Zusammenfassung
Hintergrund
In dieser Studie soll die Wirksamkeit der Ex-vivo-Expansion von autologem Limbusepithel zur Oberflächenrekonstruktion bei limbaler Stammzellinsuffizienz (LSZI) untersucht werden.
Patienten und Methoden
Bei 30 Augen von 28 Patienten (m:w 22:6) mit einer kompletten (n=18) oder partiellen (n=12) LSZI erfolgte eine autologe Transplantation von kultiviertem Limbusepithel. Folgende Ätiologien einer LSZI wurden behandelt: Verätzungen/Verbrennungen (n=16), Pterygium (n=9), Z. n. Tumorexzision (n=2), Z. n. Perforationstrauma, Mitomycin-C-induzierte LSZI, und Epidermolysis bullosa, (jeweils n=1). Nur Augen mit einem Nachbeobachtungszeitraum von mindestens 9 Monaten wurden in die Studie eingeschlossen.
Ergebnisse
Der Nachbeobachtungszeitraum betrug im Mittel 28,9±15,5 Monate. Ein stabiles okuläres Oberflächenepithel wurde bei 23 Augen (76,7%) erzielt. Die Sehschärfe stieg bei 21 Augen (70%) an, war stabil bei 8 Augen (26,7%) und verschlechterte sich bei einem Auge (3,3%). Der durchschnittliche LogMAR-Visus verbesserte sich signifikant (p<0,0001) von präoperativ 1,58±0,97 zu postoperativ 0,6±0,49.
Diskussion
Transplantation von ex-vivo-expandiertem Limbusepithel führt zur Stabilisierung des kornealen Oberflächenepithels und zu einem signifikanten Visusgewinn. Autologe Verfahren haben auch nach Langzeitbeobachtung eine sehr gute Prognose.
Abstract
Objective
In this study the clinical outcome of ex vivo expansion of autologous limbal epithelial cells on intact amniotic membranes (AM) for ocular surface reconstruction in limbal stem cell deficiency (LSCD) was investigated.
Patients and Methods
A total of 30 eyes in 28 patients (22 male and 6 female) with total (n=18) or partial (n=12) LSCD were treated by transplantation of autologous limbal epithelial cells after expansion on intact AM. The causes of LSCD in the patients were chemical and thermal burns (n=16), pterygium (n=9), tumor excision (n=2), perforating injury, mitomycin C-induced LSCD and epidermolysis bullosa (each n=1). Only eyes with a follow-up time of at least 9 months were included in the analysis. The main outcome criteria were restoration of ocular surface integrity and improvement of visual acuity (VA).
Results
The mean follow-up time was 28.9±15.5 months. An entirely stable corneal surface was reconstructed in 23 (76.7%) eyes. Visual acuity increased significantly in 21 (70%) eyes, was stable in 8 (26.7%) eyes and decreased in 1 (3.3%) eye. The mean visual acuity increased significantly (p<0.0001) from a preoperative value of 1.58±0.97 LogMAR to 0.6±0.49 LogMAR.
Conclusion
Transplantation of limbal epithelium cultivated on intact AM restores a stable corneal surface and results in a significant increase in visual acuity in most cases of LSCD. Autologous transplantation of cultivated limbal epithelium showed an excellent prognosis and outcome after long-term follow-up.
Literatur
Basti S, Mathur U (1999) Unusual intermediate-term outcome in three cases of limbal autograft transplantation. Ophthalmology 106:958–963
Fuchsluger T, Tuerkeli E, Westekemper H et al (2007) Rate of epithelialisation and re-operations in corneal ulcers treated with amniotic membrane transplantation combined with botulinum toxin-induced ptosis. Graefe’s archive for clinical and experimental ophthalmology 245:955–964
Hernandez Galindo EE, Theiss C, Pauklin M et al (2009) Correlation of cell cycle kinetics with p63 expression in human limbal epithelial cells expanded on intact human amniotic membrane. Ophthalmic Res 41:83–90
Hernandez Galindo EE, Theiss C, Steuhl KP et al (2003) Expression of Delta Np63 in response to phorbol ester in human limbal epithelial cells expanded on intact human amniotic membrane. Invest Ophthalmol Vis Sci 44:2959–2965
Hernandez Galindo EE, Theiss C, Steuhl KP et al (2003) Gap junctional communication in microinjected human limbal and peripheral corneal epithelial cells cultured on intact amniotic membrane. Exp Eye Res 76:303–314
Holland EJ (1996) Epithelial transplantation for the management of severe ocular surface disease. Trans Am Ophthalmol Soc 94:677–743
Kruse FE (1994) Stem cells and corneal epithelial regeneration. Eye (London, England) 8 (Pt 2):170–183
Lavker RM, Tseng SC, Sun TT (2004) Corneal epithelial stem cells at the limbus: looking at some old problems from a new angle. Exp Eye Res 78:433–446
Meller D, Fuchsluger T, Pauklin M et al (2009) Ocular surface reconstruction in graft-versus-host disease with HLA-identical living-related allogeneic cultivated limbal epithelium after hematopoietic stem cell transplantation from the same donor. Cornea 28:233–236
Meller D, Kruse F (2001) Ex-vivo expansion of cornea stem cells. Experimental principles and initial clinical results. Ophthalmologe 98:811–817
Meller D, Pires RT, Tseng SC (2002) Ex vivo preservation and expansion of human limbal epithelial stem cells on amniotic membrane cultures. Br J Ophthalmol 86:463–471
Pauklin M, Kakkassery V, Steuhl KP et al (2009) Expression of membrane-associated mucins in limbal stem cell deficiency and after transplantation of cultivated limbal epithelium. Curr Eye Res 34:221–230
Pauklin M, Steuhl KP, Meller D (2009) Characterization of the corneal surface in limbal stem cell deficiency and after transplantation of cultivated limbal epithelium. Ophthalmology 116:1048–1056
Pauklin M, Steuhl KP, Meller D (2009) Limbal stem cell deficiency after chemical burns: investigations on the epithelial phenotype and inflammation status. Ophthalmologe 106:995–998
Pellegrini G, Traverso CE, Franzi AT et al (1997) Long-term restoration of damaged corneal surfaces with autologous cultivated corneal epithelium. Lancet 349:990–993
Puangsricharern V, Tseng SC (1995) Cytologic evidence of corneal diseases with limbal stem cell deficiency. Ophthalmology 102:1476–1485
Schermer A, Galvin S, Sun TT (1986) Differentiation-related expression of a major 64 K corneal keratin in vivo and in culture suggests limbal location of corneal epithelial stem cells. J Cell Biol 103:49–62
Shortt AJ, Secker GA, Notara MD et al (2007) Transplantation of ex vivo cultured limbal epithelial stem cells: a review of techniques and clinical results. Surv Ophthalmol 52:483–502
Thanos M, Pauklin M, Steuhl KP et al (2010) Ocular surface reconstruction with cultivated limbal epithelium in a patient with unilateral stem cell deficiency caused by epidermolysis bullosa dystrophica hallopeau-siemens. Cornea, in press
Thoft RA, Friend J (1983) The X, Y, Z hypothesis of corneal epithelial maintenance. Invest Ophthalmol Vis Sci 24:1442–1443
Tsai RJ, Li LM, Chen JK (2000) Reconstruction of damaged corneas by transplantation of autologous limbal epithelial cells. N Engl J Med 343:86–93
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Beide Autoren (DM, MK) haben gleichen Anteil an der Studie und sollten als Erstautoren gewertet werden.
Unterstützt mit Drittmitteln der estnischen Forschungsgemeinschaft (ETF Grant 5832); der Deutschen Ophthalmologischen Gesellschaft (DOG); der Deutschen Forschungsgemeinschaft (DFG, Bonn, ME 1623/3–1) und der Forschungsförderung AG Trockenes Auge (Berlin, Deutschland).
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Meller, D., Pauklin, M., Westekemper, H. et al. Autologe Transplantation von kultiviertem Limbusepithel. Ophthalmologe 107, 1133–1138 (2010). https://doi.org/10.1007/s00347-010-2205-9
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DOI: https://doi.org/10.1007/s00347-010-2205-9