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

Abstract

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.

ENT characteristics and therapeutic results in multisystemic disorders of mitochondrial encephalomyopathy

“…Patients who underwent surgery should have intravenous sugar-containing fluids administered before anesthesia to avoid catabolism. Vitamin supplementation and various coenzyme treatments, such as idebenone, coenzyme Q10, L-carnitine, arginine, and lipoic acid [ 21 , 27 , 28 ], canimprove energy and glycolipid metabolism while applying free radical scavenging drugs, low-dose hormones, and cyclosporine A canimprove autophagy. Patients with encephalopathy should be treatedwith folic acid supplements [ 29 ], and arginine also needs to be supplemented when insufficient.…”

“…Coenzyme Q10 was used to treat MELAS patients for a period of time, and it was found that it can promote insulin secretion, delay hearing loss, improve myopathy symptoms, congestive heart failure, and other complications [ 49 ]. Carlot [ 28 ] presented a potential therapeutic effect of idebenone treatment for > 12 months in 53 chronic LHON patients. Other cofactors, including carnitine and vitamins B, C, and K, can also improve ATP synthesis in some mitochondrial diseases [ 50 ].…”