Living-Related Conjunctival Limbal Allograft

Introduction

Limbal stem cell deficiency (LSCD) manifests following dysfunction or destruction of the limbal stem cells, leading to the hallmark characteristic of corneal conjunctivalization with invasion of conjunctival goblet cells onto the corneal surface. Conjunctival deficiency occurs after extensive conjunctival inflammation, leading to symblepharon formation, forniceal loss, and extensive goblet cell loss with subsequent mucin deficiency. The end result of conjunctival deficiency is keratinization of the ocular surface, including the conjunctiva and cornea.

Living-related conjunctival limbal allograft (LR-CLAL) is a type of ocular surface stem cell transplantation (OSST) procedure that transfers allogenic limbal and conjunctival tissue from a matched living relative for treatment of symptomatic partial or total LSCD. ^,

Indications/Contraindications

LR-CLAL allows for transplantation of conjunctiva and limbal stem cells when one or both eyes are affected. While typically utilized in the setting of bilateral LSCD, LR-CLAL may be required in unilateral LSCD in which the fellow eye is a poor donor, such as with significant prior contact lens use or extensive ocular surgery. Compared with keratolimbal allografts (KLAL), LR-CLAL has the additional benefit of providing fresh conjunctiva. Cases of LSCD with accompanying conjunctival disease may be more suitable to LR-CLAL over allograft simple limbal epithelial transplantation, cultivated limbal epithelial transplantation (CLET), and KLAL, which may not adequately address the conjunctival deficiency.

Contraindications for LR-CLAL include medical contraindications for systemic immunosuppression, significantly decreased mucin and aqueous tear deficiency, and ocular surface keratinization. Although the latter contraindications (tear deficiency, keratinization) have a poor prognosis, LR-CLAL has been shown to stabilize the ocular surface, despite these settings, by providing both limbal and conjunctival stem cells when prior KLAL has failed.

Preoperative Considerations

In preparation for a LR-CLAL, the ocular surface should be optimized by addressing eyelid malposition, significant symblepharon, and trichiasis. In addition, uncontrolled glaucoma must also be managed preoperatively. If there is significant conjunctival inflammation and scarring, a combination OSST (see below) may be more suitable for ocular surface rehabilitation. For chemical injuries, the authors recommend waiting a minimum of 12 months following the injury to allow the ocular surface to stabilize prior to LR-CLAL. An optical keratoplasty may be performed a minimum of 3 months after successful OSST, as indicated by quiet conjunctiva and corneal reepithelialization.

Successful LR-CLAL depends on providing limbal stem cells and conjunctiva from an ABO- and human leukocyte antigen (HLA)–matched living relative. Therefore systemic immunosuppression (SI; e.g., tacrolimus, mycophenolate mofetil, and prednisone) is necessary for long-term allograft survival, given the limbal vasculature and increased number of Langerhans and antigen-presenting cells. Recipients need to be suitable candidates for SI, which is crucial to the success of LR-CLAL in stabilizing the ocular surface. The authors believe that proper donor selection maximizes the success of the procedure by minimizing the antigenic burden through identification of the best living-related donor candidate. Our current donor selection protocol utilizes information from ABO-typing, HLA typing (broad antigen classes I and II), panel reactive antibody (PRA), and donor specific antibody (DSA) testing.

LR-CLAL donor eyes should be examined carefully for subtle stem cell deficiency (i.e., late fluorescein staining) and cannot have a history of long-term contact lens wear or significant ocular surface disease (e.g., prior surgery, trauma). Our group studied a cohort of LR-CLAL donors with short-term follow-up for 109 eyes and long-term follow-up for 68 eyes (mean 52 months, range 6–269 months). None of these eyes developed ocular surface complications. Harvesting approximately 2–2.5 clock hours of limbal stem cells per conjunctival-limbal segment (total amount harvested less than 5 clock hours) may avoid inducing LSCD in a donor eye.