Conjunctival Limbal Autograft

Published on 08/03/2015 by admin

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Last modified 22/04/2025

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Conjunctival Limbal Autograft

Steven J. Wiffen

Introduction

In a discussion at the Cornea World Congress in 1964, José Barraquer described the use of an autograft of limbus from the unaffected eye in cases of superficial burns as a preparatory procedure before keratoplasty.¹ He noted that this improved the state of the corneal epithelium but the mechanism was not discussed. In 1966, Strampelli et al. reported two cases of improvement in vascularized opaque corneas with transplantation of a complete ring of limbus from the other eye.² They described the technique in more detail at the Second International Corneo-Plastic Conference in London in 1967.³ It was not until some time later that the role of the limbus as the niche for the stem cells responsible for the corneal epithelium was elucidated, and Kenyon and Tseng reported on the use of autografts of conjunctiva and limbus for management of diffuse unilateral limbal deficiency in 1989.⁴ Conjunctival limbal autografts (CLAU) were described within a classification system for epithelial transplantation proposed by Holland and Schwartz in 1996.⁵ Since then, there have been many reports describing the use of limbal autografts, and the role of CLAU in management of unilateral ocular surface disease has been comprehensively reviewed.^6–9

Indications

Conjunctival limbal autograft (CLAU) is indicated for management of symptomatic partial or total unilateral limbal deficiency.

Clinical signs of limbal deficiency include varying combinations of conjunctivalization of the cornea, with associated vascularization and fibrovascular pannus, persistent or recurrent epithelial defects and scarring or stromal haze.⁹ Symptoms include poor vision, chronic or recurrent discomfort and photophobia.

Limbal deficiency may be primary, as in aniridia, or secondary to chemical or thermal trauma, multiple surgeries, chronic inflammation, contact lens-induced keratopathy, or ocular surface squamous neoplasia.

Probably the most common use of limbal autografts has been in surgery for pterygium in the form of an ipsilateral limbal translocation, though there is little evidence that the limbal part of the autograft adds any benefit over a standard conjunctival autograft.¹⁰ In most other forms of unilateral limbal deficiency the autograft is harvested from the other eye. In this situation, a unilateral chemical injury is probably the most common clinical scenario. Figure 40.1 demonstrates improvement in the ocular surface with CLAU after chemical injury.

Figure 40.1 Conjunctival limbal autograft (CLAU) in chronic phase of unilateral chemical injury. (A, B) Preoperative photographs showing conjunctivalization of entire cornea. (C, D) Photographs at 6 weeks post CLAU. Note the smooth surface but some persisting subepithelial haze or scar.

Preoperative Assessment and Considerations

It has been recognized that the state of the rest of the ocular surface is critical to the outcome of limbal transplantation. Preoperative assessment must include thorough examination of the ocular adnexa and ocular surface. The nature of chemical injuries and many of the other causes of limbal deficiency is such that other ocular surface or adnexal problems are commonly associated. Two important considerations in determining management are whether the condition is unilateral or bilateral and whether there is conjunctival involvement.⁵

Lid malposition, symblepharon, and trichiasis all need to be dealt with prior to limbal transplantation. The most common pre-existing problem is that of dry eye and this is a major prognostic factor.¹¹ If aqueous tear function is inadequate, then punctal occlusion should be performed. Blepharitis or ocular surface inflammation should be controlled optimally before surgery if possible.

In chemical injury cases, timing of CLAU is an important factor. CLAU may be performed either in the acute phase to aid healing or later once the cornea has conjunctivalized and inflammation has settled. In the acute phase, a limbal graft will not survive if the limbus is ischemic, and Tenon’s advancement may be required. In addition, the inflammation that occurs in the acute and subacute stages of a chemical injury will often cause the CLAU to fail. Therefore it is advisable to wait until the inflammation has resolved before performing a CLAU. The delay in CLAU surgery is especially critical as the fellow eye can only be used once as a donor.

Intraocular pressure should be estimated, taking into account that tonometry may not be accurate with an abnormal ocular surface and cornea. Secondary glaucoma is common in the context of chemical injuries and steroid-related intraocular pressure rises may occur postoperatively. It is easy to overlook glaucoma when there are severe ocular surface problems, and loss of vision may occur even when epithelial transplantation is successful.

An assessment of the visual potential of the affected eye is required. If the eye has no visual potential, then it is not sensible to risk the donor eye, when another procedure, such as a conjunctival flap, may stabilize the ocular surface and provide comfort. Thorough discussion with the patient of the risks and benefits of surgery are required. In particular, the risk to the donor eye needs to be discussed. If the fellow eye has a history of trauma, then a careful examination of the conjunctiva, limbus and cornea is critical before recommending a CLAU. In addition, a history of long-term contact lens wear can result in subclinical damage to the limbal stem cells and may be a contraindication for CLAU.

Surgical Technique

Surgery may be performed under local or general anesthetic but the patient will need to be able to manage having both eyes operated on both during and after the procedure under local anesthetic.

Both eyes are prepped and draped. A well-fitting speculum is required. At the start of surgery vasoconstriction may be achieved with topical epinephrine 1/10 000 or, with apraclonidine 0.5% (Iopidine) or brimonidine 0.1% (Alphagan P) to avoid pupil dilation.

Recipient Preparation

It is best to prepare the recipient eye first so that bleeding can be controlled. For complete limbal deficiency, a 360° limbal peritomy is performed with Westcott scissors (Fig. 40.2A). The conjunctiva is undermined to allow it to be recessed several millimeters in the superior and inferior locations. The pannus on the cornea will be easily removed except where the stroma has been damaged. In those areas it will be more adherent but can be removed with blunt dissection or scraping with a hockey-stick blade (Fig. 40.2B). With full conjunctivalization of the cornea, the usual adherence of the limbal tissue is lost and usually it is easily removed around the limbus. Cautery is applied lightly, if required, to minimize further trauma. Bleeding will generally stop with the wait during preparation of the donor. A bed can be prepared for the donor as described below. The ocular surface is moistened and the speculum removed, and the eye closed or covered while the donor is prepared.

Figure 40.2 Schematic of the conjunctival limbal autograft procedure. (A) Marking and harvesting of the conjunctival and limbal grafts of the donor tissue at 12 and 6 o’clock. (B) Preparation of the recipient site with a 360° peritomy and resection of the conjunctiva at 12 and 6’clock for placement of the donor tissue. (C) Superficial keratectomy of the recipient cornea. (D) Placement of the CLAU grafts.

Donor Preparation

Several techniques have been described for donor preparation and fixation.⁶ The general approach is to remove 2 to 3 clock-hours (60–90°) of limbus from the superior and inferior locations of the donor eye (Fig. 40.2C).

The corneal extent of the dissection can be marked with an inked 10 or 11-mm trephine about 1 mm central and concentric to the end of the vascular arcades. A calibrated diamond knife or the trephine itself may be used to score the cornea to a shallow depth to provide a discrete central edge. The diamond knife can be used to create discrete vertical nasal and temporal edges to the dissection as well. The conjunctival extent of the donor is marked with a pen in a fashion to allow easy orientation once it is transferred. The size of the conjunctiva section of the CLAU depends on the status of the injured eye. If there is primarily limbal deficiency and the conjunctiva is healthy appearing, a small conjunctival carrier section (2–3 mm) is all that is needed to carry the limbal cells. If the fellow eye has significant conjunctival disease with scarring and symblepharon formation, the conjunctival section should be larger to provide conjunctival epithelial and goblet cells. This section can be 4–6 mm superiorly, where there is redundant conjunctiva.

The conjunctiva is dissected, leaving as much Tenon’s as possible, down to the adherence at the limbus. Some prefer to elevate conjunctiva with subconjunctival injection of balanced salt solution or anesthetic solution but it is not necessary. Conjunctiva is best handled with non-toothed or Moorfields forceps to avoid tissue damage. Westcott scissors are used to undermine the conjunctiva and it is easiest to do this with the conjunctiva under tension. That can be achieved by making the vertical incisions to the limbus first, then undermining between and then cutting the posterior conjunctival edge last.

Once the conjunctiva is undermined up to the limbus it can be reflected over the cornea and a crescent, or similar, blade is used to undermine the stroma to a shallow depth at the limbus up to the prepared corneal edges. It helps to have an assistant gently elevate the conjunctiva so that the blade tip can be seen just beneath the surface. If the corneal edges have not been scored at the start, the donor can be freed with straight Vannas scissors or the edge of the crescent blade, though the edge tends to me more irregular with this technique.

The donor tissue is transferred epithelial side up to a sterile dish and kept wet with balanced salt solution. If superior and inferior autografts are to be used, then the process is repeated for the inferior graft.

The donor site may be left as is, or the bulbar conjunctiva advanced toward the limbus and sutured or glued to reduce the size of the epithelial defect. The speculum is removed and the eye is closed while the tissue is secured in the recipient eye.

Placement of the Donor Tissue

The recipient limbus can be prepared in the same fashion as the donor to provide a discrete corneal edge for the donor tissue to butt against. Care is needed not to make the recipient bed too deep or there will be a step up at the corneal edge that will inhibit epithelial healing. Otherwise, the donor tissue may be just placed on the recipient limbus (Fig. 40.2D). Fibrin glue is applied to the recipient and the donor tissue placed in anatomical position and smoothed out. Alternatively, the graft is sutured in place at each end to the sclera either with 10-0 polyglactin (Vicryl) or 10-0 nylon. Braided polyglactin, though easier to handle, causes more tissue reaction and inflammation and loosens very quickly. The corners of the conjunctival part of the graft are then tacked to episclera and the recipient conjunctival edge with enough tension to keep it evenly spread out. Even with glue, it is prudent to place sutures at each end of the graft to prevent any chance of it dislodging. The donor conjunctival edge can be approximated carefully to the recessed recipient conjunctiva with sutures of just two single throws of 10-0 polyglactin as it should not be under tension. It is important for the assistant to keep the surface wet with balanced salt solution during this part of the procedure. A viscoelastic can be used to protect the surface but it tends to make suturing somewhat more difficult as the fine suture material sticks to it.

Subconjunctival and/or topical antibiotic and steroid are applied to both eyes. Bandage contact lenses are applied and the recipient eye has a patch and shield applied until the first postoperative day. The donor eye can be left open and topical therapy with antibiotic, steroid and lubricants started the same day.

Postoperative Management

Preservative-free topical steroid and antibiotics are given every 2–4 hours for the first week and then reduced as the surface heals. The bandage lenses are removed once the epithelium has closed and is stable.

There is generally some immediate swelling of the transplanted conjunctiva. The graft typically revascularizes within 5 days; there is then gradual thinning of the conjunctiva over weeks. Corneal epithelium extends from the central edges of the graft in a convex pattern and progresses centrally over days (Fig. 40.3). The rate of healing depends on the state of the ocular surface at the time of transplantation and presumably other general factors, such as the age of the patient. The advancing edges of the corneal epithelium meet in the central cornea and may produce a typical healing line. The last part to heal is usually in the 3 and 9 o’clock zones of the peripheral cornea when superior and inferior grafts are used. If the conjunctival epithelium reaches the limbus before the corneal epithelium has healed, it may need to be removed by sequential sector conjunctival epitheliectomy (SSCE) as suggested for management of partial limbal deficiency⁹ to prevent recurrent conjunctivalization of the cornea.

Figure 40.3 Conjunctival limbal autograft for limbal deficiency after multiple surgeries for conjunctival melanosis. Photograph at 5 days post surgery showing healing epithelium from superior and inferior grafts heading toward corneal centre. Note the conjunctival epithelial defects in the horizontal meridian.

The donor site heals with slight thinning and some superficial vascularization of the cornea (Fig. 40.4).

Figure 40.4 Conjunctival limbal autograft donor site at 1 year after surgery. Note mild thinning and some vascularization but smooth and clear adjacent cornea.

Problems

Complications may occur with CLAU surgery and have been reviewed recently.¹² These may relate to case selection and preoperative management, as well as to surgical technique. Damage to the donor eye is a major concern. There is one report of limbal deficiency developing in a donor eye in a case of contact lens-induced epitheliopathy that was not strictly unilateral.¹³

There has been one report of medium-term attenuation in viability of CLAU with progressive conjunctival ingrowth within a year of transplantation in three consecutive cases.¹⁴ This has not been reported elsewhere.