Assessing clinical evidence for idebenone in the treatment of chronic Leber Hereditary Optic Neuropathy: a systematic literature review

Abstract

AbstractPurposeLeber 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.