The National Institute for Health and Care Excellence (NICE) has today announced the approval of a new treatment for a form of hereditary blindness for use on the NHS in England. Cambridge researchers played a pivotal role in providing the evidence that led to this important development.
This will bring hope to those who have experienced significant visual loss from this mitochondrial genetic disorder
Patrick Yu-Wai-Man
Leber hereditary optic neuropathy (LHON) affects around 2,500 people in the United Kingdom. It causes rapidly progressive loss of vision in both eyes. Within weeks of onset, an affected individual reaches the legal threshold to be considered as severely sight impaired (blind).
The condition tends to affect young men, with a peak age of onset between the ages of 15 and 35 years old, but women can also be affected and the loss of vision can occur at any age. The prognosis is poor, with only around one in 10 affected individuals experiencing some spontaneous visual improvement, which is invariably partial.
LHON is caused by the loss of retinal ganglion cells, specialised nerve cells in the innermost layer of the retina. The projections, or 'axons', from these cells converge to form the optic nerve, the cable that transmits visual information from the eye to the brain. Once these retinal ganglion cells are lost, the damage becomes irreversible. LHON is primarily caused by genetic defects within the mitochondrial genome, which is transmitted down the maternal line.
In 2011, the journal Brain published the results of a landmark randomised placebo-controlled trial of the drug idebenone to treat LHON. The RHODOS trial was led by Patrick Chinnery, at the time a researcher at Newcastle University and now Professor of Neurology at the University of Cambridge. It found some potential benefit in a subgroup of patients. However, treatment with idebenone was only given for six months, and it was not clear whether there was any benefit in treating individuals who had been affected for more than one year.
"At the time, we had only anecdotal evidence that idebenone would work for patients with LHON," said Professor Chinnery. "Our clinical trial was the first strong evidence that it could help stabilise vision in some patients. It was an important step towards providing a new treatment."
One of Professor Chinnery's collaborators on the RHODOS trial was Patrick Yu-Wai-Man, Professor of Ophthalmology at the University of Cambridge, who led the follow-up LEROS trial. This assessed the efficacy and safety of idebenone treatment in patients with LHON up to five years after symptom onset and over a treatment period of 24 months. This second trial found that the drug can help stabilise vision in some patients and, in certain cases, may even lead to improvement when treatment is provided within five years of vision being affected.
These studies provided crucial evidence to support the use of idebenone to treat LHON patients. The drug was licenced for limited use by patients in Scotland, Wales and Northern Ireland and it has now been approved by NICE for use in patients aged 12 years and over in England.
Professor Yu-Wai-Man said: "LHON causes devastating visual loss and it is a life-changing diagnosis for the affected individual and their family. England is now in line with the rest of the United Kingdom with idebenone now available through the NHS. This will come as a great relief to the LHON community in this country bringing hope to those who have experienced significant visual loss from this mitochondrial genetic disorder."
The development has been welcomed by charities that have been arguing for idebenone to be made available across the UK. A LHON Society spokesperson said: "This is a critical step towards full access to idebenone for patients, that may alleviate some of the impacts of LHON."
Katie Waller, Head of Patient Programmes at The Lily Foundation, a charity that supports patients affected by mitochondrial diseases, said: "This is a huge win for the mito community and we're proud to have been a key stakeholder throughout the process. While it isn't a cure, this treatment offers real potential for patients to preserve or improve vision, giving the chance to regain independence, confidence and a better quality of life."
Idebenone will not work for everyone, and responses vary from person to person. LHON patients are encouraged to speak with the healthcare professional responsible for their care to understand whether idebenone is the right treatment for them.
