Visual acuity changes in idebenone treatment‑naïve patients with Leber hereditary optic neuropathy: insights from the CRS-2 study.
25 affiliations
- 1Department of Medical Genetics, Poznan University of Medical Sciences, 60-806, Poznan, Poland.
- 2GENESIS - Centers for Medical Genetics, 60-529, Poznan, Poland.
- 3Department of Neuro-Ophthalmology, The Rotterdam Eye Hospital (OZR), 3011 BH, Rotterdam, The Netherlands.
- 4The Rotterdam Ophthalmologic Institute (ROI), 3011 BH, Rotterdam, The Netherlands.
- 5Department of Ophthalmology & Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
- 6Department of Head & Skin, Ghent University, Ghent, Belgium.
- 7Centre de Référence des Maladies Neurogénétiques, Département de Neurologie, CHU d'Angers, Angers, France.
- 8MitoLab Team, UMR CNRS 6015 - INSERM U1083, Institut MitoVasc, SFR ICAT, Université Angers, Angers, France.
- 9University Eye Clinic Maastricht, Maastricht University Medical Center, Maastricht, Netherlands.
- 10CHU Sart Tilman, Liege, Belgium.
- 11Department of Ophthalmology, Justus-Liebig-University and Universitätsklinikum Giessen and Marburg GmbH, Giessen Campus, Giessen, Germany.
- 12Eye Department, Cardiff & Vale University Health Board, University Hospital of Wales, Cardiff, UK.
- 13School of Vision Science, Cardiff University, Cardiff, UK.
- 14Department of Ophthalmology, University Hospital, LMU Munich, Munich, Germany.
- 15Moorfields Eye Hospital NHS Foundation Trust, London, UK.
- 16National Hospital of Neurology and Neurosurgery, University College London Hospitals, London, UK.
- 17Institute of Ophthalmology, University College London, London, UK.
- 18Chiesi Farmaceutici SpA, Parma, Emilia-Romagna, Italy.
- 19Magda Joana Silva Lda, Porto, Portugal.
- 20IRCCS Istituto di Scienze Neurologiche di Bologna, Programma di Neurogenetica, Bologna, Italy.
- 21Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.
- 22John van Geest Centre for Brain Repair and MRC Mitochondrial Biology Unit, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
- 23Cambridge Eye Unit, Addenbrooke's Hospital, Cambridge University Hospitals, Cambridge, UK.
- 24Department of Neurology, Friedrich-Baur-Institute, LMU University Hospital, LMU Medizin, Ludwig-Maximilians-Universität (LMU) München, 80336, Munich, Germany. [email protected].
- 25German Center for Neurodegenerative Diseases (DZNE), 81377, Munich, Germany. [email protected].
Abstract
Objective
Case 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
Case 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
Of 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
CRS-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
ClinicalTrials.gov NCT02796274, May 2016.
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BibTeX
@article{krawczynski2026visual,
title = {{Visual acuity changes in idebenone treatment‑naïve patients with Leber hereditary optic neuropathy: insights from the CRS-2 study.}},
author = {Maciej R Krawczynski and Judith van Everdingen and Bart P Leroy and Christophe Verny and Nöel J C Bauer and Cécile Andris and Birgit Lorenz and Marcela Votruba and Claudia Priglinger and Neringa Jurkute and Xavier Llòria and Magda Silva and Valerio Carelli and Patrick Yu-Wai-Man and Thomas Klopstock},
journal = {Journal of neurology},
year = {2026},
month = oct,
doi = {10.1007/s00415-026-14181-6},
url = {https://europepmc.org/article/MED/42955336},
note = {CC BY},
}
RIS
TY - JOUR
TI - Visual acuity changes in idebenone treatment‑naïve patients with Leber hereditary optic neuropathy: insights from the CRS-2 study.
AU - Maciej R Krawczynski
AU - Judith van Everdingen
AU - Bart P Leroy
AU - Christophe Verny
AU - Nöel J C Bauer
AU - Cécile Andris
AU - Birgit Lorenz
AU - Marcela Votruba
AU - Claudia Priglinger
AU - Neringa Jurkute
AU - Xavier Llòria
AU - Magda Silva
AU - Valerio Carelli
AU - Patrick Yu-Wai-Man
AU - Thomas Klopstock
PY - 2026
DA - 2026/10/28
JO - Journal of neurology
DO - 10.1007/s00415-026-14181-6
UR - https://europepmc.org/article/MED/42955336
AB - Objective Case 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 Case 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 Of 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 CRS-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 ClinicalTrials.gov NCT02796274, May 2016.
SN - 0340-5354
SN - 1432-1459
ER -