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. 2022 Apr;36(4):818-826.
doi: 10.1038/s41433-021-01535-9. Epub 2021 Apr 28.

Natural history of patients with Leber hereditary optic neuropathy-results from the REALITY study

Patrick Yu-Wai-Man  1   2   3   4 , Nancy J Newman  5 , Valerio Carelli  6   7 , Chiara La Morgia  6   7 , Valérie Biousse  5 , Francesco M Bandello  8   9 , Catherine Vignal Clermont  10   11 , Lorena Castillo Campillo  12 , Stephanie Leruez  13 , Mark L Moster  14 , Dean M Cestari  15 , Rod Foroozan  16 , Alfredo Sadun  17 , Rustum Karanjia  17   18 , Neringa Jurkute  19   20 , Laure Blouin  21 , Magali Taiel  21 , José-Alain Sahel  22   23   24   25 ; LHON REALITY Study Group
Collaborators, Affiliations

Natural history of patients with Leber hereditary optic neuropathy-results from the REALITY study

Patrick Yu-Wai-Man et al. Eye (Lond). 2022 Apr.

Abstract

Background/objectives: REALITY is an international observational retrospective registry of LHON patients evaluating the visual course and outcome in Leber hereditary optic neuropathy (LHON).

Subjects/methods: Demographics and visual function data were collected from medical charts of LHON patients with visual loss. The study was conducted in 11 study centres in the United States of America and Europe. The collection period extended from the presymptomatic stage to at least more than one year after onset of vision loss (chronic stage). A Locally Weighted Scatterplot Smoothing (LOWESS) local regression model was used to analyse the evolution of best-corrected visual acuity (BCVA) over time.

Results: 44 LHON patients were included; 27 (61%) carried the m.11778G>A ND4 mutation, 8 (18%) carried the m.3460G>A ND1 mutation, and 9 (20%) carried the m.14484T>C ND6 mutation. Fourteen (32%) patients were under 18 years old at onset of vision loss and 5 (11%) were below the age of 12. The average duration of follow-up was 32.5 months after onset of symptoms. At the last observed measure, mean BCVA was 1.46 LogMAR in ND4 patients, 1.52 LogMAR in ND1 patients, and 0.97 LogMAR in ND6 patients. The worst visual outcomes were reported in ND4 patients aged at least 15 years old at onset, with a mean BCVA of 1.55 LogMAR and no tendency for spontaneous recovery. The LOESS modelling curve depicted a severe and permanent deterioration of BCVA.

Conclusions: Amongst LHON patients with the three primary mtDNA mutations, adult patients with the m.11778G>A ND4 mutation had the worst visual outcomes, consistent with prior reports.

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Conflict of interest statement

PYWM is a consultant for GenSight Biologics and Stealth BioTherapeutics and has received research support from GenSight Biologies and Santhera Pharmaceuticals. NJN is a consultant for GenSight Biologics, Santhera Pharmaceuticals and Stealth BioTherapeutics, has received research support from GenSight Biologics and Santhera Pharmaceuticals, served on the Data Safety Monitoring Board for the Quark NAION study and is a medical-legal consultant. VC is a consultant for Santhera Pharmaceuticals, GenSight Biologics, and Stealth BioTherapeutics and has received research support from Santhera Pharmaceuticals and Stealth BioTherapeutics. CV-C is a consultant for Santhera Pharmaceuticals and GenSight Biologics. VB is a consultant for GenSight Biologics. MM is a consultant for GenSight Biologics and has received research support from GenSight. AAS is a consultant for Stealth BioTherapeutics. LB and MT are GenSight Biologics employees. JAS is a co-founder and shareholder of GenSight Biologics, and a patent co-author on allotopic transport. Authors declare competing financial interests in relation with the work submitted (see “Acknowledgements” for details).

Figures

Fig. 1
Fig. 1. BCVA data collection in REALITY.
The distribution of BCVA data collected in the REALITY registry is presented according to LHON genotype and age at onset (below 15 or at least 15 years old). The number of eyes is displayed for each category.
Fig. 2
Fig. 2. BCVA evolution in ND4patients aged ≥15 at onset of vision loss.
The LOWESS regression curve for ND4 patients aged at least 15 at onset of vision loss (n = 23 patients, 213 individual BCVA measures) was based on fitting a series of linear regressions around each data point collected. The regressions used a limited look back and look forward, giving distant points less weight. The starting point of the curves was set at the onset of vision loss and included presymptomatic values (missing presymptomatic data were imputed a value of 0 LogMAR).
See this image and copyright information in PMC

References

    1. Wallace DC, Singh G, Lott MT, Hodge JA, Schurr TG, Lezza AM, et al. Mitochondrial DNA mutation associated with Leber’s hereditary optic neuropathy. Science. 1988;242:1427–30. doi: 10.1126/science.3201231. - DOI - PubMed
    1. Carelli V, La Morgia C, Valentino ML, Rizzo G, Carbonelli M, De Negri AM, et al. Idebenone Treatment in Leber’s Hereditary Optic Neuropathy. Brain. 2011;134:1–5. doi: 10.1093/brain/awr180. - DOI - PubMed
    1. Newman NJ. Hereditary optic neuropathies: from the mitochondria to the optic nerve. Am J Ophthalmol. 2005;140:517–23. - PubMed
    1. Yu-Wai-Man P, Griffiths PG, Chinnery PF. Mitochondrial optic neuropathies—disease mechanisms and therapeutic strategies. Prog Retin Eye Res. 2011;30:81–14. doi: 10.1016/j.preteyeres.2010.11.002. - DOI - PMC - PubMed
    1. Yu-Wai-Man P, Votruba M, Burté F, La Morgia C, Barboni P, Carelli V. A neurodegenerative perspective on mitochondrial optic neuropathies. Acta Neuropathol. 2016;132:789–806. doi: 10.1007/s00401-016-1625-2. - DOI - PMC - PubMed

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