Steuhl Kp

Amniotic membrane transplantation for acute chemical or thermal burns

PURPOSE To determine whether preserved human amniotic membrane (AM) can be used to treat ocular burns in the acute stage. DESIGN Prospective, noncomparative, interventional case series. PARTICIPANTS Thirteen eyes from 11 patients with acute burns, 10 eyes with chemical burns and 3 with thermal burns of grades II-III (7 eyes) and grade IV (6 eyes), treated at 7 different facilities. METHODS Patients received amniotic membrane transplantation (AMT) within 2 weeks after the injury. MAIN OUTCOME MEASURES Integrity of ocular surface epithelium and visual acuity during 9 months of follow-up. RESULTS Ten patients were male and one patient was female; most were young (38.2 +/- 10.6 years). For a follow-up of 8.8 + 4.7 months, 11 of 13 eyes (84.63%) showed epithelialization within 2 to 5 weeks (23.7 +/- 9.8 days), and final visual acuity improved > or = 6 lines (6 eyes), 4 to 5 lines (2 eyes), and 1 to 3 lines (2 eyes); only one eye experienced a symblepharon. Eyes with burns of grade II to III showed more visual improvement (7.3 +/- 3 lines) than those with burns of grade IV (2.3 +/- 3.0 lines; P < 0.05, unpaired t test). In the group with grade II or III burns, none had limbal stem cell deficiency. All eyes in the group with grade IV burns did experience limbal stem cell deficiency. CONCLUSIONS Amniotic membrane transplantation is effective in promoting re-epithelialization and reducing inflammation, thus preventing scarring sequelae in the late stage. In mild to moderate burns, AMT alone rapidly restores both corneal and conjunctival surfaces. In severe burns, however, it restores the conjunctival ocular surface without debilitating symblepharon and reduces limbal stromal inflammation, but does not prevent limbal stem cell deficiency, which requires further limbal stem cell transplantation. These results underscore the importance of immediate intervention in the acute stage of eyes with severely damaged ocular surface. Further prospective randomized studies including a control group are required to determine the effectiveness of AMT in acute chemical and thermal burns of the eye.

Primary extraskeletal mesenchymal chondrosarcoma of the lid

A 15-year-old girl presented with a painless nodule in the nasal lower-lid portion of the left eye at the beginning of 1989. The tumor was excised in March 1989, and the histopathologic diagnosis was — erroneously — a chondromatous choristoma of the lid. The tumor recurred within several weeks. Another excision was performed, which led to the diagnosis of a malignant mesenchymal chondrosarcoma of the lid. Histopathology revealed the typical bimorphic pattern, with well-differentiated chondrocytes being surrounded by small anaplastic cells. The tumor cells stained positive for S100-protein and vimentin, were negative for cytokeratin and were studied ultrastructurally. Radical excision and adjuvant chemotherapy were performed in our patient; at 18 months after the onset of tumor growth, she is free of local or general tumor recurrence. To our knowledge, primary mesenchymal chondrosarcoma has not previously been described in the lid area.

[Ocular surface reconstruction in limbal stem cell deficiency : Transplantation of cultivated limbal epithelium].

Various ocular surface diseases are caused by loss of corneal epithelial stem cells or dysfunction of the limbal stem cell niche. Besides conventional transplantation of autologous or allogenic limbal tissue, recent advances in tissue engineering have led to the development of new culture and expansion techniques of human limbal stem and progenitor cells (LSPC) as a new strategy to successfully treat limbal stem cell deficiency (LSCD). From a small autologous limbal biopsy with a limited amount of LSPC an epithelium ready for transplantation is achieved. Autologous grafting of cultured limbal epithelium led in most of the treated cases to a successful reconstruction of the corneal surface. Alternative methods which have recently been introduced to treat LSCD use other stem cell sources including the transplantation of oral mucosal epithelium. In this article the challenges and controversies associated with these stem cell culture techniques for ocular surface reconstruction are reviewed.

New Nanofibrous Scaffold for Corneal Tissue Engineering

BACKGROUND An estimated 10 million people suffer worldwide from vision loss caused by corneal damage. For the worst cases, the only available treatment is transplantation with human donor corneal tissue. However, in numerous countries there is a considerable shortage of corneal tissue of good quality, leading to various efforts to develop tissue substitutes. The present study aims to introduce a nanofibrous scaffold of poly(glycerol sebacate) PGS as a biodegradable implant, for the corneal tissue engineering. MATERIALS AND METHODS Nanofibrous scaffolds were produced from PGS and poly(ε-caprolactone) (PCL) by a modified electro-spinning process. The biocompatibility of the material was tested in vitro by colorimetric MTT assay on days 3, 5, and 7 to test the cell viability of human corneal endothelium cells (HCEC). To examine a potential immunological reaction of the scaffolds, samples were exposed to mononuclear cells derived from peripheral blood (PBMCs). After an incubation period of 3 days, supernatants were assayed for apoptotic assessment and immunogenic potentials by annexin V FITC//propidium iodide and flow-cytometric analysis. RESULTS We could successfully demonstrate that cultivation of HCECs on PGS/PCL scaffolds was possible. Compared to day 3, cell density determined by microplate absorbance was significantly higher after 7 days of cultivation (p < 0.0001). According to the MTT data, none of the samples showed toxicity. Apoptotic assessments by FACS analysis showed that no composition stimulated apoptosis or activated PBMCs occurred. All the compositions were inert for native as well as activated T/B/NK cells and monocytes. It can be concluded that leukocytes and their activity was not affected by the scaffolds. CONCLUSION A tissue-like scaffold mimicking the human stroma could be developed. The results indicate that PGS/PCL scaffolds could be considered as ideal candidates for corneal tissue engineering as they are biocompatible in contact to corneal endothelial cells and blood cells.

Biologische Grundlagen der Limbusstammzellinsuffizienz

Limbal stem cell deficiency results from the loss of tissue regenerating stem and progenitor cells. Corneal epithelial regeneration is maintained by stem and progenitor cells which reside in the schlerocorneal limbus. They possess stem cell characteristics and can be stimulated to proliferate by external signals. The limbus is the stem cell niche for corneal epithelial stem cells and forms a unique microenvironment in which stem cell characteristics are conserved. Regulation of limbal epithelial stem cells is produced by a network of signals within the niche which governs cell fate decisions with regards to proliferation, differentiation or maintenance of a quiescent status.ZusammenfassungLimbustammzellinsuffizienz entsteht durch den Verlust der Population geweberegenerierender Stammzellen. Die Regeneration des kornealen Epithels erfolgt durch epitheliale Stamm- und Vorläuferzellen (SPZs), die im korneoskleralen Limbus lokalisiert sind. Sie besitzen eine Reihe von Stammzelleigenschaften und sind in der Lage, durch externe Signale zur Proliferation angeregt zu werden. Der Limbus ist die Stammzellnische der SPZs. Er formt eine Mikroumgebung, in der die Stammzelleigenschaften der SPZs erhalten bleiben. Die Regulation der limbalen SPZs erfolgt durch ein Netzwerk verschiedener Signale innerhalb der Nische, das über Proliferation, Differenzierung oder Quieszenz der SPZs entscheidet.AbstractLimbal stem cell deficiency results from the loss of tissue regenerating stem and progenitor cells. Corneal epithelial regeneration is maintained by stem and progenitor cells which reside in the schlerocorneal limbus. They possess stem cell characteristics and can be stimulated to proliferate by external signals. The limbus is the stem cell niche for corneal epithelial stem cells and forms a unique microenvironment in which stem cell characteristics are conserved. Regulation of limbal epithelial stem cells is produced by a network of signals within the niche which governs cell fate decisions with regards to proliferation, differentiation or maintenance of a quiescent status.

Langzeitergebnisse zur autologen Transplantation von ex vivo kultiviertem Limbusepithel bei limbaler Stammzellinsuffizienz

OBJECTIVE This study reports the long-term clinical outcome of autologous limbal epithelial cells cultivated ex vivo on intact amniotic membranes (AM) for ocular surface reconstruction in limbal stem cell deficiency (LSCD). PATIENTS AND METHODS A total of 61 eyes from 57 patients (46 males and 11 females) with LSCD were treated by transplantation of autologous limbal epithelial cells cultivated on intact AM. The etiology of the LSCD was chemical and thermal burns (n = 34), recurrent or primary large-sized pterygium (n = 12), mitomycin C and tumor excision-induced LSCD (n = 9), severe infectious keratitis (n = 3), perforating injury, epidermolysis bullosa and contact lens-associated keratopathy (each n = 1). Only eyes with a follow-up time of at least 12 months were included in the analysis. The main outcome end points were restoration of ocular surface integrity and improvement of visual acuity (VA). RESULTS The mean follow-up time was 50.8 ± 32.7 months. An entirely stable corneal surface was reconstructed in 46 (75.4%) eyes. Visual acuity significantly increased in 40 (65.6 %) eyes, was stable in 12 (19.7%) eyes and decreased in 9 eyes (14.8%). The mean visual acuity significantly increased (p < 0.0001) from 1.4 ± 0.91 LogMAR preoperatively to 0.8± 0.67 LogMAR postoperatively. CONCLUSION Transplantation of limbal epithelium cultivated ex vivo on intact AM leads to restoration of a stable corneal surface and resulted in a significant increase of visual acuity in most cases of LSCD. Autologous transplantation of cultivated limbal epithelium showed an excellent prognosis and outcome after long-term follow-up.

The biological basis of limbal stem cell deficiency

Limbal stem cell deficiency results from the loss of tissue regenerating stem and progenitor cells. Corneal epithelial regeneration is maintained by stem and progenitor cells which reside in the schlerocorneal limbus. They possess stem cell characteristics and can be stimulated to proliferate by external signals. The limbus is the stem cell niche for corneal epithelial stem cells and forms a unique microenvironment in which stem cell characteristics are conserved. Regulation of limbal epithelial stem cells is produced by a network of signals within the niche which governs cell fate decisions with regards to proliferation, differentiation or maintenance of a quiescent status.ZusammenfassungLimbustammzellinsuffizienz entsteht durch den Verlust der Population geweberegenerierender Stammzellen. Die Regeneration des kornealen Epithels erfolgt durch epitheliale Stamm- und Vorläuferzellen (SPZs), die im korneoskleralen Limbus lokalisiert sind. Sie besitzen eine Reihe von Stammzelleigenschaften und sind in der Lage, durch externe Signale zur Proliferation angeregt zu werden. Der Limbus ist die Stammzellnische der SPZs. Er formt eine Mikroumgebung, in der die Stammzelleigenschaften der SPZs erhalten bleiben. Die Regulation der limbalen SPZs erfolgt durch ein Netzwerk verschiedener Signale innerhalb der Nische, das über Proliferation, Differenzierung oder Quieszenz der SPZs entscheidet.AbstractLimbal stem cell deficiency results from the loss of tissue regenerating stem and progenitor cells. Corneal epithelial regeneration is maintained by stem and progenitor cells which reside in the schlerocorneal limbus. They possess stem cell characteristics and can be stimulated to proliferate by external signals. The limbus is the stem cell niche for corneal epithelial stem cells and forms a unique microenvironment in which stem cell characteristics are conserved. Regulation of limbal epithelial stem cells is produced by a network of signals within the niche which governs cell fate decisions with regards to proliferation, differentiation or maintenance of a quiescent status.

[Long-term results of autologous transplantation of limbal epithelium cultivated ex vivo for limbal stem cell deficiency].

OBJECTIVE This study reports the long-term clinical outcome of autologous limbal epithelial cells cultivated ex vivo on intact amniotic membranes (AM) for ocular surface reconstruction in limbal stem cell deficiency (LSCD). PATIENTS AND METHODS A total of 61 eyes from 57 patients (46 males and 11 females) with LSCD were treated by transplantation of autologous limbal epithelial cells cultivated on intact AM. The etiology of the LSCD was chemical and thermal burns (n = 34), recurrent or primary large-sized pterygium (n = 12), mitomycin C and tumor excision-induced LSCD (n = 9), severe infectious keratitis (n = 3), perforating injury, epidermolysis bullosa and contact lens-associated keratopathy (each n = 1). Only eyes with a follow-up time of at least 12 months were included in the analysis. The main outcome end points were restoration of ocular surface integrity and improvement of visual acuity (VA). RESULTS The mean follow-up time was 50.8 ± 32.7 months. An entirely stable corneal surface was reconstructed in 46 (75.4%) eyes. Visual acuity significantly increased in 40 (65.6 %) eyes, was stable in 12 (19.7%) eyes and decreased in 9 eyes (14.8%). The mean visual acuity significantly increased (p < 0.0001) from 1.4 ± 0.91 LogMAR preoperatively to 0.8± 0.67 LogMAR postoperatively. CONCLUSION Transplantation of limbal epithelium cultivated ex vivo on intact AM leads to restoration of a stable corneal surface and resulted in a significant increase of visual acuity in most cases of LSCD. Autologous transplantation of cultivated limbal epithelium showed an excellent prognosis and outcome after long-term follow-up.

Kurz- und Langzeitkomplikationen nach Transplantation von kultiviertem Limbusepithel

ZusammenfassungDie in den letzten Jahren erzielten Fortschritte im Tissue-Engineering ermöglichen die Rekonstruktion des okulären Oberflächenepithels. Grenzen und Möglichkeiten der Kultivierung von Limbusepithel als auch Kurz- und Langzeitkomplikationen nach Ex-vivo-Expansion von Limbusepithel zur Behandlung der limbalen Stammzellinsuffizienz werden in dieser Übersichtsarbeit dargestellt.AbstractRecent advances in tissue engineering have facilitated the development of new strategies in ocular surface reconstruction. Limitations and possibilities of ex vivo cultivation and limbal epithelium cell culture techniques as well as the short and long-term complications after transplantation of ex vivo expansion of cultivated limbal epithelium for the treatment of limbal stem cell deficiency are summarized in this review.Recent advances in tissue engineering have facilitated the development of new strategies in ocular surface reconstruction. Limitations and possibilities of ex vivo cultivation and limbal epithelium cell culture techniques as well as the short and long-term complications after transplantation of ex vivo expansion of cultivated limbal epithelium for the treatment of limbal stem cell deficiency are summarized in this review.

Wechselwirkungen zwischen Auge, Körper und Tumor (paraneoplastische Syndrome im weiteren Sinne)

ZusammenfassungIn einer Übersicht wird auf die diversen Interaktionen von Auge, Körper und Tumor eingegangen. Besondere Berücksichtigung finden dabei paraneoplastische okuläre Neuropathien, tumorbedingte Veränderungen des Immunsystems und die Metastasierung vom und zum Auge. Die Problematik der Zweittumorentwicklung wird angesprochen.SummaryA review of the different interactions between eye, body and tumor is given. Special regard is put on paraneoplastic ocular neuropathies, tumor-induced changes of the immune system and metastases. The problem of developing second tumors is discussed.