International Consensus Statement on the Clinical and Therapeutic Management of Leber Hereditary Optic Neuropathy.

Leber hereditary optic neuropathy (LHON) is currently estimated as the most frequent mitochondrial disease (1 in 27,000-45,000). Its molecular pathogenesis and natural history is now fairly well understood. LHON also is the first mitochondrial disease for which a treatment has been approved (idebenone-Raxone, Santhera Pharmaceuticals) by the European Medicine Agency, under exceptional circumstances because of the rarity and severity of the disease. However, what remains unclear includes the optimal target population, timing, dose, and frequency of administration of idebenone in LHON due to lack of accepted definitions, criteria, and general guidelines for the clinical management of LHON. To address these issues, a consensus conference with a panel of experts from Europe and North America was held in Milan, Italy, in 2016. The intent was to provide expert consensus statements for the clinical and therapeutic management of LHON based on the currently available evidence. We report the conclusions of this conference, providing the guidelines for clinical and therapeutic management of LHON.

Clinical outcomes of treatment with idebenone in Leber's hereditary optic neuropathy in the Netherlands: A national cohort study.

PURPOSE: The purpose of the study was to present results from a national Dutch cohort of patients with Leber's Hereditary Optic Neuropathy (LHON) treated with idebenone. METHODS: The multicentre, open-label, retrospective evaluation of the long-term outcome of idebenone treatment of Dutch LHON patients on visual function and on thickness of the retinal ganglion cell layer. Patients included in the analysis had a confirmed mutation in their mitochondrial DNA encoding either of the seven subunits of complex I, had a reported loss of vision in at least one eye and had a follow-up of more than 6 months after their treatment was started. Control visits involved routine clinical examinations of visual function and retinal structure at (1) the start of treatment, (2) nadir (time of lowest visual acuity), (3) the time of recovery (if any), (4) the time of termination of treatment and (5) more than 6 months after termination of the treatment. RESULTS: Data from 72 patients were analysed. Treatment duration was 23.8 ± 14.4 (mean ± SD) months. A positive response, that is either a clinically relevant recovery (CRR) or a clinically relevant stabilization (CRS), occurred in 53% and 11% of the patients, respectively. The magnitude of CRR was 0.41 ± 1.54 logMAR. CRR of visual acuity is associated with recovery of colour discrimination. The thickness of both the ganglion cell complex (GCC) and the retinal nerve fibre layer (RNFL) is irreversibly reduced. CONCLUSION: Our results confirm that idebenone may help to restore or maintain visual function. Whether this effect will persist is still unknown. Thinning of retinal neural tissue appears to be permanent.

[New treatment option for Leber hereditary optic neuropathy: early diagnosis is required]. / Nieuwe therapie voor hereditaire opticusneuropathie van Leber.

BACKGROUND: Leber hereditary optic neuropathy (LHON) is an orphan disease which leads to painless subacute loss of central vision in both eyes. It develops mainly in young adults and is more common in males. It most often leads to lifelong blindness. Idebenone has shown to have a favourable effect in promoting vision recovery in LHON-patients with recent visual impairement. CASE DESCRIPTION: Two male LHON patients, aged 27 and 54 years of age were misdiagnosed during one year with optic neuritis and conversion disorder. The delay caused unnecessary emotional suffering and took away the opportunity of idebenone treatment. This can be prevented by greater awareness of disease characteristcs and OCT-scanning. CONCLUSION: Therapy for LHON requires a timely diagnosis.

Intravenous immunoglobulin in recurrent-relapsing inflammatory optic neuropathy.

OBJECTIVE: Recurrent-relapsing inflammatory optic neuropathy, including chronic relapsing inflammatory and autoimmune optic neuropathies, is rare, but can cause severe visual loss. Long-term steroids may preserve vision, yet side effects are frequent. We describe our experience with intravenous immunoglobulins (IVIg). DESIGN: A semi-prospective case series from 4 medical centres. PARTICIPANTS: Patients with steroid responsive recurrent-relapsing optic neuropathy. METHODS: Semiprospective case series of IVIg treatment in steroid-responsive recurrent-relapsing optic neuropathy at 4 medical centres. Outcome measures included visual outcome; time to, and duration of, remission; duration of corticosteroid use; and adverse events. RESULTS: Vision stabilized in all 6 patients treated with IVIg without steroids for extended periods of time. None improved and none worsened. One adverse event occurred during an IVIg infusion after 3 uneventful years of IVIg maintenance. Average steroid use prior to IVIg was 12 months. After IVIg treatment, 5/6 patients no longer required corticosteroids. Two patients experienced late relapses on IVIg, one of whom was treated with cyclosporine, the other with steroids. CONCLUSIONS: IVIg can be considered an effective steroid-sparing agent in selected cases with steroid-dependent recurrent-relapsing autoimmune optic neuropathy.