Nicole Stübiger

Immunsuppressive Therapie mit Mycophenolat Mofetil (CellCept®) in der Behandlung der Uveitis

ZusammenfassungFragestellung. Ziel der vorliegenden multizentrischen Studie war, die Wirksamkeit von Mycophenolat Mofetil (MMF) als Monotherapeutikum bei verschiedenen Formen der Uveitis zu untersuchen. Patienten und Methode. Zehn Patienten mit anteriorer Uveitis (n=3), intermediärer Uveitis (n=2), Panuveitis (n=4) und retinaler Vaskulitis (n=1) wurden in einer prospektiven Studie mit 2×1 g MMF/Tag therapiert. Ergebnisse. Der Behandlungszeitraum betrug 1–12 Monate. Bei 8 Patienten zeigte sich unter der MMF-Therapie kein weiteres Rezidiv. Zwei Patientinnen wurden erst durch Umstellung auf Methotrexat bzw. durch eine begleitende Steroidmedikation rezidivfrei. An Nebenwirkungen klagte ein Patient über Diarrhö, die zum Absetzen der Therapie führte. Bei einer Patientin kam es 10 Monate nach Therapiebeginn zu Übelkeit, Erbrechen und Haarausfall. Schlussfolgerung. Die Immunsuppression mit MMF hat bei 8 von 10 Uveitispatienten zu einer Beruhigung der Entzündungsaktivität geführt. Die Nebenwirkungen sind eher milde verglichen mit denen anderer Immunsuppressiva.AbstractBackground. 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 2×1 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.

Interferon-α Therapy in Noninfectious Uveitis

Interferon (IFN)-α and IFN-β are naturally occurring cytokines which seem to have similar effects on the immune system. One of the effects of IFN seems to increase regulatory T cells. There are numerous case reports and studies reporting about the effect of IFN-α against Behçets disease (BD), but also against chronic uveitic macular edema and a few other types of uveitis. Within 2-4 weeks, approximately 94% of patients reach complete or partial remission in the case of BD-associated uveitis. So far, IFN-α is the only drug that leads to stable remission even after discontinuation of the treatment. It is recommended to start treatment with 3-6 million IU per day. Administering less than daily dosages seems to increase the recurrence rate for BD-associated uveitis. Flu-like symptoms are expected in all patients as a sign of nonexisting anti-IFN antibodies. They are treated with nonsteroidal anti-inflammatory drugs like paracetamol and disappear normally after some days. Depression(8%) and mild leukopenia (30%) are additional side effects of concern; all other side effects are reported to appear in ≤1% of cases. This chapter updates the mechanisms and pharmacology of IFN and its effects in experimental studies. This is followed by a summary of clinical studies in intraocular inflammation and the spectrum of side effects.

Successful Treatment of Chronic Pseudophakic Macular Edema (Irvine-Gass Syndrome) with Interferon Alpha: A Report of Three Cases

Purpose: To describe treatment of chronic Irvine-Gass syndrome (CME) with interferon (IFN) alpha. Methods: Interventional retrospective case series. IFN alpha-2a was administered at a dose of 3 million IU/day subcutaneously for 4 weeks, and was tapered thereafter. Treatment efficacy was assessed by best-corrected visual acuity (BCVA) and by optical coherence tomography (OCT). Results: Three patients (4 eyes) with chronic Irvine-Gass syndrome were treated. Ineffective pretreatment included local and systemic corticosteroids. Within 4 weeks, IFN alpha led to resolution of CME in all eyes. BCVA improved in 3 eyes and remained unchanged in 1 eye. During follow-up of 3–11 months no relapse of CME occurred. No systemic or local side effects were noted. Conclusions: IFN alpha has been demonstrated to be a successful and well-tolerated treatment option for resistant chronic pseudophakic CME. Further studies are necessary to evaluate the role of IFN alpha in Irvine-Gass syndrome.

Cogan I-Syndrom: Klinik, Therapie und Prognose

Hintergrund: Das Cogan I-Syndrom ist eine seltene, entzündliche Systemerkrankung, die hauptsächlich durch eine meist schwerwiegende Innenohrschwerhörigkeit sowie verschiedene, entzündliche Veränderungen des Auges gekennzeichnet ist. Patienten und Methode: Zwischen 1978 und 1996 wurden 10 Patienten mit Cogan I-Syndrom in der Augenklinik, HNO-Klinik und Medizinischen Klinik der Universität Tübingen untersucht und behandelt. Die Krankenakten dieser Patienten wurden retrospektiv ausgewertet. Ergebnisse: Das mittlere Erkrankungsalter betrug 37 Jahre (18–78 Jahre). Acht von 10 Patienten waren weiblichen Geschlechts. Bei 9 von 10 Patienten traten Veränderungen an beiden Augen auf. Es handelte sich bei 6 Patienten um eine Uveitis, bei 5 Patienten um eine Keratitis, bei 3 Patienten um eine Episkleritis und bei 2 Patienten um eine Skleritis. Die bei beiden Patienten bilaterale Skleritis (nodulär bzw. nekrotisierend) erwies sich als schwerste Manifestation. Alle Patienten zeigten eine schwere Hörminderung, die sich nur teilweise zurückbildete. Weitere Veränderungen waren eine Perikarditis mit assoziierter Arthritis und Polyserositis bei einem Patienten und eine Fibromyalgie bei 2 Patienten. Schlussfolgerung: Die verschiedenen okulären, entzündlichen Veränderungen im Rahmen eines Cogan I-Syndroms treten fast immer bilateral auf, zeigen eine erhebliche Variabilität hinsichtlich Schwere, Chronizität und Therapierbarkeit, führen zumeist aber nicht zu einer dauerhaften Visusminderung. Dies unterscheidet die okulären Veränderungen grundsätzlich von der praktisch immer schweren Hörminderung mit nur eingeschränkter Reversibilität selbst bei frühem Therapiebeginn.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 Cogans 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.

Therapy of uveitis in children.

With an incidence of approximately 4.3 to 6 and a prevalence of 30 patients in 100,000 population, uveitis in children may affect approximately 5% to 10% of all uveitis patients. There is general consensus that uveitis in children is different as compared with uveitis in adult patients with regard to both the nature of the underlying disorders and the general course of the various diseases. It also seems that the lens, macula, and optic disc are more susceptible to developing irreversible changes compared with adults, and that druginduced side effects can be both more common and problematic in children. This article will give an update on management of uveitis in children. We will first cover treatment for anterior, intermediate, and posterior uveitis, followed by an update of the drugs used to treat uveitis in children. Finally, the role of the pediatrician in therapy will be discussed. Studies published in the last years have provided considerable information concerning new drugs for the treatment of uveitis in

Colour vision in normal subjects tested by the colour arrangement test ‘Roth 28-hue desaturated’

The aim of the study was to obtain normal values for the colour-arrangement test, Roth 28-hue desaturated. In 146 healthy non-smokers colour vision was tested monocularly. The subjects were divided into four age groups: 0-19, 20-39, 40-59, and 60-79 years. The overall error score for all groups was 54 +/- 24 (median +/- mean absolute deviation). The values for the 20-39 year group were significantly lower than those for the other groups (Kruskal-Wallis: P < 0.0001 with subsequent multiple Mann-Whitney test). An increasing predominance of errors along the blue-yellow-axis was observed with increasing age. The error scores of normal subjects tested by the Roth 28-hue desaturated were comparable with those on the well-known Farnsworth-Munsell 100-hue (FM-100). Because the Roth 28-hue desaturated is shorter and simpler to administer, it is an alternative to the FM-100 in situations that need to assess colour discrimination and error axis quantitatively and quickly.

Influence of interferon-alpha on lymphocyte subpopulations in Behçet's disease.

In Behcet’s disease (BD)‚ several abnormalities of lymphocyte subpopulations such as an elevation of NK and T-cells have been described. Standard treatment comprises immunosuppressive drugs. We successfully treated 50 patients with ocular BD with interferon (response rate 92%) which is counterintuitive because is immunostimulatory and can sometimes even induce autoimmune diseases such as SLE or RA. The aim of this study was to elucidate the immunomodulatory effects that might exert in BD.

Behçet's Disease: Visual Acuity after 5 Years in Patients with Alpha-Interferon Treatment

Compared to conventional immunosuppressants, IFN-α2a seems to be much more effective to prevent a loss or decrease of visual acuity over a long period of time in patients with severe ocular BD.

Comparing “suprathreshhold” and “threshhold splitting perimetry” using the Tübinger Automatic Perimeter CC

Background: We compared the standard suprathreshhold strategy to the so-called threshhold splitting strategy with 5 and 2 dB steps. The aim of the study was to establish whether the threshhold splitting strategy had advantages over the suprathreshhold strategy that has been used to date. Method: We examined the 30 ° visual field in 49 volunteers using suprathreshhold perimetry and on the same day threshhold splitting perimetry on the Tübinger Automatic Perimeter CC. A total of 191 test points were examined in suprathreshhold strategy. Using the threshhold splitting strategy, 67 test points were examined, with a test-point design similar to other perimeters with the threshhold splitting strategy. The criteria for inclusion in the study were central light sensitivity differences greater than 25 dB, fixation better than 80 % and an illumination class density < 2. Results/Discussion: The average duration of the examination using the suprathreshhold strategy was 2–3 min quicker than the threshhold splitting strategy in normal visual fields or small scotomas, but it took up to 15 min longer if large scotomas were present. Interpretation of the scotoma configuration showed subjective differences: the smaller the scotoma, the greater the differences because of the fact that threshhold splitting perimetry utilizes test points that are farther apart than those used in suprathreshhold perimetry.Einleitung: Am Tübinger Automatikperimeter CC wurde eine vergleichende Studie zwischen der bekannten, schwellenorientiert überschwelligen Strategie und einer Schwellenwertstrategie mit 2 facher Eingabelung in 4- und 2-dB-Schritten durchgeführt. Ziel der Untersuchung war es, festzustellen, ob die Schwellenwertstrategie Vorteile gegenüber der bisher eingesetzten schwellenorientiert überschwelligen Strategie bietet. Methode: 49 freiwillige Patienten wurden am gleichen Tag mit der schwellenorientiert überschwelligen Perimetrie und der Schwellenwertperimetrie am Tübinger Automatikperimeter im 30 °-Gesichtsfeld untersucht. Die Untersuchung erfolgte mit 191 Punkten bei der schwellenorientiert überschwelligen Strategie. 67 Punkte wurden bei der Schwellenwertstrategie eingesetzt, ähnlich der Prüfpunktanordnung anderer Perimeter mit Schwellenwertstrategie. Einschlußkriterien waren: zentrale Lichtunterschiedsempfindlichkeit > 25 dB, Fixation > 80 %, geprüfte Leuchtdichteklasse < − 2. Ergebnisse/Diskussion: Bei unauffälligen Gesichtsfeldbefunden oder kleinen Skotomen war die schwellenorientiert überschwellige Strategie um 2–3 min schneller als die Schwellenwertstrategie, bei großen Skotomen um bis zu 15 min langsamer. Auch in der subjektiven Prüfung der Ausfallskonfiguration fanden sich Unterschiede. Bei großflächigen Skotomen war die Erkennbarkeit der Ausfallskonfiguration für beide Strategien gegeben. Mit Abnahme der Skotomgröße führte das grobe, bei der Schwellenwertperimetrie verwendete Raster dazu, daß im Vergleich zur schwellenorientiert überschwelligen Perimetrie mit größerer Rasterdichte die Erkennbarkeit der Ausfallskonfiguration nachließ.