What are corneal epithelial stem cells?
Corneal epithelial stem cells are responsible for creating the corneal epithelial cells that form the cornea’s outer protective layer. These cells live where the cornea and sclera meet and are responsible for growing epithelial cells that grow across and cover the cornea. These stem cells live throughout our entire lives and generally never “run out.”
The epithelium protects the underlying corneal stroma from infection, scarring, drying out, and other potential harm. Just like the outer layer of the skin, this outer corneal layer sheds and regenerates itself every week. If the corneal surface is irritated or if a section of its epithelial cells erode away, the epithelial stem cells ramp up their production to quickly create a new layer of cells to cover the defect so that infection or scarring cannot set in.
What is corneal epithelial stem cell deficiency?
This is a condition where corneal epithelial stem cells die and the remaining cells cannot produce new epithelial cells fast enough. It is critical that the epithelial stem cells can produce new epithelial cells at a fast enough rate to keep up with how quickly old cells are shed. When the production is deficient, the corneal epithelium becomes compromised or incomplete.
What causes corneal epithelial stem cell deficiency?
There are genetic causes, autoimmune causes, and environmental causes.
There are various conditions such as aniridia that are associated with epithelial stem cell deficiency. Generally, these patients have normally functioning stem cells early in life, but with time they begin to die off. Beyond a certain point, they become deficient.
There are several auto-immune conditions, including Stevens-Johnson Syndrome and ocular cicatricial pemphigoid. that can lead to inflammation and scarring of the eye surface. This scarring can lead to loss of some or all of the epithelial stem cells.
Severe chemical burns, particularly strong bases, can kill the epithelial stem cells. Bases are far more devastating than acids, because unlike acids, they penetrate past the outer layers of the eye to damage its interior. Rarely other chronic trauma such as excessive contact lens wear or inwardly turned eye lashes (trichiasis) can cause loss of epithelial stem cells in susceptible individuals. Most patients do not lose epithelial stem cells from contact lens wear, but a small percentage may show early signs of cell loss after wearing them extensively. Such patients may have to have their contact type and wearing schedules changed or stopped entirely.
What problems can corneal epithelial stem cell deficiency lead to?
If old cells are not replaced in time they stay in place longer than they are designed to. They have to “stay in the workforce” long after they should have “retired.” Old epithelial cells can turn gray and opaque, which can cause blurry vision.
Old epithelial cells may fail to function as a barrier to bacteria, which can lead to corneal infections. Further, if the deficiency is prominent enough, large areas of the oldest epithelial cells typically towards the central cornea, fall off in large sections leading to painful corneal erosions. In an ideal situation, the stem cells ramp up production after erosions develop to cover the defect and prevent infection. With epithelial stem cell deficiency, the cells cannot do this so there is a greater risk for infection.
Corneal ulcers or infections are very serious because they can cause severe corneal scarring. The infection may even spread into the eye (endophthalmitis) which can cause blindness or loss of the eye if not treated immediately.
In some with severe stem cell deficiency, the cornea has no epithelium at all. In such patients, the conjunctiva may grow over the cornea to protect it. While the conjunctiva may protect the cornea from infections or ulcers, it is opaque and will block the patient’s vision unless it is surgically moved off the cornea in conjunction with a stem cell transplant or other procedure.
How is corneal epithelial stem cell deficiency treated?
First, infection must be prevented. Patients with severe epithelial stem cell deficiency are at higher risk of infection, so if severe enough, they may require daily topical antibiotic drops. We generally prefer a preservative free antibiotic (such as Vigamox) to minimize irritation to and maximize the life span of the surrounding epithelial cells.
Other treatments are aimed at maximizing the lifespan of the reduced number of epithelial cells that the stem cells are capable of making. The corneal epithelial cells must be lubricated well to reduce eyelid friction on them and drying. Any dry eye syndrome must be treated thoroughly. Sometimes, bandage contact lenses are used to help prevent friction between eyelid and the cornea. Any in-turned lashes must be treated. Significant scarring on the surface of the eye may need to be addressed either to prevent loss of epithelial stem cells or to prepare for epithelial stem cell transplantation so the transplanted cells are not damaged by the scars.
Some data suggests that serum tears and amniotic membrane treatments may help improve the epithelial stem cells functionality.
If conservative measures fail, surgeons consider a corneal epithelial stem cell transplant or a prosthetic cornea. Both have their own separate risk profiles.
What is a corneal epithelial stem cell transplant?
In corneal epithelial stem cell transplants, corneal epithelial stem cells are taken from another cornea and are transplanted into the patient’s diseased cornea. If only one of the patient’s eyes need the transplant, some stem cells may be taken from the patient’s good eye and transplanted to the bad eye. Alternatively, the stem cells can be taken from a living related donor or from an organ donor who has passed away. The advantage of having the cells come from a living related donor is that there is less chance of rejection.
Sometimes, the corneal epithelial stem cell transplant is performed with a conjunctival transplant In eyes with severe scarring and dry eye, If the surface of the eye is like a dessert, no cornea can survive, not the original cornea and certainly not a transplanted one. Such eyes likely need eyelid and eye surface surgeries to help with the scarring and dryness so that a stem cell transplant has a chance of success. Adding conjunctiva to the corneal epithelial stem cell transplant provides tissue that can help nurture the stem cells so they are more likely to survive. A conjunctival transplant likely has to come from a living related donor so that it is not rejected. The exact order of these surgeries is determined by the transplant surgeon. Generally, the stem cell transplant is done last. after the eye surface has been made healthier.
If I receive a DALK or PK corneal transplant, wouldn’t this include new epithelial cells? Would a scarred cornea needing a transplant in the setting of epithelial stem cell deficiency also need a corneal epithelial stem cell transplant?
It is true that a PK or DALK has epithelial cells on it. These are the epithelial cells that happened to be the most recent layer that the donor’s epithelial stem cells made before the donor passed away. These epithelial cells shed in less than a week and need to be replaced by new epithelial cells from the host’s stem cells, which reside in the area where the cornea and sclera come together.
If it is determined that a patient needs a PK or DALK, but also that they have corneal epithelial stem cell deficiency, then the corneal epithelial stem cell transplant must be done before the PK or DALK. Another option would be a prosthetic cornea, since this does not need a complete cornea epithelium to maintain good vision.
Do all cornea surgeons do epithelial stem cell transplants?
No. At the moment, we do not offer these transplants at Bennett & Bloom. They are not as common and they require a special team to help prevent rejection. Often, oculoplastic consultation is necessary before the transplant, and patients also need co-treatment with a rheumatologist who is familiar with this procedure. There is a team of eye care professionals and rheumatologists, however, within 50 to 100 miles of our offices who are experienced in performing and managing epithelial stem cell transplants, and we can arrange a consultation if we feel this surgery is needed.
Do epithelial stem cell transplants require systemic immunosuppressive medications to prevent rejection?
Yes. Unlike other forms of corneal transplantation where the transplanted tissue has no blood flow, the epithelial stem cells do have a significant blood supply. With blood flow, many white blood cells course through the transplant. White cells are responsible for the immune response that attacks non-self tissues and fights infections. Strong systemic immunosuppressive therapy is therefore necessary to prevent the white blood cells from seeing the transplant as ‘non-self’ and killing it. These medications are administered by a rheumatologist who is familiar with this type of transplant.
What are the risks and alternatives to a corneal epithelial stem cell transplant?
The main risk of a corneal epithelial stem cell transplant is failure of the graft. If immune rejection kills the graft, it may need to be repeated.
Strong steroid drops are part of the postoperative regimen that prevents rejection. Steroid drops can elevate the eye pressure and cause glaucoma in some individuals. Patients with corneal epithelial stem cell transplants are therefore at an increased risk for glaucoma. Monitoring for glaucoma is necessary every few months throughout life, because there are typically no symptoms of elevated eye pressure and glaucoma until irreversible damage is done. If the patient is being monitored closely, any elevated pressure can be detected earlier so that it could be treated and lowered as necessary.
Another risk from the procedure is the immunosuppression itself. Immunosuppression increases the risk of unique opportunistic infections and even of cancers that a normal immune system would be more likely to prevent. The rheumatologist will help weigh the risk factors here in determining if the patient should pursue a stem cell transplant versus other options.
Another option besides a stem cell transplant would be a prosthetic cornea. These have their own risks, particularly glaucoma and infection.
A Gundersen Flap is another option with severe epithelial stem cell deficiency if a patient’s other eye is normal. This surgery allows patients to avoid a more invasive option on their bad eye with less follow up visits and recovery. A Gundersen Flap pulls conjunctiva over the cornea to protect it so that one does not need to worry about corneal infection or break down. While the conjunctiva protects the cornea, it also blocks the vision. The purpose of a Gundersen Flap is therefore to protect an eye that has visual potential so that it is there and ready for rehabilitative surgery in the event that the patient ever wishes to pursue it in the future, especially if anything ever happens to their good eye.