Each month, members of the LHON community gather online for LHON Live. During each session, patients interact on topics related to living with LHON.

LHON vision loss can onset at any age. Onset in females is fairly evenly distributed throughout the lifespan. In males there is a peak of onset at ages 14-26, though it also occurs at younger and older ages. Males are about three times more likely to become affected and lose central vision than females.

After nadir (greatest vision loss), which usually occurs around six to eight months after onset in each affected eye, most affected individuals note no significant change in vision over time. In some cases, the scotoma (blurry spot) gradually decreases in size, so there’s more peripheral vision, or fenestrations (windows) emerge within the scotoma that the person can see through, or both. The outcome tends to be more favorable when onset occurs in childhood, and with certain variants, most notably mt.14484T>C [i]. The affected individual can also become accustomed to their LHON vision over time and learn to use their remaining vision more effectively, perceiving this change as improvement. On the other hand, in some individuals there can be additional, very gradual vision loss over time, which may be more likely if there is ongoing exposure to harmful environmental factors such as smoking. 

Most individuals with a LHON variant live their lives without visual symptoms[i].  Some LHON carriers experience conversion when they notice a change in their vision, and this is accompanied by swelling of the optic nerve in a characteristic pattern. The optic nerve is the main cable which transfers information from the eye to the brain and is composed of the axons of the retinal ganglion cells, which are responsible for sending the signal from the eye to the brain. This signal is impaired in the swollen optic nerve, where the retinal ganglion cells are sick and, as some of the retinal ganglion cells die, the optic nerve atrophies. This reduces the amount of information sent to the brain from the eye; so while the eye may function normally in a patient with LHON, the information is not being sent to the brain leading to visual impairment.

It is unclear why some individuals who carry a LHON variant become affected while others do not. Additional genetic factors may play a role in determining which individuals with a LHON variant lose vision, such as the high correlation between the J haplogroup and onset.  Environmental factors such as smoking have been shown to increase the risk of onset among those who carry a LHON variant. Other factors, such as heavy alcohol use, exposure to other forms of smoke, head trauma[ii], long term use of antibiotics toxic to the mitochondria,[iii] a drop in estrogen[iv], etc., may also play a role in impacting risk of onset.

• sudden, profound blurring and clouding of the central field of vision (scotoma)
• severe loss of the sharpness of vision (visual acuity) to legal blindness and worse
• color vision may be affected
• Charles Bonnet Syndrome (visual hallucinations) may occur [i]
• anxiety and depression are common reactions to sudden onset vision loss[ii]

In addition, many individuals who carry a LHON variant report non-vision symptoms that may be associated with their LHON variant. These symptoms include muscle weakness, peripheral neuropathy, tremors, migraine, cardiac issues, bladder issues, and more. The term LHON Plus is commonly used to describe these symptoms.

• eye dilation
• visual tests (visual acuity; visual field test, color vision)
• eye imaging through optical coherence tomography (OCT)
• brain imaging and other testing to assist with ruling out other potential causes of sudden onset vision loss (brain tumor, MS, NMO, MOG, etc.)
• an examination of family history
• molecular genetic testing for a LHON variant

A neuro-ophthalmologist specializes in diseases of the optic nerve, and is most likely to be familiar with LHON.

Some evidence suggests that Idebenone, a synthetic form of CoQ10, can help some individuals have a somewhat better outcome if taken over a long period of time, and especially if initiated early.  Idebenone should not be taken by unaffected carriers of a LHON variant, as its effects are unknown in this population. There is concern that Idebenone could disrupt the balance in patients who are carriers of LHON and thus trigger onset of vision loss in someone who otherwise would not become affected[i].

Options for managing LHON include:

• behavioral management (e.g., discontinuing smoking; limiting alcohol)
• support for emotional well-being (e.g., grief/loss counseling)
• educating about Charles Bonnet Syndrome
• visual aids (e.g. ZoomText, JAWS, CCTV, iPhone apps, audio description)
• occupational/vocational rehabilitation, support in the educational environment
• registration with relevant social services
• referral to relevant specialists for those individuals experiencing problems with other body systems

Genetic counseling for the family of the affected individual can be helpful since LHON is an inherited disorder. Since there is no treatment for LHON that avoids legal blindness once onset begins, prevention of onset among those who carry a LHON variant is a consideration.  Individuals who have genetic confirmation of a LHON variant may wish to inform maternal relatives of their genetic risk, and a genetic counselor can be helpful in that process.

Are there any clinical trials for LHON?

To see what trials you may qualify for, visit our Clinical Trials page – which also included a Clinical Trials Finder Tool. We also highly encourage you to join our patient registry, mitoSHARE, where we are actively recruiting LHON families.

For an archive of past monthly LHON calls visit umdf.org/LHON-Live.

What are the next steps if my loved one has LHON?

• Get Support
  Connect with our Support & Education Team online, via email at support@umdf.org or phone at (888) 900-6486.

• Check our Clinical Trials Finder
  Use our Clinical Trials Finder to see if you qualify for any clinical trials.

• Join our patient registry, mitoSHARE
  We are actively recruiting LHON families to participate in our patient registry, mitoSHARE. Patient registries like mitoSHARE are an integral part in charting a course toward treatments and cures for LHON and other mitochondrial diseases. There are currently over 30 active mitochondrial disease clinical trials. Next generation patient registries like mitoSHARE are an integral part of expanding that number.

• Become an advocate
  Ask your representatives to prioritize mitochondrial disease research and support via the UMDF Advocacy Center. We’ll send regular action items so you – and your friends and family – can let Congress know where we need their support. Click here to sign up.

• Join the conversation online
  – UMDF Social Media Support Groups: Facebook Support Group
  – UMDF News & Updates: Facebook | Twitter | Instagram | YouTube

• Get involved
  Join the fight by giving your voice, generosity, time, or energy. Click here to see how you can help.

UMDF is helping chart a path toward treatments and eventual cure of mitochondrial diseases like LHON through:

• Research & Funding: UMDF has provided more than $15 million in research funding to find treatments for diseases like LHON. UMDF advocacy has helped secure an additional $55 million in federal funding via the Department of Defense and National Institutes of Health.
• Data: Over two decades ago, UMDF pioneered patient registries for the mitochondrial disease community. Today, our next generation patient registry, mitoSHARE, is helping chart a path toward the treatment and eventual cure of mitochondrial diseases.
• Patient Support: Thousands of families just like you depend upon UMDF for support and education on diseases like LHON. Attendance at our support meetings annually tops 7,000, including disease specific support meetings for families.
• Clinician Support: To help educate clinicians on diseases like LHON, we feature monthly Bench to Bedside clinician seminars, host the annual Mitochondrial Medicine Symposium, support the Mitochondrial Care Network, and educate clinicians on our Mito U platform.

If you wish to support these vital efforts, consider making a donation to the LHON Project at UMDF.

• www.LHON.org
• The National Organization for Rare Disorders (NORD): Leber hereditary optic neuropathy (LHON)
• The National Institutes of Health (NIH) National Library of Medicine: Leber hereditary optic neuropathy
• DNA Today podcast about living with LHON.

Where can I find a neuro-ophthalmologist? 

https://www.nanosweb.org/i4a/memberDirectory/index.cfm?directory_id=3&pageID=3390

Where can I find a genetic counselor? 

https://findageneticcounselor.nsgc.org

How can I tell my family about LHON? 

https://www.youtube.com/playlist?list=PLYlX-8FXeWbDF9iC-G008Iahjl2HJ7Q6P

1. Poincenot L, Pearson AL, Karanjia R. Demographics of a Large International Population of Patients Affected by Leber’s Hereditary Optic Neuropathy. Ophthalmology. 2020 May;127(5):679-688. doi: 10.1016/j.ophtha.2019.11.014. Epub 2019 Nov 25. PMID: 31932089.

2. Siedlecki J, Koenig S, Catarino C, et al. Childhood versus early-teenage onset Leber’s hereditary optic neuropathy: visual prognosis and capacity for recovery [published online ahead of print, 2022 Feb 21]. Br J Ophthalmol. 2022;bjophthalmol-2021-320580. doi:10.1136/bjophthalmol-2021-320580

3. Guo DY, Wang XW, Hong N, Gu YS. A Meta-analysis of the association between different genotypes (G11778A, T14484Cand G3460A) of Leber hereditary optic neuropathy and visual prognosis. Int J Ophthalmol. 2016;9(10):1493-1498. Published 2016 Oct 18. doi:10.18240/ijo.2016.10.21

4. Lopez Sanchez MIG, Kearns LS, Staffieri SE, Clarke L, McGuinness MB, Meteoukki W, Samuel S, Ruddle JB, Chen C, Fraser CL, Harrison J, Hewitt AW, Howell N, Mackey DA. Establishing risk of vision loss in Leber hereditary optic neuropathy. Am J Hum Genet. 2021 Nov 4;108(11):2159-2170. doi: 10.1016/j.ajhg.2021.09.015. Epub 2021 Oct 19. PMID: 34670133; PMCID: PMC8595929.

5. Valerio Carelli, Alessandro Achilli, Maria Lucia Valentino, Chiara Rengo, Ornella Semino, Maria Pala, Anna Olivieri, Marina Mattiazzi, Francesco Pallotti, Franco Carrara, Massimo Zeviani, Vincenzo Leuzzi, Carla Carducci, Giorgio Valle, Barbara Simionati, Luana Mendieta, Solange Salomao, Rubens Belfort, Alfredo A. Sadun, Antonio Torroni. Haplogroup Effects and Recombination of Mitochondrial DNA: Novel Clues from the Analysis of Leber Hereditary Optic Neuropathy Pedigrees, The American Journal of Human Genetics, Volume 78, Issue 4, 2006, Pages 564-574, ISSN 0002-9297, https://doi.org/10.1086/501236. (https://www.sciencedirect.com/science/article/pii/S0002929707636969)

6. Giordano L, Deceglie S, d’Adamo P, et al. Cigarette toxicity triggers Leber’s hereditary optic neuropathy by affecting mtDNA copy number, oxidative phosphorylation and ROS detoxification pathways. Cell Death Dis. 2015;6(12):e2021. Published 2015 Dec 17. doi:10.1038/cddis.2015.364

7. Matthew Anthony Kirkman, Patrick Yu-Wai-Man, Alex Korsten, Miriam Leonhardt, Konstantin Dimitriadis, Ireneaus F. De Coo, Thomas Klopstock, Patrick Francis Chinnery, Gene–environment interactions in Leber hereditary optic neuropathy, Brain, Volume 132, Issue 9, September 2009, Pages 2317–2326, https://doi.org/10.1093/brain/awp158