1. What is LHON?
Leber Hereditary Optic Neuropathy (LHON) symptoms usually begin as sudden, painless loss of central vision. The classic pattern is for one eye to suddenly lose central vision, then within weeks to months the other eye also loses central vision. Each eye quickly gets worse than 20/200 (the threshold for legal blindness) as the central scotoma (blurry blind spot) rapidly expands over about 6-8 months. Severe vision loss in both eyes is the usual outcome. In rare cases the interval between eyes can be years, and in some cases both eyes onset at the same time. Reading standard-sized text, driving, and recognizing faces become impossible.
The affected person usually retains some amount of peripheral vision, varying significantly by individual. This allows the person to walk around independently, though in many cases a white cane or guide dog is required for safe mobility. Since the LHON affected individual often does not “look blind,” those around them struggle to understand their situation and don’t realize how profound their vision loss is. Color vision usually becomes impaired also, usually with red lost first, and bright royal blue the most visible.
The first video below was filmed at the 2015 LHON Conference and addresses the most commonly-asked medical questions about LHON with three of the world’s LHON leaders [Dr. Patrick Yu-Wai-Man (UK), Dr. Valerio Carelli (Italy), Dr. Alfredo Sadun (USA)]. Next is an LHON overview at the 2017 LHON Conference with Dr. Nancy Newman, another global LHON expert.
Additional LHON overviews can be found here:
About 100 people in the U.S. experience onset of LHON vision loss each year, joining the 4,000 or so in the U.S. who are already legally blind due to LHON. Thousands more are unaffected carriers of an LHON genetic mutation, and could suddenly become affected by LHON vision loss at any time. It’s estimated that about 35,000 people worldwide have LHON vision. About 25% of those affected are female; 75% are male. Onset of vision loss can happen at any age. Females have no peak onset age. Males have a peak onset at ages 12-26. Individuals carrying an LHON mutation are never “too young” or “too old” to become affected. Prior to the era of genetic testing, it was estimated that 50% of males who carry an LHON mutation will become affected and that figure is still commonly quoted. However, recent studies indicate that less than 20% is a better estimate among families with someone affected by vision loss, and even lower when families with no one yet affected are included.
LHON is a mitochondrial disease. It is usually caused by one of several pathogenic genetic mutations in the mitochondria. Those who have a mitochondrial LHON mutation without vision loss are referred to as “carriers” or "unaffected carriers." In some individuals who carry an LHON mutation, the optic nerves suddenly begin to swell then atrophy. This causes a disruption in the signals between the eyes and the brain, leading to vision loss. Those who have central vision loss due to LHON are referred to as “affected.”
The most common LHON mutation is the 11778 (ND4) mutation, causing over 65% of all LHON cases. Most of the remaining LHON cases are caused by the 14484 (ND6) and 3460 (ND1) mutations. Several very rare mitochondrial mutations cause most of the other cases. Recently some nuclear mutations that impact the mitochondria, including DNAJC30, have been associated with LHON vision loss.
At the 2014 LHON Conference, Dr. Valerio Carelli discussed what may influence the risk of onset of vision loss in individuals carrying an LHON mutation. Dr. Alfredo Sadun discussed Environmental Factors at the 2021 LHON Conference. The Gene-Environment Interactions article provides additional information.
Those who are not aware of any family members with LHON are taken by surprise when they suddenly lose central vision, and usually struggle to identify the cause. Since LHON is so rare, the medical community usually suspects, tests for, and treats other causes of sudden vision loss. An MRI may be conducted to rule out a brain tumor and to view any optic nerve swelling. Since there is no visible damage to the eye or brain, there may be a diagnosis of Functional or Non-Organic Vision Loss which suggests a psychological component, an upsetting misdiagnosis since the vision loss is quite real. It's helpful to see a neuro-ophthalmologist, who is trained and equipped to assess the optic nerves.
Since vision loss usually begins in just one eye, a tentative diagnosis of Optic Neuritis is often made and steroid treatment may be prescribed. Optic Neuritis involves eye pain about 90% of the time while LHON onset is painless, which can help in differentiating LHON from Optic Neuritis. Optic Neuritis usually involves just one eye while LHON usually affects both eyes, so when loss of vision in the second eye begins it may cause the Optic Neuritis diagnosis to be questioned. Testing for Neuromyelitis Optica (NMO) and other possible causes of sudden, bilateral, painless loss of central vision, as well as genetic testing for LHON, may be initiated.
A genetic test usually determines if someone carries an LHON mutation, which confirms the diagnosis. Some labs do a panel test for just the three most common LHON mutations while others include the rare LHON mutations on their panel test. Comprehensive testing of the mitochondrial genome identifies rare LHON mutations. This video provides an overview of various approaches to LHON genetic testing.
Genetic testing can be ordered by a physician or a genetic counselor. It can take weeks to months to get genetic test results. Some labs offer discount programs when it's not covered by insurance.
This organization has a Genetic Counselor knowledgeable about LHON (Devin Shuman) who does phone counseling and others:
The National Society of Genetic Counselors (NSGC) maintains a database of Genetic Counselors.
When a family member has obtained genetic test results, it can usually be assumed that everyone on the maternal bloodline carries the same mutation with no additional testing, especially if all the mitochondria have the LHON mutation (homoplasmy). In some cases there is a desire to confirm that a maternal relative has a LHON mutation, especially when the genetic test reveals a mix of normal and mutated mitochondria (heteroplasmy). Rather than repeating the panel test or the comprehensive mitochondrial test, a more targeted and less expensive option (Known Familial Mutation test) tests for just the specific mutation already identified in a maternal relative. Because there is usually a clear pattern of genetic inheritance when an LHON mitochondrial mutation has been identified, those with a family member on the maternal inheritance bloodline with an LHON mutation should expect that any sudden, painless central vision loss they experience is likely caused by LHON and quickly have an examination of the optic nerves for confirmation.
When LHON vision loss begins in childhood, the onset may be different from the typical pattern of sudden onset in both eyes, making it particularly difficult to diagnose. Vision loss may be gradual, and perhaps in just one eye. In very young children it may be diagnosed as amblyopia or strabismus, rather than as LHON.
5. Patient Care
It's helpful to find a medical professional who is aware of the most current research about LHON. The condition is so rare that most medical professionals are not up-to-date on recent developments. Leading centers for LHON research and patient care in the U.S. include:
Outside the U.S., some of the leading LHON researchers and clinicians are at:
Most neuro-ophthalmologists have some experience with and knowledge of LHON, and you can locate one near you with this directory of NANOS (North American Neuro-Ophthalmology Society) members. Information about various neuro-ophthalmologists can be obtained by asking at the Register tab or by joining a local Facebook group and requesting suggestions.
Directory of Neuro-Ophthalmologists
To see a LHON specialist when travel costs are prohibitive, consider an organization that offers free flights to those with a medical need.
Some of the tests used to assess those with LHON are discussed in the Understanding LHON Vision Tests video. One is a Visual Field Test, which tests where your eye can and cannot see within the visual field. Those with LHON tend to have a central scotoma, which is a blurry area in the center of the visual field. Another is an OCT (Optical Coherence Tomography), which measures the thickness of each part of the optic nerve. The optic nerve becomes unusually thick in specific areas at onset of vision loss as some of the optic nerve fibers are swollen, then the fibers atrophy and the optic nerve becomes unusually thin.
Most LHON experts suggest that people carrying an LHON mutation, both affected and unaffected carriers, avoid environmental factors that could create additional mitochondrial stress including:
Quaternary Ammonium Compounds
Having a discussion with your own LHON medical professional about these factors that are discussed in this article is encouraged. Any individual who is affected by LHON or is likely to carry a LHON mutation and smokes anything would be wise to stop immediately to reduce risk of harm. A smoking cessation program may be helpful in achieving that goal.
Research suggests that estrogen may protect women who carry an LHON mutation. Women who carry an LHON mutation, affected and unaffected, may wish to share this article with their health care providers and discuss its implications for them.
LHON and Estrogen-article
LHON and Estrogen-video
Some research indicates that some individuals with an LHON mutation may be more likely to have low B12 than the general population, so it may be helpful to share the information in this handout with one's physician.
Some individuals with LHON vision loss experience a phenomenon known as Charles Bonnet Syndrome, where they see phantom images. Information about it is in this video and handout.
Many experience photophobia/sensitivity to light and glare. Specialized glasses such as these may be used indoors to limit the impact.
Some individuals experience a worsening of vision during exercise and in heat. This is temporary, and is commonly known as Uhthoff Phenomenon.
It's important for individuals with LHON vision loss to continue having regular eye exams over time. Other eye conditions may develop in those affected by LHON just as in others, and losing any of the vision that remains after LHON onset can be devastating. Treatment for glaucoma or other eye conditions is available if detected early, so regular eye exams are important.
Therapeutic options and treatment strategies for LHON were discussed by Dr. Valerio Carelli and Dr. Patrick Yu-Wai-Man.
In the U.S. and most other countries, there is no approved treatment for LHON. In Europe, a product called Raxone made by Santhera Pharmaceuticals and distributed by Chiesi Pharmaceuticals was approved by the European Medicine Agency (EMA) for use soon after LHON onset and is available in some countries. Raxone is the pharmaceutical grade of idebenone, a synthetic form of CoQ10. The RHODOS clinical trial led to approval.
There has been much additional research about idebenone, including this:
Results of another, larger, longer study about idebenone/Raxone called LEROS are expected to publish soon.
It's important to note that LHON experts strongly discourage unaffected LHON carriers from taking idebenone.
Some LHON experts encourage those taking idebenone to avoid taking CoQ10 at the same time, as explained in this video.
LHON experts strongly encourage LHON patients to avoid getting caught up in the hype of for-profit organizations offering “stem cell treatments” to “cure” LHON and other disorders, as they are basically “selling hope to desperation”. There has not been a single scientific, peer-reviewed paper backing up the claims made by these organizations as this type of treatment simply cannot work because:
It’s literally impossible for cells injected either in the blood or CSF (spinal fluid) to get to where they belong in the retina,
There’s no way these cells would know to become Retinal Ganglion Cells (RCG’s), the cells that atrophy in LHON,
Making new RCG’s means nothing if they don’t know where their axons need to connect to.
Further, LHON experts warn against other, unproven "treatments."
7. Explaining LHON
Many medical challenges are immediately understood by the general public. With a diagnosis of cancer or Alzheimer’s, for example, people generally have a sense of the situation. LHON is different since most people have never heard of it, nor have they had any interaction with anyone with severe vision loss. Blindness is usually thought to be as an all-or-nothing condition, so those with LHON find themselves explaining again and again what they can and cannot see, and how they’ve lost central vision but may can get around using peripheral vision. Macular degeneration is a very different eye condition but the impact on vision is similar to LHON, so that can be a helpful comparison.
People often ask if you can have an operation to “fix” the eyes, or have an eye transplant. With LHON the eyes are working fine. The problem is with the optic nerves that transmit information between the eyes and the brain. The Retinal Ganglion Cells and their axons that form the optic nerves become unhealthy and atrophy. It’s like a TV cord that’s become frayed so the signal doesn't work. Since optic nerve cells can’t regenerate, the ‘cord’ can’t be fixed. In some cases, the optic nerve cells don’t die, they’re just sick, hence in those cases there may be partial recovery.
People affected by LHON are often told they "don't look blind.” If they don’t use a cane or a guide dog, people may not understand they have a vision issue. When people walk by and the person with LHON vision “ignores them,” or doesn’t say "hi" back because they can’t see the person who said “hello,” it’s awkward for everyone. Teaching friends to say “hi, this is so-and-so” upon approaching someone with LHON vision, and encouraging other friends ‘in the know’ to tell the person with LHON vision someone they know is approaching, can be a big help in overcoming this social awkwardness.
Since those with LHON vision usually have some peripheral vision, they tend to use that peripheral vision to see. They may look straight ahead so that others don’t find their gaze disconcerting, yet will look upward or to the side to see what they can using peripheral vision.
Truly looking straight ahead using LHON vision
Looking straight ahead trying to appear fully sighted
In social situations it's difficult to know who to talk to, and impossible to make eye contact or ‘read’ another person’s facial expressions. This can cause a sense of apprehension or unease and the more that sighted supporters can help out, the better.
8. LHON Confusion
Everything about LHON is confusing...even its name! Leber Hereditary Optic Neuropathy is often referred to by its initials; “L-H-O-N”. It is also referred to simply as “Leber” (pronounced LAY-ber), the name of the German doctor (Theodore Leber) who in 1871 described several patients with the disorder. Dr. Leber's name is also associated with a completely different genetic eye condition called Leber Congenital Amaurosis (LCA). It’s important to be sure you’re talking about the ‘right’ disease when reading or hearing about “Leber”.