Changes In Retinal Microvasculature Research Articles

Association between deep learning measured retinal vessel calibre and incident myocardial infarction in a retrospective cohort from the UK Biobank

BackgroundCardiovascular disease is a leading cause of global death. Prospective population-based studies have found that changes in retinal microvasculature are associated with the development of coronary artery disease. Recently, artificial...

Characterization of retinal microvasculature and structure in atrial fibrillation.

Quantitative changes in retinal microvasculature are associated with subclinical cardiac alterations and clinical cardiovascular diseases (i.e., heart failure and coronary artery disease). Nonetheless, very little is known about the retinal vascular and structural changes in patients with atrial fibrillation (AF). Our study aims to characterize the microvasculature and structure of the retina in AF patients and explore their differences in different types of AF (paroxysmal and sustained AF). This cross-sectional study was conducted at the Departments of Neurology and Cardiology in West China Hospital, Chengdu, China. Individuals aged 40 years or older with a diagnosis of AF were eligible for inclusion and underwent an evaluation and diagnosis confirmation before enrollment. Control individuals aged 40 years or older and without a history of AF, ocular abnormalities/disease, or any significant systemic illness were recruited. The retinal vascular and structural parameters were assessed using swept-source optical coherence tomography (SS-OCT)/SS-OCT angiography. Echocardiographic data of left atrium (LA) diameter were collected in patients with AF at the time of inclusion. A total of 242 eyes of 125 participants [71 men (56.8%); mean (SD) age, 61.98 (8.73) years] with AF and 219 eyes of 111 control participants [53 men (47.7%); mean (SD) age, 62.31 (6.47) years] were analyzed. In our AF cohort, 71 patients with paroxysmal AF and 54 patients with sustained AF (i.e., persistent/permanent AF) were included. Decreased retinal microvascular perfusion (β coefficient = -0.08; 95% CI, -0.14 to -0.03) and densities (β coefficient = -1.86; 95% CI, -3.11 to -0.60) in superficial vascular plexus (SVC) were found in the eyes of the participants with AF. In regard to retinal structures, thinner ganglion cell-inner plexiform layer (GCIPL; β coefficient = -2.34; 95% CI, -4.32 to -0.36) and retinal nerve fiber layer (RNFL) thicknesses (β coefficient = -0.63; 95% CI, -2.09 to -0.18) were observed in the eyes of the participants with AF. The retinal parameters did not significantly differ between paroxysmal and sustained AF (all P > 0.05). However, significant interactions were observed between LA diameter and AF subtypes with the perfusion and densities in SVC (P < 0.05). This study found that individuals with AF had decreased retinal vascular densities and perfusion in SVC, as well as thinner GCIPL and RNFL thickness compared with age- and sex-matched control participants. The differences of the retinal microvasculature in SVC between paroxysmal and sustained AF depend on the LA diameter. Given our findings, further longitudinal studies with our participants are of interest to investigate the natural history of retinal microvascular and structural changes in individuals across the clinical process of AF and AF subtypes.

Retinal microvasculature and risk of incident dementia over a 10‐year period: results from the 3C‐Alienor population‐based study

AbstractBackgroundThe retina and the brain microvasculatures share many anatomical and physiological similarities; thus, retinal microvasculature could represent a potential screening tool for cerebrovascular and neurodegenerative diseases. Changes in retinal microvasculature have been associated with dementia in previous studies. However, all the previous studies analyzing retinal vascular network features in relation to dementia or Alzheimer Disease (AD) were cross‐sectional. This study aimed to explore the longitudinal relationship between retinal microvascular features and dementia incidence over a 10‐year follow‐up period.MethodWe included 617 participants from the Three‐City (3C) population‐based cohort and its ancillary ophthalmological study, the Alienor study. Quantitative retinal vascular features (caliber, tortuosity, fractal dimension) were assessed at baseline in the Alienor study using the semi‐automated Singapore I Vessel Assessment (SIVA) software; dementia was actively screened and diagnosed over a 10‐year period. Cox proportional‐hazards models were used to estimate the risk of incident dementia and its main etiologies (i.e., probable or possible AD and mixed or vascular dementia) associated with retinal vascular features.ResultThe mean age of the participants was 79.5 years (SD 4.4) and 66.6% were women. During the follow‐up (median of 7.2 years), 134 participants developed dementia (87 probable or possible AD and 38 mixed or vascular dementia). In multivariate models adjusted for the main potential confounders (socio‐demographic factors, vascular co‐morbidities and Apolipoprotein ε4 allele), increased arteriolar tortuosity was associated with increased risk of dementia (HR per SD increase = 1.26, 95%CI: 1.07; 1.50). Despite some trends, retinal calibers were not significantly associated with dementia all‐cause. When considering the different etiologies of dementia, wider retinal venular calibers were associated with mixed or vascular dementia, but not with Alzheimer’s disease. Fractal dimensions were not associated with dementia.ConclusionChanges in retinal microvasculature were associated with risk of incident dementia. More works are needed to replicate and determine which features could help identifying persons at risk of future dementia at an early stage, and to examine the specific processes that might be involved according to dementia etiology.

Multimodal retinal imaging in individuals with frontotemporal dementia compared to controls

AbstractBackgroundA growing body of literature has shown a relationship between neurodegenerative diseases and ocular changes. Frontotemporal dementia (FTD) affects individuals under age 65. We use optical coherence tomography (OCT) and OCT angiography (OCTA) to characterize the retinal microvasculature and retinal and choroidal structure in patients with FTD vs normal cognition.MethodCross‐sectional comparison of patients with FTD to age‐ and sex‐matched controls with normal cognition. Exclusion criteria included diabetes, glaucoma, uncontrolled hypertension, and retinal or optic nerve pathology. Participants underwent OCT and OCTA imaging using the Zeiss Cirrus HD‐5000 Spectral‐Domain OCT with AngioPlex. Primary outcome measures included OCT parameters: subfoveal choroidal thickness, central subfield thickness, ganglion cell layer‐inner plexiform layer (GC‐IPL) thickness, and retinal nerve fiber layer (RNFL) thickness; and OCTA parameters: superficial capillary plexus foveal avascular zone area, 3×3mm and 6×6mm macular vessel density (VD) and perfusion density (PD), and 4.5×4.5mm peripapillary capillary perfusion density (CPD) and capillary flux index (CFI). Generalized estimating equations accounting for correlation between 2 eyes of the same subject were utilized for statistical analysis.ResultTwenty‐eight eyes of 17 participants with FTD and 85 eyes of 48 patients with normal cognition were analyzed. Individuals with FTD were matched to their normal cognition counterparts with regard to sex (64.7% vs 62.5% men, p = 0.871) and age (67.82 vs 68.98 years, p = 0.958). Compared to normal cognition participants, MMSE scores of FTD participants were significantly lower (p &lt; 0.001). In FTD, average 4.5×4.5‐mm CFI was decreased compared to controls (p = 0.032). There was no difference in average 4.5×4.5mm CPD between FTD and controls (p = 0.172).ConclusionIndividuals with FTD exhibited significantly reduced average CFI compared to controls. Retinal microvasculature changes may be useful as a biomarker for FTD diagnosis.

Long-term real-world outcomes of retinal microvasculature changes in proliferative diabetic retinopathy treated with panretinal photocoagulation vs. intravitreal conbercept

PurposeTo compare long-term real-world outcomes of retinal microvasculature changes in proliferative diabetic retinopathy (PDR) treated with panretinal photocoagulation (PRP) vs. intravitreal conbercept (IVC) and to explore the potential factors affecting these changes. MethodsThis study retrospectively included 96 treatment-naïve PDR eyes of 96 type 2 diabetes mellitus patients [59 PRP and 37 IVC]. Baseline characteristics and treatment details were collected. Optical coherence tomography angiography (OCTA) data of macular vessel density (VD) and optic disc capillary density (CD) at baseline and at the last follow-up were compared between groups. The differences between the baseline and the last follow-up OCTA data in each group were also tested for significance. The correlation between the change in each OCTA parameter from baseline and each baseline characteristic/treatment parameter was investigated in each group. ResultsDuring a mean follow-up of two years, greater superficial (SCP) (p = 0.004) and deep capillary plexus (DCP) VD (p < 0.001) were observed in the foveal area in the PRP than in the IVC. Compared to the baseline, SCP VD in the foveal area increased in the PRP (p = 0.012), while an increased SCP VD in some sectors in the parafoveal and perifoveal areas (p < 0.05), rather than the foveal area (p = 0.908), was seen in the IVC. For both groups, eyes with a higher VD/CD at baseline tended to develop capillary dropout more intensively (all p < 0.05). In the IVC group, foveal avascular zone (FAZ) area change showed a negative correlation with baseline FAZ area (p = 0.020), and complementary PRP exerted a negative influence on FAZ area change (p = 0.002). In the PRP group, SCP VD change was positively correlated with follow-up frequency, and was negatively correlated with diastolic blood pressure (all p < 0.05); DCP VD change showed a positive correlation with PRP shot number (p = 0.019). ConclusionThe aforementioned microvasculature changes should be considered when PRP or IVC is adopted in PDR long-term management.

Early Retinal Microvascular Alterations in Young Type 1 Diabetic Patients without Clinical Retinopathy.

The purpose of this study is to identify and quantify preclinical changes with the help of optical coherence tomography angiography (OCTA) within the retinal microcirculation of young type 1 diabetes (T1D) patients without clinical signs of diabetic retinopathy (DR) and to compare these results with those obtained from healthy age-matched subjects. OCTA is currently used for monitoring diabetic retinopathy; however, there is no current consensus on which OCTA parameter alterations predict the first clinical signs of diabetic retinopathy. The main challenge that young patients with T1D face during the course of the disease is that they can rapidly progress to the development of DR, especially during adolescence. Moreover, they also present an increased risk of rapid progression toward advanced stages of DR and vision loss compared to type 2 diabetes patients, indicating the importance of early diagnosis and intervention. The limitations of the currently used screening procedures that led to the conceptualization of our study are the difficulties in performing fluorescein angiography tests for diagnosing the clinical signs of DR on young patients, namely the invasive procedure of dye injection, the risk of allergic reactions and the long duration of the examination. Moreover, given the long life expectancy of young T1D patients, it is essential to identify the preclinical changes in retinal microvasculature before reaching the first clinical signs quantifiable by FFA. The clinical study enrolled 119 subjects aged between 4 and 30 years old with a mean age of 13 years old, comprising 61 T1D patients with a mean duration of the disease of 4 years and 8 months and 58 healthy age-matched subjects for the control group. OCTA scans were performed using the RevoNX 130 OCTA device (Optopol) to evaluate the following retinal parameters: foveal avascular zone (FAZ) area, perimeter and circularity, overall foveal thickness, and superficial and deep vessel densities. Statistically significant differences between the two groups were identified for the following parameters: the FAZ area in the T1D group (0.42 ± 0.17) was larger than the control group (0.26 ± 0.080), the FAZ circularity (0.41 ± 0.11) was decreased compared to the control group (0.61 ± 0.08) and the FAZ perimeter was larger (3.63 ± 0.97) compared to the control group (2.30 ± 0.50). The overall foveal thickness was decreased in the T1D group (222.98 ± 17.33) compared to the control group (230.64 ± 20.82). The total vessel density of the superficial capillary plexus (SCP) on an investigated area of 6 X 6 mm centered around the fovea was decreased in the T1D group (37.4164 ± 2.14) compared to the control group (38.0241 ± 2.44). Our data suggest that specific imaging biomarkers such as FAZ perimeter, area and circularity, decreased overall foveal thickness and decreased vessel density in the SCP precede the clinical diagnosis of DR in young T1D patients and represent useful parameters in quantifying capillary nonperfusion in T1D patients without clinical signs of DR.

The association between diabetic retinopathy, cognitive impairment, and quality of life – a cross sectional study

BackgroundDiabetic retinopathy (DR), a microangiopathy caused by Type 2 Diabetes Mellitus (T2DM), is associated with significant visual disability leading to suboptimal quality of life. Retinal microvasculature changes can reflect similar changes in the grey matter and blood-brain barrier. Microvascular changes in the brain are associated with cognitive dysfunction. The present study aimed to find the association between Diabetic Retinopathy (DR) and Cognitive Impairment (CI) and its relationship with Quality of Life (QoL). MethodologyA cross-sectional observational study was conducted in a tertiary care hospital among patients (aged 18 years and above) with pre-existing T2DM as per Standards of Care in Diabetes-2023 criteria. Patients with visual acuity less than 3/60, or education below 6th grade, or with comorbid mental or neurocognitive disorders illness were excluded from the study. DR grading was done using the Early Treatment Diabetic Retinopathy Study (ETDRS) criteria. Cognitive functions and quality of life were measured using Montreal cognitive assessment (MoCA) and World Health Organization – Quality of Life scale – brief version (WHO-QOL BREF). The primary outcome measures (cognitive impairment and quality of life) were compared between patients with DR (DR+) and patients without DR (DR-). A P < 0.05 was considered statistically significant. ResultsDiabetic retinopathy was diagnosed in 48.5% (83 out of 171) of the sample. The DR+ group were predominantly male, significantly older, had comorbid immature cataract and hypertension than the DR- group. Also, the DR+ group had significantly reduced scores in all domains of MoCA and QoL. among patients with DR, those with severe and moderate NPDR had more cognitive impairment than mild NPDR. Age and duration of diabetes did not correlate with MoCA and QoL scores. ConclusionThe presence of diabetic retinopathy is associated with cognitive impairment and reduced quality of life in this study population. The association is independent of the age of patient and the duration of diabetes mellitus.

Deep segmentation of OCTA for evaluation and association of changes of retinal microvasculature with Alzheimer’s disease and mild cognitive impairment

BackgroundOptical coherence tomography angiography (OCTA) enables fast and non-invasive high-resolution imaging of retinal microvasculature and is suggested as a potential tool in the early detection of retinal microvascular changes in...

Combining retinal neuronal and microvascular measurements improves discriminative power for multiple sclerosis patients without previous optic neuritis

AbstractPurpose: Quantitative thinning of optic nerves and changes in retinal microvasculature have been detected in multiple sclerosis patients without optic neuritis (MSNON). However, data on how both retinal neuronal and microvascular parameters jointly influence the diagnostic performance is lacking. To investigate the diagnostic performance of neuronal and microvascular changes to detect the presence of MSNON from normal controls.Methods: This is a cross‐sectional study of 51 MS participants (n = 76 eyes) and 71 age‐ and sex‐matched healthy controls (n = 117 eyes). Retinal macular ganglion cell complex (GCC) and retinal nerve fibre layer (RNFL) thicknesses and capillary densities from the superficial (SCP) and deep capillary plexuses (DCP) were obtained from the optical coherence tomography (Cirrus AngioPlex model HD‐OCT 5000). We also compensated RNFL thickness for ocular anatomical factors. Thickness and vascular measurements and their corresponding areas under the receiver operating characteristic curves (AUCs) were compared between groups.Results: All retinal structural and vascular parameters were significantly altered in MS (p ≤ 0.012). The best neuronal parameter for detecting MS was compensated RNFL from the optic nerve head region (AUC = 0.85), followed by GCC from the macular region (AUC = 0.79) while the best microvasculature parameter was the SCP (AUC = 0.66). Combining retinal neuronal and microvascular parameters improved its diagnostic performance for MS detection (AUC = 0.90; P &lt; 0.001). The joint model including both neuronal and microvasculature significantly improved the discrimination between MS and normal compared with each parameter separately (p = 0.027).Conclusions: Combining retinal neuronal and microvasculature parameters improved the discrimination of MSNON. Further studies may be warranted to evaluate the clinical utility of retinal parameters in risk prediction for disease progression.

Optical coherence tomography angiography reveals retinal microvascular changes in patients with multiple sclerosis without optic neuritis

AbstractPurpose: Retinal imaging has attracted much interest as a non‐invasive low‐budget biomarker for neurological diseases such as multiple sclerosis (MS). Optical coherence tomography angiography (OCTA) is a functional extension of OCT and allows for the non‐invasive visualization of the retinal and choroidal microvasculature. We investigated retinal microvasculature changes in patients with relapsing–remitting MS (RRMS) without history of optic neuritis (ON) and compared them to a healthy control group.Methods: The study was performed in a prospective, case–control design, including 58 participants (n = 100 eyes) with RRMS without ON and 78 age‐ and sex‐matched control participants (n = 136 eyes). OCTA images of the superficial capillary plexus (SCP), deep capillary plexus (DCP) and choriocapillaris (CC) were obtained using a commercial OCTA system (Zeiss Cirrus HD‐5000 Spectral‐Domain OCT with AngioPlex OCTA, Carl Zeiss Meditec, Dublin, CA). Perfusion density (PD) and foveal avascular zone (FAZ) features (area and circularity) in both the SCP and DCP, as well as flow deficit in the CC were used as outcome variables.Results: MS patients showed significantly increased PD in SCP (p = 0.003) and decreased PD in DCP (p &lt; 0.001) as compared to controls when data were corrected for confounders. A significant difference was also noted when large vessels (LV) in the SCP were removed from the PD calculation (p = 0.004). Deep FAZ was significantly larger (p = 0.005) and less circular (p &lt; 0.001) in the eyes of MS patients compared to healthy controls. Neither LV, PD or FAZ features in the SCP, nor flow deficits in the CC showed any statistically significant differences between the MS patients and the controls (p &gt; 0.186).Conclusions: Our study shows that MS patients have microvascular changes in the macular parafoveal retina even without ON. They show increased PD in SCP and decreased PD in DCP. To which degree retinal biomarkers in MS are associated with the progression of MS remains to be studied.

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.

Comparative study on retinal microvasculature changes between acute and chronic central serous chorioretinopathy.

Central serous chorioretinopathy (CSC) is generally a common fundus disease in young and middle-aged Asian men. Acute and chronic CSC can lead to different degrees of injury to the retinal blood flow. This study aims to observe and compare the blood flow density in different retinal capillary layers in patients with acute and chronic CSC using optical coherence tomography angiography (OCTA) technology. Twelve patients with acute CSC and 8 patients with chronic CSC including 12 eyes with acute CSC (acute CSC eye group), 11 eyes with chronic CSC (chronic CSC eye group), and 17 normal eyes (normal eye group) were enrolled in this study. All patients underwent 3 mm×3 mm, 6 mm×6 mm macular OCTA scanning. The retinal microvascu-lature was divided into superficial vascular complexes (SVC), intermediate capillary plexuses (ICP), and deep capillary plexuses (DCP) using the projection resolved-OCTA algorithm. Inner retina includes SVC, ICP, and DCP. The vessel density in each retinal layer and the inner retina were calculated and compared. Macular OCTA scanning of 3 mm×3 mm showed that there was no significant difference in blood flow density of SVC and ICP among the 3 groups (both P>0.05); blood flow density of DCP and inner retina in the chronic CSC eye group was significantly lower than that in the acute CSC eye group and the normal eye group (all P<0.05); there was no significant difference in retinal blood flow density of different layer between the acute CSC eye group and the normal eye group (all P>0.05). Macular OCTA scanning of 6 mm×6 mm showed that inner retinal blood flow density of the chronic CSC eye group was significantly lower than that of the acute CSC eye group and the normal eye group (both P<0.05); there was no significant difference in blood flow density of SVC among the 3 groups (P>0.05). The vessel density of DCP and inner retina in the eyes with chronic CSC are significantly reduced, which may result in impaired visual function. Therefore, we recommend that patients with acute CSC should be properly treated to avoid progressing into chronic CSC.

Retinal microvasculature and imaging markers of brain frailty in normal aging adults.

BackgroundThe retina and brain share a similar embryologic origin, blood barriers, and microvasculature features. Thus, retinal imaging has been of interest in the aging population to help in the early detection of brain disorders. Imaging evaluation of brain frailty, including brain atrophy and markers of cerebral small vessel disease (CSVD), could reflect brain health in normal aging, but is costly and time-consuming. In this study, we aimed to evaluate the retinal microvasculature and its association with radiological indicators of brain frailty in normal aging adults.MethodsSwept-source optical coherence tomography angiography (SS-OCTA) and 3T-MRI brain scanning were performed on normal aging adults (aged ≥ 50 years). Using a deep learning algorithm, microvascular tortuosity (VT) and fractal dimension parameter (Dbox) were used to evaluate the superficial vascular complex (SVC) and deep vascular complex (DVC) of the retina. MRI markers of brain frailty include brain volumetric measures and CSVD markers that were assessed.ResultsOf the 139 normal aging individuals included, the mean age was 59.43 ± 7.31 years, and 64.0% (n = 89) of the participants were females. After adjustment of age, sex, and vascular risk factors, Dbox in the DVC showed a significant association with the presence of lacunes (β = 0.58, p = 0.007), while VT in the SVC significantly correlated with the score of cerebral deep white matter hyperintensity (β = 0.31, p = 0.027). No correlations were found between brain volumes and retinal microvasculature changes (P > 0.05).ConclusionOur report suggests that imaging of the retinal microvasculature may give clues to brain frailty in the aging population.

Association Between Retinal Microvascular Metrics Using Optical Coherence Tomography Angiography and Carotid Artery Stenosis in a Chinese Cohort.

Objectives: The main aim was to investigate the association between retinal microvascular metrics using optical coherence tomography angiography (OCTA) and carotid artery stenosis (CAS) in an aging Chinese cohort. Methods: In this cross-sectional and observational study, 138 eyes of 138 participants were examined. Indices of the microcirculation measured by OCTA included mean vessel density (VD), skeleton density (SD), vessel diameter index (VDI), fractal dimension (FD) and foveal avascular zone (FAZ) of the superficial retinal layer (SRL) and deep retinal layer (DRL), and peripapillary vessel caliber. The correlation of these indices with the carotid atherosclerotic lesions including carotid intima media thickness (CIMT) and common carotid artery (CCA) plaque was assessed. Results: A total of 72 of 138 eyes demonstrated an increased (≥1 mm) CIMT, and 32 of the eyes presented common carotid plaques. Macular VD, SD, and FD were decreased with the increasing CCA caliber diameter (p < 0.05, respectively). Superficial and deep macular FDs were negatively associated with CIMT as well as the existence of CCA plaques (p < 0.05, respectively). Conclusion: Changes in retinal microvasculature accessed by OCTA may be used as one of the non-invasive early indicators to monitor asymptomatic CAS.

System-wide vitreous proteome dissection reveals impaired sheddase activity in diabetic retinopathy.

Rationale: Diabetic retinopathy (DR) is a major complication of diabetes mellitus causing significant vision loss. DR is a multifactorial disease involving changes in retinal microvasculature and neuronal layers, and aberrations in vascular endothelial growth factors (VEGF) and inflammatory pathways. Despite the success of anti-VEGF therapy, many DR patients do not respond well to the treatment, emphasizing the involvement of other molecular players in neuronal and vascular aberrations in DR.Methods: We employed advanced mass spectrometry-based proteome profiling to obtain a global snapshot of altered protein abundances in vitreous humor from patients with proliferative DR (PDR) in comparison to individuals with epiretinal membrane without active DR or other retinal vascular complications. Global proteome correlation map and protein-protein interaction networks were used to probe into the functional inclination of proteins and aberrated molecular networks in PDR vitreous. In addition, peptide-centric analysis of the proteome data was carried out to identify proteolytic processing, primarily ectodomain shedding events in PDR vitreous. Functional validation experiments were performed using preclinical models of ocular angiogenesis.Results: The vitreous proteome landscape revealed distinct dysregulations in several metabolic, signaling, and immune networks in PDR. Systematic analysis of altered proteins uncovered specific impairment in ectodomain shedding of several transmembrane proteins playing critical roles in neurodegeneration and angiogenesis, pointing to defects in their regulating sheddases, particularly ADAM10, which emerged as the predominant sheddase. We confirmed that ADAM10 protease activity was reduced in animal models of ocular angiogenesis and established that activation of ADAM10 can suppress endothelial cell activation and angiogenesis. Furthermore, we identified the impaired ADAM10-AXL axis as a driver of retinal angiogenesis.Conclusion: We demonstrate restoration of aberrant ectodomain shedding as an effective strategy for treating PDR and propose ADAM10 as an attractive therapeutic target. In all, our study uncovered impaired ectodomain shedding as a prominent feature of PDR, opening new possibilities for advancement in the DR therapeutic space.

Retinal Microvasculature Changes in Patients With Coronary Total Occlusion on Optical Coherence Tomography Angiography.

Background: Retinal microvasculature has been associated with coronary artery disease (CAD), but the exact contributory role in coronary total occlusion (CTO) is unclear. We aimed to investigate whether retinal vasculature is associated with CTO and could provide incremental value in the assessment of CTO.Methods: A total of 218 CAD patients including 102 CTO and 116 non-CTO were enrolled. Retinal vasculature was measured by optical coherence tomography angiography (OCTA) for all patients. Receiver operating characteristic (ROC) curve was used to assess the performance of retinal vasculature in differentiating CTO from non-CTO patients.Results: In non-CTO CAD patients, vessel density (VD) of mean superficial capillary plexus (SCP) and parafovea SCP were 49.85 and 52.56%, respectively; in CTO patients, VD of mean SCP and parafovea SCP were 47.77, and 49.58%, respectively. After multiple adjustment, VD in the SCP was significantly lower in CTO patients compared to non-CTO patients. VD of superior hemi in the parafovea SCP combined with the clinical variates showed the best ability to predict CTO from CAD with an area under the curve (AUC) of 0.812 (specificity of 89.0% and sensitivity of 65.9%).Conclusions: In CTO patients, retinal VD was significantly decreased, and microvascular damage might specifically target to arterioles than capillaries. Retinal vasculature could thus be a surrogate for detecting the microvascular damage and assist in the assessment of CTO patients. OCTA examination could be suggested to monitor the process of coronary arteries lesions.

Change of Retinal Vessel Density After Lowering Intraocular Pressure in Ocular Hypertension.

Purpose: To investigate the relationship between retinal microvasculature changes and intraocular pressure (IOP) for ocular hypertension (OHT) patients and further assess the factors associated with retinal microcirculation changes.Methods: This was a single-center prospective study designed for OHT patients, which consisted of two visits. After collecting baseline data of those who met the eligibility criteria, these patients were treated with latanoprost 0.005% ophthalmic solution for 4 weeks. Peripapillary vessel density (VD) of radial peripapillary capillaries (RPC) layer, macular VD in both superficial and deep layers, and foveal avascular zone (FAZ) area were measured by optical coherence tomography angiography (OCTA) before and after the treatment. We compared the changes in IOP and VD among the two visits by paired-sample t-test. Bonferroni correction was applied. Factors associated with VD changes were analyzed by linear regression analysis.Results: Thirty-four eyes of thirty-four patients were included. The mean IOP decreased by 6.5 ± 2.2 mmHg (p < 0.001). The peripapillary RPC VD increased significantly from 51.8 ± 2.5 to 53.0 ± 3.1% (Adjusted-p = 0.012). We found no significant difference in detailed sectors of the peripapillary region after correction. In the macular area, both the superficial and deep layers in foveal (superficial: 0.2 ± 1.9%, p = 0.523; deep: 0.0 ± 2.3%, p = 0.969) and parafoveal (superficial: 0.3 ± 3.0%, p = 0.565; deep: 0.5 ± 3.1%, p = 0.423) VD remained unchanged. The decrease of the mean FAZ area was insignificant (p = 0.295). The percentage of IOP reduction (β = 0.330, p = 0.031) and the baseline RNFL thickness (β = 0.450, p = 0.004) significantly correlated with the percentage of peripapillary RPC VD improvement in the multivariate linear regression analysis.Conclusion: The peripapillary VD in OHT patients increased after the reduction of IOP. The mild change of IOP did not alter the microcirculation in the macula. In addition, the percentage of IOP change and the baseline RNFL thickness were independent factors for the peripapillary RPC VD improvement.

Retinal optical coherence tomography angiography findings of acute anterior uveitis.

To evaluate the changes in retinal microvasculature in eyes with anterior uveitis (AU) using optical coherence tomography angiography. Foveal avascular zone (FAZ) of superficial capillary plexus (SCP) and deep capillary plexus (DCP), vessel density (VD) of SCP, DCP, and choriocapillaris, and central macular thickness (CMT) and central foveal thickness (CFT) were calculated from 34 healthy and 41 uveitic eyes. The parameters were compared between the two groups. The deep FAZ was significantly smaller in the eyes with AU during the attack than after recovery and the control group (p = 0.001 and p = 0.003, respectively). The VD in deep capillary plexus (DCP) in eyes with AU during the attack was significantly higher than the control group (p = 0.048). The VD in the foveal sector of DCP in eyes with AU during the attack and after recovery was significantly higher than the control group (p = 0.001 and p = 0.031, respectively). There was no significant difference regarding CMT, CFT, VDs of each segment and each sector, and superficial and deep FAZ between eyes with first uveitis attack and those with recurrent uveitis during the attack and after recovery (p > 0.05). The results of this study show that there is a reduction in the FAZ and an increase in the VD of the DCP of the retina during active AU, and these findings are reversible. Acute AU may affect the macular microvasculature, which is usually temporary, especially in the DCP.

Quantitative evaluation of retinal microvasculature and retrobulbar vessels after intravenous chemotherapy for retinoblastoma

BackgroudTo evaluate the changes in retinal microvasculature and retrobulbar blood flow, using optical coherence tomography angiography (OCTA) and Color Doppler imaging (CDI) after intravenous chemotherapy (IVC) in patients with retinoblastoma (RB).MethodsThis was a retrospective comparative case control series involving 30 patients. Ten bilateral RB patients that had a preserved eye with extramacular tumours (group I), 10 unilateral RB treated with IVC that had a normal fellow study eye (group II), and 10 age-matched healthy controls. The macular retinal thickness, foveal avascular zone (FAZ) area, and the macular and peripapillary retinal vessel densities (RVD) were measured. The peak systolic and end diastolic velocities of the ophthalmic, central retinal and posterior ciliary arteries were determined. A comparison among the three groups was conducted.ResultsBetween the three cohorts, OCTA revealed no significant difference in FAZ area, superficial foveal and parafoveal RVD, deep parafoveal RVD and peripapillary RVD, (P > 0.05). By contrast, the mean deep foveal RVD, the full, inner and outer foveal and the parafoveal retinal thickness were significantly lower in group I compared with the controls, (P = 0.0329, 0.0153, 0.0311 0.0352, 0.0215). No significant difference in the blood flow velocities occurred in the retrobulbar circulation (P > 0.05).ConclusionsIn patients with retinoblastoma, OCTA did not detect significant changes of retinal thickness and vessel density in the eyes treated with IVC, but a slight reduction in retinal thickness and the deep foveal RVD seemed to occur in bilateral RB eyes. The retrobulbar blood flow parameters showed no measurable changes.

Histopathological assessments reveal retinal vascular changes, inflammation, and gliosis in patients with lethal COVID-19

PurposeThe purpose of this study is to assess for histopathological changes within the retina and the choroid and determine the long-term sequelae of the SARS-CoV-2 infection.MethodsEyes from seven COVID-19-positive and six similar age-matched control donors with a negative test for SARS-CoV-2 were assessed. Globes were evaluated ex vivo with macroscopic, SLO and OCT imaging. Macula and peripheral regions were processed for Epon embedding and immunocytochemistry.ResultsFundus analysis shows hemorrhagic spots and increased vitreous debris in several of the COVID-19 eyes compared to the controls. OCT-based measurements indicated an increased trend in retinal thickness in the COVID-19 eyes; however, the difference was not statistically significant. Histology of the retina showed presence of hemorrhages and central cystoid degeneration in several of the donors. Whole mount analysis of the retina labeled with markers showed changes in retinal microvasculature, increased inflammation, and gliosis in the COVID-19 eyes compared to the controls. The choroidal vasculature displayed localized changes in density and signs of increased inflammation in the COVID-19 samples.ConclusionsIn situ analysis of the retinal tissue suggests that there are severe subclinical abnormalities that could be detected in the COVID-19 eyes. This study provides a rationale for evaluating the ocular physiology of patients that have recovered from COVID-19 infections to further understand the long-term effects caused by this virus.