Long term follow-up of alloCLET RCT patients
Research type
Research Study
Full title
Allogeneic Ex Vivo Expanded Corneal Epithelial Stem Cell Transplantation: A Randomized Controlled Clinical Trial 10-year follow-up
IRAS ID
310239
Contact name
Sajjad Ahmad
Contact email
Sponsor organisation
Moorfields Eye Hospital NHS Trust
ISRCTN Number
ISRCTN54055321
Duration of Study in the UK
0 years, 6 months, 1 days
Research summary
Summary of Research
This study is an extension of an initial trial which completed several years earlier. The initial trial focused on limbal stem cell deficiency (LSCD), which can result from damage to eye from chemicals or heat, or be caused by a disease called aniridia. It leads to scarring and severe vision loss in both eyes as well as chronic pain and redness. LSCD is a significant cause of sight loss especially in countries where resources and services are limited but it does not typically respond to standard treatments.
To carry out the initial trial, we isolated stem cells in the eye's protective layer, known as the cornea. A normal healthy cornea is transparent, but becomes scarred and opaque when specialised stem cells are lost in LSCD. These cornea samples were taken from people who had donated their eyes after death. We then grew the stem cells which have the unique ability to transform into other cell types into tissue ready to be transplanted.
Sixteen patients were split into two groups with both given eye drops and medicines to suppress their immune system to reduce transplant rejection. One group was also given the stem cells. This is the first time that stem cells have been used in this way in a randomised clinical trial which is the gold standard scientific method for testing a new treatment. Patients who had received the stem cells showed significant repair of their eyes' surface, the outermost layer, over 18 months. This improvement was not seen in those who did not receive the treatment.
In this present follow-up study we are simply going to examine the treated and untreated patients to see what the long term effects are of the stem cell transplant by performing routine clinical examinations in one visit. There will be no new treatment or intervention.
Summary of Results
What was the study about?
The cornea is the clear front surface of the eye. It is kept healthy by special stem cells located at its edge (called limbal stem cells). Some people lose these stem cells due to injury, burns, or genetic conditions like aniridia (being born without a colored part of the eye). When this happens, the cornea becomes cloudy and blood vessels grow across it, causing severe vision loss or blindness. This condition is called limbal stem cell deficiency.
In 2012-2014, researchers in Edinburgh, Glasgow and Liverpool carried out a clinical trial to test whether transplanting stem cells grown from donated eye tissue could help restore vision in people with this condition affecting both eyes (EudraCT 2010-024409-11). Patients received either the stem cell treatment on a special membrane, or just the membrane alone (without stem cells). Both groups also received medicines to prevent rejection and eye drops made from their own blood.
The original trial, published in 2019, followed patients for 18 months. This new analysis reports what happened to 8 of those patients over approximately 10 years.
What did the researchers find?
Who was followed up?
Only 8 of the original 16 patients could be traced for long-term follow-up. Three had received the stem cell treatment and five had received the membrane alone.
Vision outcomes
Patients who received stem cells generally maintained better vision over 10 years than those who received the membrane alone. One patient, who had one eye treated with stem cells and the other with just the membrane, showed the stem cell-treated eye kept useful vision (able to see the top letter on an eye chart).
What was the study about?
The cornea is the clear front surface of the eye. It is kept healthy by special stem cells located at its edge (called limbal stem cells). Some people lose these stem cells due to injury, burns, or genetic conditions like aniridia (being born without a coloured part of the eye). When this happens, the cornea becomes cloudy and blood vessels grow across it, causing severe vision loss or blindness. This condition is called limbal stem cell deficiency.
In 2012-2014, researchers in Edinburgh, Glasgow and Liverpool carried out a clinical trial to test whether transplanting stem cells grown from donated eye tissue could help restore vision in people with this condition affecting both eyes (EudraCT 2010-024409-11). Patients received either the stem cell treatment on a special membrane, or just the membrane alone (without stem cells). Both groups also received medicines to prevent rejection and eye drops made from their own blood.
The original trial, published in 2019, followed patients for 18 months. This new analysis reports what happened to 8 of those patients over approximately 10 years.
What did the researchers find?
Who was followed up?
Only 8 of the original 16 patients could be traced for long-term follow-up. Three had received the stem cell treatment and five had received the membrane alone.
Vision outcomes
Patients who received stem cells generally maintained better vision over 10 years than those who received the membrane alone. One patient, who had one eye treated with stem cells and the other with just the membrane, showed the stem cell-treated eye kept useful vision (able to see the top letter on an eye chart).
Eye surface health
The health of the eye surface was measured using a scoring system (0 being normal, 15 being severe disease). After 10 years, patients who received stem cells had scores of 7-8 (moderate disease), whilst those without stem cells had scores of 10-15 (severe disease).
Need for further treatment
Three of the five patients who received only the membrane (60%) eventually needed additional treatments.
Safety
No patients died or experienced serious side effects from the stem cell treatment or the anti-rejection medicines over the 10-year period.
What does this mean?
These results suggest that stem cell treatment may provide longer-lasting benefits for people with severe corneal stem cell deficiency compared to treatment without stem cells. However, this conclusion must be treated with caution because:
• Only 8 of the original 16 patients were followed up (50% lost to follow-up)
• The numbers in each group were very small (3 versus 5 patients)
• Some patients needed additional eye operations for other problems like glaucoma or cataracts
Despite these limitations, the finding that most patients in the control group eventually required rescue stem cell therapy supports the original trial's conclusion that adding stem cells provides meaningful, lasting benefit for this serious eye condition and that larger studies with further long-term are required to provide firm conclusions.REC name
South East Scotland REC 02
REC reference
23/SS/0085
Date of REC Opinion
8 Aug 2023
REC opinion
Further Information Favourable Opinion