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Long-Term Results of Allogenic Penetrating Limbo-Keratoplasty

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Long-Term Results of Allogenic Penetrating Limbo-Keratoplasty Eye (2017) 31, 372–378 © 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved 0950-222X/17 www.nature.com/eye 1 1 2 CLINICAL STUDY Long-term results of SJ Lang , D Böhringer , G Geerling and T Reinhard1 allogenic penetrating limbo-keratoplasty: 20 years of experience Abstract Aim The objective of the study was to in the case of conjunctivalization of the visual evaluate the long-term results of allogenic axis. This may restore a clear corneal centre in penetrating limbo-keratoplasy. This method those cases without the need for stem cells. allows simultaneous transplantation of a Amniotic membrane transplantation is an corneal graft and limbal stem cells of the additional method.3 Total failure of the limbal donor by means of eccentric trephination of stem cells results in severe alteration of the the donor button. corneal surface, and may lead to complete Method The data of 192 consecutive cases of conjunctivalisation of the cornea, with recurrent allogenic penetrating limbo-keratoplasty from ulcerations.4 This results in corneal opacification 1995 to 2015 were reviewed. These had been and visual impairment. There are a multitude of performed exclusively in eyes with complete causes for complete limbal stem cell failure. failure of the limbal stem cells, in Chemical burns can produce severe damage to combination with deep corneal scarring. the corneal limbus, the corneal stroma, and the Indications were predominantly eye burns, anterior ocular segment. Thus, the degree of fl in ammatory conditions, and congenital ischemia and necrosis in limbus, conjunctiva, aniridia. Graft survival and rejection rates and sclera may permit the estimation of the – were assessed using Kaplan Meier analysis. damage to the limbal stem cells.5 Aniridia ± Results Follow-up averaged 2.1 2.2 years. syndrome is associated with several corneal Median graft survival was 3.4 years in eye abnormalities, including epithelial erosions and burns, 3.9 years in inflammatory disease, and the formation of conjunctival pannus. The 1Eye Center, Medical 3.2 years in congenital aniridia. Median abnormality of the limbal stem cell niche due to Center, Faculty of survival was 3.9 years in the heterogenous Medicine, University of PAX6 failure is a suspected pathogenesis.6 group of other indications. Freiburg, Freiburg im Chronic inflammatory diseases may also lead to Conclusion Allogenic limbo-keratoplasty is a Breisgau, Germany stem cell failure. This is because the suitable option used to treat patients with inflammation in proximity to the limbal stem 2Department of bilateral complete failure of the limbal stem cells causes ‘bystander’ damage to the stem cells Ophthalmology, Heinrich- cells and deep opacification of the central and their niche. This occurs, for example, in Heine-University, cornea. The main reasons for graft failure are Düsseldorf, Germany ocular cicatricial pemphigoid,7 blepharitis, the loss of graft-limbal stem cell functioning atopy, Stevens–Johnson syndrome, and toxic and endothelial graft rejection. Correspondence: epidermal necrolysis.8 The treatment options for SJ Lang, Eye Center, Eye (2017) 31, 372–378; doi:10.1038/eye.2016.217; partial and total limbal stem cell failure are Medical Center, Faculty of published online 21 October 2016 Medicine, University of summarised in Figure 1.Total limbal stem cell Freiburg, Killianstr. 5, failure can only be cured by the transplantation Freiburg im Breisgau, Introduction of viable limbal stem cells. The in vitro expansion 79106, Germany of autologous stem cells taken from small limbal Tel: +4976127040010; Limbal stem cells have a key role in maintaining 9 Fax: +4976127041217. biopsies is one therapeutic option. This method E-mail: stefan.lang@ the epithelial layer of the cornea and in corneal relies upon the cultivation of autologous stem uniklinik-freiburg.de wound healing.1 They are the regenerative cells, either in epithelial cell cultures or in source of an avascular, stable, and clear corneal fibrin.10 En bloc grafting using the other eye is a Received: 27 November 2015 epithelium.2 Limbal stem cell failure may be less expensive alternative,11 for which large Accepted in revised form: either partial or total (Figure 1). Partial 7 September 2016 grafts, that cause discomfort and surgical risk in fi Published online: de ciency of the limbal stem cells can usually be the donor eye, are usually required. This 21 October 2016 treated with selective mechanical debridement technique can only be applied if the stem cell Long-term results of penetrating limbo-keratoplasty SJ Lang et al 373 Figure 1 Possible pathways for the treatment of limbal stem cell failure. failure is not bilateral. The advantage of autologous stem with this technique, including the ‘learning curve’, and cell grafts is that immunological reactions are avoided.9–11 the use of MMC and amniotic membrane transplantation. If both eyes suffer from stem cell failure, the homologous transplantation of the limbal stem cells can be a last resort. Materials and methods Central limbo-keratoplasty was first introduced by Sundmacher et al in 1993.12 The main purpose is to The data of all consecutive cases of allogenic penetrating transplant stem cells in their limbal niche together with limbo-keratoplasty from 1995 to 2015 were analysed. penetrating keratoplasty from the same donor. This is Ethics committee approval was obtained at Albert- achieved simply by eccentric trephination of the donor Ludwigs-University Freiburg (88/12). The patient fi button. The graft may contain up to 40% of limbal tissue13 information was anonymised and de-identi ed prior to analysis. The data from 1995 to 2003 pertained to patients and is sutured centrally in the recipient bed of the patient, from the Department of Ophthalmology, University as is the case in conventional penetrating keratoplasty. Hospital, Düsseldorf, Germany, and those from 2003 to Advantages of this technique are rapid restoration of the 2015 to patients from the Eye Center at the Medical visual acuity owing to the clear donor stroma in the visual Center, University of Freiburg, Germany. axis, and the simultaneous transplantation of the limbal – stem cells together with their niche,12 14 in a single procedure.However, the prognosis of all allogenic Surgical technique techniques is limited due to immunological reactions and The technique for limbo-keratoplasty has been described 15 conjunctivalisation of the graft. The use of mitomycin C by Sundmacher et al12 The graft tissue is eccentrically (MMC) and amniotic membrane transplantation were trephined in order to obtain limbal tissue for later introduced to improve the outcome of limbal stem transplantation. The recipient cornea is removed with a 16 cell transplantation. Subsequently, these additions have trephine, usually 0.25 mm smaller than that used for the 17 been used in allogenic penetrating limbo-keratoplasty. preparation of the graft. Suturing of the graft is performed Human leukocyte antigen (HLA) matching can be with a double-running Hoffmann suture (10-0 nylon). performed additionally to reduce immunogenicity.15,18 A concentration of 0.02% was intraoperatively The purpose of this retrospective study was to evaluate administered for 2 minutes for MMC use. Thereafter, the long-term results of the full cohort of allogenic intensive rinsing of the cornea was performed before penetrating limbo-keratoplasty in 20 years of experience trephination of the host cornea. The amniotic membrane Eye Long-term results of penetrating limbo-keratoplasty SJ Lang et al 374 was additionally grafted to cover the grafted limbal syndrome, Lyell’s syndrome, or ocular citatrical tissue. After transplantation, a bandage contact lens was pemphigoid. placed on the eye. K Other indications: This group included patients with any other disease with consecutive complete limbal Postoperative treatment stem cell failure, that is, corneal ulcers, blepharoker- atoconjunctivitis and various corneal dystrophies. Supportive treatment included the administration of topical and systemic steroids, as well as systemic Any other ocular surface pathology, such as immunosuppression with mycophenolate mofetil or symblepharon or lid margin, were treated before the cyclosporine A. limbo-keratoplasty. The number of HLA mismatches and fi Topical steroids were administered ve times daily for the postoperative use of systemic immunosuppressive the first month after keratoplasty. The number of eye agents, either with mycophenolate mofetil, cyclosporine A, drops was reduced over a period of 5 months. Thereafter, or a combination of both, was also recorded. The topical steroids were administered at least once a day recurrence-free survival of the graft and rejection-free permanently unless side-effects occurred, which justified graft survival were estimated using Kaplan–Meier termination of the treatment. analysis. The grafted limbus and the donor endothelium Cyclosporin A was administered orally. The dosage are capable of being rejected independently. Therefore, was adapted according to the patient’s plasma levels. the immune reaction to the graft endothelium and Mycophenolate mofetil was administered orally at 1 g rejection of the graft limbus were assessed separately. twice daily. During immunosuppression, the patients underwent a regular examination and blood testing at The endothelial immune reaction was diagnosed when their general practitioner in order to timeously diagnose the graft showed endothelial precipitates and/or corneal the side effects of the medication.
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