Corneal Limbal Stem Cell Transplant
Chat Highlights
October 19, 2005

On Wednesday, October 19, 2005, Dr. Parveen Nagra, a glaucoma specialist at Wills, and the glaucoma chat group discussed "Corneal Limbal Stem Cell Transplant."

Moderator:  We are pleased to have with us tonight Dr. Parveen Nagra, a cornea specialist in Philadelphia, to discuss "Corneal Limbal Stem Cell Transplant."  Welcome, Dr. Nagra.  First of all, what are stem cells?

Dr. Parveen Nagra:  Stem cells are immature cells that have the great ability to replicate themselves and mature or differentiate into other cells.  Corneal limbal stem cells are epithelium stem cells located at the limbus, or in the periphery of the cornea, that help replenish the smooth, clear epithelium of the cornea.

P:  How do corneal limbal stem cells differ from those in the controversial stem cell research?

Dr. Parveen Nagra:  The controversial stem cells we hear about are embryonic stem cells.  Corneal limbal stem cells are epithelial and cannot differentiate into non-epithelial tissues, such as muscles.

P:  What makes the cornea good territory for stem cell work?

Dr. Parveen Nagra:  There is easy access to the cornea, as it is on the surface of the eye.  The limbal stem cells are also in a clearly visible area, and can be seen with a microscopic or slit-lamp examination.

P:  How do limbal stem cells get damaged, and what is the consequence of the damage?

Dr. Parveen Nagra:  There are several reasons for the deficiency of limbal stem cells.  Chemical burns, Steven-Johnson's syndrome, and ocular pemphigoid are conditions in which the limbus can become damaged and scarred, leading to loss of the limbal stem cells.  Other ocular conditions, such as aniridia, are also associated with deficiency of limbal stem cells.

P:  What is the purpose of transplanting corneal stem cells?

Dr. Parveen Nagra:  As I mentioned before, the purpose of the limbal stem cells is to replenish the corneal epithelium, to keep it clear and smooth.  That allows the cornea to serve as a "window" for the eye.  When the limbal stem cells become damaged, the cornea epithelium loses its transparency, and adopts a more vascular pattern of the conjunctiva.

P:  How are corneal stem cells transplanted?

Dr. Parveen Nagra:  We can transplant corneal stem cells in a number of ways.  For people with stem cell deficiency in one eye, we can do an autologous, limbal stem cell transplant, taking about half, or roughly six clock hours, of limbal stem cells from the "good" eye, and transplanting them to the eye with the deficiency.

Allografts can also be performed, meaning the limbal stem cells are taken from donors, either living (usually related) or cadaveric.  That, however, requires systemic immunosuppression with medicines like oral prednisone and cyclosporin.  There have also been studies looking at tissue culture stem cells or transplanting oral mucosal (epithelial) cells, but those methods have not yet become mainstream.

P:  Does the donor area for the limbal cells regenerate?

Dr. Parveen Nagra:  Excellent question. Once the source of the limbal stem cells is removed, they cannot regenerate.  So, when we perform an autologous limbal stem cell transplant, we like to remove only half of the limbal stem cells, because we do not want that eye to develop a deficiency of limbal stem cells.

Moderator:  Then half of the cells can still do the job?

Dr. Parveen Nagra:  Half of the cells often work for more localized conditions, such as a chemical burn that may have only affected one eye (especially, part of one eye).  For more diffuse conditions, such as aniridia, where both eyes are affected, an allograft is necessary, and 360 degrees of limbal stem cells are transplanted if a cadaveric source is used.

P:  After an allograft limbal cell transplant, how long are immunosuppression medications needed?

Dr. Parveen Nagra:  There was a recent report suggesting two years may be sufficient for immunosuppression.

P:  Do the optic nerve and trabecular meshwork have epithelial cells?  If so, can stem cells rejuvenate them?

Dr. Parveen Nagra:  Well, there have been some studies looking at other types of stem cells and rejuvenating nerves.  Very preliminary studies have shown some success looking at replicating nerves in the eye.  It is an exciting prospect.  These corneal limbal stem cells differentiate into corneal epithelium, not trabecular meshwork or optic nerve tissue.

P:  My corneal endothelial cells are damaged from ICE (irido-corneal endothelium) syndrome.  Is there some hope that the damaged endothelial cells could be replaced or repaired?

Dr. Parveen Nagra:  I think there is very exciting potential for the future that endothelial cells may be replicated.  At this time, we typically replace damaged endothelial cells with a corneal transplant.  Unlike a corneal limbal stem cell transplant, a corneal transplant does not contain any stem cells, that we know of.

P:  I plan to save cord stem cells from my son's birth.  Do you think they hold any promise for future use in the treatment of glaucoma?

Dr. Parveen Nagra:  Cord stem cells, which are considered adult stem cells, most likely have the potential to differentiate into many different types of cells, unlike corneal epithelial stem cells, which differentiate into corneal epithelium.  Therefore, they may hold great promise for the future, as we look for ways to use these cells to treat medical conditions. It is still early, and much research is needed before we can make use of many stem cells to treat medical conditions.  However, some type of stem cell transplants, such as corneal limbal stem cell transplants, are being used directly to successfully treat certain conditions, such as chemical burns.

P:  How are limbal stem cells delivered to the needed area?

Dr. Parveen Nagra:  Great question.  The limbal stem cells are at the periphery of the cornea, at the junction of the cornea and conjunctiva.  So, at the time of surgery, a superficial piece of tissue is excised from the limbus containing these cells.  The tissue is then sutured onto the limbus of the eye with the stem cell deficiency.

Moderator:  Is that what "carrier" cells are?

Dr. Parveen Nagra:  Actually, carrier cells are a bit different.  Stem cells may be an effective way to carry certain genes, allowing the tissue into which they are incorporated to replicate those genes.  Different treatments or therapies can be administered through carrier cells.

P:  It's my understanding that stem cells have a remarkable potential to either remain a stem cell or become another type of cell.  Is it true that limbal stems cells are "immortal," whereas amniotic epithelial cells may not be?

Dr. Parveen Nagra:  That is true.  Stem cells are known to have "error-free" replication, and can either reproduce themselves or differentiate.  Amniotic epithelial cells do not have the same potential.  In ophthalmology, amniotic membrane transplants are often performed at the same time as limbal stem cell transplants, because the amniotic membrane provides a wonderful substrate to encourage growth.

P:  Due to a childhood accident in one eye 20 years ago, I have very limited vision, with no lens and extensive iris damage, but an undamaged optic nerve.  I had a corneal graft at the time, and recently had a second graft.  Since then, my pressures have been high.  Pilocarpine, timolol, and Diamox have not helped.  The second graft may be failing, perhaps because of the high pressures.  I'm reluctant to have a shunt implanted, and am scheduled for cyclodiode laser therapy next week.  Is there any evidence suggesting that cyclodiode could cause a four-month-old cornea graft to be rejected?

Dr. Parveen Nagra:  Limbal stem cells are important in keeping the corneal epithelium clear.  Limbal stem cell deficiency and corneal transplant rejection are not related.  One of the biggest risk factors for corneal transplant rejection is uncontrolled high intraocular pressures.  While cyclodiode may lead to some damage of the limbal stem cells, it is important to keep the pressure under good control to optimize the success of the transplant.

P:  Some lens debris may have fallen into the eye chamber.  Could that be blocking the draining of the eye and thus be causing high eye pressure?  If so, would it be possible to remove it?

Dr. Parveen Nagra:  It is possible that lens debris may be associated with high intraocular pressure.  If it is visible, it could be removed.

P:  If the graft fails due to the pressure increase, could stem cells be used to rectify this problem or would the cornea graft have to be repeated?

Dr. Parveen Nagra:  When corneal transplants fail, they can be repeated.  However, the success rate of each successive corneal transplant decreases a little.  If the source of the cornea pathology is superficial, and felt to be related to conjunctival tissue on the cornea, or limbal stem cell deficiency, then a limbal stem cell transplant would be beneficial, either alone or before a corneal transplant.

P:  Can the transplants be used for ICE when the cornea is affected, since it is only in one eye?

Dr. Parveen Nagra:  If a patient with ICE has limbal stem cell deficiency, because only one eye is affected, they would be good candidates for an autologous graft.  Typically, however, the source of the problem with ICE syndrome is the endothelium, not the epithelium, and we do not have stem cells transplants to treat corneal endothelial conditions yet.

P:  Do glaucoma medicines have a pitting effect on the cornea? If so, can that affect vision?

Dr. Parveen Nagra:  Great question. Long-term use of glaucoma medications may lead to a mild limbal stem cell deficiency.  Typically, however, the limbal stem cell changes from the chronic use of medication do not significantly affect the vision.

P:  How long have corneal stem cells been transplanted?

Dr. Parveen Nagra:  With improvements in immunosuppresion, limbal stem cell transplantation has really gained a lot of success over the past few years.

P:  What is the rate of success?

Dr. Parveen Nagra:  The success rate really depends on the underlying cause of the stem cell deficiency.  For example, the success rate of stem cell transplants for chemical burns is better than for ocular cicatricial pemphigoid conditions.  [Ocular cicatricial pemphigoid (OCP) is a rare inflammatory syndrome involving primarily the oral and ocular mucous membranes.] In chemical burns, there is no continuing inflammatory process.  In ocular cicatricial pemphigoid, however, continued inflammation can jeopardize the success of the transplant.

P:  Are most cornea specialists performing this type of surgery yet?

Dr. Parveen Nagra:  Some, but not all corneal specialists, are doing this procedure.

Moderator:  Thank you, Dr. Nagra, for taking the time to meet with us.  The topic was interesting and your answers were very informative.

Dr. Parveen Nagra:  Thank you.  And have a great night!  

On October 26, Dr. Wilson discussed "Visual Fields & Functional Vision" in the Chat room. Click here for highlights of that meeting.

Click here for the most recent glaucoma chat highlights and links to the chat archives.

Click here for upcoming glaucoma chat events.