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About LHON

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  • What is LHON?
  • Symptoms
  • How LHON impacts vision
  • Demographics
  • Role of genetics and inheritance
  • Potential risk factors
and triggers
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What is LHON?

Leber hereditary optic neuropathy (LHON) is an inherited condition that results in rapid central vision loss.1,2

Symptoms in LHON usually begin with sudden, painless blurring and clouding of central vision in one eye and then both eyes.3 It results from cell dysfunction in the optic nerve that relays visual signals from the eye to the brain.3 It affects how patients can see things.3 Each eye gets worse as the blurry blind spot rapidly expands over 6 to 12 months.3,4 The duration in which the eyesight gets worse varies from a few months to more than 2 years.3,4

Symptoms

LHON begins with the following symptoms3-6
Sudden central vision loss usually in one eye followed by the other eye within 8 weeks (75% of the cases); or in both eyes simultaneously (25% of the cases)5,6
Painless blurring in the center of the eye3,4
Blurring of vision4
Loss of sharpness4
Loss of color vision4
Symptoms Symptoms-mobile glass-symptoms Sebastian, Living with LHON

How LHON impacts vision

Normal visionvs LHON vision

Normal vision
LHON vision

In many cases, individuals develop visual blurring affecting the central vision; however, in some cases the peripheral vision is preserved.1,4

LHON affects the central vision needed for routine tasks such as reading, driving, and recognizing people. If you have LHON, you might become legally blind.1,7

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Central vision loss is typically
the only symptom of LHON.

Demographics

Men are three times more likely to be affected by LHON than women.5 The first signs of vision loss usually appear between the ages of 15 and 35 years.8 In rare cases, however, symptoms can occur between 2 and 87 years of age.8 The age of onset tends to be higher in women; LHON shows a marked bias of vision loss in menopausal women.5

Even if LHON runs in your family, one can’t predict the age at which it might trigger, who would be affected (men or women), or the severity of the vision loss.4,5

Knowing the symptoms of LHON can speed up the diagnosis journey

Demographics Demographics-mobile

LHON vision loss can occur at any age in men and women.

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In men
Men are three times more likely to be affected by LHON than women.5
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In women
Unlike men, women have no peak onset age.5

Role of genetics and inheritance

LHON is a condition mostly caused by mutations in the mitochondrial DNA.8 A mother with a mitochondrial mutation passes it on to all her children.8 However, a father who has LHON cannot pass it on to any of his children.8 So, any mutations in the mitochondria can only be inherited maternally.8
Leber hereditary optic neuropathy inheritance diagram showing maternal transmission of mitochondrial DNA mutations and no inheritance from affected fathers. Leber hereditary optic neuropathy inheritance diagram showing maternal transmission of mitochondrial DNA mutations and no inheritance from affected fathers.

The mitochondria produce most of the energy that cells need to function.8 In LHON, these inherited mutations disrupt the mitochondria and cause cells in the optic nerve to stop working or eventually die.8

Mutations in one of the three major genes in mitochondria are responsible for LHON in more than 90% of patients.8 Other rare mitochondrial DNA mutations account for approximately 5% of the LHON cases.9 In the absence of maternally inherited LHON, mutations in a nuclear encoded gene, DNAJC30, have also been established, leading to an autosomal recessive mode of inheritance for LHON (arLHON).9

The genetic mutation in the mitochondria disrupts the normal functioning of the cells in the optic nerve called the retinal ganglion cells.10 The human eyes have over a million retinal ganglion cells.10 These cells process the visual information entering our eyes. They enable us to see things by sending the image to our brain.11

Although all the cells in the body have the same mitochondrial mutations, LHON damages the cells in the eye.12 The number of mitochondria in a cell depends on the energy demands of that particular cell, and retinal ganglion cells need a lot of energy.12 Genetic mutations in LHON make the retinal ganglion cells susceptible to mitochondrial diseases.12 LHON leads to progressive loss of the retinal ganglion cells, resulting in significant visual loss.10

Understanding the role of mitochondria in LHON

Mitochondria are organelles within a cell.10 They have their own set of DNA known as mitochondrial DNA.10,13 They are powerhouses that help convert the energy from food into energy the cell can use.10,13

LHON mutations

Many mutations have been identified in people with LHON. However, approximately 90% of patients affected by LHON have one of the three common mtDNA mutations (m.3460G>A in MT-ND1, m.11778G>A in MT-ND4, and m.14484T>C in MT-ND6).4 In the absence of maternally inherited LHON, mutations in a nuclear encoded gene DNAJC30 have also been established.9

The mutations responsible for LHON affect the generation of energy in the mitochondria.10
Illustration of a mitochondrion showing labeled structures including outer and inner membranes, cristae, matrix, mitochondrial DNA, ribosomes, and ATP synthase, used to explain mitochondrial genetics in LHON. Illustration of a mitochondrion showing labeled structures including outer and inner membranes, cristae, matrix, mitochondrial DNA, ribosomes, and ATP synthase, used to explain mitochondrial genetics in LHON.

Potential risk factors
and triggers

Risk factors for carriers of LHON1,4
Age and sex are important risk factors for LHON.4
Young men have an estimated lifetime risk of about 17% if someone in their family has been affected, and about 2.5% if no family members have yet been affected. These percentages fall if the person who carries a LHON mutation avoids potential triggers.14,15
The threat of acquiring LHON never vanishes, as it can present late in life.16
Sebastian Sebastian Sebastian, Living with LHON
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Triggers
While women are less likely to be affected, sometimes, menopause or stopping hormone replacement therapies is also known to trigger LHON.17
Environmental factors could also contribute to vision loss, and additional medical problems have been associated with LHON.18
Eliane Eliane Eliane, Living with LHON
Shard-eliane Shard-eliane
If you are an LHON carrier, you will be advised of the following4
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Do not smoke

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Drink alcohol
moderately

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Avoid binge-drinking
episodes

Some drugs are known to cause damage to the mitochondria. Talk to your treating physician to better understand how LHON can be affected by certain medications.4
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Talk to your treating physician
about the potential risks and
triggers for developing LHON.
LEARN HOW LHON IS DIAGNOSED arrow-right

References:

  1. Theodorou-Kanakari A, et al. Adv Ther. 2018;35(10):1510-1518.
  2. Kirches E, et al. Curr Genomics. 2011;12(1):44-54.
  3. Carelli V, et al. European Ophthalmic Review. 2019;13(Suppl 2).
  4. Yu-Wai-Man P, et al. Leber Hereditary Optic Neuropathy. 2000. In: Adam MP, Bick S, Mirzaa GM, et al., eds. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. Updated March 2021.
  5. Poincenot L, et al. Ophthalmology. 2020;127(5):679-688.
  6. Yu-Wai-Man P, et al. Prog Retin Eye Res. 2011;30(2):81-114.
  7. Kirkman MA, et al. Invest Ophthalmol Vis Sci. 2009;50(7):3112-3115.
  8. Fraser JA, et al. Surv Ophthalmol. 2010;55(4):299-334.
  9. Stenton SL, et al. J Clin Invest. 2021;131(6):e138267. 
  10. Yu-Wai-Man P, et al. Hum Mol Genet. 2017;26(R1):R12-R20.
  11. Weinbar S, et al. Prog Retin Eye Res. 2018;67:102-117. 
  12. Meyersen C, et al. Clin Ophthalmol. 2015;9:1165-1176.
  13. Newmeyer DD, et al. Cell. 2003;112(4):481-490. 
  14. Mackey DA, et al. Am J Hum Genet. 2023;110(1):170-176.
  15. López Sánchez MIG, et al. Am J Hum Genet. 2021;108(11):2159-2170.
  16. Shah MP, et al. J Neuroophthalmol. 2024;44(4):e528-e529.
  17. Asanad S, et al. J Curr Ophthalmol. 2019;31(3):251-253.
  18. Sadun A, et al. Curr Treat Options Neurol. 2011;13(1):109-117.