Limbal Stem Cell Transplantation

The peripheral corneal epithelium is derived from stem cells residing in the basal layer of the corneal limbus. However, when the limbal stem cells are not functioning properly, the conjunctival epithelium proliferates over the surface of the cornea. Conjunctival cells do not have the pluripotency of limbal stem cells and cannot differentiate into the corneal phenotype. Replacement of the corneal epithelium by conjunctival epithelium is characterized by abnormal epithelium on the cornea, vascularization, surface irregularity, absence of the limbal palisades of Vogt, and poor epithelial adhesion, a process called conjunctivalization.

Minor disturbances to the corneal limbal stem cell function or surface may be reversible with medical therapy using topical corticosteroid drops, topical cyclosporine, oral doxycycline, punctal occlusion, frequent topical lubrication, or a combination of these modalities.

If total loss of limbal stem cells occurs unilaterally, an autograft of limbal epithelium from the fellow eye can repopulate the diseased cornea with normal corneal epithelium (Fig 13-6). In this procedure, the unhealthy corneal epithelium, conjunctiva, and any pannus are removed from within 2 mm of the limbus of the recipient eye, and 2 thin limbal autografts from the fellow eye are then attached to the limbus to facilitate the regeneration and proliferation of corneal epithelial cells.

If total loss of limbal stem cells occurs bilaterally, the patient may receive stem cells from a living related donor (ie, a limbal stem cell allograft) or from an eye bank donor cornea (ie, a keratolimbal allograft). A limbal stem cell allograft may decrease the risk of rejection but requires immunosuppression; it also enables more conjunctiva to be harvested and transplanted than does a keratolimbal allograft. Although host cells may eventually reject or replace such tissue, good long-term results have been reported using both techniques. Poor epithelial viability and complications from systemic immunosuppression are considerable obstacles to be overcome, but dramatic success has been observed in some cases.

Figure 13-6 Limbal autograft procedure. A, With disposable cautery, the area of bulbar conjunctiva to be resected is marked approximately 2 mm posterior to the limbus. B, After conjunctival resection, abnormal corneal epithelium and fibrovascular pannus are stripped by blunt dissection using cellulose sponges, metal spatula blades, and/or tissue forceps. C, Additional surface polishing smooths the stromal surface and improves visual acuity. D, Superior and inferior limbal grafts are delineated in the donor eye with focal applications of cautery approximately 2 mm posterior to the limbus. The initial incision is made superficially within clear cornea using a disposable knife. E, The bulbar conjunctival portion of the graft is undermined and thinly dissected from its limbal attachment. F, The limbal grafts are transferred to their corresponding sites in the recipient eye and are secured with interrupted sutures, a 10-0 nylon suture at the corneal edge, and an 8-0 polyglactin suture at the conjunctival margin.

(Reproduced from Kenyon KR, Tseng SC. Limbal autograft transplantation for ocular surface disorders. Ophthalmology. 1989;96(5):709–723.)

Simple limbal epithelial transplantation (SLET) is a promising new technique for unilateral stem cell injury that obviates the need for intensive systemic immunosuppression, which conventional transplantation requires (see also Pterygium Excision, earlier in the chapter). After the abnormal cornea is denuded of pannus with a superficial keratectomy and covered with amniotic membrane, a small 2 × 2-mm strip of donor limbal tissue from the healthy fellow eye is divided into 8 or 10 pieces; these are placed evenly over the cornea with fibrin adhesive and then covered with a bandage contact lens.

Cell culture of corneal stem cells has been shown to be an effective source of corneal surface repopulation; however, the long-term survival of these grafts remains uncertain. Epithelial cells present in the oral mucosa and the human umbilical cord are emerging as important sources of cultured stem cells; at present, these approaches remain experimental and are available in few centers worldwide.

Basu S, Sureka SP, Shanbhag SS, Kethiri AR, Singh V, Sangwan VS. Simple limbal epithelial transplantation: long-term clinical outcomes in 125 cases of unilateral chronic ocular surface burns. Ophthalmology. 2016;123(5):1000–1010.

Biber JM, Skeens HM, Neff KD, Holland EJ. The Cincinnati procedure: technique and outcomes of combined living-related conjunctival limbal allografts and keratolimbal allografts in severe ocular surface failure. Cornea. 2011;30(7):765–771.

Holland EJ, Mogilishetty G, Skeens HM, et al. Systemic immunosuppression in ocular surface stem cell transplantation: results of a 10-year experience. Cornea. 2012;31(6):655–661.

Kim BY, Riaz KM, Bakhtiari P, et al. Medically reversible limbal stem cell disease: clinical features and management strategies. Ophthalmology. 2014;121(10):2053–2058.

Sangwan VS, Basu S, MacNeil S, Balasubramanian D. Simple limbal epithelial transplantation (SLET): a novel surgical technique for the treatment of unilateral limbal stem cell deficiency. Br J Ophthalmol. 2012;96(7):931–934.

Suh LH, Chuck RS. Limbal stem cell transplantation. In: Basic Techniques of Ophthalmic Surgery. 2nd ed. San Francisco: American Academy of Ophthalmology; 2015:115–120.

Zhao Y, Ma L. Systematic review and meta-analysis on transplantation of ex vivo cultivated limbal epithelial stem cell on amniotic membrane in limbal stem cell deficiency. Cornea. 2015;34(5):592–600.

Excerpted from BCSC 2020-2021 series: Section 10 - Glaucoma. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.