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.

[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.

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.

Characteristics of retinal microcirculation after phacoemulsification and factors affecting visual acuity / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To investigate the changes of retinal microcirculation after phacoemulsification and the influencing factors of visual acuity.METHODS: Retrospective analysis. A total of 264 cataract patients(264 eyes)who underwent phacoemulsification in our hospital from January 2022 to December 2022 were selected as the study objects. Patients were divided into &#x0026;#x003C; 0.3 group(66 eyes)and ≥0.3 group(198 eyes)according to the recovery of best corrected visual acuity(BCVA)at 3 mo after surgery. The changes of retinal microcirculation indexes were compared before and after treatment. Logistic regression and LASSO regression models were used to screen the influencing factors of postoperative BCVA. A nomogram prediction model of postoperative BCVA was constructed and verified. A restricted cubic spline Logistic regression model was established to analyze the dose-response relationship between end-diastolic velocity(EDV), peak systolic velocity(PSV)and the risk of BCVA recovery.RESULTS: At 3 mo postoperatively, EDV and PSV were significantly improved compared with those before treatment, and resistance index(RI)levels were significantly lower than those before treatment(all P&#x0026;#x003C;0.05). Preoperative EDV, PSV, aqueous humor cell grade, fundus lesion grade, advanced age and Emery grade were influencing factors for poor BCVA recovery after phacoemulsification in cataract patients(P&#x0026;#x003C;0.05). The AUC before and after validation of the nomogram model by Bootstrap method were 0.869(95%CI: 0.815-0.903)and 0.866(95%CI: 0.802-0.895), respectively. The sensitivity was 88.36% and 88.27%, and the specificity was 91.82% and 91.78%, respectively. Restricted cubic spline model analysis showed no nonlinear dose-response relationship between EDV and PSV levels and the risk of poor BCVA recovery in either male or female(P&#x0026;#x003E;0.05).CONCLUSION: After phacoemulsification, retinal microcirculation in cataract patients improved significantly. EDV, PSV, aqueous humor cell grade, fundus lesion grade, advanced age and Emery grade are all factors influencing poor BCVA recovery after cataract surgery.

Maximal incremental exercise improves macular photostress recovery time and lowers intraocular pressure in healthy athletes.

OBJECTIVES: Better visual performance in athletes compared to non-athletes could suggest improved macular function through physical exertion. The study aimed to investigate the effect of maximal incremental treadmill (MIT) exercise on macular function. DESIGN: An interventional study comparing the effect of maximal incremental treadmill (MIT) exercise until volitional exhaustion between athletes (n = 26) and non-athletes (n = 26). METHODS: Participants underwent an ophthalmological assessment involving repeated measurements of the photostress recovery time (PSRT) at baseline and post-exercise. PSRT was recorded after a 10-second exposure of the macular to an intense light source from an ophthalmoscope positioned 2 cm in front of the eye. Secondary outcome measures also recorded included the best-corrected visual acuity (BCVA) and the intraocular pressure (IOP). RESULTS: Compared to the baseline, MIT exercise markedly improved the PSRT of athletes from 42.7 ±â€¯1.6 s to 39.6 ±â€¯1.4 s (P < 0.001), while having no significant changes in the PSRT of non-athletes. After adjusting for exercise duration, the exercise intervention showed significant effects on the PSRT improvement in the athletes compared to non-athletes after exercise [F(1,49) = 16.941, P < 0.001], with estimated marginal means of 3.00 s and 0.47 s, respectively. Also, the exercise intervention resulted in significant improvements in IOP (P < 0.001) and BCVA (P < 0.01) of both groups. CONCLUSIONS: MIT exercise improves macular function, BCVA, and reduced IOP in healthy athletes. Maximal incremental exercise may be recommended for competitive sports athletes seeking optimal visual performance, as long as it does not adversely impact other relevant non-visual factors.

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.

Retinal Photoreceptors and Microvascular Changes in the Assessment of Diabetic Retinopathy Progression: A Two-Year Follow-Up Study.

BACKGROUND: With the increasing global incidence of diabetes mellitus (DM), diabetic retinopathy (DR) has become one of the leading causes of blindness in developed countries. DR leads to changes in retinal neurons and microcirculation. Rtx1TM (Imagine Eyes, Orsay, France) is a retinal camera that allows histological visualisations of cones and retinal microcirculation throughout the DM duration. OBJECTIVE: This study aimed to analyse the cones and retinal microvascular changes in 50 diabetic individuals and 18 healthy volunteers. The patients participated in the initial visit and two follow-up appointments, one and two years after the study, beginning with Rtx1TM image acquisition, visual acuity assessment, macular OCT scans and blood measurements. RESULTS: The study revealed significant differences in the cone density, mosaic arrangement and vascular morphology between healthy and diabetic patients. The final measurements showed decreased photoreceptor and microvascular parameters in the DR group compared with the control group. Furthermore, in the 2-year follow-up, both groups' Rtx1TM-acquired morphological changes were statistically significant. CONCLUSIONS: Rtx1TM technology was successfully used as a non-invasive method of photoreceptors and retinal vasculature assessment over time in patients with diabetic retinopathy. The study revealed a trend toward more vascular morphological changes occurring over time in diabetic patients.

VEGFR-2 adhesive nanoprobes reveal early diabetic retinopathy in vivo.

Diabetic retinopathy (DR) is a debilitating organ manifestation of diabetes. Absent of early diagnosis and intervention, vision tends to drastically and irreversibly decline. Previously, we showed higher vascular endothelial growth factor receptor 2 (VEGFR-2) expression in diabetic microvessels, and the suitability of this molecule as a biomarker for early DR diagnosis. However, a hurdle to translation remained generation of biodegradable nanoprobes that are sufficiently bright for in vivo detection. Here, an adhesive fluorescent nanoprobe with high brightness was developed using biodegradable materials. To achieve that, a fluorophore with bulky hydrophobic groups was encapsulated in the nanoparticles to minimize fluorophore π-π stacking, which diminishes brightness at higher loading contents. The nanoprobe selectively targeted the VEGFR-2 under dynamic flow conditions. Upon systemic injection, the nanoprobes adhered in the retinal microvessels of diabetic mice and were visualized as bright spots in live retinal microscopy. Histology validated the in vivo results and showed binding of the nanoprobes to the microvascular endothelium and firmly adhering leukocytes. Leukocytes were found laden with nanoprobes, indicating the potential for payload transport across the blood-retinal barrier. Our results establish the translational potential of these newly generated nanoprobes in early diagnosis of DR.

Optical coherence tomography angiography characteristics of retinochoroidal and optic nerve head microcirculation in cryptogenic organizing pneumonia.

BACKGROUND: To assess retinochoroidal and optic nerve head microcirculation alterations in cryptogenic organizing pneumonia. METHODS: Thirty cryptogenic organizing pneumonia patients in the resolution phase (group 1, 30 right eyes) and 33 healthy subjects (group 2, 33 right eyes) were compared. Patients had 40 mg/day corticosteroids for 8-10 days, and a pulmonary function test, which revealed only minimally restrictive ventilation features. After gathering demographic data, a comprehensive ophthalmological exam and optical coherence tomography angiography were performed three months following maximum disease resolution with corticosteroid therapy RESULTS: Groups 1 and 2 had mean ages of 54.37±14.87 and 49.61±12.36 years, respectively (P = 0.171). Despite the lack of statistical significance, superficial and deep capillary plexus vessel densities in all macular regions were lower in group 1, as were foveal avascular zone parameters (P>0.05). However, the outer retinal and choriocapillaris flows increased significantly in group 1, especially in select areas (P<0.001, for both). There were no significant differences in whole image (P = 0.346), inside disk (P = 0.438), or peripapillary (P = 0.185) optic nerve head vessel densities between the two groups; however, nasal (P<0.001) and inferior quadrant (P = 0.006) vessel densities differed significantly. Global retinal nerve fiber layer thickness did not differ significantly between groups 1 and 2 (112.83±14.71 versus 111.45±12.74 µm, respectively; P = 0.692). Group 1, however, had significantly higher superior, nasal, and inferior quadrant, and significantly lower temporal quadrant retinal nerve fiber layer thickness (P<0.001, for all). CONCLUSIONS: Concerning the impact of probable cryptogenic organizing pneumonia-induced hypoxia on ocular tissues, optical coherence tomography angiography assessments of retinochoroidal and optic nerve head microcirculation could be employed as a biomarker for cerebral microcirculation.

Studies of the retinal microcirculation using human donor eyes and high-resolution clinical imaging: Insights gained to guide future research in diabetic retinopathy.

The microcirculation plays a key role in delivering oxygen to and removing metabolic wastes from energy-intensive retinal neurons. Microvascular changes are a hallmark feature of diabetic retinopathy (DR), a major cause of irreversible vision loss globally. Early investigators have performed landmark studies characterising the pathologic manifestations of DR. Previous works have collectively informed us of the clinical stages of DR and the retinal manifestations associated with devastating vision loss. Since these reports, major advancements in histologic techniques coupled with three-dimensional image processing has facilitated a deeper understanding of the structural characteristics in the healthy and diseased retinal circulation. Furthermore, breakthroughs in high-resolution retinal imaging have facilitated clinical translation of histologic knowledge to detect and monitor progression of microcirculatory disturbances with greater precision. Isolated perfusion techniques have been applied to human donor eyes to further our understanding of the cytoarchitectural characteristics of the normal human retinal circulation as well as provide novel insights into the pathophysiology of DR. Histology has been used to validate emerging in vivo retinal imaging techniques such as optical coherence tomography angiography. This report provides an overview of our research on the human retinal microcirculation in the context of the current ophthalmic literature. We commence by proposing a standardised histologic lexicon for characterising the human retinal microcirculation and subsequently discuss the pathophysiologic mechanisms underlying key manifestations of DR, with a focus on microaneurysms and retinal ischaemia. The advantages and limitations of current retinal imaging modalities as determined using histologic validation are also presented. We conclude with an overview of the implications of our research and provide a perspective on future directions in DR research.

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.

Effects of Methylenetetrahydrofolate Reductase (MTHFR) Polymorphisms on Retinal Tissue Perfusion in Mild Diabetic Retinopathy Patients Receiving the Medical Food, Ocufolin®.

Purpose: We evaluate the effects of methylenetetrahydrofolate reductase (MTHFR) polymorphisms on retinal tissue perfusion in patients with mild diabetic retinopathy (DR + PM) taking the medical food, Ocufolin®, for 6 months. Methods: Prospective, case-controlled study. Eight early diabetic retinopathy patients with common reduced function MTHFR polymorphisms (DR+PM) and 15 normal controls (NC) were recruited. MTHFR polymorphisms were subtyped as normal, C677T, or A1298C. Best corrected visual acuity (BCVA) was evaluated. Retinal blood flow velocity (BFV) was measured using Retinal Function Imager. Retinal tissue perfusion (RTP, blood flow rate per inner retinal volume) was calculated within a 2.5 mm diameter circle centered on the fovea. The medical food is intended to address ocular ischemia with high doses of vitamin B-complexes and antioxidants, including L-methylfolate, methylcobalamin, zinc, copper, lutein, vitamins C, D, E, and n-acetylcysteine. The subjects were provided with a medical food for a period of 6 months. Results: BCVA and vascular indices of DR + PM patients at baseline were initially below those of NC and improved after medical food. Compared to baseline, DR + PM patients after the medical food had significantly improved BCVA during the follow-up period (P < 0.05). In comparison, overall RTP and arteriolar BFV were significantly increased at 6 months (P < 0.05). The changes varied with MTHFR subtypes. In patients with the C677T and the C677T/A1298C compound mutations, RTP was increased at 6 months as compared to that at baseline and 4 months (P < 0.05). In patients with only the A1298C mutation, all microcirculation metrics were increased from baseline at 4 and 6 months, but with less improvement at 6 months than at 4 months (P < 0.05). Conclusion: Medical food was effective in improving both visual acuity and retinal tissue perfusion in DR + PM patients. The degree of improvement of retinal microcirculation varied among MTHFR 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.

Rational and design of the REMOTE trial: An exploratory, pilot study to analyze REtinal MicrOcirculaTion in wEightlessness.

BACKGROUND: "Spaceflight associated neuro-ocular syndrome" (SANS) represents a challenging health condition in modern space medicine. Forty-eight percent of astronauts are diagnosed with SANS after long-term space missions. The pathophysiological mechanism seems to be multifactorial, and yet remains unknown. In this proof-of-concept study we plan to investigate retinal microcirculatory changes in weightlessness and aim to identify their role in the development of SANS. METHODS AND DESIGN: Healthy individuals will take part in a parabolic flight campaign, which recreates fractioned total weightlessness periods. The airplane is specifically equipped, and designed for the execution of parabolic flight maneuvers and scientific research in microgravity. Retinal microcirculation will be assessed with a modified fundus camera, which allows dynamic vessel analysis. We will additionally measure intra-ocular pressure and hemodynamic changes during each phase of the flight. Blood samples will be analyzed at baseline, one hour and 24 hours after exposure to weightlessness. CONCLUSIONS: This pilot study aims to investigate the feasibility of retinal microcirculation assessment during varying gravity. Results of this study may generate insights whether venous stasis in the eye, surrogated by the dilatation of retinal vessels and increase in intraocular pressure as signs of venous insufficiency, may potentially contribute to the development of SANS.

SGLSA: Sphygmus gated laser speckle angiography for microcirculation hemodynamics imaging.

Hemodynamics imaging of the retinal microcirculation has been demonstrated to be potential access to evaluating ophthalmic diseases, cardio-cerebrovascular diseases, and metabolic diseases. However, existing structural and functional imaging techniques are insufficient in spatial or temporal resolution. The sphygmus gated laser speckle angiography (SGLSA) is proposed for structural and functional imaging with high spatiotemporal resolution. Compared with classic LSCI algorithms, SGLSA presents a much clearer perfusion image and higher signal-to-noise ratio pulsatility. The SGLSA algorithm also shows better performance on patients than traditional LSCI methods. The high spatiotemporal resolution provided by the SGLSA algorithm greatly enhances the ability of retinal microcirculation analysis, which makes up for the deficiency of the LSCI technology, and attaches great significance to retinal hemodynamic imaging, biomarker research, and clinical diagnosis.

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.

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.

Retinal microvascular changes in patients with familial mediterranean fever: a study based on optical coherence tomography angiography / Alterações microvasculares da retina em pacientes com febre mediterrânea familiar: estudo baseado em angiotomografia de coerência óptica

ABSTRACT Purpose: In this study, we aimed to show whether a difference exists between retinal and choroidal microcirculation findings between patients with familial Mediterranean fever and healthy controls. Methods: Thirty-two patients with familial Mediterranean fever and 30 healthy controls were included in the study. All the patients underwent a complete ophthalmologic examination, including best-corrected visual acuity and intraocular pressure measurement. The AngioVue optical coherence tomography angiography device (Optovue, Fremont, CA) with split-spectrum amplitude-decorrelation angiography was used to evaluate and examine the retinal microvascular structure. Three-dimensional en face Optical coherence tomography angiography images were obtained by examining the macula using the 3 x 3 mm scanning protocol in the Angio Retina mode and the optic nerve using the 3 x 3 mm scanning protocol in the Angio Disk mode. All the patients' right eyes were examined. Results: A total of 62 subjects were included in the study, of whom 32 (53.3%) were female and 30 (46.7%) were male. No statistically significant difference was found between the two groups in terms of optic nerve head or radial peripapillary capillary vessel density. On examination, the superficial capillary plexuses were statistically similar between the two groups, but the deep capillary plexus vessel density in the parafovea, superior hemi, temporal, and superior areas were significantly lower in the patients with familial Mediterranean fever. Conclusions: We found that the capillary plexus vessel density was significantly lower in the parafovea, superior hemi, temporal, and superior regions in the patients with familial Mediterranean fever than in the control group. Therefore, OCTA, a noninvasive study, may be useful for understanding the systemic effects of familial Mediterranean fever.

RESUMO Objetivos: Este estudo teve como objetivo mostrar se há diferença entre os achados da microcirculação retiniana e coroidal entre pacientes com febre mediterrânica familiar e um grupo controle saudável. Métodos: Trinta e dois pacientes com febre mediterrânica familiar e 30 controles saudáveis foram incluídos neste estudo. Todos os pacientes foram submetidos a um exame oftalmológico completo, incluindo a acuidade visual melhor corrigida e medida da pressão intraocular. O aparelho AngioVue Optical coherence tomography angiography (Optovue, Fremont, CA) com angiografia de correlação de amplitude de espectro dividido foi utilizado para avaliar e examinar a estrutura microvascular da retina. As angiotomografias de coerência ópticas en face tridimensionais foram obtidas examinando o protocolo de varredura macular 3 x 3 mm (modo angio retina) e o nervo óptico com o protocolo de varredura 3 x 3 mm (modo angio-disco). Todos os olhos direitos dos pacientes foram examinados. Resultados: Foram incluídos neste estudo, 62 sujeitos, dos quais 32 (53,3%) eram do sexo feminino e 30 (46,7%) do sexo masculino. Não houve diferença estatisticamente significativa entre os dois grupos quanto à densidade dos vasos da cabeça do nervo óptico ou da densidade dos vasos capilares peripapilares radiais. Durante o exame, os plexos capilares superficiais foram estatisticamente semelhantes entre esses dois grupos, mas a densidade profunda dos vasos do plexo capilar nas areas parafovea, hemi superior, temporal e superior foram significativamente menores nos pacientes com febre mediterrânica familiar. Conclusões: Verificamos que a densidade dos vasos do plexo capilar foi significativamente menor nas regiões parafovea, hemi superior, temporal e superior em pacientes com febre mediterrânica familiar em comparação com o grupo controle. Portanto, pode ser útil usar a angiotomografia de coerência óptica, por tratar-se de um estudo não invasivo, para melhor compreensão dos efeitos sistêmicos da febre mediterrânica familiar.

Analysis of Microcirculation Changes in the Macular Area and Para-Optic Disk Region After Implantable Collamer Lens Implantation in Patients With High Myopia.

Myopia has become an important public health problem to be solved urgently. Posterior chamber phakic implantable Collamer lens (ICL) implantation is one of the latest and safest products for myopia correction worldwide. This prospective cross-sectional case series aimed to observe changes in the macular retinal thickness, retinal nerve fiber layer (RNFL) thickness of para-optic disk region, and blood flow density after posterior ICL implantation in patients with high myopia using optical coherence tomography angiography (OCTA). A total of 67 eyes of 67 patients with high myopia, who underwent ICL implantation at The Affiliated Eye Hospital of Nanjing Medical University from January 2020 and December 2020, were included. The spherical equivalent (SE) of the operative eyes was >-6.00 D. The changes in vision, intraocular pressure (IOP), SE, and vault were observed pre-operatively, and follow-up were performed 1 week, 1 month, and 3 months. OCTA was used to observe the changes in the CRT, retinal thickness of paracentral fovea, FAZ, superficial and deep retinal blood flow density in the macular area, RNFL thickness of para-optic disk region, and blood flow density before and after ICL implantation. The uncorrected distance visual acuity (UDVA) and best corrected distance visual acuity (CDVA) of the patients post-operation were significantly improved (P < 0.001). The IOP increased in comparison with other time points at 1 week post-operation (P < 0.05). There were no significant changes in CRT post-operation. The retinal thickness in the upper, lower, nasal, and temporal quadrants of the paracentral fovea increased significantly at 1 month and 3 months post-operation (P < 0.05). The FAZ area at all postoperative time points were decreased (P < 0.001). At 3 months post-operation, the blood flow density of the superficial and deep retinal layers in the upper, lower, and nasal macular area were significantly reduced (P < 0.05). At 1 month post-operation, the RNFL thickness in the temporal para-optic disk region and blood flow density were significantly reduced (P = 0.001 and P < 0.05, respectively). ICL implantation for highly myopic eyes led to an increase of the retinal thickness in the upper, lower, nasal, and temporal regions of the paracentral fovea; reduction of RNFL thickness in the temporal area of para-optic disk; decrease in FAZ area; and decrease in the blood flow density of some deep and superficial retinal layers as well as that of the temporal para-optic disk region.

Peripapillary Vascular Reactivity in Primary Open-Angle Glaucoma With High Myopia by Using Optical Coherence Tomography Angiography.

Purpose: To evaluate peripapillary vascular reactivity in primary open-angle glaucoma (POAG) with and without high myopia (HM) by using optical coherence tomography angiography (OCTA). Methods: This prospective study enrolled 48 eyes with POAG, including 16 and 32 eyes with and without HM, respectively. The retinal peripapillary vessel density (VD) was repeatedly assessed using OCTA at baseline and after a hyperoxia test (breathing 80% oxygen). The VD changes between different oxygenation conditions were calculated to reflect the vasoreactivity. Linear regression was performed to determine the relationship between myopia and retinal vascular reactivity in patients with POAG. Systemic hemodynamic characteristics were also evaluated under both conditions. Results: The VD was significantly reduced after hyperoxia in the whole image (baseline and hyperoxia: 41.4 ± 4.5 and 38.8 ± 4.4, respectively, P < 0.001) and in the peripapillary regions (44.3 ± 5.7 and 41.1 ± 5.4, respectively, P < 0.001) in POAG eyes without HM. However, in eyes with HM, the whole-image VD in hyperoxia was not significantly different from the baseline (baseline and hyperoxia: 40.5 ± 6.2 and 40.2 ± 6.2, respectively, P = 0.481). The VD changes in eyes with HM were significantly smaller than those in eyes without HM in both the whole image (0.3 ± 1.8 and 2.6 ± 2.0, respectively, P < 0.001) and peripapillary regions (1.1 ± 2.0 and 3.2 ± 2.3, respectively, P = 0.003). Linear regression results showed a significant correlation between retinal vascular reactivity and spherical equivalent (SE) (ß = 0.28, P < 0.001, R 2 = 0.31) and axial length (AL) (ß = -0.72, P < 0.001, R 2 = 0.33). Conclusion: Retinal vasoreactivity of peripapillary capillaries in POAG eyes with HM was significantly impaired in comparison with that in POAG eyes without HM. A lower peripapillary vascular response was significantly associated with worse SE and elongated AL.