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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.
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.
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.
Ein 34-jähriger männlicher Patient stellte sich zur Abklärung einer seit dem 9. Lebensjahr bestehenden und im letzten Jahr rasch progredienten Visusminderung beider Augen bei uns vor. Er beschrieb eine subjektiv zunehmende, im Spiegel für ihn selbst sichtbare, weißliche Trübung in der Pupille beidseits und eine starke Blendempfindlichkeit. Nebenbefundlich gab er rezidivierende Konjunktivitiden und morgens verklebte Lider an. Eine Allergie auf Gräserpollen und eine Unverträglichkeit auf Alkohol sowie mehrere Lebensmittel seien ebenfalls bekannt.
Zusätzlich leidet der Patient an stark ausgeprägtem atopischem Ekzem. Dieses wurde nie systemisch, sondern nur bei Bedarf mit kortisonhaltiger Salbe therapiert.
Retinal endothelial function in cardiovascular risk patients: A randomized controlled exercise trial
(2020)
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.
Masked hypertension is known to induce microvascular complications. However, it is unclear whether early microvascular changes are already occurring in young, otherwise healthy adults. We therefore investigated whether retinal microvascular calibers and acute responses to a flicker stimulus are related to masked hypertension. We used the baseline data of 889 participants aged 20–30 years who were taking part in the African Prospective study on the Early Detection and Identification of Cardiovascular Disease and Hypertension. Clinic and 24-h ambulatory blood pressure were measured. The central retinal artery equivalent (CRAE) and central retinal vein equivalent were calculated from fundus images, and retinal vessel dilation was determined in response to flicker light-induced provocation. A smaller CRAE was observed in those with masked hypertension vs. those with normotension (157.1 vs. 161.2 measuring units, P < 0.001). In forward multivariable-adjusted regression analysis, only CRAE was negatively related to masked hypertension [adjusted R² = 0.267, β = −0.097 (95% CI = −0.165; −0.029), P = 0.005], but other retinal microvascular parameters were not associated with masked hypertension. In multivariable logistic regression analyses, masked hypertension [OR = 2.333, (95% CI = 1.316; 4.241), P = 0.004] was associated with a narrower CRAE. In young healthy adults, masked hypertension was associated with retinal arteriolar narrowing, thereby reflecting early microvascular alterations known to predict cardiovascular outcomes in later life.