Ocular Behcet's Disease Research Articles

Short-term Effects and Side Effects of Tacrolimus for Behçet's Uveitis

Purpose: To investigate the clinical effects and side effects of Tacrolimus for ocular Behcet's disease. Methods: Eight patients (male: 5, age: 35±7.5 (25-48) years) with Behcet's uveitis, refractory posterior uveitis unresponsive to combination treatment with cyclosporine, azathioprine, and oral steroid or significant cyclosporine-related adverse effects were recruited prospectively, and cyclosporine was switched to Tacrolimus. Visual acuity, degree of anterior chamber, and vitreous haze were compared before the conversion and three months after. Oral glucose tolerance, plasma insulin, cholesterol, creatinine, and aspartate (AST)/alanine aminotransferase (ALT) were measured to monitor systemic effects. Results: Visual acuity did not change significantly after conversion to Tacrolimus. Anterior chamber (seven patients) and vitreous (four patients) inflammation were found before conversion and decreased or disappeared after conversion. Overall plasma levels of glucose, insulin, creatinine, and AST/ALT were similar before and after conversion. However, cholesterol was significantly decreased after conversion (p=0.028). One patient developed diabetes mellitus. Conclusions: Tacrolimus may be effective for Behcet's uveitis unresponsive to or intolerable of traditional treatments. In addition, periodic monitoring for side effects, such as hyperglycemia and diabetes mellitus, may be necessary.

Performance analysis of classical, model-based and eigenvector methods: Ophthalmic arterial disorders detection case

In this study, ophthalmic arterial Doppler signals recorded from 214 subjects were processed using classical, model-based, and eigenvector methods. The classical method (fast Fourier transform), two model-based methods (Burg autoregressive, least squares modified Yule–Walker autoregressive moving average methods), and three eigenvector methods (Pisarenko, multiple signal classification, and Minimum-Norm methods) were selected for performing spectral analysis of the ophthalmic arterial Doppler signals. Doppler power spectral density estimates of the ophthalmic arterial Doppler signals were obtained using these spectrum analysis techniques. The variations in the shape of the Doppler power spectra were examined in order to detect variabilities such as stenosis, ocular Behcet disease, and uveitis disease in the physical state of ophthalmic arterial Doppler signals. These power spectra were then used to compare the applied methods in terms of their frequency resolution and the effects in detecting stenosis, Behcet disease and uveitis disease in ophthalmic arteries.

Granulocytapheresis in patients with refractory ocular Behcet's disease

Intraocular inflammation (uveoretinitis) is one major complication of Behcet's disease (BD) and responds poorly to drug therapy. This open prospective study was to assess the efficacy of selective granulocytapheresis in patients with refractory uveoretinitis of BD. Fourteen patients aged 20-56 years were treated. Granulocytapheresis was done with an Adacolumn filled with cellulose acetate leucocyte carries or beads that adsorb granulocytes and monocytes from the blood in the column. Each patient received 5 Adacolumn sessions at one session/week over 5 consecutive weeks. The study was designed to allow each patient to serve as his or her own control. The total numbers of ocular attacks (OA) were monitored for 6 months before and after 5 Adacolumn sessions. The number of OA (mean +/- SD) per patient for the 6 months before Adacolumn was 4.21 +/- 1.6 and for the 6 months post Adacolumn was 2.93 +/- 1.39 ( P = 0.0275). Nine patients (64%) improved and 5 did not change or worsened. Further, for a sub-group (n = 7) with duration of BD > or =5 years, the number of OA were 4.71 +/- 1.89 for the first 6 months and 2.29 +/- 1.38 for the second 6 months ( P = 0.0054). The corresponding values for a sub-group (n = 7) with duration of BD<5 years were 3.71 +/- 1.25 and 3.57 +/- 1.13, indicating that patients with long duration of BD are better responders. We conclude that granulocytapheresis might be effective and safe for patients with refractory ocular BD. Further studies are necessary to fully evaluate the clinical efficacy of granulocytapheresis for BD.

Analysis of Doppler ultrasound signals based on fuzzy similarity index

Abstract In this paper, we introduced fuzzy similarity index for analysis of the Doppler ultrasound signals. Doppler ultrasonography is a reliable technique, which demonstrates the flow characteristics and resistance of arteries in various arterial diseases. The analyzed ophthalmic arterial (OA) Doppler signals were recorded from healthy subjects and subjects suffering from ophthalmic artery stenosis, ocular Behcet disease and uveitis disease. The OA Doppler signals were decomposed into time–frequency representations using discrete wavelet transform and wavelet coefficients were calculated to represent the signals. The aim of the study is discriminating the OA Doppler signals by the combination of wavelet coefficients and fuzzy similarity index. Toward achieving this aim, fuzzy sets were obtained from the feature sets (wavelet coefficients) of the signals under study. Our results demonstrated that the similarity between the fuzzy sets of the studied signals indicated the variabilities in the OA Doppler signals. Thus, the fuzzy similarity index could discriminate the healthy OA Doppler signals and the other three disease states (stenosis, ocular Behcet disease and uveitis).

Determining variability of ophthalmic arterial Doppler signals using Lyapunov exponents

The new method presented in this study was directly based on the consideration that ophthalmic arterial Doppler signals are chaotic signals. This consideration was tested successfully using the nonlinear dynamics tools, like the computation of Lyapunov exponents. Multilayer perceptron neural network (MLPNN) architecture was formulated and used as a basis for determining variabilities such as stenosis, ocular Behcet disease, and uveitis disease in the physical state of ophthalmic arterial Doppler signals. The computed Lyapunov exponents of the ophthalmic arterial Doppler signals were used as inputs of the MLPNN. Receiver operating characteristic (ROC) curve was used to assess the performance of the detection process. The ophthalmic arterial Doppler signals were classified with the accuracy varying from 93.75% to 97.06%. The results confirmed that the proposed MLPNN trained with Levenberg–Marquardt algorithm has potential in detecting stenosis, Behcet disease and uveitis disease in ophthalmic arteries.

Detection of ophthalmic arterial doppler signals with Behcet disease using multilayer perceptron neural network

Doppler ultrasound is known as a reliable technique, which demonstrates the flow characteristics and resistance of ophthalmic arteries. In this study, ophthalmic arterial Doppler signals were obtained from 106 subjects, 54 of whom suffered from ocular Behcet disease while the rest were healthy subjects. Multilayer perceptron neural network (MLPNN) employing delta-bar-delta training algorithm was used to detect the presence of ocular Behcet disease. Spectral analysis of the ophthalmic arterial Doppler signals was performed by least squares (LS) autoregressive (AR) method for determining the MLPNN inputs. The MLPNN was trained with training set, cross validated with cross validation set and tested with testing set. All these data sets were obtained from ophthalmic arteries of healthy subjects and subjects suffering from ocular Behcet disease. Performance indicators and statistical measures were used for evaluating the MLPNN. The correct classification rate was 96.43% for healthy subjects and 93.75% for unhealthy subjects suffering from ocular Behcet disease. The classification results showed that the MLPNN employing delta-bar-delta training algorithm was effective to detect the ophthalmic arterial Doppler signals with Behcet disease.

TNF and anti-TNF agents in Behçet's disease

The rapid response and effectiveness of anti-TNF agents in the treatment of many immune mediated inflammatory disorders draws comparison to the response of rheumatoid arthritis to cortisone, first witnessed over 50 years ago by Philip Hench and colleagues at the Mayo Clinic. It is now known that many of the anti-inflammatory effects of corticosteroids are due to their inhibition of TNF production. A new dimension of efficacy is possible with TNF agents, however, in that inhibition of disease progression is now possible. Might these agents be considered the corticosteroids of the new millennium? Like rheumatoid arthritis and Crohn's disease, Behcet's disease is believed to be associated with a Th1-mediated immune response. Increased levels of TNF-α are found in Behcet's disease and has provided support for the empiric use of anti-TNF-α therapies used in a number of published cases and small case series. Hassard (2001) reported rapid and dramatic improvement in gastrointestinal and extraintestinal symptoms and findings of the disorder after treatment with infliximab. Similar response was seen in two other patients treated by Travis (2001). This experience was followed by the report of Robertson (2001) of a patient free of oral and genital ulcerations for the first time in 10 years after three infusions of infliximab. Remission of mucocutaneous symptoms for one year followed two infusions of infliximab in a patient previously uncontrolled by multiple immunosuppressive agents (Goossens, 2001). Mucocutaneous lesions remitted with infliximab in a patient with Behcet's disease associated with rheumatoid arthritis (Rozenbaum, 2002). At EULAR 2002, Turkish investigators reported the results of the first double-masked, placebo-controlled study (n = 40) of anti-TNF therapy with etanercept in mucocutaneous Behcet's disease (Melikoglu, 2002). This agent suppressed disease manifestations with resurgence after the drug was discontinued. Additional recent reports of anti-TNF therapies in Behcet's disease were presented at several international meetings. The experience with anti-TNF-α treatments for the ocular manifestations of Behcet's disease has been growing and very positive. Sfikakis (2001) reported the benefits of infliximab in five patients with panuveitis in Behcet's disease. This included two patients treated with infliximab therapy without an increase in conventional treatment. At the ACR meeting in 2002 these Greek investigators reported successful monotherapy with infliximab in acute ocular inflammation in Behcet's disease in 14 patients. The authors suggested that the dramatic and rapid response in these patients would favor the use of this agent over conventional therapy. Positive responses to anti-TNF agents in ocular Behcet's disease have been documented in numerous case reports in the literature or presentations at international meetings. Significant differences exist between currently available anti-TNF-α agents, including mechanism of TNF-α inhibition, avidity, half life, immunogenicity, ability to bind lymphotoxin (TNF-β), ability to bind membrane bound TNF-α, as well as the mode and frequency of administration. One or more of these differences may account for the variable efficacy of these agents in certain diseases, such as Crohn's disease, and the variable side-effect profile of these drugs. We believe that it is appropriate to study all available agents, including adalimumab, for their efficacy and safety in Behcet's disease. The efficacy of these new biologic agents for the more serious manifestations of Behcet's disease, in particular, should be investigated.

Perspectives of the Working Group on Drug Trials including Collaborative Trials of the ISBD and rationale for new clinical trials

The goals of the working group are to contact and recruit members; to contact other working groups and propagate their work particularly in the context of established criteria of diagnosis and disease activity in Behcet's disease (BD); to exchange experience via direct contact, home page, journal and/or newsletter; to plan collaborative trials; to contact pharmaceutical companies and research institutes for possible cooperation in clinical trials; to prepare a workshop on clinical trials at ISBD congresses; and to support and alert patients concerning treatment modalities. Additional clinical trials are needed. From both the physicians' and the patients' perspective, current therapy does not satisfy the goals of treatment (e.g. preventing blindness in ocular BD, preventing morbidity and mortality of neurologic and vascular events, improving the quality of life). Serious adverse effects may result from current therapies. Professor S Assaad-Khalil reported the results of a retrospective evaluation of therapeutic agents commonly used in BD, which he had recently carried out in 127 patients (110 males, 17 females; 20–65 years old) randomly selected from the Alexandria BD registry to assess the efficacy of different therapeutic agents in daily practice for a mean duration of 11.07 years by the same group of observers. A special focus was made on the ocular sequelae of the disease, with detailed ocular documentation carried out in 254 eyes (visual acuity, intraocular pressure, state of the lens, presence of uveitis, retinal vessels and optic nerve). Of BD patients 16.6% lost effective vision and another 17.6% of the patients had reduced vision lower than 6/60. Uveitis was found in 37.4%, lens opacity in 44.9%, retinal vessel affection occurred in 23.3% and optic nerve affection in 29.9%. In conclusion, it can be seen that eye sequelae are still very devastating in BD, with a delay in diagnosis having a significant deleterious effect on the outcome of the disease. There is still no ideal therapeutic regimen resulting in full remission of BD and preventing its sequelae. At present, combination therapy seems to be the most appropriate approach when considering efficacy and safety. However, there is a great need for a controlled and masked multicentre trial to re-evaluate the efficacy and safety of the different therapeutic modalities on a long term basis. Investigators must continue to have strong ethical commitments to patients in designing clinical trials. Trials serving patients, patients' life, health and well-being is our goal. There should be actual representation of the patients in the design of the clinical trials. A prospective study design, predetermined specific primary endpoints and blinding should ensure the integrity of the study. Improvement should be quantified as objectively and accurately as possible, putting into consideration patient's quality of life, and measuring all adverse effects. Statistics should depend on strict criteria for statistical significance, avoiding post hoc analysis.

Ocular and neurological Behcet's disease without orogenital ulceration?

A 28 year old West Indian patient is described who had a relapsing and remitting steroid-sensitive illness for 3 years. The clinical features included uveitis and widespread CNS involvement. The patient was treated as though he had neurosarcoidosis. Post mortem examination revealed histological changes compatible with a diagnosis of Behçet's disease, but at no time did he suffer from oral or genital ulceration or arthritis. The authors suggest a new term to encompass such an entity: the "Behçet's MINUS" syndrome (multifocal intermittent neurological and uveitic syndrome).

Low-dose Cyclosporin a in uveitis a long-term follow-up

Seventy patients suffering from bilateral endogenous chronic uveitis or ocular Behcet's disease have been treated with 5 mg/kg/day Cyclosporin A. All patients were followed at regular intervals for up to eight years. In this group of patients, we observed that CsA is an effective drug for the treatment of intraocular inflammation. Patients have needed continuous treatment with CsA for an average period of 31 months. Exacerbations of the inflammatory processes have been observed in 95% of the patients on initial attempts to lower the CsA dosage. These exacerbations were controlled either by local treatment or a combination of low-dose systemic corticosteroids. Elevation of the serum creatinine was initially observed in all patients when under the higher doses of CsA. However, only 15 patients (21.4%) had levels which were higher than the upper normal limit. Elevation of the bilirubin level of 50% or more above baseline was observed in 45 patients (64.3%) but only 11 patients (15.7%) showed levels which were above the upper normal limit. During this period of follow-up, cure was achieved in 25 patients and no exacerbations were observed up to five years after discontinuation of treatment.

Antibodies to Oral Mucosa in Patients with Ocular Behcet's Disease

A method is reported for the identification of cytoplasmic antibodies in patients with Behcet's disease and uveitis. The assay appears positive in at least 80% of patients in an American population with definite or probable Behcet's disease and 60% of patients from a Turkish population with definite Behcet's disease, with a false-positive rate of 6.5% among non-Behcet's ocular inflammatory disorders with vasculitis. When refined, this test may prove useful to the ophthalmologist in selecting out those patients with Behcet's disease from the larger group of patients with uveitis for whom no systemic etiology is identified.