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Ex vivo stem cell allograft aids in corneal surface reconstruction
Allogeneic stem cells reduced inflammation, epithelial defects, photophobia and pain, and restored corneal phenotype.
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NEW ORLEANS — Ex vivo expanded stem cell allografts enhanced corneal stability with a low rejection rate in treating acute limbal stem cell deficiency, according to a surgeon speaking here.
Sheraz M. Daya, MD, speaking on behalf of colleague Omar J. Hakim, MD, presented the results of a study at the American Academy of Ophthalmology annual meeting.
Dr. Daya focused on early results of 10 procedures that he and colleagues published in Ophthalmology in 2005 and later findings on the same cases and a further 28 procedures.
 Sheraz M. Daya |
He also cited a study published in Lancet in which Graziella Pellegrini, PhD, and colleagues reported on autologous stem cell transplantation. The 1997 Lancet report was a pioneering work in corneal surface reconstruction, Dr. Daya noted.
For their study, Dr. Daya and colleagues grew grafts on plastic using Pellegrini’s method.
Allogeneic corneal limbal stem cells were transplanted to the recipient eye after the conjunctival pannus was removed. The postop treatment regimen included the immune-suppressive agent cyclosporine (2 mg/kg to 3 mg/kg daily for 9 months) and topical steroids, Dr. Daya said.
“We also demonstrated that there was no donor DNA 9 months after allograft transplantation,” he said, suggesting the host restored its own stem cells.
The procedure
The researchers took limbal tissue cells from corneal transplant tissue and cultured about three or four sheets at a time. These sheets took 2 to 3 weeks to form and were transferred to the operating theater for grafting.
Cells cultured on plastic showed more normal characteristics than cells cultured on amniotic membrane, Dr. Daya said.
“This is our choice based on preliminary basic science we did looking at histology of this type of culture vs. growing cells on amnion,” he said. “Cells grown on amnion did not look normal in terms of polarity and morphology.”
Ex vivo allograft is feasible for treating bilateral limbal stem cell deficiency, Dr. Daya said.
“We learned that allograft culture can be used in bilateral disease,” he said. “There’s no harm to any fellow eye or any donating eye from which we grafted.”
In the Pellegrini study, the researchers noted that unilateral limbal stem cell deficiency can be treated with limbal grafts taken from the unaffected eye, but a limbal graft must be taken from the fellow eye, a potential risk. Autologous grafting is not feasible for bilateral limbal stem cell deficiency, as there is no donor limbus available, they said.
The ex vivo allograft may involve a lower risk of rejection than other methods, Dr. Daya said.
“There’s theoretically less chance of rejection because there are no antigen-presenting Langerhans cells and only a large volume of what we presume are stem cells,” he said. “DNA evidence showed a reduced or no need for immune suppression for more than 9 months following the procedure, as donor stem cells appeared to be replaced by host cells.”
Study results for the first 10 eyes treated for limbal stem cell deficiency showed no presence of donor cell DNA after 1 year, Dr. Daya said.
In one patient, who underwent a penetrating graft, the central epithelial cells underwent marker studies and were found to be similar to those found at the limbus, Dr. Daya said.
“There’s some type of activity taking place, as the epithelial layer had multiple layers and were not the usual corneal phenotype found in central corneal epithelium,” he said. “So what is the origin of these cells? One of our theories, we believe that these are cells from the bone marrow circulating in the blood stream and recruited to and populate the limbal area. There’s some stimulating activity taking place as a result of the transplantation that we had done.”
Ocular surface stability
The current study focused on 38 allografts performed on 35 eyes of 34 patients. All procedures involved allografts, and some eyes later underwent penetrating or deep anterior lamellar keratoplasty.
Study results showed 11 procedures failed in nine eyes; six failures were primary and five were secondary after initial success, Dr. Daya said.
Surface stability was maintained in 26 eyes (74%), Dr. Daya said. The researchers focused on six outcome measures: inflammation, conjunctivalization, persistent epithelial defect, photophobia, pain before surgery and pain at final follow-up.
“You can see a definite decrease in these parameters,” Dr. Daya said. Corneal opacification was also reduced.
Inflammation and the presence of lid disease were other key variables that affected long-term outcome.
“We took a look at a patient’s conjunctival involvement, and you can see here that the ones that did not have continued inflammation did better than those that had persistent inflammation,” Dr. Daya said. “We also found that good lid apposition is very important, as it ensures a watertight closure, ensuring the eyes remain moist.”
Overall results showed satisfactory clinical outcomes, Dr. Daya said.
“We did achieve our goal of improving the ocular surface and corneal stability,” he said. “We feel that these grafts are promising in patients with difficult ocular surface disease.”
For more information:
- Sheraz M. Daya, MD, can be reached at Centre for Sight Corneoplastic Unit and Eye Bank, Queen Victoria Hospital, East Grinstead, W. Sussex RH19 3DZ, United Kingdom; 44-1342-321-201; fax: 44-1342-325-873; e-mail: sdaya@centreforsight.com.
References:
- Daya SM, Watson A, et al. Outcomes and DNA analysis of ex vivo expanded stem cell allograft for ocular surface reconstruction. Ophthalmology. 2005;112:470-477.
- Pellegrini G, Traverso CE, et al. Long-term restoration of damaged corneal surfaces with autologous cultivated corneal epithelium; Lancet. 1997;349:900-993.
- Matt Hasson is an OSN Staff Writer who covers all aspects of ophthalmology. He focuses on regulatory, legislative and practice management topics.