Simple Limbal Epithelial Transplantation (SLET)

All content on Eyewiki is protected by copyright law and the Terms of Service. This content may not be reproduced, copied, or put into any artificial intelligence program, including large language and generative AI models, without permission from the Academy.

Article initiated by:

Esteban A. Santiago, MD.

All contributors:

Hinali Patel, Vatinee Y. Bunya, MD, MSCE, Esteban A. Santiago, MD., Christina Moon, M.D., Colleen Halfpenny, M.D., Maria D. Bernal, MD, Kendra L. Hong, MD

Assigned editor:

Maria D. Bernal, MD

Review:

Assigned status Up to Date

 by Maria D. Bernal, MD on February 28, 2026.

add
Contributing Editors:	add

Introduction

Figure 1: Unilateral LCSD in an eye after an alkaline corneal burn from an oven cleaner splash injury.

Simple limbal epithelial transplant (SLET) is a surgical technique used to treat unilateral limbal stem cell deficiency (LSCD) and was first described by Sangwan, et al. in 2012. In LCSD, the corneal epithelium is unable to repair itself, leading to persistent corneal epithelial defects, conjunctivalization, neovascularization, scarring, inflammation, and vision loss (Figure 1). SLET restores the limbal stem cells by transplanting healthy limbal stem cells from the healthy contralateral eye onto the affected cornea, facilitating regeneration of a transparent corneal epithelium.

Background

Historical Evolution of Autologous Limbal Stem Cell Transplantation

Autologous limbal stem cell transplantation for unilateral LCSD has evolved over several decades, and many transplantations techniques were performed prior to SLET. In these surgeries, the affected eye first undergoes a peritomy and keratectomy to remove the fibrovascular pannus on the cornea, which is followed by graft harvesting and implantation. The techniques are described below:

• Conjunctival limbal autografting (CLAU) (Kenyon and Tseng, 1989): Two conjunctival-limbal lenticules measured at 4 clock hours each are harvested from the healthy eye and sutured to the limbus in the recipient eye. CLAU requires removal of substantial limbal tissue of up to 50% and can be associated with iatrogenic LSCD in the healthy eye.
• Cultivated limbal epithelial transplantation (CLET) (Pellegrini et al., 1997): A small 2x2 mm limbal tissue is first harvested from the healthy eye and then undergoes ex-vivo cellular expansion in a clinical laboratory for 10-21 days to create a multilayered sheet of corneal epithelium. This sheet is transplanted onto the cornea in the affected eye and secured with 10-0 sutures. Although less limbal tissue was harvested, this technique requires a laboratory to cultivate the stem cells and is a two-stage procedure, making it challenging in resource-limited settings.
• Simple Limbal Epithelial Transplantation (SLET) (Sangwan et al., 2012): SLET combines the advantages of CLAU and CLET. A 2 to 3-mm segment of limbal tissue is harvested from the contralateral healthy eye, divided into 10-12 pieces, and then glued evenly on an amniotic membrane in the recipient eye cornea. The amniotic membrane acts as a scaffold to support the in-vivo expansion of limbal cells.

Pathophysiology of LCSD

Figure 2: Limbal epithelial stem cells are found at the limbus in the palisades of Vogt, migrate centripetally, and differentiate into corneal epithelial cells. Reference: Mannis MJ, et al. Cornea. 2021

The limbus is located at the corneoscleral junction and houses stem cells in the palisades of Vogt that are responsible for constant regeneration and renewal of the corneal epithelium. The stem cells generate epithelial progenitor cells that migrate centripetally and eventually differentiate into corneal epithelial cells to maintain epithelial integrity and heal epithelial defects (Figure 2). Approximately 25-33% of limbus must be present to maintain corneal epithelial integrity.

Causes for LCSD include chemical exposure, thermal burns, autoimmune cicatrizing disease (Stevens-Johnson Syndrome, mucous membrane pemphigoid), chronic inflammation or infection, severe dry eyes, and iatrogenic damage from surgery or medications. Clinical signs of LCSD are persistent corneal epithelial defects, pannus formation, conjunctivalization, neovascularization, and inflammation.

Patient Selection

Indications

Unilateral LSCD is the primary indication. The pathology in the recipient eye should be limited to the epithelium with minimal stromal opacification. Causes of unilateral LSCD include:

• Trauma: chemical exposure, thermal burns
• Ocular disease: Anterior segment ischemia, neoplasia, infection (e.g., herpes, trachoma), degeneration (e.g., pterygium), neurotrophic keratitis
• Iatrogenic: prior ocular surgery such as pterygium excision, mitomycin C exposure, cryotherapy, and conjunctival resection

Contraindications

SLET is not recommended for bilateral LSCD such as Stevens-Johnson Syndrome (SJS) and toxic epidermal necrolysis, mucous membrane pemphigoid, ocular graft versus host disease, bilateral burns, and bilateral infections because there is no suitable donor eye. These patients could benefit from allogenic SLET from cadavers or related living donors but would likely require long-term systemic immunosuppression. Patients with chronic bilateral contact lens wear are also poor candidates due to reduced limbal stem cell reserve from chronic mechanical trauma and hypoxia.

Preoperative Evaluation

Successful SLET outcomes depend on preoperative optimization of the recipient and donor eye.

Recipient Eye

• Ocular surface optimization: The tear film should be optimized with frequent non-preserved artificial tears, and dry eye syndrome should be treated. Punctal occlusion and serum tears can be considered.  
• Inflammation control: Ocular surface inflammation should be minimized and can be optimized with oral doxycycline, topical cyclosporine, vitamin C, and frequent non-preserved artificial tears.
• Imaging: Anterior segment OCT can help assess epithelial thickness in addition to the extent and depth of corneal involvement. Eyes with extremely thin corneas may benefit from concurrent lamellar keratoplasty.
• Adnexal structures: Eyelid abnormalities such as lagophthalmos, malposition, and trichiasis should be corrected.

Donor Eye

The donor limbus should be carefully examined to ensure good limbal stem cell reserve for transplantation to the recipient eye while maintaining sufficient stem cells for epithelial regeneration in the donor eye after graft harvest. Signs of a healthy limbus include intact limbal palisades and absence of epithelial sloughing. Harvesting limbal stem cells is not recommended in donor eyes with severe dryness, corneal neovascularization, conjunctivalization, stromal opacification, endothelial dysfunction, and adnexal abnormalities like lagophthalmos and eyelid malposition.

Figure 3: Fluorescein staining on POD4 demonstrates that epithelium grows from the limbal stem cells and merge together at the white and green arrows. Red and black arrows point at less active explants. Reference: Mittal V, et al. Cornea. 2015.

Mechanism of Action

SLET relies on in-vivo expansion of limbal stem cells. Mittal, et al. imaged post-SLET corneas using fluorescein staining. At each limbal explant, epithelial cells proliferate and migrate in a multidirectional manner until the individual epithelial islands coalesce to form a confluent sheet of epithelium on the corneal surface. The amniotic membrane provides a scaffold for the epithelial cells to attach to and supports the proliferation and migration of epithelial cells (Figure 3).

This hypothesis was further supported by Basu, et al, who performed immunohistochemistry analysis in post-SLET corneas. Like normal corneas, the post-SLET corneas expressed normal corneal epithelium markers (CK3/12) in addition to nuclear epithelial progenitor markers (p63) and limbal epithelial stem cell markers (ΔNp63a, and ABCG2) at explant sites. These findings suggest that post-SLET corneas retain the limbal stem cells at explant sites and can continue regenerating and repairing the epithelium.

Surgical Technique

See video by Basu, et al. and Figures 4-5 for surgical technique.

Anesthesia and Preparation

In adults, topical or peribulbar anesthesia is given to both eyes. In children, general anesthesia is advised. Phenylephrine may help reduce intraoperative bleeding.

Figure 4: Surgical technique of SLET. A) 2-mm length of healthy limbus is excised in donor eye and stored in balanced salt solution. B-C) Peritomy is performed to remove the fibrovascular pannus in the LCSD eye. D) Human amniotic membrane graft is secured onto the cornea with fibrin glue. E-F) Donor limbal tissue is divided into 8-10 pieces and secured onto the amniotic membrane in the LCSD eye using fibrin glue.

Donor Eye Graft Harvesting

Figure 5: Clinical photographs showing SLET surgical technique. A-C) 2 mm of limbal tissue is marked, dissected at subconjunctival level, and excised in donor eye. D-E) Peritomy is performed to excise fibrovascular pannus. F) Human amniotic membrane graft is placed onto the cornea and secured with fibrin glue. G-H) Donor limbal tissue is cut into 8-10 small piece and secured onto the amniotic membrane using fibrin glue. Reference: Sangwan VS, et al. British Journal of Ophthalmology. 2012.

One clock hour or a 2-mm length of healthy limbus, often in the superior sector to prevent infection, is marked. Local anesthesia is used to elevate the conjunctival flap posterior to the limbus, and Vannas scissors dissects the posterior edge of the conjunctiva to the limbus. A Crescent blade or 15-blade is used to excise the healthy limbus 1 mm into clear cornea, and the graft is stored in balanced salt solution. The remaining conjunctiva is re-approximated with fibrin glue or sutures (Figure 4A, Figure 5A-C).

Recipient Eye Preparation and Amniotic Membrane Placement

A 360-degree peritomy extending 2-3 mm posterior to the limbus is performed. Keratectomy is done with careful blunt and sharp dissection to remove the pannus. Healthy corneal and limbal epithelium should be left untouched. An amniotic membrane is placed with stromal side down and epithelial side up onto the cornea, tucked beneath the conjunctival edges, and secured with fibrin glue (Figure 4B-D, Figure 5D-F).

Graft Placement and Positioning

The harvested limbal graft is divided into 10 to 12 small pieces and distributed evenly over the amniotic membrane with the epithelial side up. Fibrin glue is applied onto the graft, and a bandage contact lens is placed (Figure 4E-F, Figure 5G-H). In children, a temporary tarsorrhaphy can be considered.

Successful glueless SLET with femtosecond laser and without has been published.

SLET without amniotic membrane case reports have demonstrated comparable success. In this technique, limbal explants are placed directly on the denuded cornea and covered with a bandage contact lens. Larger studies are needed to validate this scaffold-free approach.

Figure 6: Serial clinical photos of recipient eyes after undergoing SLET for an acid injury to the right eye at pre-op (E), POD1 (F), POW1 in which individual explant locations are visualized (G), and POM6 in which clear cornea is achieved (H). Reference: Sangwan VS, et al. British Journal of Ophthalmology. 2012.

Postoperative Management

A typical postoperative drop regimen includes:

• Topical antibiotics: ciprofloxacin 0.3%, ofloxacin 0.3%, or moxifloxacin 0.5% 4 times/day while the epithelial defect persists
• Topical corticosteroids: prednisolone acetate 1% 6x/day and tapered down by one drop every week for 6 weeks

At POD1, the eye should be examined to ensure that the graft and amniotic membrane are in place. At POW1, the explant locations are visualized, and fluorescein staining should reveals epithelial growth around explant sites (Figure 3). At POM6, a clear cornea can be achieved (Figure 6).

In the recipient eye, the bandage contact lens is usually removed on POW1. If the epithelium has not completely healed, the bandage contact lens can be replaced for another week. If there is persistent haze or inflammation, topical cyclosporine 0.05% can be used. Long-term steroids are not necessary for autologous transplants.

The donor eye should be monitored closely to ensure proper epithelial and limbal healing.  

Prognosis and Outcomes

Success is defined as a completely epithelialized stable avascular corneal surface and improved visual acuity. The rate has been reported at 77-84% at a mean follow-up of 1.5 years. The success rate is comparable to CLET and CLAU but avoids the complications and challenges associated with these techniques.

Basu, et al. followed 125 cases for 1.5 years and found that 76% maintained a successful regenerated epithelialized clear cornea. Two-line visual acuity improvement was observed in 75.2%, and 67% achieved 20/60 vision or better.

Poor prognostic factors includes acid injury, severe symblepharon, SLET combined with keratoplasty, and postoperative loss of transplants.

Risks and Complications

Most clinical failure occur in the first 6 months after surgery and occur due to the following reasons:

• Recurrent LCSD (18-31%): Recurrent LSCD is the most common complication and often manifests as recurrent conjunctivalization, pannus formation, or persistent epithelial defects. Risk factors include acid injury, symblepharon, combination with keratoplasty, and postoperative loss of explants.
• Symblepharon (16.8%): Pre-existing severe symblepharon extending onto the cornea may indicate underlying conjunctival deficiency and is associated with a higher rate of failure.  
• Keratitis (6.4%): Patients should be followed closely in the post-operative period and started on antibiotics and steroids to prevent microbial and sterile keratitis.
• Displacement of graft (5.6%) and/or amniotic membrane (3.2%): In all the reported cases, the patient lost the bandage contact lens in the first week. To prevent this complication, fibrin glue and bandage contact lenses for at least 7 days should be used.
• Corneal perforation (1.6%): If the corneal stroma beneath the pannus is too thin and perforates during pannus dissection, penetrating keratoplasty may be required.
• Iatrogenic LCSD in donor eye (<1%): Only one case of donor eye LCSD has been reported and occurred focally at the site of limbal tissue harvest. Compared to CLAU, the rates of iatrogenic LCSD are low. The donor eye should be carefully assessed in the post-operative period for signs of LCSD.

Future Directions

Allogenic SLET has emerged as an important extension of SLET, particularly in patients with bilateral LSCD who lack suitable autologous donor limbal stem cells. In this approach, limbal stem cells are harvested from cadaveric or living related donors and transplanted onto the recipient eye using the same principles as autologous SLET.

Allogenic SLET is indicated in:

• Bilateral LSCD such as Stevens Johnson Syndrome, mucous membrane pemphigoid
• Ocular surface injuries requiring rapid epithelization such as severe burns

In the acute setting, allogenic SLET may also serve as a temporizing therapy to stabilize the ocular surface and reduce inflammation prior to more definitive autologous reconstruction.

Key advantages of allogenic SLET include increased amount of limbal stem cells that can be harvested and faster epithelization. In a study of 18 eyes, 94% of patients achieved complete epithelization with a mean of 22.5 days versus 4-6 weeks in SLET. However, patients often need lifelong immunosuppression with steroids and often cyclosporine. Ongoing research aims to improve the success of allogenic SLET through refined immunosuppression protocols, alternative stem cell sources such as oral mucosal cells, and bioengineer scaffolds to enhance proliferation.