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1.
Scand J Med Sci Sports ; 34(5): e14649, 2024 May.
Article En | MEDLINE | ID: mdl-38757450

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.


Diabetes Mellitus, Type 2 , Exercise , Vascular Stiffness , Humans , Female , Vascular Stiffness/physiology , Male , Middle Aged , Diabetes Mellitus, Type 2/physiopathology , Exercise/physiology , Aged , Hyperemia/physiopathology , Accelerometry , Carotid-Femoral Pulse Wave Velocity , Adult , Pulse Wave Analysis , Retinal Vessels/physiology
2.
Ophthalmol Retina ; 8(2): 204-206, 2024 Feb.
Article En | MEDLINE | ID: mdl-38707762

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.


Fluorescein Angiography , Fluorescein , Fundus Oculi , Retinal Diseases , Humans , Fluorescein Angiography/methods , Child , Retinal Diseases/diagnosis , Fluorescein/administration & dosage , Male , Female , Adolescent , Retinal Vessels/diagnostic imaging , Child, Preschool , Ambulatory Care Facilities , Administration, Oral
3.
Ophthalmol Retina ; 8(4): 331-339, 2024 Apr.
Article En | MEDLINE | ID: mdl-38752998

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.


Electroretinography , Fluorescein Angiography , Leukoencephalopathies , Multimodal Imaging , Tomography, Optical Coherence , Visual Acuity , Humans , Male , Female , Cross-Sectional Studies , Tomography, Optical Coherence/methods , Adult , Fluorescein Angiography/methods , Electroretinography/methods , Middle Aged , Leukoencephalopathies/diagnosis , Leukoencephalopathies/physiopathology , Visual Fields/physiology , Retinal Diseases/diagnosis , Retinal Diseases/physiopathology , Retinal Diseases/etiology , Retinal Vessels/diagnostic imaging , Retinal Vessels/physiopathology , Retinal Vessels/pathology , Young Adult , Fundus Oculi , Adolescent
4.
Vestn Oftalmol ; 140(2): 63-70, 2024.
Article Ru | MEDLINE | ID: mdl-38742500

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.


Disease Progression , Multiple Sclerosis , Retinal Vessels , Tomography, Optical Coherence , Humans , Tomography, Optical Coherence/methods , Male , Female , Adult , Middle Aged , Multiple Sclerosis/diagnosis , Multiple Sclerosis/diagnostic imaging , Multiple Sclerosis/physiopathology , Retinal Vessels/diagnostic imaging , Fluorescein Angiography/methods , Microcirculation/physiology , Optic Neuritis/diagnosis , Optic Neuritis/etiology , Optic Neuritis/diagnostic imaging , Optic Neuritis/physiopathology , Reproducibility of Results
5.
Diabetes Metab Res Rev ; 40(4): e3812, 2024 May.
Article En | MEDLINE | ID: mdl-38738481

AIMS: To evaluate the effectiveness of optical coherence tomography angiography (OCTA) in detecting early intraocular microvascular changes in diabetic patients. MATERIALS AND METHODS: A systematic study search was performed on PubMed, Medline, Embase, and the Cochrane Library, ranging from January 2012 to March 2023. Controlled studies compared diabetes mellitus (DM) patients with non-diabetic retinopathy (NDR) or patients with mild non-proliferative diabetic retinopathy (mild NPDR) to healthy people. These studies included parameters of OCTA such as foveal avascular zone (FAZ), vessel density of superficial capillary plexus (VDscp), vessel density of deep capillary plexus (VDdcp), and peripapillary VD. The relevant effect model was used according to the heterogeneity, and the mean difference and 95% confidence intervals were calculated. RESULTS: A total of 18 studies with 2101 eyes were eventually included in this meta-analysis. Our results demonstrated that early alterations of VDscp, VDdcp, and peripapillary VD in NDR patients had a significant difference compared with healthy people by OCTA (VDscp: WMD = -1.34, 95% CI: -1.99 to -0.68, P < 0.0001. VDdcp: WMD = -2.00, 95% CI: -2.95 to -1.04, P < 0.0001. Peripapillary VD: WMD = -1.07, 95% CI: -1.70 to -0.43, P = 0.0010). However, there was no statistically significant difference in total FAZ between them (WMD = -0.00, 95% CI: -0.02-0.01, P = 0.84). In addition, for patients with mild NPDR, OCTA could illustrate prominent changes in VDscp, VDdcp, and total FAZ compared with healthy people (VDscp: WMD = -6.11, 95% CI: -9.90 to -2.32, P = 0.002. VDdcp: WMD = -4.26, 95% CI: -5.95 to -2.57, P < 0.00001. FAZ: WMD = 0.06, 95% CI: 0.01-0.11, P = 0.03). CONCLUSIONS: In diabetic patients with or without retinopathy, the parameters of OCTA such as VDscp, VDdcp, and peripapillary vessel density were demonstrated as potential biomarkers in monitoring the early alterations of retinal microangiopathy, while total FAZ may have no significant changes in diabetic patients without retinopathy.


Diabetic Retinopathy , Retinal Vessels , Tomography, Optical Coherence , Humans , Tomography, Optical Coherence/methods , Diabetic Retinopathy/diagnostic imaging , Diabetic Retinopathy/etiology , Retinal Vessels/diagnostic imaging , Retinal Vessels/pathology , Fluorescein Angiography/methods , Microvessels/diagnostic imaging , Microvessels/pathology , Diabetes Mellitus/diagnostic imaging , Prognosis
6.
Sci Rep ; 14(1): 10306, 2024 05 05.
Article En | MEDLINE | ID: mdl-38705883

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.


Glaucoma , Retinal Vessels , Tomography, Optical Coherence , Tomography, Optical Coherence/methods , Humans , Glaucoma/diagnostic imaging , Glaucoma/diagnosis , Retinal Vessels/diagnostic imaging , Retinal Vessels/pathology , Female , Male , Middle Aged , Image Processing, Computer-Assisted/methods , Capillaries/diagnostic imaging , Capillaries/pathology
7.
BMC Ophthalmol ; 24(1): 201, 2024 May 03.
Article En | MEDLINE | ID: mdl-38698363

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.


Collagen , Cross-Linking Reagents , Fluorescein Angiography , Keratoconus , Optic Disk , Retinal Vessels , Tomography, Optical Coherence , Humans , Tomography, Optical Coherence/methods , Keratoconus/physiopathology , Keratoconus/diagnosis , Male , Female , Collagen/metabolism , Young Adult , Adult , Fluorescein Angiography/methods , Retinal Vessels/diagnostic imaging , Retinal Vessels/physiopathology , Optic Disk/blood supply , Adolescent , Prospective Studies , Photosensitizing Agents/therapeutic use , Photochemotherapy/methods , Macula Lutea/diagnostic imaging , Macula Lutea/blood supply
8.
Nat Commun ; 15(1): 4405, 2024 May 23.
Article En | MEDLINE | ID: mdl-38782923

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.


Endothelial Cells , Y-Box-Binding Protein 1 , Zonula Occludens-1 Protein , Animals , Y-Box-Binding Protein 1/metabolism , Y-Box-Binding Protein 1/genetics , Zonula Occludens-1 Protein/metabolism , Zonula Occludens-1 Protein/genetics , Mice , Humans , Endothelial Cells/metabolism , Stress Granules/metabolism , Neovascularization, Physiologic , Retinal Vessels/metabolism , Human Umbilical Vein Endothelial Cells/metabolism , Mice, Inbred C57BL , Mice, Knockout , Angiogenesis , Transcription Factors
9.
Alzheimers Res Ther ; 16(1): 100, 2024 May 06.
Article En | MEDLINE | ID: mdl-38711107

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.


Amyloid beta-Peptides , Aniline Compounds , Brain , Positron-Emission Tomography , Retinal Vessels , Humans , Female , Male , Amyloid beta-Peptides/metabolism , Positron-Emission Tomography/methods , Aged , Middle Aged , Brain/diagnostic imaging , Brain/metabolism , Retinal Vessels/diagnostic imaging , Retinal Diseases/diagnostic imaging , Retinal Diseases/metabolism , Microvessels/diagnostic imaging , Microvessels/metabolism , Alzheimer Disease/diagnostic imaging , Alzheimer Disease/metabolism , Ethylene Glycols
10.
FASEB J ; 38(10): e23679, 2024 May 31.
Article En | MEDLINE | ID: mdl-38780117

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.


Pericytes , Pericytes/metabolism , Humans , Animals , Retinal Vessels/metabolism , Retinal Vessels/pathology , Retinal Diseases/therapy , Retinal Diseases/metabolism , Retinal Diseases/pathology , Diabetic Retinopathy/metabolism , Diabetic Retinopathy/therapy , Diabetic Retinopathy/pathology
11.
Transl Vis Sci Technol ; 13(5): 21, 2024 May 01.
Article En | MEDLINE | ID: mdl-38780954

Purpose: This study aimed to investigate the possible relationship between retinal vascular abnormalities and amblyopia by analyzing vascular structures of fundus images. Methods: In this observational study, retinal fundus images were collected from 36 patients with unilateral amblyopia, 33 patients with bilateral amblyopia, and 36 healthy control volunteers. We developed a customized training algorithm based on U-Net to digitalize the vasculature in the fundus images to quantify vascular density (area and fractal dimension), skeleton length, and number of bifurcation points. For statistical comparisons, this study divided participants into two groups. The amblyopic eyes and the fellow eyes of patients with unilateral amblyopia formed the paired group, while bilateral amblyopic patients and healthy controls formed the independent group. Results: In the paired group, the vascular area (P = 0.007), vascular fractal dimension (P = 0.007), and vascular skeleton length (P = 0.002) of the amblyopic eyes were significantly smaller than those of the fellow eyes. In the independent group, significant decreases in the vascular fractal dimension (P = 0.006) and skeleton length (P = 0.048) were observed in bilateral amblyopia compared to control. The vascular area was also significantly correlated with best-corrected visual acuity in amblyopic eyes. Conclusions: This study demonstrated that retinal vascular density and skeleton length in amblyopic eyes were significantly smaller compared to control, indicating an association between the changes in retinal vascular features and the state of amblyopia. Translational Relevance: Our algorithm presents amblyopic retinal vascular changes that are more biologically interpretable for both clinicians and researchers.


Algorithms , Amblyopia , Retinal Vessels , Visual Acuity , Humans , Amblyopia/physiopathology , Amblyopia/pathology , Female , Male , Retinal Vessels/diagnostic imaging , Retinal Vessels/pathology , Visual Acuity/physiology , Adult , Young Adult , Adolescent , Child , Fractals , Microvascular Density
12.
Transl Vis Sci Technol ; 13(5): 22, 2024 May 01.
Article En | MEDLINE | ID: mdl-38780953

Purpose: To identify progression of nonproliferative diabetic retinopathy (NPDR) in patients with type 2 diabetes by combining optical coherence tomography angiography (OCTA) metrics and color fundus photography (CFP) images. Methods: This study was a post hoc analysis of a prospective longitudinal cohort study (CORDIS, NCT03696810) with 2-year duration. This study enrolled 122 eyes. Ophthalmological examinations included OCTA and CFP. OCTA metrics included skeletonized vessel density (SVD) and perfusion density (PD) at the superficial capillary plexus (SCP) and deep capillary plexus (DCP). Microaneurysm turnover analysis and Early Treatment Diabetic Retinopathy Study (ETDRS) grading for diabetic retinopathy (DR) severity assessment were performed on 7-field CFP. Results: Eyes graded as ETDRS level 20 showed significant capillary nonperfusion predominantly in the inner ring area in the SCP (P < 0.001), whereas eyes graded as ETDRS level 35 and ETDRS levels 43 and 47 showed significant capillary nonperfusion in both the SCP and DCP in both inner and outer rings (P < 0.001). When evaluating rates of progression in capillary nonperfusion for the 2-year period of follow-up, changes were found predominantly in the DCP for SVD and PD and were better identified in the outer ring area. Microaneurysm turnover contributes to the characterization of NPDR progression by discriminating ETDRS level 35 from ETDRS levels 43 and 47 (P < 0.001), which could not be achieved using only OCTA metrics. Conclusions: Patterns of progression of NPDR can be identified combining OCTA examinations of the superficial and deep retinal capillary plexi of central retina and determination of microaneurysm turnover from fundus photographs. Translational Relevance: Our study reports results from a registered clinical trial that advances understanding of disease progression in NPDR.


Diabetic Retinopathy , Disease Progression , Fluorescein Angiography , Retinal Vessels , Tomography, Optical Coherence , Humans , Diabetic Retinopathy/diagnostic imaging , Diabetic Retinopathy/pathology , Male , Female , Middle Aged , Tomography, Optical Coherence/methods , Prospective Studies , Retinal Vessels/diagnostic imaging , Retinal Vessels/pathology , Aged , Fluorescein Angiography/methods , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/pathology , Photography
13.
BMJ Case Rep ; 17(5)2024 May 08.
Article En | MEDLINE | ID: mdl-38719246

Cutis marmorata telangiectatica congenita is a rare congenital vascular malformation characterised by cutaneous vascular abnormalities, typically diagnosed at birth or in the early postnatal period. Although typically benign, this disease is associated with other systemic abnormalities, including rare ocular alterations, such as congenital glaucoma, cataracts and retinopathy.This manuscript describes a female infant, who presented with generalised livedo reticularis, a band of alopecia and cutaneous atrophy in the temporal region above the coronal suture. The patient was diagnosed with cutis marmorata telangiectatica congenita by a paediatrician, and an ophthalmological evaluation was requested. A funduscopy examination in both eyes showed temporal and superior retina with avascular areas with new vessels, venous dilations and shunts, and no retinal detachments. Given these findings, we performed retinal photocoagulation laser treatment with excellent results.This case report highlights the importance of early ophthalmological evaluation of children with this disease to prevent secondary complications, such as vitreous haemorrhage and tractional retinal detachment.


Livedo Reticularis , Skin Diseases, Vascular , Telangiectasis , Humans , Female , Telangiectasis/congenital , Telangiectasis/complications , Telangiectasis/diagnosis , Skin Diseases, Vascular/diagnosis , Skin Diseases, Vascular/complications , Infant , Laser Coagulation/methods , Retinal Vessels/abnormalities , Retinal Vessels/diagnostic imaging , Retina/abnormalities , Retina/diagnostic imaging
14.
Nat Commun ; 15(1): 4097, 2024 May 16.
Article En | MEDLINE | ID: mdl-38755144

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.


Blood-Retinal Barrier , Endothelial Cells , Forkhead Transcription Factors , Retinal Neovascularization , Animals , Forkhead Transcription Factors/metabolism , Forkhead Transcription Factors/genetics , Retinal Neovascularization/metabolism , Retinal Neovascularization/genetics , Retinal Neovascularization/pathology , Mice , Endothelial Cells/metabolism , Blood-Retinal Barrier/metabolism , TOR Serine-Threonine Kinases/metabolism , Pericytes/metabolism , Fusion Regulatory Protein 1, Heavy Chain/metabolism , Fusion Regulatory Protein 1, Heavy Chain/genetics , Retinal Vessels/metabolism , Humans , Large Neutral Amino Acid-Transporter 1/metabolism , Large Neutral Amino Acid-Transporter 1/genetics , Mice, Knockout , Mice, Inbred C57BL , Retina/metabolism , Male , Angiogenesis
15.
Retina ; 44(6): 982-990, 2024 Jun 01.
Article En | MEDLINE | ID: mdl-38767849

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).


Diabetic Retinopathy , Fluorescein Angiography , Macula Lutea , Tomography, Optical Coherence , Visual Acuity , Visual Field Tests , Vitrectomy , Humans , Diabetic Retinopathy/physiopathology , Diabetic Retinopathy/surgery , Diabetic Retinopathy/diagnosis , Vitrectomy/methods , Male , Female , Tomography, Optical Coherence/methods , Visual Acuity/physiology , Middle Aged , Visual Field Tests/methods , Fluorescein Angiography/methods , Macula Lutea/blood supply , Macula Lutea/diagnostic imaging , Aged , Adult , Visual Fields/physiology , Retinal Vessels/physiopathology , Retinal Vessels/diagnostic imaging , Postoperative Period
16.
Invest Ophthalmol Vis Sci ; 65(5): 25, 2024 May 01.
Article En | MEDLINE | ID: mdl-38758640

Purpose: To quantitatively characterize retinal changes across different quantiles of refractive error in 34,414 normal eyes of 23,064 healthy adults in the UK Biobank. Methods: Twelve optic disc (OD), foveal and vascular parameters were derived from color fundus photographs, correcting for ocular magnification as appropriate. Quantile regression was used to test the independent associations between these parameters and spherical equivalent refraction (SER) across 34 refractive quantiles (high hyperopia to high myopia)-controlling for age, sex and corneal radius. Results: More negative SER was nonlinearly associated with greater Euclidian (largely horizontal) OD-fovea distance, larger OD, less circular OD, more obliquely orientated OD (superior pole tilted towards the fovea), brighter fovea, lower vascular complexity, less tortuous vessels, more concave (straightened out towards the fovea) papillomacular arterial/venous arcade and wider central retinal arterioles/venules. In myopia, these parameters varied more strongly with SER as myopia increased. For example, while every standard deviation (SD) decrease in vascular complexity was associated with 0.63 D (right eye: 95% confidence interval [CI], 0.58-0.68) to 0.68 D (left eye: 95% CI, 0.63-0.73) higher myopia in the quantile corresponding to -0.60 D, it was associated with 1.61 D (right eye: 95% CI, 1.40-1.82) to 1.70 D (left eye: 95% CI, 1.56-1.84) higher myopia in the most myopic quantile. OD-fovea angle (degree of vertical separation between OD and fovea) was found to vary linearly with SER, but the magnitude was of little practical importance (less than 0.10 D variation per SD change in angle in almost all refractive quantiles) compared with the changes in OD-fovea distance. Conclusions: Several interrelated retinal changes indicative of an increasing (nonconstant) rate of mechanical stretching are evident at the posterior pole as myopia increases. These changes also suggest that the posterior pole stretches predominantly in the temporal horizontal direction.


Hyperopia , Myopia , Refraction, Ocular , Humans , Male , Hyperopia/physiopathology , Female , Myopia/physiopathology , Refraction, Ocular/physiology , Middle Aged , Adult , Retinal Vessels/physiopathology , Retinal Vessels/diagnostic imaging , Retinal Vessels/pathology , Aged , Optic Disk/blood supply , Fovea Centralis/diagnostic imaging , Fovea Centralis/pathology , Visual Acuity/physiology
17.
BMC Ophthalmol ; 24(1): 208, 2024 May 07.
Article En | MEDLINE | ID: mdl-38715011

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.


Choroid , Fluorescein Angiography , Myopia , Retinal Vessels , Tomography, Optical Coherence , Humans , Tomography, Optical Coherence/methods , Choroid/blood supply , Choroid/diagnostic imaging , Choroid/pathology , Male , Female , Young Adult , Myopia/physiopathology , Adult , Retinal Vessels/diagnostic imaging , Retinal Vessels/pathology , Fluorescein Angiography/methods , Retina/diagnostic imaging , Retina/pathology , Disease Progression , Adolescent , Fundus Oculi
18.
BMJ Open Ophthalmol ; 9(1)2024 May 15.
Article En | MEDLINE | ID: mdl-38754892

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.


Fluorescein Angiography , Lipids , Tomography, Optical Coherence , Uveitis , Humans , Cross-Sectional Studies , Male , Uveitis/diagnostic imaging , Uveitis/blood , Female , Adult , Fluorescein Angiography/methods , Lipids/blood , Middle Aged , Retinal Vessels/diagnostic imaging , Retinal Vessels/pathology , Fundus Oculi , Lipid Metabolism , Triglycerides/blood
19.
Jpn J Ophthalmol ; 68(3): 174-182, 2024 May.
Article En | MEDLINE | ID: mdl-38658452

PURPOSE: To evaluate the influence of systemic factors on macular vessel density in quantitative Optical Coherence Tomography Angiography (OCTA) by sex. STUDY DESIGN: A cross-sectional study. METHODS: A total of 2018 adults were recruited in this study. Participants were excluded (n=964) due to missing data, eye-related problems, or low OCTA scan quality. Macular vessel densities were measured with OCTA using split-spectrum amplitude decorrelation angiography algorithm. Only the data from the right eyes were selected for analysis. Multivariable linear regression analysis was performed to determine the associations between macular vessel density and obesity-related systemic factors in each gender group. RESULTS: The right eyes of 1054 participants (59.6% women) were enrolled. Men had significantly higher obesity parameters and associated risk factors. In multivariable linear regression analysis in men, older age and type 2 diabetes mellitus were independently associated with lower superficial retinal vessel density (ß = -0.37, p = 0.002; ß = -1.22, p = 0.03) and deep retinal vessel density, respectively (ß = -0.66, p < 0.001; ß = -1.76, p = 0.02); positive association was also observed between body mass index (BMI) and superficial retinal vessel density (ß = 0.56, p = 0.02). In women, only higher systolic blood pressure was independently associated with a lower deep retinal vessel density (ß = -0.50, p = 0.003). CONCLUSIONS: This large cross-sectional study shows that older age and type 2 diabetes mellitus are associated with lower superficial and deep retinal capillary vessel density in men. This may help clinicians better understand how systemic factors influence retinal vessel density in different genders and future studies can ascertain more potential sex differences.


Fluorescein Angiography , Macula Lutea , Retinal Vessels , Tomography, Optical Coherence , Humans , Male , Cross-Sectional Studies , Female , Tomography, Optical Coherence/methods , Retinal Vessels/diagnostic imaging , Middle Aged , Fluorescein Angiography/methods , Sex Factors , Macula Lutea/blood supply , Macula Lutea/diagnostic imaging , Fundus Oculi , Aged , Adult , Risk Factors , Body Mass Index , Microvascular Density , Population Surveillance , Retrospective Studies
20.
Chin Med J (Engl) ; 137(9): 1054-1068, 2024 May 05.
Article En | MEDLINE | ID: mdl-38563217

BACKGROUND: Alterations in macular thickness and vascular density before clinically visible diabetic retinopathy (DR) remain inconclusive. This study aimed to determine whether retinal manifestations in abnormal glucose metabolism (AGM) patients differ from those in the healthy individuals. METHODS: PubMed, Embase, and Web of Science were searched between 2000 and 2021. The eligibility criteria were AGM patients without DR. Primary and secondary outcomes measured by optical coherence tomography (OCT) and OCT angiography (OCTA) were analyzed and expressed as standardized mean differences (SMDs) with 95% confidence intervals (CIs). A random-effects model was used in the data synthesis. The potential publication bias for the variables was evaluated using Egger's test. RESULTS: A total of 86 observational studies involving 13,773 participants and 15,416 eyes were included. OCT revealed that compared to healthy controls, the total macular thickness of AGM patients was thinner, including the thickness of fovea (-0.24, 95% CI [-0.39, -0.08]; P  = 0.002, I2  = 87.7%), all regions of parafovea (-0.32, 95% CI [-0.54, -0.11]; P  = 0.003; I2  = 71.7%) and the four quadrants of perifovea; the thickness of peripapillary retinal nerve fiber layer (pRNFL), macular retinal nerve fiber layer (mRNFL), and ganglion cell layer (GCL) also decreased. OCTA indicated that the superficial and deep vascular density decreased, the foveal avascular zone (FAZ) area enlarged, and the acircularity index (AI) reduced in AGM individuals. CONCLUSIONS: Retinal thinning and microvascular lesions have occurred before the advent of clinically detectable DR; OCT and OCTA may have the potential to detect these preclinical changes. REGISTRATION: PROSPERO; http://www.crd.york.ac.uk/prospero/ ; No. CRD42021269885.


Macula Lutea , Tomography, Optical Coherence , Tomography, Optical Coherence/methods , Humans , Macula Lutea/diagnostic imaging , Macula Lutea/blood supply , Macula Lutea/metabolism , Diabetic Retinopathy/diagnostic imaging , Diabetic Retinopathy/metabolism , Glucose/metabolism , Retinal Vessels/diagnostic imaging , Retinal Vessels/pathology
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