EyeWorld is the official news magazine of the American Society of Cataract & Refractive Surgery.
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28 EW CORNEA July 2012 Cornea editor's corner of the world Advances in treating ocular surface stem cell deficiencies by Michelle Dalton EyeWorld Contributing Editor evere ocular surface disease with limbal stem cell deficiency is the most challenging condition that faces the corneal specialist. Routine corneal transplantation procedures have no chance of success because the patient cannot provide viable epithelium for the donor cornea. Ultimately the transplant will fail due to the recurrence of the surface disease. S Over the last several years, improve- ments in the visual outcomes in surgical procedures for severe ocular surface disease have been achieved with new surgical techniques, improved immuno- suppression regimens to prevent rejec- tion, and the use of keratoprosthetic (KPro) devices. There are several etiolo- gies, including chemical and thermal in- juries, autoimmune conjunctivitis (Stevens-Johnson syndrome and mucous membrane pemphigoid), hereditary eye disease such as congenital aniridia, long- term contact lenses, and ocular treat- ment-related side effects such as mitomycin-C. Corneal surgeons must decide if they will recommend ocular surface stem cell transplantation (OSST) or a KPro pro- cedure. If the recommendation is for an OSST then the decision about the source of ocular surface tissue must be made. The choices of tissue include the fellow eye, a relative, cadaver donor, or cultured tissue. The decision to use one of the tis- sue choices available for an OSST or to use a KPro depends on a variety of factors including the age and health of the pa- tient, the etiology of stem cell disease in- cluding the health of the conjunctiva, and the availability of related donors. The important thing for clinicians not performing these procedures to under- stand is that patients with severe ocular surface disease do have a reasonable chance to achieve visual improvement and should be referred for an evaluation. We have asked two corneal specialists, Anthony J. Aldave, M.D., and Clara Chan, M.D., to discuss their approach to these most complex patients. Edward J. Holland, M.D., cornea editor Ocular surface stem cell transplantation and keratoprosthesis are viable options for patients who need corneal reconstruction O cular surface disease with limbal stem cell deficien- cies (LSCD) can be treated via keratolimbal allo- grafts, keratoprostheses, or oral mucosal epithelial autografts, with the latter being evaluated more in Asia than the U.S. "Ocular surface stem cell trans- plantation (OSST) stabilizes the ocu- lar surface to allow for subsequent keratoplasty if necessary," said Clara Chan, M.D., clinical instructor of ophthalmology, University of Toronto. "OSST also allows for easy monitoring of intraocular pressure." Ideally, patients should be younger and in overall good health (aside from the corneal problems) because they require systemic immunosup- pression to prevent rejection. Eyes that are considered a high risk for corneal graft failure would be better served by a keratoprosthesis as the primary treatment, said Anthony J. Aldave, M.D., associate professor of ophthalmology, and director, Cornea Service, Jules Stein Eye Institute, University of Califor- nia, Los Angeles (UCLA). "When I see patients with a uni- lateral stem cell deficiency, I talk to them about taking cells from the other eye," he said. "In my experi- ence, though, the contralateral eye is rarely completely normal. I give the option of taking cells from the con- tralateral eye or a keratoprosthesis." Dr. Aldave uses sterile irradiated corneas from Tissue Banks Interna- tional (Baltimore) to serve as the donor carrier for the Boston type 1 keratoprosthesis (KPro). "Corneas with low cell counts or those that have something that prevents them from being used for normal corneal transplants can be irradiated so they're sterilized, stored in albumin, and kept in a jar for up to a year." Studies at UCLA suggest "there's no difference in outcomes or complica- tions with irradiated tissue versus ca- daveric tissue," Dr. Aldave said. "Complications after OSST result in ocular surface failure only, whereas complications such as endophthalmitis, corneal melt, and infectious keratitis after KPro im- plantation can lead to loss of the eye," Dr. Chan cautioned. Source of tissue The decision on what donor tissue to use depends on whether the con- dition is unilateral or bilateral, availability of a relative to serve as a donor, and the health of the patient's conjunctiva. In unilateral disease, "trans- planting limbal stem cells from the patient's unaffected fellow eye would be ideal. No systemic im- munosuppression would be needed in these cases. If the fellow eye is normal, there has not been a prob- lem for this eye to be used as a donor," Dr. Chan said. Dr. Aldave has a different view. "There's always the potential con- cern that the second eye develops limbal stem cell problems down the road," he said. If the disease is truly unilateral, taking healthy limbus from the donor eye to transfer to the recipient eye makes sense, he said, but he rarely sees donor eyes that are normal. "If the disease is bilateral then the decision is whether to use a rela- tive or cadaver donor. If there is a relative with a healthy eye and a good tissue match then a conjuncti- val limbal allograft is the desirable procedure. The good tissue match re- duces the risk of rejection. Cadaver The Cincinnati Procedure Eyes with severe combined limbal stem cell and conjunctival deficiency may benefit from "the Cincinnati Procedure,"1 where both cadaver and living donor tissue are used, Dr. Chan said. "An advantage of the procedure is that the limbus is surrounded 360 degrees by limbal stem cells that act as a barrier for possible invasion and spread of conjunctival inflamma- tion," she said. "The transplanted conjunctiva also provides additional goblet cells that supply mucin needed in the tear film to allow for better spreading of tears over the ocular surface." "A disadvantage to the proce- dure is its greater antigenic chal- lenge because of the exposure to both cadaver and living donor tissue," Dr. Chan explained. Dr. Aldave believes those with bilateral disease are best served by a KPro, which also boasts a low inci- dence of complications and signifi- cant improvement in distance vision (20/50 or better in more than 66% of eyes in one study).2 Dr. Chan said the KPro "is best suited for older patients with eyes at high risk for corneal graft failure, for donors are also a good source of lim- bal stem cells and are the best choice when there is not a good tissue match with a relative," Dr. Chan said. A schematic of the Cincinnati Procedure. Conjunctival limbal allograft tissue is harvested from a living donor; the central cornea is trephined, and the kera- tolimbal allograft tissue is prepared from a cadaver donor corneal-scleral rim; conjunctival peritomy and superficial keratectomy is performed; and allograft pieces are secured to the recipient's eye using sutures and tissue glue Source: Clara Chan, M.D.