CHAPTER 14
Treatment of Ocular Surface Disorders
This chapter covers some of the common therapeutic options used for maintenance and restoration of the ocular surface of the eye (Table 14-1).
Table 14-1
The corneal epithelium is a highly differentiated cell type that is entirely regenerated approximately every 7 days. In the mechanically abraded cornea (eg, total epithelial debridement during vitrectomy surgery or following photorefractive keratectomy), reepithelialization and restoration of a relatively normal corneal surface occur in 5 days, on average. Numerous studies have demonstrated that the central corneal epithelium is maintained by continued centripetal movement of peripheral corneal epithelium toward the visual axis, as well as by anterior movement of the basal epithelial cells.
The source of the peripheral corneal epithelium is believed to be stem cells that reside in the basal layer of the limbus. Eyes that have a normal reservoir of functioning stem cells possess the ability to rapidly replace and maintain the corneal epithelium. However, when there is damage to the limbal stem cells, the conjunctival epithelium resurfaces the cornea. It was long believed that conjunctival cells retained the capacity for phenotypic change into corneal epithelium, but we now know this is not the case. 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.
Surgical Procedures of the Ocular Surface
Limbal Transplantation
As discussed in the previous section, the absolute necessity of repopulating the corneal surface epithelium with stem cells forms the rationale for syngeneic or allogeneic (cultured cell or tissue) limbal stem cell transplantation.
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 14-1). In this procedure, corneal epithelium, conjunctiva, and superficial pannus are removed from within 2 mm outside the limbus of the recipient eye, and 2 thin limbal autografts from the fellow eye are then attached to the limbus and allowed to regenerate and proliferate.
Figure 14-1 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 and tissue forceps. C, Additional surface polishing smooths the stromal surface and improves clarity. 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, 10-0 nylon suture at the corneal edge and 8-0 polyglycolic acid suture at the conjunctival margin.
(Reproduced by permission from Kenyon KR, Tseng SC. Limbal autograft transplantation for ocular surface disorders. Ophthalmology. 1989;96(5):709– 723.)
If total loss of limbal stem cells occurs bilaterally, the options for ocular surface transplantation are more limited. A limbal stem cell allograft from a living related donor may be considered. A similar procedure, keratolimbal allograft, uses corneolimbal rims from eye bank donor eyes. Although host cells may eventually reject or replace such tissue, good long-term results have been reported. Technical difficulties, poor epithelial viability, and rejection problems requiring systemic immunosuppression have limited the usefulness of this modality, but dramatic success has been observed in selected desperate cases.
Stem cell expansion by means of cell culture has proven an effective method of cell surface repopulation. Corneal stem cells have been used for this purpose, but 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 are experimental and available in few centers worldwide.
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.
Burillon C, Huot L, Justin V, et al. Cultured autologous oral mucosal epithelial cell-sheet (CAOMECS) transplantation for the treatment of corneal limbal epithelial stem cell deficiency. Invest Ophthalmol Vis Sci. 2012;53(3):1325–1331.
Chan CC, Biber JM, Holland EJ. The modified Cincinnati procedure: combined conjunctival limbal autografts and keratolimbal allografts for severe unilateral ocular surface failure. Cornea. 2012;31(11):1264–1272.
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.
O’Callaghan AR, Daniels JT. Concise review: limbal epithelial stem cell therapy: controversies and challenges. Stem Cells. 2011;29(12):1923–1932.
Sangwan VS, Basu S, Vemuganti GK, et al. Clinical outcomes of xeno-free autologous cultivated limbal epithelial transplantation: a 10-year study. Br J Ophthalmol. 2011;95(11):1525–1529.
Autologous Conjunctival Transplantation
Autologous conjunctival transplantation is appropriate for cases in which conjunctival loss, inflammation, or scarring is not complicated by extensive damage to or destruction of the limbal epithelial stem cells. This technique is essentially a free conjunctival graft designed to repair a focal or localized defect in the conjunctiva. The most common indication for conjunctival autograft transplantation is advanced primary and recurrent pterygium. See Chapter 12 for additional discussion of pterygium. Pterygium excision and conjunctival autografting, including surgical technique, are discussed in the following section.
Another indication is an enlarged pinguecula, which, in rare cases, may cause chronic irritation, requiring removal combined with an autologous conjunctival replacement graft. Occasionally, unilateral fornix foreshortening occurs after localized disease, retinal detachment surgery, strabismus surgery, or excision of ocular surface tumors or nevi. This foreshortening can be remedied with placement of a conjunctival autograft from the fellow eye. Usually, however, conditions associated with fornix obliteration (mucous membrane pemphigoid, Stevens-Johnson syndrome) are bilateral,