Leber Hereditary Optic Neuropathy

What is Leber Hereditary Optic Neuropathy?

Leber Hereditary Optic Neuropathy (LHON), also known as Leber Optic Atrophy, was named after Doctor Theodore Leber, who described in 1871 a characteristic pattern of sudden vision loss in young men with family history of blindness. It is the most common hereditary optic neuropathy, it is caused by a mitochondrial mutation and has a low prevalence, although in most geographic areas it is still unknown. In northeast England and Finland, it affects 1 person every 31,000 or 50,000 respectively.

It affects most usually young men aged between 18 and 35 years old, although it can also affect children of lower ages and adults over 35 years old. In women it has a much lower incidence.

It generally causes a sever vision loss in both eyes. In most cases, an eye is first affected, and several weeks or months after, the second eye is affected.

Which is the cause of LHON? What is mitochondrial inheritance?

Even though most of our genetic material (DNA) is localized on the cell nucleus, a small part of it is located in mitochondria (mitochondrial DNA).

Genes within the nucleus are inherited from both biological parents. Nevertheless, mitochondrial genes are only inherited from the mother. This means a male with a mitochondrial DNA mutation won’t transmit it genetically to any of his biological sons, while a woman with a mitochondrial DNA mutation will transfer it to all her biological descendants.

90-95% of LHON cases are caused by one of the three concrete mitochondrial DNA mutations. However, a significant percentage of people who have these mutations never develop the disease symptoms. More specifically, only a 10% of women and 50% of men who are carriers of any of these mutations will develop optic neuropathy. This means other genetic (mitochondrial or nuclear) and/or environmental factors must act in order to trigger the vision loss. For example, exposure to tobacco or high amounts of alcohol in carriers of these mutations increases the risk to develop the disease.

What are the symptoms of Leber hereditary optic neuropathy?

Typically, LHON carriers remain asymptomatic until they experience a loss of vision, more or less sudden, in an eye, and a few weeks or months later, in the other eye. Vision keeps worsening for some weeks until is deep and, in most cases, central vision (essential for tasks such as reading, driving or recognizing faces) is severely and permanently affected in both eyes, although some people experience some visual recovery after some time. This permanent vision loss is due to the death of optic nerve cells, responsible for sending images from eyes to the brain.

Although vision loss is the only symptom in most LHON patients, arrhythmias, and neurological troubles (postural tremors or other movement disorders) have been described in some of them.

How is it diagnosed? Does it have a treatment?

For several reasons, it is a disease with a difficult diagnosis. First of all, it is a hereditary disease, but it does not manifest itself in all people suffering the mutation. For this reason, it may arise with no evidence of a family history of the disease.

In order to diagnose it, it is usually necessary to perform a comprehensive neuro-ophthalmology examination and a blood test that examines the mitochondrial DNA.

In an eye fundus examination, a microangiopathy and a may be seen initially, and a puffiness of the peripapillary nervous fibers layer, which progresses to an optic atrophy.

Currently, the prognosis is usually a permanent and severe vision loss. Several researches are being performed in order to find a treatment for the disease. ICR has an ongoing study on it, which is currently in the selection phase.