J. Stuart Tims and W. Barry Lee

Introduction

Ocular surface disease can range from mild keratoconjunctivitis sicca to severe conditions that damage limbal stem cells. Severe cases of stem cell deficiency may require limbal stem cell transplantation and ultimately penetrating or lamellar keratoplasty to clear the visual axis. Optimization of the ocular surface prior to keratoplasty is essential to achieve success and includes maximizing tear function, restoring normal lid anatomy and function, and ensuring an adequate supply of limbal stem cells. These vital steps help enhance survival and clarity of the corneal graft.

Approximately 50% of ocular surface reconstruction procedures will require keratoplasty for visual rehabilitation.¹ The outcome of the corneal graft is dependent on several important factors, including the extent of the limbal stem cell deficiency (largely determined by the underlying etiology) and the presence or absence of conjunctival inflammation (Fig. 48.1).² It is also important to consider whether other components of the ocular surface, besides limbal stem cells, are involved in the pathologic process. The consequences of ignoring any one of these items may result in non-healing epithelial defects, secondary ulceration, infectious keratitis, corneal vascularization, conjunctivalization of the cornea, and ultimate graft rejection or corneal melting. Even with perfect surgical technique and the best tissue available, poor outcomes may result without an adequate stem cell reserve, optimal tear function, and anatomically functional lids.¹

In this chapter, the authors review the relevant literature that describes methods and results for keratoplasty in the setting of ocular surface and limbal stem cell dysfunction, and discuss a logical approach for managing these very challenging patients.

Preoperative Considerations

Prior to keratoplasty, all patients should undergo evaluation for ocular co-morbidities, such as eyelid malposition, eyelid disorders and glaucoma. In addition, the ocular surface should be screened for dry eye and dysfunctional tear syndrome states, limbal stem cell deficiency, conjunctival dysfunction, scarring and keratinization of the cornea, corneal vascularization, corneal sensation, and the status of the corneal epithelium (Fig. 48.2). If the conditions mentioned above are not addressed prior to keratoplasty, postoperative outcomes can be disappointing and potentially devastating.

Preoperative punctal occlusion, punctal cautery, entropion or ectropion repair, treatment of lagophthalmos, and trichiasis correction remain important preoperative treatment options for patients with concurrent eyelid disorders and dry eye conditions. Preservative-free artificial tears, gels, and lubricant ointments, as well as use of topical antiinflammatory agents can also be important adjuncts to management of preoperative conditions. Anterior and posterior blepharitis must also be controlled prior to keratoplasty in ocular surface disease, as detailed in Chapter 10. Glaucoma can also impact the outcome of keratoplasty, whether from the toxicity of glaucoma drops, high pressure exerting optic nerve damage and poor visual outcomes, or compromised endothelial dysfunction from certain glaucoma drops, high intraocular pressure or prior glaucoma surgery.^3,4 Intraocular pressure must be managed prior to keratoplasty, with care to minimize corneal complications from glaucoma treatment.

Once the tear film and lid function have been optimized and ocular co-morbidities addressed, the limbal stem cell reserve must be replenished in the presence of limbal stem cell deficiency. Chapters 40–45 detail surgical techniques for limbal stem cell transplantation. Given the scientific evidence and clinical experience, the authors prefer to perform keratoplasty as a staged procedure at least 3 months following stem cell transplantation (Fig. 48.3).

Surgical Technique and Considerations

Penetrating keratoplasty (PK) in conjunction with or following stem cell transplant is performed with several unique considerations, compared to routine keratoplasty. Larger-diameter grafts are preferred to provide better apposition to the keratolimbal graft segments and lessen the risk of epithelial ingrowth.⁵ Same-size recipient trephination is often performed to prevent overlap between the peripheral donor cornea and stem cell segments. One important exception to same size trephination is chemical injury patients, who are oversized 0.5–0.75 mm, because the recipient bed in chemical burn cases often contracts following trephination. Because there is often asymmetric wound healing at the graft–host junction, interrupted sutures are preferred over running sutures to allow for selective removal to manage astigmatism (Fig. 48.4). Interrupted sutures also allow for easier suture removal and better wound stability after removal with a decreased risk of dehiscence, compared to running suture removal.^6,7 Ocular surface disease patients must be watched closer for loose or vascularized sutures after keratoplasty as they are at increased risk of developing suture-related complications (Fig. 48.5).

In terms of donor tissue selection, some authors prefer to use pediatric or neonatal limbal tissue to allow for the greatest density of limbal stem cells for transplantation.⁸ Since pediatric donor corneal tissue is not commonly available, performing staged procedures allows for use of adult donor cornea tissue at a later date for keratoplasty. Optimizing keratoplasty donor tissue quality, especially relative to the donor ocular surface, can help prevent postoperative epithelial defects that could become persistent.⁹

Another consideration with keratoplasty in ocular surface disease is the choice of technique. The majority of reports in the literature on keratoplasty in ocular surface disease discuss PK; however, advances in deep anterior lamellar keratoplasty (DALK) and keratoprosthesis (KPro) make these procedures advantageous in selected circumstances. Femtosecond lasers and Anwar’s big bubble technique allow for deeper tissue dissections with DALK and decreased risk of interface haze/opacity, compared to lamellar techniques abandoned in the mid-twentieth century.10–13 The main advantages of DALK over PK include elimination of endothelial tissue rejection, extraocular rather than intraocular surgery, minor endothelial cell damage, faster potential suture removal, and the potential for increased tectonic wound strength (Fig. 48.6).^10–14

The keratoprosthesis provides another viable alternative to limbal stem cell rehabilitation and cadaveric keratoplasty in this patient population. The advantages of a KPro over cadaveric tissue include elimination of endothelial tissue rejection, decreased dependence on limbal stem cell function and epithelial status, and less concern over conjunctival and eyelid status (Fig. 48.7).^15,16 In particular, patients with Stevens–Johnson syndrome may do better with a KPro, as long as the inflammation is controlled to avoid melt and extrusion and the surface protected from trauma by a bandage contact lens.^17,18 Patients who are elderly and/or cannot tolerate systemic immunosuppression risks or those who are not candidates for autologous tissue transplantation may also be better suited for KPro (Fig. 48.8). However, a KPro carries continued risks of endophthalmitis, glaucoma, extrusion after melt, and retroprosthetic membranes.^15–18 Although the stem cell transplant patient will have a period of systemic immunosuppression typically lasting 6 to 24 months, the KPro patient must adhere indefinitely to post-perative measures, such as bandage contact lens wear, lifetime topical antibiotic prophylaxis, and lifetime glaucoma management. The surgeon must weigh these factors before deciding to proceed with KPro surgery.