Options for limbal stem cell deficiency

New developments in ocular surface reconstruction expand treatment choices.

Dermot McGrath

Posted: Tuesday, November 3, 2020

Harminder Dua CBE, MD, Ph

Recent advances in transplantation techniques and tissue engineering have greatly improved outcomes in limbal stem cell deficiency (LSCD) and other indications requiring ocular surface reconstruction, according to Harminder Dua CBE, MD, PhD.
“A lot of progress has been in recent years in the surgical management of these challenging cases. Our goal is to save the eye, regenerate the ocular surface and restore sight and we have a variety of techniques now available to us to help us achieve that,” he said at the World Ophthalmology Congress Virtual 2020.
Reviewing the options for ocular surface reconstruction in LSCD, Prof Dua, Professor of Ophthalmology and Visual Sciences, at the University of Nottingham, United Kingdom, said it was important first of all to establish an accurate diagnosis and then treat accordingly.
“There are several steps to consider. It is vital to determine whether the inflammation is active or not. We need to establish corneal and conjunctival involvement with fluorescein staining and slit lamp examination, impression cytology and in vivo confocal microscopy (IVCM). We need to know if the disease is limited or progressive. We then need to evaluate the extent of stem cell deficiency; is it partial or total, unilateral or bilateral and is the visual axis involved or not,” he said.
Prof Dua said that the final consideration is to look at every other structure of the eye taking account of eyelids, tear function, cataract, fundus and IOP – and consider their potential to impact on any surgical procedure related to ocular surface reconstruction.
“We really need to ensure there is nothing that needs to be treated first in order to obtain the best possible outcomes from our reconstructive procedure and to establish the visual potential of the eye. The key message is that we should only operate when all inflammation is controlled,” he said.
For partial limbal stem cell deficiency, with conjunctivalised, metaplastic epithelium on the cornea where the visual axis is not involved, Dr Dua said non-intervention might be the wisest approach for such cases.
“However, if the visual axis is involved then the first minor procedure, I would recommend is sequential sectoral conjunctival epitheliectomy (SSCE),” he said.
He explained that SSCE is a procedure designed to prevent conjunctival epithelial cells migrating on to the corneal surface as this can compromise the healing process of the corneal epithelium and negatively affect vision and corneal transparency. To illustrate the point, he discussed the case of a patient with severe chemical burn.
“In this patient the upper part of the limbus and conjunctiva have survived the chemical burn. As healing progresses the conjunctiva is approaching close to the limbus. If this is allowed to cross on to the limbus, we will get an admixture of corneal and conjunctival epithelium on the cornea and this is not desirable. We therefore scrape that conjunctival epithelium away and it may need to be done more than once to allow the entire corneal surface to heal from limbus-derived epithelium,” he said.
For cases of total limbal stem cell deficiency there are several viable surgical options, said Prof Dua.

“We can either do in vivo expansion techniques such as auto limbal transplant, Simple limbal epithelial transplant (SLET) or an allo limbal transplant for bilateral cases either from a cadaver donor or a living relative or friend. We can also perform ex vivo expansion techniques with limbal, conjunctival, or buccal mucosal cells on amniotic membrane or fibrin, collagen or other substances,” he said.
Although SSCE has proven effective at preventing admixture of corneal and conjunctival epithelium, the technique is onerous in that the patients need to be seen every day or every other day to monitor the spread of conjunctival epithelial cells and perform scraping if necessary, said Prof Dua. Bleeding can also occur, and it can be painful.
To try to overcome these issues, Prof Dua introduced an alternative procedure – amnion-assisted conjunctival epithelial redirection (ACER).
“With ACER, we perform a 360-degree peritomy and we take away all of the fibrovascular pannus. We then take two explants from the other eye and suture them top and bottom. If the substrate is not healthy, we can put a small amniotic membrane graft inside. The key step is to put a large amniotic membrane graft outside covering all the affected area such that the edge of the amniotic membrane goes underneath the edge of the conjunctiva. This forces conjunctival epithelial cells to grow on the amniotic membrane,” he said.
In a recent study of 26 patients undergoing limbal stem cell transplantation with either ACER or SCCE, the former technique was found to reduce multiple patient visits, bleeding and pain compared to those treated with SSCE.
Prof Dua noted that allografts, whether from a cadaver or a living donor, require long-term systemic immunosuppression.
“The outcomes are best for auto limbal grafts and worst for cadaver transplants, with living relative grafts being somewhere in between,” he concluded.

Harminder Dua: