What is Leber hereditary optic neuropathy?

Leber hereditary optic neuropathy (LHON) is an inherited eye condition that typically causes sudden, painless loss of central vision. The progression can occur over a period of days, weeks or even months rather than being immediate.

The condition affects the optic nerve  – a bundle of fibres at the back of the eye that acts as the communication pathway between the eye and the brain.

While vision loss usually occurs quickly, progression can occur over days or weeks.

An unhealthy optic nerve in LHON typically causes central vision loss; however, complete blindness is not usual in LHON - even in severe cases, the peripheral vision remains preserved.

What are the causes of Leber Hereditary Optic Neuropathy?

The main reason for developing LHON is inheriting a faulty mitochondrial gene from your mother. But not everyone who inherits the genetic mutation will lose their vision. Current research suggests that approximately 50% of men and 10% of women  who carry a mutation that causes LHON will be affected by vision loss.

Around 90% of cases of LHON  are caused by one of three mitochondrial DNA gene mutations, sometimes called the three primary mutations. There are also other rare mitochondrial gene defects which can cause the condition.

A mutation in one of these genes disrupts the energy production process. The retinal nerve cells that make up the optic nerve have very high energy demands, so they are particularly vulnerable to problems with the mitochondria.

The reduced energy supply and the damaging waste products that build up can cause the optic nerve cells to become stressed, damaged, and eventually die, meaning they can no longer send visual signals to the brain. This cell death leads to narrowing and weakening of the optic nerve and to the resulting vision loss.

In many cases, there will be a family history of blindness at a relatively young age. Others have no known family history of the condition. It is also possible, though rare, for the genetic mutation to appear for the first time in an individual.

Who is typically affected by LHON?

LHON most often affects young adult men. It can also affect women, but less frequently. Vision loss can occur at any age, but it is most common before age 35.

The condition is named after Dr Theodor Leber, who first described it in 1871.

It may also be called Leber’s optic neuropathy or Leber's optic atrophy.

What causes Leber hereditary optic neuropathy?

LHON is a type of mitochondrial disease. Mitochondria are tiny structures inside our cells. They’re sometimes called ‘powerhouses’ because they use oxygen to extract energy from food and package it in a form our cells need to function. 

In LHON, a problem exists with one of three mitochondrial genes that regulate energy production in the optic nerve.  This means the mitochondria cannot produce enough energy, which causes the cells to malfunction and eventually die, leading to vision loss. 

Vision loss in LHON can often, but not always, occur quickly. It often begins with blurring or clouding of the central vision in one eye, with the other eye usually affected within a few weeks or months. 
Because LHON is a genetic condition, it is passed down through families, from the mother.

This is because we only inherit mitochondria from our mother's egg cell. A mother who carries the genetic fault will pass it on to all her children, but a father cannot pass it on to his children.

How common is Leber Hereditary Optic Neuropathy?

Leber hereditary optic neuropathy is a rare condition.

While prevalence varies regionally, estimates suggest it affects between 1 in 30,000 to 1 in 50,000 people in Europe.

There is variation in the effects of LHON – in addition to the sex differences – as some people with the genetic mutation do not ever experience sight loss. Additional genetic and environmental factors (such as smoking, alcohol and diet) could therefore play a role in triggering LHON, rather than the mitochondrial faults alone.

Who is at risk of Leber Hereditary Optic Neuropathy?

Factors that can increase the risk of LHON include:

• Sex: Men are significantly more likely to be affected than women. Around 70-90%  of people who lose their vision from LHON are male.
• Age: Most people develop the condition between the ages of 15 and 35. ,  But it can occur at any age, including early childhood or later in adulthood.
• Family history: Around 60% of people with LHON  have a family history of vision loss on their mother’s side.

What are the signs and symptoms of Leber hereditary optic neuropathy?

You can carry the gene mutation that causes LHON without ever having symptoms. There are usually no symptoms until vision loss starts to develop.

The main symptoms include:

• Blurred or clouded central vision: This is often the first sign, making it hard to see details needed for reading, driving, or recognising faces.
• Rapid vision loss: Vision loss typically starts in one eye, but sometimes both at once, and is followed by the other eye within a few weeks or months. In some cases, there might be some improvement in vision, months or years later.
• Loss of colour vision: The ability to see colours clearly, especially red and green, is often reduced.
• A blind spot: A dense blind spot (scotoma) develops in the centre of the field of vision. It is unlikely that your peripheral (side) vision will change.

How is Leber hereditary optic neuropathy diagnosed?

If you experience sudden changes to your central vision, you should see an eye specialist (an ophthalmologist). If they suspect LHON, they might refer you to a neuro-ophthalmologist, a specialist in vision problems related to the nervous system.

The diagnosis usually involves:

• A detailed eye examination: The specialist will check your vision sharpness, colour vision, and your visual field to look for a central blind spot. They will also examine the back of your eye to look at the optic nerve.
• Imaging tests: A test called optical coherence tomography (OCT) is often used. This is a scanner that takes detailed pictures of the layers of your retina at the back of the eye, allowing the specialist to measure the thickness of the optic nerve and detect any swelling or damage.
• Genetic testing: A definitive diagnosis is made after a genetic test. This is usually done with a blood sample and confirms the presence of one of the mutations known to cause LHON.

Because some symptoms of LHON can be similar to other conditions, your doctor may also order brain scans to rule out other causes of vision loss.

Is Leber hereditary optic neuropathy serious?

Yes, LHON often leads to significant visual impairment and can have a major impact on daily life and activities.

In rare cases, known as "LHON Plus", some people with LHON may experience other non-visual symptoms . These additional symptoms can include:

• Movement disorders
• Tremors
• Muscle weakness
• Heart rhythm problems (cardiac conduction defects)

Get support for coping with sight loss

How is Leber hereditary optic neuropathy diagnosed?

If you experience sudden changes to your central vision, you should see an eye specialist (an ophthalmologist). If they suspect LHON, they might refer you to a neuro-ophthalmologist, a specialist in vision problems related to the nervous system.

The diagnosis usually involves:

• A detailed eye examination: The specialist will check your vision sharpness, colour vision, and your visual field to look for a central blind spot. They will also examine the back of your eye to look at the optic nerve.
• Imaging tests: A test called optical coherence tomography (OCT) is often used. This is a scanner that takes detailed pictures of the layers of your retina at the back of the eye, allowing the specialist to measure the thickness of the optic nerve and detect any swelling or damage.
• Genetic testing: A definitive diagnosis is made after a genetic test. This is usually done with a blood sample and confirms the presence of one of the mutations known to cause LHON.

Because some symptoms of LHON can be similar to other conditions, your doctor may also order brain scans to rule out other causes of vision loss.

Is there a cure for Leber Hereditary Optic Neuropathy?

Currently, there is no treatment that can fully restore vision lost to LHON. However, treatment with Idebenone is now approved in the UK and has been shown to help stabilise or improve vision in some patients, particularly when started early. Vision loss can be severe, but the availability of Idebenone offers hope for better outcomes when treatment is initiated promptly. Researchers are also actively working on developing new treatments, including promising gene therapies.

In some cases, vision improves on its own, months or years later, but does not recover . The likelihood of improvement seems to vary according to which gene variant is causing the condition. 

What are the treatments for Leber hereditary optic neuropathy?

There are treatments that can help to manage Leber hereditary optic neuropathy.

Medications for Leber Hereditary Optic Neuropathy

The drug Idebenone has been approved for use in some countries, including the UK , for treating LHON in people aged 12 and over. Idebenone is thought to help bypass the faulty energy production process in the mitochondria, potentially protecting the optic nerve cells from further damage. Clinical studies suggest it may help around half of people with LHON.

Treatments to help manage the condition

• Vitamin supplements: While not a proven treatment, your specialist may discuss the use of specific vitamins, since there is some evidence that LHON can be linked to deficiencies including vitamin B12 deficiency. It’s important to speak to your specialist before deciding to take supplements, as some might have a negative effect on the condition.
• Lifestyle advice: People diagnosed with LHON are strongly advised to avoid smoking, heavy drinking, and certain medications, as these may put additional stress on the mitochondria and potentially worsen the condition.
• Low vision aids: A low vision specialist can help you make the most of your remaining peripheral vision. This can involve using tools like magnifiers, specialised lighting, and assistive technology for computers and mobile phones.
• Support services: Your doctor can refer you to visual rehabilitation services that can provide support and training to help you adapt to life with central vision loss.

What can help Leber hereditary optic neuropathy?

Although there is no treatment, smoking and alcohol may make symptoms worse, so avoiding these is important. Supportive measures like visual aids can help you to cope with vision loss.

Can Leber hereditary optic neuropathy be prevented?

Leber hereditary optic neuropathy is a genetic condition that can’t be prevented. If you are a carrier of an LHON mutation, there are some lifestyle choices that might reduce your risk of developing vision loss, but this is not always the case.

Speaking with a genetic counsellor can be very helpful. A genetic counsellor is a healthcare professional who can help you understand how genetic conditions are inherited and what the risks are for your family members.

Living with Leber Hereditary Optic Neuropathy

The severe loss of central vision caused by LHON can have a big impact on daily life. Central vision is what we use for detailed tasks, so its loss makes activities like reading, using a computer, watching television, driving and recognising faces very difficult.

Adjusting to this new reality can be challenging, both practically and emotionally. It’s important to remember that you are not alone and support is available.

Low vision services and rehabilitation specialists can provide useful support. They can help you learn new ways of doing things and introduce you to a wide range of aids and technologies that can help you maintain your independence.

Peer support groups, either online or in person, can connect you with other people living with LHON, providing a space to share experiences and advice.

What research is there into Leber hereditary optic neuropathy?

Research into Leber hereditary optic neuropathy aims to find a treatment that can prevent vision loss and, perhaps even restore vision that has been lost. This could be through gene therapy or drug treatments.

We also need to understand more about the causes. At the moment we don’t know who in a family will develop symptoms and who won’t, or whether there are any unknown factors that make symptoms more likely to develop. We also don’t know for sure why women are affected less often than men.

Fight for Sight is committed to funding informed and innovative research that brings us closer to a future without vision loss.

Investigating retinal cell recovery in LHON

We are currently funding Professor Marcela Votruba to investigate how some retinal ganglion cells (retinal nerve cells) in LHON might be capable of recovery. The aim is to establish a scientific basis for developing new treatments that could reverse vision loss. The research team is studying cell and mouse models of the disease to understand the structure and function of these cells in detail. They will also test the effects of the drug Idebenone. This research could pave the way for new treatments that offer the incredible hope of reversing vision loss for people with LHON.

Using advanced imaging to predict changes in LHON

A project we funded, led by Professor Patrick Yu Wai Man, used powerful MRI scanners to get high-resolution, real-time images of the visual pathways from the eye to the brain in people with LHON. Following this work, additional funding was secured to expand the study. The team went on to use these advanced imaging tools to investigate a larger group of patients, comparing those who have recently lost vision with those who have had the condition for longer. This informed approach helps us better understand the disease process and could provide a tool for predicting changes and measuring the effectiveness of future treatments.

See our research projects