Genetics and stem cells

Gene therapy offers hope for sight loss

Gene therapy "could be used to treat blindness," BBC News reports. This is just one of the many headlines reporting on the exciting application of gene therapy in visual impairment.

The news come from a small study involving just six male patients with a rare genetic condition called choroideremia. This condition causes progressive damage to the retina (the light-sensitive film of tissue at the back of the eye). There is currently no effective treatment for choroideremia and most people affected are legally blind by the time they are 50.

Choroideremia is associated with a defective version of the CHM gene. This study used a new technique to inject a healthy version of the CHM gene into parts of the retina that were still alive. Researchers hoped that this would halt the progression of the disease. They also wanted to assess whether this technique would cause any damage to the eye.

The injection proved to be safe in six men with the condition. It dramatically improved the visual accuracy for two men, although they were not "cured", as the operation was not able to reverse the loss of retina that occurs with the condition. Ongoing research is looking at how long the effects will last.

The researchers are hopeful that this study may open the door to improving or halting other more common progressive disorders of the eye, such as age-related macular degeneration, the leading cause of visual impairment in the UK.


Where did the story come from?

The study was carried out by researchers from multiple centres, including the Oxford Eye Hospital and Moorfields Eye Hospital in London, and the universities of Manchester, Southampton, Imperial College London and University College London in the UK, Ohio State in the US, and Radboud in the Netherlands. It was funded by the UK Department of Health and the Wellcome Trust.

Two of the researchers have made a patent application for the use of gene therapy for choroideremia. No other potential conflicts of interest were stated.

The study was published in the peer-reviewed medical journal The Lancet.

The media generally reported the story accurately, highlighting that this is an early study into a particular type of blindness, with many sources carrying a series of useful diagrams.

The Daily Mail's headline was possibly a little over-enthusiastic about the long-term effects of the treatment and its potential use in other genetic disorders, saying that, "Gene breakthrough restores the sight of people with inherited eye disease and could save thousands from blindness".

Sight was not fully restored in this research, with all of the men continuing to have a very restricted field of vision. However, that is not to say that this is not exciting and promising work.

What kind of research was this?

This was a study combining both phase 1 and phase 2 trials into a genetic injection for an inherited condition called choroideremia. It aimed to see if the technique was safe to use without causing any damage to the eye or vision.

What did the research involve?

Six males with choroideremia aged between 35 and 63 were enrolled in the trial. The vision in each eye was assessed using the internationally accepted ETDRS charts, performed by an independent tester who did not know the details of the study. An ETDRS chart is a more advanced version of a Snellen chart, the chart of letters that an optician may use during an eye test.

This assessment gave the researchers the number of letters each man was able to see with each eye. High-tech equipment was also used on at least three occasions to obtain baseline measurements of which parts of their retina were still working and how sensitive the retina was to light.

All of the men had very reduced areas of active retina, meaning that they had tunnel vision, but four of them were still able to see accurately in this small field of vision with better than 6/9 vision.

A score of 6/9 means that they could only read a letter from six metres away that a person with healthy eyesight can read from nine metres away. Two of them had reduced ability to see details, with vision of 6/96 (extremely poor) and 6/24 (relatively poor) in the eye that was to be treated.

An operation was then performed using a two-step procedure. The technique involved making a space behind a small part of the retina by injecting a saline solution to "detach" it. They then injected fluid containing the gene therapy into this space.

In five of the patients, the researchers injected 0.1mL of fluid, but they had to inject a smaller volume into the sixth patient because of difficulty detaching the retina and concerns about causing any damage to the nerves. The patients were also given a 10-day course of oral steroids that commenced two days before the surgery.

Vision in each eye and the light sensitivity of the retina were reassessed six months after the operation.

What were the basic results?

In the two patients who had low baseline vision:

  • the first began with 6/96 vision, which improved to 6/36 – an improvement of 21 letters, or four lines, on the visual chart
  • the second began with 6/24 vision, which improved to 6/15 – an improvement of 11 letters, or two lines, on the visual chart

The four other patients had better than 6/9 vision at baseline and recovered this to within one or two letters.

The mean area of surviving retina was similar at baseline and six months after surgery (4.0mm2 and 3.9mm2), meaning that the surgery did not change the level of tunnel vision.

There was also an increase in light sensitivity in the treated retina. This increase was proportional to the dose of gene therapy given and the amount of working retina.

The light sensitivity of the retina in the untreated eye reduced over six months, but this was in keeping with the slow progression of the disease.

How did the researchers interpret the results?

The researchers say that, "To our knowledge, this study is the first assessment of retinal gene therapy administered to patients who have normal visual acuity. It is also the first report of targeting a gene expressed in the photoreceptors.

"The results show the potential for gene therapy, not just in the treatment of choroideremia, but also for other chronic retinal degenerations that require early intervention before the onset of visual loss. These retinal degenerative diseases include retinitis pigmentosa and age-related macular degeneration."


The primary aim of the study was to see if it was safe to inject the genetic therapy into the back of the eye without causing any damage. Six months after the surgery, it appears that this objective has been achieved. The bonus of this study is that a vast improvement in sight has occurred in two of the patients.

This is very exciting, but the patients will need to be followed up for a longer period of time to monitor for any side effects and to see how long the improvements last. Encouragingly, a previous study using a similar technique for a different genetic disorder showed improvements for at least three years, although degeneration still occurred.

The men in the study had a very small amount of functioning retina at the beginning of this study and the amount of fluid injected into this area was tiny. The researchers aim to be able to halt the disease at a much earlier point in the disease process when much more of the retina is still functioning. This may require multiple injections and will require further research.

As the researchers point out, this technique involves detaching the retina, so it would not be suitable for conditions where the retina has become too thin.

A final point is that as encouraging as this study is, it involved patients with a rare condition – choroideremia only affects around 1 in 50,000 people. It is uncertain whether similar techniques could be used for more common eye conditions.

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