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Diabetes Apr 2022Microaneurysms are biomarkers of microvascular injury in diabetic retinopathy (DR). Impaired retinal capillary perfusion is a critical pathogenic mechanism in the...
Microaneurysms are biomarkers of microvascular injury in diabetic retinopathy (DR). Impaired retinal capillary perfusion is a critical pathogenic mechanism in the development of microvascular abnormalities. Targeting fundamental molecular disturbances resulting from capillary nonperfusion, such as increased vascular endothelial growth factor expression, does not always reverse the anatomic complications of DR, suggesting that other pathogenic mechanisms independent of perfusion also play a role. We stratify the effects of capillary nonperfusion, inflammation, and pericyte loss on microaneurysm size and leakage in DR through three-dimensional analysis of 636 microaneurysms using high-resolution confocal scanning laser microscopy. Capillary nonperfusion, pericyte loss, and inflammatory cells were found to be independent predictors of microaneurysm size. Nonperfusion alone without pericyte loss or inflammation was not a significant predictor of microaneurysm leakage. Microaneurysms found in regions without nonperfusion were significantly smaller than those found in regions with nonperfusion, and their size was not associated with pericyte loss or inflammation. In addition, microaneurysm size was a significant predictor of leakage in regions with nonperfusion only. This report refines our understanding of the disparate pathophysiologic mechanisms in DR and provides a histologic rationale for understanding treatment failure for microvascular complications in DR.
Topics: Diabetes Mellitus; Diabetic Retinopathy; Humans; Inflammation; Microaneurysm; Pericytes; Retinal Vessels; Vascular Endothelial Growth Factor A
PubMed: 35043147
DOI: 10.2337/db21-0737 -
Clinical Practice and Cases in... Aug 2022We present the case of an older male with point-of-care-ultrasound (POCUS) imaging consistent with retinal detachment who was instead found by ophthalmology to have a...
CASE PRESENTATION
We present the case of an older male with point-of-care-ultrasound (POCUS) imaging consistent with retinal detachment who was instead found by ophthalmology to have a ruptured arterial microaneurysm with vitreous and preretinal hemorrhage. The patient later had complete resolution of his symptoms. We discuss this retinal detachment "mimic."
DISCUSSION
Preretinal hemorrhage is an uncommon condition that can be mistaken for ophthalmologic emergencies such as retinal detachment. The images and videos shown here add to the body of evidence that POCUS is useful in diagnosing pre-retinal hemorrhage but must be differ-entiated from retinal detachment. These images also emphasize the need for further research and application of POCUS for the identification of preretinal hemorrhage.
PubMed: 36049192
DOI: 10.5811/cpcem2022.4.55301 -
Medicina (Kaunas, Lithuania) Feb 2023This study aims to elucidate the role of microaneurysms (MAs) in the pathogenesis and treatment of diabetic retinopathy (DR) and diabetic macular edema (DME), the major... (Review)
Review
This study aims to elucidate the role of microaneurysms (MAs) in the pathogenesis and treatment of diabetic retinopathy (DR) and diabetic macular edema (DME), the major causes of acquired visual impairment. We synthesized the relevance of findings on the clinical characteristics, pathogenesis, and etiology of MAs in DR and DME and their role in anti-vascular endothelial growth factor (VEGF) therapy. MAs, a characteristic feature in DR and DME, can be detected by fluorescein angiography, optical coherence tomography (OCT) and OCT angiography. These instrumental analyses demonstrated a geographic and functional association between MA and ischemic areas. MA turnover, the production and loss of MA, reflects the activity of DME and DR. Several cytokines are involved in the pathogenesis of MAs, which is characterized by pericyte loss and endothelial cell proliferation in a VEGF-dependent or -independent manner. Ischemia and MAs localized in the deep retinal layers are characteristic of refractory DME cases. Even in the current anti-VEGF era, laser photocoagulation targeting MAs in the focal residual edema is still an effective therapeutic tool, but it is necessary to be creative in accurately identifying the location of MAs and performing highly precise and minimally invasive coagulation. MAs play a distinctive and important role in the pathogenesis of the onset, progression of DR and DME, and response to anti-VEGF treatment. Further research on MA is significant not only for understanding the pathogenesis of DME but also for improving the effectiveness of treatment.
Topics: Humans; Diabetic Retinopathy; Macular Edema; Microaneurysm; Retina; Fluorescein Angiography; Tomography, Optical Coherence; Diabetes Mellitus
PubMed: 36984436
DOI: 10.3390/medicina59030435 -
Case Reports in Nephrology and Dialysis 2021Nintedanib is a unique tyrosine kinase inhibitor used to suppress fibrosis in patients with idiopathic pulmonary fibrosis (IPF). Nintedanib has been shown to suppress...
Nintedanib is a unique tyrosine kinase inhibitor used to suppress fibrosis in patients with idiopathic pulmonary fibrosis (IPF). Nintedanib has been shown to suppress multiple processes of fibrosis, thereby reducing the rate of lung function decline in patients with IPF. Since vascular endothelial growth factor is one of this agent's targets, nephrotoxicity, including renal thrombotic microangiopathy (TMA), is a possible major adverse effect. However, only 2 previous cases of nintedanib-induced renal TMA have been published. Our patient was an 83-year-old man with IPF. As adverse effects including liver enzyme level elevation, diarrhoea, anorexia, and nephrotoxicity developed, the nintedanib dosage was reduced after 9 months. The digestive symptoms resolved promptly, but the proteinuria and reduced kidney function remained. Although the kidney injury had improved to some extent, we performed a percutaneous renal biopsy. The biopsy revealed typical TMA findings such as microaneurysms filled with pale material, segmental double contours of glomerular basement membranes, and intracapillary foam cells. After discontinuation of nintedanib, the patient's nephrotoxicity improved. Nintedanib-induced renal TMA is reversible and is possibly dose-dependent. Here, we report the clinical course of our case and review the characteristics of nintedanib-induced renal TMA.
PubMed: 34414215
DOI: 10.1159/000517692 -
International Journal of Retina and... 2017In diabetic retinopathy (DR), macular involvement can present as either macular edema or ischemia. Fluorescein angiography remains the gold standard in the evaluation of... (Review)
Review
In diabetic retinopathy (DR), macular involvement can present as either macular edema or ischemia. Fluorescein angiography remains the gold standard in the evaluation of retinal vascular perfusion and diagnosis of macular ischemia. However, it is a costly, time-consuming technique, it requires venipuncture, and reports of anaphylaxis and death related to fluorescein injections have been documented, despite their rarity. Optical coherence tomography (OCT) provides a fast and non-invasive method to assess retinal structures at a microscopic level. OCT angiography permits the noninvasive study of retinal and choroid circulation via motion contrast imaging. Split-spectrum amplitude decorrelation angiography combined with OCT angiography has furthered the understanding of retinal and choroidal vascular diseases, allowing the evaluation of retinal microvasculature and identification of subsequent disorders, including DR. Previous studies using OCT angiography have demonstrated that it may demonstrate DR findings such as microaneurysms, arteriolar wall staining, retinal neovascularization, and intraretinal microvascular abnormalities. The purpose of this article is to describe and discuss different concepts regarding OCT angiography, as well as its role in the diagnosis of DR and maculopathy.
PubMed: 28293432
DOI: 10.1186/s40942-017-0062-2 -
Ophthalmology. Retina Jan 2020To examine the relationship between diabetic macular edema (DME) and quantitative ultra-widefield fluorescein angiography (UWFA) metrics of ischemia, leakage, and...
PURPOSE
To examine the relationship between diabetic macular edema (DME) and quantitative ultra-widefield fluorescein angiography (UWFA) metrics of ischemia, leakage, and microaneurysms.
DESIGN
Retrospective image analysis study.
PARTICIPANTS
Eyes with diabetic retinopathy that had undergone spectral-domain OCT, UWFA, and ultra-widefield fundus photography.
METHODS
OCT images were analyzed to determine the presence or absence of DME, central subfield thickness (CST), and subretinal fluid. Using a semiautomated analysis platform, UWFA images were segmented for ischemia, leakage, and microaneurysms with manual correction as needed. Clinical variables, including age, gender, race, hemoglobin A1C levels, blood pressure, cholesterol levels, use of blood thinners, smoking status, and lens status also were evaluated.
MAIN OUTCOME MEASURES
Factors associated with the presence and severity of DME.
RESULTS
A total of 304 eyes (156 right eyes, 148 left eyes) from 178 diabetic patients were analyzed in the study. Panretinal leakage index, microaneurysm count, and ischemic index were not significantly different between eyes with and without DME in univariate assessment. Zonal assessments of macular microaneurysms and macular leakage index values revealed that eyes with DME showed a significantly higher microaneurysm count (P = 0.001) and leakage index (P < 0.0001) in the posterior pole compared with eyes without DME. Severity of macular thickening (i.e., CST) was associated significantly with macular leakage index and posterior pole microaneurysm count (P = 0.0002 and P = 0.03, respectively). In addition to posterior pole leakage index and microaneurysm count, DME was associated with older age (P < 0.01), higher systolic blood pressure (P < 0.001), and white race (P = 0.03). Multivariate assessment confirmed the independent association of presence of DME with macular leakage index and macular microaneurysm count (P < 0.01).
CONCLUSIONS
Quantitative measures of leakage index and microaneurysm count in the posterior pole on UWFA images were associated with the presence and severity of DME. Panretinal analyses were not linked to DME as strongly. Additional research is needed to determine the role of quantitative UWFA in predicting DME development and characterizing patient prognosis.
Topics: Diabetic Retinopathy; Female; Fluorescein Angiography; Fundus Oculi; Humans; Macula Lutea; Macular Edema; Male; Middle Aged; Reproducibility of Results; Retrospective Studies; Visual Acuity
PubMed: 31690541
DOI: 10.1016/j.oret.2019.08.008 -
FEBS Letters Apr 2023Senile plaques are a pathological hallmark of Alzheimer's disease (AD), yet the mechanism underlying their generation remains unknown. Beta-amyloid peptide (Aβ) is a...
Senile plaques are a pathological hallmark of Alzheimer's disease (AD), yet the mechanism underlying their generation remains unknown. Beta-amyloid peptide (Aβ) is a major component of senile plaques. We analysed AD brain tissues with histochemistry, immunohistochemistry and fluorescence imaging to examine the neural, vascular or blood Aβ contribution to senile plaque development. We found little neural marker co-expression with plaque Aβ, while co-expression of blood markers, such as Haemin and ApoE, was abundant. The plaque cores were structured with vascular and glial proteins outside and blood metabolites inside, co-localizing with a characteristic of Hoechst staining-independent blue autofluorescence. Erythrocyte-interacting Aβ is linked to coagulation, elevated calcium and blue autofluorescence, and it is associated with intravascular haemolysis, atherosclerosis, cerebral amyloid angiopathy, microaneurysm, and often with Cathepsin D co-expression. We identified microaneurysms as major sites of amyloid formation. Our data suggest that senile plaques arise from Aβ- and Cathepsin D-enriched mixtures leaking out during intravascular haemolysis and microaneurysm rupture.
Topics: Humans; Alzheimer Disease; Plaque, Amyloid; Microaneurysm; Cathepsin D; Hemolysis; Amyloid beta-Peptides; Brain
PubMed: 36448495
DOI: 10.1002/1873-3468.14549 -
ArXiv Oct 2023Microaneurysms (MAs) have distinct, oval-shaped, hyperreflective walls on structural OCT, and inconsistent flow signal in the lumen with OCT angiography (OCTA). Their...
PURPOSE
Microaneurysms (MAs) have distinct, oval-shaped, hyperreflective walls on structural OCT, and inconsistent flow signal in the lumen with OCT angiography (OCTA). Their relationship to regional macular edema in diabetic retinopathy (DR) has not been quantitatively explored.
DESIGN
Retrospective, cross-sectional study.
PARTICIPANTS
A total of 99 participants, including 23 with mild, nonproliferative DR (NPDR), 25 with moderate NPDR, 34 with severe NPDR, and 17 with proliferative DR.
METHODS
We obtained 3 × 3-mm scans with a commercial device (Solix, Visionix/Optovue) in 99 patients with DR. Trained graders manually identified MAs and their location relative to the anatomic layers from cross-sectional OCT. Microaneurysms were first classified as perfused if flow signal was present in the OCTA channel. Then, perfused MAs were further classified into fully and partially perfused MAs based on the flow characteristics in OCTA. The presence of retinal fluid based on OCT near MAs was compared between perfused and nonperfused types. We also compared OCT-based MA detection to fundus photography (FP)- and fluorescein angiography (FA)-based detection.
MAIN OUTCOME MEASURES
OCT-identified MAs can be classified according to colocalized OCTA flow signal into fully perfused, partially perfused, and nonperfused types. Fully perfused MAs may be more likely to be associated with diabetic macular edema (DME) than those without flow.
RESULTS
We identified 308 MAs (166 fully perfused, 88 partially perfused, 54 nonperfused) in 42 eyes using OCT and OCTA. Nearly half of the MAs identified in this study straddle the inner nuclear layer and outer plexiform layer. Compared with partially perfused and nonperfused MAs, fully perfused MAs were more likely to be associated with local retinal fluid. The associated fluid volumes were larger with fully perfused MAs compared with other types. OCT/OCTA detected all MAs found on FP. Although not all MAs seen with FA were identified with OCT, some MAs seen with OCT were not visible with FA or FP.
CONCLUSIONS
OCT-identified MAs with colocalized flow on OCTA are more likely to be associated with DME than those without flow.
FINANCIAL DISCLOSURES
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article. ;■- © (http://creativecommons.org/licenses/by-nc-nd/4.0/).
PubMed: 37873013
DOI: No ID Found -
Inflammopharmacology Apr 2023Diabetic retinopathy is regarded as a common manifestation of diabetes mellitus, being a prominent cause of visual impairment and blindness. This microvascular... (Review)
Review
Diabetic retinopathy is regarded as a common manifestation of diabetes mellitus, being a prominent cause of visual impairment and blindness. This microvascular complication is marked by the appearance of microaneurysms, elevated vascular permeability, capillary blockage, and proliferation of neovasculature. The etiology behind retinopathy is ambiguous and the efficacy of current treatment strategies is minimal. Early diagnosis of this complication using a biomarker with high sensitivity and specificity is very essential for providing better therapeutic strategies. The current available therapeutic options are limited with various adverse effects. Laser treatment is not beneficial in all the situations, economic constraints being the major challenge. Surgical interventions are employed when pharmacotherapy and laser treatment fail. New pharmacological treatments are becoming a necessity for treating the condition. This review highlights the use of various diagnostic tools, emerging biomarkers for early detection of diabetic retinopathy, pathological mechanisms associated with the disease, current therapeutic approaches used and future strategies for more enhanced treatment options and more potent pharmacological actions.
Topics: Humans; Diabetic Retinopathy; Biomarkers; Diabetes Mellitus
PubMed: 36745243
DOI: 10.1007/s10787-023-01143-x -
BMC Ophthalmology Oct 2020To investigate the clinical features of diabetic macular edema (DME) in eyes with pachychoroid phenotypes using multimodal retinal imaging.
BACKGROUND
To investigate the clinical features of diabetic macular edema (DME) in eyes with pachychoroid phenotypes using multimodal retinal imaging.
METHODS
We retrospectively reviewed 210 eyes from 210 DME patients and analyzed the clinical and imaging parameters, including visual acuity, central macular thickness (CMT), subfoveal choroidal thickness (SFCT) and neural retina layer thickness (NRT). The DME eyes were divided into two groups: group 1 (80 eyes with submacular detachment [SMD]) and group 2 (130 eyes without SMD). The clinical and imaging parameters of 285 eyes from 285 diabetic patients without DME were collected as a control group.
RESULTS
DME eyes with pachychoroid phenotypes were more frequent in group 1 than in group 2 (53 eyes [66.25%] and 53 eyes [40.77%], respectively, P < 0.001). Pachychoroid phenotypes were identified in 108 (37.90%) of the control eyes. CMT and NRT were greater in group 1 than in group 2. In group 1, 37 eyes had SMD combined with focal edema, and 43 eyes had SMD combined with diffuse-type edema. No significant difference in pachychoroid phenotypes was found between the focal and diffuse types (26 [70.27%] and 27 [62.79%], respectively, P = 0.481). In group 2, 70 eyes had focal-type edema, and 60 eyes had diffuse-type edema. No significant difference in the frequency of pachychoroid phenotypes was found (32 [45.71%] and 21 [35.00%], respectively, P = 0.215). Interestingly, among the 70 eyes with focal edema in group 2, 13 (40.6%) and 5 (13.2%) eyes with and without pachychoroid phenotypes showed no definite microaneurysms, respectively.
CONCLUSION
SMD and focal edema without definite microaneurysms may be clinical manifestations of DME with pachychoroid phenotypes and possibly related to choroidal circulation disturbance in DME.
Topics: Choroid; Diabetes Mellitus; Diabetic Retinopathy; Humans; Macular Edema; Retrospective Studies; Tomography, Optical Coherence
PubMed: 33008430
DOI: 10.1186/s12886-020-01663-y