Visual acuity changes in idebenone treatment‑naïve patients with Leber hereditary optic neuropathy: insights from the CRS-2 study

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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Journal
Journal of Neurology
Published
2026-10-28
DOI
https://doi.org/10.1007/s00415-026-14181-6
Primary Topic
Glaucoma and retinal disorders
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article
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article

Visual acuity changes in idebenone treatment‑naïve patients with Leber hereditary optic neuropathy: insights from the CRS-2 study

Neringa Jurkutė, Patrick Yu‐Wai‐Man, Marcela Votruba, Xavier Llòria et al.
Journal of Neurology
Glaucoma and retinal disorders
article

Visual acuity changes in idebenone treatment‑naïve patients with Leber hereditary optic neuropathy: insights from the CRS-2 study

Neringa Jurkutė, Patrick Yu‐Wai‐Man, Marcela Votruba, Xavier Llòria, Bart Peter Leroy, Thomas Klopstock, Judith Van Everdingen, Maciej Robert Krawczynski, Claudia Priglinger, Birgit Lorenz, Valério Carelli, Christophe Verny, Cécile Andris, Nöel J. C. Bauer, Magda Silva
article en

Abstract

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.

Journal of NeurologyVol. 273(11)
Poznan University of Medical Sciences (PL), Centre National de la Recherche Scientifique (FR), Cardiff and Vale University Health Board (GB), Moorfields Eye Hospital NHS Foundation Trust (GB), Inserm (FR), University of Liège (BE), Justus-Liebig-Universität Gießen (DE), University of Cambridge (GB), Universitätsklinikum Gießen und Marburg (DE), Maastricht University Medical Centre (NL), University Hospital of Wales (GB), Ghent University Hospital (BE), German Center for Neurodegenerative Diseases (DE), LMU Klinikum (DE), Ghent University (BE), Maastricht University (NL), Centre Hospitalier Universitaire d'Angers (FR), Rotterdam Eye Hospital (NL), Istituto delle Scienze Neurologiche di Bologna (IT), Combined Ophthalmic Research Rotterdam (NL), Centre Hospitalier Universitaire de Liège (BE), National Hospital for Neurology and Neurosurgery (GB), Addenbrooke's Hospital (GB), Chiesi (Italy) (IT), Mitochondrial and Cardiovascular Physiopathology (FR), University College London (GB), Université d'Angers (FR), MRC Mitochondrial Biology Unit (GB), Cardiff University (GB), Ludwig-Maximilians-Universität München (DE), University of Bologna (IT)
Openalex Percentile: Top 8%
Glaucoma and retinal disorders
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