[Fusarium keratitis with dramatic outcome]. / Fusarienkeratitis mit dramatischem Ausgang.

BACKGROUND: Fungal keratitis is much less common in Europe than in Asia. Antifungal therapy can be applied topically as well as systemically and in advanced situations surgical intervention can become necessary. CASE REPORT: We present the case of a 60-year-old woman who suffered from Fusarium keratitis that showed progression to endophthalmitis following contact lens wearing. Due to numerous resistances against antimycotic drugs the eye had to be enucleated to prevent the pathogens from spreading. Histologically, major inflammatory activity could be detected but no causative organism could be found. The failure to detect a pathogen was in clear contrast to the clinical findings and was interpreted as being an overreaction of the immune response even after the Fusarium had been destroyed. CONCLUSION: If a fungal infection of the cornea is suspected, antimycotic therapy should be initiated as early as possible. In cases involving highly resistant pathogens the eye cannot always be saved.

[Immunotherapy of uveal melanoma: vaccination against cancer. Multicenter adjuvant phase 3 vaccination study using dendritic cells laden with tumor RNA for large newly diagnosed uveal melanoma]. / Immuntherapie beim Aderhautmelanom: Vakzination gegen Krebs. Multizentrische adjuvante Phase-III-Impfstudie mit Tumor-RNA-beladenen dendritischen Zellen bei neu diagnostizierten, großen Uveamelanomen.

Uveal melanomas are the most common malignant tumors of the eye. With modern molecular biological diagnostic methods, such as chromosome 3 typing and gene expression analysis, these tumors can be categorized into highly aggressive (monosomy 3, class II) and less aggressive forms. This molecular biological stratification is primarily important for determining the risk of these tumors as no therapy is currently available that is able to prevent or delay metastases. A randomized study of patients with a poor prognosis (monosomy 3) is currently being carried out in order to determine whether a cancer vaccine prepared from autologous (patient's own) dendritic cells and uveal melanoma RNA can prevent or delay progression and further metastases of this extremely aggressive form of cancer. Inclusion in the uveal melanoma study, which hopes to provide a potential therapeutic option for patients, is only possible if patients are referred to an institution that is able to manufacture and provide this vaccination before the patient is operated on or treated with radiation. Untreated tumor material is necessary for producing the vaccine on an individualized patient basis.

[The German Acanthamoeba keratitis register: Initial results of a multicenter study]. / Das Deutsche Akanthamöbenkeratitis-Register : Erste Ergebnisse einer multizentrischen Erhebung.

BACKGROUND AND PURPOSE: In September 2011 the cornea section of the German Ophthalmological Society (DOG) established the first German Acanthamoeba keratitis registry. The data of this multicenter survey are being collected, compiled and evaluated at the Department of Ophthalmology at the Saarland University. The aim of this article is to present an intermediate report. PATIENTS AND METHODS: Data from 172 eyes with Acanthamoeba keratitis were collected during the last 10 years. For this interim report we actually evaluated 121 eyes (60.2 % female patients, average age 41.3 years) and collected the following data: date of onset of symptoms, date and method of diagnosis, initial diagnosis, anamnestic data, clinical symptoms and signs at diagnosis and during follow-up, conservative and surgical therapy. Criteria for inclusion in the Acanthamoeba registry was the established diagnosis of an Acanthamoeba keratitis with at least one of the methods described in this article. RESULTS: Acanthamoeba keratitis could be histologically proven in 55.3 % of the cases, via PCR in 25.6 %, with confocal microscopy in 20.4 % and using in vitro cultivation in 15.5 %. Clinical symptoms and signs in Acanthamoeba keratitis were pain in 67.0 %, ring infiltrates in 53.4 %, pseudodendritiform epitheliopathy in 11.7 % and keratoneuritis in 5.8 %. In 47.6 % of the cases the initial diagnosis was herpes simplex virus keratitis followed by bacterial keratitis in 25.2 % and fungal keratitis in 3.9 %. Acanthamoeba keratitis was the correct initial diagnosis in only 23.2 % of cases. The average time period between first symptoms and diagnosis was 2.8 ± 4.0 months (range 0-23 months). A triple therapy with Brolene® Lavasept® and antibiotic eye drops at least 5 ×/day was used in 54.5 % of eyes (n = 66). Penetrating keratoplasty was performed in 40.4 %, in 18 cases in combination with cryotherapy of the cornea. The mean graft diameter was 7.9 ± 1.1 mm (range 3.5-11.0 mm). The final visual acuity (Snellen visual acuity chart at 5 m) was comparable in the two groups of eyes with (5/40 ± 5/25) and without (5/32 ± 5/25) keratoplasty. CONCLUSION: Acanthamoeba keratitis is a rare and often very late diagnosed disease and two thirds of the cases were initially misdiagnosed. The early recognition of the typical symptoms is crucial for the prognosis of the disease. All ophthalmological departments in Germany are invited to submit further data of all confirmed cases (berthold.seitz@uks.eu), whether retrospectively or prospectively in order to generate an adequate standardized diagnostic and therapeutic approach for this potentially devastating disease.

[Beyond TGF-beta: wound healing modulation in filtering glaucoma surgery]. / Wundheilungsmodulation nach filtrierenden Glaukomoperationen: Was kommt nach TGF-beta?

Conjunctival scarring remains the major problem in filtering glaucoma surgery. Antimetabolites afford a reduction of scar formation, but considerable side effects limit their application. Here, we review the mechanisms and peculiarities of wound healing following glaucoma surgery and report on new developments in the field of wound healing modulation. The growth factor TGF-beta has a central role in wound healing and scarring. Therefore, novel concepts of wound healing modulation comprise scavenging of TGF-beta and specific inhibition of disinct downstream intracellular signalling pathways. Several compounds have entered preclinical evaluation and offer new potential to modulate scarring in future combination therapies.

[Malignant melanoma of the conjunctiva]. / Malignes Melanom der Bindehaut.

BACKGROUND: Malignant melanoma of the conjunctiva is a rare tumour. Early disease stages may be difficult to distinguish from benign lesions such as pigmented nevi or primary acquired melanosis. We describe the therapeutic procedure and histological findings in two patients and review the epidemiology and pathogenesis of malignant conjunctival melanoma. Two female patients (84 and 85 years old, respectively) presented with a pigmented tumor close to the limbus with surrounding conjunctival pigmentation and involvement of the cornea. RESULTS: Following complete excision of the tumour, conjunctival malignant melanoma arising from primary acquired melanosis was diagnosed histologically. Subsequent treatment with mitomycin C eye drops was initiated. There was no recurrence of the tumor within the follow-up period (24 and 6 months). DISCUSSION: Patients with primary acquired melanosis need to be reviewed on a regular basis to detect malignant transformation at an early stage.

[Mucous membrane pemphigoid with ocular involvement. Part II: therapy]. / Schleimhautpemphigoid mit okulärer Beteiligung. Teil II: Therapie.

Treatment of mucous membrane pemphigoid (MMP) aims at reduction of conjunctival inflammation by means of systemic immunosuppression. In addition, cicatricial progression and management of the resulting ocular surface disease requires topical conservative or surgical measures. The former includes systemic immunosuppression with steroids and other immunosuppressive agents: dapsone in mild to moderate disease and cyclophosphamide in severe cases have been established in two randomized trials. Other agents such as methotrexate, azathioprine, mycophenolate mofetil or monoclonal antibodies including daclizumab or rituximab were found to be effective in uncontrolled small studies. Surgery is primarily focused on eyelid problems such as entropium and trichiasis. Ocular surface disease and secondary complications, e.g. cataract formation and glaucoma, may need surgical treatment. Any surgery is associated with the risk of a relapse of inflammation and should be postponed until inflammation is controlled by systemic therapy. Management of MMP patients requires close collaboration of a specialized ophthalmologist with specialists from dermatology and internal medicine.

[Mucous membrane pemphigoid with ocular involvement. Part I: Clinical manifestations, pathogenesis and diagnosis]. / Schleimhautpemphigoid mit okulärer beteiligung. Teil I: Klinik, pathogenese und diagnostik.

Mucous membrane pemphigoid is a subepidermal blistering autoimmune disorder characterized by predominant involvement of mucous membranes and the presence of autoantibodies against proteins of the dermal-epidermal junction. Lesions most frequently develop in the oral cavity followed, in descending order of frequency, by conjunctiva, nasopharynx, the anogenital region, skin, larynx, and oesophagus. When the lesions are restricted to the conjunctiva, the term ocular pemphigoid may be applied. Cicatrization of the plica is considered a pathognomonic sign in early disease. Recurrent conjunctival inflammation results in subepithelial fibrosis, which leads to fornix shortening, symblepharon formation and subsequent trichiasis and entropion. Even in the absence of conjunctival inflammation, ankyloblepharon may occur. In end stage disease, limbal stem cell deficiency, tear deficiency, and lid malpositions may occur and result in a total keratinization of the ocular surface. The diagnosis is based on clinical findings and the detection of linear deposits of IgG and/or IgA and/or C3 at the dermal-epidermal junction by direct immunofluorescence microscopy of a perilesional biopsy. Autoantibodies (against type XVII and VII collagen, laminin 5 and 6, alpha6beta4 integrin, BP230) have been detected in patient serum. In the case of ocular involvement, preferential reactivity against beta4 integrin has been described.

Helicobacter pylori activates mitogen-activated protein kinase cascades and induces expression of the proto-oncogenes c-fos and c-jun.

Helicobacter pylori is an etiological agent in the development of mucosa-associated lymphoid tissue lymphoma and gastric adenocarcinoma. Patients infected with H. pylori carry a 3-6-fold increased risk of developing cancer compared with uninfected individuals. H. pylori strains expressing the cytotoxin-associated antigen A (CagA) are more frequently associated with the development of neoplasia than cagA-negative strains. However, the molecular mechanism by which H. pylori causes neoplastic transformation remains unclear. Here we report that exposure of gastric epithelial cells to H. pylori induces activation of the transcription factor activator protein 1. Activation of the proto-oncogenes c-fos and c-jun is strongly induced. We show that H. pylori activates the ERK/MAP kinase cascade, resulting in Elk-1 phosphorylation and increased c-fos transcription. H. pylori strains that do not express CagA or that are mutated in cag genes encoded by the CagI pathogenicity island do not induce activator protein 1, MAP kinase activity, or c-fos or c-jun activation. Proto-oncogene activation may represent a crucial step in the pathomechanism of H. pylori induced neoplasia.