Stem cells used to improve low vision

"Embryonic stem cells transplanted into eyes of blind restore sight," The Daily Telegraph reports, covering a study where human stem cells were transplanted into the eyes of people with visual impairment. This led to a significant improvement in their vision.

This new research involved nine women with age-related macular degeneration and nine people with a rare condition called Stargardt's macular dystrophy, both of which cause progressive damage to the retina. Macular degeneration is the leading cause of visual impairment in the UK, and until now there has been no treatment.

The participants had retina cells derived from human embryonic stem cells transplanted into the space behind the retina in the eye with the worst vision. Before surgery, they had severe visual loss. After 12 months, vision in the treated eye improved significantly.

Some papers reported how some participants were able to read a watch or use a computer after receiving treatment, though this is not mentioned in the actual study. What is described is a marked improvement in Snellen test scores, where you read a chart of letters that get progressively smaller.

Contrary to headlines, there were some side effects, but these all resolved. And over an average of 22 months' follow-up, there were no signs of transplant rejection or major complications.

Further larger studies will doubtless now be underway to determine the optimal dosage and conditions for success.

Where did the story come from?

The study was carried out by researchers from the University of California, Wills Eye Hospital and Thomas Jefferson University, the University of Miami, the Massachusetts Eye and Ear Infirmary and Harvard Medical School, Advanced Cell Technology, and the Medical University of South Carolina.

It was funded by Advanced Cell Technology, a biotechnology company that develops and commercialises stem cell therapies.

Researchers from the company were involved in the study design, data collection, analysis, interpretation and writing the report.

This means there is potential for bias of the results. However, the other authors had full access to all of the data and responsibility for arranging publication.

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

In general, the media reported on the study accurately, and The Guardian provided expert quotes about the positive effect the improvement in sight had on some of the participants.

Contrary to The Independent's headline, however, a number of side effects were experienced as a result of the surgical procedure and immunosuppression.

Claims the participants were blind are also not entirely technically correct, as they had some degree of vision. Blindness – complete loss of vision – is actually uncommon. Most people with visual impairment have some limited degree of low vision.

What kind of research was this?

This research described two phase one/two trials that aimed to test the long-term safety and effectiveness of transplanting retinal pigment epithelium cells derived from human embryonic stem cells into the eye.

Phase one trials are the first type of study for new treatments conducted in humans. They aim to test the safety and suitability of the treatment for humans.

Phase two trials look at the effectiveness of the treatment and help determine the optimal dose. They also further assess any side effects. These trials were a combination of the two.

What did the research involve?

Nine women with age-related macular degeneration (median age 77, range 70 to 88) and nine people with Stargardt's macular dystrophy (median age 50, range 20 to 71) were recruited to the study from four US hospitals.

The researchers took human embryonic stem cells, which are able to become any tissue type, and developed them into retinal pigment epithelium cells. These cells were injected just behind the retina of the eye with the worst vision.

Three different doses were tested: 50,000 cells, 100,000 cells or 150,000 cells. Each dose was given to three people with age-related macular degeneration and three people with Stargardt's macular dystrophy.

All of the participants were given drugs to suppress their immune system (immunosuppressants) from one week before the transplant to 12 weeks afterwards to reduce the risk of transplant rejection.

The groups were followed up with numerous eye and physical examinations over a median period of 22 months (four people for less than 12 months, 12 people for 12 to 36 months, and two people for more than 36 months).

What were the basic results?

Before treatment, the best visual ability ranged from 20/200 (severe visual loss) to near blindness. (The 20/200 score means they could only read words from 20 metres away that a person with healthy vision would be able to read from 200 metres away).

In the age-related macular degeneration group, after six months:

four people could see at least 15 more letters in the treated eye during the Snellen test (equivalent to three lines on the standard visual chart)
two people could see at least 11 to 14 more letters
three people remained stable or could see up to 10 more letters

After 12 months:

three people could see at least 15 more letters in the treated eye
one person could see at least 13 more letters
three people remained stable or could see up to 10 more letters
two people did not have a 12-month assessment

In the Stargardt's macular dystrophy group, after six months:

three people could see at least 15 more letters in the treated eye
four people remained stable or could see up to 10 more letters
one person had a deterioration of 11 letters
one person did not have a six-month assessment

After 12 months:

three people could see at least 15 more letters in the treated eye
three people remained stable or could see up to 10 more letters
one person had a deterioration of more than 10 letters
two people did not have a 12-month assessment

The higher dose of cells – 150,000 – gave better results in the age-related macular degeneration group. A lower dose of 50,000 gave the best results in the Stargardt's macular dystrophy group.

Participants also had, on average, improved quality of life, as measured by a questionnaire.

Nobody had acute transplant rejection, abnormal excess growth of the transplanted stem cells, or tumour formation. In addition, they did not experience retinal detachment or changes in the blood vessels of the retina.

There were some side effects from the treatment, however, including:

retinal cells grew in front of the retina in three people, but did not cause any problems
four eyes developed cataracts, which were treated with surgery – one with age-related macular degeneration, and three with Stargardt's macular dystrophy
one person had severe inflammation of the fluid compartment inside the eye after surgery and an infection with Staphylococcus epidermidis – this took two months to resolve and sight returned to pre-operation level after three months
another person also had inflammation of the fluid compartment three weeks after the transplant, which resolved slowly over six months
several systemic adverse events were reported as a result of immunosuppression

How did the researchers interpret the results?

The researchers concluded that they "have shown the medium-term to long-term safety, graft survival, and possible biological activity of pluripotent stem cell progeny in individuals with atrophic age-related macular degeneration and Stargardt's macular dystrophy.

They go on to say that, "Our results suggest that hESC-derived cells [human embryonic stem cells] could provide a potentially safe new source of cells for the treatment of a variety of unmet medical conditions caused by tissue loss or dysfunction.

"The goal should be to treat patients early in the disease, potentially increasing the likelihood of photoreceptor and central visual maintenance or rescue in amenable retinal disorders."

Conclusion

These phase one/two studies have shown human embryonic stem cells can be developed into retinal cells in the laboratory and successfully transplanted into the eye, causing clinically significant visual improvements.

The technique does come with the usual potential surgical complications, but other major side effects were not found.

Limitations of the study include the small size, but this is normal in early trials whose primary aim is to determine safety.

Larger studies will be required to determine the optimal dose and the most appropriate candidates for the technique, as it was detrimental in one person and did not improve – or gave minimal improvement to – six other people.

There will also be ongoing ethical considerations for the technique, which currently uses cells left over from in vitro fertilisation (IVF).

Overall, these studies show a promising treatment for two of the commonest causes of visual impairment in the developed world, though it will take a few more years of trials to optimise the technique.