[Optical coherence tomography angiography in the diagnosis of multiple sclerosis]. / Opticheskaya kogerentnaya tomografiya-angiografiya v diagnostike rasseyannogo skleroza.

PURPOSE: This study analyzes the main changes in retinal microcirculation in patients with multiple sclerosis (MS) and their relationship with the type of disease course. MATERIAL AND METHODS: 159 patients (318 eyes) were examined. The groups were formed according to the type of course and duration of MS: group 1 - 37 patients (74 eyes; 23.27%) with relapsing-remitting MS (RRMS) less than 1 year; group 2 - 47 patients (94 eyes; 29.56%) with RRMS from 1 year to 10 years; group 3 - 44 patients (86 eyes; 27.05%) with RRMS >10 years; group 4 - 32 patients (64 eyes; 20.12%) with secondary progressive MS (SPMS). Subgroups A and B were allocated within each group depending on the absence or presence of optic neuritis (ON). Patients underwent standard ophthalmological examination, including optical coherence tomography angiography (OCTA). RESULTS: A decrease in the vessel density (wiVD) and perfusion density (wiPD) in the macular and peripapillary regions was revealed, progressing with the duration of the disease and with its transition to the progressive type. The minimum values were observed in patients with SPMS (group 4), with the most pronounced in the subgroup with ON (wiVD = 16.06±3.65 mm/mm2, wiPD = 39.38±9.46%, ppwiPD = 44.06±3.09%, ppwiF = 0.41±0.05). CONCLUSION: OCTA provides the ability to detect subclinical vascular changes and can be considered a comprehensive, reliable method for early diagnosis and monitoring of MS progression.

Impaired retinal microcirculation in patients with non-obstructive coronary artery disease.

PURPOSE: To quantitatively investigate alterations of retinal microcirculation in patients with non-obstructive coronary artery disease (NOCAD) using optical coherence tomography angiography (OCTA), and to identify the ability of retinal microcirculation parameters in differentiating coronary artery disease (CAD) subtypes. METHODS: All participants with angina pectoris underwent coronary computed tomography angiography. Patients with lumen diameter reduction of 20-50 % in all major coronary arteries were defined as NOCAD, while patients with at least one major coronary artery lumen diameter reduction ≥ 50 % were recruited as obstructive coronary artery disease (OCAD). Participants without a history of ophthalmic or systemic vascular disease were recruited as healthy controls. Retinal neural-vasculature was measured quantitatively by OCTA, including peripapillary retinal nerve fiber layer (RNFL) thickness and vessel density (VD) of the optic disc, superficial vessel plexus (SVP), deep vessel plexus (DVP), and foveal density (FD 300). p < 0.017 is considered significant in multiple comparisons. RESULTS: A total of 185 participants (65 NOCAD, 62 OCAD, and 58 controls) were enrolled. Except for the DVP fovea (p = 0.069), significantly reduced VD in all other regions of SVP and DVP was detected in both the NOCAD and OCAD groups compared to control group (all p < 0.017), while a more significant decrease was found in OCAD compared to NOCAD. Multivariate regression analysis showed that lower VD in superior hemi part of whole SVP (OR: 0.582, 95 % CI: 0.451-0.752) was an independent risk factor for NOCAD compared to controls, while lower VD in the whole SVP (OR: 0.550, 95 % CI: 0.421-0.719) was an independent risk factor for OCAD compared to NOCAD. Using the integration of retinal microvascular parameters, the area under the receiver operating characteristic curve (AUC) for NOCAD versus control and OCAD versus NOCAD were 0.840 and 0.830, respectively. CONCLUSION: Significant retinal microcirculation impairment, while milder than that in OCAD was observed in NOCAD patients, indicating retinal microvasculature assessment might provide a new systemic microcirculation observation window for NOCAD. Furthermore, retinal microvasculature may serve as a new indicator to assess the severity of CAD with good performance of retinal microvascular parameters in identifying different CAD subtypes.

Impact of type 1 diabetes and its duration on wall-to-lumen ratio and blood flow in retinal arterioles.

BACKGROUND: Subclinical damage to both the small and large vessels may contribute to the development and progression of cardiovascular disease. Scanning laser Doppler flowmetry (SLDF), an established method used to measure retinal microcirculation, has been successfully applied in hypertensive and post-stroke patients. METHODS: Retinal microcirculation was assessed in 158 patients with type 1 diabetes and 38 age-matched healthy controls. The diabetics were divided into 3 groups: group A with diabetes duration <12 months, group B with diabetes with 1-10 years, and group C >10 years of diabetes. Retinal capillary structure and perfusion were evaluated using a Heidelberg retina flowmeter and automatically analyzed with full-field perfusion imaging. RESULTS: Age and BMI were comparable in all the diabetic patients and the controls (mean age 24.8 ± 4.7 years, mean BMI 22.9 ± 4.1). In the univariate analyses, RCF (retinal capillary flow) was significantly higher in group A (297 ± 121 arbitrary units [AU]) vs group B (236 ± 52 AU; p = 0.007) and group C (236 ± 70 AU; p = 0.008) and comparable to that of the controls (p = 0.46). Additionally, the WLR (Wall-to-Lumen Ratio) was highest in group C compared to the other diabetic subgroups and controls (p = 0.001). Multivariate regression analyses including age, BMI, sex, HbA1c, smoking, systolic blood pressure, and diabetes duration as covariates, showed, that only diabetes duration was significantly associated with WLR variations, whereas HbA1c was significantly linked to retinal capillary flow levels. CONCLUSIONS: New-onset diabetes is associated with an increase in RCF, which then gradually decreased with the duration of the disease. Structural changes of the retinal arterioles estimated via WLR are evident later in the course of diabetes, especially when the disease duration exceeded 10 years.

A moderate dosage of coffee causes acute retinal capillary perfusion decrease in healthy young individuals.

AIM: Caffeinated beverages are very popular across populations and cultures, but quantitative evidence of the acute effects of moderate coffee doses on retinal perfusion is sparse and contradicting. Thus, the aim of this randomized, cross-over and parallel-group design study was to investigate whether moderate consumption of coffee alters macular retinal capillary perfusion in young healthy individuals. METHODS: Twenty-seven young healthy individuals were recruited for this study. Acute changes in retinal microvasculature were assessed using spectral-domain optical coherence tomography angiography (SD-OCTA) at baseline, 0.5 h, and 2 h after intake of coffee, or water. Meanwhile, cerebral blood flow (CBF) and retina-choroid blood flow were evaluated in a parallel-group design (4 participants each in coffee or water group) using magnetic resonance imaging (MRI) with pseudo-continuous arterial spin labeling sequences. RESULTS: Two hours after coffee intake, blood caffeine concentration increased from 0 to 5.05 ± 1.36 µg/mL. Coffee caused a significant decrease in retinal vessel diameter index (VDI) (19.05 ± 0.24 versus [vs] 19.13 ± 0.26; p < 0.001) and CBF in the frontal lobe (77.47 ± 15.21 mL/100 mL/min vs. 84.13 ± 15.55 mL/100 mL/min; p < 0.05) 2 h after intake. However, it significantly increased retina-choroid blood flow after 0.5 and 2 h (163.18 ± 61.07 mL/100 mL/min vs. 132.68 ± 70.47 mL/100 mL/min, p < 0.001, and 161.21 ± 47.95 vs. 132.68 ± 70.47; p < 0.001, respectively). CONCLUSION: This is the first study to demonstrate the acute effects of daily dose coffee consumption on retinal capillary perfusion using SD-OCTA combinate with blood flow MRI. The findings imply that although moderate coffee intake caused a significant increase in retina-choroid blood flow, there was a significant acute decrease both in macular retinal capillary perfusion and CBF.

Post-COVID-19 Syndrome: Retinal Microcirculation as a Potential Marker for Chronic Fatigue.

Post-COVID-19 syndrome (PCS) is characterized by persisting sequelae after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). PCS can affect patients with all COVID-19 disease severities. As previous studies have revealed impaired blood flow as a provoking factor triggering PCS, it was the aim of the present study to investigate the potential association between self-reported chronic fatigue and retinal microcirculation in patients with PCS, potentially indicating an objective biomarker. A prospective study was performed, including 201 subjects: 173 patients with PCS and 28 controls. Retinal microcirculation was visualized by OCT angiography (OCT-A) and quantified using the Erlangen-Angio-Tool as macula and peripapillary vessel density (VD). Chronic fatigue (CF) was assessed according to the variables of Bell's score, age and gender. VDs in the superficial vascular plexus (SVP), intermediate capillary plexus (ICP) and deep capillary plexus (DCP) were analyzed, considering the repetitions (12 times). Seropositivity for autoantibodies targeting G protein-coupled receptors (GPCR-AAbs) was determined by an established cardiomyocyte bioassay. Taking account of the repetitions, a mixed model was performed to detect possible differences in the least square means between the different groups included in the analysis. An age effect in relation to VD was observed between patients and controls (p < 0.0001). Gender analysis showed that women with PCS showed lower VD levels in the SVP compared to male patients (p = 0.0015). The PCS patients showed significantly lower VDs in the ICP as compared to the controls (p = 0.0001 (CI: 0.32; 1)). Moreover, considering PCS patients, the mixed model revealed a significant difference between those with chronic fatigue (CF) and those without CF with respect to VDs in the SVP (p = 0.0033 (CI: −4.5; −0.92)). The model included variables of age, gender and Bell's score, representing a subjective marker for CF. Consequently, retinal microcirculation might serve as an objective biomarker in subjectively reported chronic fatigue in patients with PCS.

Retinal microvasculature and time to pregnancy in a multi-ethnic pre-conception cohort in Singapore.

STUDY QUESTION: Can abnormalities in retinal microvasculature representing adverse microcirculatory perfusion and inflammation shed light on the pathophysiology of female fecundability? SUMMARY ANSWER: In our prospective study, abnormalities in retinal vascular geometric morphology (i.e. sparser arteriolar fractal and larger venular bifurcation) during pre-conception phase are temporarily associated with a prolonged time-to-pregnancy (TTP). WHAT IS KNOWN ALREADY: Suboptimal retinal microcirculatory morphology has been associated with obesity, psychological stress and hypertension, all of which are known risk factors for reduced female fecundability. STUDY DESIGN, SIZE, DURATION: A total of 652 women of Chinese, Malay or Indian ethnicity 18-45 years of age and planning to conceive spontaneously within the next 12 months were recruited during the pre-conception period into the Singapore PREconception Study of long-Term maternal and child Outcomes (S-PRESTO), from February 2015 to October 2017. PARTICIPANTS/MATERIALS, SETTING, METHODS: During recruitment, we collected information on socio-demographic factors, menstrual characteristics and lifestyle behaviors and made anthropometric measurements. We assessed the following retinal microvascular features: caliber, branching angle and fractal dimension. We conducted follow-up telephone surveys to track each participant's pregnancy status at 6, 9 and 12 months after enrolment. We ascertained clinical pregnancies via ultrasonography, with TTP measured by the number of menstrual cycles required to achieve a clinical pregnancy over a 1-year follow-up. Then, we performed discrete-time proportional hazards models to estimate the fecundability odds ratio (FOR) and 95% CI for each retinal microvascular feature in association with TTP, after adjusting for major confounders, including body mass index and fasting glycemic level at study entry. MAIN RESULTS AND THE ROLE OF THE CHANCE: Among 652 recruited women, 276 (42.3%) successfully conceived within 1 year of follow-up. The mean (and SD) was 1.24 (0.05) Df for retinal arteriolar dimension fraction and 78.45 (9.79) degrees for retinal venular branching angle, respectively. Non-linear relationship testing was performed before multiple adjustment in all associations and a non-monotonic association was detected between retinal venular branching angle and TTP. Compared with women in the highest tertile of retinal arteriolar fractal dimension, women in the second tertile had a prolonged TTP (FOR: 0.68; 95% CI: 0.51-0.92), as did women in the lowest tertile (FOR: 0.73; 95% CI: 0.55-0.98). Compared with women in the middle tertile of retinal venular branching angle, women in the highest tertile had a borderline prolonged TTP (FOR: 0.75; 95% CI: 0.56-1.02). No other retinal vascular features were significantly associated with TTP. LIMITATIONS, REASONS FOR CAUTION: We were unable to adjust for other potential confounding factors such as female sexual function (e.g. frequency of sexual intercourse), which might introduce a residual bias. Moreover, even though this is a prospective cohort design, our findings can identify the temporal relationship but not necessarily infer a causal relationship between maternal microvasculature and TTP. Lastly, our study involving mainly Chinese, Malay and Indian ethnicities might not be generalizable to other races or ethnicities. WIDER IMPLICATIONS OF THE FINDINGS: Suboptimal microcirculation may lead to reduced female fecundability. In the future, in addition to conventional ultrasonographic evaluation of ovarian and uterine physiological function, assessing the retinal microvasculature might be useful for assessment of ovarian age, fertility prediction and endometrial evaluation before assisted reproductive techniques for fertility treatments. STUDY FUNDING/COMPETING INTEREST(S): This research is supported by the Singapore National Research Foundation (NRF) under its Translational and Clinical Research (TCR) Flagship Programme and administered by the Singapore Ministry of Health's National Medical Research Council (NMRC) (Singapore-NMRC/TCR/004-NUS/2008; NMRC/TCR/012-NUHS/2014) and Singapore National Medical Research Council Transition Award (NMRC TA/0027/2014). The authors have no competing interests to declare. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, NCT03531658.

Vascular Density and Retinal Function in Patients with Retinitis Pigmentosa Evaluated by Swept-Source OCT Angiography and Microperimetry.

PURPOSE: To determine the retinal and choroidal vessel density in the macular area with swept-source optical coherence tomography (OCT) angiography (SS-OCTA) in patients affected by retinitis pigmentosa (RP), to compare their data with those on healthy subjects, and to study a possible morphofunctional correlation by microperimetry (MP-1). METHODS: A total of 40 eyes of 40 patients affected by RP and 24 eyes of 24 healthy subjects were included in the study. Manually moving down the segmentation line of the SS-OCTA, we have evaluated the vessel density for the superficial retinal plexus, deep retinal plexus, choriocapillaris, and three levels of the choroid. RESULTS: Linear regression analyses were performed of the retinal structure and function. No significant correlation was detected in any case (R2 = 0, p > 0.05). A comparison between RP and healthy controls revealed a significant reduction in SS-OCTA mean capillary density in the RP group (p = 0.0011). This relationship was consistent across vascular layers (p = 0.2413). A significant association between the capillary density of the various vascular complexes was detected within individual eyes (p < 0.0001). CONCLUSIONS: This study represents the first comparing MP-1 and SS-OCTA data in the largest cohort of patients. RP patients showed a reduction in both the retinal and the choroidal vascular network in the macular area compared to healthy subjects.

High-intensity interval training modulates retinal microvascular phenotype and DNA methylation of p66Shc gene: a randomized controlled trial (EXAMIN AGE).

AIMS: Impairments of retinal vessel diameter are associated with major adverse cardiovascular (CV) events. Promoter DNA methylation is a repressor of the mitochondrial adaptor p66Shc gene transcription, a key driver of ageing-induced reactive oxygen species. The study aimed to investigate whether high-intensity interval training (HIIT) affects retinal microvascular phenotype as well as p66Shc expression and oxidative stress in ageing subjects with increased CV risk from the EXAMIN AGE cohort. METHODS AND RESULTS: Eighty-four sedentary subjects (mean age 59.4 ± 7.0 years) with ≥2 CV risk factors were randomized into either a 12-week HIIT or standard physical activity recommendations. Retinal arteriolar and venular diameters were measured by use of a retinal vessel analyser. As a marker of oxidative stress plasma 3-nitrotyrosine (3-NT) level was determined by ELISA. Gene expression of p66Shc and DNA methylation were assessed in mononuclear cells by RT-qPCR and methylated-DNA capture (MethylMiner Enrichment Kit) coupled with qPCR, respectively. High-intensity interval training reduced body mass index, fat mass, low-density lipoprotein and increased muscle mass, as well as maximal oxygen uptake (VO2max). Moreover, HIIT restored microvascular phenotype by inducing retinal arteriolar widening (pre: 175 ± 14 µm vs. post: 181 ± 13 µm, P = 0.001) and venular narrowing (pre: 222 ± 14 µm vs. post: 220 ± 14 µm, P = 0.007). After HIIT, restoration of p66Shc promoter methylation (P = 0.034) reduced p66Shc gene expression (P = 0.037) and, in turn, blunted 3-NT plasma levels (P = 0.002). CONCLUSION: High-intensity interval training rescues microvascular dysfunction in ageing subjects at increased CV risk. Exercise-induced reprogramming of DNA methylation of p66Shc gene may represent a putative mechanistic link whereby exercise protects against age-related oxidative stress. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: NCT02796976 (https://clinicaltrials.gov/ct2/show/NCT02796976).

Impacts of Camellia sinensis fermentation end-product (black tea) on retinal microvasculature: an updated OCTA analysis.

BACKGROUND: Tea, second only to water, is one of the most regularly consumed drinks in the world. Its potentially beneficial effects on general health may be enormously important. Optical coherence tomography angiography (OCTA) now allows clinicians to examine the acute retinal morphological changes caused by black tea consumption. The purpose of this study was to investigate the acute impacts of a Camellia sinensis fermentation end-product (black tea) on retinal microvasculature in healthy individuals using OCTA. RESULTS: In this study, 60 healthy people were divided into two groups: group 1 (n = 30) received black tea (2 mg/250 mL of water) and group 2 (n = 30) received only 250 mL of water. Following consumption, AngioVue Analytics software automatically analyzed the foveal, parafoveal, perifoveal macular superficial and deep vascular plexus densities, foveal avascular zone (FAZ) area, FAZ perimeter and foveal vessel density in a 300 µm wide region around the FAZ (FD-300). Male-to-female ratios were 19:11 and 15:15 in groups 1 and 2, respectively (P = 0.217). Mean age was 33.27 ± 7.92 years in group 1 and 31.00 ± 7.30 years in group 2 (P = 0.254). Changes in foveal, perifoveal and parafoveal macular vessel density between groups 1 and 2 were not statistically significant. In addition, no significant differences regarding FAZ, FAZ perimeter and FD-300 were observed. CONCLUSION: There were no acute effects of black tea on macular microcirculation in healthy individuals. The authors, however, believe that this study could serve as a model for future research on the relationship between regular tea consumption and general ocular physiology. © 2021 Society of Chemical Industry.

Early changes in retinal microcirculation after uncomplicated cataract surgery using an active-fluidics system.

PURPOSE: To evaluate the early changes in retinal microcirculation after uncomplicated cataract surgery using an active-fluidics system. MATERIALS AND METHODS: Patients underwent uncomplicated cataract surgery for both eyes were enrolled. The two eyes of the patients were randomly assigned to two groups, the active-fluidics group and the gravity-fluidics group. One eye using an active-fluidics system, and the other using a gravity-fluidics system. Optical coherence tomography angiography (OCTA) was performed at 1 day, 7 days, 30 days, and 90 days after surgery. RESULTS: Fifty eyes (25 patients) were included in the final analysis. A significantly lower cumulative dissipated energy (CDE), estimated fluid usage (EFU), and total aspiration time (TAT) were observed in the active-fluidics group (all P<0.05). The superficial vessel density at parafoveal region increased at 7 days and 30 days after cataract surgery in the eyes of both the active-fluidics and gravity-fluidics groups, with the fluctuation in eyes of the gravity-fluidics group more significant. The vessel density of deep capillary plexus remained stable during the follow-up period. Significant changes of retinal thickness in macular region (fovea, parafovea) were observed in eyes of the gravity-fluidics group through the comparison of corresponding values at different time points (p = 0.008, 0.005). No significant change in retinal thickness was observed in eyes of the active-fluidics. CONCLUSIONS: Retinal microcirculation and thickness were disturbed after cataract surgery using the gravity-fluidics infusion system. The active-fluidics system not only improved the surgical efficacy but also protected the retinal vasculature during cataract surgery. CLINICAL TRIALS REGISTRATION: The study has been registered at www.clinicaltrials.gov with its clinical trial accession number of NCT0130500.

Optical coherence tomography angiography-derived flow density: a review of the influencing factors.

Research interest in the possibility of quantifying macular and optic nerve head perfusion through optical coherence tomography angiography (OCTA) is rapidly advancing. Numerous scientific trials have furthered our understanding of the capabilities and the limitations of this novel technology, while applying OCTA to various ocular pathologies. In recent years, different parameters such as age, gender, intraocular pressure, spherical equivalent, physical activity, systemic diseases, and medication have been shown to have a significant impact on quantitative OCTA metrics. Since OCTA is likely to remain a "hot topic" in the near future, it is crucial to be aware of influencing factors in order to ensure correct interpretation of imaging results. This article reviews the factors currently known to influence flow density (FD) as measured by OCTA in healthy eyes.

Retinal endothelial function in cardiovascular risk patients: A randomized controlled exercise trial.

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.

Ion channels and myogenic activity in retinal arterioles.

Retinal pressure autoregulation is an important mechanism that protects the retina by stabilizing retinal blood flow during changes in arterial or intraocular pressure. Similar to other vascular beds, retinal pressure autoregulation is thought to be mediated largely through the myogenic response of small arteries and arterioles which constrict when transmural pressure increases or dilate when it decreases. Over recent years, we and others have investigated the signaling pathways underlying the myogenic response in retinal arterioles, with particular emphasis on the involvement of different ion channels expressed in the smooth muscle layer of these vessels. Here, we review and extend previous work on the expression and spatial distribution of the plasma membrane and sarcoplasmic reticulum ion channels present in retinal vascular smooth muscle cells (VSMCs) and discuss their contribution to pressure-induced myogenic tone in retinal arterioles. This includes new data demonstrating that several key players and modulators of the myogenic response show distinctively heterogeneous expression along the length of the retinal arteriolar network, suggesting differences in myogenic signaling between larger and smaller pre-capillary arterioles. Our immunohistochemical investigations have also highlighted the presence of actin-containing microstructures called myobridges that connect the retinal VSMCs to one another. Although further work is still needed, studies to date investigating myogenic mechanisms in the retina have contributed to a better understanding of how blood flow is regulated in this tissue. They also provide a basis to direct future research into retinal diseases where blood flow changes contribute to the pathology.

Development of a novel noninvasive system for measurement and imaging of the arterial phase oxygen density ratio in the retinal microcirculation.

PURPOSE: This study was conducted in order to develop a novel noninvasive system for measurement and imaging of the arterial oxygen density ratio (ODR) in the retinal microcirculation. METHODS: We developed a system composed of two digital cameras with two different filters, which were attached to a fundus camera capable of simultaneously obtaining two images. Actual measurements were performed on healthy volunteer eyes (n = 61). A new algorithm for ODR measurement and pixel-level imaging of erythrocytes was constructed from these data. The algorithm was based on the morphological closing operation and the line convergence index filter. For system calibration, we compared and verified the ODR values in arterioles and venules that were specified in advance for 56 eyes with reproducibility. In 10 additional volunteers, ODR measurements and imaging of the arterial phase in the retinal microcirculation corresponding to changes in oxygen saturation of the peripheral arteries at normal breathing and breath holding were performed. RESULTS: Estimation of incident light to erythrocytes and pixel-level ODR calculation were achieved using the algorithm. The mean ODR values of arterioles and venules were 0.77 ± 0.060 and 1.02 ± 0.067, respectively. It was possible to separate these regions, calibrate at the pixel level, and estimate the arterial phase. In each of the 10 volunteers, changes in the arterial phase ODR corresponding to changes in oxygen saturation of the peripheral arteries were observed before and after breath holding on ODR images. The mean ODR in 10 volunteers was increased by breath holding (p < 0.05). CONCLUSIONS: We developed a basic system for arterial phase ODR measurement and imaging of the retinal microcirculation. With further validation and development, this may provide a useful tool for evaluating retinal oxygen metabolism in the retinal microcirculation.

Impaired retinal microcirculation in multiple sclerosis.

BACKGROUND: The transparent ocular structure enables quantitative analysis of microvasculature of retina, a neuronal tissue affected by multiple sclerosis (MS). OBJECTIVE: The aim of this study was to determine whether the retinal blood flow velocity and flow volume at the macula are impaired in patients with relapsing remitting multiple sclerosis (RRMS). METHODS: A total of 17 RRMS patients and 17 age- and gender-matched healthy subjects were assessed. A retinal function imager was used to measure the blood flow velocity of retinal arterioles and venules and to calculate the total perifoveal blood flow volume. RESULTS: The blood flow velocities of the retinal arterioles (3.34 ± 0.89 mm/s) and venules (2.61 ± 0.6 mm/s) were significantly lower in MS patients than normal subjects (arteriole: 4.10 ± 0.87 mm/s; venule: 3.22 ± 0.65 mm/s, both p = 0.01). In addition, the total perifoveal blood flow volume in arterioles (3.74 ± 1.64 nL/s) and venules (3.81 ± 1.60 nL/s) were significantly lower in MS patients than in normal subjects (arteriole: 4.87 ± 1.41 nL/s, p = 0.02; venule: 4.71 ± 1.64 nL/s, p = 0.04). CONCLUSION: The impaired retinal microcirculation in RRMS patients indicates microvascular dysfunction in MS.

Influence of physical fitness and activity behavior on retinal vessel diameters in primary schoolchildren.

Retinal vessel alterations have been shown to be associated with cardiovascular risk factors and physical inactivity as early as childhood. In this context, the analysis of physical activity in children has solely been based on questionnaire assessments. The study aimed to examine the association of physical fitness performance and self-reported physical activity with retinal vessel diameters in young children. Three hundred ninety-one primary schoolchildren [7.3 years (SD 0.4)] were examined in this cross-sectional study. The primary outcome was endurance performance measured with the 20-m shuttle run. The additional tests consisted of a 20-m sprint, jumping sidewards and balancing backwards. Retinal microcirculation was assessed using a static retinal vessel analyzer. Parents completed questionnaires about physical and sedentary activities. Endurance performance was associated with narrower retinal venular diameters [-0.9 (95%CI: -1.8; -0.1) measuring units (mu)/ unit shuttle run, P = 0.04] and a higher arteriolar to venular ratio [0.003 (-0.001; 0.006)/unit shuttle run, P = 0.06]. The sprint performance was associated with narrower retinal arterioles [4.7 (0.8; 8.6) mu/unit sprint, P = 0.02]. Indoor playing activity correlated with narrower retinal venules [-0.04 (-0.07; -0.01) mu/per unit, P = 0.02]. Our data suggest that objectively measured endurance performance relates with better retinal vessel health in early childhood.

Retinal Microcirculation Measurements in Response to Endurance Exercises Analysed by Adaptive Optics Retinal Camera.

This study aimed to precisely investigate the effects of intensive physical exercise on retinal microvascular regulation in healthy volunteers through adaptive optics retinal camera (AO) measurement. We included healthy volunteers (11 men and 14 women) aged 20.6 ± 0.9. The heart rate (HR) and systolic and diastolic blood pressures (SBP, DBP) were recorded before and after a submaximal physical exertion of continuously riding a training ergometer. The superior temporal retinal artery measurements were captured using the AO-rtx1TM (Imagine Eyes, Orsay, France) without pupil dilation. We compared measures of vessel diameter (VD), lumen diameter (LD), two walls (Wall 1, 2), wall-to-lumen ratio (WLR), and wall cross-sectional analysis (WCSA) before and immediately after the cessation of exercise. Cardiovascular parameter results: After exercise, SBP, DBP, and HR changed significantly from 130.2 ± 13.2 to 159.7 ± 15.6 mm Hg, 81.2 ± 6.3 to 77.1 ± 8.2 mm Hg, and 80.8 ± 16.1 to 175.0 ± 6.2 bpm, respectively (p < 0.002). Retinal microcirculation analysis showed no significant decrease in LD, Wall 1 after exercise: from 96.0 ± 6.8 to 94.9 ± 6.7 (p = 0.258), from 11.0 ± 1.5 to 10.4 ± 1.5 (p = 0.107), respectively, and significant reduction in VD from 118.5 ± 8.3 to 115.9 ± 8.3 (p = 0.047), Wall 2 from 11.5 ± 1.0 to 10.7 ± 1.3 (p = 0.017), WLR from 0.234 ± 0.02 to 0.222 ± 0.010 (p = 0.046), WCSA from 3802.8 ± 577.6 to 3512.3 ± 535.3 (p = 0.016). The AO is a promising technique for investigating the effects of exercise on microcirculation, allowing for the tracking of changes throughout the observation. Intensive dynamic physical exertion increases blood pressure and heart rate and causes the vasoconstriction of small retinal arterioles due to the autoregulation mechanism.

OCTA-based research on changes of retinal microcirculation in digestive tract malignancy.

PURPOSE: This cross-sectional study measured retinal vessel density (VD) in patients with digestive tract malignancy by optical coherence tomography angiography (OCTA), and compared them with healthy controls to explore the retinal microcirculation changes in patients with digestive tract malignancy. METHODS: 106 eligible participants were divided into three groups: gastric cancer (GC) group (36 individuals), colorectal cancer (CRC) group (34 individuals), and healthy control group (36 individuals). Angio 6 × 6 512 × 512 R4 and ONH Angio 6 × 6 512 × 512 R4 modes were performed to collect retinal vessel density data centered on fovea and papillary, respectively. The retina was automatically segmented into different layers (superficial vascular plexus (SVP), the inner retinal layer, radial peripapillary capillary plexus (RPCP), deep vascular plexus (DVP)) and areas to analyze. RESULTS: At the optic nerve head (ONH) region, the VD of the inner retinal layer increased in both GC and CRC groups in all quadrants and areas. In the papillary area, VD in the inner retinal layer, SVP, and RPCP increased in the GC and CRC groups. In the parapapillary area, VD in the inner retinal layer increased in the GC and the CRC groups. Significant increase in the global VD were found in the GC group of the RPCP and SVP. Regarding the macular region, no statistical differences were observed in each layer. CONCLUSIONS: The study suggested that retinal vessel density changed in patients with digestive tract malignancy, especially in the inner retinal layer of the ONH region, revealing the potential relevance of the relation between gastrointestinal cancer and retinal microcirculation.

High-intensity interval training in patients with glaucoma (HIT-GLAUCOMA): protocol for a multicenter randomized controlled exercise trial.

Background: Glaucoma stands as a prominent global cause of irreversible blindness and the primary treatment approach involves reducing intraocular pressure (IOP). However, around one-third of patients exhibit disease progression despite effective IOP reduction. Microvascular endothelial function, chronic inflammation, and oxidative stress are known to affect retinal neuronal networks and have been associated with disease severity and progression. Exercise training has the potential to counteract these mechanisms as add-on treatment to usual care. Aims: The HIT-GLAUCOMA study will investigate the effects of a 6-month high-intensity interval training (HIIT) on intermediate endpoints such as local retinal microvascular and systemic large artery function, inflammation, and oxidative stress as well as clinical endpoints such as visual field indices, optic nerve rim assessment, retinal nerve fiber layer thickness, IOP, number of eye drops, vision-related quality of life and ocular surface disease symptomatology. Methods: The study is a multi-center randomized controlled clinical trial in patients with both normal tension and high-tension primary open angle glaucoma. Across two study centers, 128 patients will be enrolled and randomized on a 1:1 basis into an exercise intervention group and a usual care control group. The primary microvascular endpoints are retinal arteriolar and venular flicker light-induced dilation at 6 months. The primary endpoint in the systemic circulation is brachial artery flow-mediated dilation at 6 months. Anticipated results: We hypothesize that exercise therapy will improve retinal microvascular function and thus ocular blood flow in patients with glaucoma. As clinical outcomes, we will investigate the effect of exercise on visual field indices, optic nerve rim assessment, retinal nerve fiber layer thickness, IOP, number of eye drops, vision-related quality of life and ocular surface disease symptomatology. Discussion: HIT-GLAUCOMA is a blueprint trial design to study the effect of exercise training on neurodegenerative and cardiovascular diseases. Importantly, patients are also expected to benefit from improvements in general health and cardiovascular co-morbidities. If proven effective, exercise may offer a new add-on treatment strategy to slow glaucoma progression. Clinical Trial Registration Number: The trial is registered at Clinicaltrials.gov under the identifier NCT06058598 and is currently in the recruitment stage.

Investigation of OCTA Biomarkers in Fabry Disease: A Long Term Follow-Up of Macular Vessel Area Density and Foveal Avascular Zone Metrics.

INTRODUCTION: Retinal microvasculature is known to be altered in patients with Fabry disease (FD). We aimed to investigate the long-term changes in macular microvasculature and explore a reliable retinal biomarker for treatment monitoring in FD. METHODS: Prospective study of 26 eyes with FD followed up to 48 months (mean 24, range 8-48). OCT angiography (OCTA) images (2.9 × 2.9 mm) were obtained using Heidelberg Spectralis II at baseline and follow-up. Macular vessel area density (VAD, %) was measured in three layers: superficial vascular plexus (SVP), intermediate capillary plexus (ICP) and deep capillary plexus (DCP) in three peri-macular circular sectors (c1, c2, c3). Additionally, foveal avascular zone (FAZ) area (mm2) and horizontal and vertical diameters (µm) were assessed. RESULTS: VAD decreased over time in SVP, ICP (in sectors c2 and c3) and DCP (all sectors) (p < 0.04). VAD reduction was predominantly seen in treated FD patients. FAZ and horizontal diameters increased at follow-up in FD patients compared to baseline (p ≤ 0.025). Correlation analysis showed a moderate to strong negative correlation between VAD of SVP and DCP in the innermost circle and FAZ in treated patients (r = - 0.6; p < 0.0001). CONCLUSIONS: This is the first long-term follow-up OCTA study in FD to our knowledge. A decrease in VAD, pronounced in the peripheral circle and deeper layers, as well as an enlargement of the FAZ could be observed over time. These changes reflect the vascular remodelling during the course of the disease. Interestingly, the reduction of VAD was more pronounced in treated patients. This could be a result of enzyme replacement therapy and could be potentially used as a reliable biomarker for monitoring the treatment of the disease. A baseline examination of VAD and FAZ before treatment initiation is meaningful. Larger studies are needed to establish the use of VAD and FAZ as biomarkers for treatment monitoring.