LHON 101
1. What is LHON?
2. Demographics
3. Cause
4. Diagnosis
5. Patient Care and Treatments
6. Research & Clinical Trials
7. Explaining LHON
8. LHON Confusion
1. What is LHON?
Leber’s 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 8 months or so. Severe vision loss in both eyes remains in most cases. Reading standard-sized text, driving and recognizing faces become impossible. Peripheral vision often remains intact so the affected individual can walk around independently, though in many cases a white cane or guide dog are 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 is their vision loss. Color vision also becomes impaired.
The first video below was filmed at the 2015 LHON Conference and provides a comprehensive overview, with answers to most of the common questions about the medical/scientific issues of LHON from three of the world’s leaders in the field [Dr. Patrick Yu-Wai-Man (UK), Dr. Valerio Carelli (Italy), Dr. Alfredo Sadun (USA)]. The second video is a LHON overview by another LHON expert, Dr. Nancy Newman.
A written medical explanation of LHON can be found here:
Gene Reviews-Leber Hereditary Optic Neuropathy
This article also provides a good medical overview:
Inherited Mitochondrial Optic Neuropathies
2. Demographics
About 100 people in the United States lose central vision due to LHON each year, joining the 4,000 or so Americans who are already legally blind due to LHON. Thousands more carry a LHON genetic mutation, and each could suddenly lose their central vision at any time. It’s estimated that about 35,000 people worldwide have LHON vision. About 25% of those affected are female; 75% male. Onset of vision loss can happen at any age. Males have a peak onset around ages 14-26, while there is no peak onset age in females, as shown in the chart below. In all cases, if you carry a LHON mutation, you’re never “too young” or “too old” to be affected.
3. Cause
LHON is a genetic disorder that can cause the optic nerve to atrophy but does not always do so and usually does not. It is a mitochondrial disease, as it is caused by a genetic mutation (variance) in the mitochondria. The most common LHON mutation is the 11778 mutation, accounting for over 65% of all LHON cases. Most of the remaining LHON cases are caused by the 14484 mutation or the 3460 mutation, while about 5-10% are one of several very rare mutations. A woman carrying a LHON mutation will pass it to all of her children; men with a LHON mutation never pass it to their children. Those who have lost their central vision due to LHON are referred to as “affected;” those with a LHON mutation in their mitochondria but without vision loss are called “carriers” or "unaffected carriers." At the 2013 & 2014 LHON Conferences, Dr. Alfredo Sadun provided an overview of LHON and Dr. Valerio Carelli discussed what triggers vision loss in LHON among some individuals carrying a LHON mutation..
4. Diagnosis
Because there is a clear pattern of LHON genetic inheritance, those with a family member on the maternal inheritance bloodline with a LHON mutation should expect that any sudden, painless central vision loss they experience is likely caused by LHON. However, carrying the LHON mutation does not mean that a LHON carrier will lose central vision; most who carry a LHON mutation do not.
Those who are not aware of any family members with LHON are taken by surprise when they suddenly lose central vision. Since LHON is so rare, the medical community usually suspects, tests and treats for 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 vision loss usually begins in just one eye, the tentative diagnosis of Optic Neuritis is often made and a 3 or 5 day steroid treatment is often prescribed. Optic Neuritis involves eye pain about 90% of the time while LHON onset is painless. Optic Neuritis usually involves just one eye, so when the second eye begins losing vision, there may be more tests to rule out other possible causes of sudden, bilateral, painless loss of central vision and color vision abnormalities.
A specific test of the blood or saliva can usually determine if someone carries a LHON mutation. Some labs test for just the 3 most common LHON mutations. Others such as GeneDx test for 20 LHON mutations which includes many of the very rare mutations. GeneDx offers a variety of programs designed to ensure that their LHON genetic testing is affordable to all.
In some cases, more comprehensive testing of the mitochondria is required. Labs such as EGL Genetics and others can analyze the full mitochondrial genome to locate common and rare variances.
When a family member has obtained genetic test results, they often assume that everyone on the maternal bloodline carries the same mutation, and do no additional testing unless/until another family member becomes affected. In some cases there is a desire or a need to confirm that a maternal relative has a LHON mutation. Rather than repeating the panel test or the comprehensive test of the mitochondria, a more targeted and less expensive option is available. Analysis of a Known Familial Mutation can be done by labs such as MNG Laboratories.
MNG Laboratories Known Familial Mutation
Genetic testing can be ordered by a physician or a genetic counselor. Genetic counseling with a LHON expert is available by phone at:
5. Patient Care & Treatments
It is important to find a medical professional who is aware of the most current research regarding LHON, as there has been much new learning in recent years and 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:
UCLA Doheny Eye Institute - Pasadena, CA
Emory University - Atlanta, GA
Wills Eye - Philadelphia, PA
Outside the U.S., leading LHON researchers and clinicians are at:
The Ottawa Hospital - Canada
Cambridge University - Cambridge, UK
Royal Victorian Eye & Ear Hospital - Australia
University of Bologna - Bologna, Italy
If you wish to see one of these LHON specialists but cannot afford the travel costs, consider an organization that offers free flights to those with a medical need such as Miracle Flights.
A neuro-ophthalmologist is most likely to have experience with and knowledge of LHON. To find a neuro-ophthalmologist near you, use this directory of NANOS (North American Neuro-Ophthalmology Society) members.
Directory of Neuro-Ophthalmologists
Another option is to use the Register tab on this site, and request a referral to an experienced LHON doctor.
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 in the early phase of LHON. Raxone is the pharmaceutical grade of idebenone, a synthetic form of CoQ10. The major clinical trial that led to this approval is reported here:
Idebenone Clinical Trial as Reported in Brain, 2011
Additional research about this supplement can be found at:
Idebenone Retrospective Report in Brain, 2011
The company that developed Raxone continues to evaluate the product, and additional information about it can be found on the website of Santhera Pharmaceuticals.
Many LHON specialists suggest that people carrying a LHON mutation, both carriers and affected, should avoid environmental factors that could create additional stress on the mitochondria. These factors include:
Smoke (all forms - tobacco, wood stoves, bonfires, wildfires, chemical factory fires, etc.)
Vaping
Alcohol
Antimicrobials:
-Erythromycin
-Ethambutol
-Linezolid
-Chloramphenicol
-Aminoglycosides
-Tetracyclines
Hyperbaric Oxygen
Quaternary Ammonium Compounds
Ringer's lactate
Having a discussion with your own LHON medical professional about these factors is encouraged. They may wish to obtain and review this article:
Toxic Medications in Leber's Hereditary Optic Neuropathy
Research suggests that estrogen may protect women who carry a LHON mutation. Female LHON carriers and affecteds may wish to read this article, and discuss its implications with their health care providers.
LHON and Estrogen-article
LHON and Estrogen-video
At the 2013 LHON conference Dr. Valerio Carelli described LHON therapeutic options and in 2014 Dr. Patrick Yu-Wai-Man provided additional information on the topic. Click on the photos below to watch their presentations.
It is important to avoid getting caught up in the hype of for-profit organizations who offer “stem cell treatments” to “cure” LHON and other disorders. These organizations are basically “selling hope to desperation”, at high prices. 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:
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It’s literally impossible for cells injected either in the blood or CSF (spinal fluid) to get to where they belong in the retina,
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There’s no way these cells would know to become Retinal Ganglion Cells (RCG’s), the cells that atrophy in LHON,
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Making new RCG’s means nothing if they don’t know where their axons need to connect to.
FDA Warns About Stem Cell Claims
One of the most important tests taken by those with LHON is a Visual Field Test. It tests where your eye can see and where it can’t. Those with LHON tend to have what’s called a central scotoma; an area in the center of the visual field where no information is transmitted from the eye to the brain. Another important test is an OCT (Optical Coherence Tomography). This test measures the thickness of the optic nerve. Generally the optic nerve is unusually thick at onset of vision loss, as the fibers are swollen. Later the nerve becomes unusually thin, as the fibers atrophy. These tests are explained in the video below.
Here are videos about LHON Treatments and Trials, as well as an explanation of the Research Process.
6. Research & Clinical Trials
There are several research centers around the world where LHON is being studied, including clinical trials. Even though there are relatively few people affected by LHON, there are many researchers working on it because as a mitochondrial disorder it is similar in nature to diseases such as Alzheimer’s, Huntington’s and Parkinson’s, which impact large numbers of patients. Several clinical trials are fully recruited, and data is being collected.
To support LHON research so that a treatment or cure is found as soon as possible, click this Donate button:
7. Explaining LHON
There are many medical challenges people face that are immediately understood by the general public. When the diagnosis is cancer or Alzheimer’s, for example, people generally have a sense of the situation. LHON is different—most people you speak with will have no reason to know what LHON is. They’ll never have heard of mitochondrial disease. And most will have had no real contact with anyone who is legally blind. Often blindness is perceived as an all-or-nothing condition, so those with LHON find themselves explaining again and again what they can and can’t see, and how they’ve lost central vision but perhaps can get around using peripheral vision. Often times people know someone with macular degeneration, and while macular degeneration is a retinal disorder which tends to onset gradually, late in life unlike LHON which is an optic nerve disease which tends to onset suddenly at a younger age, the impact on vision is similar in both cases which can help in explaining what LHON vision is like.
People often ask if you can have an operation to “fix” the eyes, or to have an eye transplant. It’s helpful to explain that there are three key aspects to vision: the eyes, the brain, and the optic nerve. With LHON the eyes and the brain work just fine. What’s not working is the optic nerve which functions similarly to a wire that transmits information from the eye to the brain and back. With LHON the cells in the optic nerve are overdoing it on apoptosis—preprogrammed cell death—too many cells are committing suicide, causing the optic nerve to atrophy. It’s like a TV cord that’s been chewed by a mouse. Since optic nerve cells can’t regenerate, the ‘cord’ can’t be fixed (though some with LHON are fortunate in that their optic nerve cells don’t die, they’re just sick, hence there can be spontaneous recovery in some cases).
Someone with LHON may not “look blind,” and if they don’t use a cane or a guide dog, people may not understand their problems. 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 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 really see.
Truly looking straight ahead using LHON vision
Looking straight ahead trying to appear fully sighted
In social situations with strangers one cannot choose who to talk to, let alone make eye contact or ‘read’ another person’s facial expressions. This can cause a sense of apprehension or unease in social situations and the more that friends can help out, the better.
8. LHON Confusion
Everything about LHON is confusing...even its name! Leber’s Hereditary Optic Neuropathy is often referred to by its initials; “L-H-O-N”. It is also referred to simply as “Leber’s,” (pronounced LAY-bers), the name of the German doctor who first described the disorder (Theodore Leber). However, that same doctor also described a completely different eye condition called Leber’s Congenital Amaurosis (LCA) which is also genetic in origin but affects the retina not the optic nerve. The two conditions have nothing in common other than the founding doctor’s name, so it’s important to be sure you’re talking about the ‘right’ Leber’s when someone tells you about something they’ve heard about “Leber’s”.