Leber Hereditary Optic Neuropathy (LHON)

What is Leber hereditary optic neuropathy (LHON)?

Leber hereditary optic neuropathy (LHON) is a genetically inherited disease that causes vision loss. Most people who inherit the condition develop blurred vision that gets progressively worse over a course of about six months. Vision loss may start in one eye and then progress to both eyes several months later. It usually starts in late childhood to early adulthood. Most people with LHON will become legally blind.

Leber hereditary optic neuropathy is also called Leber’s disease. It’s named for Dr. Theodore Leber, who studied the disease. “Hereditary” means that you inherit it, and “optic neuropathy” means it’s a disease that affects your optic nerve. Your optic nerve is what carries visual signals from your eye to your brain so that your brain can “see.” Damage to your optic nerve is one way that you can lose your vision.

Are there different types of LHON?

The standard version of Leber hereditary optic neuropathy (LHON) only affects your optic nerves, and vision loss is its only symptom. This is the case for the vast majority of people with Leber’s disease. But in rare cases, some people with LHON have additional symptoms that affect other parts of their nervous system, and sometimes their heart. Healthcare providers call this version of the disease “Leber plus.”

How common is Leber hereditary optic neuropathy?

The true incidence of LHON is unknown. Estimates suggest that it occurs in approximately 1 in 25,000 to 50,000 people. Approximately 80% to 90% of people with LHON are male.

What are the symptoms of LHON (Leber’s disease)?

Vision loss with LHON is painless and subacute, meaning it progresses over several months. You’re likely to notice changes in your central vision first. That’s what you see when you look straight ahead — what you use to drive, read and recognize faces. Your central vision might start to seem blurry, or you might develop a blind spot in the middle of your field of vision. It might occur in one eye first, then the other.

This will continue to worsen over the following months. You also may begin to lose your color vision — the ability to see certain colors or tell colors apart. Vision loss tends to stabilize within six months to a year of the first symptoms. By this time, most people have a visual acuity of 20/200 or worse, which is legally blind. You’ll still have some light perception, but you’ll need to learn to live with low vision.

What are the symptoms of Leber’s plus?

People with Leber’s plus can have a variety of symptoms beyond vision loss, including:

• Movement disorders, like tremors.
• Coordination and balance problems (ataxia).
• Cardiac conduction problems, like arrhythmias (irregular heartbeats).
• Symptoms of multiple sclerosis (MS), like muscle weakness and fatigue.

What causes Leber hereditary optic neuropathy?

Leber hereditary optic neuropathy is a mitochondrial disease, a genetic disorder that you inherit through the mitochondria in your cells. Mitochondria are the energy generators in your cells. They convert oxygen and nutrients into the energy your cells need to operate. Mitochondrial diseases interfere with this process, leaving a lack of energy in your cells. This can cause some cells to malfunction or die.

When your mitochondria aren’t working right, the parts of your body that rely on mitochondrial energy the most will feel it first. These include parts of your eye, especially your optic nerve. If enough of your mitochondria are defective, these parts won’t have the energy they need to function right. In Leber’s disease, the effect is that your optic nerve deteriorates. This is how LHON causes vision loss.

How do you get Leber hereditary optic neuropathy?

LHON happens because of a gene mutation in your mitochondria’s DNA. Mutations in the MT-ND1, MT-ND4, MT-ND4L or MT-ND6 genes can cause LHON. You inherit all of your mitochondria from your birth mother, so only female parents can pass the gene mutation to their biological children. But not everyone who carries the mutation develops symptoms of LHON, so not everyone realizes they carry it.

What risk factors might contribute to LHON?

Researchers don’t know exactly why some people with the gene mutation develop symptoms of LHON and others don’t. Some evidence suggests that physiological stress and environmental toxins may contribute to triggering the onset of symptoms. The theory is that these factors may add to the overall stress on body systems affected by LHON. Over time, they add up until they finally trigger symptoms.

Potential risk factors include:

• Smoking.
• Alcohol use.
• Exposure to environmental toxins.
• Systemic illness.
• Psychological stress.

How is Leber hereditary optic neuropathy diagnosed?

Your eye care specialist will conduct standard eye exams to test your vision and look for the cause of the problem. They might not be able to see anything wrong with your eye or your optic nerve at first. The damage becomes more obvious after the first six months of symptoms. When your provider suspects LHON, they’ll recommend genetic testing to confirm that you have one of the gene mutations involved.

Is there any treatment or cure for Leber hereditary optic neuropathy?

There’s no definitive cure for LHON. Idebenone, which is a synthetic form of Coenzyme Q10, is the only FDA-approved medication. In randomized controlled trials, idebenone has been associated with improvements in visual acuity in people with LHON. Other similar medications are currently in trials. Researchers are also studying gene therapy as a possible future treatment for Leber’s disease.

Is there any way to prevent LHON?

While many people who inherit genes associated with LHON will never develop vision loss, there’s no known way to prevent it from happening. It’s possible, but not proven, that taking antioxidants and avoiding neurotoxins like alcohol and tobacco might reduce your risk. All females who have the genes will pass them to their biological children. Genetic counseling can help you consider this risk.

What is the outlook with Leber hereditary optic neuropathy?

When LHON causes vision loss, it’s likely to be rapid, severe and permanent. Most people will have to learn a new way of living with low vision. Low vision means moderate to severe visual impairment, but not total blindness. Moderate low vision scores 20/70 on a visual acuity test, while severe low vision scores 20/200 or worse. This is still a fairly wide range of visual acuity that you could end up with.

Whether you end up on the moderate or severe side of this range is mostly a matter of luck. Treatment might make some difference, but the gene mutation you have makes the most difference. Some people with LHON recover some of their vision unexpectedly after a year of decline. Different gene mutations have different chances of recovery. But even with some recovery, you’ll likely still have low vision.