@article{KotliarOrtnerConradietal.2022, author = {Kotliar, Konstantin and Ortner, Marion and Conradi, Anna and Hacker, Patricia and Hauser, Christine and G{\"u}nthner, Roman and Moser, Michaela and Muggenthaler, Claudia and Diehl-Schmid, Janine and Priller, Josef and Schmaderer, Christoph and Grimmer, Timo}, title = {Altered retinal cerebral vessel oscillation frequencies in Alzheimer's disease compatible with impaired amyloid clearance}, series = {Neurobiology of Aging}, volume = {120}, journal = {Neurobiology of Aging}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0197-4580}, doi = {10.1016/j.neurobiolaging.2022.08.012}, pages = {117 -- 127}, year = {2022}, abstract = {Retinal vessels are similar to cerebral vessels in their structure and function. Moderately low oscillation frequencies of around 0.1 Hz have been reported as the driving force for paravascular drainage in gray matter in mice and are known as the frequencies of lymphatic vessels in humans. We aimed to elucidate whether retinal vessel oscillations are altered in Alzheimer's disease (AD) at the stage of dementia or mild cognitive impairment (MCI). Seventeen patients with mild-to-moderate dementia due to AD (ADD); 23 patients with MCI due to AD, and 18 cognitively healthy controls (HC) were examined using Dynamic Retinal Vessel Analyzer. Oscillatory temporal changes of retinal vessel diameters were evaluated using mathematical signal analysis. Especially at moderately low frequencies around 0.1 Hz, arterial oscillations in ADD and MCI significantly prevailed over HC oscillations and correlated with disease severity. The pronounced retinal arterial vasomotion at moderately low frequencies in the ADD and MCI groups would be compatible with the view of a compensatory upregulation of paravascular drainage in AD and strengthen the amyloid clearance hypothesis.}, language = {en} } @article{NeumaierWeissVeldemanetal.2021, author = {Neumaier, Felix and Weiss, Miriam and Veldeman, Michael and Kotliar, Konstantin and Wiesmann, Martin and Schulze-Steinen, Henna and H{\"o}llig, Anke and Clusmann, Hans and Schubert, Gerrit Alexander and Albanna, Walid}, title = {Changes in endogenous daytime melatonin levels after aneurysmal subarachnoid hemorrhage - preliminary findings from an observational cohort study}, series = {Clinical Neurology and Neurosurgery}, volume = {208}, journal = {Clinical Neurology and Neurosurgery}, number = {Article No.: 106870}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0303-8467}, doi = {10.1016/j.clineuro.2021.106870}, year = {2021}, abstract = {Aneurysmal subarachnoid hemorrhage (aSAH) is associated with early and delayed brain injury due to several underlying and interrelated processes, which include inflammation, oxidative stress, endothelial, and neuronal apoptosis. Treatment with melatonin, a cytoprotective neurohormone with anti-inflammatory, anti-oxidant and anti-apoptotic effects, has been shown to attenuate early brain injury (EBI) and to prevent delayed cerebral vasospasm in experimental aSAH models. Less is known about the role of endogenous melatonin for aSAH outcome and how its production is altered by the pathophysiological cascades initiated during EBI. In the present observational study, we analyzed changes in melatonin levels during the first three weeks after aSAH.}, language = {en} } @article{KuchlerGuenthnerRibeiroetal.2023, author = {Kuchler, Timon and G{\"u}nthner, Roman and Ribeiro, Andrea and Hausinger, Renate and Streese, Lukas and W{\"o}hnl, Anna and Kesseler, Veronika and Negele, Johanna and Assali, Tarek and Carbajo-Lozoya, Javier and Lech, Maciej and Adorjan, Kristina and Stubbe, Hans Christian and Hanssen, Henner and Kotliar, Konstantin and Haller, Berhard and Heemann, Uwe and Schmaderer, Christoph}, title = {Persistent endothelial dysfunction in post-COVID-19 syndrome and its associations with symptom severity and chronic inflammation}, volume = {26}, publisher = {Springer Nature}, address = {Dordrecht}, doi = {10.1007/s10456-023-09885-6}, pages = {547 -- 563}, year = {2023}, abstract = {Background Post-COVID-19 syndrome (PCS) is a lingering disease with ongoing symptoms such as fatigue and cognitive impairment resulting in a high impact on the daily life of patients. Understanding the pathophysiology of PCS is a public health priority, as it still poses a diagnostic and treatment challenge for physicians. Methods In this prospective observational cohort study, we analyzed the retinal microcirculation using Retinal Vessel Analysis (RVA) in a cohort of patients with PCS and compared it to an age- and gender-matched healthy cohort (n = 41, matched out of n = 204). Measurements and main results PCS patients exhibit persistent endothelial dysfunction (ED), as indicated by significantly lower venular flicker-induced dilation (vFID; 3.42\% ± 1.77\% vs. 4.64\% ± 2.59\%; p = 0.02), narrower central retinal artery equivalent (CRAE; 178.1 [167.5-190.2] vs. 189.1 [179.4-197.2], p = 0.01) and lower arteriolar-venular ratio (AVR; (0.84 [0.8-0.9] vs. 0.88 [0.8-0.9], p = 0.007). When combining AVR and vFID, predicted scores reached good ability to discriminate groups (area under the curve: 0.75). Higher PCS severity scores correlated with lower AVR (R = - 0.37 p = 0.017). The association of microvascular changes with PCS severity were amplified in PCS patients exhibiting higher levels of inflammatory parameters. Conclusion Our results demonstrate that prolonged endothelial dysfunction is a hallmark of PCS, and impairments of the microcirculation seem to explain ongoing symptoms in patients. As potential therapies for PCS emerge, RVA parameters may become relevant as clinical biomarkers for diagnosis and therapy management.}, language = {en} } @article{KuertenKotliarFuestetal.2021, author = {Kuerten, David and Kotliar, Konstantin and Fuest, Matthias and Walter, Peter and Hollstein, Muriel and Plange, Niklas}, title = {Does hemispheric vascular regulation differ significantly in glaucoma patients with altitudinal visual field asymmetry? A single-center, prospective study}, series = {International Ophthalmology}, volume = {41}, journal = {International Ophthalmology}, number = {41}, editor = {Neri, Piergiorgio}, publisher = {Springer}, address = {Berlin}, isbn = {1573-2630}, doi = {10.1007/s10792-021-01876-0}, pages = {3109 -- 3119}, year = {2021}, abstract = {Purpose Vascular risk factors and ocular perfusion are heatedly discussed in the pathogenesis of glaucoma. The retinal vessel analyzer (RVA, IMEDOS Systems, Germany) allows noninvasive measurement of retinal vessel regulation. Significant differences especially in the veins between healthy subjects and patients suffering from glaucoma were previously reported. In this pilot-study we investigated if localized vascular regulation is altered in glaucoma patients with altitudinal visual field defect asymmetry. Methods 15 eyes of 12 glaucoma patients with advanced altitudinal visual field defect asymmetry were included. The mean defect was calculated for each hemisphere separately (-20.99 ± 10.49 pro- found hemispheric visual field defect vs -7.36 ± 3.97 dB less profound hemisphere). After pupil dilation, RVA measurements of retinal arteries and veins were conducted using the standard protocol. The superior and inferior retinal vessel reactivity were measured consecutively in each eye. Results Significant differences were recorded in venous vessel constriction after flicker light stimulation and overall amplitude of the reaction (p \ 0.04 and p \ 0.02 respectively) in-between the hemispheres spheres. Vessel reaction was higher in the hemisphere corresponding to the more advanced visual field defect. Arterial diameters reacted similarly, failing to reach statistical significance. Conclusion Localized retinal vessel regulation is significantly altered in glaucoma patients with asymmetri altitudinal visual field defects. Veins supplying the hemisphere concordant to a less profound visual field defect show diminished diameter changes. Vascular dysregulation might be particularly important in early glaucoma stages prior to a significant visual field defect.}, language = {en} } @article{AlbannaConzenWeissetal.2021, author = {Albanna, Walid and Conzen, Catharina and Weiss, Miriam and Seyfried, Katharina and Kotliar, Konstantin and Schmidt, Tobias Philip and Kuerten, David and Hescheler, J{\"u}rgen and Bruecken, Anne and Schmidt-Trucks{\"a}ss, Arno and Neumaier, Felix and Wiesmann, Martin and Clusmann, Hans and Schubert, Gerrit Alexander}, title = {Non-invasive assessment of neurovascular coupling after aneurysmal subarachnoid hemorrhage: a prospective observational trial using retinal vessel analysis}, series = {Frontiers in Neurology}, volume = {12}, journal = {Frontiers in Neurology}, number = {12}, issn = {1664-2295}, doi = {10.3389/fneur.2021.690183}, pages = {1 -- 15}, year = {2021}, abstract = {Delayed cerebral ischemia (DCI) is a common complication after aneurysmal subarachnoid hemorrhage (aSAH) and can lead to infarction and poor clinical outcome. The underlying mechanisms are still incompletely understood, but animal models indicate that vasoactive metabolites and inflammatory cytokines produced within the subarachnoid space may progressively impair and partially invert neurovascular coupling (NVC) in the brain. Because cerebral and retinal microvasculature are governed by comparable regulatory mechanisms and may be connected by perivascular pathways, retinal vascular changes are increasingly recognized as a potential surrogate for altered NVC in the brain. Here, we used non-invasive retinal vessel analysis (RVA) to assess microvascular function in aSAH patients at different times after the ictus.}, language = {en} } @incollection{Kotliar2021, author = {Kotliar, Konstantin}, title = {Ocular rigidity: clinical approach}, series = {Ocular Rigidity, Biomechanics and Hydrodynamics of the Eye}, booktitle = {Ocular Rigidity, Biomechanics and Hydrodynamics of the Eye}, editor = {Pallikaris, I. and Tsilimbaris, M. K. and Dastiridou, A. I.}, publisher = {Springer}, address = {Cham}, isbn = {978-3-030-64422-2}, doi = {10.1007/978-3-030-64422-2_2}, pages = {15 -- 43}, year = {2021}, abstract = {The term ocular rigidity is widely used in clinical ophthalmology. Generally it is assumed as a resistance of the whole eyeball to mechanical deformation and relates to biomechanical properties of the eye and its tissues. Basic principles and formulas for clinical tonometry, tonography and pulsatile ocular blood flow measurements are based on the concept of ocular rigidity. There is evidence for altered ocular rigidity in aging, in several eye diseases and after eye surgery. Unfortunately, there is no consensual view on ocular rigidity: it used to make a quite different sense for different people but still the same name. Foremost there is no clear consent between biomechanical engineers and ophthalmologists on the concept. Moreover ocular rigidity is occasionally characterized using various parameters with their different physical dimensions. In contrast to engineering approach, clinical approach to ocular rigidity claims to characterize the total mechanical response of the eyeball to its deformation without any detailed considerations on eye morphology or material properties of its tissues. Further to the previous chapter this section aims to describe clinical approach to ocular rigidity from the perspective of an engineer in an attempt to straighten out this concept, to show its advantages, disadvantages and various applications.}, language = {en} } @inproceedings{IomdinaKiselevaKotliaretal.2020, author = {Iomdina, Elena N. and Kiseleva, Anna A. and Kotliar, Konstantin and Luzhnov, Petr V.}, title = {Quantification of Choroidal Blood Flow Using the OCT-A System Based on Voxel Scan Processing}, series = {Proceedings of the International Conference on Biomedical Innovations and Applications- BIA 2020}, booktitle = {Proceedings of the International Conference on Biomedical Innovations and Applications- BIA 2020}, publisher = {IEEE}, address = {New York, NY}, isbn = {978-1-7281-7073-2}, doi = {10.1109/BIA50171.2020.9244511}, pages = {41 -- 44}, year = {2020}, abstract = {The paper presents a method for the quantitative assessment of choroidal blood flow using an OCT-A system. The developed technique for processing of OCT-A scans is divided into two stages. At the first stage, the identification of the boundaries in the selected portion was performed. At the second stage, each pixel mark on the selected layer was represented as a volume unit, a voxel, which characterizes the region of moving blood. Three geometric shapes were considered to represent the voxel. On the example of one OCT-A scan, this work presents a quantitative assessment of the blood flow index. A possible modification of two-stage algorithm based on voxel scan processing is presented.}, language = {en} } @article{WerfelGuenthnerHapfelmeieretal.2022, author = {Werfel, Stanislas and G{\"u}nthner, Roman and Hapfelmeier, Alexander and Hanssen, Henner and Kotliar, Konstantin and Heemann, Uwe and Schmaderer, Christoph}, title = {Identification of cardiovascular high-risk groups from dynamic retinal vessel signals using untargeted machine learning}, series = {Cardiovascular Research}, volume = {118}, journal = {Cardiovascular Research}, number = {2}, editor = {Guzik, Tomasz J.}, publisher = {Oxford University Press}, address = {Oxford}, issn = {0008-6363}, doi = {10.1093/cvr/cvab040}, pages = {612 -- 621}, year = {2022}, abstract = {Dynamic retinal vessel analysis (DVA) provides a non-invasive way to assess microvascular function in patients and potentially to improve predictions of individual cardiovascular (CV) risk. The aim of our study was to use untargeted machine learning on DVA in order to improve CV mortality prediction and identify corresponding response alterations.}, language = {en} } @article{MalanHamerKaeneletal.2020, author = {Malan, Leone and Hamer, Mark and K{\"a}nel, Roland von and Kotliar, Konstantin and Wyk, Roelof D. van and Lambert, Gavin W. and Vilser, Walthard and Ziemssen, Tjalf and Schlaich, Markus P. and Smith, Wayne and Magnusson, Martin and Wentzel, Annemarie and Myburgh, Carlien E. and Steyn, Hendrik S. and Malan, Nico T.}, title = {Delayed retinal vein recovery responses indicate both non-adaptation to stress as well as increased risk for stroke: the SABPA study}, series = {Cardiovascular Journal of Africa}, volume = {26}, journal = {Cardiovascular Journal of Africa}, number = {31}, publisher = {Clinics Cardive Publishing}, address = {Durbanville}, issn = {1680-0745}, doi = {10.5830/CVJA-2020-031}, pages = {1 -- 12}, year = {2020}, language = {en} } @article{StreeseKotliarDeiserothetal.2020, author = {Streese, Lukas and Kotliar, Konstantin and Deiseroth, Arne and Infanger, Denis and Gugleta, Konstantin and Schmaderer, Christoph and Hanssen, Henner}, title = {Retinal endothelial function in cardiovascular risk patients: A randomized controlled exercise trial}, series = {Scandinavian Journal of Medicine and Science in Sports}, volume = {30}, journal = {Scandinavian Journal of Medicine and Science in Sports}, number = {2}, publisher = {Wiley}, address = {Oxford}, issn = {1600-0838}, doi = {10.1111/sms.13560}, pages = {272 -- 280}, year = {2020}, abstract = {The aim of this study was to investigate, for the first time, the effects of high-intensity interval training (HIIT) on retinal microvascular endothelial function in cardiovascular (CV) risk patients. In the randomized controlled trial, middle-aged and previously sedentary patients with increased CV risk (aged 58 ± 6 years) with ≥ two CV risk factors were randomized into a 12-week HIIT (n = 33) or control group (CG, n = 36) with standard physical activity recommendations. A blinded examiner measured retinal endothelial function by flicker light-induced maximal arteriolar (ADmax) and venular (VDmax) dilatation as well as the area under the arteriolar (AFarea) and venular (VFarea) flicker curve using a retinal vessel analyzer. Standardized assessments of CV risk factors, cardiorespiratory fitness, and retinal endothelial function were performed before and after HIIT. HIIT reduced body mass index, fat mass, and low-density lipoprotein and increased muscle mass and peak oxygen uptake (VO2peak). Both ADmax (pre: 2.7 ± 2.1\%, post: 3.0 ± 2.2\%, P = .018) and AFarea (pre: 32.6 ± 28.4\%*s, post: 37.7 ± 30.6\%*s, P = .016) increased after HIIT compared with CG (ADmax, pre: 3.2 ± 1.8\%, post: 2.9 ± 1.8\%, P = .254; AFarea, pre: 41.6 ± 28.5\%*s, post: 37.8 ± 27.0\%*s, P = .186). Venular function remained unchanged after HIIT. There was a significant association between ∆-change VO2peak and ∆-changes ADmax and AFarea (P = .026, R² = 0.073; P = .019, R² = 0.081, respectively). 12-weeks of HIIT improved retinal endothelial function in middle-aged patients with increased CV risk independent of the reduction in classical CV risk factors. Exercise has the potential to reverse or at least postpone progression of small vessel disease in older adults with increased CV risk under standard medication. Dynamic retinal vessel analysis seems to be a sensitive tool to detect treatment effects of exercise interventions on retinal microvascular endothelial function in middle-aged individuals with increased CV risk.}, language = {en} }