Simple limbal epithelial transplantation (SLET)

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Simple Limbal Epithelial Transplantation (SLET)

Simple Limbal Epithelial Transplantation (SLET) is a surgical technique first described by Dr. Sangwan in 2012 (1) 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 (2).

History

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(3). 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 (4) 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 (5,6). On the other hand, Tan et al (7) 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 (8). This is an effective technique in which we harvest only 1 or 2mm of healthy limbus from the contralateral eye and expand it in a laboratory. Different culture medias and techniques have been described with good results (9,10,11). It allows us to implant a larger graft in the receiving eye and to save 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.

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 us to harvest 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 (1,2).

Indications

This surgery was originally described for unilateral 360 stem cell deficiency, but lately it has also been used for cases of partial LSCD. Before offering this surgery to the patient, a sine qua non requirement is a healthy contralateral eye (1). The causes of unilateral LSCD are chemical or thermal injuries, iatrogenic (topical Mitomycin C, large ocular surface surgeries, etc), contact lens wear, immunologic diseases (Steven Johnson’s Syndrome, TEN syndrome, Ocular Cicatricial Pemphigoid), etc (1,2,9).

Contraindications

 As we explained before, one of the requirements is a contralateral healthy eye. This being said, we shouldn’t try to harvest limbus from a contralateral eye if this can motivate a stem cell deficiency 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 an LSCD. A similar thinking process should be followed when a systemic condition was the cause of the deficiency, for example Steven Johnson’s Syndrome. The former condition, as many others, affect both eyes even if this is very asymmetric and the non-symptomatic contralateral eye looks healthy.

Pre-operative preparation

 We need to optimize the ocular surface before surgery in order to provide to the new stem cells a proper environment for their expansion. It is common in eyes that have experienced a chemical trauma, firework trauma, or there is a longstanding stem cell deficiency to have some inflammation. This inflammation should be tackled before we attempt the SLET which can be done with the use of topical and/or systemic medications. According to the need of every specific case we can use oral Doxycycline, topical Cyclosporine, non-preserved artificial tears, etc. Using non-preserved drops is important in order to avoid adding more toxicity to the eye. This treatment should last as long as it is needed before the surgery and continued after it.

Surgical Technique

Step 1: We will prep both eyes as usual and will drape first the donor eye. We will use topical anesthesia in both eyes and a peribulbar in the LSCD eye. Some surgeons prefer to do peribulbar in both eyes.

Step 2: We will mark a 2mm (12) area in the superior limbus and then create a small conjunctival flap 1 to 2 mm away from the limbus; dissection is continued toward the limbus. When the limbus is reached, using Crescent or N15 Surgical blade we will cut 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. We need to preserve the limbus in balanced saline solution to prevent drying until it is needed.

Step 3: Now we will focus on the receiving eye. After prepping and draping we will perform a 360 peritomy and will remove all the vascular pannus. Removing the pannus is a crucial step to provide the proper surface for the stem cells to expand. After the cornea is clear and all the bleeding vessels are cauterized (not in excess to prevent further inflammation), the cornea and bare sclera is covered with human amniotic membrane (HAM). The HAM is held in place with fibrin sealant or sutures, which has to be well positioned and stable to prevent post-op complications. The peripheral HAM will be tucked under the surrounding conjunctiva. There are several brands of fibrin sealant and there is no report that indicate the use of one over the other. The one used in most of the reports and by myself with good results is the Tisseel (Baxter Healthcare Corp).

Step 4: After the HAM is fixed in place, we will spread the small pieces of limbus (epithelium side up) around the visual axis in a circular fashion. We will cut 10 to 15 pieces using Vannas scissors or N15 surgical blade over a stable surface or directly over the HAM surface if we are using scissors. We have to be careful not to place these pieces covering the visual axis. The explants are glued in place with fibrin sealant.

Step 5: When the fibrin sealant is polymerized and everything looks stable we will place a large diameter contact lens, antibiotics and steroid drops.

Post-operative care

We need to follow up these patients on day one, day three, 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 8th week. In the same publication Dr. Mittal et al. showed that the epithelialization and explants transparency process was faster in children than in adults (13). 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 (14). None of the donor eyes developed stem cell deficiency (2).

Complications

Some common complications during the post-op period are displacement of the grafts or the HAM, the former is more common when we have a posterior membrane bleeding after the surgery. The most commonly reported complication is the recurrence of conjunctivalization. Clinical factors that have been informed to be associated with failure are acid injury, severe symblepharon, combination with keratoplasty and postoperative loss of explants (2,14).

Conclusion

SLET has shown to be an efficient and cost-effective surgical technique for the restoration of the ocular surface even in cases with severe burns and complete LSCD (1,2,12,13,14,15,16,17). R Aurora et al. did a prospective study comparing SLET vs CLAU, and they concluded that both procedures were equally effective, and both provided stable results (15).

References

  1. Sangwan VS, Basu S, MacNeil S, Balasubramanian D. Simple limbal epithelial transplantation (SLET): a novel surgical technique for the treatment of unilateral limbal stem cell deficiency. Br J Ophthalmol. 2012 Jul;96(7):931-4. doi: 10.1136/bjophthalmol-2011-301164. Epub 2012 Feb 10.
  2. Basu S, Sureka SP, Shanbhag SS, et al. Simple limbal epithelial transplantation: long-term clinical outcomes in 125 cases of unilateral chronic ocular surface burns. Ophthalmology 2016; 123:1000–1010.
 
  3. Kenyon KR, Tseng SC. Limbal autograft transplantation for ocular surface disorders. 
Ophthalmology 1989;96:709e22.
  4. Daya SM, Ilari FA. Living related conjunctival limbal allograft for the treatment of stem cell deficiency. Ophthalmology 108:126--33, discussion 133--4, 2001. 

  5. Harminder S. Dua, MD, MS, FRCS, FRCOphth, PhD, Augusto Azuara-Blanco, MD, PhD. Limbal Stem Cells of the Corneal Epithelium. Surv Ophthalmol 44: 415–425, 2000.
  6. Rao SK, Rajagopal R, Sitalakshmi G, Padmanabhan P: Limbal allografting from related live donors for corneal surface reconstruction. Ophthalmology 106: 822–8, 1999.
  7. Tan DT, Ficker LA, Buckley RJ: Limbal transplantation. Ophthalmology 103: 29–36, 1996.
  8. Pellegrini G, Traverso CE, Franzi AT, et al. Long-term restoration of damaged corneal surfaces with autologous cultivated corneal epithelium. Lancet 1997;349:990e3.

  9. Alex J. Shortt, MSc, MRCOphth, Genevieve A. Secker, BSc,
Maria D. Notara, PhD, G. Astrid Limb, PhD, Peng T. Khaw, PhD, FRCOphth,  Stephen J. Tuft, MD, FRCOphth, and Julie T. Daniels, PhD. Transplantation of Ex Vivo Cultured Limbal Epithelial Stem Cells: A Review of Techniques and Clinical Results. Surv Ophthalmol 52:483--502, 2007.
  10. K. Ramaesh, B. Dhillon. Ex vivo expansion of corneal limbal epithelial/stem cells for corneal surface reconstruction. Eur J Ophthalmol 2003; 13: 515-24.
  11. Martin Grueterich, MD, Edgar M. Espana, MD, Scheffer C.G. Tseng, MD, PhD. Ex Vivo Expansion of Limbal Epithelial Stem Cells: Amniotic Membrane Serving as a Stem Cell Niche Surv Ophthalmol 48:631–646,2003.
  12. Virender S. Sangwan; John A.H. Sharp. Simple limbal epithelial transplantation. Curr Opin Ophthalmol 2017, 28:382–386.

  13. Vikas Mittal, MS, Rajat Jain, MS, Ruchi Mittal, MS. Ocular Surface Epithelialization Pattern After Simple Limbal Epithelial Transplantation: An In Vivo Observational Study  Cornea 2015;34:1227–1232.
  14. Vazirani J, Ali MH, Sharma N, et al. Autologous simple limbal epithelial transplantation for unilateral limbal stem cell deficiency: multicenter results. Br J Ophthalmol Published Online First: January 27, 2016 doi:10.1136/bjophthalmol- 2015-307348.
  15. Arora R, Dokania P, Manudhane A, Goyal JL. Preliminary results from the comparison of simple limbal epithelial transplantation with conjunctival limbal autologous transplantation in severe unilateral chronic ocular burns. Indian J Ophthalmol 2017;65:35-40.
  16. Mittal V, Jain R, Mittal R, et al. Successful management of severe unilateral chemical burns in children using simple limbal epithelial transplantation (SLET). Br J Ophthalmol Published Online First: December 23, 2016 doi:10.1136/bjophthalmol- 2015-307179.
  17. Vazirani J, Basu S, Sangwan V. Successful simple limbal epithelial transplantation (SLET) in lime injury-induced limbal stem cell deficiency with ocular surface granuloma. BMJ Case Rep Published online: Jun 19, 2013 doi:10.1136/bcr-2013- 009405.
  18. Marwan Raymond Atallah; Sotiria Palioura;
Victor L Perez;
Guillermo Amescua. Limbal stem cell transplantation: current perspectives. Clinical Ophthalmology 2016:10 593–602.