Corneal epithelial restoration after penetrating keratoplasty in repeated failed cultivated limbal stem cell grafts (original) (raw)
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BioMed Research International, 2015
Objective. To evaluate outcomes of cultivated limbal epithelial transplantation (CLET) for management of ocular surface failure due to limbal stem cell deficiency (LSCD).Design. Prospective, noncomparative, interventional case series and extensive comparison with recent similar studies.Participants. Twenty eyes with LSCD underwent CLET (11 autologous; 9 allogeneic) and were followed up for 3 years. Etiologies were divided into 3 prognostic categories: Group 1, chemical injuries (7 eyes); Group 2, immune-based inflammation (4 eyes); and Group 3, noninflammatory diseases (9 eyes).Intervention. Autologous and allogeneic limbal epithelial cells were cultivated on amniotic membranes and transplanted. Evaluations were based on clinical parameters, survival analysis, and in vivo confocal microscopy (IVCM). European Union Tissues/Cells Directive and good manufacturing procedures were followed.Main Outcome Measures. Improved clinical parameters, absence of epithelial defects, and improved ce...
Efficacy of cultivated corneal epithelial stem cells for ocular surface reconstruction
Clinical Ophthalmology, 2012
To investigate the clinical outcomes of cultivated corneal limbal epithelial transplantation (CLET) using human amniotic membrane for corneal limbal stem-cell deficiency. Methods: Prospective, noncomparative case series. Eighteen patients (19 eyes) with severe ocular surface diseases were chosen to undergo CLET using human amniotic membrane. Twelve eyes received auto-CLET, and seven eyes received allo-CLET. Clinical outcomes of corneal surface epithelialization, conjunctivalization, inflammation, visual acuity, graft status, and complications were observed. Results: Corneal epithelium cultivated on amniotic membrane (two to four layers) was positive for molecular markers p63, ABCG2, CK3, and CK12. The mean patient age was 44.7 ± 15.2 years. A successful clinical outcome, defined as corneal epithelialization without central conjunctivalization or severe inflammation, was obtained in 14 (73.7%) of 19 eyes (mean follow-up 26.1 ± 13.5 months; range 6-47). A histopathologic success, defined as absence of goblet cells at the central cornea, was achieved in 12 (63.2%) eyes. Clinical failures occurred in five (26.3%) of 19 eyes, and histopathologic failures occurred in seven (36.8%) of 19 eyes. Survival analysis at 1 year showed that the clinical success rate was 77.9% and the pathological success rate was 72.3%. Fourteen of 19 (73.7%) eyes had visual acuity improvements after CLET. Six cases underwent penetrating keratoplasty; five of these grafts remained clear after 20.4 ± 6.9 months (range, 12-31) of follow-up. Complications included infectious keratitis (three cases) and recurrent symblepharon (one case). All complicated cases had lid abnormalities. Factors affecting the final clinical outcomes were lid abnormalities, abnormal corneal stromal beds, and complications. Conclusion: CLET can successfully restore ocular surface damage in most cases with corneal limbal stem cell deficiency.
Limbal Stem-Cell Therapy and Long-Term Corneal Regeneration
New England Journal of Medicine, 2010
Corneal renewal and repair are mediated by stem cells of the limbus, the narrow zone between the cornea and the bulbar conjunctiva. Ocular burns may destroy the limbus, causing limbal stem-cell deficiency. We investigated the long-term clinical results of cell therapy in patients with burn-related corneal destruction associated with limbal stem-cell deficiency, a highly disabling ocular disease.
Concise review: the coming of age of stem cell treatment for corneal surface damage
Stem cells translational medicine, 2014
The cornea is a vital component of the eye because it provides approximately 70% of the refraction and focusing of incoming light. Being the outermost surface of the eye, it faces continuous stress from dryness, photodamage, infection, and injury; however, like the skin, the cornea regularly refreshes itself by shedding its epithelial cells, which are readily replaced, keeping the ocular surface stable and functional. This regular turnover of the corneal epithelial cells occurs through the stem cells in the limbus, an annular ring of a tissue surrounding the cornea, separating it from the sclera and the conjunctival membrane. The loss of this reserve of stem cells leads to a condition called limbal stem cell deficiency. Treatment for this disorder has evolved from transplanting whole limbal tissues to the affected eye to transplanting laboratory cultured limbal cells. This procedure is called cultivated limbal epithelial transplantation (CLET). Since its start in 1997, more than 1,0...
Stem cells (Dayton, Ohio), 2018
The purpose of this study is to investigate the outcomes of penetrating keratoplasty (PKP) following autologous cultivated limbal epithelial stem cell transplantation (CLET). A prospective, single center, interventional cohort study investigating patients with unilateral total limbal stem cell deficiency (LSCD) treated with CLET who underwent PKP. Patients with confirmed corneal re-epithelialization > 6 months post-CLET, and with best-corrected visual acuity (BCVA) <0.3 logMAR were offered PKP. CLET survival assessed by slit lamp, corneal impression cytology (CIC), and in vivo confocal microscopy. Confirmation of corneal re-epithelialization by histological and immunocytochemical (ICC) examination of trephined corneal buttons. Mean change in best-corrected visual acuity (logMAR) following PKP and PKP survival at 12 months were calculated. Twenty patients underwent PKP. Mean time of PKP was 19 months (range 11-41 months, SD 7.26) post-CLET. Median follow-up time post-PKP was 15...
Mini-Review: Regenerating the Corneal Epithelium With Simple Limbal Epithelial Transplantation
Frontiers in Medicine, 2021
Simple limbal epithelial transplantation (SLET) is an ingenious, low cost and effective technique of limbal stem cell transplantation (LSCT) that is increasingly being undertaken in practice across the world. Since it was first described a decade ago, the technique has been performed in a variety of cases of limbal stem cell deficiency (LSCD) and has underwent several innovative modifications. Published literature on SLET has progressively increased over time and successful outcomes in various clinical scenarios have been reported. This concise review attempts to present a crisp account of SLET covering the indications and contraindications of performing the procedure; detailed account of pre-operative work up and preparation; surgical technique and its modifications; post-operative course, care and possible complications as well as published outcomes of surgery from across the world. Comparative analysis of various techniques of LSCT have been discussed and common concerns of surge...
Safety of Cultivated Limbal Epithelial Stem Cell Transplantation for Human Corneal Regeneration
Stem Cells International
Ex vivo cultivated limbal stem cell transplantation is a promising technique for the treatment of limbal stem cell deficiency. While the results of the clinical trials have been extensively reported since the introduction of the technique in 1997, little has been reported regarding the potential health risks associated with production processes and transplantation techniques. Culture procedures require the use of animal and/or human-derived products, which carry the potential of introducing toxic or infectious agents through contamination with known or unknown additives. Protocols vary widely, and the risks depend on the local institutional methods. Good manufacturing practice and xeno-free culture protocols could reduce potential health risks but are not yet a common practice worldwide. In this review, we focus on the safety of both autologous- and allogeneic-cultivated limbal stem cell transplantation, with respect to culture processes, surgical approaches, and postoperative strat...
Molecular vision, 2016
To determine the corneal regenerative capacity of sequentially generated primary, secondary, and tertiary limbal explant outgrowths in a limbal stem cell deficiency (LSCD) surgical model. Two-millimeter-long limbal shallow biopsies were surgically excised from the upper quadrant of the right eye of rabbits and set on preserved amniotic membrane for explant culture. After the generation of primary outgrowth, the biopsies were sequentially transferred to new amniotic membrane to generate secondary and then tertiary outgrowths. Eighteen rabbits were subjected to a 360° limbal peritomy extending into the scleral zone and combined with superficial keratectomy of the corneal periphery and thorough mechanical debridement of the central cornea in their left eye. Right eye outgrowths, six of each generation, were engrafted on the ocular surface. Clinical outcomes (neovascularization, corneal clarity, and corneal fluorescein staining) were graded after 6 months. Post-mortem corneas were compa...
2010
Purpose: To report the midterm outcomes of autologous limbal stem cell transplantation cultivated on amniotic membrane (AM) with or without subsequent penetrating keratoplasty (PKP) in patients with total unilateral limbal stem cell deficiency (LSCD). Methods: Eight eyes of 8 consecutive patients with unilateral total LSCD underwent autologous limbal stem cell transplantation cultivated on AM. Four eyes underwent subsequent optical PKP. Main outcome measures were corneal vascularization and transparency. Results: The patients were followed for 34.0 6 13.5 months (6-48 months). Seven cases had a stable corneal epithelium with marked decrease in opacification and vascularization. Progressive sectorial conjunctivalization was evident in all cases with subsequent PKP at the last follow-up. Primary failure was observed in one case because of exposure. Conclusions: Transplantation of autologous stem cells cultivated on AM with or without subsequent PKP seems to be an effective way for visual rehabilitation in total LSCD. More work with more cases and longer follow-up are needed to optimize this procedure to provide and maintain an adequate supply of limbal stem cells in these patients.
Repairing the corneal epithelium using limbal stem cells or alternative cell-based therapies
Expert opinion on biological therapy, 2018
The corneal epithelium is maintained by limbal stem cells (LSCs) that reside in the basal epithelial layer of the tissue surrounding the cornea termed the limbus. Loss of LSCs results in limbal stem cell deficiency (LSCD) that can cause severe visual impairment. Patients with partial LSCD may respond to conservative therapies designed to rehabilitate the remaining LSCs. However, if these conservative approaches fail or, if complete loss of LSCs occurs, transplantation of LSCs or their alternatives is the only option. While a number of clinical studies utilizing diverse surgical and cell culture techniques have shown favorable results, a universal cure for LSCD is still not available. Knowledge of the potential risks and benefits of current approaches, and development of new technologies, is essential for further improvement of LSCD therapies. Areas covered: This review focuses on cell-based LSCD treatment approaches ranging from current available clinical therapies to preclinical st...