Description

Leber hereditary optic neuropathy (LHON) is an inherited optic nerve disease that leads to sudden, painless vision loss during young adult life, most commonly affecting men. It is caused by mutations in the genetic code of the mitochondria, which are small subunits that reside within the cell.

Mitochondria are also known as the “powerhouses of the cell” as they constantly convert energy locked in our food into energy that the cell can use. Our eyes are our most energy hungry organs and a lack of energy production can lead to degeneration and death of retinal ganglion cells (RGCs), which are the nerve cells that communicate visual information to the brain. Loss of these cells leads to subsequent degeneration of the optic nerve and visual loss. However, it is worth noting that a significant percentage of people who possess a mutation that causes LHON do not develop any features of the disorder.

Loss of vision due to LHON can be quite an alarming experience as the loss of central vision presents suddenly and can progress quite quickly, leaving only peripheral vision. This means that the majority of people with LHON retain independent mobility but cannot focus on anything straight ahead or see fine detail. The prevalence of this condition is thought to be around 1 in 50,000 people worldwide.

Symptoms

The symptoms of Leber’s Hereditary Optic Neuropathy (LHON) typically present when a person is in their teens or twenties, although in some rarer instances, LHON has been diagnosed in young children and in older adults.

Affected individuals do not usually present any symptoms until they develop visual blurring or clouding affecting their central vision. These vision problems may begin in one eye or both simultaneously. If one eye is affected, then similar symptoms appear in the other eye on average eight weeks later.

Over time, the vision in both eyes worsens with a severe loss of sharpness and a fading of colour vision. The vision loss mainly affects central vision, which is needed for tasks such as reading, driving and recognising faces. Optic atrophy follows, in which the cells of the optic nerve (which carries the visual information from the eyes to the brain) becomes damaged or die. In a small percentage of cases, central vision loss can improve but in most cases loss of vision is permanent.

The severity of symptoms may vary from one affected individual to another, even within the same family, due to a ‘dosage’ effect. This is due to the fact that we have many mitochondria in each cell. In one individual, if only a small proportion of mitochondria in each cell have the mutation, symptoms will be mild. In another individual, if a higher proportion of mitochondria in each cell carry the mutation, symptoms will be more severe.

Generally, vision loss is the only symptom of LHON; however, there are cases where additional neurological symptoms have been identified such as tremors, movement disorders and electrical signal abnormalities affecting the heartbeat. This is referred to as “LHON plus”.

Causes

Leber’s Hereditary Optic Neuropathy (LHON) is a genetic condition. It is caused by mutations in the DNA of the mitochondria, the powerhouses of the cell that generate energy for the cell to use in normal activity in the human body. Within this DNA, which is separate to the DNA of the cell, the genes affected by mutations include MT-ND1, MT-ND4, MT-ND4L and MT-ND6. This leads to disrupted energy production within the mitochondria. However, it remains unknown as to how these gene mutations lead to death of cells within the optic nerve, causing optic atrophy.

LHON follows a mitochondrial pattern of inheritance, which is also known as maternal inheritance. Only egg cells (and not sperm cells) contribute mitochondria to a developing embryo, therefore only females can pass mitochondrial conditions to their children. Fathers affected by LHON or carrying LHON mutations do not pass the condition to their children.

***Click here for more information about inheritance patterns.

Often, people who develop LHON have no family history of the condition. However, it is currently impossible to predict which members of a family who carry a mutation will eventually develop vision loss. More than 50% of men and more than 85% of women with a mitochondrial mutation will never experience vision loss.

Diagnosis

Leber’s Hereditary Optic Neuropathy (LHON) is diagnosed through a number of assessments which help with providing the correct diagnosis.

The eye doctor will ask about a person’s medical history, including any family history of eye conditions. Individuals will receive a clinical eye examination where they may be asked to read letters off a chart (Snellen chart). They may also check intraocular pressure and examine visual acuity and the visual field.

An individual may receive a number of imaging tests. Information about the condition may be identified using colour or wide-field fundus photography (which essentially takes photos of the back of the eye). Fundus autofluorescence may be used to identify stress or damage to the retinal pigment epithelium. Optical coherence tomography (OCT) can also be used to assess the various layers at the back of the eye.

An individual may also have an electroretinogram (known as an ERG), which is used to evaluate the functioning of the different types of photoreceptor cells (rods and cones).

A genetic test is also an important component of testing, to ensure the correct condition is diagnosed. For people living in Ireland, genetic testing for LHON can be performed through the Target 5000 programme.

Genetic Diagnosis

It’s often impossible to tell which type of retinal disease a person has just by looking into the eye. As such, a genetic test may be necessary to confirm the diagnosis.

The Target 5000 programme provides free genetic and clinical testing to all individuals living in Ireland with a genetic retinal degeneration, including Leber’s Hereditary Optic Neuropathy (LHON). Through genetic screening of the person awaiting diagnosis and their family members, the Target 5000 programme will provide more detailed information about the nature and inheritance pattern of the condition.

As gene-specific clinical trials and treatments become available, knowing the genetic mutation associated with a genetic retinal degeneration will become even more important. Taking part in this programme ensures participants are included on a national registry from which participants can be identified for clinical trials and treatments and from which further information about each of the genetic retinal degenerations can be defined. For further information on the Target 5000 programme, please contact the Research Department on 01 6789004 or email research@fightingblindness.ie.

Treatment

The progress made by dedicated research teams has led to the development of one therapeutic option so far for Leber’s Hereditary Optic Neuropathy (LHON), with the hope that through the many ongoing clinical trials, other treatments will become available in the near future. To find out more about advances made in this area, please visit the ‘Latest Research’ section.

Raxone®** which contains the active substance idebenone is the only treatment option available at present for people who have been diagnosed with LHON. It is thought to work by improving the energy production from mitochondria. There are suggestions that it may be suited for individuals who have had a recent onset of symptoms. This therapy has been approved by the European Medicines Agency (EMA) in ‘exceptional circumstances’ which has allowed it to be authorised for therapeutic use in the absence of complete knowledge of the medicine. This is due to the challenges in gathering information from a treatment used for a rare condition.

In terms of lifestyle, people diagnosed with LHON are advised to avoid alcohol and smoking, as these may seriously affect the condition. Certain antibiotics may also need to be avoided, so it is important to speak with your ophthalmologist if you are taking any of these medications.

Maximising an individual’s remaining vision is a crucial step to take, and there are many low vision aids which may offer benefit. General eye check-ups are important for people living with LHON, as these individuals may still be at risk of developing other kinds of eye problems that can affect the general population, some of which may be treatable.

No matter what level of vision a person may have, it is important to look after the eyes. To find out more about what can be done to take care of the eyes on a daily basis, please visit our Tips for Good Eye Health.

For further information, please contact the Research Department on 01 6789004.

** Fighting Blindness does not endorse any of the products, medications, treatments or information reported here, or on any of our communication platforms. Articles on Fighting Blindness websites and social media are intended for informational purposes only. We strongly advise that you discuss all medications, treatments, and/or products with your doctor.

Research

Research teams have made notable advances in their quest to gain a deeper understanding of Leber’s Hereditary Optic Neuropathy (LHON) and in finding ways to target this condition to improve quality of life.

Research is ongoing to investigate the only currently approved therapy, Raxone® and its use in individuals living with LHON. As it was authorised by the European Medicines Agency under ‘exceptional circumstances’, it is important that further information is gathered to gain a greater understanding of the treatment.

A number of research teams are investigating gene-based therapies for the treatment of LHON. With this technique, researchers use small, safe viruses which aim to deliver the correct version of the gene of interest to the mitochondria. However, progress in preparing gene therapies for LHON has been more challenging as there was a need to deliver such a therapy to the mitochondria, of which there may be hundreds or thousands within a single cell. Thankfully, many of these barriers have been overcome. Many gene therapy-based clinical trials have or are currently investigating ways to correct for some of the mitochondrial gene mutations associated with this condition.

Stem cells are another area of investigation. Stem cells are like precursor cells which have the potential to self-renew and generate many different types of cells. Bone marrow derived stem cells are being investigated in a clinical trial for LHON which is currently ongoing.

Other interventions being examined currently in clinical trials include agents which aim to reduce the amount of toxic reactive oxygen species present, which is thought to have a significant role in LHON development.

Information about clinical trials can be found on their website by clicking the following link: Clinical Trials Website and can be searched by condition and trial location.

Fighting Blindness currently support a number of research initiatives which aim to improve the diagnosis, care and quality of life of individuals living with LHON.

Target 5000 research, largely funded by Fighting Blindness aims to determine the genetic cause and understand the nature of the condition over time. Through Target 5000, a national registry will also be developed which will greatly improve access to suitable clinical trials and treatments for people living in Ireland with LHON. For further information, please visit ***(insert link to Target 5000).

Dr Sarah Doyle based in Trinity College Dublin is conducting a study to investigate if a protein known as SARM1 plays a role in retinal degeneration, a key component of Leber’s Hereditary Optic Neuropathy. This work aims to further understand the underlying mechanisms of retinal degeneration and identify potentially new therapeutic targets. To find out more about this study, please visit ***(insert link to Dr Doyle’s research project).

A study conducted by Professor Breandán Kennedy is investigating a group of neuroprotective drugs, known as HDAC inhibitors, for their potential to delay vision loss in retinal degenerations. This work seeks to identify new therapeutics which could provide significant benefit to individuals. To find out more about this study, please visit ***(insert link to Prof Kennedy’s research project).

For further information, please contact the Research Department on 01 6789004.

Support

Receiving a diagnosis can be overwhelming for anyone, but this is not a journey that you have to make alone. There are many groups and resources available to provide support for people living with Leber’s Hereditary Optic Neuropathy.

Fighting Blindness offers a free and confidential counselling service (Insight Counselling). For further information please contact insight@fightingblindness.ie or call 01 6746496.

A mindfulness group is also available on every Wednesday at the Fighting Blindness office at 11am.

For technology support and guidance, the Dublin-based Technology Exchange Club meets every Monday at the Fighting Blindness office at 11am. Another Technology Exchange Club, based in Cork, meet every Saturday in the Cork City Library, Grand Parade, Cork City at 11am. The Cork-based club do not meet on Bank Holiday weekends or on the second Saturday of the month. For further information please contact insight@fightingblindness.ie or call 01 6746496.

Resources

Féach provides support for parents of children living with sight loss in Ireland.
Click the following link to view their website: Feach Website

ChildVision is the national education centre for children with sight loss in Ireland.
Click the following link to view their website: ChildVision Website

NCBI (National Council for the Blind in Ireland) provides support and services for people living with sight loss in Ireland.
Click the following link to view their website: NCBI Website

Irish Guide Dogs for the blind helps individuals and their families to achieve improved mobility and independence.
Click the following link to view their website: Irish Guide Dogs Website

LHON Society is a society based in the UK which provides information and support for those and their families living with LHON.
Click the following link to view their website: LHON Society Website

 

Last Updated: 4th February 2019