@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{AngermannGuenthnerHanssenetal.2022,
  author    = {Angermann, Susanne and G{\"u}nthner, Roman and Hanssen, Henner and Lorenz, Georg and Braunisch, Matthias C. and Steubl, Dominik and Matschkal, Julia and Kemmner, Stephan and Hausinger, Renate and Block, Zenonas and Haller, Bernhard and Heemann, Uwe and Kotliar, Konstantin and Grimmer, Timo and Schmaderer, Christoph},
  title     = {Cognitive impairment and microvascular function in end-stage renal disease},
  series = {International Journal of Methods in Psychiatric Research (MPR)},
  volume    = {31},
  journal   = {International Journal of Methods in Psychiatric Research (MPR)},
  number    = {2},
  publisher = {Wiley},
  issn      = {1049-8931 (Print)},
  doi       = {10.1002/mpr.1909},
  pages     = {1 -- 10},
  year      = {2022},
  abstract  = {Objective Hemodialysis patients show an approximately threefold higher prevalence of cognitive impairment compared to the age-matched general population. Impaired microcirculatory function is one of the assumed causes. Dynamic retinal vessel analysis is a quantitative method for measuring neurovascular coupling and microvascular endothelial function. We hypothesize that cognitive impairment is associated with altered microcirculation of retinal vessels. Methods 152 chronic hemodialysis patients underwent cognitive testing using the Montreal Cognitive Assessment. Retinal microcirculation was assessed by Dynamic Retinal Vessel Analysis, which carries out an examination recording retinal vessels' reaction to a flicker light stimulus under standardized conditions. Results In unadjusted as well as in adjusted linear regression analyses a significant association between the visuospatial executive function domain score of the Montreal Cognitive Assessment and the maximum arteriolar dilation as response of retinal arterioles to the flicker light stimulation was obtained. Conclusion This is the first study determining retinal microvascular function as surrogate for cerebral microvascular function and cognition in hemodialysis patients. The relationship between impairment in executive function and reduced arteriolar reaction to flicker light stimulation supports the involvement of cerebral small vessel disease as contributing factor for the development of cognitive impairment in this patient population and might be a target for noninvasive disease monitoring and therapeutic intervention.},
  language  = {en}
}
@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{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{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}
}
@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}
}
@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}
}
@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{NeumaierKotliarHaerenetal.2021,
  author    = {Neumaier, Felix and Kotliar, Konstantin and Haeren, Roel Hubert Louis and Temel, Yasin and L{\"u}ke, Jan Niklas and Seyam, Osama and Lindauer, Ute and Clusmann, Hans and Hescheler, J{\"u}rgen and Schubert, Gerrit Alexander and Schneider, Toni and Albanna, Walid},
  title     = {Retinal Vessel Responses to Flicker Stimulation Are Impaired in Ca v 2.3-Deficient Mice—An in- vivo Evaluation Using Retinal Vessel Analysis (RVA)},
  series = {Frontiers in Neurology},
  volume    = {12},
  journal   = {Frontiers in Neurology},
  publisher = {Frontiers},
  doi       = {10.3389/fneur.2021.659890},
  pages     = {1 -- 11},
  year      = {2021},
  language  = {en}
}
@article{ConzenAlbannaWeissetal.2018,
  author    = {Conzen, Catharina and Albanna, Walid and Weiss, Miriam and K{\"u}rten, David and Vilser, Walthard and Kotliar, Konstantin and Z{\"a}ske, Charlotte and Clusmann, Hans and Schubert, Gerrit Alexander},
  title     = {Vasoconstriction and Impairment of Neurovascular Coupling after Subarachnoid Hemorrhage: a Descriptive Analysis of Retinal Changes},
  series = {Translational Stroke Research},
  journal   = {Translational Stroke Research},
  number    = {9},
  publisher = {Springer Nature},
  address   = {Cham},
  issn      = {1868-601X},
  doi       = {10.1007/s12975-017-0585-8},
  pages     = {284 -- 293},
  year      = {2018},
  abstract  = {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.},
  language  = {en}
}