Background Behcet`s disease (BD) is a variable vessel vasculitis. To date, there are only retrospective case series showing efficacy of interferon alpha for ocular BD. This trial was started in 2007. Objectives To prove that interferon alpha2a is at least as effective as cyclosporin A. Methods Maintenance dosage of IFN was 3 to 9 Mill iU 3x/week, CSA dosage 3 to 5 mg/kg, adapted to response every two weeks. In case of nonresponse, the patients were switched to the alternative treatment arm after week six. Efficacy was measured by Posterior Uveitis scoring system (PUS), Behcet`s disease current activity form (BDCAF), Health assessment questionnaire (HAQ) and Beck depression Inventory (BDI) were also used. Primary endpoints were time to remission by PUS and number of cross over from one arm to the other. Results The study was stopped in 2013 after 37 patients due to slow recruitment. 13 patients per treatment arm (n=26, 65% male, 35% female, 38% German, 50% Turkish, 12% other, mean age 30.5 years) were evaluated. All 13 patients with primarily IFN achieved remission of their ocular disease, 9 of 13 in the CSA arm (p=0.096). The median time to complete PUS remission was 84 vs. 72 days, p=0.899. The probability to achieve remission after one year was 0.92 for IFN (95% CI 0.49–0.99) and 0.62 for CSA (95%CI 0.24–0.81). There were significantly more switches from CSA to IFN (n=7) than vice versa (n=1) (p=0.030). The main reasons were inefficacy (n=4 for CSA) and/or side effects (n=3 for CSA). PUS of the affected eyes improved significantly in both arms during the first year (p<0.001). Visual acuity at baseline was significantly better in the CSA arm than in the IFN arm, hence a significant improvement over time could only be shown in the IFN arm (p<0.003 week 30). BDCAF improved in both arms (p>0.001), as did HAQ (p=0.047). Safety analysis revealed more hair loss (p=0.004) and cytopenia (p<0.001) in the IFN and hypertension (p=0.048) in the CSA arm. Conclusions Both treatments are effective for ocular and extraocular BD. There is a tendency towards superiority of interferon alpha considering that there were more switches from CSA to IFN due to inefficacy and side effects. Due to the small sample size, this did not reach significance. A prospective international multicenter trial may help to overcome these limitations. Acknowledgement This trial was supported by the German Ministry of Health (BMBF/DLR, No. 01KG0706) and by Roche (supply of interferon alpha2a) Disclosure of Interest None declared
Ein 21-jähriger Patient stellte sich vor wegen Kopfschmerzen, Verschwommensehen und der Wahrnehmung von Farbringen um Lichtquellen. Bei gering herabgesetzter Sehschärfe betrug der intraokulare Druck auf dem rechten Auge 44 mmHg und auf dem linken Auge 49 mmHg. Der Vorderabschnittsbefund ergab beidseits einen Vorderkammerreizzustand mit Zellen und Tyndall 2 +, vereinzelt retrokorneale, speckige Endothelpräzipitate und ein umschriebenes entzündliches Irisinfiltrat. Der hintere Augenabschnitt war beidseits unauffällig. Als Ursache für die klinische Verdachtsdiagnose eines akuten sekundären Offenwinkelglaukoms bei granulomatöser Uveitis anterior konnte mittels erhöhter Werte von Angiotensin-Converting-Enzym (ACE), „soluble interleukin-2 receptor“ (sIL-2R) und einer Hiluslymphadenopathie in der Thoraxröntgenaufnahme eine Sarkoidose diagnostiziert werden, die auf eine lokale und systemische Kortikosteroidtherapie schnell und gut ansprach – mit Normalisierung des intraokularen Drucks.
A 21-year-old male presented with headache and blurred vision associated with halos around sources of light. The visual acuity was slightly reduced and the intraocular pressure in the left eye was elevated to 44 mmHg and in the right eye to 49 mmHg. Slit lamp examination of the anterior segment revealed bilateral cells and a Tyndall phenomenon 2 +, several cell clumps adherent to the corneal endothelium, known as mutton-fat keratic precipitates and a circumscribed inflammatory infiltration of the right iris. The posterior segment of both eyes was normal. The cause of the presumed clinical diagnosis secondary open angle glaucoma due to anterior granulomatous uveitis was sarcoidosis, confirmed by elevated serological markers of angiotensin-converting enzyme (ACE), soluble interleukin-2 receptor (sIL-2R) and by pulmonary hilar lymphadenopathy. The local and systemic corticosteroid therapy was successful and also normalized the intraocular pressure.
We report the endophthalmitis rate after cataract surgery in patients preoperatively given topical povidone-iodine and gentamicin-containing irrigation fluid as prophylaxis without intracameral cefuroxime or perioperative topical antibiotics. In a retrospective clinical study, we included patients undergoing cataract surgery over a 12-year period at one large university teaching hospital. Data from 26,566 cataract procedures were analysed. Cases of postoperative endophthalmitis were identified and diagnosed both clinically and microbiologically. A total of 26,566 cataract procedures were reviewed, and we identified 16 patients with postoperative endophthalmitis (rate: 0.6 per 1000 operations, or 0.06%; 95% confidence interval: 0.03-0.09%). A causative micro-organism was detected in 81.3% (13/16) of the cases. Most organisms were Gram-positive bacteria (10/13) with susceptibility to cefuroxime (9/10) and/or fluoroquinolones (4/8), and/or resistance to aminoglycosides (10/10). The three Gram-negative pathogens were susceptible to cefuroxime, aminoglycosides, and fluoroquinolones. Using our regimen of topical povidone-iodine and gentamicin irrigation, we observed a low postoperative endophthalmitis rate not differing from the infection rates recently reported in other large studies. We speculate that neither intracameral cefuroxime nor perioperative levofloxacin eye drops are necessary to minimise postoperative infectious complications following cataract surgery, and we suggest that the European Society of Cataract and Refractive Surgery guidelines (in which perioperative antibiotics are mandatory) therefore be revisited to permit alternative effective regimens for the prevention of postoperative infections following cataract surgery.
Die Uveitis intermedia betrifft 10 - 20 % aller Kinder, die an einer Uveitis erkranken. Im Vergleich zur anterioren Uveitis ist eine Zuordnung der zugrunde liegenden Systemerkrankung komplexer. Neben der häufigen idiopathischen Pars planitis kann die Uveitis intermedia postinfektiöser oder autoimmunogener Ursache sein. Gerade bei seltenen zugrunde liegenden systemischen Begleiterkrankungen ist es notwendig, dass an eine Assoziation gedacht wird und eine gezielte Differenzialdiagnostik eingeleitet wird. Der Artikel informiert über mögliche Ursachen einer Uveitis intermedia im Kindesalter und vergleicht die Inzidenz dieser assoziierten Erkrankungen mit dem Vorkommen im Erwachsenenalter.
Intraocular inflammation in children differs considerably from that found in adults. Therefore the diagnostic work-up has to be adapted to the age and specific diseases.The published literature was reviewed for results of clinical trials and consensus meetings. In addition, the authors have incorporated their own experience.Recommendations for a systematic and complete diagnostic work-up are given using tables where possible.A close cooperation between ophthalmologists and paediatricians is very important.
In this paper, we investigate possibilities and limitations of temperature change as a method for information display in mobile applications. While some widespread and well-recognized haptic displays such as force-feedback often trigger the user's immediate attention, we will focus on ambient strategies for tactile information display, that is, the display of gradual state changes in the user's periphery that do not unexpectedly interrupt her current tasks, but builds on the mind's ability for subliminal perception of environmental change instead [1, 2]. To this end, we present a series of prototypes of mobile devices that display ambient information by means of thermal change based on the thermo-electric effect [3]. In order to assess the expedience and feasibility of such a display, a series of user tests have been conducted with respect to both, the ability for thermal change recognition and a concrete application scenario for such a display.
Objective: Behcet disease (BD) is a multisystem vasculitis of unknown origin. Standard treatment mainly comprises systemic immunosuppressive agents. In a study primarily designed for refractory ocular disease, we additionally evaluated the efficacy of recombinant human interferon-alpha2a (rhIFN-alpha2a) on the extraocular manifestations of BD.Methods: Fifty patients were included in the study. RhIFN-alpha2a was applied at a dose of 6 x 10(6) units subcutaneously daily. Dose reduction was performed according to a decision tree until discontinuation. Disease activity was evaluated by the Behcet's Disease Activity Scoring System and the Uveitis Scoring System.Results: Response rate of the ocular manifestations was 92%. Visual acuity rose significantly from 0.56 to 0.84 at week 24 (P < .0001). Mean Behcet's Disease Activity Score fell in a dose-dependent fashion by 1.2 points in the first week (P < .0001) and 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, 17 patients have been off treatment and disease-free for 29.5 months (mean). In the other patients, maintenance IFN dosage is 3 million units 3 times weekly. Whereas extraocular manifestations such as genital ulcerations, arthritis, and skin lesions remitted with IFN, only 36% of oral aphthous ulcers responded.Conclusions: RhIFN-a2a is effective in ocular BD, resulting in significant improvement of vision and complete remission of ocular vasculitis in the majority of patients. It is also beneficial for the extraocular manifestations of the disease, although less so for oral aphthous ulcers.
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.
Background: Behcet'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 Behcets 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<0.000 1). 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 Behcet'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 Behcet's disease, leading to significant improvement of vision and complete remission of ocular vasculitis in the majority of the patients.