Dynamic changes of circulating miRNAs induced by the Ebola virus vaccine VSV-EBOV.

VSV-EBOV is a replication-competent Ebola virus (EBOV) vaccine, which was tested in clinical trials as response to the Ebola virus disease (EVD) outbreak 2013-2016. It is the most advanced EBOV candidate currently in the licensure process. The experimental vaccine was again administered as response to outbreaks in the Democratic Republic of Congo. However, underlying molecular mechanisms that convey protection remain incompletely understood. MicroRNAs (miRNAs) are known key regulators that influence gene expression on a post-transcriptional level. The miRNA-mediated control has emerged as a critical regulatory principle in the immune system, which strongly influences the balance of innate and adaptive immune responses by modulation of signaling pathways critical for differentiation of immune cells. We investigated expression levels of circulating miRNAs (c-miRNAs) in plasma from healthy vaccinees, as they may reflect cellular dynamics following VSV-EBOV immunization and additionally may serve as potential biomarkers for vaccine efficacy. As part of the WHO-led VEBCON consortium, we investigated safety and immunogenicity of VSV-EBOV in a phase I trial. A comprehensive analysis of expression levels on c-miRNAs from plasma samples following VSV-EBOV immunization (day 0, 1, 3 post vaccination) was conducted using RT-qPCR assays. Potential biological relevance was assessed using in silico analyses. Additionally, we correlated dynamics of miRNA expressions with our previously reported data on vaccine-induced antibody and cytokine responses and finally evaluated the prognostic power by generating ROC curves. We identified four promising miRNAs (hsa-miR-146a, hsa-miR-126, hsa-miR-199a, hsa-miR-484), showing a strong association with adaptive immune responses, exhibited favourable prognostic performance and are implicated in immunology-related functions. Our results provide evidence that miRNAs may serve as useful biomarkers for prediction of vaccine-induced immunogenicity. Furthermore, our unique data set provides insight into molecular mechanisms that underlie VSV-EBOV-mediated protective immune responses, which may help to decipher VSV-EBOV immune signature and accelerate strategic vaccine design or personalized approaches.

[A 34-year-old patient with retinal vascular abnormality as a coincidental finding]. / 34-jähriger Patient mit auffälligen retinalen Gefäßen als Zufallsbefund.

A young patient presented with recurring blurred vision. Abnormal vessels were found on the retina, which extended as far as the fovea. The diagnosis was congenital vascular malformation in terms of retinal macrovessels.

[Experience with the artificial iris diaphragm in hypotonic eyes]. / Klinische Erfahrungen bei der Verwendung eines Irisdiaphragmas.

BACKGROUND: As a result of a partial or complete loss of the natural iris diaphragm,longstanding silicone oil tamponade frequently causes keratopathy. An artificial iris diaphragm can avoid such a complication. In hypotony, with insufficient circulation of aqueous humor, the "closed" artificial iris diaphragm is used. METHODS: In this retrospective study 41 patients (41 eyes) were reviewed. Each patient had a single aphakic eye, in which a closed iris diaphragm was implanted after silicone oil surgery. The underlying diagnosis included in these 41 cases included trauma (22 eyes, 54%), retinal detachment due to proliferative vitreoretinopathy (12 eyes, 29%), severe uveitis (4 eyes, 10%), and proliferative diabetic retinopathy (3 eyes, 7%). The mean follow-up time was 12 month. RESULTS: In 25 eyes (61%) silicone oil was retained behind the diaphragm. In 14 eyes (34%), silicone oil prolapsed in the anterior chamber. In 2 eyes (5%) the silicone oil could not been assessed due to a corneal opacity.A deteriorated corneal situation after implantation of the diaphragm was observed in 11 eyes (27%). As a longstanding complication permanent hypotony (< or = 5 mmHg) developed in 29 eyes (71%), fibrous reaction in 13 eyes (32%) within fibrotic membranes (9 eyes, 22%). The visual acuity remained stable in 39 eyes (95%), improved in none, and deteriorated in 2 eyes (5%). CONCLUSION: Despite all complications, the artificial iris diaphragm represents an important progress in the salvage of severely traumatized eyes though persistent hypotony remains in 29 eyes (71%). Contact of silicone oil with the endothelium was avoided in 25 eyes (61%). There was no phthisis bulbi or enucleation. Improvement of anterior-posterior separation is necessary.

[Amiodarone-induced bilateral optic atrophy--a case report]. / Amiodaron-induzierte bilaterale Optikusneuropathie. Eine Kasuistik.

We report a case of visual loss and bilateral papilloedema under therapy with the antiarrhythmic substance amiodarone, which is used in treatment of refractory and life-threatening supraventricular and ventricular cardial tachyarrhythmias. After excluding intracranial hypertension, local tumors and an inflammatory genesis we consider this case to be an amiodarone-induced toxic opticusneuropathy. Amiodarone, a diiodated benzofuran derivative, is a cationic amphiphilic drug, which is able to cause ceratopathy and neuropathy. The rarely described and less known opticusneuropathy caused problems in differential diagnosis. A brief review about current knowledge of pathophysiology, differential diagnosis and course of illness is presented.

[Amblyopic eyes produce an abnormal electroretinogram in pattern presentation with the on-off technique]. / Amblyope Augen zeigen ein abnormes Elektroretinogramm bei Musterdarbietung in On-off-Technik.

In amblyopic subjects the electroretinogram in response to pattern stimuli (P-ERG) has been variously described as normal or abnormal. While this was found with a reversing stimulus pattern, we presently recorded the P-ERG by exposing the eye to a checkerboard pattern (element size 10, 30, or 60 min of arc) alternating with a uniform field of equal mean luminance (5 or 500 cd/m2). Eight subjects with anisometropic or squint amblyopia and ten normal subjects took part in the investigation. No differences in P-ERG amplitudes were found in amblyopic eyes in response to pattern offset. However, the P-ERG to pattern onset was diminished in the amblyopic eyes compared with the healthy fellow eyes and with the eyes of normal subjects. Both the early positive (p-q) and the late negative (q-r) components of the onset response were affected. Furthermore, the normal amplitude profile of the onset response (largest response at 30 min, smaller responses at 10 and 60 min, i.e. pattern tuning) was lost in the amblyopic eyes. According to Arden [2] and Korth [9], the P-ERG in response to pattern onset represents the pattern component and that in response to pattern offset, the luminance component. From this we conclude that in subjects with anisometropic and squint amblyopia the retinal information processing of pattern stimuli is disturbed, whereas that for luminance discrimination remains normal.

[Value of corticosteroids in after-care of patients after cataract extraction and lens implantation]. / Zur Bedeutung der Kortikosteroide in der Nachsorge von Patienten nach Kataraktextraktion und Linsenimplantation.

In two double-blind controlled trials the anti-inflammatory effects of dexamethasone were examined in post-cataract extraction eyes after lens implantation in 321 patients. In the first trial, 103 patients were included. 49 eyes received eye-drops with 0.1% dexamethasone and antibiotics, the control-group of 54 eyes received the same antibiotics without any steroids. The follow-up was 2 months. In the case of unexpected complications, the patients dropped out. This was the case in 48% of the steroid-group and in 79% of the control-group. The main reason for this statistically significant difference were inflammatory complications in the control-group, which are difficult to quantify. The incidence of fibrinous reactions was not significantly different in the two groups, probably because of small numbers. In the second trial, we looked for fibrinous reactions. The follow-up was 3 weeks, 218 patients participated. They were divided into three groups: 71 patients received eyedrops with 0.1% dexamethasone 4x daily, 77 patients received the same drops 4x daily up to the fifth postoperative day, from then on 1x daily. 70 patients received the same drops 1x daily. A mild fibrinous reaction was seen in 10% of the high-dose-group, in 6% of the medium-dose-group and in 21% of the low-dose-group. Only the difference between the last two groups is statistically significant. We conclude that the therapy with corticosteroids after cataract extraction and lens implantation may be reduced early in the postoperative course.