "subjects": [ { "field": "medicine", "origin": "openalex:2731|Glaucoma and retinal disorders", "subfield": "general" } ], "title": "Visual acuity changes in idebenone treatment‑naïve patients with Leber hereditary optic neuropathy: insights from the CRS-2 study.", "title_text": "Visual acuity changes in idebenone treatment‑naïve patients with Leber hereditary optic neuropathy: insights from the CRS-2 study.", "type": "peer-reviewed", "updated_at": "2026-11-03T12:20:46Z", "url": "https://research.draconitic.com/paper/a02knnyd1cmjc", "venue": "Journal of neurology", "versions": [] }