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ABSTRACT: 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.
Der Ophthalmologe 09/2012; 109(9):843-9. · 0.62 Impact Factor
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ABSTRACT: 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.
Der Ophthalmologe 09/2012; 109(9):863-8. · 0.62 Impact Factor
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ABSTRACT: Eine Hornhautbank/Gewebebank muss über eine Organisationsstruktur verfügen, in der Verantwortlichkeiten und Weisungsbefugnisse
eindeutig definiert sind. Sie muss ein dokumentiertes Qualitätsmanagementsystem nach den Grundsätzen der „guten fachlichen
Praxis“ verwenden und dieses auf dem neuesten Stand halten. Das Personal der Hornhautbank/Gewebebank muss in ausreichender
Anzahl vorhanden und qualifiziert sein. Eine Hornhautbank/Gewebebank muss über geeignete Einrichtungen verfügen, die dem Zweck
der Gewinnung von kryokonservierter humaner Amnionmembran aus Spenderplazenta entsprechen. Sämtliche Ausrüstungen müssen entsprechend
ihres Verwendungszwecks gestaltet und gewartet werden. Abweichungen von den vorgeschriebenen Qualitäts- und Sicherheitsstandards
müssen zu dokumentierten Untersuchungen führen, die eine Entscheidung über mögliche Korrektur- und Präventivmaßnahmen einschließen.
Spendergewinnung und Gewebeentnahme müssen streng kontrolliert und dokumentiert werden. Dasselbe gilt für den Eingang der
Spendergewebe in der Hornhautbank/Gewebebank. Die Gewinnung einer kryokonservierten humanen Amnionmembran kann nur erfolgen,
wenn bei der Spenderin eine Sectio caesarea erfolgte und keine bekannte Infektion des physiologischerweise keimarmen Bauchraums
oder gar systemische Infektionen (Sepsis) vorliegen. Bei der Präparation/Konservierung ist mindestens eine Sterilitätsprüfung
einer Plazentaprobe im Konservierungsmittel durchzuführen. Es sind Maßnahmen zu ergreifen, um das Kontaminationsrisiko so
gering wie möglich zu halten. Die humane Amnionmembran, kryokonserviert, aus Spenderplazenta darf erst freigegeben werden,
wenn sie festgelegte Anforderungen erfüllt. Der Verdacht auf schwerwiegende unerwünschte Reaktionen und schwerwiegende Zwischenfälle
beim Empfänger eines Amnionmembrantransplantats ist der zuständigen Behörde zu melden. Die Tätigkeiten der Hornhautbank/Gewebebank
sind zeitnah an den wissenschaftlichen Fortschritt anzupassen.
A cornea/tissue bank must have an organizational structure in which responsibility and authority to issue directives are clearly
defined. It must also use a documented quality management system on the basis of good practice procedures which is maintained
to the current standards. The personnel of a cornea/tissue bank must be present in sufficient numbers and be suitably qualified.
A cornea/tissue bank must be in possession of appropriate facilities which are suitable for the main purpose of preparation
of cryopreserved human amniotic membranes from donor placentas. All equipment must be designed and maintained corresponding
to the intended purpose. Deviations from the stipulated quality and safety standards must give rise to documented investigations
which include decisions on options for correctional and preventive measures. Acquisition of donors and tissue sampling must
be strictly controlled and documented. This also applies to entry of donor tissue in the cornea/tissue bank. Cryopreserved
human amniotic membranes can only be preserved from donors undergoing caesarean section and who did not present any known
infection of the abdominal cavity or any systemic blood borne infection. Contamination of media used for cryopreservation
of donor placenta must be ruled out at least once. Measures must be taken to keep the risk of contamination as low as possible.
Cryopreserved human amniotic membranes from donor placentas can only be released if defined criteria are fulfilled. Any suspicion
of severe undesired reactions and events for the recipient of an amniotic membrane transplant must be registered with the
authorities. The activities of a cornea/tissue bank must maintain and adapt to the state-of-the-art with respect to scientific
progress.
SchlüsselworteGewebebanken-Amnionmembran-Spenderplazenta-Kryokonservierung-Gute fachliche Praxis
KeywordsTissue banks-Amniotic membrane-Donor placenta-Cryopreservation-Good practice procedures
Der Ophthalmologe 05/2012; 107(11):1020-1031. · 0.62 Impact Factor
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ABSTRACT: HintergrundIn dieser Studie soll die Wirksamkeit der Ex-vivo-Expansion von autologem Limbusepithel zur Oberflächenrekonstruktion bei
limbaler Stammzellinsuffizienz (LSZI) untersucht werden.
Patienten und MethodenBei 30Augen von 28Patienten (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 9Monaten wurden in die Studie eingeschlossen.
ErgebnisseDer Nachbeobachtungszeitraum betrug im Mittel 28,9±15,5Monate. Ein stabiles okuläres Oberflächenepithel wurde bei 23Augen
(76,7%) erzielt. Die Sehschärfe stieg bei 21Augen (70%) an, war stabil bei 8Augen (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.
DiskussionTransplantation 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.
ObjectiveIn 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 MethodsA total of 30eyes in 28patients (22male and 6female) 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).
ResultsThe 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.
ConclusionTransplantation 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.
SchlüsselworteLimbale Stammzellinsuffizienz-Ex-vivo-Expansion-Stammzellen-Hornhaut-Epithel
KeywordsLimbal stem cell deficiency-Ex vivo expansion-Stem cells-Cornea-Epithelium
Der Ophthalmologe 04/2012; 107(12):1133-1138. · 0.62 Impact Factor
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ABSTRACT: HintergrundBulbusverletzungen führen häufig zu einer dauerhaften Beeinträchtigung des Sehvermögens. Insbesondere bei Bulbusrupturen ist
die Chance, einen Visus >0,1 zu erreichen 50-mal geringer als nach Bulbuskontusion. Neben Netzhaut- und Aderhauttrauma kommt
dem Iris-Linsendiaphragma (ca. 10% Irisdefekte und 1% Aniridie nach stumpfer Verletzung) bei der visuellen Rehabilitation
eine häufig unterschätzte Rolle zu. Vor diesem Hintergrund wurden die operativen Ergebnisse nach Implantation von Aniridie-Intraokularlinsen
untersucht.
Patienten und Methoden11Patienten (41,9±19,6Jahre) mit Z.n. Bulbustrauma (3-mal Bulbusruptur, 8-mal penetrierende Bulbusverletzung mit Iris-Linsenbeteiligung)
wurden mit einem Aniridie-Implantat versorgt.
ErgebnisseDie Implantation der Aniridie-IOL erfolgte im Mittel 1,0±0,6Jahre (Spanne 0,4–2,3Jahre) nach der primären Wundversorgung.
Bei 10 Augen wurde eine Aniridie-IOL Modell HMK ANI 2 (Ophtec/Polytech), bei 1 Auge eine Aniridie-IOL Modell 67 (Morcher)
implantiert. Die postoperative Patientenzufriedenheit war hoch (korrigierter Visus im Mittel 0,48; 0,05–1,0). 63% der operierten
Augen erreichten einen Visus ≥0,4. Alle Patienten erfuhren eine Reduktion der präoperativ bestandenen Blendungsempfindlichkeit.
Die Inzidenz von Sekundärglaukomen wurde durch die Sekundärimplantation nicht erhöht. Ein Patient erlitt 3Monate nach Implantation
eine Netzhautablösung, die durch ppV und Gastamponade behoben werden konnte.
SchlussfolgerungBei Trauma-Augen mit partieller oder vollständiger Aniridie und gleichzeitig bestehender Aphakie erscheint die Implantation
von Aniridie-IOLs als eine therapeutische Option mit z.T. guter visueller Rehabilitation. Bei der postoperativen Verlaufskontrolle
ist auf ausreichende Tensionseinstellung und Ablatioprodromi zu achten.
BackgroundGlobe injuries frequently are the cause of permanent loss of visual function. Especially ruptures of the globe have a 50 times
lower chance of achieving a final visual acuity better than 20/200 as compared to contusions of the globe. Besides injury
to the retina and choroids, injury of the iris-lens diaphragm plays an important role for visual rehabilitation (10% iris
defects and 1% aniridia after blunt trauma). Against this background the surgical results after implantation of aniridia intraocular
lenses were investigated.
Patients and methodsEleven patients (41.9±19.6years of age) after globe injury (three ruptures of the globe, eight penetrating injuries with
trauma of the iris) were implanted with an aniridia IOL.
ResultsThe implantation of an aniridia IOL was performed on average 1.0±0.6years (range: 0.4–2.3years) after the primary injury.
In ten eyes an aniridia IOL model HMK ANI 2 (Ophtec/Polytech) was implanted and in one eye an aniridia IOL model 67 (Morcher).
Most patients were very satisfied with the results achieved (average corrected visual acuity 0.48; 0.05–1.0). Of the operated
eyes, 63% reached a visual acuity ≥0.4. All patients noticed a significant reduction in glare disability as compared to the
preoperative condition. The incidence of secondary glaucoma remained unchanged after the secondary implantation. One patient
demonstrated retinal detachment 3months after receiving the secondary implant, which was successfully treated with vitrectomy
and gas tamponade.
ConclusionsThe implantation of aniridia IOLs seems to be a beneficial therapeutic option in post-traumatic eyes with partial or complete
aniridia and aphakia with good visual recovery. During the postoperative follow-up special attention must be paid to sufficient
regulation of intraocular pressure and to the retinal situation.
Der Ophthalmologe 04/2012; 105(8):744-752. · 0.62 Impact Factor
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ABSTRACT: Die limbale Stammzellinsuffizienz (LSZI) ist klinisch durch die Bildung eines fibrovasculären Pannus auf der Hornhautoberfläche,
chronische Entzündung und Visusverlust gekennzeichnet. Ziel der Studie war es, das Pannusgewebe zu charakterisieren. Aus dem
Pannusgewebe bei LSZI aufgrund einer Verätzung wurden die RNS (n=6) und Gesamtproteine (n=3) isoliert. Normale Horn- und Bindehaut
(jeweils n=6) dienten als Kontrollgewebe. Die Expression von Markern zur Bestimmung des epithelialen Ursprungs (Keratin 3,
K3; Keratin 19, K19; Mucin 5AC, MUC5AC), Entzündungsmarkern (Interleukin-1β, IL-1β; „intercellular adhesion molecule 1“, ICAM-1)
und „vascular endothelial growth factor“ (VEGF) wurde mittels Western Blotting und/oder Real-Time-PCR untersucht. Normale
Hornhaut zeigte eine höhere Expression von K3, aber eine geringere Expression von K19 und MUC5AC, die charakteristischerweise
in der Bindehaut zu finden sind. Die Entzündungsmarker waren in der Bindehaut stärker exprimiert als in der Hornhaut. Das
untersuchte Pannusgewebe zeigte eine ähnliche Expression von Gewebemarkern wie die normale Bindehaut, aber eine höhere Expression
der meisten Entzündungsmarker als bei beiden Kontrollgeweben. Das Pannusgewebe bei LSZI ist durch einen bindehautähnlichen
Phänotyp und eine chronische Entzündung charakterisiert.
Limbal stem cell deficiency (LSCD) is clinically characterized by growth of fibrovascular pannus onto the corneal surface,
chronic inflammation and impaired visual acuity. The aim of this study was to characterize the pannus tissue. Total RNA was
isolated from six pannus samples and protein from three pannus samples from patients with LSCD caused by chemical burns. Normal
human corneal tissue (n=6) and conjunctiva (n=6) were used as control tissues. The expression of the epithelial lineage markers
keratin 3 (K3), K19 and MUC5AC, the inflammatory markers IL-1β, ICAM-1 and VEGF was analyzed by Western Blotting and/or real-time
PCR. Normal corneal tissue had a higher expression of K3 and a lower expression of K19 and MUC5AC in comparison to normal
conjunctiva. A higher expression of inflammatory markers was seen in conjunctiva compared to corneal tissue. The pannus tissue
showed a similar expression of lineage markers to conjunctiva but a higher expression of most inflammatory markers as compared
to both control tissues. The analyzed samples of pannus in LSCD resembled conjunctiva and not cornea and showed a high expression
of inflammatory markers indicating chronic inflammation.
Der Ophthalmologe 04/2012; 106(11):995-998. · 0.62 Impact Factor
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ABSTRACT: Die komplette Exzision mit tumorfreien Schnitträndern gilt sowohl bei der Therapie der Plattenepithelneoplasien als auch bei
der Behandlung melanozytärer Neoplasien der Bindehaut als Therapie der Wahl. Dennoch ist bei diffuser Ausdehnung oder großen
Tumoren eine komplette Exzision des Tumors im Gesunden nicht immer möglich. In diesem Fall sind alternative oder adjuvante
Therapiemethoden notwendig. Die topische Chemotherapie mit Mitomycin C (MMC) gewinnt hierbei immer mehr an Bedeutung; die
Vorteile bestehen vor allem in der guten Verträglichkeit und den geringen Nebenwirkungen.
Nach bisherigen Studienergebnissen stellt MMC bei Plattenepithelneoplasien der Bindehaut eine gute Therapieoption dar. Die
positiven Ergebnisse müssen jedoch in großen Multizenterstudien mit Langzeitnachbeobachtungen bestätigt werden.
Melanozytäre Tumore der Bindehaut scheinen nicht so gut auf MMC anzusprechen. Bei einer primär erworbenen Melanose (PAM; „primary
acquired melanosis“) kann MMC eine Therapieoption darstellen. Bei Verdacht auf ein malignes Melanom ist eine primäre Chemotherapie
mit MMC jedoch obsolet. Es sollte hier allenfalls adjuvant eingesetzt werden, da sonst keine ausreichende Tumorkontrolle gewährleistet
werden kann. Um die Wirksamkeit von MMC bei melanozytären Tumoren der Bindehaut abschließend bewerten zu können, sind weitere
größere prospektive Studien nötig.
Surgical excision with tumour free margins is the gold standard for squamous cell and melanocytic tumours of the conjunctiva.
In cases of diffuse and extensive tumours a complete surgical excision is sometimes not possible. Therefore, alternative or
adjuvant therapies are required. Topical chemotherapy with mitomycin C (MMC) is increasingly finding use in clinical practice.
MMC has several advantages such as good tolerability and mild side effects. Present studies have shown that mitomycin C is
a good option in squamous cell neoplasia of the conjunctiva. However, further multi-centre studies and long-term follow-up
are needed.
The results in treating melanocytic tumours of the conjunctiva with MMC are less convincing. MMC seems to be an option for
the treatment of primary acquired melanosis (PAM); but, if the tumour is suspicious for melanoma primary chemotherapy with
MMC is obsolete. In these cases MMC can only be used as an adjuvant therapy, otherwise tumour control is not assured. However,
prospective randomized controlled trials are necessary for a final evaluation of MMC therapy in melanocytic tumours of the
conjunctiva.
Der Ophthalmologe 04/2012; 105(8):777-784. · 0.62 Impact Factor
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ABSTRACT: In this article we discuss the complex diagnostic approaches and therapeutic options for the most important conjunctival malignancies. Conjunctival melanoma can be a diagnostic challenge as it can be difficult to distinguish from benign melanocytic conjunctival tumours. Complete surgical excision accompanied by a coherent adjuvant concept is the key for a curative therapy. Moderate and severe conjunctival intraepithelial neoplasias (CIN) are precancerous lesions and can progress to invasive squamous cell carcinoma. The involvement of large parts of the ocular surface can prevent an R 0-resection. Adjuvant therapeutic concepts are therefore especially important to gain tumour control and preserve the function of the affected eye. Lymphomas are the most common malignant primary tumours of the orbit and ocular adnexa. They can present as primary or secondary tumours of the conjunctiva, the lacrimal gland, the orbital fat, the eye lid or the lacrimal sac. The most common manifestation site of ocular MALT lymphoma is the conjunctiva with 20 - 33 % of all epibulbar lymphomas. More than 75 % of ocular lymphoma patients develop only one lymphomatous lesion. Immunophenotyping allows the exact differentiation between the lymphoma entities. Infectious agents (e.g., Chlamydia psittaci) seem to play a role in the pathogenesis. An overview over radiotherapeutic approaches that are conclusively applicable at the conjunctiva completes the article.
Klinische Monatsblätter für Augenheilkunde 04/2011; 228(9):780-92. · 0.51 Impact Factor
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ABSTRACT: Cryopreserved amniotic membrane (AM) is widely used in ophthalmology because of its anti-angiogenic, anti-inflammatory, and wound healing promoting capabilities. A common method to conserve the tissue is the storage in cryo-medium containing 50% glycerol at -80°C. The aim of this study was to examine the influence of storage time on the sterility as well as the histological and biological properties of cryopreserved AM.
Amniotic membrane from different donors was stored in cell culture media containing 50% glycerol for different time periods, on average 4 months (group 1), 15 months (group 2), and 24 months (group 3), at -80°C. Samples of the tissue and cryo-medium were examined for bacterial and fungal contamination. Tissue samples were incubated in 0.5 ml/cm(2) serum-free medium at 37°C. The medium was changed after 1, 2, and 3 days. The proteins released by AM were TCA-precipitated and the presence of the proteins TIMP-1 and IL-1ra was analyzed using Western blotting and semi quantified by means of image analysis. Integrity of the amniotic epithelium and the basement membrane components collagen IV, collagen VII, laminin, laminin 5, and fibronectin were examined by haematoxylin eosin stain and immunohistochemistry in cryosections of AM.
None of the examined samples showed bacterial or fungal contamination. The soluble proteins TIMP-1 and IL-1ra were found in all samples of medium incubated for all time periods. The examined proteins were detectable after one-day incubation but the staining signal diminished significantly in the second and third wash after 48 hr and 72 hr. Differences in the intensity of the Western blot signal between the three particular groups were statistically not significant. The epithelia of all samples were intact. The basement membranes of all samples showed a similar distribution of collagen IV, collagen VII, laminin, laminin 5, and fibronectin.
Long-term storage of amniotic membrane in cell culture media with 50% glycerol does not significantly impair sterility, histology, or biological properties of AM.
Current eye research 03/2011; 36(3):247-55. · 1.51 Impact Factor
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ABSTRACT: 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.
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).
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.
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.
Der Ophthalmologe 12/2010; 107(12):1133-8. · 0.62 Impact Factor
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ABSTRACT: A cornea/tissue bank must have an organizational structure in which responsibility and authority to issue directives are clearly defined. It must also use a documented quality management system on the basis of good practice procedures which is maintained to the current standards. The personnel of a cornea/tissue bank must be present in sufficient numbers and be suitably qualified. A cornea/tissue bank must be in possession of appropriate facilities which are suitable for the main purpose of preparation of cryopreserved human amniotic membranes from donor placentas. All equipment must be designed and maintained corresponding to the intended purpose. Deviations from the stipulated quality and safety standards must give rise to documented investigations which include decisions on options for correctional and preventive measures. Acquisition of donors and tissue sampling must be strictly controlled and documented. This also applies to entry of donor tissue in the cornea/tissue bank. Cryopreserved human amniotic membranes can only be preserved from donors undergoing caesarean section and who did not present any known infection of the abdominal cavity or any systemic blood borne infection. Contamination of media used for cryopreservation of donor placenta must be ruled out at least once. Measures must be taken to keep the risk of contamination as low as possible. Cryopreserved human amniotic membranes from donor placentas can only be released if defined criteria are fulfilled. Any suspicion of severe undesired reactions and events for the recipient of an amniotic membrane transplant must be registered with the authorities. The activities of a cornea/tissue bank must maintain and adapt to the state-of-the-art with respect to scientific progress.
Der Ophthalmologe 11/2010; 107(11):1020-31. · 0.62 Impact Factor
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[hide abstract]
ABSTRACT: Severe infectious corneal ulceration such as herpetic stromal keratitis commonly causes loss of vision and may lead to blindness. Treatment depending on the underlying disease includes antimicrobial medication and the development of surgical strategies to restore the integrity of the corneal ocular surface. Ulcerative herpetic stromal keratitis and/or neurotrophic keratopathy with the risk of corneal perforation are still clinically challenging conditions in ophthalmic surgery of the ocular surface. Since the introduction of newly developed preservation methods, amniotic membrane (AM) functioning as a basement membrane substitute has gained widespread popularity in ocular surface reconstruction. Various ways of clinical application such as the use of AM as a graft, patch or culture substrate and carrier system to expand ocular surface epithelia have been recently reported. In this article, the basis and clinical application of amniotic membrane transplantation for the management of corneal infections with Herpes simplex and Herpes zoster virus are reviewed.
Klinische Monatsblätter für Augenheilkunde 05/2010; 227(5):393-9. · 0.51 Impact Factor
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ABSTRACT: In chronic GVHD after BMT, the conjunctiva represents a target organ. GVHD can lead to severe inflammation and dry-eye syndrome (sicca syndrome). The molecular mechanisms are largely unknown. We examined the expression of chemokines in the conjunctiva in cases of chronic GVHD. In this study, we included 10 patients with chronic GVHD and 10 healthy controls. Clinical data were collected and tear film analysis and conjunctival cytology were carried out. Conjunctival biopsies were taken from all participants. Gene expression profiles of chemokines and their corresponding receptors were evaluated by means of quantitative real-time PCR. Chemokine protein expression was analysed by immunohistochemical analyses. Expressions of the Th1-associated chemokines, chemokine (C-X-C motif) ligand (CXCL) 9 (Mig), CXCL10 (IP-10), and their receptor chemokine (C-X-C motif) receptor 3 (CXCR3) were significantly increased in GVHD patients. Immunohistochemical analysis confirmed marked expression of the inflammatory CXCR3 ligands. A total of six patients had a moderate or severe sicca syndrome. Impression cytology revealed a mild keratinisation, moderate keratinisation or severe squamous metaplasia in three patients, respectively. Chronic GVHD of the conjunctiva is characterised by the expression of Th1-associated chemokines. Taken together, our results confirm that the conjunctiva is a target organ in this T cell-mediated process and add to molecular understanding of conjunctival GVHD.
Bone marrow transplantation 02/2010; 45(8):1340-6. · 3.00 Impact Factor
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[hide abstract]
ABSTRACT: Limbal stem cell deficiency (LSCD) is clinically characterized by growth of fibrovascular pannus onto the corneal surface, chronic inflammation and impaired visual acuity. The aim of this study was to characterize the pannus tissue. Total RNA was isolated from six pannus samples and protein from three pannus samples from patients with LSCD caused by chemical burns. Normal human corneal tissue (n=6) and conjunctiva (n=6) were used as control tissues. The expression of the epithelial lineage markers keratin 3 (K3), K19 and MUC5AC, the inflammatory markers IL-1beta, ICAM-1 and VEGF was analyzed by Western Blotting and/or real-time PCR. Normal corneal tissue had a higher expression of K3 and a lower expression of K19 and MUC5AC in comparison to normal conjunctiva. A higher expression of inflammatory markers was seen in conjunctiva compared to corneal tissue. The pannus tissue showed a similar expression of lineage markers to conjunctiva but a higher expression of most inflammatory markers as compared to both control tissues. The analyzed samples of pannus in LSCD resembled conjunctiva and not cornea and showed a high expression of inflammatory markers indicating chronic inflammation.
Der Ophthalmologe 02/2009; 106(11):995-8. · 0.62 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: Surgical excision with tumour free margins is the gold standard for squamous cell and melanocytic tumours of the conjunctiva. In cases of diffuse and extensive tumours a complete surgical excision is sometimes not possible. Therefore, alternative or adjuvant therapies are required. Topical chemotherapy with mitomycin C (MMC) is increasingly finding use in clinical practice. MMC has several advantages such as good tolerability and mild side effects. Present studies have shown that mitomycin C is a good option in squamous cell neoplasia of the conjunctiva. However, further multi-centre studies and long-term follow-up are needed.The results in treating melanocytic tumours of the conjunctiva with MMC are less convincing. MMC seems to be an option for the treatment of primary acquired melanosis (PAM); but, if the tumour is suspicious for melanoma primary chemotherapy with MMC is obsolete. In these cases MMC can only be used as an adjuvant therapy, otherwise tumour control is not assured. However, prospective randomized controlled trials are necessary for a final evaluation of MMC therapy in melanocytic tumours of the conjunctiva.
Der Ophthalmologe 08/2008; 105(8):777-84. · 0.62 Impact Factor
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ABSTRACT: BACKGROUND: Globe injuries are frequently the cause of permanent loss of visual function. In particular, globe ruptures have a 50 times lower chance of achieving final visual acuity better than 20/200 compared with globe contusions. Besides injury to the retina and choroid, injury of the iris-lens diaphragm plays an important role in visual rehabilitation (10% iris defects and 1% aniridia after blunt trauma). Considering this background, the surgical results after implantation of aniridia intraocular lenses (IOLs) were investigated. PATIENTS AND METHODS: Eleven patients (41.9+/-19.6 years of age) were implanted with an aniridia IOL after globe injury (rupture of the globe in three, penetrating injury with iris trauma in eight). RESULTS: The implantation was performed an average of 1.0+/-0.6 years (range 0.4-2.3 years) after the primary injury. An aniridia IOL model HMK ANI 2 (Ophtec/Polytech) was implanted in 10 eyes and an aniridia IOL model 67 (Morcher) in one eye. Most patients were very satisfied with the achieved results (average corrected visual acuity 0.48 [0.05-1.0]). Sixty-three percent of operated eyes reached a visual acuity of 0.4. All patients noticed a significant reduction in glare disability compared with their preoperative condition. The incidence of secondary glaucoma remained unchanged after the secondary implantation. One patient demonstrated retinal detachment 3 months after receiving the secondary implant, which was successfully treated with vitrectomy and gas tamponade. CONCLUSION: Implantation of aniridia IOLs seems to be a beneficial therapeutic option in posttraumatic eyes with partial or complete aniridia and aphakia with good visual recovery. During the postoperative follow-up, special attention must be paid to sufficient regulation of intraocular pressure and the retinal situation.
Der Ophthalmologe 05/2008; · 0.62 Impact Factor
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ABSTRACT: In cases of large, diffuse or multilocular growth pattern of conjunctival melanoma, proton beam irradiation can serve as an alternative therapy to exenteration. In extended tumours, ocular surface problems can result after therapy. In this study we examined ocular surface integrity of ten patients who underwent proton beam radiation between 1996 and 2002.
The patients were examined during their follow-up. Eight of the ten cases who underwent proton radiotherapy were recurrent tumours, which were previously treated with other adjuvant therapies. We performed a standard ophthalmological examination and detailed tear film diagnostics.
The follow-up was 17-87 months (mean: 40.9+/-20.1). In six cases more than 50% of the upper and lower eyelids were included in the radiation field. All of these cases showed moderate to severe sicca symptoms. The impression cytology revealed squamous metaplasia of conjunctival cells in nine of ten cases.
Squamous metaplasia of conjunctival epithelia indicates a radiogenic, persisting disturbance of differentiation of the conjunctival epithelial cells. The tear film instability correlates with the loss of mucin-secreting goblet cells and meibomian gland dysfunction.
Der Ophthalmologe 08/2006; 103(7):588-95. · 0.62 Impact Factor
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ABSTRACT: The aim of this study was to evaluate the role of topical interferon-alpha-2b in the adjuvant treatment of corneal and conjunctival tumors.
In this noncomparative, prospective, interventional case series, five patients with histologically proven conjunctival intraepithelial neoplasia (CIN) after primary excision and amniotic membrane transplantation were treated with interferon (IFN)-alpha-2b eye drops five times daily over a period of 6 weeks (1 million IU/ml Intron A, Schering). An in situ hybridization technique was used to detect human papillomavirus (HPV) in all specimens. Frequent follow-up was undertaken clinically and photographically for evidence of tumor recurrence.
In the follow-up period (13.2+/-4,97 months) no clinical evidence of recurrence with only limited treatment side effects such as mild conjunctival hyperemia were recorded after 6 weeks of interferon. In one CIN specimen HPV 16/18 could be detected.
The combination of excisional biopsy and topical interferon-alpha-2b application seems to be an effective and safe treatment for conjunctival intraepithelial neoplasias. Therefore, we prefer this combined treatment to topical interferon-alpha-2b treatment alone, more destructive approaches such as radiation and cryotherapy, or treatment with antimetabolites such as 5-fluorouracil or mitomycin C.
Der Ophthalmologe 03/2006; 103(2):124-8. · 0.62 Impact Factor
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ABSTRACT: HintergrundBei groflchiger, diffuser oder multilokulrer Ausdehnung des Bindehautmelanoms kann die Protonenbestrahlung bei bestimmten Indikationen eine mgliche Alternative zur Exenteratio darstellen. Bei ausgedehnten Tumoren kann es in der Folge zu Problemen der Augenoberflche und der Trnenproduktion kommen. In dieser Studie untersuchten wir die Beschaffenheit der Augenoberflche von 10Patienten, die zwischen 1996 und 2002 mit Protonen behandelt worden waren.MethodeDie Patienten wurden im Rahmen der Nachbeobachtung untersucht. Dabei waren 8 der 10 durch Protonenbestrahlung behandelten Flle Melanomrezidive, die zuvor bereits adjuvant vorbehandelt worden waren. Neben der ophthalmologischen Grunduntersuchung wurde eine ausfhrliche Trnenfilmdiagnostik und Analyse der okulren Oberflche durchgefhrt.ErgebnisseDer Nachbeobachtungszeitraum betrug 17 bis 87Monate (Mittel 40,920,1). Bei 6Patienten wurden mehr als 50% des Ober- und Unterlids in das Strahlenfeld eingeschlossen. Bei diesen lag in allen Fllen eine mittlere bis schwere Sicca-Symptomatik vor. Die Impressionszytologie der Bindehaut zeigte eine squamse Metaplasie in 9 von 10Fllen.SchlussfolgerungenDie squamse Metaplasie der konjunktivalen Epithelien deutet auf eine radiogene, dauerhafte Differenzierungsstrung der konjunktivalen Zellverbnde hin. Die Trnenfilminstabilitt korreliert mit dem Verlust von muzinbildenden Becherzellen und der Atrophie von Meibomschen Drsen.BackgroundIn cases of large, diffuse or multilocular growth pattern of conjunctival melanoma, proton beam irradiation can serve as an alternative therapy to exenteration. In extended tumours, ocular surface problems can result after therapy. In this study we examined ocular surface integrity of ten patients who underwent proton beam radiation between 1996 and 2002.MethodsThe patients were examined during their follow-up. Eight of the ten cases who underwent proton radiotherapy were recurrent tumours, which were previously treated with other adjuvant therapies. We performed a standard ophthalmological examination and detailed tear film diagnostics.ResultsThe follow-up was 17–87months (mean: 40.920.1). In six cases more than 50% of the upper and lower eyelids were included in the radiation field. All of these cases showed moderate to severe sicca symptoms. The impression cytology revealed squamous metaplasia of conjunctival cells in nine of ten cases.ConclusionsSquamous metaplasia of conjunctival epithelia indicates a radiogenic, persisting disturbance of differentiation of the conjunctival epithelial cells. The tear film instability correlates with the loss of mucin-secreting goblet cells and meibomian gland dysfunction.
Der Ophthalmologe 01/2006; 103(7):588-595. · 0.62 Impact Factor
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ABSTRACT: Neurotrophic keratopathy is a degenerative affection of the cornea caused by impairment of corneal sensitivity and represents a therapeutic challenge for ophthalmologists. The present article concentrates on the etiology, pathogenesis, diagnosis, therapeutic aspects and future therapeutic models for treating neurotrophic keratopathy and will present a case report: Also we evaluate the effects of autologous serum eye drops in bilateral LASIK-induced neurotrophic keratopathy with epithelial breakdown revealed by positive fluorescence and rose bengal staining and reduced tear film break-up time.
We treated a 42-year-old patient with post-LASIK neurotrophic keratopathy and tear film instability with autologous serum eye drops (5 x daily) and emulsion eye drops (Refresh Endura, Allergan, Irvine, CA, USA) after insertion of punctal plugs.
Stabilization of vision, healing of the epithelium and reduction of the previously experienced symptoms like redness, itching and burning were achieved within 6 weeks. 10 months after changing therapy, the patient only complained about slight pain during lid movement.
Severe denervation after bilateral LASIK disrupts ocular tear film dynamics and causes irritation symptoms of the ocular surface. Autologous serum eye drops may be an effective treatment of severe epithelial breakdown and be helpful to reestablish the disturbed ocular surface integrity, as shown by negative vital staining. Therefore, autologous serum eye drops represent a significant approach in the therapy of LASIK-induced severe dry eye and associated pain.
Klinische Monatsblätter für Augenheilkunde 12/2005; 222(11):901-4. · 0.51 Impact Factor
