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Subspecialties Cornea / Ocular Surface, Basic & Translational Research, Health Economics and Policy

Unlocked Potential

Stem cells are essential to the maintenance of a healthy corneal epithelium. Without a continuous supply; for example, in limbal stem cell deficiency (LSCD), the ocular surface becomes unstable, leading to ocular pain, corneal erosions and decreased vision from stromal scarring or epithelial irregularity. Stem cells are typically damaged in one of two ways: through trauma, such as chemical assault or burn, or as a result of genetic disease. Rare congenital conditions, such as aniridia or ectodermal dysplasia, Stevens Johnson’s syndrome and mucous membrane pemphigoid can all cause significant damage to the surface of the eye. But with the advent of new therapies, there is hope for patients with LSCD. We can now take cells from a patient’s healthy eye and grow them in the lab, amplifying the cells until there are enough to transplant into the deficient eye. In my practice, we outsource our cells to an Italian lab with EMA-approval and NHS England-authorization. In cases where both patient’s eyes are diseased, we rely on external sources. For this, we take stem cells from donor eye tissue and immune suppress the patient to reduce risk of rejection. We recently published the world’s first randomized control trial for allogeneic stem cell treatment and the results were extremely promising (1). Interestingly, treatment options are no longer dependent on the availability of donor tissue. If there are no ocular stem cells available, we can take cells from non-ocular sources, such as the mouth – a process known as cultivated oral mucosal epithelial transplantation, or COMET. In cases where the clinician cannot – or does not want to – immune suppress the patient, COMET is an option; however, the results are not as good as those derived from corneal stem cells.

There are still unanswered questions surrounding the long-term outcomes of donated stem cells.

Practical challenges also stand in the way of stem cell therapy development. I have worked in the field for 15 years, which is roughly how much time it takes for a treatment to reach patients. Not only is the process long – it is also expensive; many clinicians who enjoy success in early clinical trials are unable to continue their work because they don’t have commercial funding from a pharmaceutical partner.

We have been awarded £2.8 million (over $3.5 million) from the Medical Research Council to conduct the first human trial for aniridia-related keratopathy, a rare form of stem cell deficiency. Hopefully, we will know how effective that treatment is within the next five years. Unfortunately, for other deficiencies, the future isn’t quite so certain; there is no currently available funding for patients with disease in both eyes. And though there are therapies in the research setting, none that have traversed into the commercial environment. And the most promising option may still need further clinical trials...

One of the big challenges for our community is finding a treatment that is commercially available on the NHS. There are still unanswered questions surrounding the long-term outcomes of donated stem cells. Studies have found that transplanted donor cells seem to disappear after around a year, causing the surface of the eye to normalize. So far, no one knows why. The industry is also looking to molecular therapies as potential treatment options, which will hopefully come to fruition in the next five to 10 years.

In the meantime, society must address a growing and disturbing root cause of stem cell deficiency: chemical attacks. I see patients on a weekly basis – mostly young men – suffering from corneal burns. The issue may be underreported in the media, but it is ever present in the clinic. Though we, as ophthalmologists, can help victims of chemical assaults, more work needs to be done to prevent these attacks from happening in the first place.  

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  1. JDM Campbell et al., “Allogeneic ex vivo expanded corneal epithelial stem cell transplantation: a randomized controlled clinical trial”, Stem Cells Transl Med, 8, 323 (2019). PMID: 30688407.
About the Author
Sajjad Ahmad

Consultant Ophthalmologist at Moorfields Eye Hospital, London.

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