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OTO Open 2023We investigated the association between retinal microvascular changes and hearing loss based on the hypothesis that both may result from shared microvascular pathology....
We investigated the association between retinal microvascular changes and hearing loss based on the hypothesis that both may result from shared microvascular pathology. Data from 536 older adults from the National Health and Nutritional Examination Survey 2005 to 2006 including sociodemographic and health characteristics, pure-tone hearing thresholds, and retinal pathologies were collected and analyzed. Associations between retinal and hearing pathologies were modeled with multivariable-adjusted linear regressions. 75% of participants had hearing loss and 15% of participants had retinopathy. The association between retinopathy, microaneurysms, and blot hemorrhages with better speech-frequency pure tone average was -2.81 (95% confidence interval [CI]: -5.72 to 0.10), -4.75 (95% CI: -8.73 to -0.78), and -5.34 (95% CI: -8.68 to -2.00), respectively. The presence of retinopathy, microaneurysms, and blot hemorrhages was inversely associated with hearing loss. Further studies are needed to better understand the potential relationship between microvascular pathologies of the eye and ear.
PubMed: 38093719
DOI: 10.1002/oto2.99 -
Nature Communications Dec 2023We report the case of a 79-year-old woman with Alzheimer's disease who participated in a Phase III randomized controlled trial called CLARITY-AD testing the experimental...
We report the case of a 79-year-old woman with Alzheimer's disease who participated in a Phase III randomized controlled trial called CLARITY-AD testing the experimental drug lecanemab. She was randomized to the placebo group and subsequently enrolled in an open-label extension which guaranteed she received the active drug. After the third biweekly infusion, she suffered a seizure characterized by speech arrest and a generalized convulsion. Magnetic resonance imaging revealed she had multifocal swelling and a marked increase in the number of cerebral microhemorrhages. She was treated with an antiepileptic regimen and high-dose intravenous corticosteroids but continued to worsen and died after 5 days. Post-mortem MRI confirmed extensive microhemorrhages in the temporal, parietal and occipital lobes. The autopsy confirmed the presence of two copies of APOE4, a gene associated with a higher risk of Alzheimer's disease, and neuropathological features of moderate severity Alzheimer's disease and severe cerebral amyloid angiopathy with perivascular lymphocytic infiltrates, reactive macrophages and fibrinoid degeneration of vessel walls. There were deposits of β-amyloid in meningeal vessels and penetrating arterioles with numerous microaneurysms. We conclude that the patient likely died as a result of severe cerebral amyloid-related inflammation.
Topics: Aged; Female; Humans; Alzheimer Disease; Amyloid beta-Peptides; Arteritis; Brain; Cerebral Amyloid Angiopathy; Iatrogenic Disease; Vasculitis, Central Nervous System; Clinical Trials, Phase III as Topic; Randomized Controlled Trials as Topic
PubMed: 38086820
DOI: 10.1038/s41467-023-43933-5 -
Diagnostics (Basel, Switzerland) Nov 2023The aims of this study were to evaluate the feasibility of allergy test dosage of fluorescein sodium (1%) for Diabetic Retinopathy (DR) detection in Fundus Fluorescein...
BACKGROUND
The aims of this study were to evaluate the feasibility of allergy test dosage of fluorescein sodium (1%) for Diabetic Retinopathy (DR) detection in Fundus Fluorescein Angiography (FFA) examination as compared to the regular dosage (20%).
METHODS
Totally 77 eyes from 42 DR patients were included in this prospective study. Capillary non-perfusion area, neovascularization, diabetic macular edema and microaneurysms were measured by FFA and compared at 1, 5 and 15 min after intravenous injection of 1% or 20% fluorescein sodium.
RESULTS
There was no statistically significant difference in the proportions of capillary non-perfusion area and diabetic macular edema as well as the amount of neovascularization between the 1% and 20% fluorescein sodium groups. Yet, the 1% group had a significantly a smaller number of microaneurysms than the 20% group at 1 min ( < 0.001) and a smaller number of eyes with diabetic macular edema than the 20% group at 5 ( = 0.032) and 15 min ( = 0.015). The images from patients with clear vitreous had better quality than the images from patients with vitreous opacity (all < 0.05, except comparison on neovascularization at 5 min: > 0.999). All examined indexes showed high correlations between the 1% and 20% groups (r > 0.8, < 0.001).
CONCLUSIONS
This study demonstrated that 1% fluorescein sodium could detect the changes of DR comparably to the regular dosage.
PubMed: 38066760
DOI: 10.3390/diagnostics13233519 -
Vascular Medicine (London, England) Apr 2024This study aimed to review the current literature exploring the utility of noninvasive ocular imaging for the diagnosis of peripheral artery disease (PAD). Our search... (Review)
Review
This study aimed to review the current literature exploring the utility of noninvasive ocular imaging for the diagnosis of peripheral artery disease (PAD). Our search was conducted in early April 2022 and included the databases Medline, Scopus, Embase, Cochrane, and others. Five articles were included in the final review. Of the five studies that used ocular imaging in PAD, two studies used retinal color fundus photography, one used optical coherence tomography (OCT), and two used optical coherence tomography angiography (OCTA) to assess the ocular changes in PAD. PAD was associated with both structural and functional changes in the retina. Structural alterations around the optic disc and temporal retinal vascular arcades were seen in color fundus photography of patients with PAD compared to healthy individuals. The presence of retinal hemorrhages, exudates, and microaneurysms in color fundus photography was associated with an increased future risk of PAD, especially the severe form of the disease. The retinal nerve fiber layer (RNFL) was significantly thinner in the nasal quadrant in patients with PAD compared to age-matched healthy individuals in OCT. Similarly, the choroidal thickness in the subfoveal region was significantly thinner in patients with PAD compared to controls. Patients with PAD also had a significant reduction in the retinal and choroidal circulation in OCTA compared to healthy controls. As PAD causes thinning and ischemic changes in retinal vessels, examination of the retinal vessels using retinal imaging techniques can provide useful information about early microvascular damage in PAD. Ocular imaging could potentially serve as a biomarker for PAD. .
Topics: Humans; Optic Disk; Tomography, Optical Coherence; Photography; Peripheral Arterial Disease; Biomarkers; Retinal Vessels
PubMed: 38054219
DOI: 10.1177/1358863X231210866 -
The Journal of Clinical Investigation Jan 2024Vascular aging affects multiple organ systems, including the brain, where it can lead to vascular dementia. However, a concrete understanding of how aging specifically...
Vascular aging affects multiple organ systems, including the brain, where it can lead to vascular dementia. However, a concrete understanding of how aging specifically affects the brain vasculature, along with molecular readouts, remains vastly incomplete. Here, we demonstrate that aging is associated with a marked decline in Notch3 signaling in both murine and human brain vessels. To clarify the consequences of Notch3 loss in the brain vasculature, we used single-cell transcriptomics and found that Notch3 inactivation alters regulation of calcium and contractile function and promotes a notable increase in extracellular matrix. These alterations adversely impact vascular reactivity, manifesting as dilation, tortuosity, microaneurysms, and decreased cerebral blood flow, as observed by MRI. Combined, these vascular impairments hinder glymphatic flow and result in buildup of glycosaminoglycans within the brain parenchyma. Remarkably, this phenomenon mirrors a key pathological feature found in brains of patients with CADASIL, a hereditary vascular dementia associated with NOTCH3 missense mutations. Additionally, single-cell RNA sequencing of the neuronal compartment in aging Notch3-null mice unveiled patterns reminiscent of those observed in neurodegenerative diseases. These findings offer direct evidence that age-related NOTCH3 deficiencies trigger a progressive decline in vascular function, subsequently affecting glymphatic flow and culminating in neurodegeneration.
Topics: Animals; Humans; Mice; Brain; CADASIL; Dementia, Vascular; Mice, Knockout; Mutation; Receptor, Notch3
PubMed: 38015629
DOI: 10.1172/JCI166134 -
Journal of Clinical Medicine Nov 2023Microvascular disorders represent an uncommon site of tissue hypo-perfusion and damage. Various genetic and acquired causes can be involved. A 65-year-old man was...
BACKGROUND
Microvascular disorders represent an uncommon site of tissue hypo-perfusion and damage. Various genetic and acquired causes can be involved. A 65-year-old man was admitted because of refractory angina, which he had had since the age of 30 years, micro-hematuria, and recurrent transitory ischemic attacks from the age of 64.
METHODS
Hematochemical studies, ECG, Holter monitoring, 2D-echo, cardiac magnetic resonance (CMR), CTA of cerebral vessels, endomyocardial coronary angiography, and kidney biopsy processes were undertaken. Gene mutation analysis was conducted using next-generation sequencing, which included more than 5000 genes associated with inherited diseases.
RESULTS
Hematochemical findings were unremarkable. The ECG, Holter, 2D-echo, and CTA of brain vessels were normal. Cerebral magnetic resonance showed the presence of multiple small foci of ischemia. Coronary and ventricular angiography showed normal arteries with remarkably slow flow and multiple biventricular micro-aneurysms. At the endomyocardial biopsy, five of seven arterioles presented severe lumen obstruction due to hypertrophy and disarray of the muscular coat. Similarly, obstructed pre-glomerular arteries with glomerular sclerosis were seen at the renal biopsy. Genetics identified mutations in the ABCC6, MMP2, and XYLT1 genes, which play pivotal roles in the extracellular matrix.
CONCLUSION
This study described a new genetic microvascular obstructive disease causing progressive hypo-perfusion of the human brain, heart, and kidney.
PubMed: 38002762
DOI: 10.3390/jcm12227150 -
Diagnostics (Basel, Switzerland) Nov 2023Diseases such as diabetes affect the retinal vasculature and the health of the neural retina, leading to vision problems. We describe here an imaging method and analysis...
Diseases such as diabetes affect the retinal vasculature and the health of the neural retina, leading to vision problems. We describe here an imaging method and analysis procedure that enables characterization of the retinal vessel walls with cellular-level resolution, potentially providing markers for eye diseases. Adaptive optics scanning laser ophthalmoscopy is used with a modified detection scheme to include four simultaneous offset aperture channels. The magnitude of the phase gradient derived from these offset images is used to visualize the structural characteristics of the vessels. The average standard deviation image provides motion contrast and enables segmentation of the vessel lumen. Segmentation of blood vessel walls provides quantitative measures of geometrical characteristics of the vessel walls, including vessel and lumen diameters, wall thickness, and wall-to-lumen ratio. Retinal diseases may affect the structural integrity of the vessel walls, their elasticity, their permeability, and their geometrical characteristics. The ability to measure these changes is valuable for understanding the vascular effects of retinal diseases, monitoring disease progression, and drug testing. In addition, loss of structural integrity of the blood vessel wall may result in microaneurysms, a hallmark lesion of diabetic retinopathy, which may rupture or leak and further create vision impairment. Early identification of such structural abnormalities may open new treatment avenues for disease management and vision preservation. Functional testing of retinal circuitry through high-resolution measurement of vasodilation as a response to controlled light stimulation of the retina (neurovascular coupling) is another application of our method and can provide an unbiased evaluation of one's vision and enable early detection of retinal diseases and monitoring treatment results.
PubMed: 37998535
DOI: 10.3390/diagnostics13223399 -
World Journal of Diabetes Oct 2023Diabetes mellitus is one of the most common causes of chronic kidney disease. Kidney involvement in patients with diabetes has a wide spectrum of clinical presentations... (Review)
Review
Diabetes mellitus is one of the most common causes of chronic kidney disease. Kidney involvement in patients with diabetes has a wide spectrum of clinical presentations ranging from asymptomatic to overt proteinuria and kidney failure. The development of kidney disease in diabetes is associated with structural changes in multiple kidney compartments, such as the vascular system and glomeruli. Glomerular alterations include thickening of the glomerular basement membrane, loss of podocytes, and segmental mesangiolysis, which may lead to microaneurysms and the development of pathognomonic Kimmelstiel-Wilson nodules. Beyond lesions directly related to diabetes, awareness of the possible coexistence of nondiabetic kidney disease in patients with diabetes is increasing. These nondiabetic lesions include focal segmental glomerulosclerosis, IgA nephropathy, and other primary or secondary renal disorders. Differential diagnosis of these conditions is crucial in guiding clinical management and therapeutic approaches. However, the relationship between diabetes and the kidney is bidirectional; thus, new-onset diabetes may also occur as a complication of the treatment in patients with renal diseases. Here, we review the complex and multifaceted correlation between diabetes and kidney diseases and discuss clinical presentation and course, differential diagnosis, and therapeutic oppor-tunities offered by novel drugs.
PubMed: 37970131
DOI: 10.4239/wjd.v14.i10.1450 -
Scientific Reports Nov 2023Coats' disease is an idiopathic retinal vascular disorder, known to usually occur unilaterally; however, recent studies have highlighted vascular abnormalities in the...
Coats' disease is an idiopathic retinal vascular disorder, known to usually occur unilaterally; however, recent studies have highlighted vascular abnormalities in the fellow unaffected eyes. This retrospective study investigated the peripheral vascular features and macular vascular structure of unaffected fellow eyes in patients with unilateral Coats' disease using multimodal imaging tools. We analysed images of patients, including bilateral ultra-widefield imaging, fluorescein angiography (FA), ultra-widefield FA, or standard fundus photography. Available bilateral optical coherence tomography angiography (OCT-A) images were used for macular vascular structure analysis. OCT-A parameters, including foveal avascular zone (FAZ), perfusion index, and vessel density (VD) in the superficial and deep capillary plexuses (SCP, DCP), were calculated using Image J software. The mean age at diagnosis was 34.5 ± 17.9 years. The mean final best-corrected visual acuity of the affected eyes was logMAR 0.78 ± 0.79, while that of the fellow eyes was logMAR 0.04 ± 0.12. Ten fellow eyes had microaneurysms (47.6%), two had tortuous vessel abnormalities (9.5%), and 11(52.4%) had abnormal vascular findings on FA. Although there was a trend towards larger DCP FAZ (1.201 ± 0.086 vs. 1.072 ± 0.226), and lower DCP VD (8.593 ± 1.583 vs. 10.827 ± 3.392) in the affected eyes as measured by the Cirrus machine, the difference was not statistically significant between affected and fellow eyes when measured using the Zeiss Cirrus machine (P = 0.686, P = 0.343, respectively). However, when measured with the Spectralis machine, DCP FAZ was larger in affected eyes (0.828 ± 0.426 vs. 0.254 ± 0.092, P = 0.002) and DCP VD was lower in affected eyes (6.901 ± 2.634 vs. 17.451 ± 7.207, P = 0.002) compared to the fellow eyes, while other parameters showed no significant variations. These findings indicate that there may be subtle vascular abnormalities primarily located in the peripheral regions of the unaffected fellow eyes in patients with unilateral Coats' disease, while the macular microvasculature remains unaffected.
Topics: Humans; Adolescent; Young Adult; Adult; Middle Aged; Retinal Telangiectasis; Retrospective Studies; Tomography, Optical Coherence; Fluorescein Angiography; Macula Lutea
PubMed: 37938623
DOI: 10.1038/s41598-023-45838-1 -
Medicine Nov 2023Although anti-vascular endothelial growth factor (VEGF) treatment is effective for treating diabetic macular edema (DME), the effect of the microaneurysm (MA) status on...
Although anti-vascular endothelial growth factor (VEGF) treatment is effective for treating diabetic macular edema (DME), the effect of the microaneurysm (MA) status on the therapeutic efficacy of an anti-VEGF treatment remains unclear. Our current study investigated the effects of the number and the presence or absence of leaking MAs on DME and the efficacy of anti-VEGF therapy. A total of 51 eyes of 47 DME patients were administered anti-VEGF treatment. Fluorescence angiography results were used to determine the number of MAs and the presence or absence of leakage, with these findings matched to the optical coherence tomography maps. The correlation between the number of MAs and the retinal thicknesses and the influence of the leaking MAs was examined in order to definitively determine the effect of the anti-VEGF treatment. There was a correlation between the number of MAs and the retinal thickness of the sector in both the 6 mm (correlation coefficients: 0.42) and 3 mm (0.34) sectors (P < .001). There was also a correlation between the number of MAs and the retinal thickness in both the 6 mm (0.31) and 3 mm (0.24) sectors after undergoing the treatment (P < .01). There was a significant difference between the mean thickness of the leaking versus the non-leaking MAs in the 6 mm (388 ± 87 μm) and 3 mm (477 ± 108 μm) sectors before treatment (P < .01). There was also a significant difference for the retinal thickness between the sectors with and without leaking MAs after the treatment (P < .01). The degree of retinal edema before treatment is associated with the number of MAs and the presence of leaking MAs. Anti-VEGF treatment is less effective for focal macular edema with large numbers of MAs, which includes leaking MAs.
Topics: Humans; Macular Edema; Diabetic Retinopathy; Cross-Sectional Studies; Retrospective Studies; Angiogenesis Inhibitors; Microaneurysm; Retina; Fluorescein Angiography; Vascular Endothelial Growth Factors; Tomography, Optical Coherence; Intravitreal Injections; Diabetes Mellitus
PubMed: 37932987
DOI: 10.1097/MD.0000000000035888