Cyclosporine A does not prevent second-eye involvement in Leber’s hereditary optic neuropathy

Orphanet Journal of Rare Diseases

Xavier Zanlonghi¹  Vincent Procaccio²  Guy Lenaers²  Adriana Prundean²  Dominique Bonneau²  Patrizia Amati-Bonneau²  Christophe Verny²  Pascal Reynier²  Clarisse Scherer²  Stéphanie Leruez³  Dan Miléa³  Marie-Bénédicte Rougier⁴  Christophe Orssaud⁵  Caroline Tilikete⁶ 

[1] Centre de compétence maladie rare, Clinique Jules Verne;Institut MITOVASC, UMR CNRS 6015-INSERM1083, Université d’Angers;Service d’Ophtalmologie, CHU Angers;Service d’Ophtalmologie, CHU de Bordeaux;Unité Fonctionnelle d’Ophtalmologie, Centre de référence des Maladies Rares en Ophtalmologie OPHTARA, Hôpital Européen Georges Pompidou, Assistance Publique Hôpitaux de Paris;Unité de Neuro-Ophtalmologie, Hospices Civils de Lyon, Hôpital Neurologique;

关键词: Leber’s hereditary optic neuropathy;    Second-eye involvement;    Cyclosporine;   

DOI  :  10.1186/s13023-018-0773-y

来源: DOAJ

【 摘 要 】

Abstract Backrground Evaluation of the efficacy of oral cyclosporine A as a prophylactic agent in preventing second-eye involvement in Leber’s hereditary optic neuropathy (LHON) in a prospective, open-label, non-randomized, multicenter pilot study. Only LHON patients aged 18 years or more, with confirmed primary mitochondrial DNA mutations and strictly unilateral optic neuropathy occurring within 6 months prior to enrolment, were included in the study. All these patients, receiving treatment with oral cyclosporine (Neoral®, Novartis) at 2.5 mg/kg/day, were examined at three-month intervals for a year. The primary endpoint was the best corrected visual acuity in the unaffected eye; the secondary endpoints were the best corrected visual acuity in the first eye affected, the mean visual field defect on automated perimetry, the thickness of the perifoveal retinal ganglion cell inner plexiform layer, and the thickness of the peripapillary retinal nerve fiber layer in both eyes. Results Among the 24 patients referred to our institution with genetically confirmed LHON, between July 2011 and April 2014, only five patients, four males and one female, fulfilled the inclusion criteria. Age at enrolment ranged from 19 to 42 years (mean: 27.2 years; median: 26 years), four patients harbored the m.11778G > A pathogenic variant, and one the m.14484 T > C pathogenic variant. The time-interval between the onset of symptoms and inclusion in the study ranged from 7 to 17 weeks (mean: 11.8 weeks; median: 9 weeks). Despite treatment with oral cyclosporine A, all patients eventually experienced bilateral eye involvement, occurring within 11–65 weeks after the initiation of treatment. Over the study time period, the average best corrected visual acuity worsened in the first eye affected; by the end of the study, both eyes were equally affected. Conclusions Oral cyclosporine, at 2.5 mg/kg/day, did not prevent second-eye involvement in patients with strictly unilateral Leber’s hereditary optic neuropathy. Trial registration ClinicalTrials.gov Identifier: NCT02176733. Registrated June 25, 2014.

【 授权许可】

Unknown