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

• Type of Material: Article
• Authors: Patrick Yu-Wai-Man, University of Cambridge; Nancy Newman, Emory University; Valerio Carelli, UOC Clinica Neurologica; Chiara La Morgia, UOC Clinica Neurologica; Valerie Biousse, Emory University; Francesco M Bandello, Vita-Salute San Raffaele University; Catherine Vignal Clermont, Rothschild Foundation Hospital; Lorena Castillo Campillo, Institut Catala de Retina; Stephanie Leruez, CHU Angers - Hôpital Hôtel Dieu; Mark L Moster, Wills Eye Hospital and Thomas Jefferson University; Dean M Cestari, Massachusetts Eye and Ear Infirmary; Rod Foroozan, Alkek Eye Center; Alfredo Sadun, University of California Los Angeles; Rustum Karanjia, University of California Los Angeles; Neringa Jurkute, Moorfields Eye Hospital; Laure Blouin, GenSight Biologics; Magali Taiel, GenSight Biologics; José-Alain Sahel, Sorbonne Universite
• Language: English
• Date: 2021-04-28
• Publisher: SPRINGERNATURE
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2021
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/s41433-021-01535-9
• Title of Journal or Parent Work: EYE
• Volume: 36
• Issue: 4
• Start Page: 818
• End Page: 826
• Grant/Funding Information: GenSight Biologics (Paris, France) fully funded and sponsored the study.
• Keywords: DYSFUNCTION; Ophthalmology; IDEBENONE; Life Sciences & Biomedicine; G11778A; PENETRANCE; CLINICAL-FEATURES; Science & Technology
• Research Categories: Health Sciences, Medicine and Surgery

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.