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Mit modernen nicht invasiven bildgebenden Verfahren lassen sich anhand der Fundusfotografie bzw. der optischen Verfilmung Aspekte der funktionellen und strukturellen retinalen Gefäßveränderungen objektiv untersuchen. Der Zustand und das Verhalten retinaler Gefäße beeinflussen im prä-, post- und kapillaren Bereich den Blutfluss und strömungsbedingte Stoffwechselverhältnisse passiv und aktiv über den Gefäßdurchmesser. Retinale Gefäße gleichen von Aufbau und Funktion den zerebralen Gefäßen und spiegeln den Zustand der Mikrozirkulation wider. Mithilfe von aus den Gefäßweiten berechneten Biomarkern soll eine Aussage über die Prognose von systemischen vaskulär bedingten Erkrankungen getroffen werden. Die statische retinale Gefäßanalyse befasst sich mit der Untersuchung des Zustandes der prä- und postkapillaren Gefäßdurchmesser der retinalen Mikrozirkulation anhand einer optischen Fundusaufnahme. Bei der dynamischen retinalen Gefäßanalyse wird der Längsschnitt eines retinalen Gefäßes nicht invasiv funktionell und strukturell über einen Zeitraum vor, während und nach einer spezifischen vaskulären Stimulation untersucht. Die genaue Methodologie der Auswertung und die Bezeichnung der Parameter variieren bei unterschiedlichen Ansätzen. Mittels retinaler Gefäßanalyse wurden bislang mehrere klinische Querschnitts- und Interventionsstudien in der Augenheilkunde und anderen Fachgebieten, inkl. Kardiologie, Neurologie, Neurochirurgie, Nephrologie, Gynäkologie, Sportmedizin, Diabetologie, Hypertensiologie usw. durchgeführt. Mit der statischen retinalen Gefäßanalyse steht eine kostengünstige, reproduzierbare, nicht invasive Screeningtechnik zur Verfügung, um eine prognostische Aussage über die Gefäßgesundheit eines individuellen Patienten zu treffen. Die dynamische retinale Gefäßanalyse besitzt ein weiteres diagnostisches Anwendungsspektrum als die statische, da sie das Verhalten retinaler Gefäße zeitkontinuierlich untersucht. Die Evaluation vaskulärer Erkrankungen sowie zerebro- bzw. kardiovaskulärer Morbidität und Mortalität mittels mehrerer methodologischer Modalitäten retinaler Gefäßanalyse mit ihren jeweiligen quantitativen Biomarkern bietet eine zukunftsträchtige diagnostische Perspektive. Die interdisziplinäre klinische Anwendung dieser vaskulären Biomarker gewinnt zunehmend an Bedeutung, sowohl in der Augenheilkunde als auch in anderen Fachgebieten.
Impaired cerebral autoregulation and neurovascular coupling (NVC) contribute to delayed cerebral ischemia after subarachnoid hemorrhage (SAH). Retinal vessel analysis (RVA) allows non-invasive assessment of vessel dimension and NVC hereby demonstrating a predictive value in the context of various neurovascular diseases. Using RVA as a translational approach, we aimed to assess the retinal vessels in patients with SAH. RVA was performed prospectively in 24 patients with acute SAH (group A: day 5–14), in 11 patients 3 months after ictus (group B: day 90 ± 35), and in 35 age-matched healthy controls (group C). Data was acquired using a Retinal Vessel Analyzer (Imedos Systems UG, Jena) for examination of retinal vessel dimension and NVC using flicker-light excitation. Diameter of retinal vessels—central retinal arteriolar and venular equivalent—was significantly reduced in the acute phase (p < 0.001) with gradual improvement in group B (p < 0.05). Arterial NVC of group A was significantly impaired with diminished dilatation (p < 0.001) and reduced area under the curve (p < 0.01) when compared to group C. Group B showed persistent prolonged latency of arterial dilation (p < 0.05). Venous NVC was significantly delayed after SAH compared to group C (A p < 0.001; B p < 0.05). To our knowledge, this is the first clinical study to document retinal vasoconstriction and impairment of NVC in patients with SAH. Using non-invasive RVA as a translational approach, characteristic patterns of compromise were detected for the arterial and venous compartment of the neurovascular unit in a time-dependent fashion. Recruitment will continue to facilitate a correlation analysis with clinical course and outcome.
Purpose — to compare the chemical elemental composition of vitreous cavity content taken from cadaveric eyes compared to samples taken from the eyes with terminal stage refractory glaucoma with decompensated intraocular pressure (IOP). Material and methods. The vitreous contents of the eyes from 2 groups were studied. The 1st group included 15 cadaveric eyes; the 2nd group included 15 eyes with refractory glaucoma in the terminal stage of the disease with decompensated IOP in patients with hypertension pain. The vitreal content samples were taken in the course of antiglaucoma surgery aimed at preserving the eye as an organ and involving employment of drainage in the vitreous cavity. The study of virtual contents was carried out on energy dispersive spectrometer Oxford X-Max 50 integrated into scanning electron microscope Zeiss EVO LS10. Results. Increased concentrations of Kalium and Phosphorus were detected in the vitreous content of cadaveric eyes compared with the vitreal content from the eyes with terminal glaucoma with decompensated IOP taken in vivo (K — 0.172/0.093; P — 0.045/0.025 mmol/L). In the vitreous cavity in the eyes with end-stage glaucoma with decompensated IOP, the concentration of Nitrogen was higher in comparison with human cadaver eyes (2.030/1.424 mmol/L). Conclusion. The increased concentrations of Kalium and Phosphorus in the vitreous content of cadaveric eyes is associated with postmortem autolytic processes and with the release of intracellular content in the destruction of cell membranes. The increased Nitrogen concentration in the vitreal contents of the eyes with terminal stage glaucoma with decompensated IOP may be associated with the presence of osmotically active nitrogen-containing compounds in the eyes with increased IOP.
Background
Impairment of neurovascular coupling (NVC) was recently reported in the context of subarachnoid hemorrhage and may correlate with disease severity and outcome. However, previous techniques to evaluate NVC required invasive procedures. Retinal vessels may represent an alternative option for non-invasive assessment of NVC.
Methods
A prototype of an adapted retinal vessel analyzer was used to assess retinal vessel diameter in mice. Dynamic vessel analysis (DVA) included an application of monochromatic flicker light impulses in predefined frequencies for evaluating NVC. All retinae were harvested after DVA and electroretinograms were performed.
Results
A total of 104 retinal scans were conducted in 21 male mice (90 scans). Quantitative arterial recordings were feasible only in a minority of animals, showing an emphasized reaction to flicker light impulses (8 mice; 14 scans). A characteristic venous response to flicker light, however, could observed in the majority of animals. Repeated measurements resulted in a significant decrease of baseline venous diameter (7 mice; 7 scans, p < 0.05). Ex-vivo electroretinograms, performed after in-vivo DVA, demonstrated a significant reduction of transretinal signaling in animals with repeated DVA (n = 6, p < 0.001).
Conclusions
To the best of our knowledge, this is the first non-invasive study assessing murine retinal vessel response to flicker light with characteristic changes in NVC. The imaging system can be used for basic research and enables the investigation of retinal vessel dimension and function in control mice and genetically modified animals.
Altered neurovascular coupling as measured by optical imaging: a biomarker for Alzheimer’s disease
(2017)
Hintergrund
Die Anwendung und das Verständnis von Statistik sind sehr wichtig für die biomedizinische Forschung und für die klinische Praxis. Dies gilt insbesondere auch zur Abschätzung der Möglichkeiten unterschiedlichster Diagnostik- und Therapieoptionen beim Glaukom. Die scheinbare Komplexität der Statistik, die zum Teil dem „gesunden Menschenverstand“ zu widersprechen scheint, zusammen mit der nur vorsichtigen Akzeptanz der Statistik bei vielen Medizinern können zu bewussten und unbewussten Manipulationen bei der Datendarstellung und -interpretation führen.
Ziel der Arbeit
Ziel ist die verständliche Darstellung einiger typischer Fehler in der medizinisch-statistischen Datenbehandlung.
Material und Methoden
Anhand hypothetischer Beispiele aus der Glaukomdiagnostik erfolgen die Darstellung der Wirkung eines hypotensiven Medikamentes sowie die Beurteilung der Ergebnisse eines diagnostischen Tests. Es werden die typischsten statistischen Einsatzbereiche und Irrtumsquellen ausführlich und verständlich analysiert
Ergebnisse
Mechanismen von Datenmanipulation und falscher Dateninterpretation werden aufgeklärt. Typische Irrtumsquellen bei der statistischen Auswertung und Datendarstellung werden dabei erläutert.
Schlussfolgerungen
Die erläuterten praktischen Beispiele zeigen die Notwendigkeit, die Grundlagen der Statistik zu verstehen und korrekt anwenden zu können. Fehlendes Grundlagenwissen und Halbwissen der medizinischen Statistik können zu folgenschweren Missverständnissen und falschen Entscheidungen in der medizinischen Forschung, aber auch in der klinischen Praxis führen.
Retinal Vessel Analysis (RVA) in the context of subarachnoid hemorrhage: A proof of concept study
(2016)
Background
Timely detection of impending delayed cerebral ischemia after subarachnoid hemorrhage (SAH) is essential to improve outcome, but poses a diagnostic challenge. Retinal vessels as an embryological part of the intracranial vasculature are easily accessible for analysis and may hold the key to a new and non-invasive monitoring technique. This investigation aims to determine the feasibility of standardized retinal vessel analysis (RVA) in the context of SAH.
Methods
In a prospective pilot study, we performed RVA in six patients awake and cooperative with SAH in the acute phase (day 2–14) and eight patients at the time of follow-up (mean 4.6±1.7months after SAH), and included 33 age-matched healthy controls. Data was acquired using a manoeuvrable Dynamic Vessel Analyzer (Imedos Systems UG, Jena) for examination of retinal vessel dimension and neurovascular coupling.
Results
Image quality was satisfactory in the majority of cases (93.3%). In the acute phase after SAH, retinal arteries were significantly dilated when compared to the control group (124.2±4.3MU vs 110.9±11.4MU, p<0.01), a difference that persisted to a lesser extent in the later stage of the disease (122.7±17.2MU, p<0.05). Testing for neurovascular coupling showed a trend towards impaired primary vasodilation and secondary vasoconstriction (p = 0.08, p = 0.09 resp.) initially and partial recovery at the time of follow-up, indicating a relative improvement in a time-dependent fashion.
Conclusion
RVA is technically feasible in patients with SAH and can detect fluctuations in vessel diameter and autoregulation even in less severely affected patients. Preliminary data suggests potential for RVA as a new and non-invasive tool for advanced SAH monitoring, but clinical relevance and prognostic value will have to be determined in a larger cohort.
Purpose: It was demonstrated previously that retinal pulse wave velocity (rPWV) as a measure of retinal arterial stiffness is increased in aged anamnestically healthy volunteers compared with young healthy subjects. Using novel methodology of rPWV assessment this finding was confirmed and investigated whether it might relate to the increased blood pressure usually accompanying the aging process, rather than to the aging itself.
Methods: A total of 12 young 25.5-year-old (24.0–28.8) [median(1st quartile–3rd quartile)] and 12 senior 68.5-year-old (63.8–71.8) anamnestically healthy volunteers; and 12 senior 63.0-year-old (60.8–65.0) validated healthy volunteers and 12 young 33.0-year-old (29.5–35.0) hypertensive patients were examined. Time-dependent alterations of vessel diameter were assessed by the Dynamic Vessel Analyzer in a retinal artery of each subject. The data were filtered and processed using mathematical signal analysis and rPWVs were calculated.
Results: rPWV amounted to 1200 (990-1470) RU (relative units)/s in the hypertensive group and to 1040 (700-2230) RU/s in anamnestically healthy seniors. These differed significantly from rPWVs in young healthy group (410 [280–500] RU/s) and in validated healthy seniors (400 [320–510] RU/s). rPWV associated with age and mean arterial pressure (MAP) in the pooled cohort excluded validated healthy seniors. In a regression model these associations remain when alternately adjusted for MAP and age. When including validated healthy seniors in the pooled cohort only association with MAP remains.
Conclusions: Both aging (with not excluded cardiovascular risk factors) and mild hypertension are associated with elevated rPWV. rPWV increases to a similar extent both in young mildly hypertensive subjects and in aged anamnestically healthy persons. Healthy aging is not associated with increased rPWV.