Simple limbal epithelial transplantation (SLET): Review of indications, surgical technique, mechanism, outcomes, limitations, and impact

Simple limbal epithelial transplantation (SLET) is an innovative limbal stem cell transplantation technique that has gained increasing popularity over the last few years. Different groups from across the world have published the clinical results of SLET in large case series with varying types and severities of limbal stem cell deficiency (LSCD). This review attempts to place all the available knowledge on SLET together in one place for the benefit of not only cornea specialists and trainees but also for residents and general ophthalmologists. It follows a balanced approach of blending evidence with experience by providing an objective analysis of published results along with helpful insights from subject experts, starting from preoperative considerations including the role of newer imaging modalities to the technical aspects of the surgery itself and the management of possible complications. Original data and novel insights on allogeneic SLET for bilateral LSCD are included in the review to address the few remaining lacunae in the existing literature on this topic. This review intends to inform, educate, and empower all aspiring and practicing SLET surgeons to optimize their clinical outcomes and to have maximal positive impact on the lives of the individuals affected by unilateral or bilateral chronic LSCD.

Transforming ocular surface stem cell research into successful clinical practice.

It has only been a quarter of a century since the discovery of adult stem cells at the human corneo-scleral limbus. These limbal stem cells are responsible for generating a constant and unending supply of corneal epithelial cells throughout life, thus maintaining a stable and uniformly refractive corneal surface. Establishing this hitherto unknown association between ocular surface disease and limbal dysfunction helped usher in therapeutic approaches that successfully addressed blinding conditions such as ocular burns, which were previously considered incurable. Subsequent advances in ocular surface biology through basic science research have translated into innovations that have made the surgical technique of limbal stem cell transplantation simpler and more predictable. This review recapitulates the basic biology of the limbus and the rationale and principles of limbal stem cell transplantation in ocular surface disease. An evidence-based algorithm is presented, which is tailored to clinical considerations such as laterality of affl iction, severity of limbal damage and concurrent need for other procedures. Additionally, novel fi ndings in the form of factors infl uencing the survival and function of limbal stem cells aft er transplantation and the possibility of substituting limbal cells with epithelial stem cells of other lineages is also discussed. Finally this review focuses on the future directions in which both basic science and clinical research in this fi eld is headed.

Two Cases of Whole Corneo-Limbal Transplantation

PURPOSE: To report the clinical outcomes of total corneolimbal transplantation in two cases. CASE SUMMARY: One patient, who previously underwent three rounds of penetrating keratoplasty and limbal transplantation for uncontrollable peripheral and central corneal melting, received total corneolimbal transplantation. The other patient who underwent penetrating keratoplasty with limbal transplanation for a chemical burn and who did not experience corneal perforation also received total corneolimbal transplantation. During the average 19 months of follow-up, cyclophotocoagulation was performed to control high intraocular pressure in both patients. Both eyes were tectonically maintained without further corneal destruction despite poor visual acuity and rejection. CONCLUSIONS: Total corneolimbal transplantation may be an effective tectonic procedure for corneal melting. This procedure can be considered as another option for patients with corneal melting after failed limbal and corneal transplantation.

Limbal Transplantation: A Midterm Clinical Outcome with Continuous Systemic Immune Suppression

PURPOSE: To investigate the midterm outcome of limbal transplantation combined with continuous systemic immune suppression. METHODS: The medical records of 15 eyes in 14 patients who underwent limbal transplantation were reviewed retrospectively. All had been followed up for 6 months or more. Limbal transplantation was performed with 360 degrees of 0.19 mm partial corneal trephined tissues, accompanied with transient amniotic membrane transplantation. The procedure was accomplished with systemic cyclosporine or mycophenolate. We defined complete success as neither rejection nor epithelial defect; partial success as partial conjunctival ingrowth and neovascularization without epithelial defect; and graft failure as persistent epithelial defect or total conunctivalization with neovascularization. RESULTS: Mean age at surgery was 45.1 years. 9 eyes yielded complete success, 2 had partial success, and graft failure occurred in 4 on an average of 23.4 months postoperatively. Success including complete and partial success showed 67% incidence (4 of 6) of chemical burn, 33% (1 of 3) with Stevens-Johnson syndrome, and 100% (6 of 6) experienced another intractable ocular surface disease. Of 10 eyes (67%), which experienced graft rejection in an average of 2.7 months; 4 demonstrated full recovery with oral corticosteroid and enhanced immunosuppression, 2 presented with chronic graft rejection, and the other 4 ended in graft failure. CONCLUSIONS: Total success rate was revealed as 73.3% for on average 23.4 months in limbal transplantation with continuous systemic immune suppression, utilized for chronic intractable ocular surface disease.

Limbal Transplantation: A Midterm Clinical Outcome with Continuous Systemic Immune Suppression

PURPOSE: To investigate the midterm outcome of limbal transplantation combined with continuous systemic immune suppression. METHODS: The medical records of 15 eyes in 14 patients who underwent limbal transplantation were reviewed retrospectively. All had been followed up for 6 months or more. Limbal transplantation was performed with 360 degrees of 0.19 mm partial corneal trephined tissues, accompanied with transient amniotic membrane transplantation. The procedure was accomplished with systemic cyclosporine or mycophenolate. We defined complete success as neither rejection nor epithelial defect; partial success as partial conjunctival ingrowth and neovascularization without epithelial defect; and graft failure as persistent epithelial defect or total conunctivalization with neovascularization. RESULTS: Mean age at surgery was 45.1 years. 9 eyes yielded complete success, 2 had partial success, and graft failure occurred in 4 on an average of 23.4 months postoperatively. Success including complete and partial success showed 67% incidence (4 of 6) of chemical burn, 33% (1 of 3) with Stevens-Johnson syndrome, and 100% (6 of 6) experienced another intractable ocular surface disease. Of 10 eyes (67%), which experienced graft rejection in an average of 2.7 months; 4 demonstrated full recovery with oral corticosteroid and enhanced immunosuppression, 2 presented with chronic graft rejection, and the other 4 ended in graft failure. CONCLUSIONS: Total success rate was revealed as 73.3% for on average 23.4 months in limbal transplantation with continuous systemic immune suppression, utilized for chronic intractable ocular surface disease.

Early Effect of Autologous Limbal Transplantation Immediately following Total Limbal Injury in Rabbits

Limbal epithelium plays a great role in reconstruction of damaged corneal epithelium and early limbal transplantation showed better results in limbal injury.However, there is no consensus about the appropriate time for limbal transplantation.We, therefore, investigated the results of autologous limbal transplantation (ALT)immediately following limbal epithelial injury in rabbits.We classified the rabbits in three groups whether the application of ALT and therapeutic contact lens were done or not.Injury of limbal and corneal epithelium was made by application of n-heptanol and tarsorrhaphy was done in all groups.ALT from the healthy fellow eye was done in Group 1 and Group 2 but not in Group 3, control group.Therapeutic soft contact lens was applied to Group 2 after ALT.We evaluated epithelial defect, haze, and neovascularization of corneas at 3 days, 1 week, and 2 weeks after operation.We also examined tissue specimen of corneas after two weeks of operation.Epithelial defect was almost healed within 2 weeks after operation in Group 1 and Group 2, but Group 3 showed persistent epithelial defect. Corneal neovascularization and haze were the most severe in Group 3, but was not so severe in Group 1 and Group 2, and there was no significant difference between the two groups.On histopathologic examination, Group 1 and Group 2 showed almost normal corneal epithelium though a few inflammatory cells and goblet cells were observed in some cases but control group showed severe inflammaton and many new vessels and goblet cells.In conclusion, ALT immediately following severe limbal injury is effective in reconstructing corneal epithelium.

Combined Surgery of the Penetrating Keratoplasty and the Limbal Cell Transplantation

If the corneal opacity and the corneal neovascularization are severe and broad, it should be taken the penetrating keratoplasty. But there is a high risk of the persistent epithelial defect, the neovascularization and the rejection. Recently, there were many reports that support the limbal stem cell theory. Based on the stem cell conception of the corneal epithelium, the authors have evaluated the clinical effects of the penetrating keratoplasty combined with the allograftic limbal transplantation or the penetrating keratoplastty combined with the autologousl imbal transplantation in 4 patients (4 eyes) whose corneas were severly opaque and heavily neovasculized. As a result, the visual improvement was achieved in 3 eyes (as a corrected vision, from hand motion to finger count, from hand motion to 0.05, from hand motion to 0.15), the prompt reepithelialization was accomplished in 3 eyes (the mean time: 5.7 days) and even in case of the failed reepithelialization, the epithelial side at which the limbal transplantion was done showed a rapid recovery. Therefore we think that the combined surgery of the panetrating keratoplasty and the limbal transplantation is useful because it can increase the success rate of the penetrating keratoplasty by the rapid and firm reepithelialization and the suppression of the neovascularization. Futhermore the donor cornea can be used effectively (the central portion is used for a penetrating keratoplasty and the limbal portion is used for a limbal transplantation), and we can expect a rapid visual recovery through a simultaneous surgery of the two other operation.