Melanoma inhibitory activity (MIA) Evaluierung eines neuen tumorassoziierten Antigens als Serummarker für uveale Melanome

BACKGROUND: Currently no serological marker for the monitoring of uveal melanoma and its metastases is available. The novel tumor associated antigen Melanoma inhibitory activity (MIA) is expressed in the uveal melanoma and it's metastatic lesions. METHOD: We report about the serum samples of 38 patients with uveal melanomas. 4 of these patients had overt metastatic disease. A nonradioactive one step ELISA was used to quantify the MIA serum levels. RESULTS: In the 34 patients without overt metastatic disease the serum concentration of MIA was mean (+/- 1 SD) 3.6 +/- 1.0 ng/ml. In the 4 patients with overt metastatic disease the serum concentration of MIA was mean (+/- 1 SD) 27.7 +/- 3.0 ng/ml. The difference was statistically highly significant (student t test: p = 0.0001). CONCLUSION: MIA is expressed in primary and metastatic lesions of uveal melanomas. The elevation of MIA serum levels in patients with metastatic disease from melanomas suggests a promising role as a serum marker for monitoring patients with uveal melanoma.     

Okuläres vernarbendes Pemphigoid Retrospektive Analyse von Risikofaktoren und Komplikationen

Cicatricial pemphigoid (CP) is a rare autoimmune disease characterized by subepidermal blistering and progressive cicatrization affecting the skin and mucosa. Ocular involvement occurs in approximately 70% of the patients. METHODS: The course of the disease, complications and putative risk factors in patients with ocular cicatricial pemphigoid (OCP) treated at the Departments of Ophthalmology and Dermatology were analyzed retrospectively from 1986 to 1998. RESULTS: Eighteen of 28 patients (64%) with CP demonstrated ocular involvement. The mean age of patients with OCP was 73 years; 61% were female. At the time of referral to our hospital, all patients had reached advanced stage III (83%) or IV (17%) of OCP. In 38% of patients vision was already reduced to < 20/200 at first presentation. Twenty-eight percent of patients additionally suffered from glaucoma. Two patients exhibited life-threatening extraocular manifestations of CP (larynx stricture, esophagus stricture). Conjunctival or mucosal biopsies were performed in 15 patients with OCP and showed typical immuno-deposits at the basement membrane zone in 12/15 patients. Therapy with dapsone (12 patients), oral steroids (11 patients), azathioprine (5 patients), cyclophosphamide (4 patients), colchicine (2 patients) and methotrexate (1 patient) was used concomitantly or consecutively. Complications of OCP including entropion, recurrent epithelial erosions, corneal ulcers, keratitis, and corneal perforations required multiple surgical interventions such as entropion surgery (8 patients), tarsorrhaphy (3 patients), mucous membrane grafting (1 patient), amniotic membrane transplantation (1 patient), tectonic keratoplasty (1 patient), keratoprosthesis (1 patient) and enucleation (1 patient). Despite control of the inflammatory process, further visual loss occurred in 53% of eyes. Reading visual acuity could only be maintained in 35% of eyes. DISCUSSION: Early diagnosis and therapy can prevent ocular complications of OCP. This study indicates that advanced stages of the disease often result in irreversible visual loss despite institution of immunosuppressive therapy. Whether or not the high association of OCP with glaucoma and/or anti-glaucomatous treatment in our patients represents part of the underlying disease process or plays a role in the pathogenesis of OCP must still be clarified.     

Die Rolle der vitreoretinalen Grenzfläche in der Pathogenese und Therapie der Makulopathie bei Grubenpapille

PURPOSE: Although the relationship between optic pits and macular lesions was described nearly a century ago, the pathology and pathogenesis of macular detachment remain unclear. Recent OCT studies have shown schisislike spaces in connection with the disc. None of the hypotheses of pathogenesis proposed so far could have been proven. Besides the hypothesis of exudation, the role of the vitreoretinal interface is kept in the background of discussion. We describe a case of macular detachment associated with optic pit that regained full vision after pars plana vitrectomy with laser coagulation and gas tamponade over a follow-up of 26 months. The purpose of our case report is to emphasize the role of the vitreoretinal interface in the pathogenesis of macular detachment associated with optic pits. CASE REPORT AND THERAPY: A 32-year-Caucasian woman developed macular detachment associated with an optic pit on her right eye. The vision deteriorated to 24/60. A standard three-port pars plana vitrectomy was performed. After creating a posterior vitreous detachment, all vitreoretinal adhesions were removed carefully. Peripapillary laser coagulation and gas tamponade with 15% C2F6-air mixture followed. For 26 months after surgery the macula has been flat. The vision is 60/60. CONCLUSIONS: Besides the exudative component of macular detachment, the vitreoretinal interface seems to play an underestimated role in the pathogenesis of maculopathy associated with optic pits. Tractional forces could explain the delay of macular detachment in young adulthood and the frequency of treatment failure after laser coagulation and gas tamponade. Pars plana vitrectomy with complete removal of all vitreoretinal adhesions should be a suitable technique in the treatment of macular detachment associated with optic pits.     

Retinal pigment epithelium is protected against apoptosis by alphaB-crystallin

PURPOSE: The degeneration of retinal pigment epithelial (RPE) cells is considered to be a crucial event in the pathophysiology of age-related macular degeneration (AMD). Cumulative oxidative damage has been implicated in the development of the changes seen in AMD. The present study was undertaken to evaluate the expression of the small heat shock protein alphaB-crystallin in the RPE in response to oxidative stress and to explore whether alphaB-crystallin expression confers an antiapoptotic cytoprotective effect on RPE cells. METHODS: Native human RPE cells from the macula and retinal periphery were analyzed by RT-PCR and Western blot analysis for expression of alphaB-crystallin. Monolayer cultures of human RPE cells were stressed by heat shock (42 degrees C for 20 minutes) or oxidant-mediated injury (50-300 micro M H(2)O(2) for 1 hour). Induction of alphaB-crystallin and the corresponding mRNA was assessed by Western and Northern blot analyses. To study the cytoprotective effect of alphaB-crystallin, human RPE cells were transfected with either a neomycin-selectable expression vector containing alphaB-crystallin cDNA or a control vector without alphaB-crystallin cDNA. Caspase-3 activity was determined by observing the cleavage of a colorimetric peptide substrate. Cell viability was quantified by combined propidium iodide and Hoechst 33342 staining. RESULTS: alphaB-crystallin is constitutively expressed in RPE under in vivo and in vitro conditions. Western blot analysis of freshly isolated RPE showed greater baseline expression levels in RPE derived from the macular area than in that from the more peripheral regions. Heat shock treatment and oxidative stress caused a significant increase in alphaB-crystallin mRNA and protein. Oxidant-mediated injury in RPE cells with baseline expression levels of alphaB-crystallin resulted in apoptotic cell death, as measured by caspase-3 activity, whereas RPE cells that had been stably transfected with alphaB-crystallin were more resistant to H(2)O(2)-induced cellular injury. CONCLUSIONS: alphaB-crystallin may function as a stress-inducible antiapoptotic protein in human RPE and is inducible by oxidative stress, a condition implicated in the pathogenesis of AMD. Overexpression of alphaB-crystallin may be an important mechanism for the RPE to prevent apoptotic cell death in response to cellular stress.     

Testing for glaucoma with frequency-doubling perimetry in normals, ocular hypertensives, and glaucoma patients

BACKGROUND: The aim of this study was to evaluate the diagnostic usefulness of the FDT perimeter protocol (C-20-5) in combination with a database system for analysis of single test locations. METHODS: One hundred seventy-three ocular hypertensive eyes, 116 "preperimetric" open-angle glaucoma eyes (glaucomatous optic disc atrophy, elevated intraocular pressure, no visual field defects in standard white-on-white perimetry), 199 "perimetric" open-angle glaucoma eyes (glaucomatous optic disc atrophy and visual field defects), and 151 control eyes underwent FDT screening and conventional white-on-white perimetry. Four repeated measurements were carried out in 15 glaucoma patients at 2-h intervals to judge reproducibility of all test locations. The present screening strategy begins testing at the normal 5% probability level. If a stimulus is not detected, further targets are presented. FDT-Viewfinder and statistics software were used for case-wise recalculation of all missed localized probability levels and correlation with corresponding test locations using conventional perimetry. RESULTS: Analysis of repeated measurements in patients reveals that variation of single test points can be considerable. However, the numbers of missed test-stimuli calculated globally or in quadrants are significantly correlated with corresponding Octopus visual field defects (Spearman rank correlation P<0.001). Using a predefined specificity of 96% in control eyes, 11% of ocular hypertensive eyes, 28.5% of "preperimetric" glaucoma eyes and 86.9% of "perimetric" glaucoma eyes have been classified glaucomatous using an overall score and with consideration of different cut-off points in right and left eyes. CONCLUSION: Point-wise analysis of FDT screening results can be helpful for classification of patient groups and consideration of the individual learning curve in repeated measurements. The C-20-5 protocol of the FDT perimeter is able to detect a considerable proportion of glaucomatous patients.     

Life threatening acute epiglottitis in acute leukemia

We report an 8-year-old boy who developed a life-threatening acute epiglottitis during induction chemotherapy for acute promyelocytic leukemia. He survived the infection with emergency tracheostomy, treatment with broad spectrum antibiotics and amphotericin, and the use of granulocyte-macrophage colony stimulating factor. No organism was identified. A literature review identified 18 cases of acute epiglottitis in cancer patients. Sixteen of them were suffering from hematologic malignancies and three patients had received bone marrow transplantation. Unlike the usual case of epiglottitis, the majority (15 out of 18) of affected patients were adults and none of the infections was associated with Haemophilus influenzae. Streptococcus pneumoniae and Candida albicans were the most frequently identified pathogens. Early recognition and aggressive supportive care are required for successful management.