Retinal blood flow association with age and weight in infants at risk for retinopathy of prematurity.

This prospective study evaluated the relationship between laser speckle contrast imaging (LSCI) ocular blood flow velocity (BFV) and five birth parameters: gestational age (GA), postmenstrual age (PMA) and chronological age (CA) at the time of measurement, birth weight (BW), and current weight (CW) in preterm neonates at risk for retinopathy of prematurity (ROP). 38 Neonates with BW < 2 kg, GA < 32 weeks, and PMA between 27 and 47 weeks underwent 91 LSCI sessions. Correlation tests and regression analysis were performed to quantify relationships between birth parameters and ocular BFV. Mean ocular BFV index in this cohort was 8.8 +/- 4.0 IU. BFV positively correlated with PMA (r = 0.3, p = 0.01), CA (r = 0.3, p = 0.005), and CW (r = 0.3, p = 0.02). BFV did not correlate with GA nor BW (r = - 0.2 and r = - 0.05, p > 0.05). Regression analysis with mixed models demonstrated that BFV increased by 1.2 for every kilogram of CW, by 0.34 for every week of CA, and by 0.36 for every week of PMA (p = 0.03, 0.004, 0.007, respectively). Our findings indicate that increased age and weight are associated with increased ocular BFV measured using LSCI in premature infants. Future studies investigating the associations between ocular BFV and ROP clinical severity must control for age and/or weight of the infant.

Intereye Microvascular Differences in Patients With Same-Stage Diabetic Retinopathy Revealed by OCTA.

Purpose: To evaluate microvascular intereye differences in diabetic patients with same-stage diabetic retinopathy (DR) in both eyes as assessed using optical coherence tomography angiography (OCTA). Methods: In this cross-sectional study, fovea-centered swept-source 6 × 6 mm OCTA scans were acquired using a 200 kHz OCTA device. Vessel density (VD) and fractal dimension were calculated on binarized, vessel-segmented images in the superficial capillary plexus (SCP) and deep capillary plexus (DCP). Foveal avascular zone (FAZ) area (FAZA) and perimeter (FAZP) was measured and FAZ circularity (FAZC) calculated. Absolute difference (δabs) and asymmetry index between eyes was assessed and compared across DR stages. Differences of VD, FD, and FAZ parameters between left and right eye were evaluated using linear mixed models. Results: A total of 336 eyes of 168 diabetic patients without DR and with DR stages ranging from mild nonproliferative to proliferative DR were included for analysis. The intereye comparison revealed significantly lower VD in the SCP (estimate [95% CI] = -0.009 [-0.01; -0.006], P < 0.01), as well as a significantly lower FD in the SCP (-0.007 [-0.009; -0.005], P < 0.01) of the left compared to the right eye. FAZC of the left compared to the right eye was lower in eyes without DR, moderate DR, and PDR (P < 0.05). FAZ δabs and asymmetry index were higher in more advanced disease stages (P < 0.05). Conclusions: OCTA metrics provide important information on the retinal microvasculature in systemic diseases such as DR. Our results reveal a significant intereye difference with lower VD and FD in the SCP as well as higher FAZ impairment of the left compared to the right eye.

Applicability of Oculomics for Individual Risk Prediction: Repeatability and Robustness of Retinal Fractal Dimension Using DART and AutoMorph.

Purpose: To investigate whether fractal dimension (FD)-based oculomics could be used for individual risk prediction by evaluating repeatability and robustness. Methods: We used two datasets: "Caledonia," healthy adults imaged multiple times in quick succession for research (26 subjects, 39 eyes, 377 color fundus images), and GRAPE, glaucoma patients with baseline and follow-up visits (106 subjects, 196 eyes, 392 images). Mean follow-up time was 18.3 months in GRAPE; thus it provides a pessimistic lower bound because vasculature could change. FD was computed with DART and AutoMorph. Image quality was assessed with QuickQual, but no images were initially excluded. Pearson, Spearman, and intraclass correlation (ICC) were used for population-level repeatability. For individual-level repeatability, we introduce measurement noise parameter λ, which is within-eye standard deviation (SD) of FD measurements in units of between-eyes SD. Results: In Caledonia, ICC was 0.8153 for DART and 0.5779 for AutoMorph, Pearson/Spearman correlation (first and last image) 0.7857/0.7824 for DART, and 0.3933/0.6253 for AutoMorph. In GRAPE, Pearson/Spearman correlation (first and next visit) was 0.7479/0.7474 for DART, and 0.7109/0.7208 for AutoMorph (all P < 0.0001). Median λ in Caledonia without exclusions was 3.55% for DART and 12.65% for AutoMorph and improved to up to 1.67% and 6.64% with quality-based exclusions, respectively. Quality exclusions primarily mitigated large outliers. Worst quality in an eye correlated strongly with λ (Pearson 0.5350-0.7550, depending on dataset and method, all P < 0.0001). Conclusions: Repeatability was sufficient for individual-level predictions in heterogeneous populations. DART performed better on all metrics and might be able to detect small, longitudinal changes, highlighting the potential of robust methods.

Time-Resolved Dynamic Optical Coherence Tomography for Retinal Blood Flow Analysis.

Purpose: Optical coherence tomography (OCT) representations in clinical practice are static and do not allow for a dynamic visualization and quantification of blood flow. This study aims to present a method to analyze retinal blood flow dynamics using time-resolved structural OCT. Methods: We developed novel imaging protocols to acquire video-rate time-resolved OCT B-scans (1024 × 496 pixels, 10 degrees field of view) at four different sensor integration times (integration time of 44.8 µs at a nominal A-scan rate of 20 kHz, 22.4 µs at 40 kHz, 11.2 µs at 85 kHz, and 7.24 µs at 125 kHz). The vessel centers were manually annotated for each B-scan and surrounding subvolumes were extracted. We used a velocity model based on signal-to-noise ratio (SNR) drops due to fringe washout to calculate blood flow velocity profiles in vessels within five optic disc diameters of the optic disc rim. Results: Time-resolved dynamic structural OCT revealed pulsatile SNR changes in the analyzed vessels and allowed the calculation of potential blood flow velocities at all integration times. Fringe washout was stronger in acquisitions with longer integration times; however, the ratio of the average SNR to the peak SNR inside the vessel was similar across all integration times. Conclusions: We demonstrated the feasibility of estimating blood flow profiles based on fringe washout analysis, showing pulsatile dynamics in vessels close to the optic nerve head using structural OCT. Time-resolved dynamic OCT has the potential to uncover valuable blood flow information in clinical settings.

New findings on retinal microvascular changes in patients with primary COVID-19 infection: a longitudinal study.

Purpose: To investigate the longitudinal alterations of retinal microvasculature in patients with primary coronavirus disease 2019 (COVID-19) infection. Methods: A cohort of participants, who had never been infected with COVID-19, was recruited between December 2022 and May 2023 at Peking Union Medical College Hospital in Beijing, China. Participants underwent comprehensive ophthalmologic examinations and fundus imaging, which included color fundus photography, autofluorescence photography, swept-source optical coherence tomography (SS-OCT) and SS-OCT angiography (SS-OCTA). If participants were infected with COVID-19 during the study, follow-ups with consistent imaging modality were conducted within one week and two months after recovery from the infection. Results: 31 patients (61 eyes), with a mean age of 31.0 ± 7.2 years old, were eligible for this study. All participants contracted mild COVID-19 infection within one month of baseline data collection. The average period was 10.9 ± 2.0 days post-infection for the first follow-up and 61.0 ± 3.5 days for the second follow-up. No clinical retinal microvasculopathy features were observed during the follow-ups. However, SS-OCTA analysis showed a significant increase in macular vessel density (MVD) from 60.76 ± 2.88% at baseline to 61.59 ± 3.72%(p=0.015) at the first follow-up, which subsequently returned to the baseline level of 60.23 ± 3.33% (p=0.162) at the two-month follow-up. The foveal avascular zone (FAZ) remained stable during the follow-ups with areas of 0.339 ± 0.097mm2, 0.342 ± 0.093mm2, and 0.344 ± 0.098mm2 at the baseline, first follow-up (p=0.09) and second follow-up (p=0.052), respectively. Central macular thickness, cube volume and ganglion cell-inner plexiform layer showed a transient decrease at the first follow-up(p<0.001, p=0.039, p=0.002, respectively), and increased to baseline level at the two-month follow-up(p=0.401, p=0.368, p=0.438, respectively). Conclusion: Mild COVID-19 infection may temporarily and reversibly impact retinal microvasculature, characterized by a transient increase in retinal blood flow during the early recovery phase, which returns to the pre-infection level two months post-infection.

Assessment of retinal and choroidal microvasculature in night shift medical workers by OCT angiography.

This study evaluated retinal and choroidal microvascular changes in night shift medical workers and its correlation with melatonin level. Night shift medical workers (group A, 25 workers) and non-night shift workers (group B, 25 workers) were recruited. The images of macula and optic nerve head were obtained by swept-source OCT-angiography. Vessel density of retina, choriocapillaris (CC), choriocapillaris flow deficit (CC FD), choroidal thickness (CT) and choroidal vascularity index (CVI) were measured. 6-sulfatoxymelatonin concentration was analyzed from the morning urine. CC FD and CVI were significantly decreased and CT was significantly increased in group A (all P < 0.05). 6-sulfatoxymelatonin concentration was significantly lower in group A (P < 0.05), which was significantly positively correlated with CC FD size (r = 0.318, P = 0.024) and CVI of the most regions (maximum r-value was 0.482, P < 0.001), and was significantly negatively associated with CT of all regions (maximum r-value was - 0.477, P < 0.001). In night shift medical workers, the reduction of melatonin was significantly correlated with CT thickening, CVI reduction and CC FD reduction, which suggested that they might have a higher risk of eye diseases. CC FD could be a sensitive and accurate indicator to reflect CC perfusion.

Choroidalyzer: An Open-Source, End-to-End Pipeline for Choroidal Analysis in Optical Coherence Tomography.

Purpose: To develop Choroidalyzer, an open-source, end-to-end pipeline for segmenting the choroid region, vessels, and fovea, and deriving choroidal thickness, area, and vascular index. Methods: We used 5600 OCT B-scans (233 subjects, six systemic disease cohorts, three device types, two manufacturers). To generate region and vessel ground-truths, we used state-of-the-art automatic methods following manual correction of inaccurate segmentations, with foveal positions manually annotated. We trained a U-Net deep learning model to detect the region, vessels, and fovea to calculate choroid thickness, area, and vascular index in a fovea-centered region of interest. We analyzed segmentation agreement (AUC, Dice) and choroid metrics agreement (Pearson, Spearman, mean absolute error [MAE]) in internal and external test sets. We compared Choroidalyzer to two manual graders on a small subset of external test images and examined cases of high error. Results: Choroidalyzer took 0.299 seconds per image on a standard laptop and achieved excellent region (Dice: internal 0.9789, external 0.9749), very good vessel segmentation performance (Dice: internal 0.8817, external 0.8703), and excellent fovea location prediction (MAE: internal 3.9 pixels, external 3.4 pixels). For thickness, area, and vascular index, Pearson correlations were 0.9754, 0.9815, and 0.8285 (internal)/0.9831, 0.9779, 0.7948 (external), respectively (all P < 0.0001). Choroidalyzer's agreement with graders was comparable to the intergrader agreement across all metrics. Conclusions: Choroidalyzer is an open-source, end-to-end pipeline that accurately segments the choroid and reliably extracts thickness, area, and vascular index. Especially choroidal vessel segmentation is a difficult and subjective task, and fully automatic methods like Choroidalyzer could provide objectivity and standardization.

Observation of structural and vascular features of retina and choroid in myopia using ultra-widefield SS-OCTA.

BACKGROUND: To find the relationship between the changes of retinal and choriodal structure/ vascular densities (VD) and the myopia progress. METHODS: 126 eyes of 126 age-matched young participants were divided into three groups: Emmetropia and Low Myopia (EaLM) (33 eyes), Moderate Myopia (MM) (39 eyes), and High Myopia (HM) (54 eyes). Fundus images measuring 12 × 12 mm were captured using ultra-widefield swept-source optical coherence tomography angiography (SS-OCTA). Each image was uniformly divided into nine regions: supra-temporal (ST), temporal (T), infra-temporal (IT), superior (S), central macular area (C), inferior (I), supra-nasal (SN), nasal (N), and infra-nasal (IN). Various structural parameters, including inner retina thickness (IRT), outer retina thickness (ORT), and choroid thickness (CT), were assessed, and the VD of the superficial capillary plexus (SCP), deep capillary plexus (DCP), choriocapillaries (CC), and choroid vessels (ChdV) were quantified. RESULTS: CT in upper fundus exhibited a significant reduction from EaLM to MM. Additionally, ORT (ST, S. SN, C, N, IT, I, IN), CT (ST, S, SN, T, C, N, IT, I, IN) and VDs of SCP (ST, S, C, I, IN), DCP (ST, S, T, C, I) and ChdV (T, N, I, IN) were statistically diminished in EaLM compared to HM. Furthermore, IRT (N), ORT (N, IN), CT (S, SN, T, C, IT, I) and VDs of SCP (I, IN) and DCP (I) exhibited significant decreases as MM progressed towards HM. Intriguingly, there was a notable increase in the VD of CC (ST, S, T, C, N) as myopia progressed from MM to HM. CONCLUSION: Significant changes in retinal and choroid structure and vascular density occur as moderate myopia advances to high myopia. Efforts to curb myopia progression to this stage are essential, as the failure to do so may lead to the development of corresponding retinopathy.

Does collagen cross linking have any effect on retinal circulation in patients with keratoconus? An optical coherence tomography angiography (OCTA) study.

BACKGROUND: We aimed to employ Optical Coherence Tomography Angiography (OCTA) to comprehensively assess changes in the optic nerve head (ONH) and macular perfusion before and after the Corneal Collagen Cross-Linking (CCL) procedure in patients with keratoconus. METHODS: A total of 22 keratoconus patient's candidate for CCL procedures were included based on specific criteria, with meticulous exclusion criteria in place to minimize potential confounders. Participants underwent OCTA assessments of the ONH and macula using the Spectralis OCT (Heidelberg) before CCL, as well as at 1- and 3-months post-CCL. MATLAB software was utilized for image analysis. RESULTS: The mean age of the participants was 20.09 ± 6.11, including 59% male, and the mean intraocular pressure (IOP) before the surgery was 13.59 ± 2.85 mmHg. Peripapillary Retinal nerve fiber layer (ppRNFL) thickness and overall retinal thickness remained stable post-CCL. However, significant alterations were observed in macular vessel density, emphasizing regional variations in vascular response. For macular large vessel density (LVD), both superficial and deep vascular complex (SVC and DVC) demonstrated significant differences between before surgery and the 3 months post-surgery follow-up (p < 0.001 and p = 0.002, respectively). Optic nerve head markers demonstrated relative stability, except for changes in avascular complex density, which was 49.2 ± 2.2% before the surgery and decrease to 47.6 ± 1.7% three months after the operation (P-value = 0.005). CONCLUSION: While CCL appears to maintain the integrity of certain ocular structures, alterations in macular perfusion post-CCL suggest potential effects on retinal blood supply. Long-term monitoring is crucial to understand the implications of these changes, particularly in the context of conditions such as diabetes.

Diagnostic Role of Oral Fluorescein Angiography in Pediatric Ambulatory Clinics.

Oral ingestion of fluorescein can be done in ambulatory pediatric clinics. We show that oral ultra-widefield fluorescein angiography is a non-invasive approach to rapidly diagnose and manage a diverse set of pediatric retinal vascular diseases.

Glaucoma detection using non-perfused areas in OCTA.

Multiple ophthalmic diseases lead to decreased capillary perfusion that can be visualized using optical coherence tomography angiography images. To quantify the decrease in perfusion, past studies have often used the vessel density, which is the percentage of vessel pixels in the image. However, this method is often not sensitive enough to detect subtle changes in early pathology. More recent methods are based on quantifying non-perfused or intercapillary areas between the vessels. These methods rely upon the accuracy of vessel segmentation, which is a challenging task and therefore a limiting factor for reliability. Intercapillary areas computed from perfusion-distance measures are less sensitive to errors in the vessel segmentation since the distance to the next vessel is only slightly changing if gaps are present in the segmentation. We present a novel method for distinguishing between glaucoma patients and healthy controls based on features computed from the probability density function of these perfusion-distance areas. The proposed approach is evaluated on different capillary plexuses and outperforms previously proposed methods that use handcrafted features for classification. Moreover the results of the proposed method are in the same range as the ones of convolutional neural networks trained on the raw input images and is therefore a computationally efficient, simple to implement and explainable alternative to deep learning-based approaches.

[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.

Associations of between- and within-day patterns of physical activity accumulation with arterial stiffness and indices of microvascular health-Evidence from The Maastricht study.

While physical activity (PA) is understood to promote vascular health, little is known about whether the daily and weekly patterns of PA accumulation associate with vascular health. Accelerometer-derived (activPAL3) 6- or 7-day stepping was analyzed for 6430 participants in The Maastricht Study (50.4% women; 22.4% Type 2 diabetes mellitus (T2DM)). Multivariable regression models examined associations between stepping metrics (average step count, and time spent slower and faster paced stepping) with arterial stiffness (measured as carotid-femoral pulse wave velocity (cfPWV)), and several indices of microvascular health (heat-induced skin hyperemia, retinal vessel reactivity and diameter), adjusting for confounders and moderators. PA pattern metrics were added to the regression models to identify associations with vascular health beyond that of stepping metrics. Analyses were stratified by T2DM status if an interaction effect was present. Average step count and time spent faster paced stepping was associated with better vascular health, and the association was stronger in those with compared to those without T2DM. In fully adjusted models a higher step count inter-daily stability was associated with a higher (worse) cfPWV in those without T2DM (std ß = 0.04, p = 0.007) and retinal venular diameter in the whole cohort (std ß = 0.07, p = 0.002). A higher within-day variability in faster paced stepping was associated with a lower (worse) heat-induced skin hyperemia in those with T2DM (std ß = -0.31, p = 0.008). Above and beyond PA volume, the daily and weekly patterns in which PA was accumulated were additionally associated with improved macro- and microvascular health, which may have implications for the prevention of vascular disease.

Lipid profile alterations in non-infectious uveitis: correlation with quantitative optical coherence tomography angiography parameters.

BACKGROUND/AIMS: Lipid profiles have been changed in numerous chronic conditions. The impact of uveitis on lipid metabolism remains unclear. METHODS: This is a cross-sectional study included 416 patients with non-infectious uveitis (NIU) and 416 healthy subjects. Standard techniques were used to measure total cholesterol (TC), triglycerides (TG), high-density lipoprotein-cholesterol (HDLc), low-density lipoprotein-cholesterol (LDLc) levels. Quantitative optical coherence tomography angiography (OCTA) parameters were obtained from 500 eyes in each group. Correlation analysis examined the relationship between lipid profile and OCTA parameters. RESULTS: Patients with NIU exhibited significantly elevated TC, TG and LDLc levels compared with controls (p=0.003; p<0.001; p<0.001, respectively). Subgroup analysis revealed that HDLc was significantly lower in Behçet's disease (p=0.024) compared with controls. Vascular density (VD) in the superficial capillary plexus (SCP), deep capillary plexus (DCP), choriocapillaris and optic disk were significantly decreased in NIU eyes (p<0.05, respectively) compared with controls. HDLc exhibited a significant negative correlation with VDs in the whole and parafovea SCP (r=-0.489, p=0.008; r=-0.480, p=0.0026, respectively), while LDLc showed a significant positive correlation with VDs in the whole and parafovea DCP in NIU patients (r=0.576, p=0.032; r=0.267, p=0.034, respectively). CONCLUSIONS: The lipid profile is altered in NIU, and there are correlations between HDLc and LDLc levels and VD as measured by OCTA. Lipid profile analysis may offer valuable insights into evaluating vascular and metabolic aspects of NIU.

Multimodal Structural and Functional Characterization of Retinal Vasculopathy with Cerebral Leukoencephalopathy.

OBJECTIVE: To describe and quantify the structural and functional consequences of retinal vasculopathy with cerebral leukoencephalopathy (RVCL) on the neurosensory retina. DESIGN: Cross sectional descriptive study from December 2021 to December 2022. PARTICIPANTS: Retinal vasculopathy with cerebral leukoencephalopathy patients (n = 9, 18 eyes) recruited from the RVCL Research Center at Washington University in St. Louis. METHODS: Retinal vasculopathy with cerebral leukoencephalopathy patients underwent comprehensive ophthalmological evaluation including OCT, OCT angiography (OCTA), ultrawidefield fundus imaging, retinal autofluorescence, dark adaptation, electroretinography (ERG), Goldmann kinetic perimetry, and fluorescein angiography (FA). MAIN OUTCOME MEASURES: Comprehensive characterization from various modalities including best-corrected visual acuity, central subfield thickness (µm) from OCT, foveal avascular zone (mm2) from OCTA, dark adaptation rod intercept (seconds), cone response in ERG, and presence or absence of vascular abnormalities, leakage, neovascularization, and nonperfusion on FA. RESULTS: A total of 18 eyes from 9 individuals were included in this study. The best-corrected visual acuity ranged from 20/15 to 20/70. The mean central subfield thickness from OCT was 275.8 µm (range, 217-488 µm). The mean foveal avascular zone (FAZ) from OCTA was 0.65 (range, 0.18-1.76) mm2. On dark adaptometry, the mean time was 5.02 (range, 2.9-6.5) minutes, and 1 individual had impaired dark adaptation. Electroretinography demonstrated mild cone response impairment in 4 eyes. On FA, there was evidence of macular and peripheral capillary nonperfusion in 16 of 18 eyes and notable areas of vascular leakage and retinal edema in 5 of the 18 eyes. CONCLUSIONS: This study illustrates the phenotypic spectrum of disease and may be clinically valuable for aiding diagnosis, monitoring disease progression, and further elucidating the pathophysiology of RVCL to aid in the development of therapies. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

ASSOCIATION OF MACULAR STRUCTURE WITH MICROPERIMETRY SENSITIVITY FOLLOWING VITRECTOMY FOR PROLIFERATE DIABETIC RETINOPATHY.

PURPOSE: To evaluate macular sensitivity using microperimetry in patients with proliferate diabetic retinopathy following vitrectomy and to investigate the relationship between the sensitivity and foveal microstructures with optical coherence tomography/angiography. METHODS: Eighty-four eyes of 84 patients with proliferative diabetic retinopathy, who were indicated for vitrectomy, had no intraocular surgery history 3 months preoperatively, and were able to ensure fundus examination after the vitrectomy, were included. A logMAR best-corrected visual acuity, macular sensitivity of microperimetry, macular retinal thickness, and macular vessel perfusion using optical coherence tomography/angiography were examined at 1 week, 1 month, and 3 months postoperatively. RESULTS: The logMAR best-corrected visual acuity and mean macular sensitivity of patients with proliferative diabetic retinopathy improved postoperatively (P < 0.05). There was a significant correlation between best-corrected visual acuity and mean sensitivity (P < 0.05). Postoperative mean macular sensitivity was significantly correlated with outer retinal thickness in the 0 to 6 mm macular area (P < 0.05) and also significantly correlated with deep capillary plexus perfusion (P < 0.05). Fixation stability and mean macular sensitivity did not show any correlation with glycated hemoglobin, triglyceride, serum total cholesterol, carbamide, and creatinine and duration of diabetes mellitus (P > 0.05). CONCLUSION: Postoperative mean macular sensitivity was significantly correlated with outer retinal thickness and deep capillary plexus perfusion for patients with proliferative diabetic retinopathy. The authors found that the visual performance of patients can be evaluated by the outer retinal thickness and deep capillary plexus perfusion, so optical coherence tomography/angiography examination can be an important prognostic factor for visual performance in patients.Clinical Trial Registration: This trial is registered with the Chinese Clinical Trial Registry (http://www.chictr.org.cn; Registration No.: ChiCTR2100043399).

FOXC1 regulates endothelial CD98 (LAT1/4F2hc) expression in retinal angiogenesis and blood-retina barrier formation.

Angiogenesis, the growth of new blood vessels from pre-existing vasculature, is essential for the development of new organ systems, but transcriptional control of angiogenesis remains incompletely understood. Here we show that FOXC1 is essential for retinal angiogenesis. Endothelial cell (EC)-specific loss of Foxc1 impairs retinal vascular growth and expression of Slc3a2 and Slc7a5, which encode the heterodimeric CD98 (LAT1/4F2hc) amino acid transporter and regulate the intracellular transport of essential amino acids and activation of the mammalian target of rapamycin (mTOR). EC-Foxc1 deficiency diminishes mTOR activity, while administration of the mTOR agonist MHY-1485 rescues perturbed retinal angiogenesis. EC-Foxc1 expression is required for retinal revascularization and resolution of neovascular tufts in a model of oxygen-induced retinopathy. Foxc1 is also indispensable for pericytes, a critical component of the blood-retina barrier during retinal angiogenesis. Our findings establish FOXC1 as a crucial regulator of retinal vessels and identify therapeutic targets for treating retinal vascular disease.

Pericyte in retinal vascular diseases: A multifunctional regulator and potential therapeutic target.

Retinal vascular diseases (RVDs), in particular diabetic retinopathy, retinal vein occlusion, and retinopathy of prematurity, are leading contributors to blindness. The pathogenesis of RVD involves vessel dilatation, leakage, and occlusion; however, the specific underlying mechanisms remain unclear. Recent findings have indicated that pericytes (PCs), as critical members of the vascular mural cells, significantly contribute to the progression of RVDs, including detachment from microvessels, alteration of contractile and secretory properties, and excessive production of the extracellular matrix. Moreover, PCs are believed to have mesenchymal stem properties and, therefore, might contribute to regenerative therapy. Here, we review novel ideas concerning PC characteristics and functions in RVDs and discuss potential therapeutic strategies based on PCs, including the targeting of pathological signals and cell-based regenerative treatments.

ZO-1 interacts with YB-1 in endothelial cells to regulate stress granule formation during angiogenesis.

Zonula occludens-1 (ZO-1) is involved in the regulation of cell-cell junctions between endothelial cells (ECs). Here we identify the ZO-1 protein interactome and uncover ZO-1 interactions with RNA-binding proteins that are part of stress granules (SGs). Downregulation of ZO-1 increased SG formation in response to stress and protected ECs from cellular insults. The ZO-1 interactome uncovered an association between ZO-1 and Y-box binding protein 1 (YB-1), a constituent of SGs. Arsenite treatment of ECs decreased the interaction between ZO-1 and YB-1, and drove SG assembly. YB-1 expression is essential for SG formation and for the cytoprotective effects induced by ZO-1 downregulation. In the developing retinal vascular plexus of newborn mice, ECs at the front of growing vessels express less ZO-1 but display more YB-1-positive granules than ECs located in the vascular plexus. Endothelial-specific deletion of ZO-1 in mice at post-natal day 7 markedly increased the presence of YB-1-positive granules in ECs of retinal blood vessels, altered tip EC morphology and vascular patterning, resulting in aberrant endothelial proliferation, and arrest in the expansion of the retinal vasculature. Our findings suggest that, through its interaction with YB-1, ZO-1 controls SG formation and the response of ECs to stress during angiogenesis.

Association between retinal microvascular abnormalities and late-life brain amyloid-ß deposition: the ARIC-PET study.

BACKGROUND: Retinal microvascular signs are accessible measures of early alterations in microvascular dysregulation and have been associated with dementia; it is unclear if they are associated with AD (Alzheimer's disease) pathogenesis as a potential mechanistic link. This study aimed to test the association of retinal microvascular abnormalities in mid and late life and late life cerebral amyloid. METHODS: Participants from the ARIC-PET (Atherosclerosis Risk in Communities-Positron Emission Tomography) study with a valid retinal measure (N = 285) were included. The associations of mid- and late-life retinal signs with late-life amyloid-ß (Aß) by florbetapir PET were tested. Two different measures of Aß burden were included: (1) elevated amyloid (SUVR > 1.2) and (2) continuous amyloid SUVR. The retinal measures' association with Aß burden was assessed using logistic and robust linear regression models. A newly created retinal score, incorporating multiple markers of retinal abnormalities, was also evaluated in association with greater Aß burden. RESULTS: Retinopathy in midlife (OR (95% CI) = 0.36 (0.08, 1.40)) was not significantly associated with elevated amyloid burden. In late life, retinopathy was associated with increased continuous amyloid standardized value uptake ratio (SUVR) (ß (95%CI) = 0.16 (0.02, 0.32)) but not elevated amyloid burden (OR (95%CI) = 2.37 (0.66, 9.88)) when accounting for demographic, genetic and clinical risk factors. A high retinal score in late life, indicating a higher burden of retinal abnormalities, was also significantly associated with increased continuous amyloid SUVR (ß (95% CI) = 0.16 (0.04, 0.32)) independent of vascular risk factors. CONCLUSIONS: Retinopathy in late life may be an easily obtainable marker to help evaluate the mechanistic vascular pathway between retinal measures and dementia, perhaps acting via AD pathogenesis. Well-powered future studies with a greater number of retinal features and other microvascular signs are needed to test these findings.