Promising first results in gene therapy trial for inherited blindness

Moorfields’ patients and consultants have been involved in the first clinical trial of a gene therapy for an inherited cause of progressive blindness called choroideremia. 

The promising initial results (at the six month stage) for the first six patients were published in The Lancet on 16 January 2014 and surpassed the expectations of the researchers leading the study. The aim of the treatment in this study was to get the gene therapy into the cells in the retina of the eye without causing damage. After six months, however, the patients actually showed improvements in their vision in dim light and two of the six were able to read more lines on the eye chart.

This is a multi-centre trial involving a total of nine patients, three of whom are patients at Moorfields, who have had one eye treated with the gene therapy. The therapy is given in one eye to allow comparison with progression of the disease in the other eye. Planning is also underway for a phase II trial which will be led by Moorfields consultant Professor Andrew Webster at the National Institute of Health Research (NIHR) Biomedical Research Centre at Moorfields.

The phase I clinical trial was funded by the Health Innovation Challenge Fund, a partnership between the Wellcome Trust and the Department of Health. The research study also received additional charitable support, including a substantial generous donation from Moorfields Eye Charity and the Lanvern Foundation.  This was a collaborative study involving the University of Oxford, Moorfields Eye Hospital, Manchester Eye Hospital and the University of Southampton. The majority of the patients were diagnosed and managed at Moorfields.

The first patient to have the operation has now been followed up for over two years. Based on the success of the treatment in the first six patients, three more have recently been tested at a higher dose.

Professor Robert MacLaren of the Nuffield Laboratory of Ophthalmology at the University of Oxford and an honorary consultant at Moorfields, led the development of the retinal gene therapy and this first clinical trial.  He said: ‘It is still too early to know if the gene therapy treatment will last indefinitely, but we can say that the vision improvements have been maintained for as long as we have been following up with the patients, which is two years in one case.  In truth, we did not expect to see such dramatic improvements in visual acuity and so we contacted both patients’ home opticians to get current and historical data on their vision in former years, long before the gene therapy trial started. These readings confirmed exactly what we had seen in our study and provided an independent verification.

“The results showing improvement in vision in the first six patients confirmed that the virus can deliver its DNA payload without causing significant damage to the retina. This has huge implications for anyone with a genetic retinal disease such as age-related macular degeneration or retinitis pigmentosa, because it shown for the first time that gene therapy can be applied safely before the onset of vision loss.” 

Professor Webster who was the lead at Moorfields for the phase 1 trial said: “Although it is still early days, these first signs are promising, and suggest that a treatment has been developed that has the potential to prevent the blindness that would otherwise occur in men affected by this disorder. Importantly, this trial is a further step forwards towards treating other blinding retinal disorders using a similar strategy.”

Choroideremia is a rare inherited cause of blindness that affects around 1 in 50,000 people. The first signs tend to be seen in boys in late childhood, with the disease slowly progressing until vision is lost. There is currently no cure. It is caused by defects in the CHM gene on the X chromosome, which explains why it is almost always boys that are affected. Without the protein produced by the CHM gene, pigment cells in the retina of the eye slowly stop working, and then die off. As the disease progresses, the surviving retina gradually shrinks in size, reducing vision. 

The gene therapy approach taken in this trial uses a small, safe virus to carry the missing CHM gene into the light-sensing cells in the retina. In an operation similar to cataract surgery, the patient’s retina is first detached and then the virus is injected underneath using a very fine needle.

Professor Miguel Seabra, whose research at Imperial College London studied the protein encoded by the gene, says: ‘My team has spent 20 years trying to understand choroideraemia and develop a cure, so to finally see the rewards reaching patients is extremely gratifying, both for us and the families who supported our research.”

The phase I trial began with six patients: two with excellent visual acuity, two with good acuity and two with reduced acuity. Visual acuity is the acuteness or clearness of vision, and is measured by reading lines of letters on a sight chart.  Six months after the operation, those with excellent or good acuity had the same level of acuity they began with, but could see more in the dark when tested – despite the detachment of the retina during the operation.  The two patients with reduced acuity saw improvements in their visions, and were able to read two and four more lines on the sight chart.

One of these was Toby Stroh, a solicitor in London and a patient at Moorfields who has shown continued improvement at one year. Describing his condition and participation in the trial, Mr Stroh said:

 “After a medical at school when I was 12 or 13, the comment from the doctor was 'vision merits further examination'. After various tests, I was given a diagnosis of retinitis pigmentosa.  I had noticed from an early age (and before that examination) that my vision in the dark wasn’t great, but it wasn’t a disaster. Others talked about things I couldn’t see. My choroideraemia has been a gradual progression and deterioration in vision. The effect was minimal for a long time as core vision was unaffected. I played a lot of tennis for many years in both singles and doubles and enjoyed it greatly. At college, I played table tennis and my vision, at that stage, was fine when it came to a fast moving ball. Over time, however, my peripheral vision reduced. I haven’t been able to follow the rapid movement in table tennis for many years. And doubles, as I used to play it, is unfortunately no longer possible.

“Several months ago I started using a stick, largely to warn people that despite looking absolutely fine, I do, in fact, have a problem in that I am only partially sighted. My straight-ahead vision is fine, albeit limited in breadth (like looking down a telescope) which is why I can read and play singles but why crowds are extremely challenging. Unmarked steps – particularly patterned carpet steps and marble steps without edging – are a nightmare. Going down them is worse as it is very difficult for me to see where they start. Going up is less difficult, possibly due to inherent shadow. I simply can’t tell where the steps start.  I had the operation as part of this trial in February 2012. The operation was in my worse eye, my left eye.

“There’s been a marked improvement in the number of letters I can read on a sight chart. I cannot remember how hard I used to try to read the lines before the operation, but it is such a dramatic improvement that as far as I am concerned, it must be as a result of the trial.  I still don’t use my left eye for reading due to the core being affected by the choroideraemia. I can do so (using that eye alone) but it takes time and it’s tiring. A little bit of sight has come back and, to me, that’s fantastic. I don’t know how long it will last, but a few months ago it was still there.

“I have been living under this cloud for many years and have been concerned I’m going blind. I’m a solicitor and, although I know there are various software packages to help, at the moment I depend on my sight to read. It becomes particularly precious when I think it’s not going to last.  This result does not make me swing from chandeliers and I refuse to say everything is going to be roses. But, there is hope.  I have said for a long time that as long as I can read and play tennis, I’ll be happy. As a result of this trial there is now a chance I’ll be able to do both these things for longer. From an emotional perspective, it was great. Really was. Long may it last.”

This is the first time a gene therapy for an eye condition has been tested in people with full 6/6 visual acuity. This suggests the approach has promise for treating people early on before too many cells in the retina have been lost.

It is also the first time that a gene therapy has targeted the principal light-sensing cells in the retina. This means the approach has relevance for other far more common causes of blindness, where these light-sensing cells are affected, such as retinitis pigmentosa and age-related macular degeneration.

Professor Sir Peng Tee Khaw Director of the NIHR BRC at Moorfields and the UCL Institute of Ophthalmology said: “This study is excellent news for our patients. It confirms the safety to date of the first human retinal gene therapy in the world, performed at Moorfields, giving great hope for many patients with other currently untreatable conditions. It confirms the importance of the UK having centres with large numbers of patients with rare diseases and combining this with the leading university research centre to change our patients’ lives.”

Notes to editors

  • The paper ‘Initial observations in patients undergoing retinal gene therapy for choroideraemia’ was published in the Lancet 
  • Choroideremia is a rare inherited cause of blindness that affects around 1 in 50,000 people. The first signs tend to be seen in boys in late childhood, with the disease slowly progressing until vision is lost. There is currently no cure. It’s caused by defects in the CHM gene on the X chromosome, which explains why it is almost always boys that are affected. The loss of the protein encoded by the CHM gene leads pigment cells in the retina of the eye to stop working then die off. People will first notice that their vision is lower than other people’s, particularly at night. Then as the disease progresses, their surviving retina becomes smaller until it is a little slit in the centre of their vision.
  • The gene therapy uses a small virus called AAV to deliver the correct version of the CHM gene into the pigment cells of the retina. The AAV delivery vehicle was developed and tested by Professor Robert MacLaren’s group at University of Oxford in collaboration with Professor Miguel Seabra at Imperial College London, with funding from The Tommy Salisbury Fund at Fight for Sight and Moorfields Eye Charity.  While it can carry only a small amount of genetic material, it is enough to carry the CHM gene to the retinal cells, switch the gene on and produce the missing protein – hopefully halting the loss of cells and the slow degeneration of vision. The therapy should require just one injection, as once the AAV virus has delivered the missing CHM gene, the DNA is incorporated into the cells of the retina. 
  • The clinical trial also involved developing a new surgery technique. This involved separate stages in which the patient’s retina was first detached in a controlled and gradual process, and only once that had been done was the virus encapsulating the gene therapy injected under the retina. This separation of the operation into two consecutive steps, rather than doing both together, minimised damage and improved recovery with no discernible effect on the patient’s vision. 
  • The technology is covered by a patent application owned by Isis Innovation, the technology transfer company of Oxford University. Work is in progress to develop the gene therapy into an approved clinical product through further clinical trials.

About the Health Innovation Challenge Fund

The Health Innovation Challenge Fund is a parallel funding partnership between the Wellcome Trust and the Department of Health, aiming to stimulate the creation of innovative healthcare products, technologies and interventions, facilitating their development for the benefit of patients in the NHS and beyond.

About the Department of Health
The Department of Health (DH) helps people to live better for longer. The Department leads, shapes and funds health and care in England, making sure people have the support, care and treatment they need, with the compassion, respect and dignity they deserve. The Department funds health research and encourages the use of new technologies because it’s important to the development of new, more effective treatments for NHS patients. Innovation is needed so that decisions about health and care are based on the best and latest evidence.

About the Wellcome Trust
The Wellcome Trust is a global charitable foundation dedicated to achieving extraordinary improvements in human and animal health. It supports the brightest minds in biomedical research and the medical humanities. The Trust's breadth of support includes public engagement, education and the application of research to improve health. It is independent of both political and commercial interests.

The National Institute for Health Research (NIHR) is funded by the Department of Health to improve the health and wealth of the nation through research. Since its establishment in April 2006, the NIHR has transformed research in the NHS. It has increased the volume of applied health research for the benefit of patients and the public, driven faster translation of basic science discoveries into tangible benefits for patients and the economy, and developed and supported the people who conduct and contribute to applied health research. The NIHR plays a key role in the government’s strategy for economic growth, attracting investment by the life-sciences industries through its world-class infrastructure for health research. Together, the NIHR people, programmes, centres of excellence and systems represent the most integrated health research system in the world. For further information, visit the NIHR website (

NIHR Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology is a partnership between Moorfields Eye Hospital NHS Foundation Trust and the UCL Institute of Ophthalmology.  Established in April 2007, its purpose is to conduct 'translational research' that is designed to take advances in basic medical research from the laboratory to the clinic, enabling patients to benefit more quickly from new scientific breakthroughs.  Our centre is currently one of 12 biomedical research centres that were awarded in 2007 to NHS/university partnerships with an outstanding international reputation for medical research and expertise, and experience of translating that research into the clinical setting.  For further information, please visit 

Moorfields Eye Hospital NHS Foundation Trust is one of the world’s leading eye hospitals, providing expertise in clinical care, research and education.  We have provided excellence in eye care for more than 200 years and we continue to be at the forefront of new breakthroughs and developments.  We are an integral part of one of the UK’s first academic health science centres, UCL Partners, and now we are part of one of the first science health networks. We  were one of the first organisations to become an NHS foundation trust in 2004.  For further information, please visit

The UCL Institute of Ophthalmology is one of a number of specialised research centres within UCL (University College London) and together with Moorfields Eye Hospital, is one of the leading centres for eye research worldwide. The most recent Research Assessment Exercise confirmed the outstanding quality of research carried out at the Institute, with 40 per cent of investigators ranked 4* (world-leading) together with a further 30 per cent ranked as internationally excellent. The combination of the Institute’s research resource with the resources of Moorfields Eye Hospital, which has the largest ophthalmic patient population in the Western World, opens the way for advances at the forefront of vision research.  For further information, please visit


Was this information useful? Please rate the page.