L eber hereditary optic neuropathy (LHON) is a form of blindness due to retinal ganglion cell dysfunction (1), caused by mutations in mitochondrial DNA (mtDNA), which affect complex I (NADH-ubiquinone oxidoreductase) of the mitochondrial respiratory chain (2,3). Although rare (estimated prevalence of 1 in 27,000-45,000), it affects all ages and gender, causing rapid and severe, bilateral (usually sequential), painless loss of central vision (4-7). Spon

Previously reported results of bosentan efficacy in DU management are reproducible in clinical practice. This efficacy is maintained in the longterm followup. Bosentan treatment was well tolerated and adverse events were comparable with those observed in previous reports.

Purpose LHON is a mitochondrial disease resulting in progressive, severe central vision loss, which in >95% of patients is characterized by 1 of 3 primary mitochondrial DNA mutations. However, further rare mutations have also been identified. To date the only treatment approved for LHON is idebenone, which is safe and effective at a dose of 900 mg/day; however, there is little information about its use in patients with rare mutations. Methods The Expanded Access Program (EAP) assessed idebenone's therapeutic potential in patients with onset of symptoms within 1 year prior to enrollment, in a real‐world setting. Efficacy was assessed as clinically relevant recovery (CRR) or clinically relevant stabilization (CRS). CRR is defined as improvement from off‐chart to reading 5 letters on the ETDRS chart, or as an improvement of 10 letters. CRS is defined as maintenance of VA <1.0 logMAR (20/200). Results Of 111 patients, 7 carried a rare mutation (A14495G, C3461T, G13051A, G3958A, T14487C, T4216C and T11253C+A14970G). The median age was 16.7 years, 57% were female and the time since onset was 2.8 months at the start of treatment. Patients presented with best visual acuity (VA) from 0.2 to 1.3 logMAR, and 3 patients presented with both eyes <1.0 logMAR at baseline (BL). One patient had only BL data currently available while 6 provided follow‐up data, with a median treatment duration of 9.2 months at last observation. All 6 experienced a CRR (10/12 eyes total) and the range for magnitude of recovery was between 2 and 13 lines on the ETDRS chart. The 2 eyes which did not experience CRR maintained VA <1.0 logMAR at last observation. Conclusions LHON patients harboring rare mitochondrial mutations who received early treatment with idebenone presented with moderate VA loss at BL and experienced a very favorable outcome. All patients showed recovery of vision.

PurposeLeber Hereditary Optic Neuropathy (LHON) is a mitochondrial genetic disorder causing severe, bilateral loss of visual acuity (VA). Idebenone is the only treatment for LHON currently approved in Europe. Due to the rarity of the disease, information about outcome in patients starting treatment >12 months since disease onset in the most recent eye (chronic LHON) is scarce.MethodsThe search for clinical evidence included any published study or conference abstract evaluating oral idebenone at the approved dose of 900 mg/day, in patients with confirmed diagnosis of LHON starting treatment >12 months since disease onset in the most recent eye. Literature search was carried out on Medline, Embase, InsightMeme and Cochrane Libraries up to March 2020.ResultsEvidence for idebenone treatment of chronic LHON is based on four uncontrolled, retrospective case series and one post‐hoc analysis of a randomized controlled study. All studies included patients (n = 4–53) with confirmed primary LHON mutations and evaluated changes in VA with the Early Treatment Diabetic Retinopathy Study (ETDRS) chart. The post‐hoc analysis (n = 53, idebenone:34; placebo:19) assessed efficacy as rate of clinically relevant recovery (CRR; defined as improvement from off‐chart to reading five letters, or improvement of 10 letters) from baseline (BL) after 6‐month therapy. 35.3% of idebenone‐treated versus 10.5% of placebo patients achieved CRR (p = 0.059); by eyes: 23.5% versus 5.3% (p = 0.016). All 4 retrospective studies (n = 4–16) assessed efficacy as average VA improvement (all eyes) from BL after 9 to 12 months of therapy. Improvements ranged from −0.20 to −0.31 logMAR (2–3 ETDRS lines). One retrospective study compared the effect of idebenone in two subgroups according to time from LHON onset (1–5 years, n = 7; >5 years, n = 8) showing no difference between groups.ConclusionsData presented indicates a potential therapeutic effect of idebenone in chronic LHON patients, which may be explained by the reactivation of dysfunctional retinal ganglion cells and deserved further investigation.

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