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Stem Cell Therapy for Corneal Epithelium Regeneration following Good Manufacturing and Clinical Procedures.

Ramírez BE, Sánchez A, Herreras JM, Fernández I, García-Sancho J, Nieto-Miguel T, Calonge M - Biomed Res Int (2015)

Bottom Line: All clinical parameters improved substantially.By IVCM, 80% of cases improved in epithelial status.These results confirm that CLET is a valid therapy for ocular surface failure.

View Article: PubMed Central - PubMed

Affiliation: Institute of Applied Ophthalmobiology (IOBA), University of Valladolid, Campus Universitario Miguel Delibes, Paseo de Belén 17, 47011 Valladolid, Spain.

ABSTRACT

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 central corneal epithelial phenotype.

Results: Success rate was 80% at 1-2 years and 75% at 3 years. Autografts and allografts had similar survival. Success rate was significantly lower in prognostic Group 1 (42.9%) than in Groups 2-3 (100% each). All clinical parameters improved substantially. By IVCM, 80% of cases improved in epithelial status.

Conclusions: CLET improved corneal epithelium quality, with subsequent improvement in symptoms, quality of life, and vision. These results confirm that CLET is a valid therapy for ocular surface failure.

No MeSH data available.


Related in: MedlinePlus

Case 11 (Table 1) before and after cultivated limbal epithelial transplantation (CLET). This 27-year-old male had a total limbal stem cell deficiency due to an early failed penetrating keratoplasty 7 years before. It was performed 5 years after a contact lens-related Acanthamoeba keratitis (a). (a1) In vivo confocal microscopy (IVCM) in the central cornea showed intense fibrosis (black arrows) and a conjunctival epithelial phenotype. (a2) Limbal cells for cultivated limbal epithelial transplantation (CLET) were obtained from his contralateral healthy eye, the biopsy site of which is shown 3 months after biopsy. (b) Twelve months after autologous CLET, corneal neovascularization had almost vanished and IVCM showed a mixed epithelium phenotype (b1), conjunctival phenotype (star), and corneal phenotype (square). (b2) Limbal donor site 12 months after biopsy. (c) Fourteen months after CLET, a penetrating keratoplasty and cataract removal were performed, followed 12 months later with a compact and clear graft. IVCM showed a corneal phenotype (c1). (c2) The corneal transplant was still successful after 2 years (3 years after CLET) although an Ahmed valve was implanted 10 months after corneal transplant to treat his elevated intraocular pressure.
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fig5: Case 11 (Table 1) before and after cultivated limbal epithelial transplantation (CLET). This 27-year-old male had a total limbal stem cell deficiency due to an early failed penetrating keratoplasty 7 years before. It was performed 5 years after a contact lens-related Acanthamoeba keratitis (a). (a1) In vivo confocal microscopy (IVCM) in the central cornea showed intense fibrosis (black arrows) and a conjunctival epithelial phenotype. (a2) Limbal cells for cultivated limbal epithelial transplantation (CLET) were obtained from his contralateral healthy eye, the biopsy site of which is shown 3 months after biopsy. (b) Twelve months after autologous CLET, corneal neovascularization had almost vanished and IVCM showed a mixed epithelium phenotype (b1), conjunctival phenotype (star), and corneal phenotype (square). (b2) Limbal donor site 12 months after biopsy. (c) Fourteen months after CLET, a penetrating keratoplasty and cataract removal were performed, followed 12 months later with a compact and clear graft. IVCM showed a corneal phenotype (c1). (c2) The corneal transplant was still successful after 2 years (3 years after CLET) although an Ahmed valve was implanted 10 months after corneal transplant to treat his elevated intraocular pressure.

Mentions: Evaluation of the central corneal epithelial cell phenotypes by laser IVCM was the most objective primary endpoint [24, 33]. Before CLET, 13 eyes (65%; Cases 3, 4, 8, 9–17, and 20) had a conjunctival epithelial phenotype in the central cornea (Figures 3–5). One year after CLET, 6 of the 13 cases (Cases 3, 8–10, 13, and 20) improved to the corneal-like epithelium phenotype (Figure 4), and 5 eyes (Cases 4, 11, 12, 14, and 15) evolved to a mixed phenotype (Figure 5). The partially successful case (Case 17) and one of the 3 failed cases (Case 17) maintained the conjunctival phenotype. The remaining 7 eyes (Cases 1, 2, 5–7, 18, and 19) were classified in the initial examination as having the mixed epithelium phenotype. One year after CLET, 5 of these eyes (71.43%) changed to the corneal phenotype (Cases 2, 5–7, and 19). The 2 remaining cases (Cases 1 and 18) worsened to the conjunctival phenotype and were consequently considered failures. The type of transplant, autograft or allograft, had no influence in these results (Fisher's exact test, initial visit p = 0.6424, final visit p = 0.3359).


Stem Cell Therapy for Corneal Epithelium Regeneration following Good Manufacturing and Clinical Procedures.

Ramírez BE, Sánchez A, Herreras JM, Fernández I, García-Sancho J, Nieto-Miguel T, Calonge M - Biomed Res Int (2015)

Case 11 (Table 1) before and after cultivated limbal epithelial transplantation (CLET). This 27-year-old male had a total limbal stem cell deficiency due to an early failed penetrating keratoplasty 7 years before. It was performed 5 years after a contact lens-related Acanthamoeba keratitis (a). (a1) In vivo confocal microscopy (IVCM) in the central cornea showed intense fibrosis (black arrows) and a conjunctival epithelial phenotype. (a2) Limbal cells for cultivated limbal epithelial transplantation (CLET) were obtained from his contralateral healthy eye, the biopsy site of which is shown 3 months after biopsy. (b) Twelve months after autologous CLET, corneal neovascularization had almost vanished and IVCM showed a mixed epithelium phenotype (b1), conjunctival phenotype (star), and corneal phenotype (square). (b2) Limbal donor site 12 months after biopsy. (c) Fourteen months after CLET, a penetrating keratoplasty and cataract removal were performed, followed 12 months later with a compact and clear graft. IVCM showed a corneal phenotype (c1). (c2) The corneal transplant was still successful after 2 years (3 years after CLET) although an Ahmed valve was implanted 10 months after corneal transplant to treat his elevated intraocular pressure.
© Copyright Policy - open-access
Related In: Results  -  Collection

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fig5: Case 11 (Table 1) before and after cultivated limbal epithelial transplantation (CLET). This 27-year-old male had a total limbal stem cell deficiency due to an early failed penetrating keratoplasty 7 years before. It was performed 5 years after a contact lens-related Acanthamoeba keratitis (a). (a1) In vivo confocal microscopy (IVCM) in the central cornea showed intense fibrosis (black arrows) and a conjunctival epithelial phenotype. (a2) Limbal cells for cultivated limbal epithelial transplantation (CLET) were obtained from his contralateral healthy eye, the biopsy site of which is shown 3 months after biopsy. (b) Twelve months after autologous CLET, corneal neovascularization had almost vanished and IVCM showed a mixed epithelium phenotype (b1), conjunctival phenotype (star), and corneal phenotype (square). (b2) Limbal donor site 12 months after biopsy. (c) Fourteen months after CLET, a penetrating keratoplasty and cataract removal were performed, followed 12 months later with a compact and clear graft. IVCM showed a corneal phenotype (c1). (c2) The corneal transplant was still successful after 2 years (3 years after CLET) although an Ahmed valve was implanted 10 months after corneal transplant to treat his elevated intraocular pressure.
Mentions: Evaluation of the central corneal epithelial cell phenotypes by laser IVCM was the most objective primary endpoint [24, 33]. Before CLET, 13 eyes (65%; Cases 3, 4, 8, 9–17, and 20) had a conjunctival epithelial phenotype in the central cornea (Figures 3–5). One year after CLET, 6 of the 13 cases (Cases 3, 8–10, 13, and 20) improved to the corneal-like epithelium phenotype (Figure 4), and 5 eyes (Cases 4, 11, 12, 14, and 15) evolved to a mixed phenotype (Figure 5). The partially successful case (Case 17) and one of the 3 failed cases (Case 17) maintained the conjunctival phenotype. The remaining 7 eyes (Cases 1, 2, 5–7, 18, and 19) were classified in the initial examination as having the mixed epithelium phenotype. One year after CLET, 5 of these eyes (71.43%) changed to the corneal phenotype (Cases 2, 5–7, and 19). The 2 remaining cases (Cases 1 and 18) worsened to the conjunctival phenotype and were consequently considered failures. The type of transplant, autograft or allograft, had no influence in these results (Fisher's exact test, initial visit p = 0.6424, final visit p = 0.3359).

Bottom Line: All clinical parameters improved substantially.By IVCM, 80% of cases improved in epithelial status.These results confirm that CLET is a valid therapy for ocular surface failure.

View Article: PubMed Central - PubMed

Affiliation: Institute of Applied Ophthalmobiology (IOBA), University of Valladolid, Campus Universitario Miguel Delibes, Paseo de Belén 17, 47011 Valladolid, Spain.

ABSTRACT

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 central corneal epithelial phenotype.

Results: Success rate was 80% at 1-2 years and 75% at 3 years. Autografts and allografts had similar survival. Success rate was significantly lower in prognostic Group 1 (42.9%) than in Groups 2-3 (100% each). All clinical parameters improved substantially. By IVCM, 80% of cases improved in epithelial status.

Conclusions: CLET improved corneal epithelium quality, with subsequent improvement in symptoms, quality of life, and vision. These results confirm that CLET is a valid therapy for ocular surface failure.

No MeSH data available.


Related in: MedlinePlus