Simple Limbal Epithelial Transplantation (SLET)

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Article initiated by:

Esteban A. Santiago, MD.

All contributors:

Vatinee Y. Bunya, MD, MSCE, Esteban A. Santiago, MD., Christina Moon, M.D., Colleen Halfpenny, M.D., Maria D. Bernal, MD

Assigned editor:

Maria D. Bernal, MD

Review:

Assigned status Up to Date

 by Maria D. Bernal, MD on June 30, 2024.

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Surgical Therapy

Simple Limbal Epithelial Transplantation (SLET) is a surgical technique first described by Dr. Sangwan in 2012 for the treatment of limbal stem cell deficiency (LSCD). Since then, several papers have validated its efficacy restoring the ocular surface, renewing the corneal epithelium and avoiding the re-conjunctivalization of the cornea .

Background

Several surgical techniques have been described aiming for a successful limbal transplantation. We will briefly describe the most commonly used techniques.

Conjunctival limbal autograft (CLAU): First described by Dr. K. Kenyon and Dr. G. Tseng. They published their first results in 1986, since then this technique showed to be efficient re-establishing the ocular surface. This is not the first attempt described for limbal transplantation, but it is the first one describing a sectorial limbal harvesting from the donor eye. The original technique described an autologous transplantation harvesting two free grafts from the contralateral eye.

Keratolimbal allograft (KLAL): harvesting the tissue from a living related or a cadaveric donor is an option when it is not possible to perform an autologous transplantation. When performing an allograft transplantation, a systemic immunosuppression should be considered . On the other hand, Tan et al reported three cases of allo-limbal transplantation, using living related donors, in which he didn’t start systemic immunosuppression and the tissue didn’t reject. 

Cultivated limbal epithelial transplantation (CLET): Introduced by Dr. Pellegrini et al . This is an effective technique in which only 1 or 2mm of healthy limbus are harvested from the contralateral eye and expanded in a laboratory. Different culture medias and techniques have been described with good results . It allows implantation of a larger graft in the recipient eye and saves donor cells in case there is a need for a second intervention. The drawback of this technique is the need for a laboratory with a special set up to cultivate the stem cells, and that it is a two-stage procedure. This kind of setup can be a challenge for developing countries or clinics with low resources.

Patient Selection

Advantages of Simple Limbal Epithelial Transplantation

SLET is a reproducible, single stage technique without the need of a special laboratory setup. It is more conservative for the donor eye, allowing harvest of a smaller limbal graft than CLAU. Because it is an autologous transplant, there is no need for systemic immunosuppression. This is a one stage procedure and because there is no special setup it is cost effective for smaller centers .

Indications

This surgery was originally described for unilateral 360 stem cell deficiency, but it is also used for cases of partial LSCD. Before offering this surgery to the patient, a sine qua non requirement is a healthy contralateral eye . In order for SLET to improve the vision, the recipient eye should have a clear corneal stroma. An anterior segment OCT (AS-OCT) helps assess the stromal opacification and thickness in the recipient eye. SLET has been used to treat causes of unilateral LSCD such as chemical or thermal injuries, iatrogenic (topical Mitomycin C), contact lens wear, ocular surface neoplasia (OSSN) excision , failed prior LSCD and pterygium surgery. Bilateral cases of LSCD such as Steven Johnson’s Syndrome, TEN syndrome and Mucous Membrane Pemphigoid can be treated with allogeneic SLET (cadaveric or live-related) but will require long term systemic immunosuppression for graft survival .

Contraindications

Harvesting limbus from the contralateral (donor) eye should not be done if this can motivate a limbal stem cell deficiency in the donor eye in the future. Contact lens users are at a higher risk for developing symptomatic LSCD. In contact lens wearers, even if the eye looks healthy the stem cell population might be diminished and harvesting limbus might be the trigger for a LSCD. A similar thinking process should be followed when a systemic condition is the cause of the LSCD, even if it is very asymmetric and the non-symptomatic contralateral eye looks healthy. The following conditions in the recipient eye are contraindications for SLET: conjunctival or corneal keratinization, dry ocular surface (low Schirmer's), blind eye with no visual potential and uncorrected adnexal pathologies such as lagophthalmos, ectropion, entropion, etc. SLET is an epithelial regenerative procedure and therefore cases with corneal stromal opacification will need corneal transplantation in addition to SLET. In unilateral cases of LSCD with severe symblepharon, SLET alone is not effective and there is a need for both limbal and conjunctival grafting.

Pre-operative preparation

The ocular surface needs to be optimized before surgery in order to provide the new stem cells a proper environment for their expansion. It is common to find ocular surface inflammation in eyes with chemical or thermal burns or other causes of longstanding limbal stem cell deficiency. This inflammation needs to be treated before performing SLET. Depending on the specific case, options such as oral Doxycycline, topical Cyclosporine, non-preserved artificial tears, etc should be used. Using non-preserved drops is important in order to avoid adding more toxicity to the eye and should be used before and after surgery. Eyelid problems need to be corrected before SLET.

Surgical Technique

Step 1: Application of brimonidine 0.15% and phenylephrine 5% drops 5-10 minutes before surgery reduces intraoperative bleeding in the donor and recipient eyes. Use topical anesthesia in both eyes and a peribulbar in the LSCD eye. Some surgeons prefer to do peribulbar in both eyes. General anesthesia for children. Prep both eyes as usual and drape first the donor eye.

Step 2: An approximate 2mm area in the superior limbus is identified (the donor limbus is not marked with a skin-marking pen, as the alcohol in the ink can damage the delicate limbal stem cells) and marking is done slightly behind the limbus on the conjunctiva. A conjunctival bleb is created with fluid just behind the selected area of the biopsy and a limbus based conjunctival flap is created 1 to 2 mm away from the limbus; dissection is continued toward the limbus. When the limbus is reached, using a Crescent blade or N15 Surgical blade dissection continues for 1mm into clear cornea. The conjunctival flap will be cut apart from the donor limbus and the limbus excised using forceps and Vannas scissors. The conjunctiva will be repositioned and held in place using fibrin glue or sutures. The limbal tissue is preserved in balanced saline solution to prevent drying.

Step 3: After prepping and draping of the recipient eye, a 360 peritomy about 2-3 mm beyond the estimated limbus is done and all the vascular pannus removed from the cornea with careful blunt and sharp dissection. Attempts to manually debulk the cornea stroma to reach a clearer plane is strongly discouraged. Removing the pannus is a crucial step to provide the proper surface for the stem cells to expand. The cornea and bare sclera are covered with human amniotic membrane (HAM, basement membrane side up). The HAM is held in place with fibrin sealant. It is critical to ensure that the HAM is tucked under the conjunctival edge in all quadrants. The HAM is smoothened out over the cornea with a blunt spatula to make sure there are no folds.

Step 4: After the HAM is glued in place, the limbal tissue is removed from the BSS and cut in about 6-10 pieces with Vannas scissors directly over the HAM. These pieces are placed (epithelium side up) in the mid peripheral cornea in a circular fashion. The correct orientation of the small pieces can be identified from the pigmentation and/or smooth surface of the epithelial side and the white fibrous strands on the stromal side. Care is taken to ensure that the pieces are not placed over the pupillary area or the limbus. A drop of fibrin sealant is placed over each piece of limbal tissue.

Step 5: When the fibrin sealant is polymerized and everything looks stable, a large diameter contact lens is placed followed by antibiotic and steroid drops.

Post-operative care

Patients are usually followed up on day one, 1 week and 1 month after surgery, and thereafter according to specific needs. The contact lens should stay in place for 7 to 10 days. V Mittal et al. reported a complete epithelialization of the corneal surface by the second week, and a transparency of the explants by the 8^th week. In the same publication Dr. Mittal et al. showed that the epithelialization and explants transparency process was faster in children than in adults . The HAM will take a few weeks to dissolve and the time will depend on its thickness. The reports have shown an efficacy of 83% restoring the ocular surface and preventing the conjuntivalization of the cornea . None of the donor eyes developed stem cell deficiency.

Complications

Some common complications during the post-op period are displacement of the grafts or the HAM, the former is more common when there is bleeding under the HAM after the surgery. The most commonly reported complication is the recurrence of conjunctivalization. Clinical factors that have been associated with failure are acid injury, severe symblepharon, combination with keratoplasty and postoperative loss of explants .

Conclusion

SLET has shown to be an efficient and cost-effective surgical technique for the restoration of the ocular surface in cases of partial and complete LSCD . R. Arora et al. did a prospective study comparing SLET vs CLAU, and they concluded that both procedures were equally effective, and both provided stable results . SLET has a relatively short learning curve and has made life easier for corneal surgeons.

References

21. Marwan Raymond Atallah; Sotiria Palioura;
Victor L Perez;
Guillermo Amescua. Limbal stem cell transplantation: current perspectives. Clinical Ophthalmology 2016:10 593–602.