T. Lapp

[Old immune system- new information? Importance of mononuclear phagocytes in corneal allograft rejection].

Mononuclear phagocytes are derived from bone marrow precursor cells and are part of the innate immune system. These cells circulate in the blood as monocytes but differentiate in the peripheral circulation into tissue macrophages and dendritic cells under the influence of various cytokines. In addition to antimicrobial properties, macrophages also participate in wound healing; however, they also support degenerative and inflammatory processes. In cases of acute corneal allograft rejection, mononuclear cells initially form the main component of the cellular anterior chamber infiltrate. How monocytes are recruited into the anterior chamber is currently uncertain. Furthermore, no information is available about the possible cytotoxic effects on corneal endothelial cells. Gaining insight into these mechanisms may lead to potential pharmacological interventions.ZusammenfassungZellen des mononukleären phagozytären Systems entstammen Vorläuferzellen des Knochenmarks und sind ein Teil des angeborenen Immunsystems. Während sie im Blut noch als Monozyten zirkulieren, differenzieren sie sich in der Peripherie unter dem Einfluss verschiedener Zytokine in gewebeständige Makrophagen und dendritische Zellen. Neben antimikrobiellen Fähigkeiten sind Makrophagen auch an Wundheilungsprozessen beteiligt. Sie unterhalten allerdings auch degenerative und inflammatorische Prozesse. Im Fall einer akuten allogenen Hornhauttransplantatabstoßung bilden mononukleäre Zellen den Hauptteil des zellulären Vorderkammerinfiltrates. Hinsichtlich ihrer Funktion bei kornealen Abstoßungsreaktionen, der verschiedenen Wege ihrer Rekrutierung in die Vorderkammer, evtl. zytotoxischer Effekte auf korneale Endothelzellen sowie pharmakologischer Interventionsmöglichkeiten ist der derzeitige Kenntnisstand unzureichend.AbstractMononuclear phagocytes are derived from bone marrow precursor cells and are part of the innate immune system. These cells circulate in the blood as monocytes but differentiate in the peripheral circulation into tissue macrophages and dendritic cells under the influence of various cytokines. In addition to antimicrobial properties, macrophages also participate in wound healing; however, they also support degenerative and inflammatory processes. In cases of acute corneal allograft rejection, mononuclear cells initially form the main component of the cellular anterior chamber infiltrate. How monocytes are recruited into the anterior chamber is currently uncertain. Furthermore, no information is available about the possible cytotoxic effects on corneal endothelial cells. Gaining insight into these mechanisms may lead to potential pharmacological interventions.

Immunosuppressives to prevent rejection reactions after allogeneic corneal transplantation

In order to prevent rejection of an allogeneic corneal transplant after perforating (high risk) keratoplasty, active agents from different classes of pharmacological substances are used, as with solid organ transplantation. In addition to glucocorticoids, antiproliferative agents, small molecule inhibitors and antibodies, those belonging to the group of macrolides with their many derivatives represent an interesting class of substances in this context. As a supplement to cyclosporin A (CSA) the most successful macrolide in transplantation medicine, animal experiments are currently being carried out to test newer macrolide derivatives, such as sanglifehrin A (SFA). This overview describes the classes of drugs and modes of action of currently administered standard medications in the clinical routine and new developments are presented.

Immunsuppressiva zur Verhinderung von Abstoßungsreaktionen nach allogenen Hornhauttransplantationen

In order to prevent rejection of an allogeneic corneal transplant after perforating (high risk) keratoplasty, active agents from different classes of pharmacological substances are used, as with solid organ transplantation. In addition to glucocorticoids, antiproliferative agents, small molecule inhibitors and antibodies, those belonging to the group of macrolides with their many derivatives represent an interesting class of substances in this context. As a supplement to cyclosporin A (CSA) the most successful macrolide in transplantation medicine, animal experiments are currently being carried out to test newer macrolide derivatives, such as sanglifehrin A (SFA). This overview describes the classes of drugs and modes of action of currently administered standard medications in the clinical routine and new developments are presented.

Human leukocyte antigen (HLA) system in ophthalmology

Various inflammatory and non-inflammatory eye diseases are associated with specific HLA isotypes. Therefore, HLA isotyping can be a useful diagnostic tool for these diseases and has already been shown to reduce the rejection rate of corneal allografts. Unfortunately, the volume of published data and the varying quality of these publications complicate obtaining good overview in this field. This review briefly summarizes the genetic structure of the HLA system and elucidates differences between HLA classes I and II in the context of antigen presentation. Possible mechanisms of HLA associations in the field of ophthalmology are discussed, and finally different tools (e.g. genome wide association studies) for assessing associations of HLA isotypes with different ocular diseases are examined.

Pathophysiologie der atopischen Blepharokeratokonjunktivitis

ZusammenfassungDie atopische Dermatitis (AD, syn.: atopisches Ekzem, Neurodermitis) ist eine zum Formenkreis der atopischen Erkrankungen gehörende, chronisch persistierende oder chronisch rezidivierende, inflammatorische Systemerkrankung, die insbesondere mit einem unterschiedlich stark ausgeprägten Ekzem und Pruritus einhergeht. Neben dem möglichen Befall des gesamten Integuments findet sich häufig auch eine Beteiligung der periokulären Lidhaut sowie der Augenoberfläche. Ein okulärer Befund kann auch ohne Beteiligung der Gesichts- oder Körperhaut auftreten. Pathophysiologisch stehen neben einer Fehlregulation des Immunsystems genetische Veränderungen in verschiedenen dermalen Strukturproteinen im Vordergrund, die zu einer gestörten Hautbarriere führen. Zusätzlich bestehen regelhaft eine gehäufte Kolonisation mit bakteriellen Erregern und eine erhöhte Anfälligkeit für virale Infektionen der Haut. An den Lidern und auf der Augenoberfläche kommt es zu einem Verlust von Meibomdrüsen und Becherzellen. Konsekutiv bilden sich Augenoberflächendefekte und rezidivierende Binde- und Hornhautinfekte. Eine erhöhte mechanische Manipulation bei Atopie-assoziiertem Pruritus wird als Ursache für die erhöhte Komorbidität mit Keratokonus gesehen. Zudem liegen Einzelfallberichte über verschiedene Malignome der Augenoberfläche bei Atopikern vor. Das Verstehen der pathophysiologischen Zusammenhänge ist essenziell für eine korrekte Diagnostik und Therapie dieses klinisch sehr komplexen Krankheitsbildes.AbstractAtopic dermatitis (AD) is a systemic inflammatory disease, which is characterized by pronounced eczema and pruritus. In addition to the involvement of the entire integument, the periocular lid skin and the surface of the eye are frequently involved. Ocular involvement may occur solely without dermatitis of facial or body skin. Pathophysiologically, besides a dysregulated immune response, genetic changes can occur in various dermal structural proteins which will lead to a disturbed skin barrier. Furthermore, there is a regular colonization with bacterial pathogens and an increased susceptibility for viral skin infections. The lid margin reveals a loss of Meibomian glands whereas the conjunctiva shows reduced goblet cells. Consecutively, eye surface defects and recurrent conjunctival and corneal defects can be found. Increased mechanical manipulation in atopia-associated pruritus is seen as a cause of increased comorbidity with keratoconus. In addition, individual cases are reported of various malignomas of the eye surface, which are present in patients with AD. Understanding of the pathophysiological connections is essential for the correct diagnosis and therapy of this clinically very complex disease picture.

Augenbeteiligung bei atopischer Dermatitis@@@Ocular involvement in atopic dermatitis: Klinik und Therapie@@@Clinical aspects and therapy

Patients with atopic dermatitis frequently complain of ocular symptoms. The general dermatitis can directly affect the periocular skin and patients often present with chronic atopic blepharokeratoconjunctivitis. Early diagnosis of the characteristic ophthalmological alterations, such as blepharitis, allergic conjunctivitis, keratoconjunctivitis sicca, conjunctival scarring with formation of symblepharon and lid malpositioning, filiform keratitis, corneal plaques, (persistent) epithelial defects, corneal ulcers and keratoconus as well as appropriate stage-adapted treatment, including lid hygiene with preservative-free lubricants, topical and sometimes systemic anti-inflammatory therapy and surgical treatment are important for patients to prevent long-term damage of the ocular surface leading to severe visual impairment.ZusammenfassungPatienten mit einer atopischer Dermatitis klagen häufig im Krankheitsverlauf über Beschwerden mit den Augen. Dabei ist zum einen die periokuläre Haut direkt an der Dermatitis beteiligt, und zum anderen kommt es häufig zu einer chronisch verlaufenden Blepharokeratokonjunktivitis. Die frühzeitige Diagnosestellung der charakteristischen ophthalmologischen Veränderungen (wie Blepharitis, allergische Konjunktivitis, Conjunctivitis sicca, Bindehautvernarbungen mit Symblepharonbildung und Lidfehlstellung, filiforme Keratitis, Bildung kornealer Plaques, [persistierende] Erosio, Hornhautulzera, Keratokonus etc.) und die entsprechende stadiengerechte Therapie (von der Lidrandpflege mit konservierungsmittelfreier Benetzung über eine topische und ggf. systemische antiinflammatorische Therapie bis zu chirurgischen Maßnahmen etc.) sind für die Betroffenen von großer Bedeutung, um langfristige Schäden an den Augen und eine damit einhergehende Sehbehinderung zu verhindern.AbstractPatients with atopic dermatitis frequently complain of ocular symptoms. The general dermatitis can directly affect the periocular skin and patients often present with chronic atopic blepharokeratoconjunctivitis. Early diagnosis of the characteristic ophthalmological alterations, such as blepharitis, allergic conjunctivitis, keratoconjunctivitis sicca, conjunctival scarring with formation of symblepharon and lid malpositioning, filiform keratitis, corneal plaques, (persistent) epithelial defects, corneal ulcers and keratoconus as well as appropriate stage-adapted treatment, including lid hygiene with preservative-free lubricants, topical and sometimes systemic anti-inflammatory therapy and surgical treatment are important for patients to prevent long-term damage of the ocular surface leading to severe visual impairment.

Augenbeteiligung bei atopischer Dermatitis

Patienten mit einer atopischer Dermatitis klagen haufig im Krankheitsverlauf uber Beschwerden mit den Augen. Dabei ist zum einen die periokulare Haut direkt an der Dermatitis beteiligt, und zum anderen kommt es haufig zu einer chronisch verlaufenden Blepharokeratokonjunktivitis. Die fruhzeitige Diagnosestellung der charakteristischen ophthalmologischen Veranderungen (wie Blepharitis, allergische Konjunktivitis, Conjunctivitis sicca, Bindehautvernarbungen mit Symblepharonbildung und Lidfehlstellung, filiforme Keratitis, Bildung kornealer Plaques, [persistierende] Erosio, Hornhautulzera, Keratokonus etc.) und die entsprechende stadiengerechte Therapie (von der Lidrandpflege mit konservierungsmittelfreier Benetzung uber eine topische und ggf. systemische antiinflammatorische Therapie bis zu chirurgischen Masnahmen etc.) sind fur die Betroffenen von groser Bedeutung, um langfristige Schaden an den Augen und eine damit einhergehende Sehbehinderung zu verhindern.

Immunsuppressiva zur Verhinderung von Abstoßungsreaktionen nach allogenen Hornhauttransplantationen@@@Immunosuppressives to prevent rejection reactions after allogeneic corneal transplantation

In order to prevent rejection of an allogeneic corneal transplant after perforating (high risk) keratoplasty, active agents from different classes of pharmacological substances are used, as with solid organ transplantation. In addition to glucocorticoids, antiproliferative agents, small molecule inhibitors and antibodies, those belonging to the group of macrolides with their many derivatives represent an interesting class of substances in this context. As a supplement to cyclosporin A (CSA) the most successful macrolide in transplantation medicine, animal experiments are currently being carried out to test newer macrolide derivatives, such as sanglifehrin A (SFA). This overview describes the classes of drugs and modes of action of currently administered standard medications in the clinical routine and new developments are presented.

Ultrastrukturelle Analyse von Hornhautlentikeln nach fs-Lentikelextraktion gibt es einen Zusammenhang mit den refraktiven Ergebnissen?

BACKGROUND ReLEx®flex is a corneal refractive procedure performed by removing corneal lenticules with a femtosecond (fs) laser system. Using electron microscopy, tissue parameters of extracted lenticules were analysed for potential correlations to the refractive results. Furthermore, the effect of previous contact lens (CL) wear on refractive stability (regression) was tested. PATIENTS AND METHODS 19 lenticules from 11 patients (age 24-56 years, 8 f, 3 m) were prepared for EM. The central areas of the samples were photographed and the distance between the collagen fibres and their diameters were digitally measured. ANOVA analysis was used to correlate postoperative refractional stability with time of preoperative CL use, fibre diameter and the coefficient of variation (CV) of fibre distance. RESULTS 14 of 19 lenticules were from patients who had worn CL preoperatively. The cumulative duration of CL wear averaged around 31.2 ± 35.5 thousand hours. Preoperative CL use significantly influenced the postoperative regression: the longer time patients had worn CL, the greater was the regression towards myopia (p = 0.01). Additionally, the morphological parameters collagen fibre diameter (p = 0.09) and CV of fibre distance (p = 0.07) had an impact on regression. CONCLUSIONS Prolonged CL use and alterations in ultrastructural patterns affected the refractive stability after ReLExflex. Although the pathophysiological relationships between CL use, corneal morphological parameters, and refractive stability are still poorly understood, these findings could potentially be used as prognostic markers for postoperative refraction after ReLExflex.

Humanes Leukozytenantigensystem in der Augenheilkunde@@@Human leukocyte antigen (HLA) system in ophthalmology

Various inflammatory and non-inflammatory eye diseases are associated with specific HLA isotypes. Therefore, HLA isotyping can be a useful diagnostic tool for these diseases and has already been shown to reduce the rejection rate of corneal allografts. Unfortunately, the volume of published data and the varying quality of these publications complicate obtaining good overview in this field. This review briefly summarizes the genetic structure of the HLA system and elucidates differences between HLA classes I and II in the context of antigen presentation. Possible mechanisms of HLA associations in the field of ophthalmology are discussed, and finally different tools (e.g. genome wide association studies) for assessing associations of HLA isotypes with different ocular diseases are examined.