Abstract
BackrgroundEvaluation 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.ResultsAmong 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.ConclusionsOral cyclosporine, at 2.5 mg/kg/day, did not prevent second-eye involvement in patients with strictly unilateral Leber’s hereditary optic neuropathy.Trial registrationClinicalTrials.gov Identifier: NCT02176733. Registrated June 25, 2014.
Highlights
Leber’s hereditary optic neuropathy (LHON, OMIM 535000), with a prevalence higher than 3/100,000, is the most common primary mitochondrial DNA disorder
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 affected
Thirteen French centers participated in this prospective, open-label, phase II, non-randomized, multicenter trial aimed at evaluating the efficacy and tolerance of low doses of oral cyclosporine A in patients with unilateral LHON, occurring within 6 months of onset
Summary
Leber’s hereditary optic neuropathy (LHON, OMIM 535000), with a prevalence higher than 3/100,000, is the most common primary mitochondrial DNA (mtDNA) disorder. LHON is clinically characterized by an acute and painless visual loss occurring typically but not exclusively in young men [1], sequentially affecting both eyes within weeks or months [2]. The median delay of inter-eye involvement is 6–8 weeks [3], retarded bilateralization has been reported [4]. Simultaneous bilateral involvement may occur in up to 25% of cases [3]. Three primary mtDNA mutations, at positions m.11778G > A, m.3460G > A and m.14484. T > C mutation, has the best visual prognosis, with spontaneous recovery occurring in up to 65% of cases [6] LHON, associated with the m.14484 T > C mutation, has the best visual prognosis, with spontaneous recovery occurring in up to 65% of cases [6]
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