[Intraocular inflammation in multiple sclerosis]. / Intraokulare Entzündung bei multipler Sklerose.

Multiple sclerosis (MS) is a chronic inflammatory disorder of the brain and the spinal cord occurring mostly in young adults and is associated with temporary or permanent neurological deficits. An association between uveitis and MS has been recognized for a long time. Current data indicate an approximately 10 times higher prevalence of uveitis in patients with MS compared to the general population. In particular, MS is associated with intermediate uveitis and typically with concomitant retinal vasculitis. The treatment of uveitis should not only take the severity of intraocular inflammation into account but a coordination of the active agents must also consider the neurological manifestations. Since uveitis and MS are pathogenetically based on an immune-mediated genesis, immunomodulatory treatment approaches are dominant but it is important to bear in mind that tumor necrosis factor(TNF)-alpha blocking agents may worsen MS.

[Ocular involvement in rheumatoid arthritis, connective tissue diseases and vasculitis]. / Augenbeteiligung bei rheumatoider Arthritis, Kollagenosen und Vaskulitiden.

There are many interfaces between ophthalmologists and rheumatologists. On the one hand ophthalmologists face the question if an inflammation of the eye is caused by systemic inflammatory rheumatic diseases and on the other hand rheumatologists have to consider that ocular manifestations are relatively common in some inflammatory rheumatic diseases. Furthermore, these ocular manifestations may influence therapeutic decisions of the rheumatologist. This article summarizes which ocular inflammations can be associated with rheumatoid arthritis, connective tissue diseases and vasculitides. The description of acute anterior uveitis in spondyloarthritis and in juvenile idiopathic arthritis is omitted in this article but will be dealt with elsewhere in this issue.

[Treatment of posterior noninfectious uveitis : Current situation and future developments]. / Therapie der posterioren, nichtinfektiösen Uveitis : Aktueller Stand und künftige Entwicklungen.

Treatment of autoimmune diseases has undergone significant changes and developments in recent years. New classes of active substances, in particular biologics and small molecules have resulted in previously unknown success in the treatment of many diseases. In particular patients suffering from autoimmune rheumatic or dermatological diseases have benefited. For autoimmune uveitis there are numerous reports indicating excellent therapeutic and preventive effects; however, statutory approval for therapy in adults is still pending. This article outlines recent advances and future therapeutic options for the treatment of posterior segment noninfectious uveitis.

[Diagnostics and treatment of primary vitreoretinal lymphoma]. / Diagnostik und Therapie des primären vitreoretinalen Lymphoms.

BACKGROUND: Primary vitreoretinal lymphoma (PVRL) is a rare ocular lymphoid malignancy, mostly a diffuse large B-cell lymphoma. The PVRL, previously called primary intraocular lymphoma (PIOL), is a subset of primary central nervous system lymphoma (PCNSL). DIAGNOSIS: The diagnosis of PVRL is often difficult as it often mimics chronic intermediate or posterior uveitis; therefore, PVRL requires various procedures for the diagnostics, e.g. immunohistochemistry, cytology, pathology, molecular pathology and cytokine analysis (interleukin 10) after surgically obtaining ocular specimens. THERAPY: Treatment forms that are effective for systemic lymphomas have not been reliably successful for PVRL and PCNSL. Current management of PVRL consists of chemotherapy, such as methotrexate or rituximab, possibly combined with external beam radiation whereby both chemotherapeutic agents are administered systemically as well as intravitreally. Intravitreal treatment alone is recommended solely in the case of monocular PVRL, which is highly controversial. A PVRL usually responds well to initial treatment; however, relapse rates and CNS involvement are high, resulting in a poor prognosis and limited survival.

[Lymphoma of the ocular adnexa]. / Lymphome der okulären Adnexe.

BACKGROUND: Lymphomas of the ocular adnexa are heterogeneous and demonstrate a wide range of clinical, histological, immunohistochemical and molecular genetic characteristics. AIM: The aim of this article is to give an overview of the interdisciplinary diagnostics and individually adapted lymphoma subtype-based therapy. DIAGNOSTICS: Depending on the lymphoma localisation, i.e. whether in the eyelid, the conjunctiva or in the orbit, a photograph or a radiological scan is required to record the tumor extent. Visual function is more likely to be impacted when the lymphoma arises in the posterior orbit, close to the optic nerve and imaging diagnostics are therefore necessary. Histological investigations are essential for confirming the lymphoma diagnosis and give information about the particular subtype, which in turn will determine subsequent patient management, Clinical staging investigations for determining the systemic extent of the lymphoma manifestation (e.g. imaging, blood analyses as well as bone marrow biopsy) are mandatory. THERAPY: External beam radiation, local and systemic chemotherapy or in some cases antibiotics are treatment options after surgical excision in isolated ocular adnexal lymphoma. The TNM classification of the American Joint Committee on Cancer or the Ann Arbor staging system, as well as the guidelines of the German Society of Hematology and Medical Oncology are all tools to aid the choice of the appropriate individually adapted therapy for systemic disease, which includes psycho-oncological care.

[Behcet's disease--ophthalmological and general aspects: Part 2: Therapy]. / Morbus Behçet--ophthalmologische und allgemeine Aspekte: Teil 2: Therapie.

Behcet's disease (also called Admantiades-Behcet syndrome) is a chronic vasculitis. The disease is characterized by exacerbations and remissions of symptoms and organ manifestations and may produce only mild mucocutaneous lesions, whereas ocular lesions can cause blindness. In addition, involvement of the gastrointestinal tract, central nervous system (CNS) and large blood vessels is sometimes life-threatening. Cyclosporin A is the only agent for treatment of ocular lesions registered in Germany; however, the neurotoxicity and nephrotoxicity restrict usage of the drug. In patients suffering from severe uveitis, biologics have been a breakthrough. Interferon (IFN) alpha therapy has shown significant efficacy for intraocular inflammation. Monoclonal antibodies to TNF-alpha and interleukin-1 have been successful in clinical trials and are approved in some countries. This article summarizes the current state of knowledge and emphasizes the important role of the ophthalmologist in the therapy of Behcet's disease.

[Behçet's disease - ophthalmological and general aspects part I : etiology, pathogenesis and diagnostics]. / Morbus Behçet - ophthalmologische und allgemeine Aspekte Teil I : Ätiologie, Pathogenese und Diagnostik.

Behçet's disease (also known as morbus Behcet or Admantiades-Behcet syndrome) is a chronic vasculitis mainly characterized by recurrent mucocutaneous lesions and sight threatening uveitis. It may also involve joints, vessels of all sizes and the central nervous system. Because of its severe morbidity and considerable mortality early diagnosis and treatment is important. Treatment and prognosis of this disorder have profited considerably in recent years following the introduction of biologic agents. This article summarizes the current state of knowledge and emphasizes the important role of the ophthalmologist in the diagnosis and therapy of Behçet's disease.

[Inflammatory choroidal neovascularisations]. / Inflammatorische choroidale Neovaskularisationen.

Inflammation plays a key role in the induction of choroidal neovascular membranes (CNV). This explains why each form of posterior uveitis may lead to CNV formation. Diseases like presumed ocular histoplasmosis syndrome (POHS), multifocal choroiditis (MFC) or punctate inner choroidopathy (PIC) carry a high risk of CNV creation. Inflammatory processes mostly cause classical membranes. Because of the classical membrane form, smaller membrane size and the younger age of the patients' inflammatory membranes are often better treatable than membranes in AMD patients. In the times before VEGF inhibition inflammatory membranes were treated with argon laser coagulation and later with PDT. Nowadays better visual acuity results are achievable through VEGF inhibitor injections with or without PDT. This is proven by a few publications with greater numbers of patients because of the rarity of the diseases and several case reports in the literature. In addition to CNV treatment the control of intraocular inflammation should never be forgotten because it forms the leading CNV trigger.

[Typical and atypical ocular manifestations of Behçet's disease]. / Typische und untypische okuläre Manifestationen beim Morbus Behçet.

The first ocular symptom in 50-87% of patients with Behçet's disease (BD) is unilateral anterior uveitis. As a characteristic sign of ocular BD the appearance of hypopyon iritis was originally described by Adamantiades and Behçet, but nowadays, probably due to an earlier and more aggressive treatment, this rarely occurs. In the further course of the disease up to 75% of BD patients develop a bilateral chronic relapsing form of posterior uveitis or panuveitis. In addition occlusive retinal vasculitis, which involves arteries as well as veins, is frequently present. A typical complication consists of a cystoid macular edema, which is, besides the retinal vasculitis, responsible for the limited prognosis of visual acuity.

[Comments on the pathogenesis of Behçet's disease. A key to understanding new therapies?]. / Anmerkungen zur Pathogenese des Morbus Behçet. Ein Schlüssel zum Verständnis neuer Therapien?

The etiology and pathogenesis of Behçet's syndrome remains unclear. It has been postulated that an infectious agent may induce an immune-mediated, generalized vasculitis in genetically predisposed individuals (HLA-B51 +). There is accumulating evidence that an abnormality of the innate and adaptive immune response, e.g. directed against heat shock proteins plays an important role in Behçet's syndrome. This article is intended to evaluate the more recent knowledge on this disorder and evaluate new therapeutic options.

[Janus-faced?: Effects and side-effects of interferon therapy in ophthalmology]. / Ein Januskopf?: Wirkungen und Nebenwirkungen der Interferontherapie in der Augenheilkunde.

Interferon alpha (IFN-α) and interferon beta (IFN-ß) are naturally occurring cytokines, which belong to the type I interferons and share the same receptor leading to very similar therapeutic effects. The immunomodulatory effect of type I interferons includes modulation of antibody production, inhibition of lymphocyte proliferation, inhibition of delayed-type hypersensitivity and enhancement of T-cell and NK-cell cytotoxicity. An increasing number of open clinical studies and case reports have demonstrated the efficacy of IFN-α for severe ocular inflammation in patients with Behçet's disease and of interferon-ß, which has been used mainly for the treatment of multiple sclerosis.

[Anti-TNF-α treatment for uveitis. Analysis of the current situation]. / Anti-TNF-Therapie bei Uveitis. Eine Standortbestimmung.

Biologicals are selectively acting proteins that demonstrated high efficacy in the treatment of chronic disorders. In particular, biologicals blocking tumor necrosis factor α (TNF-α), an essential cytokine in chronic inflammatory diseases, have demonstrated great promise. Experimental and clinical data indicate that TNF-α plays an important role in intraocular inflammation. Neutralization of TNF-α might therefore be a promising strategy for prevention and treatment of uveitis. Here we review the principle effects, therapeutic value, and potential side effects of anti-TNF agents in uveitis.

[Arthrogryposis multiplex congenita and retinitis pigmentosa]. / Arthrogryposis multiplex congenita und Retinitis pigmentosa.

BACKGROUND: Arthrogryposis multiplex congenita (AMC) is a heterogeneous pattern of symptoms consisting of clinically different types. AMC is a non-progressive condition, which is characterized by congenital contracture of several joints in different body areas and may also occur as a manifestation of other syndromes. In such syndromes retinopathy as an ophthalmological manifestation of AMC has been described in the literature in only two patients. CASE REPORT: A 12-year-old girl with AMC presented with progressive visual loss since 1 year. Visual acuity was 0.5 in the right and 0.8 in the left eye. Visual fields were concentrically constricted. Funduscopy revealed an atrophic retinal pigment epithelium of the whole fundus with vital optic discs. In the scotopic electroretinogram (ERG) amplitudes were dramatically decreased or absent and cone signals were delayed. The multifocal ERG (mfERG) presented pathologically reduced amplitudes in the macular region as well as in the periphery. Examinations 5 and 8 years later revealed a reduction of visual acuity to 0.05 in the right and to 0.1 in the left eye, in addition the results of perimetry and of the Ganzfeld-ERG had deceased and the mfERG was no longer measurable. CONCLUSION: This young female demonstrated an AMC in combination with retinitis pigmentosa, but other disease manifestations or cerebral retardation could not be found. We present here an unusual case of what seems to be a new athrogryposis syndrome.

Efficacy and tolerability of interferon alpha treatment in patients with chronic cystoid macular oedema due to non-infectious uveitis.

AIM: To assess the efficacy and tolerability of interferon (IFN) alpha in chronic cystoid macular oedema (CMO) due to non-infectious uveitis. METHODS: Retrospective analysis of an interventional case series. IFN alpha-2a was administered at an initial dose of 3 or 6 million IU per day subcutaneously and tapered afterwards to the lowest possible dose to maintain the absence of CMO. Treatment efficacy was assessed by optical coherence tomography. RESULTS: Twenty-four patients with chronic CMO (median duration 36.0 months) due to non-infectious anterior (n = 2), intermediate (n = 18) or posterior (n = 4) uveitis have been analysed. Ineffective pretreatment included systemic corticosteroids (all patients), acetazolamide (22 patients) and at least one immunosuppressive drug (18 patients). IFN therapy was shown to be effective (= complete resolution of CMO within 3 months, able to taper IFN) in 15 patients (62.5%), partly effective (= incomplete resolution of CMO, unable to taper IFN) in six patients (25.0%) and not effective (= no response or recurrence of CMO) in three patients (12.5%). IFN treatment was generally well tolerated. Common side effects including flu-like symptoms, fatigue or increased liver enzymes were dose-dependent and led to discontinuation of IFN in only one patient. CONCLUSION: The data demonstrate IFN alpha to be an effective and well-tolerated therapy for chronic refractory uveitic CMO.