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Biomedical subjects

M Zierhut

Publications and source records attributed to M Zierhut.

At least 19 recordsLinked to original sources

Mycophenolate mofetil in the treatment of uveitis in children.

BACKGROUND: Mycophenolate mofetil (MMF) is a new immunosuppressive agent that effectively controls the intraocular inflammation in adults. PURPOSE: To assess the efficacy of MMF in uveitis in children and to analyse the possible side effects. PARTICIPANTS AND METHODS: A retrospective analysis was carried out on 17 children (32 eyes) with intraocular inflammation treated with MMF and followed up at the University Eye Hospital Tuebingen, Tuebingen, Germany, between 2000 and 2005. All children had chronic non-infectious uveitis and received MMF for at least 6 months. All patients were given steroids or other immunosuppressive agents before initiating treatment with MMF. RESULTS: 17 children (10 boys and 7 girls) with a mean age of 8 (range 2-13) years at the onset of uveitis were examined. The average duration of follow-up after initiation of MMF was 3 (range 2-5) years. A steroid-sparing effect was achieved in 88% of the patients. The oral prednisolone was successfully discontinued in 41% children and reduced to a daily dose of < or =5 mg in 47% of the children. 24% of the patients remained relapse-free during the treatment, but a reduction in the relapse rate was observed in all other patients except one. Visual acuity was increased or maintained in 13 children (76%). Mild side effects (headache, rash, gastrointestinal discomfort) occurred in 7 patients (41%) and were the cause of discontinuation of MMF in 1 patient. CONCLUSION: The results of our study are encouraging and suggest that MMF is an effective agent also in the treatment for uveitis in children, with marked steroid-sparing potential and an acceptable side effect profile.

Adolescent↗

[Uveitis and the aging].

Uveitis can be found in all age groups, but the age of disease onset may provide important information on the etiology of the disease. New data on the epidemiology of uveitis disclose a higher incidence and prevalence in older patients then has previously been found. Masquerade syndromes which mimic uveitis may be found especially in younger and older patients. These have to be excluded from regular intraocular inflammation. Here, intraocular lymphoma plays a major role which is most often associated with severe clinical, diagnostic and therapeutic challenges. One of the major complications of uveitis is cataract formation. Keeping in mind the importance of pre- and postoperative treatment, even implantation of an intraocular lens in older patients with uveitis is currently a safe procedure.

Age Factors↗

[Epidemic keratoconjunctivitis. Detecting adenoviruses].

OBJECTIVE: The validity of the 15-min adenovirus assay SAS Adenotest was evaluated compared with virus detection by polymerase chain reaction (PCR) from conjunctival swabs. METHODS: In 75 patients with assumed epidemic keratoconjunctivitis, adenovirus detection from conjunctival swabs was performed by the immunochromatographic assay SAS Adenotest and PCR. RESULTS: In 25 patients adenovirus was detected by PCR, 18 of whom were detected by the SAS Adenotest and 7 of whom were not. No false positive results occurred. Sensitivity was 72% and specificity was 100%. CONCLUSIONS: The results indicate that rapid adenovirus detection with the SAS Adenotest is a useful tool in early epidemic keratoconjunctivitis. An additional PCR should be performed when clinical symptoms persist for 5 days or more.

Adenoviridae↗

[Fuchs uveitis syndrome--heterochromia is no "conditio sine qua non"].

Fuchs uveitis syndrome (FUS) is typically a unilateral, chronic, low-grade inflammation of the anterior segment which manifests in young adulthood. It is underdiagnosed because of its variable clinical spectrum. Although it can mimic various forms of anterior uveitis, it is important to make the correct diagnosis, based on clinical grounds, because both the management and prognosis differ from those of other uveitides. While its etiology remains unknown, it is possible that the disease has multiple causes that lead through different pathogenic mechanisms to the same clinical entity. Although many patients do not require treatment, it is not a benign condition, as often perceived. The high incidence of glaucoma makes it mandatory that all patients with FUS should be screened at regular intervals, even if they are not being actively treated and are relatively asymptomatic.

Diagnosis, Differential↗

[Inflammatory glaucomas].

The prevalence of glaucoma in patients with intra- or extraocular inflammation is five to twenty percent. The etiopathogenesis is manifold, including classical secondary open and closed angle mechanisms as well as specific inflammatory elements. Diagnosis and follow-up studies of inflammatory glaucomas are often difficult. The therapeutic options are limited or are poorly evaluated. The development of a secondary glaucoma is a severe complication of intra- or extraocular inflammation and may even lead to blindness. Further investigations, especially with regard to the treatment of inflammatory glaucomas, are necessary to improve the prognosis.

Glaucoma↗

[Diagnostic and therapeutic recommendations for mucous membrane pemphigoid of the eye].

Mucous membrane pemphigoid (MMP) is often accompanied with a chronic cicatrizing conjunctivitis that may eventually lead to loss of vision. The study is intended to investigate the current scientific knowledge on the diagnosis of and therapy for MMP involving the eye. Previous studies published before December 2004 have been systematically reviewed for their level of evidence. Consequently, recommendations for patient management are provided.

Chronic Disease↗

MMF and eye disease.

Immunosuppressive treatment has shown to be effective in various ocular inflammatory disorders. Factors limiting their use are the individual response and the rate of side effects. This report summarizes our knowledge about the use of mycophenolate mofetil (MMF) in the treatment of ocular cicatricial pemphigoid (OCP), uveitis, atopic keratoconjunctivitis (AKC), prevention of graft rejection after penetrating keratoplasty (PK) and scleritis. Controlled studies have been performed for prevention of graft rejection after PK, showing MMF as effective in the prevention of graft rejection as cyclosporine A. In experimental uveitis, MMF has been demonstrated to be highly effective in prevention of retinal destruction. A number of studies have now shown that MMF also seems effective in uveitis. There are also studies with smaller patient groups which point out the effectiveness of MMF in OCP, AKC, and scleritis. In most of the studies, the spectrum of side effects was small, compared to other immunosuppressives.

Eye Diseases↗

Influence of human recombinant interferon-alpha2a (rhIFN-alpha2a) on altered lymphocyte subpopulations and monocytes in Behcet's disease.

OBJECTIVE: In Behçet's disease (BD), several abnormalities of lymphocyte subpopulations have been described. Standard treatment comprises immunosuppressive drugs. We successfully treated 50 patients with ocular BD with interferon-alpha2a (IFN-alpha2a) (response rate 92%), although this is counterintuitive because IFN-alpha is immunostimulatory and can sometimes even induce autoimmune diseases such as systemic lupus erythematosus or rheumatoid arthritis. The aim of the present study was to elucidate the immunomodulatory effects that IFN-alpha might exert on peripheral blood mononuclear cells (PBMC) in BD by examining changes in the distribution of lymphocyte subpopulations under IFN-alpha2a treatment. METHODS: Fourteen patients with ocular BD were evaluated before and at weeks 4 and 24 of IFN-alpha treatment and compared with 10 healthy controls. PBMC were stained with monoclonal antibodies and measured by flow cytometry. RESULTS: Compared with the controls there is a significant elevation of monocytes (CD14(+)), CD8(+)/gammadelta T cells, CD3(+)/gammadelta T cells, natural killer (NK) cells (CD56(+)/CD16(+)) and activated/regulatory T cells (CD4(+)/CD25(+) and CD8(+)/CD25(+)) in patients with active BD before treatment with IFN-alpha2a. Numbers of naïve T cells (CD8(+)/CD45(+)RA(+)/RO(-), CD4(+)/CD45(+)RA(+)/RO(-)) were significantly lower. Under therapy, NK cells, CD8(+)/gammadelta T cells and CD3(+)/gammadelta T cells decreased significantly, whereas B cells increased. The previously reduced expression of HLA class I on monocytes in HLA-B51-positive patients rose to levels comparable to HLA-B51-negative patients. CONCLUSION: These results implicate the participation of NK cells and gammadelta T cells, especially CD8(+)/gammadelta T cells, in the pathogenesis of BD and may explain one mechanism by which IFN-alpha2a exerts therapeutic effects. Alternatively, they may result indirectly from remission induction by IFN-alpha2a. The reduced expression of HLA class I on monocytes in HLA-B*51-positive patients might reflect an impaired expression of and antigen presentation by HLA-B*51.

Adult↗

[Ocular involvement in Behçet's disease: first 5-year-results for visual development after treatment with interferon alfa-2a].

BACKGROUND: Behçet's disease (BD) is a systemic vasculitis of unknown origin. Up to now ocular involvement has a poor visual prognosis irrespective of immunosuppressive treatment. Now recent open studies have shown that interferon alfa-2a (IFN alfa-2a) is very effective in the treatment of ocular BD. The purpose of this study was to evaluate the long-term development of visual acuity (VA) in patients with severe ocular BD who were treated with IFN alfa-2a. METHODS: We included 15 eyes of 9 patients with an active panuveitis and/or retinal vasculitis due to BD refractory to immunosuppressive treatment. VA before initiation of IFN-therapy was compared to VA at the end of the follow-up time. RESULTS: Mean follow-up time was 68.8+/-10.6 months. Mean duration of IFN-treatment was 40.6+/-17.0 months. With the exception of one patient IFN alfa-2a could be discontinued in complete remission of ocular symptoms. During the follow-up time 10 eyes showed an increase of VA of two lines or more. In 5 eyes VA remained stable. There was no decrease of VA in any eye. If a macular edema was present, a quick response to IFN alfa-2a was seen. No eye developed a pale optic disk during follow-up. CONCLUSION: Compared to conventional immunosuppressants, interferon alfa-2a seems to be much more effective to prevent a loss or decrease of VA over a long period of time in patients with severe ocular BD.

Adult↗

[Optical coherence tomography in the diagnosis and follow-up of patients with uveitic macular edema].

BACKGROUND: Optical coherence tomography (OCT) is a relatively new, noninvasive method and has been well established as an effective diagnostic procedure for the investigation of several macular diseases. Knowledge about the efficacy of OCT in the diagnosis and follow-up of macular edema in uveitis patients is still limited. PATIENTS AND METHODS: In the first part of the study, OCT was performed in 22 eyes of 18 patients with anterior or intermediate uveitis who showed angiographic and fundoscopic evidence of macular edema. The OCT results were compared with the visual acuity and fundoscopic and angiographic appearance of macular edema. In the second part of the study, the same patients were followed over a period of approximately 5 months (+/-2 months) and OCT was repeated at different time points during treatment of uveitic macula edema. RESULTS: OCT investigation also showed clear evidence of macular edema in all eyes and was not compromised by a low or medium degree of optical haze. Furthermore, OCT investigation revealed marked differences in the individual degree of macular edema (foveal heights 168-810 microm). Diffuse macular edema ( n = 4 ) and different types of cystoid macular edema (several distinguished cysts n = 6, partially or completely confluent cysts n = 11, one marked cyst n = 1) were observed. During the follow-up of the patients, OCT results, visual acuity, and fundoscopic appearance of the macula showed a comparable behavior. In some eyes, a stable visual acuity was accompanied by changes of foveal edema demonstrated by OCT. CONCLUSION: Optical coherence tomography is a safe and highly effective method in the diagnosis of macular edema in uveitis associated with low or medium haze of the optical media. Furthermore, OCT investigation seems to be useful in the follow-up of uveitic macular edema under treatment.

Fluorescein Angiography↗

[Intraocular non-Hodgkin's lymphoma and its therapy-- a case series of ten patients].

BACKGROUND: The timely and correct diagnosis of intraocular non-Hodgkin's lymphoma represents a huge challenge to clinicians. Two thirds of intraocular lymphomas are a manifestation of a primary CNS lymphoma (PCNSL) arising outside the lymphatic system and are localized in the brain, the meninges or the spinal chord. Ten to twenty percent commence as vitreous or retinal infiltrates mimicking uveitis. Ninety five percent of PCNSL are B cell lymphomas. PATIENTS: Three exemplary cases from a group of ten patients treated between 1998 and 2002 are presented. A table provides a summary of the relevant details of all ten patients. RESULTS: The mean age at presentation was 63.5 years with a female to male ratio of 6 to 4. Nine patients were diagnosed as having intermediate or posterior uveitis, in one patient choroidal metastases were suspected. Six patients had a concomitant CNS lesion while four patients showed isolated intraocular lymphoma only. The presence of a highly malignant B cell lymphoma was proven by vitreous biopsy in nine cases and by stereotactic biopsy of a CNS lesion in one patient. All patients were treated by intravenous chemotherapy, however, no binding recommendations with regard to treatment exist to date. CONCLUSIONS: We give an overview of all current treatment regimens and their pitfalls. At present it is recommended that all patients with proven PCNSL be entered in a multicenter randomized study under the auspices of the Department of Internal Medicine III of the Benjamin-Franklin-University-Hospital, Berlin and the Department of Neurology of the University Hospital of Tuebingen.

Aged↗

[Relapsing, therapy refractory episcleritis, paraproteinemia and cutaneous-subcutaneous nodules on arm and hip: manifestations of a necrobiotic xanthogranuloma (NXG)].

BACKGROUND: Necrobiotic xanthogranuloma is a rare granulomatous disease featuring nodular, sometimes ulcerating, skin lesions in association with paraproteinemia and variable organ disease. Eye involvement manifests itself often as periorbital plaque-like infiltrates but also as chronic episcleritis, conjunctivitis, keratitis and scleritis. CASE REPORT: A 49-year-old female patient presented to our hospital with a seven-year history of relapsing bilateral episcleritis refractory to treatment. Her past medical history included an IgG paraproteinemia and C4-deficiency of unknown etiology. A year prior to presentation the patient had undergone biopsy of a skin nodule on her arm which histologically was suspected to be an infectious granuloma. A recurrence of the lesion at the site of biopsy together with a new nodule on the hip prompted us to perform further histological analyses. RESULTS: The histological specimen displayed numerous giant cells of the foreign body and Touton type, some xanthomatous foam cells with cholesterol clefts and collagen necrosis, leading to the diagnosis of NXG. As part of the disease, serology showed an IgG lambda paraproteinemia, elevated cANCA values, a C4 deficiency and a negative rheumatoid factor. No other immunological dysfunction was detected. CONCLUSIONS: NXG is a severe multi-system disorder that may cause various chronic inflammatory conditions of the eye's anterior segment. Its early diagnosis is mandatory as potentially fatal organ complications may arise and the association with lymphoproliferative diseases has been described. Due to the relative rarity of the disease no binding therapeutic regimen exists. Options include alkylating agents in combination with corticosteroids, plasmapheresis and subcutaneous interferon alfa-2 b.

Arm↗

Immunology and functional genomics of Behçet's disease.

Behçet's disease (BD) is a multisystemic inflammatory disorder. Although the cause and pathogenesis of BD are still unclear, there is evidence for genetic, immunologic and infectious factors at the onset or in the course of BD. This review focuses on the functional genomics and immunology of BD. HLA-B51 is the major disease susceptibility gene locus in BD. An increased number of gammadelta T cells in the peripheral blood and in the involved tissues have been reported. However, the T cells at the sites of inflammation appear to be a phenotypically distinct subset. There is also a significant gammadelta T cell proliferative response to mycobacterial 65-kDa heat shock protein peptides. Homologous peptides derived from the human 60-kDa heat shock protein were observed in BD patients. There is evidence that natural killer T cells may also play a role in BD.

Animals↗

[Familial uveitis. Forms and incidence in patients at the University Eye Hospital Tubingen].

OBJECTIVE: A familial accumulation in some forms of uveitis has rarely been described. The objective of this study was to identify such cases and to examine both clinical course and similarities in the HLA-pattern. METHODS: From 1993 to 2000 all new uveitis patients, who were examined in the uveitis clinic of the University Eye Hospital Tuebingen, were asked about a positive family history. If possible, all affected family members underwent an ophthalmological examination and HLA-typing was performed. RESULTS: In 7 families we found a familial accumulation of uveitis. The underlying etiologies were anterior uveitis in ankylosing spondylitis with HLA-B27 association, anterior uveitis in Blau syndrome with no HLA association, anterior and intermediate uveitis in sarcoidosis with no HLA association, and panuveitis in Behçet's disease with HLA-B51 association. For familial uveitis we calculated an incidence of 0.03 cases per 100,000 persons and year. CONCLUSION: Our data confirm that familial forms of uveitis are very rare. We suggest that these may be subgroups of known uveitis syndromes (e.g. sarcoidosis, ankylosing spondylitis). The factors causing the inheritance are still unknown. By genetic examination of families with uveitis it may be possible to identify single uveitis genes or possible antigens.

Academic Medical Centers↗

[Therapeutic vitrectomy in uveitis: current status and recommendations].

With the advent of modern vitreoretinal surgical techniques, the spectrum for surgical intervention in various forms of uveitis has been notably expanded. Removal of optically relevant vitreous opacities, improvement of secondary macular edema, delamination of epiretinal membranes, and release of traction in the presence of abnormal vitreoretinal adhesions represent indications for vitreoretinal procedures in uveitis patients. Furthermore, retinal and choroidal biopsies may be obtained if the precise etiology is unknown. This in turn offers the opportunity to better target pharmacological interventions. Combined cataract surgery or intravitreal implantation of drug devices may also be of therapeutic benefit. So far no prospective, controlled clinical trials have been performed to precisely evaluate the role of pars plana vitrectomy (ppV) as a single or combined surgical procedure in patients with intraocular inflammation. Inconsistent data exist regarding prognostic determinants and the role of perioperative immunosuppression. Here, the current knowledge on the subject is reviewed and critically discussed, and recommendations for patient management are given. Further studies are needed.

Combined Modality Therapy↗

Human recombinant interferon alfa-2a for the treatment of Behçet's disease with sight threatening posterior or panuveitis.

BACKGROUND: Behçet's disease is a multisystem vasculitis of unknown origin. Standard treatment mainly comprises systemic immunosuppressive agents. Ocular involvement, mostly posterior uveitis with retinal vasculitis, leads to blindness in 20-50% of the involved eyes within 5 years. The efficacy of interferon alfa-2a was studied in patients with sight threatening posterior uveitis or retinal vasculitis. METHODS: 50 patients were included in this open, non-randomised, uncontrolled prospective study. Recombinant human interferon alfa-2a (rhIFNalpha-2a) was applied at a dose of 6 million units subcutaneously daily. Dose reduction was performed according to a decision tree until discontinuation. Disease activity was evaluated every 2 weeks by the Behçet's disease activity scoring system and the uveitis scoring system. RESULTS: Response rate of the ocular manifestations was 92% (three non-responder, one incomplete response). Mean visual acuity rose significantly from 0.56 to 0.84 at week 24 (p<0.0001). Posterior uveitis score of the affected eyes fell by 46% every week (p<0.001). Remission of retinal inflammation was achieved by week 24. Mean Behçet's disease activity score fell from 5.8 to 3.3 at week 24 and further to 2.8 at week 52. After a mean observation period of 36.4 months (range 12-72), 20 patients (40%) are off treatment and disease free for 7-58 months (mean 29.5). In the other patients maintenance IFN dosage is three million units three times weekly. CONCLUSIONS: rhIFNalpha-2a is effective in ocular Behçet's disease, leading to significant improvement of vision and complete remission of ocular vasculitis in the majority of the patients.

Adult↗

[Cyclosporin A 2% eyedrops in therapy of atopic and vernal keratoconjunctivitis].

BACKGROUND: The efficacy of Cyclosporin A 2%eyedrops (CsA2%) as an additive treatment of atopic (AKC) and vernal keratoconjunctivitis (VKC) was evaluated. PATIENTS AND METHODS: The symptoms and findings of 26 patients with AKC and 12 patients with VKC with no improvement under conventional therapy, were additionally treated with CsA2% eyedrops and compared over a minimum follow-up period of 3 months to more than 24 months. RESULTS: The therapy with CsA2% eyedrops was well tolerated and evaluated as effective by the patients. Subtarsal papillae were reduced in 69.2% of the AKC group and in 66.6% of the VKC patients. Trantas dots were reduced or disappeared in about 50% of the AKC group and in the VKC group they had disappeared in more than 50%. Subjective symptoms (e.g. itching) had also been reduced or eliminated. CONCLUSION: CsA2% eyedrops are effective in the treatment of AKC and VKC, reducing objective and subjective signs as well as the need of adding topical steroids in affected patients.

Adolescent↗