Ocular Surface Reconstruction From Tissue Transplantation to Cell Therapy

The most difficult part in ocular surface reconstruction for total limbal stem cell deficiency is restoring a healthy and stable corneal epithelium. Recently, there has been a shift toward a cellular-based transplantation that eliminates the need for harvesting large amounts of limbal tissues from a living donor. The autologous oral epithelium can be used as a source for ocular surface reconstruction instead of the limbal epithelial cells. This paper describes the method of harvesting autologous oral epithelial cells, culturing the cells on the amniotic membrane, and transplanting the amniotic membranewith the cultured oral epithelial cells on the ocular surface after removal of the fibrovascular scar tissue. Once the corneal epithelium is stable, penetrating keratoplasty may be performed at a later stage to restore the corneal clarity. (Tech Ophthalmology 2009;7: 118Y123) HISTORICAL REVIEW Ocular surface diseases with partial or total stem cell deficiency can usually be distinguished into 2 types: (a) diseases with a conjunctivalized cornea, where there is a viable tear film and the surface is wet, and (b) a completely dry and keratinized ocular surface. The former may be subject to a series of procedures collectively termed ocular surface reconstruction, whereas in the latter, only keratoprosthesis can be performed. This paper will discuss the latest advances in ocular surface reconstruction and will focus on the shift from tissue transplantation, where autologous or allogenic limbal tissue is transplanted, to cellbased therapy, where epithelial cells are isolated and transplanted to the ocular surface using different carriers. The treatment strategy in ocular surface reconstruction involves a multistep approach (Table 1). Improving the ocular surface health is the first step, which includes managing tear film problems, controlling blepharitis, suppressing inflammation, and treating recurrent corneal epithelial erosions and chronic ulcers. The second step includes the major surgical procedures, which start with reconstruction of the fornices and symblepharon repair and lid surgery to repair entropion. The next surgical step, which is the most challenging part in ocular surface reconstruction is aimed at creating a stable corneal epithelium. This includes autologous or allogenic transplantation of limbal tissue or transplantation of cultured epithelial cells that were expanded ex vivo on a carrier. These procedures will be further discussed in the following paragraphs. If a stable ocular surface was established and the corneal stroma is opaque, the next surgical step is corneal transplantation. The third step is maintaining the ocular surface defense mechanisms by continuous attention to the tear film, lid problems, and epithelial integrity (Table 1). The mainstay of ocular surface reconstruction involves the creation of a stable surface epithelium. Twomajor approaches are available today to establish this goal (Table 2). The first approach involves tissue transplantation, whereas the second is based on cell therapy that involves ex vivo cultured epithelial cells. Tissue transplantation involves transplantation of the limbal region, which may be harvested either from the contralateral healthy eye (autologous limbal transplantation), a living related donor, or a cadaveric source (allogenic limbal transplantation). Autologous limbal transplantation was first described by Kenyon and Tseng in 1989 (Table 3) and is probably the most successful surgical procedure in ocular surface reconstruction. However, this procedure is not suitable in cases of bilateral limbal deficiency andmay be avoided in patients who are afraid of operating on their only eye. The safety and favorable results of this procedure have been demonstrated in many studies. Allogenic limbal transplantation is performed in cases of bilateral limbal deficiency. Its disadvantages include the need for a long-term systemic immune suppression, a high incidence of graft rejection, and gradual loss of the donor cells with time. TABLE 1. Treatment Strategies in Ocular Surface Diseases With Limbal Deficiency: A Multi-Step Approach