Diabetic retinopathy (DR) is a common complication of diabetes mellitus that disrupts the retinal microvasculature and is a leading cause of vision loss globally. Recently, optical coherence tomography angiography (OCTA) has been developed to image the retinal microvasculature, by generating 3-dimensional images based on the motion contrast of circulating blood cells. OCTA offers numerous benefits over traditional fluorescein angiography in visualizing the retinal vasculature in that it is non-invasive and safer; while its depth-resolved ability makes it possible to visualize the finer capillaries of the retinal capillary plexuses and choriocapillaris. High-quality OCTA images have also enabled the visualization of features associated with DR, including microaneurysms and neovascularization and the quantification of alterations in retinal capillary and choriocapillaris, thereby suggesting a promising role for OCTA as an objective technology for accurate DR classification. Of interest is the potential of OCTA to examine the effect of DR on individual retinal layers, and to detect DR even before it is clinically detectable on fundus examination. We will focus the review on the clinical applicability of OCTA derived quantitative metrics that appear to be clinically relevant to the diagnosis, classification, and management of patients with diabetes or DR. Future studies with longitudinal design of multiethnic multicenter populations, as well as the inclusion of pertinent systemic information that may affect vascular changes, will improve our understanding on the benefit of OCTA biomarkers in the detection and progression of DR.

To investigate long COVID-19 syndrome (LCS) pathophysiology, we performed an exploratory study with blood plasma derived from three groups: 1) healthy vaccinated individuals without SARS-CoV-2 exposure; 2) asymptomatic recovered patients at least three months after SARS-CoV-2 infection and; 3) symptomatic patients at least 3 months after SARS-CoV-2 infection with chronic fatigue syndrome or similar symptoms, here designated as patients with long COVID-19 syndrome (LCS). Multiplex cytokine profiling indicated slightly elevated pro-inflammatory cytokine levels in recovered individuals in contrast to patients with LCS. Plasma proteomics demonstrated low levels of acute phase proteins and macrophage-derived secreted proteins in LCS. High levels of anti-inflammatory oxylipins including omega-3 fatty acids in LCS were detected by eicosadomics, whereas targeted metabolic profiling indicated high levels of anti-inflammatory osmolytes taurine and hypaphorine, but low amino acid and triglyceride levels and deregulated acylcarnitines. A model considering alternatively polarized macrophages as a major contributor to these molecular alterations is presented.

OBJECTIVE: Flicker-induced vasodilatation is reduced in patients with vascular-related diseases, which has at least partially been attributed to endothelial dysfunction of retinal vessels. Currently, the standard method to assess endothelial function in vivo is flow-mediated vasodilatation (FMD). Thus, the present study was performed to investigate whether a correlation exists between flicker-induced vasodilatation and FMD in patients with known endothelial dysfunction and healthy subjects. RESEARCH DESIGN AND METHODS: In the present study, 20 patients with type 1 diabetes, 40 patients with systemic hypertension (systolic blood pressure 140–159 mmHg; diastolic blood pressure 90–99 mmHg) and/or serum cholesterol levels ≥0.65 mmol/l, and 20 healthy control subjects were included. The flicker response was measured using the Dynamic Retinal Vessel Analyzer. FMD was determined using a high-resolution ultrasound system, measuring brachial artery diameter reactivity during reperfusion after arterial occlusion. RESULTS: The flicker response of both retinal arteries and veins was significantly reduced in the two patients groups. Likewise, FMD was significantly reduced in patients compared with healthy control subjects. However, only a weak correlation between flicker-induced vasodilatation and FMD was observed. CONCLUSIONS: The study confirms that flicker responses and FMD are reduced in the selected patient groups. Whether the weak correlation between FMD and flicker is due to the different stimulation type, the different vascular beds measured, or other mechanisms has yet to be investigated.

Neurovascular coupling, also termed functional hyperemia, is one of the physiological key mechanisms to adjust blood flow in a neural tissue in response to functional activity. In the retina, increased neural activity, such as that induced by visual stimulation, leads to the dilatation of retinal arterioles, which is accompanied by an immediate increase in retinal and optic nerve head blood flow. According to the current scientific view, functional hyperemia ensures the adequate supply of nutrients and metabolites in response to the increased metabolic demand of the neural tissue. Although the molecular mechanisms behind neurovascular coupling are not yet fully elucidated, there is compelling evidence that this regulation is impaired in a wide variety of neurodegenerative and vascular diseases. In particular, it has been shown that the breakdown of the functional hyperemic response is an early event in patients with diabetes. There is compelling evidence that alterations in neurovascular coupling precede visible signs of diabetic retinopathy. Based on these observations, it has been hypothesized that a breakdown of functional hyperemia may contribute to the retinal complications of diabetes such as diabetic retinopathy or macular edema. The present review summarizes the current evidence of impaired neurovascular coupling in patients with diabetes. In this context, the molecular mechanisms of functional hyperemia in health and disease will be covered. Finally, we will also discuss how neurovascular coupling may in future be used to monitor disease progression or risk stratification.

Purpose: The aim of this mechanistic clinical study was to explore the effect of water-free perfluorohexyloctane eye drops on tear film thickness (TFT) in patients with dry eye disease (DED). Methods: Forty-eight patients with mild to moderate DED participated in this randomized, single-masked, observer-blinded parallel group study in a 1:1 ratio to receive either perfluorohexyloctane or unpreserved 0.9% saline solution (Hydrabak ^® , Thea, France) eye drops 4 times daily in both eyes for 4 weeks. A custom-built ultrahigh-resolution optical coherence tomography system was used to measure TFT. Furthermore, evaluation of lipid layer thickness (LLT) and noninvasive tear film breakup time, as well as standard clinical tests for signs and symptoms of DED were performed. Results: Mean TFT and LLT at baseline were comparable between the 2 treatment groups. After a single drop instillation, perfluorohexyloctane eye drops temporarily increased TFT immediately. After multiple dosing, perfluorohexyloctane eye drops gradually increased TFT over time with a maximum effect at the end of the study (least square mean difference: 6.42%; P = 0.0142 at week 4). LLT values measured before drop instillation showed a more prominent increase in LLT for perfluorohexyloctane eye drops (13.36% ± 26.33% vs. 3.21% ± 28.65%). All other parameters got better in both treatment groups with no statistical difference between groups. Conclusions: These results demonstrate that perfluorohexyloctane eye drops increase TFT as well as LLT over time. These tear film reestablishing attributes are in line with the mode of action of perfluorohexyloctane eye drops to avoid evaporation through stabilization of the lipid layer.