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DOI: 10.1055/a-0972-1552
Leberʼsche hereditäre Optikusneuropathie
Leberʼs Hereditary Optic NeuropathyPublikationsverlauf
eingereicht 13. April 2019
akzeptiert 24. Juni 2019
Publikationsdatum:
22. Oktober 2019 (online)
![](https://www.thieme-connect.de/media/klimo/201911/lookinside/thumbnails/10-1055-a-0972-1552_kl2056-1.jpg)
Zusammenfassung
Die Leberʼsche hereditäre Optikusneuropathie (LHON) betrifft typischerweise junge Erwachsene mit einer Prädilektion für das männliche Geschlecht, kann letztlich aber in jedem Alter auftreten. Die Erkrankung beruht auf Punktmutationen der mitochondrialen DNA, die zu einem Defekt des Komplexes I der mitochondrialen Atmungskette führen. Dieser verursacht wiederum eine Dysfunktion und später Degeneration retinaler Ganglienzellen, gefolgt von einer aufsteigenden Optikusatrophie. Klinische Merkmale der LHON sind ein zunächst meist unilateraler subakuter Visusverlust, Farbsinnstörungen im Rot-Grün-Bereich und Gesichtsfeldausfälle in Form eines Zentral- oder Zentrozökalskotoms. Das Partnerauge ereilt innerhalb von 3 – 6 Monaten nach Erkrankungsbeginn meist eine ähnliche Symptomatik. In 25% der Fälle beginnt die Erkrankung jedoch bilateral. Im natürlichen Verlauf bleibt ein Großteil der Patienten bei einem Visus < 0,1, auch wenn ein kleiner Anteil eine spontane Visusverbesserung erfährt. Im Jahr 2015 wurde das Ubiquinonanalogon Idebenon von der Europäischen Arzneimittel-Agentur (EMA) für die Behandlung der LHON zugelassen. Ausschlaggebend für den Therapieerfolg sind ein früher Therapiebeginn und eine ausreichende Therapiedauer. Dabei ist zu beachten, dass es bei einem Anteil der Patienten zu einem verzögerten Therapieansprechen kommen kann. Eine vollständige Visuserholung ist allerdings auch unter Therapie selten. Da es sich meist um junge Erwachsene im erwerbsfähigen Alter handelt, die weitgehend akut erblinden, ist weiterhin eine umgehende Unterstützung mit vergrößernden Sehhilfen und Beratung zur sozialen und beruflichen Rehabilitation essenziell. Alternative Therapieansätze wie Gentherapie, Neuroprotektion oder stammzellbasierte Aspekte sind derzeit bereits Gegenstand von klinischen Studien und lassen auf weitere Perspektiven für die Betroffenen hoffen. Obwohl für die LHON mit Idebenon bereits eine kausale Therapie zugelassen wurde, sind gerade die Pathogenese der Erkrankung betreffend noch viele Fragen nicht restlos geklärt. Dies betrifft insbesondere die Geschlechterprävalenz und mögliche zusätzliche Trigger oder protektive Faktoren. In dieser Übersicht werden die klinischen Verlaufsformen der LHON, Diagnostik und aktuelle Therapieempfehlungen sowie die Besonderheiten und gegenwärtigen Erklärungsansätze zur inkompletten Penetranz und Symptomatik der LHON erläutert.
Abstract
Leberʼs hereditary optic neuropathy (LHON) typically affects young adults with a higher prevalence in men, but can ultimately occur at any age and also in women. LHON is caused by point mutations in the mitochondrial DNA, which lead to a defect in complex I of the mitochondrial respiratory chain. This in turn causes dysfunction and later degeneration of retinal ganglion cells, followed by ascending optic atrophy. Classically, LHON presents as a subacute unilateral loss of visual acuity, dyschromatopsia in the red-green axis and a central or centrocecal scotoma. The partner eye usually develops similar symptoms within 3 – 6 months of onset of the disease. In 25% of cases, however, the disease begins bilaterally. In the natural course of the disease, the majority of patients remain with a visual acuity less than 0.1, even though a small proportion may experience a spontaneous improvement in visual acuity. In 2015, the ubiquinone analogue Idebenone was approved by the European Medicines Agency for the treatment of LHON. The decisive factors for therapeutic success are an early start and an appropriate treatment duration. It should also be noted that a proportion of patients may experience a delayed response to therapy. However, a complete recovery of visual acuity is rare even under therapy. Since patients affected by LHON are mostly young adults of working age, who go largely blind more or less acutely, immediate support with magnifying vision aids and advice on social and vocational rehabilitation is essential. Alternative therapeutic approaches such as gene therapy, neuroprotection or stem cell-based aspects are currently the subject of clinical studies and offer hope for further perspectives for those affected. Although with Idebenone a causal therapy has already been approved for LHON, many questions regarding the pathogenesis of the disease have not yet been completely clarified. This particularly concerns gender prevalence and possible additional triggers or protective factors. In this overview, the clinical course of LHON, diagnostics and current therapy recommendations as well as the special features and current explanatory approaches to incomplete penetrance and symptoms of LHON are explained.
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