Simple Limbal Epithelial Transplantation

Introduction

The corneal epithelium, the most superficial corneal layer, functions as a barrier and possesses high regenerative capacity. Histologically, it can be described as a nonkeratinized, stratified, squamous epithelium composed of several distinct cell populations. Regeneration of the corneal epithelium is maintained by limbal stem cells (LSCs) residing in the conjunctional zone between the cornea and conjunctiva called the limbus. These limbal basal cells respond to wounds by undergoing cell division at optimal “niche” that promotes the maintenance of stem cells (SCs) in an undifferentiated state. This limbal niche is the primary determinant of limbal epithelial stem cell (LESC) function ; however, Majo et al. demonstrated that oligopotent SCs are distributed across the ocular surface of mammals.

Limbal stem cell deficiency (LSCD) occurs as a consequence of many ocular surface insults and its degree of severity may range from mild, from chronic contact lens wear, to severe as seen in chemical injuries or autoimmune disease such as Stevens-Johnson syndrome or pemphigoid. In general, LSC deficiency is characterized by conjunctival epithelial ingrowth, persistent epithelial defects, and/or chronic epithelial staining leading to destruction of the basal membrane and fibrous tissue ingrowth, with functional impairment caused by loss of transparency and/or integrity of the cornea. Historically, ocular surface transplantation as a treatment for LSCD began with Jose Ignacio Barraquer proposing “epithelial limbus, conjunctivo corneal taken from the other eye” for superficial corneal burns, with only few advancements in both technique and understanding of the role of LESC over the next few decades. In 1989, Kenyon and Tseng were the first to take the LSC theory and apply it clinically. Their “Limbal Autograft Transplantation” used conjunctival and limbal tissue from a normal fellow eye to manage unilateral LSCD, which is still the basis of the most modern and sophisticated techniques for ocular surface reconstruction.

Most of the current approaches involve either transplanting living tissue from the contralateral eye (CLAU) or from a related donor in the form of conjunctival limbal autograft (lr-CLAU), or from a deceased donor in the form of keratolimbal allograft (KLAL). Cultivated limbal epithelial transplantation (CLET) is also an approach in restoring LSCD. In CLET, a small (2 mm × 2 mm) biopsy is processed for ex vivo culture. The limbal epithelial cells can be harvested from the CLAU if healthy or from living related donors or cadaveric eyes. Culture protocols vary and may often use explants or cell suspension systems with or without amniotic membrane as a carrier for the transplanted cells.

When considering the optimal form of LSC therapy, it is important to carefully take into account the cost, the good manufacturing practices (GMPs) required particularly for ex vivo culture protocols, strict traceability and, finally, the surgical technique. In 2012, Sangwan and coworkers proposed a novel technique they named simple limbal epithelial transplantation (SLET) for the treatment of unilateral LSCD, with the aim of overcoming the difficulty associated with ex-vivo tissue culture while minimizing risks to the donor eye ( Table 168.1 ).

Indications for Simple Limbal Epithelial Transplantation

The vast majority of documented uses of SLET have been for unilateral disease, ^, the reason being that healthy limbus can be harvested from the fellow eye and, therefore, the risk of immune rejection is abated. Ocular surface burns, either chemical or thermal, are the most important group as they are often unilateral. Its use has also been reported for ocular surface reconstruction during pterygium and ocular surface squamous neoplasia (OSSN), and in a case of laryngo-onycho-cutaneous syndrome. Some of the reported cases used contralateral harvesting of healthy tissue, although most use ipsilateral.

Autoimmune diseases (such Stevens-Johnson syndrome and mucous membrane pemphigoid) and congenital LSC deficiency as seen in aniridia are considered contraindications when SLET is used as an autograft.