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Biomedical subjects

M Zierhut

Publications and source records attributed to M Zierhut.

At least 37 records · Page 2Linked to original sources

[Immunosuppressive therapy with mycophenolate mofetil (CellCept) in treatment of uveitis].

BACKGROUND: Severe forms of uveitis can often only be managed sufficiently with systemic immunosuppression. All available drugs are known for their relative high rate of side-effects. Mycophenolate mofetil (MMF), an immunosuppressant successfully used in management after organ transplantation and many autoimmune diseases, has shown remarkably less side-effects when used for various forms of uveitis in monotherapy or in combination with corticosteroids. The aim of this multicenter-study was to investigate if monotherapy with MMF is effective in various forms of uveitis. METHOD AND PATIENTS: Ten patients with anterior uveitis (n = 3), intermediate uveitis (n = 2), panuveitis (n = 4) and retinal vasculitis (n = 1) were treated in a prospective study with 2 x 1 g MMF daily. Previous immunosuppression had been discontinued because of side-effects or ineffectivity in all patients. In these patients MMF was given in addition to the other immunosuppressant at the beginning of treatment. RESULTS: The follow-up time ranged from 1 to 12 months (mean 4.5 months). Under therapy with MMF (monotherapy in 4 patients, additional prednisolone in 5 patients and additional metotrexate in 1 patient) 8 patients remained free of recurrences. In one female patient depression of inflammation activity was only achieved after cessation of therapy with Cyclosporin A in combination with MMF and a switch to methotrexate. Another patient with a bilateral uveitis was free of recurrences in only one eye, the second eye did not develop recurrence due to the additional corticosteroid treatment. Side-effects were diarrhoea in one patient and probably gastrointestinal problems in another (leading to cessation of therapy in both patients) and in another case nausea, vomitus and alopecia 10 months after beginning therapy. CONCLUSIONS: MMF as a new immunosuppressant stopped inflammation or drastically reduced the rate of recurrences in 8 out of 10 patients with uveitis which was previously not brought under control by other immunosuppressants. The side-effects were tolerable in comparison with other immunosuppressive agents. More patients, longer follow-up times and a comparative study with Cyclosporin A are required to assess the long-term therapeutical success.

Adult↗

Immunology and growth characteristics of ocular basal cell carcinoma.

BACKGROUND: Knowledge about immunological features and growth characteristics of palpebral (ocular) basal cell carcinomas (BCCs) is limited. In particular, it is unclear whether ocular BCC represents in this regard a special BCC entity or not. METHODS: Twenty BCCs of the lid area (ocular BCCs) were investigated immunohistologically using monoclonal antibodies against CD4, CD8, CD45Ro, CD50, CD68, HECA-452, Ki67 (MIB1), and the p53 epitope. For comparison, nine BCCs excised distant from the eye (non-ocular BCCs) were evaluated. RESULTS: In BCCs the distribution of the immunocompetent cells investigated is markedly irregular. These cells are localized mainly around BCC islands. Only a few of them invade tumour cell aggregates. The CD4:CD8 ratio as detected by immunohistochemistry is >1 in 82% of ocular BCCs and in 88% of nonocular BCCs. Often there are dense infiltrations of CD68+ cells (macrophages) and HECA-452+ cells adjacent to tumour cell aggregates. The growth fraction [percentage of proliferating (Ki67+/MIB 1+) cells] varies from 0% to more than 30%. Proliferative activity is enhanced at the invasion front. Additionally, the amount of p53+ cells differs considerably among the BCCs. CONCLUSIONS: CD4+ T cells seem to be the most important cell population for BCC immunosurveillance, offering the chance for conservative interferon therapy. The role of CD68+ and HECA-452+ cells has to be further elucidated. In many tumours the large amount of proliferating cells contrasts to the usually slow growth of BCCs, indicating strong apoptotic processes. The results can be regarded only as semiquantitative. So far, ocular and nonocular BCCs exhibit no essential differences regarding immunocompetent cell infiltration and growth characteristics. According to this, palpebral BCCs are "normal" BCCs and not a special BCC variant. Therefore, results from dermatological research concerning BCC can be extended without limitations to their counterparts in the lid area.

Adult↗

The ocular surface and tear film and their dysfunction in dry eye disease.

The ocular surface, tear film, lacrimal glands, and eyelids act as a functional unit to preserve the quality of the refractive surface of the eye and to resist injury and protect the eye against changing bodily and environmental conditions. Events that disturb the homeostasis of this functional unit can result in a vicious cycle of ocular surface disease. The tear film is the most dynamic structure of the functional unit, and its production and turnover is essential to maintaining the health of the ocular surface. Classically, the tear film is reported to be composed of three layers: the mucin, aqueous, and lipid layers. The boundaries and real thickness of such layers is still under discussion. A dysfunction of any of these layers can result in dry eye disease.

Cornea↗

[Early clinical results with mycophenolate mofetil in immunosuppressive therapy of ocular pemphigoid].

BACKGROUND: Ocular cicatrical pemphigoid can lead to severe structural damage or loss of vision at worst. Longterm therapy with dapsone or systemic immunosuppressive therapy, e.g. with cyclophosphamide is often inevitable. Immunosuppression may cause severe side effects in some patients. PATIENTS AND METHODS: Data are presented on 5 patients with ocular cicatrical pemphigoid who were treated with mycophenolate mofetil 2 g daily. Criterion of effectiveness was the clinical course of the condition defined as nonprogression of the morphologic alterations. Patients were initially examined and interviewed routinely every four weeks for the first four months, then every eight weeks. Patients were asked about side effects and underwent monthly blood checks. RESULTS: All patients were followed for at least 12 months. Mycophenolate mofetil proved to be effective with respect to the clinical course in 9 out of 10 eyes. All patients showed regression of inflammatory conjunctival alteration and improvement of their complaints. In one eye the inflammatory process restarted after surgery due to excessive symblephara had been performed. Gastrointestinal side effects were reported in the initial phase, e.g. lack of appetite, nausea and mild diarrhoea. CONCLUSIONS: Mycophenolate mofetil proved to be an effective immunosuppressant for the treatment of ocular cicatrical pemphigoid. Namely side effects were less severe and frequent compared to those known from other currently administered immunosuppressants. Longterm results and larger case numbers are needed to sustain these early results.

Adult↗

[Conjunctival neuromas and prominent corneal nerve fibers as diagnostic indication of multiple endocrine disease].

BACKGROUND: Multiple endocrine neoplasias (MEN-syndromes) represent diverse, mostly autosomal-dominant inherited, seldom sporadic diseases. MEN 2B-syndrome comprises medullary thyroid carcinoma, pheochromocytoma and mucosal neuromas. PATIENT: A 30 year old male patient presented with bilateral chronic irritation of the ocular surface. The biomicroscopy revealed intraconjunctival worm-like alterations, prominent corneal nerves and nodules on the upper lid margins. HISTOLOGY: The performed conjunctival biopsy showed nearly no goblet cells, but prominent intrastromal, immunohistochemical S100-positive neuromas. RESULTS: The initiated investigations revealed bilateral multifocal medullary thyroid carcinoma and a left sited pheochromocytoma. CONCLUSION: Conjunctival neuromas and prominent corneal nerves can be diagnostic for the MEN 2B-syndrom. Early diagnosis and prophylactic thyroidectomy are expected to improve the life expectancy even in asymptomatic gene-carriers.

Adult↗

[Secondary ocular syphilis with chorioretinitis of the posterior pole - a case report].

BACKGROUND: Diagnosis of syphilis is often very difficult due to the absence of typical organ manifestation. In addition syphilis has the ability to imitate any ocular inflammation. This may result in misdiagnosis and delay of appropriate antimicrobial therapy. Up to now the first choice therapy is penicillin. CASE REPORT: We report about an otherwise healthy, 40 year-old-woman, who was referred to the Department of Ophthalmology, University of Tuebingen, due to an unclear loss of visual acuity (OD 0.1 and OS 0.4). The fundus examination disclosed focal chorioretinitis on the posterior pole, which was verified in fluorescein angiography. Secondary syphilis was diagnosed due to positive serological testing. Medical treatment consisted in Penicillin (i.m.) for 2 weeks and additional oral corticosteroids, which were tapered down slowly. After 3 months visual acuity had improved to 0.9 in the right and to 1.0 in the left eye. The former chorioretinitis regions showed only hyperpigmentation. CONCLUSIONS: Laboratory syphilitic testing should be performed in every uveitis.

Adult↗

[Neurological complications in acute posterior multifocal placoid pigmentepitheliopathy (APMPPE) - a review with case report].

BACKGROUND: Acute posterior multifocal placoid pigment epitheliopathy (APMPPE) is an ocular disease of young adults with a favorable visual outcome. Up to present the etiology and pathophysiology of APMPPE have not been thoroughly understood. Serious inflammatory systemic and neurological diseases have been described in association with APMPPE. CASE REPORT: We report a single case study of a 29-year-old male patient with APMPPE. Approximately four months after diagnosis of APMPPE the patient developed a temporary tetraparesis as initial symptom of chronic inflammatory cerebral disease. We give an overview of the stated theories of the pathogenesis of APMPPE in the literature. Moreover we account on concomitant systemic symptoms and diseases. We outline neurological complications in APMPPE and discuss the reported therapies. RESULTS: Neurological complications rarely accompany APMPPE and may occur even months after the initial ocular symptoms. There have been reports of meningoencephalitis and cerebral vasculitis and two patients died of neurological complications. The recommended therapeutic regime is high-dose corticosteroids. Relapses can appear during tapering of systemic corticosteroids therapy. The role of immunsuppressive treatment remains unclear. CONCLUSION: APMPPE can be associated with serious inflammatory systemic and neurological affection. Instruction of the patient is indispensable to guarantee early and adequate treatment.

Acute Disease↗

[Behçet's disease: uveitis-therapy with interferon alpha2a - prospective clinical study in 33 patients].

INTRODUCTION: Behçet's disease (BD) is a multisystem vasculitis of unknown origin. Visual outcome in BD is bad irrespective of therapy. We investigated in a prospective, open clinical trial wether interferon alpha2a (IFN alpha2a) is effective as single agent in severe ocular BD. PATIENTS AND METHODS: 33 patients (11 female, 22 male) with severe ocular BD (posterior uveitis/panuveitis), fulfilling the Criteria of the "International Study Group of Behçet's Disease", were treated with IFN alpha2a. Other immunosuppressive drugs were stopped at the beginning of interferon-therapy. Efficacy was evaluated by the uveitis scoring system (Ben Ezra et al.), visual acuity and BD activity score (Rigby et al.). RESULTS: In 32 (97 %) patients complete remission of the inflammatory changes occured. Mean posterior uveitis score fell from 3.7 to 0.4, visual acuity rose from 0.5 to 0.9, and mean BD activity score fell from 5.1 to 3.0 during a mean observation period of 28.6 months. There was only one non-responder. Side effects were hair loss (69 %), depression (36 %), itching (33 %), fibromyalgia (10 %), and the development of autoantibodies (21 %). Fever, arthralgia and headache occured in all patients, but only during the first weeks of therapy. CONCLUSION: IFN alpha2a seems to be very effective in ocular BD. Controlled randomized studies are warranted in order to prove the efficacy of IFN alpha2a in ocular BD and to compare it with other, established treatments, such as azathioprine or cyclosporin A.

Adult↗

[Chronic keratitis and autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome - a case report].

BACKGROUND: The autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome (APECED) is a rare disease which can be associated with severe keratitis leading to blindness. Besides conjunctivitis and keratitis uveitis anterior, cataract, retinitis pigmentosa, atrophy of the optical nerve, loss of lashes and eye-brows have been described. CASE REPORT: We report on an 11-year-old girl with the history of APECED syndrom. For 6.5 years she has suffered from chronic keratoconjunctivitis including corneal infiltrates, peripheral epithelial and subepithelial scarring and peripheral neovascularisation of the cornea. Most of all she complained of recurrent conjunctivitis, photophobia and epiphora. The best therapy consisted in local application of dexamethasone and gentamycine three times daily. Under this therapy the corneal infiltration remained stable and the patient felt most comfortable. No side effects appeared by now. CONCLUSIONS: Inspite of the bad prognosis of the keratitis we managed to keep the cornea infiltrates stable. Nevertheless the search for a more effective treatment with less side effects like secondary glaucoma or cataracts will go on.

Child↗

[Cogan I syndrome: clinical aspects, therapy and prognosis].

BACKGROUND: Cogan I syndrome is a rare, inflammatory, systemic disease that is typically characterized by severe audiovestibular dysfunction and various inflammatory eye changes. PATIENTS AND METHODS: Between 1978 and 1996 ten patients with Cogan I syndrome were treated at the eye hospital, ENT clinic and medical clinic of the University of Tübingen. Retrospectively, the clinical picture, course of the disease and outcome were investigated by reviewing the charts of these patients. RESULTS: Patient ages ranged from 18 to 78 years (mean 37 years) at the time of disease manifestation. Eight patients were female. Inflammatory ocular changes were observed in nine patients in both eyes. Uveitis was found in six patients, keratitis in five, episcleritis in three and scleritis in two patients. Both patients with scleritis showed a severe, partially sight-threatening course of the disease despite immunosuppressive therapy. Severe hearing loss was seen in all patients. Further manifestations of Cogan's syndrome included pericarditis associated with arthritis, and polyserositis in one patient, and fibromyalgia in two patients. CONCLUSION: In Cogan I syndrome, typically both eyes are affected by the disease process. Various ocular inflammatory changes may occur including uveitis, scleritis, keratitis and episcleritis. The visual prognosis is mostly good, although severe sight-threatening scleritis may occur.

Adolescent↗

Transscleral diode laser cyclophotocoagulation for the treatment of refractory glaucoma secondary to inflammatory eye diseases.

BACKGROUND: Inflammatory glaucoma is still a diagnostic and therapeutic dilemma and surgical intervention is always associated with a high risk of failure or reactivation of the inflammatory disease. In this study we prospectively examined the value of transscleral diode laser cyclophotocoagulation (TDLC) for the treatment of refractory inflammatory glaucoma. METHODS: 22 eyes of 20 consecutive patients with inflammatory, medically uncontrollable, glaucoma secondary to chronic uveitis/trabeculitis (n = 18), chemical injury (n = 2), episcleritis (n = 1), and necrotising scleritis with inflammation (n = 1) were treated by TDLC. Nine eyes (41%) had had previous failed glaucoma surgery (trabeculectomy, cyclocryocoagulation) and 15 eyes (68.2%) had had previous anterior segment surgery. All patients were followed for 1 year after the initial treatment. RESULTS: Within 12 months of the first treatment the intraocular pressure was controlled in 77.3% of all eyes (72.2% of those with uveitic glaucoma). No serious side effects such as activation of the inflammatory process, phthisis bulbi or persistent hypotonia were observed, except one patient with a temporary fibrin reaction. More than one treatment was necessary in 63.6% of the patients. The use of systemic carbonic anhydrase inhibitors was reduced from 68.2% before treatment to 27.3% after 1 year. CONCLUSION: TDLC seems to be a safe and effective procedure for the treatment of inflammatory glaucoma and may become an alternative to trabeculectomy with antimetabolites in uveitic glaucoma. TDLC may become the surgical procedure of choice in treating secondary glaucoma caused by chemical injury and also in scleritis associated glaucoma, using reduced parameters for application.

Adolescent↗

[High endothelial venules. Kinetics of the expression in IRBP-induced experimental autoimmune uveitis].

UNLABELLED: Experimental autoimmune uveitis (EAU) is a T-cell-mediated disease expressing high endothelial venules (HEVs) in the retina. HEVs could be responsible for the absorption of activated T-cells. The purpose of this study was to investigate the kinetics of HEV expression in the murine IRBP (interphotoreceptor retinoid binding protein) induced EAU. METHODS: B10. A mice were immunized subcutaneously with IRBP. The eyes were analysed on days 10, 18, 24 and 28 (n = 5 for each time point). While HEVs were identified with the mAb MECA 325, the control mAb MECA 20 stained all endothelial cells. RESULTS: HEVs were detectable in the intact retina from day 10. Presence of HEVs peaked on day 18 and decreased by day 28, when maximal inflammation and retinal destruction was detectable. CONCLUSION: HEV expression could play a central role in the onset of EAU, allowing homing and migration of inflammatory cells into the eye.

Animals↗

[Experimental autoimmune uveitis. Characterization of retina infiltrating cells].

UNLABELLED: The chronic model of murine EAU induced by interphotoreceptor retinoid binding protein represents a disease similar to clinical chorioretinitis. In this study we characterized the kinetics of retina infiltrating T-cells, macrophages and expression of the adhesion molecules ICAM-1 and ICAM-2. METHODS: B10.A mice were immunized subcutaneously with IRBP, and the eyes were analyzed on days 10, 18, 24 and 28. The infiltrating cells were characterized by mAbs recognizing T-cell receptors (TCR) Vss6 and Vss8, T-cell markers, macrophages and ICAM-1 and ICAM-2. RESULTS: While CD8+ T-cells and ICAM-2 were detectable from day 10 (retina is intact) until day 28, CD4+ T-cells, macrophages and ICAM-1 appear with the onset of retinal destruction. Starting at day 10 the dominating TCR was Vss6; Vss8 was noticed from day 18 on. CONCLUSION: CD8+ T-cells infiltrating the intact retina and stimulating the expression of high endothelial venules (HEVs) could be responsible for the onset of uveitis.

Acute Disease↗