Safety outcomes and long-term effectiveness of ex vivo autologous cultured limbal epithelial transplantation for limbal stem cell deficiency

Fasolo, Adriano; Pedrotti, Emilio; Passilongo, Mattia; Marchini, Giorgio; Monterosso, Cristina; Zampini, Roberto; Böhm, Elisabetta; Birattari, Federica; Franch, Antonella; Barbaro, V.; Bertolin, Marina; Breda, Claudia; Iorio, Enzo Di; Ferrari, Barbara; Ferrari, Stefano; Meneguzzi, Mauro; Ponzin, Diego

doi:10.1136/bjophthalmol-2015-308272

Cited by 45 publications

(22 citation statements)

References 27 publications

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“…A hallmark of effective regeneration of the limbal stem cell function is the maintenance of a transparent and intact corneal epithelium, without central corneal superficial neovascularization, for a period of one year after surgery, which is consistent with a normal homeostasis of the entire human corneal epithelium estimated as ranging from nine to 12 months [7][8][9]. However, weighing the risk-benefit of further surgery after cell therapy for LSCD is a matter of concern, as approximately 50% of successful CLET procedures had shown subsequent corneal surface failure or recurrence of epithelial defects after corrective or reconstructive penetrating keratoplasty (PK) [10][11][12].…”

Section: Introductionsupporting

confidence: 69%

In Vivo Confocal Microscopy of the Corneal-Conjunctival Transition in the Evaluation of Epithelial Renewal after SLET

Pedrotti

Chierego

Cozzini

et al. 2020

JCM

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Examination of the corneal surface by in vivo confocal microscopy (IVCM) allows for objective identification of corneal and conjunctival cell phenotypes to evaluate different epithelialization patterns. Detection of a corneal-conjunctival epithelial transition could be considered as a sign of restored epithelial function following simple limbal epithelial transplantation (SLET). This is a prospective, interventional case series. We assessed patients with limbal stem cell deficiency (LSCD) by IVCM, preoperatively and at monthly intervals following SLET. Sectors in the central and peripheral cornea were scanned. Immediately upon detection of multi-layered cells with the epithelial phenotype in the central cornea and confirmation of epithelial transition in all corneal sectors, the decision for keratoplasty was taken. Ten patients were enrolled. After SLET, epithelial phenotype in the central cornea and an epithelial transition were identified within six and nine months in seven and one patients, respectively. One patient was a partial success and one failed. Five patients underwent keratoplasty, with stable results up to 12 months. Identification of the epithelial transition zone by IVCM permits assessment of the efficacy of SLET, enabling subsequent planning of keratoplasty for visual rehabilitation. The stability of the corneal surface following keratoplasty confirms that the renewal of the corneal epithelium was effectively retained.

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Section: Introductionsupporting

confidence: 69%

In Vivo Confocal Microscopy of the Corneal-Conjunctival Transition in the Evaluation of Epithelial Renewal after SLET

Pedrotti

Chierego

Cozzini

et al. 2020

JCM

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“…34 Following this, several groups have published their outcomes of this technique, however the cultivation protocols are quite variable across groups as summarized in Table 3. [35][36][37][38][39][40][41][42][43][44][45][46][47][48] Broadly there are two techniques of limbal cultivation: a) the suspension culture, where the biopsied limbal tissue is first digested enzymatically to separate the cells from the extracellular matrix and then the cell suspension is placed in culture over a suitable substrate; and b) explant culture where the limbal tissue fragment is sectioned into smaller pieces and placed directly on the substrate without enzymatic digestion. Additionally, the constituents of the culture medium may or may not contain animal-derived products or xenobiotic materials.…”

Section: Cultivated Limbal Epithelial Transplantation (Clet)mentioning

confidence: 99%

Limbal Epithelial and Mesenchymal Stem Cell Therapy for Corneal Regeneration

Shukla

Shanbhag

Tavakkoli

et al. 2019

Current Eye Research

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Corneal pathologies are a major cause of blindness and visual impairment, especially in the developing world. However, not only is there a global shortage of donor corneal tissue, but a significant proportion of these blinding pathologies also carry an unfavourable long-term prognosis for conventional corneal transplantation. In the last few decades, there has been a spurt of research on developing alternate approaches to address corneal blindness, including stem cell therapy. After the discovery of epithelial stem cells at the limbus, successful cell-based approaches to treat severe ocular surface disease were developed and have subsequently become widely practised across the world. More recently, mesenchymal stem cells were identified near the epithelial stem cells at the limbus, providing a unique opportunity to develop regenerative therapies for both corneal epithelial and stromal pathologies. This review firstly emphasises on qualifying limbal stem cells as either epithelial or mesenchymal and then summarises all the existing knowledge on both cell types and their individual roles in corneal regeneration. The review describes the history, indications, techniques, and outcomes of the different methods of limbal epithelial stem cell transplantation and elaborates on the potential applications of limbal mesenchymal stem cell therapy. ARTICLE HISTORY

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“…A recent review article on the safety of CLET reported that since CLET protocols rely on the use of animal material, there is always a potential risk to the patient, and it is possible that the impact of these elements on the outcome of CLET is underestimated 10. The latest clinical study on safety of CLET in 59 eyes with a mean follow-up of 6 years showed that within the first year of surgery 69% of eyes showed one or more adverse events, including 31% that had epithelial healing problems 17. At 1 year only 41% could be considered completely successful using subjective assessment criteria 17…”

Section: Discussionmentioning

confidence: 99%

Simple limbal epithelial transplantation (SLET) in failed cultivated limbal epithelial transplantation (CLET) for unilateral chronic ocular burns

et al. 2018

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Safety outcomes and long-term effectiveness of ex vivo autologous cultured limbal epithelial transplantation for limbal stem cell deficiency

Abstract: This study addresses important issues regarding possible risks associated with disarray of the ocular surface homeostasis following autologous CLET in patients with limbal stem cell deficiency, despite the fact that the majority of patients experienced a favourable long-term benefit.

Cited by 45 publications

References 27 publications

In Vivo Confocal Microscopy of the Corneal-Conjunctival Transition in the Evaluation of Epithelial Renewal after SLET

In Vivo Confocal Microscopy of the Corneal-Conjunctival Transition in the Evaluation of Epithelial Renewal after SLET

Limbal Epithelial and Mesenchymal Stem Cell Therapy for Corneal Regeneration

Simple limbal epithelial transplantation (SLET) in failed cultivated limbal epithelial transplantation (CLET) for unilateral chronic ocular burns

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