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Eye (London, England) Jan 2021Diabetic retinopathy (DR) is a common microvascular complication of diabetes mellitus. Optical coherence tomography angiography (OCTA) has been developed to visualize... (Review)
Review
Diabetic retinopathy (DR) is a common microvascular complication of diabetes mellitus. Optical coherence tomography angiography (OCTA) has been developed to visualize the retinal microvasculature and choriocapillaris based on the motion contrast of circulating blood cells. Depth-resolved ability and non-invasive nature of OCTA allow for repeated examinations and visualization of microvasculature at the retinal capillary plexuses and choriocapillaris. OCTA enables quantification of microvascular alterations in the retinal capillary network, in addition to the detection of classical features associated with DR, including microaneurysms, intraretinal microvascular abnormalities, and neovascularization. OCTA has a promising role as an objective tool for quantifying extent of microvascular damage and identify eyes with diabetic macular ischaemia contributed to visual loss. Furthermore, OCTA can identify preclinical microvascular abnormalities preceding the onset of clinically detectable DR. In this review, we focused on the applications of OCTA derived quantitative metrics that are relevant to early detection, staging and progression of DR. Advancement of OCTA technology in clinical research will ultimately lead to enhancement of individualised management of DR and prevention of visual impairment in patients with diabetes.
Topics: Diabetes Mellitus; Diabetic Retinopathy; Fluorescein Angiography; Humans; Microaneurysm; Retinal Vessels; Tomography, Optical Coherence
PubMed: 33099579
DOI: 10.1038/s41433-020-01233-y -
Investigative Ophthalmology & Visual... Oct 2023Microaneurysm (MA) plays an important role in the pathogenesis of diabetic macular edema (DME) progression and response to anti-vascular endothelial growth factor (VEGF)...
PURPOSE
Microaneurysm (MA) plays an important role in the pathogenesis of diabetic macular edema (DME) progression and response to anti-vascular endothelial growth factor (VEGF) therapy. This study aimed to investigate the effect of faricimab, a bispecific antibody against angiopoietin-2 and VEGF, on the number of MAs and their turnover in the treatment of DME.
METHODS
We included that patients with DME who underwent three monthly injections of faricimab in one eye, with the other eye as control. We examined central retinal thickness (CRT) based on optical coherence tomography (OCT) and best-corrected visual acuity. Turnover, including loss and newly formed MAs, and the total number of MAs were counted based on merged images of the OCT map and fluorescein angiography.
RESULTS
We enrolled 28 patients with DME. After 3 monthly injections of faricimab, CRT significantly improved, 66.0 ± 16.2% of MAs disappeared, and 6.71 ± 5.6% of new MAs were generated, resulting in total reduction to 40.7 ± 15.2%. In the treated eyes, MA disappearance (P < 0.0001) and turnover (P = 0.007) were significantly greater, and new formation was smaller (P < 0.0001) than in non-treated eyes. The size of the retained MAs decreased after treatment. Microaneurysm turnover was not significantly different between areas with and without edema before treatment.
CONCLUSIONS
In the process of improving edema in DME with faricimab, MAs shrink and disappear, and formation of MAs are inhibited, resulting in decreased total number of MAs. Intravitreal administration of faricimab suppresses vascular permeability and improves vascular structure.
Topics: Humans; Macular Edema; Diabetic Retinopathy; Vascular Endothelial Growth Factor A; Angiogenesis Inhibitors; Microaneurysm; Intravitreal Injections; Edema; Tomography, Optical Coherence; Diabetes Mellitus
PubMed: 37856112
DOI: 10.1167/iovs.64.13.31 -
Cells Jun 2022Diabetic macular edema (DME) is a major ocular complication of diabetes mellitus (DM), leading to significant visual impairment. DME's pathogenesis is multifactorial.... (Review)
Review
Diabetic macular edema (DME) is a major ocular complication of diabetes mellitus (DM), leading to significant visual impairment. DME's pathogenesis is multifactorial. Focal edema tends to occur when primary metabolic abnormalities lead to a persistent hyperglycemic state, causing the development of microaneurysms, often with extravascular lipoprotein in a circinate pattern around the focal leakage. On the other hand, diffusion edema is due to a generalized breakdown of the inner blood-retinal barrier, leading to profuse early leakage from the entire capillary bed of the posterior pole with the subsequent extravasation of fluid into the extracellular space. The pathogenesis of DME occurs through the interaction of multiple molecular mediators, including the overexpression of several growth factors, including vascular endothelial growth factor (VEGF), insulin-like growth factor-1, angiopoietin-1, and -2, stromal-derived factor-1, fibroblast growth factor-2, and tumor necrosis factor. Synergistically, these growth factors mediate angiogenesis, protease production, endothelial cell proliferation, and migration. Treatment for DME generally involves primary management of DM, laser photocoagulation, and pharmacotherapeutics targeting mediators, namely, the anti-VEGF pathway. The emergence of anti-VEGF therapies has resulted in significant clinical improvements compared to laser therapy alone. However, multiple factors influencing the visual outcome after anti-VEGF treatment and the presence of anti-VEGF non-responders have necessitated the development of new pharmacotherapies. In this review, we explore the pathophysiology of DME and current management strategies. In addition, we provide a comprehensive analysis of emerging therapeutic approaches to the treatment of DME.
Topics: Angiogenesis Inhibitors; Blood-Retinal Barrier; Diabetes Mellitus; Diabetic Retinopathy; Humans; Macular Edema; Vascular Endothelial Growth Factor A
PubMed: 35741079
DOI: 10.3390/cells11121950 -
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 -
No Shinkei Geka. Neurological Surgery Mar 2021Intracranial aneurysms or arterial dissections are major causes of subarachnoid hemorrhage(SAH). Early surgical or endovascular repair of the bleeding source is crucial...
Intracranial aneurysms or arterial dissections are major causes of subarachnoid hemorrhage(SAH). Early surgical or endovascular repair of the bleeding source is crucial because rebleeding mostly occurs within a few days after the initial attack. Radiological examination is an initial step for the appropriate diagnosis of ruptured intracranial aneurysms and arterial dissections. However, misdiagnosis may occur, especially in patients with minor bleeding or multiple aneurysms. In addition to computed tomography, magnetic resonance imaging, including FLAIR and SWI, and T2WI are useful for detecting minor SAH. Vessel-wall imaging has recently been applied to diagnosing the site of rupture in patients with multiple cerebral aneurysms or microaneurysms, but not to assessing the instability of unruptured cerebral aneurysms or intracranial arterial dissections. In this article, we discuss the current radiological modalities and their usefulness for diagnosing SAH.
Topics: Aneurysm, Ruptured; Cerebral Angiography; Humans; Intracranial Aneurysm; Magnetic Resonance Imaging; Subarachnoid Hemorrhage; Tomography, X-Ray Computed
PubMed: 33762441
DOI: 10.11477/mf.1436204382 -
Survey of Ophthalmology 2021Inflammation can involve several ocular structures, including the sclera, retina, and uvea, and cause vascular changes in these tissues. Although retinal vasculitis is... (Review)
Review
Inflammation can involve several ocular structures, including the sclera, retina, and uvea, and cause vascular changes in these tissues. Although retinal vasculitis is the most common finding associated with uveitis involving the posterior segment, other vascular abnormalities may be seen in the retina. These include capillary nonperfusion and ischemia, vascular occlusions, preretinal neovascularization, microaneurysms and macroaneurysms, and telangiectasia. Moreover, vasoproliferative tumors and subsequent coat-like response can develop secondary to uveitis. Fluorescein angiography is ideal for the investigation of retinal vascular leakage and neovascularization, while optical coherence tomography angiography can provide depth resolved images from the superficial and deep capillary plexus and can demonstrate vascular remodeling. Choroidal vascular abnormalities primarily develop in the choriocapillaris or in the choroidal stroma and can appear as flow void in optical coherence tomography angiography and filling defect and vascular leakage in indocyanine green angiography. Extensive choriocapillaris nonperfusion in the presence of choroidal inflammation can increase the risk of choroidal neovascular membrane development. Iris vascular changes may manifest as dilation of vessels in stroma due to inflammation or rubeosis that is usually from ischemia in retinal periphery secondary to chronic inflammation. More severe forms of scleral inflammation, such as necrotizing scleritis, are associated with vascular occlusion in the deep episcleral plexus, which can lead to necrosis of sclera layer and uveal exposure.
Topics: Choroid; Fluorescein Angiography; Humans; Retinal Neovascularization; Retinal Vessels; Tomography, Optical Coherence; Uveitis
PubMed: 33412171
DOI: 10.1016/j.survophthal.2020.12.006 -
Ophthalmology. Retina Jun 2023The purpose of this study was to evaluate the longitudinal change in quantitative ultrawide-field angiographic (UWFA) parameters and correlate them with functional... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
The purpose of this study was to evaluate the longitudinal change in quantitative ultrawide-field angiographic (UWFA) parameters and correlate them with functional outcomes and spectral domain-OCT metrics.
DESIGN
This study is a post hoc analysis of the phase II RUBY study: a prospective, randomized trial of patients with diabetic macular edema (DME) treated with either intravitreal aflibercept injection (IAI) or combined IAI/nesvacumab (antiangiopoietin 2 mAb).
SUBJECTS
Subjects with DME that underwent UWFA across all treatment groups (n = 44).
METHODS
A machine learning-enabled feature extraction system generated panretinal quantitative UWFA metrics, including leakage, ischemia, and microaneurysm (MA) burden. Zonal assessments were performed corresponding to the macula, midperiphery, and far periphery.
MAIN OUTCOME MEASURES
Changes in ischemic area and index (proportion of nonperfusion in analyzable retina), leakage area and index (proportion of leakage in analyzable retina), and MA count at baseline, week 12, week 24, and week 36 were analyzed. Spectral-domain-OCT quantitative metrics, such as central subfield thickness, ellipsoid zone (EZ) integrity parameters, intraretinal fluid (IRF) volume, and subretinal fluid (SRF) volume were extracted via a machine learning-enhanced OCT feature extraction platform and analyzed. Additionally, the effect of these changes on best-corrected visual acuity (BCVA) was evaluated.
RESULTS
Mean panretinal leakage index, zonal leakage area, and panretinal MA count improved significantly between baseline and week 36. Panretinal ischemic index decreased between baseline and week 36, with some aspects showing significant improvement. Mean BCVA significantly improved from baseline to week 36. There was a significant inverse correlation between change in BCVA and change in macular leakage area. A direct correlation was observed between both baseline macular leakage area and panretinal leakage index with IRF volume, SRF volume, and EZ disruption on OCT.
CONCLUSIONS
Assessment of UWFA parameters demonstrates a significant improvement in panretinal leakage index, leakage area, and MA burden in eyes treated with IAI with or without nesvacumab. A numeric reduction in panretinal ischemic index and area was noted. The analysis also shows the critical association of leakage with visual and OCT features. This highlights the potential role of UWFA in disease burden assessment, with leakage parameters serving as a primary end point.
FINANCIAL DISCLOSURE(S)
Proprietary or commercial disclosure may be found after the references.
Topics: Humans; Macular Edema; Fluorescein Angiography; Diabetic Retinopathy; Prospective Studies; Macula Lutea; Angiogenesis Inhibitors; Diabetes Mellitus
PubMed: 36736895
DOI: 10.1016/j.oret.2023.01.018