Abstract:The purpose of this work is to investigate the benefits of adaptive optics (AO) technology for optical coherence tomography angiography (OCTA). OCTA has shown great potential in non-invasively enhancing the contrast of vessels and small capillaries. Especially the capability of the technique to visualize capillaries with a lateral extension that is below the transverse resolution of the system opens unique opportunities in diagnosing retinal vascular diseases. However, there are some limitations of this technology such as shadowing and projection artifacts caused by overlying vasculature or the inability to determine the true extension of a vessel. Thus, the evaluation of the vascular structure and density based on OCTA alone can be misleading. In this paper we compare the performance of AO-OCT, AO-OCTA and OCTA for imaging retinal vasculature. The improved transverse resolution and the reduced depth of focus of AO-OCT and AO-OCTA greatly reduce shadowing artifacts allowing for a better differentiation and segmentation of different vasculature layers of the inner retina. The comparison is done on images recorded in healthy volunteers and in diabetic patients with distinct pathologies of the retinal microvasculature.
SummaryMonitoring glycoconjugates has been tremendously facilitated by the development of metabolic oligosaccharide engineering. Recently, the inverse-electron-demand Diels–Alder reaction between methylcyclopropene tags and tetrazines has become a popular ligation reaction due to the small size and high reactivity of cyclopropene tags. Attaching the cyclopropene tag to mannosamine via a carbamate linkage has made the reaction even more efficient. Here, we expand the application of cyclopropene tags to N-acylgalactosamine and N-acylglucosamine derivatives enabling the visualization of mucin-type O-glycoproteins and O-GlcNAcylated proteins through Diels–Alder chemistry. Whereas the previously reported cyclopropene-labeled N-acylmannosamine derivative leads to significantly higher fluorescence staining of cell-surface glycoconjugates, the glucosamine derivative gave higher labeling efficiency with protein preparations containing also intracellular proteins.
We present a new compact multi-modal imaging prototype that combines an adaptive optics (AO) fundus camera with AO-optical coherence tomography (OCT) in a single instrument. The prototype allows acquiring AO fundus images with a field of view of 4°x4° and with a frame rate of 10fps. The exposure time of a single image is 10 ms. The short exposure time results in nearly motion artifact-free high resolution images of the retina. The AO-OCT mode allows acquiring volumetric data of the retina at 200kHz A-scan rate with a transverse resolution of ~4 µm and an axial resolution of ~5 µm. OCT imaging is acquired within a field of view of 2°x2° located at the central part of the AO fundus image. Recording of OCT volume data takes 0.8 seconds. The performance of the new system is tested in healthy volunteers and patients with retinal diseases.
Adaptive optics OCT imaging revealed that MAs located in the inner nuclear layer were connected to the intermediate and/or deep capillary plexus. Intraluminal hyperreflectivity seen on AO fundus camera images originated from a strong reflection from the vessel wall and only in a third of the cases from intraluminal clots. Currently, AOOCT is the most expedient in vivo imaging method to capture morphologic details of retinal microvasculature in 3D and in the context of the surrounding retinal anatomy.
Metabolic imaging identified regional differences in retinal SO2 without an associated topographic variance in microvascular hemodynamics in type II diabetes without DR. Future studies should focus on the mechanisms causing this heterogeneity in metabolic demand.
Combined biomarker screening is increasingly used to diagnose invasive aspergillosis (IA) in high-risk patients. In adults, the combination of galactomannan (GM) and fungal DNA detection has proven to be beneficial in the diagnosis of IA. Data in purely pediatric cohorts are scarce. Here, we monitored 39 children shortly before and after allogeneic stem cell transplantation twice weekly by use of a commercial GM enzyme-linked immunosorbent assay (ELISA) and a PCR assay based on amplification of the pan-Aspergillus ITS1/5.8S ribosomal operon. In addition, clinical data were recorded and classification of IA was performed according to the European Organization for the Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) criteria. Among the 39 high-risk children, we identified 4 patients (10.3%) with probable and 2 (5.1%) with possible IA. All patients with probable IA were repeatedly positive for both tests (means of 9.5 and 6.8 positive GM and PCR samples, respectively), whereas both possible IA cases were detected by PCR. The sensitivity and specificity were, respectively, 67% and 89% for GM and 100% and 63% for PCR. Positive and negative predictive values were, respectively, 50% and 100% for GM and 27% and 100% for PCR. For the combined testing approach, both values were 100%. The number of positive samples seemed to be lower in patients undergoing antifungal therapy. Sporadically positive tests occurred in 12% (GM) and 42% (PCR) of unclassified patients. In summary, our data show that combined monitoring for GM and fungal DNA also results in a high diagnostic accuracy in pediatric patients. Future studies have to determine whether combined testing is suitable for early detection of subclinical disease and how antifungal prophylaxis impacts assay performance.
KEYWORDS Aspergillus fumigatus, PCR, invasive aspergillosis, pediatrics
Invasive aspergillosis (IA) is the most significant opportunistic fungal infection in neutropenic adult and pediatric patients following allogeneic hematopoietic stem cell transplantation (alloHSCT) (1). Diagnosis of IA is challenging, as clinical symptoms are often nonspecific and classical diagnosis is poor (2). Methods such as highresolution computed tomography (CT) scans show only typical signs once the infection is established, and even then specific signs can be transient (2, 3). Serological tests that detect galactomannan (GM) and -D-glucan have low positive predictive values (PPVs),
In DME therapy, reduction in RNFL thickness may have a considerable impact on retinal function, unrelated to the type of pharmacological treatment. Precise morphologic quantification of neurosensory layers by SD OCT offers new insight into disease pathology and therapeutic targets.
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