Non-targeted analytical comparison of a heated tobacco product aerosol against mainstream cigarette smoke: does heating tobacco produce an inherently different set of aerosol constituents?

Smoking-related diseases remain a significant public health concern, and heated tobacco products (HTPs) have emerged as a potential alternative to cigarettes. While several studies have confirmed that HTP aerosols contain lower levels of harmful and potentially harmful constituents (HPHCs) than cigarette smoke, less is known about constituents that are intrinsically higher in HTP aerosols. This study provides a comprehensive comparative assessment of an HTP aerosol produced with Tobacco Heating System 2.2 (THS) and comparator cigarette (CC) smoke aiming at identifying all unique or increased compounds in THS aerosol by applying a broad set of LC-MS and GC × GC-MS methods. To focus on differences due to heating versus burning tobacco, confounding factors were minimized by using the same tobacco in both test items and not adding flavorants. Of all analytical features, only 3.5%-corresponding to 31 distinctive compounds-were significantly more abundant in THS aerosol than in CC smoke. A notable subset of these compounds was identified as reaction products of glycerol. The only compound unique to THS aerosol was traced back to its presence in a non-tobacco material in the test item and not a direct product of heating tobacco. Our results demonstrate that heating a glycerol-containing tobacco substrate to the temperatures applied in THS does not introduce new compounds in the resulting aerosol compared to CC smoke which are detectable with the method portfolio applied in this study. Overall, this study contributes to a better understanding of the chemical composition of HTP aerosols and their potential impact on human health.

Suppression of pyrrolidine ring biosynthesis and its effects on gene expression and subsequent accumulation of anatabine in leaves of tobacco (N. tabacum L.).

BACKGROUND: Anatabine, although being one of four major tobacco alkaloids, is never accumulated in high quantity in any of the naturally occurring species from the Nicotiana genus. Previous studies therefore focused on transgenic approaches to synthetize anatabine, most notably by generating transgenic lines with suppressed putrescine methyltransferase (PMT) activity. This led to promising results, but the global gene expression of plants with such distinct metabolism has not been analyzed. In the current study, we describe how these plants respond to topping and the downstream effects on alkaloid biosynthesis. RESULTS: The surge in anatabine accumulation in PMT transgenic lines after topping treatment and its effects on gene expression changes were analyzed. The results revealed increases in expression of isoflavone reductase-like (A622) and berberine bridge-like enzymes (BBLs) oxidoreductase genes, previously shown to be crucial for the final steps of nicotine biosynthesis. We also observed significantly higher methylputrescine oxidase (MPO) expression in all plants subjected to topping treatment. In order to investigate if MPO suppression would have the same effects as that of PMT, we generated transgenic plants. These plants with suppressed MPO expression showed an almost complete drop in leaf nicotine content, whereas leaf anatabine was observed to increase by a factor of ~ 1.6X. CONCLUSION: Our results are the first concrete evidence that suppression of MPO leads to decreased nicotine in favor of anatabine in tobacco roots and that this anatabine is successfully transported to tobacco leaves. Alkaloid transport in plants remains to be investigated to higher detail due to high variation of its efficiency among Nicotiana species and varieties of tobacco. Our research adds important step to better understand pyrrolidine ring biosynthesis and its effects on gene expression and subsequent accumulation of anatabine.

Optical Coherence Tomography Angiography Findings in Proliferative Diabetic Retinopathy.

PURPOSE: To characterize preretinal neovascularizations (NV) and their corresponding branching routes in proliferative diabetic retinopathy (PDR) with optical coherence tomography angiography (OCTA) and compare the findings with fluorescein angiography (FA). METHODS: In patients with PDR, angiograms were acquired with spectral-domain OCTA (CIRRUS 5000, OCTA AngioPlexTMCarl Zeiss Meditec, Inc.) and FA (Zeiss FF450PlusIR fundus camera or Spectralis HRA-OCT SLO, Heidelberg Engineering Inc.) and were consecutively evaluated. Neovascularization of the disc (NVD) and neovascularization elsewhere (NVE) were analyzed with 6 × 6 and 8 × 8 mm OCTA flow images and B-scans with flow registration. Segmentations of the vitreoretinal interface (VRI) and superficial retina were performed for analysis. Two independent investigators examined OCTA findings and compared them to corresponding FA. RESULTS: Forty-two eyes of 30 patients with PDR were analyzed. A total of 76 NV with their corresponding proliferation routes were visualized and characterized, with 55 (72.4%) proliferating along the posterior hyaloid membrane (PHM), 14 (18.4%) along the epiretinal membrane, and 7 (9.2%) along the fibrovascular membrane. The posterior vitreous was partially detached in 37 of 42 eyes (88.1%), completely detached in 1 of 42 eyes (2.4%), and adherent in 1 of 42 eyes (2.4%). In 38 of 42 cases, OCTA was superior (n = 23) or equivalent (n = 15) to FA in detecting NV and provided a more detailed information of the neovascular vessels. In 4 of 42 study eyes, OCTA was inferior to FA. CONCLUSIONS: OCTA is a useful tool to detect NV in PDR. In comparison to FA, OCTA has the advantages that it is noninvasive and the image capture takes only seconds. We were able to identify all NV and characterize their corresponding proliferation routes in the VRI, the superficial retina slab, or the B-scan with flow registration. Through evading the masking effect of dye leakage in FA, OCTA is capable of better visualization of NV. FA, however, remains essential for the detection of all NV, since OCTA supplies a smaller detection field. Additionally, we identified the PHM as the main proliferating route of diabetic NV (72.4%), marking it as an important structure for sprouting vessels in neoangiogenesis in PDR.

Type of culture medium determines properties of cultivated retinal endothelial cells: induction of substantial phenotypic conversion by standard DMEM.

Contradictory behavior of microvascular retinal endothelial cells (REC) - a reliable in vitro model to study retinal diseases - have recently been reported which might result from cultivating the cells in standard DMEM not optimized for this cell type. Therefore, we studied DMEM's effects on phenotype and behavior of immortalized bovine REC. Cells were cultivated in endothelial cell growth medium (ECGM) until a confluent monolayer was reached and then further kept for 1-4 days in ECGM, DMEM, or mixes thereof all supplemented with 5% fetal bovine serum, endothelial cell growth supplement, 90 µg/ml heparin, and 100 nM hydrocortisone. Within hours of cultivation in DMEM, the cell index - measured to assess the cell layer's barrier function - dropped to ~5% of the initial value and only slowly recovered, not only accompanied by stronger expression of HSP70 mRNA and secretion of interleukin-6, but also by lower expressions of tight junction proteins claudin-5, claudin-1 or of the marker of cell type conversion caveolin-1. Altered subcellular localizations of EC-typic claudin-5, vascular endothelial cadherin and von Willebrand factor were also observed. Taken together, all experiments with (retinal) EC cultivated in common DMEM need to be interpreted very cautiously and should at least include phenotypic validation.

[Patient's Knowledge after Informed Consent for Intravitreal Injections]. / Intravitreale Injektionen ­ welche Informationen aus dem Aufklärungsgespräch bleiben Patienten im Gedächtnis?

BACKGROUND: Intravitreal treatment (IVT) is one of the most common ophthalmological procedures. Therapeutic effectiveness is however dependent on patient compliance. Unwanted treatment cessation rates are high though. The authors therefore decided to analyse the patient's knowledge and treatment expectations, as discrepancies are known to negatively affect compliance and thus treatment outcomes. PATIENTS AND METHODS: The study was designed as an exploratory survey. In total, 100 patients presenting to an outpatient clinic of a tertiary care centre from October to December 2016 were included. A structured, anonymised questionnaire was handed out, consisting mainly of question items with closed code lists as response domains. Solely descriptive analysis of results was performed. RESULTS: The median age of patients was 73 years. 70% had received more than 3 IVTs in at least one eye. Age-related macula degeneration was the most common underlying cause (52%). 64% expected improvement of visual acuity after IVT. 42% could not name one medication used in their IVT. 55% felt that the information provided during informed consent had been adequate. 69% did not know the post-surgical occurrence of endophthalmitis. Three patients were confident of being able to drive a car directly after IVT. CONCLUSION: Patient's knowledge of their underlying disease, treatment goals and complications rates exhibited some deficiencies. Standardised patient information sheets could be of significant use and were actively suggested by patients to improve the informed consent process.

[Recanalisation by Probing with a Bicanalicular Silicone Tube (Oggel Silicone Intubation) in Patients with Acquired Lacrimal Stenosis]. / Rekanalisierung durch Sondierung mit Oggel-Sonden-Implantation bei erworbener Tränenwegsstenose.

OBJECTIVES: Recanalisation and bicanalicular splinting with silicone tube is one therapeutic option for acquired lacrimal duct stenosis, and restenosis is frequently achieved. The aim was to determine the therapeutic success of Oggel silicone intubation after lacrimal syringing and probing. We also analysed other characteristics of the complaint and compared the therapeutic success with published results. METHODS: Therapeutic success was defined as subjective absence of complaints. Other complaint features - directly after explantation of the Oggel tube, one month after explantation and one year after explantation - were retrospectively collected by a patient questionnaire, and a questionnaire for the attending ophthalmologist. These were completed with information from the patient's file. We included 82 procedures performed at the Dept. of Ophthalmology, University of Ulm, between 2006 and 2015. Statistical testing of the impact of risk factors on therapeutic success was performed, using logistic regression analysis and the Mann-Whitney U test. Subgroups were compared using Pearson-Chi-square and Fisher's exact tests and a Kaplan-Meier analysis was also performed. RESULTS: Therapeutic success could be documented in 80.8% of patients after explantation of the Oggel tube, in 61.6% of patients after one month and in 42.5% of patients at one year (n = 82). There were no significant differences between the subgroups of stenosis localisation, or the patients' age or sex. There was also no significant influence of the patient's age, the preoperative duration of complaints or risk factors predisposing for lacrimal duct stenosis. For the observation period of one year, the Kaplan-Meier analysis gave a probability of complaint-freeness of 52.2% for the patient group, as well as a mean duration of the complaint-free period of 34.2 weeks. CONCLUSION: The results allow a prognostic assessment of the therapeutic success in the absence of significant differences in the subgroups. The therapeutic success of bicanalicular silicone intubation with the Oggel tube was in the lower third of comparable studies. The results conform to the observation that there is a progressive decline of therapeutic success. The comparison of the literature turned out to be methodically more difficult due to differences in study characteristics. Standardisation would make sense for future studies.

Transport and fate of aflibercept in VEGF-A165-challenged retinal endothelial cells.

Retinal vessels are at least in part involved in clearing of Fc terminus-containing proteins from the vitreous. In vitro, the Fc fusion protein aflibercept is transported through a monolayer of unchallenged immortalized bovine retinal endothelial cells (iBREC), mediated by the neonatal Fc receptor (FcRn), but part of the Fc fusion protein is also degraded. Aflibercept's target VEGF-A not only enhances the permeability of REC by destabilization of tight junctions (TJs) thereby allowing for paracellular flow, it may also lower the intracellular stability of the Fc fusion protein by changing its binding properties to the FcRn. Therefore, we investigated the transport and fate of aflibercept in VEGF-A165-challenged iBREC. All cell culture media were supplemented with 5% fetal bovine serum (FBS) as its absence results in accumulation of aflibercept in iBREC due to deregulated expression of transport proteins. Early after exposure of a confluent iBREC monolayer cultivated on gold electrodes to 5% FBS, the cell index (CI) - assessed as a measure of barrier function, cell viability and cell adhesion - transiently declined but recovered again within a few hours to high values. These values remained stable for several days associated with a strong expression of the TJ-protein claudin-1, indicative of a functional barrier formed by the iBREC monolayer. Transient changes of the plasma membrane localizations of claudin-5 and vascular endothelial cadherin - both important for regulation of paracellular flow - accompanied the transient reduction of the CI not prevented by VEGF-binding proteins. Treatment of iBREC with 50 ng/ml VEGF-A165 for one day resulted in a strong and persistent decline of the CI associated with a low expression level of the TJ-protein claudin-1; reversion to normal values was complete one day after aflibercept's addition at a final concentration of 250 µg/ml. Expressions of other proteins involved in regulation of paracellular flow or transcellular transport were not significantly changed. More aflibercept passed through the monolayer of iBREC cultivated on permeable membrane inserts pretreated with VEGF-A for one day, but this was not affected by a FcRn-inhibiting antibody. Subcellular localization of aflibercept was hardly changed in VEGF-A-exposed iBREC 3 h after its addition to the cells; inhibition of (non)-lysosomal or proteasomal proteases then only weakly affected the amount of internalized aflibercept. iBREC also internalized VEGF-A which was barely detectable as early as 2 h after addition of aflibercept. In contrast, blocking the tyrosine kinase activity of VEGF receptor(s) did not prevent VEGF-A's uptake. Inhibition of cellular proteases strongly increased the amount of internalized VEGF-A in the absence and presence of the Fc fusion protein. We therefore conclude that a FcRn-mediated transport plays a minor role in aflibercept's passage through a leaky barrier of REC. Even early after addition of aflibercept to VEGF-A-exposed iBREC, the levels of free intracellular VEGF-A are low, as aflibercept likely prevents binding of VEGF-A to its receptor. Interestingly, the growth factor's detrimental effects still persist for nearly one day.

Sitagliptin and the Blood-Retina Barrier: Effects on Retinal Endothelial Cells Manifested Only after Prolonged Exposure.

Inhibitors of dipeptidyl peptidase-4 (DPP-4) are widely used to treat diabetes mellitus, but data concerning their effects on the barrier stability of retinal endothelial cells (REC) in vivo and in vitro are inconsistent. Therefore, we studied whether the barrier properties of immortalized endothelial cells of the bovine retina (iBREC) were affected by the inhibitors of DPP-4 sitagliptin (10-1000 nM) and diprotin A (1-25 µM). Their effects were also investigated in the presence of VEGF-A165 because diabetic patients often develop macular edema caused by VEGF-A-induced permeability of REC. To detect even transient or subtle changes of paracellular and transcellular flow as well as adhesion of the cells to the extracellular matrix, we continuously monitored the cell index (CI) of confluent iBREC grown on gold electrodes. Initially, the CI remained stable but started to decline significantly and persistently at 40 h or 55 h after addition of sitagliptin or diprotin A, respectively. Both inhibitors did not modulate, prevent, or revert the persistent VEGF-A165-induced reduction of the CI. Interestingly, sitagliptin and diprotin A increased the expression of the tight-junction protein claudin-1 which is an important component of a functional barrier formed by iBREC. In contrast, expressions of CD29-a subunit of the fibronectin receptor-or of the tetraspanin CD9 were lower after extended treatment with the DPP-4 inhibitors; less of the CD9 was seen at the plasma membrane after prolonged exposure to sitagliptin. Because both associated proteins are important for adhesion of iBREC to the extracellular matrix, the observed low CI might be caused by weakened attachment of the cells. From our results, we conclude that extended inhibition of DPP-4 destabilizes the barrier formed by microvascular REC and that DPP-4 inhibitors like sitagliptin do not counteract or enhance a VEGF-A165-induced barrier dysfunction as frequently observed in DME.

Alkaloid chemophenetics and transcriptomics of the Nicotiana genus.

In this study, we determined the pyridine alkaloid content (nicotine, nornicotine, anabasine, anatabine, cotinine, and myosmine) of 58 species and 2 subspecies of the Nicotiana genus by ultra-high-performance liquid chromatography coupled with mass spectrometry. We observed clear correlation between Noctiflorae and Suaveolentes sections and their above average accumulation of anabasine in the genus. In addition, the results demonstrated the presence of not only trace amounts but quantifiable levels of myosmine, an alkaloid previously detected in only minute quantities, in the leaves and roots of 16 species. In this study, analysis of gene expression of 58 species and 2 subspecies from the Nicotiana genus by mRNA sequencing was performed for the first time. Sequencing reads were mapped against annotated genes of a Nicotiana tabacum reference genome and expression values were subsequently calculated. Hierarchical clustering of alkaloid biosynthesis pathway genes and alkaloid content composition revealed patterns clearly segregating Nicotiana sections. Correlation of gene expression with alkaloid accumulation phenotypes was evident, including low putrescine methyltransferase expression for all species in the Suaveolentes section or clear correlation of nicotine demethylase with conversion rates of nicotine to nornicotine in the majority of species. Multiple additional correlations between alkaloid accumulation and gene expression values were identified, which makes this study an important fundament toward future scientific exploration of the Nicotiana genus.

VEGF receptor 2 inhibitor nintedanib completely reverts VEGF-A165-induced disturbances of barriers formed by retinal endothelial cells or long-term cultivated ARPE-19 cells.

Various severe ocular diseases are associated with an elevated intravitreal expression of VEGF-A which increases the permeability of retinal endothelial cells (REC) or retinal pigment epithelial (RPE) cells in vivo and in vitro. Inhibition of VEGF receptor 2 (VEGFR2) is sufficient to completely prevent VEGF-A165-induced dysfunctions of barriers formed by long-term cultivated, immortal human ARPE-19 cells or immortalized bovine retinal endothelial cells (iBREC). Extended exposure to VEGF-A could result in additional activation of other growth factor receptors, potentially promoting synergistic effects of corresponding factors on various cellular processes including angiogenesis. Based on these observations, we investigated whether blocking of VEGFR2 is also sufficient to revert VEGF-A-induced changes of the barriers consisting of iBREC (i.e. inner blood-retina barrier) or ARPE-19 cells (i.e. outer blood-retina barrier) in vitro. Alterations of confluent monolayers' properties induced by treatment with VEGF-A165 for one day followed by addition of small molecule inhibitors of the VEGFR2 were determined by continuous cell index (CI) measurements using the microelectronic biosensor system for cell-based assays xCELLigence. VEGF-A165 induced a long-lasting drop of the otherwise high CI of iBREC accompanied by reduced expression of the tight junction (TJ) protein claudin-1 and subtle changes of the plasma membrane localizations of TJ-protein claudin-5 and of vascular endothelial cadherin. Blocking mainly VEGFR2 with 10 nM nintedanib, 10 nM tivozanib or 500 nM ZM323881 efficiently reverted these changes within one day; higher concentrations of nintedanib or additional inhibition of neuropilin-1 were not superior. Interestingly, the CI of short-term cultivated, confluent ARPE-19 cells slightly increased in the presence of VEGF-A165, but was not changed by nintedanib. In contrast, VEGF-A165 markedly reduced the transepithelial electrical resistance of ARPE-19 cells cultivated on porous membrane inserts for three weeks, which was also accompanied by a significant loss of the then strongly plasma membrane-expressed TJ-protein ZO-1. These alterations were completely reverted within one day by 10 nM nintedanib of which higher concentrations were not superior. None of the inhibitors tested diminished the strong barrier properties of iBREC or long-term cultivated ARPE-19 cells. Taken together, inhibition of VEGFR2 efficiently reverts VEGF-A165-induced barrier disturbances of both cell types forming and regulating the inner and outer blood-retina barrier. As synergistic actions of growth factors seem to play only a minor role in inducing a barrier dysfunction, specific inhibition of VEGFR2 could be an interesting option to treat VEGF-A-induced macular edema without obvious effects on vitality and functions of REC and RPE cells.

[The Importance of the Preoperative Information from a Patient's Perspective - a Structured Interview of 100 Ophthalmological University-Based Outpatients]. / Die Erwartungen an das Aufklärungsgespräch aus Patientensicht ­ strukturierte Befragung von 100 Patienten einer ophthalmologischen Universitätsambulanz.

BACKGROUND: The patient's knowledge about their illness, as well as their expectations regarding pre-intervention, consultation and treatment, may differ from the physician's assumptions. Therefore, it is of great importance that the physician can identify misconceptions and missing knowledge and to focus on those points in the preoperative consultation, as well as meeting patient expectations as to the consultation itself. The aim of this study was to identify such expectations and the knowledge gaps of patients scheduled for ophthalmologic treatment. METHOD: An anonymous questionnaire containing predominantly closed questions was handed out to 100 patients in an ophthalmological outpatient clinic of a tertiary care center. Answers were mostly single choice items on a rating scale. RESULTS: 55% of patients had received ophthalmological interventions prior to receiving the questionnaire; 36% received more than two. More than half had not informed themselves about the planned procedure prior to their appointment. They were worried the most about complications (59%) and least about the anaesthesia (29%). When asked, patients attributed the highest priority to provision of information regarding complications and most often requested information on implications of the planned surgery on daily activities. CONCLUSION: Roughly half of the patients came without having informed themselves prior to the consultation. A comprehensive explanation with regard to success rates and possible post-surgical impairments appears to be essential. Possibilities of new media, such as the internet, surprisingly do not seem to be of importance to patients in this context.

Comparison between Findings in Optical Coherence Tomography Angiography and in Fluorescein Angiography in Patients with Diabetic Retinopathy.

OBJECTIVE: To compare typical findings of diabetic retinopathy in optical coherence tomography angiography (OCTA) and fluorescein angiography (FA). SUBJECTS/METHODS: 42 patients were enrolled in this study. We performed FA and obtained en face 3 × 3 mm OCTA images of the macular region. The count of microaneurysms (MAs) and the size of the foveal avascular zone (FAZ) were compared. The assessability of the imaging modalities was graded in each eye. RESULTS: 53 eyes of 42 patients with a mean age of 61 years were included. 36/53 eyes revealed nonproliferative diabetic retinopathy, 17/53 eyes had proliferative diabetic retinopathy. The mean size of the FAZ was 0.39 mm2 in FA and 0.42 mm2 in OCTA. The mean MA count was 14 in FA and 13 in OCTA. The assessability was favorable to OCTA in 38-41/53 eyes regarding the FAZ and favorable to FA in 45-49/53 eyes regarding MAs. CONCLUSION: We found a good agreement for the size of the FAZ and a weak agreement regarding the count of MAs in both imaging modalities. The readers favored OCTA for the assessment of the FAZ and FA for the assessment of MAs. Complementary use of FA and OCTA ensures the best diagnostic approach in patients with diabetic retinopathy.

[Augmented Reality in Ophthalmology: Technical Innovation Complements Education for Medical Students]. / Augmented Reality in der Augenheilkunde: Technische Innovation ergänzt studentische Lehre.

BACKGROUND: At the Medical Faculty of the University of Ulm, the learning objectives of ophthalmology are taught to students in a one-week block course in the fourth year of study. According to the National Competency-based Learning Objective Catalogue Medicine (NKLM), one of these learning objectives is the clinical examination of the eye, including the eye fundus examination. In order to best train this expertise as defined in the NKLM, a novel, augmented reality-based training simulator (Eyesi Indirect, VRmagic Holding AG, Mannheim, Germany) was integrated into the teaching at the University Eye Hospital Ulm. During the block week, two key questions were examined: Does the one week block lesson increase interest in ophthalmology? How do students assess the use of an innovative e-learning technology compared to three other classical teaching methods for learning ophthalmoscopy? MATERIAL/METHODS: As part of the student teaching (block weeks July and October 2016), 292 students were questioned by questionnaire anonymously and on a voluntary basis regarding their assessment of the block week and the training simulator at the beginning and end of the one week event. The ophthalmoscopies were classically practiced on the ophthalmoscope trainer, head model and on fellow students and then performed on the new training simulator. RESULTS: Overall, there was little interest among the students in ophthalmology. However, the block week helped to increase interest (p < 0.001). The assessments of attractiveness before and after the block week of ophthalmology as a later professional goal and as an optional subject in the practical year were also significantly increased (p < 0.001 or p = 0.031). With regard to the use of e-learning technologies, it was shown that the handling of the simulator for learning ophthalmoscopy was rated more attractive by the students than the classical technology-based teaching methods (all p < 0.01). The joy of learning could only be further increased by practicing on a fellow student (p = 0.051). CONCLUSION: The results of the present study show a positive impact of the block week on the attractiveness assessment of the specialty by the participating students. Innovative e-learning methods can increase the enjoyment of learning. However, the training simulator cannot provide a complete replacement of the training on a real person.

[Invasive Eyelid Infections by ß-Hemolytic Streptococci of Serogroup A]. / Invasive Lidinfektionen durch ß-hämolysierende Streptokokken der Serogruppe A.

BACKGROUND: Invasive soft tissue infections by Streptococcus pyogenes are rapidly progressive and potentially life-threatening infectious diseases. These can also affect the eyelid. Aggressive virulence factors and the synthesis of exotoxins can lead to complications, such as periorbital necrotizing fasciitis (PONF) and streptococcal toxic shock syndrome (STSS). The clinical picture is characterized by four patients with invasive eyelid infections. MATERIALS AND METHODS: Photographic documentation, radiological imaging, laboratory and smear diagnostics and intravenous antibiotic therapy were performed on all patients according to the recommendations of the German Robert Koch Institute and the local infectiology board. RESULTS: In all patients, Streptococcus pyogenes was culturally detected in a direct swab. The antibiogram showed sensitivity to the common intravenous antibiotics. The time interval between symptom onset and presentation at the clinic was between two days and one week. All patients had high systemic inflammatory parameters on admission: Pat. 1: CRP 259 mg/l, leukocytes 20.1 giga/l; Pat. 2: CRP 375 mg/l, leukocytes 15.6 giga/l; Pat. 3: CRP 378 mg/l, leukocytes 38.7 giga/l; Pat. 4: CRP 483 mg/l, leukocytes 1.7 giga/l; normal values: CRP < 5 mg/l, leucocytes 4.4 - 11.3 giga/l. In Pat. 2 and 3, a periorbital necrotizing fasciitis was diagnosed due to rapidly progressing necrosis in the area of cutis and subcutis and systemic toxicity. Pat. 3 and 4 met the diagnostic criteria of STSS. Pat. 2, 3 and 4 had to be relocated to an intermediate or intensive care unit with sepsis, despite immediate intravenous antibiotic therapy. Patient 3 underwent surgical debridement during the stay in the intensive care unit. Thanks to interdisciplinary management (ophthalmology, infectiology, ear, nose and throat medicine, internal medicine and intensive care medicine), all patients were finally discharged from our inpatient treatment in a significantly improved general condition. CONCLUSION: Invasive streptococcal infections represent a challenge in the daily routine of an ophthalmologist. Interdisciplinary management and immediate onset of high-dose intravenous antibiotic therapy are crucial for successful treatment.

[Visualization of Retinal Neovascularization with Optical Coherence Tomography Angiography in Comparison with Fluorescein Angiography]. / Darstellung von retinalen Neovaskularisationen mit der optischen Kohärenztomografie-Angiografie im Vergleich mit der Fluoreszeinangiografie.

OBJECTIVE: Comparison of retinal neovascularizations of the disc (NVD) and elsewhere (NVE) in optical coherence tomography angiography (OCTA) and fluorescein angiography (FA) in patients with proliferative diabetic retinopathy. MATERIALS AND METHODS: 15 consecutive patients were included in this study. All patients received an OCTA with a 3 × 3 mm scan of the region of interest with the ZEISS OCT Cirrus 5000 with the AngioPlex module. The size of the neovascularization (NV) was determined manually in OCTA and FA and compared between the two methods. RESULTS: 20 eyes of 15 patients with proliferative diabetic retinopathy with an average age of 57 years were included. The mean size of NVDs was 3.44 mm2 in OCTA and 3.75 mm2 in FA, the mean size of NVDs was 1.06 mm2 in OCTA and 1.54 mm2 in FA. Taking into account a generally larger area measured in the FA, the two methods showed good overall agreement. CONCLUSION: There was a good agreement for the size of the NVs in both methods. OCTA can be used as a simple and non-invasive method to visualize retinal neovascularizations.