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Stem cell deficiency: How to recognize it, what to do about it
It is important to identify stem cell deficiency before a patient receives a premium IOL.
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While many ophthalmologists may not perform stem cell transplants on a regular basis, being able to recognize early signs of stem cell deficiency may help prevent future corneal issues for patients. Alkali injuries, many years of contact lens wear and multiple surgeries can all cause a patient with an already mildly reduced epithelial stem cell reserve to cross into the area of epithelial irregularity and persistent defects.
Signs of, testing for deficiency
Early signs of stem cell exhaustion can include whorl keratopathy and staining of the limbal epithelium in a sawtooth-like pattern that suggests the epithelium in that area has a difficult time repopulating the corneal surface. This can progress to non-healing epithelial defects and extensive irregular areas of the cornea that become so irregular that vision is affected. Conjunctivalization of the cornea is also a hallmark of stem cell deficiency.
These signs and subsequent testing may suggest that a particular patient might not receive the best benefit from a multifocal implant or heal as quickly as expected when the eye is injured. Placing a multifocal implant in an eye with poor refraction of light due to an irregular surface can lead to an unhappy premium IOL patient.
Leela V. Raju
Impression cytology can be performed to help confirm stem cell depletion or deficiency. This process consists of pressing filter paper at the limbus, contacting both the cornea and conjunctiva, and then staining the paper to confirm the presence and density of goblet cells. More recently, imaging modalities such as confocal microscopy and optical coherence tomography have been helpful in identifying and characterizing the corneal epithelial stem cell niche. At the UPMC Eye Center, Kira Lathrop, MAMS, and colleagues are working on a new method of using OCT to get a clear 360° image of the stem cell niche. OCT will allow a non-contact method of evaluating this niche, known as the palisades of Vogt, to help determine the functionality of stem cells. In the future, we may be able to use this kind of imaging to identify patients with stem cell issues earlier or identify the best location from where to harvest a graft.
An example of sawtooth fluorescein staining and conjunctivalization of the cornea in stem cell deficiency.
Image: Raju LV
Treatment
When only one eye is affected by stem cell deficiency, this can be treated by removal of the abnormal area and amniotic membrane transplant, or the unaffected eye has to act as the stem cell donor. This is done by removing one or two small areas of limbal tissue (usually 1 mm to 3 mm) and transplanting them to the other eye, either as whole pieces at the limbus or by using them to “seed” the cornea after the donor grafts have been cut into smaller pieces.
The pieces can be held in place with fibrin glue or sutures, in conjunction with amniotic membrane. This allows the new stem cells to be protected while they expand on the surface. A temporary tarsal suture can help retain moisture as well as protect the grafts while the new epithelium is migrating off the grafts. We have had good results with both techniques at the UPMC Eye Center in treating stem cell deficiency due to multiple etiologies.
There has also been a great deal of work done with expanding these stem cells ex vivo. This means that an even smaller piece of limbal tissue is all that has to be harvested and that an entire sheet of healthy epithelium can be transplanted to the injured eye as opposed to waiting for the new cells to migrate across the surface.
While autografts negate the need for immunosuppression, allografts can be performed in cases in which both eyes are affected. This tissue may come from a living related donor or a cadaveric donor. There are many different preferences regarding what and how immunosuppression should be administered, including medications such as cyclosporine, tacrolimus, mycophenolate mofetil or steroids. These medications require much closer follow-up and increase concern about possible side effects such as high blood pressure and liver and kidney damage. Many ophthalmologists choose to involve a rheumatology colleague in the follow-up of these patients.
Conclusion
Early recognition of stem cell deficiency can prevent some unpleasant situations for a premium IOL patient. Previous injuries, many years of contact lens wear and surgeries may all have an occult effect on the stem cell reserves of the cornea, and the problem may be revealed when irregular surface staining or slow or non-healing epithelial defects are noted. Early recognition can allow prevention of further insults to the cornea surface and lead to early intervention, which can be successfully done when the patient’s other eye can act as a suitable donor. Even allograft situations can have positive outcomes when immunosuppression is carefully considered and monitored.
Visit UPMCPhysicianResources.com/Ocular to learn more about stem cell deficiency. You can also submit clinical questions or read the most recent questions asked of the UPMC Eye Center’s ophthalmology experts.