Limbal Stem Cell Transplantation: Clinical Results, Limits, and Perspectives

Abstract

Limbal stem cell deficiency (LSCD) is a clinical condition characterized by damage of cornea limbal stem cells, which results in an impairment of corneal epithelium turnover and in an invasion of the cornea by the conjunctival epithelium. In these patients, the conjunctivalization of the cornea is associated with visual impairment and cornea transplantation has poor prognosis for recurrence of the conjunctivalization. Current treatments of LSCD are aimed at replacing the damaged corneal stem cells in order to restore a healthy corneal epithelium. The autotransplantation of limbal tissue from the healthy, fellow eye is effective in unilateral LSCD but leads to depauperation of the stem cell reservoir. In the last decades, novel techniques such as cultivated limbal epithelial transplantation (CLET) have been proposed in order to reduce the damage of the healthy fellow eye. Clinical and experimental evidence showed that CLET is effective in inducing long-term regeneration of a healthy corneal epithelium in patients with LSCD with a success rate of 70%-80%. Current limitations for the treatment of LSCD are represented by the lack of a marker able to unequivocally identify limbal stem cells and the treatment of total, bilateral LSCD which requires other sources of stem cells for ocular surface reconstruction.

Figure 1

Limbal stem cells are located on the basal epithelium in the limbal crypts of the Vogt's palisades located in the narrow zone between the cornea and the bulbar conjunctiva (arrow).

Figure 2

The loss of limbal stem cells results in cornea conjunctivalization (a) and pannus (b) with impairment of visual function.

Figure 3

The limbal scar of the healthy donor eye after limbal biopsy to perform limbal autotransplantation (a) is larger than that after limbal biopsy to perform cultivated limbal epithelial transplantation (b).

Figure 4

LSCD caused by chemical burn (a). Twelve months after cultivated limbal epithelial transplantation (b), the cornea showed cornea epithelial integrity, decrease of superficial neovascularization, and improvement of cornea transparency. Patients with LSCD after chemical burn with involvement of corneal stroma (c). The presence of corneal scarring required a keratoplasty after CLET to restore visual acuity (d).