Leber hereditary optic neuropathy (LHON)

What is Leber hereditary optic neuropathy?

Leber hereditary optic neuropathy (LHON) is an inherited condition that causes painless vision loss, typically in young adults. This vision loss is usually permanent and occurs over a few months, starting as blurry vision in one eye and then affecting the other eye. 

This condition impacts central vision, which is responsible for seeing fine details. The vision loss associated with LHON is due to optic neuropathy. This means that something has damaged the optic nerve. LHON most commonly impacts young males and is passed down from the mother.

Leber hereditary optic neuropathy is named for Theodor Leber, a German ophthalmologist. He was the first to recognize the pattern of inheritance of this condition.

What causes Leber hereditary optic neuropathy?

Leber hereditary optic neuropathy is a genetic mitochondrial disease. This means that it is passed from parent to child and impacts mitochondria, the source of cellular energy. 

Genetics and mitochondria

Every individual is born with two sets of genes, one from each parent. Genes are made up of DNA and are like an instruction guide for the body. Genetic conditions can occur when a gene mutates or the wrong number of genes are present. A person can inherit a genetic mutation from one or both parents. Those with LHON have inherited a genetic mutation in the DNA that impacts the mitochondria’s ability to produce energy.

Mitochondria provide energy to cells throughout the body. Cells make up the body’s tissues and organs. If they do not have enough energy, it inhibits their ability to function properly. 

Mitochondrial DNA is inherited from the mother. This means that a female carrying the mutated gene will pass it on to every child she has. Genetic counseling can benefit women who are female carriers. A male carrying the mutated gene will not pass it on. Not every person who inherits the mutated gene will develop blindness. 

The genes impacted by the genetic mutation include:

• MT-NDI1

• MT-ND4

• MT-ND4L

• MT-ND6

Optic neuropathy

Optic neuropathy refers to damage of any kind to the optic nerve. The optic nerve is what connects the eye to the brain. The back of the eye is lined with a thin tissue called the retina, which has cells called photoreceptors. When light enters the eyes, these cells transform it into nerve signals. The optic nerve sends these signals to the brain, where they are interpreted as images.

The optic nerve relies heavily on energy from mitochondria. The mitochondrial damage associated with LHON leads to optic nerve cell death, preventing the optic nerve from functioning properly and resulting in vision loss.

Leber hereditary optic neuropathy usually begins between the ages of 15 and 35. About 80-90% of cases arise in males. The reason for the higher prevalence in males is unknown. One theory is that the Y chromosome in males has a susceptibility locus. This means a particular spot in the Y chromosome may be more likely to develop one of the LHON mutations.

READ MORE: Optic neuritis and neuropathy: Symptoms, causes, treatments

What are the symptoms of Leber hereditary optic neuropathy?

Leber hereditary optic neuropathy usually begins with blurred vision and difficulty seeing color. At first, vision loss is usually unilateral (one eye), painless and limited to central vision, which helps us clearly distinguish details, color and shape. It is important for driving, reading and recognizing faces. After two to three months, vision in the second eye also will become blurry.

Only around a quarter of cases experience bilateral (both eyes) vision loss from the beginning. As LHON progresses, the affected individual may become legally blind. However, most individuals will still be able to perceive light. In most cases, vision loss is the only symptom of Leber hereditary optic neuropathy. 

LHON plus

In rare cases, a person with LHON will also present with non-visual neurological symptoms. This is referred to as LHON-plus. These additional symptoms include:

• Movement disorders – A group of conditions that result in difficulties with movement. 

• Tremors – A condition that causes shaking in the body, most frequently in the hands.

• Cardiac preexcitation syndrome – A condition that causes abnormal electrical impulses in the heart. This can result in an improper heartbeat.

• Leigh syndrome – A neurological condition that impacts mental and motor development in children.

• Multiple sclerosis-like symptoms – A condition that impacts the central nervous system. Associated symptoms include muscle weakness and numbness.

Additional mitochondrial mutations may cause LHON-plus.

READ MORE: Eye symptoms commonly seen in multiple sclerosis

What is the treatment and prognosis for Leber hereditary optic neuropathy?

Treatment for Leber hereditary optic neuropathy is mostly focused on support. Unfortunately, there is no cure at this time. Visual aids and occupational therapy are recommended. Individuals with LHON should avoid alcohol and tobacco.

Though the impact may be minimal, antioxidants can help relieve some of the stress LHON can put on the brain. Suggested supplements include:

• Vitamin B12

• Vitamin C

• Coenzyme-Q10

• Brimonidine

• Lutein

Some studies have shown possible benefits with certain therapies. A form of Coenzyme-Q10 called Idebenone and the drug EPI-743 may help with vision recovery. However, both of these medications are still being explored. Other potential treatments are also under investigation, such as:

• Hormone therapy

• Mitochondrial replacement

• Gene therapy

The overall prognosis for those with LHON depends on their specific genetic mutation. In some cases, vision may improve. However, most people with this condition will experience some degree of permanent vision loss. 

When should you see an eye doctor?

Carriers of the LHON mutation who are asymptomatic do not need constant monitoring. However, routine, comprehensive eye exams are highly recommended. If symptoms such as sudden blurred or cloudy vision are noticed, seek care from an eye doctor immediately.

Page published on Thursday, November 30, 2023

Page updated on Tuesday, December 5, 2023

Medically reviewed on Wednesday, November 15, 2023