OCT及OCTA在阿尔茨海默病诊断中的研究进展

阿尔茨海默病是一种进行性且不可逆转的神经系统疾病,由于视网膜和中枢神经系统有相似的胚胎起源和生理特征,眼科检查可提供简单无创的诊断方法。光学相干断层扫描技术(OCT)能够精确地测量视网膜各个组织层面的厚度,以评估视网膜的退行性改变,光学相干断层扫描血管成像(OCTA)可以提供高分辨率三维成像,从而更直观地检测视网膜血管的变化,间接地反映脑神经元和血管的病理特征。就OCT测量视网膜厚度及OCTA测量视网膜血流变化在阿尔茨海默病诊断中的研究进展进行综述。     

Insights into the developing fovea revealed by imaging

Early development of the fovea has been documented by histological studies over the past few decades. However, structural distortion due to sample processing and the paucity of high-quality post-mortem tissue has limited the effectiveness of this approach. With the continuous progress in high-resolution non-invasive imaging technology, most notably optical coherence tomography (OCT) and OCT angiography (OCT-A), in vivo visualization of the developing retina has become possible. Combining the information from histologic studies with this novel imaging information has provided a more complete and accurate picture of retinal development, and in particular the developing fovea.Advances in neonatal care have increased the survival rate of extremely premature infants. However, with enhanced survival there has been an attendant increase in retinal developmental complications. Several key abnormalities, including a thickening of the inner retina at the foveal center, a shallower foveal pit, a smaller foveal avascular zone, and delayed development of the photoreceptors have been described in preterm infants when compared to full-term infants. Notably these abnormalities, which are consistent with a partial arrest of foveal development, appear to persist into later childhood and adulthood in these eyes of individuals born prematurely. Understanding normal foveal development is vital to interpreting these pathologic findings associated with prematurity.In this review, we first discuss the various advanced imaging technologies that have been adapted for imaging the infant eye. We then review the key events and steps in the development of the normal structure of the fovea and contrast structural features in normal and preterm retina from infancy to childhood. Finally, we discuss the development of the perifoveal retinal microvasculature and highlight future opportunities to expand our understanding of the developing fovea.     

Medición automática de la zona avascular foveal de ojos sanos en angiografía por tomografía de coherencia óptica de dominio espectral Heidelberg

PurposeTo develop and evaluate an automated method to measure the foveal avascular zone (FAZ) area in healthy eyes on Heidelberg Spectralis Optical Coherence Tomography Angiography (HS-OCTA). This method is referred to as the modified Kanno-Saitama macro (mKSM) which is an evolution of the Kanno-Saitama macro (KSM) approach.MethodsThis cross-sectional study included 29 eyes of 25 healthy volunteers who underwent HS-OCTA at the macular area twice at the same time. Regardless of the quality of the images, all of them were included. Macular data on the superficial vascular plexus, intermediate capillary plexus (ICP) and deep capillary plexus were processed by mKSM. The FAZ area was measured twice automatically using the mKSM and KSM and twice manually by two independent examiners.ResultsFrom 174 images, KSM could not measure correctly 31% while mKSM could successfully measure all of them. Intrascan intraclass coefficient ranged from 0.948 to 0.993 for manual measurements and was 1 for mKSM method. Despite that the difference between human examiners is smaller than between human examiners and mKSM according to Bland-Altman plots, the scatterplots show a strong correlation between human and automatic measurements. The best results are obtained in ICP.ConclusionsWith mKSM, the automated determination of the FAZ area in HS-OCTA is feasible and less human-dependent. It solves the inability of KSM to measure the FAZ area in suboptimal quality images which are frequent in daily clinical practice. Therefore, the mKSM processing could contribute to our understanding of the three vascular plexuses.     

EEG functional connectivity contributes to outcome prediction of postanoxic coma

ObjectiveTo investigate the additional value of EEG functional connectivity features, in addition to non-coupling EEG features, for outcome prediction of comatose patients after cardiac arrest.MethodsProspective, multicenter cohort study. Coherence, phase locking value, and mutual information were calculated in 19-channel EEGs at 12 h, 24 h and 48 h after cardiac arrest. Three sets of machine learning classification models were trained and validated with functional connectivity, EEG non-coupling features, and a combination of these. Neurological outcome was assessed at six months and categorized as “good” (Cerebral Performance Category [CPC] 1–2) or “poor” (CPC 3–5).ResultsWe included 594 patients (46% good outcome). A sensitivity of 51% (95% CI: 34–56%) at 100% specificity in predicting poor outcome was achieved by the best functional connectivity-based classifier at 12 h after cardiac arrest, while the best non-coupling-based model reached a sensitivity of 32% (0–54%) at 100% specificity using data at 12 h and 48 h. Combination of both sets of features achieved a sensitivity of 73% (50–77%) at 100% specificity.ConclusionFunctional connectivity measures improve EEG based prediction models for poor outcome of postanoxic coma.SignificanceFunctional connectivity features derived from early EEG hold potential to improve outcome prediction of coma after cardiac arrest.     

Mapeo de activos comunitario para la salud en un asentamiento informal de Medellín (Colombia)

ObjectiveTo describe how the community from El Faro neighborhood identifies its community assets, uses them to face life's challenges through the capacity of collective agency; and by generating community development processes, applying the salutogenic theory that considers people as active subjects, with the capacity to conserve and generate health and well-being, through the use of their own resources called health assets.MethodsA map of community assets was made in 2018 in el Faro neighborhood, an informal settlement of Medellín, Colombia, following the phases recommended by other authors and from a qualitative, participatory approach that delves into the health situation of the community.ResultsIn this process were identified 12 individual community assets, 12 collective, 13 institutional and 10 in the environment. The main community asset among the 47 described was community participation, from the agency capacity, mainly of its leaders who participating in their own organizations encourage development, identity construction and well-being.ConclusionAsset mapping has served to identify intangible assets for the community and, in turn, this recognition has been useful in strengthening the agency's capacity for community development. This is a territory transformed by community reflection processes allowing to understand situations of exclusion and poverty, seeking to create a more livable place and developing a community capacity to solve their own problems, through solidarity and community support.     

Development of an IgG-Fc fusion COVID-19 subunit vaccine,AKS-452

AKS-452 is a biologically-engineered vaccine comprising an Fc fusion protein of the SARS-CoV-2 viral spike protein receptor binding domain antigen (Ag) and human IgG1 Fc (SP/RBD-Fc) in clinical development for the induction and augmentation of neutralizing IgG titers against SARS-CoV-2 viral infection to address the COVID-19 pandemic. The Fc moiety is designed to enhance immunogenicity by increasing uptake via Fc-receptors (FcγR) on Ag-presenting cells (APCs) and prolonging exposure due to neonatal Fc receptor (FcRn) recycling. AKS-452 induced approximately 20-fold greater neutralizing IgG titers in mice relative to those induced by SP/RBD without the Fc moiety and induced comparable long-term neutralizing titers with a single dose vs. two doses. To further enhance immunogenicity, AKS-452 was evaluated in formulations containing a panel of adjuvants in which the water-in-oil adjuvant, Montanide™ ISA 720, enhanced neutralizing IgG titers by approximately 7-fold after one and two doses in mice, including the neutralization of live SARS-CoV-2 virus infection of VERO-E6 cells. Furthermore, ISA 720-adjuvanted AKS-452 was immunogenic in rabbits and non-human primates (NHPs) and protected from infection and clinical symptoms with live SARS-CoV-2 virus in NHPs (USA-WA1/2020 viral strain) and the K18 human ACE2-trangenic (K18-huACE2-Tg) mouse (South African B.1.351 viral variant). These preclinical studies support the initiation of Phase I clinical studies with adjuvanted AKS-452 with the expectation that this room-temperature stable, Fc-fusion subunit vaccine can be rapidly and inexpensively manufactured to provide billions of doses per year especially in regions where the cold-chain is difficult to maintain.     

Diabetic macular ischaemia- a new therapeutic target?

Diabetic macular ischaemia (DMI) is traditionally defined and graded based on the angiographic evidence of an enlarged and irregular foveal avascular zone. However, these anatomical changes are not surrogate markers for visual impairment. We postulate that there are vascular phenotypes of DMI based on the relative perfusion deficits of various retinal capillary plexuses and choriocapillaris. This review highlights several mechanistic pathways, including the role of hypoxia and the complex relation between neurons, glia, and microvasculature. The current animal models are reviewed, with shortcomings noted. Therefore, utilising the advancing technology of optical coherence tomography angiography (OCTA) to identify the reversible DMI phenotypes may be the key to successful therapeutic interventions for DMI. However, there is a need to standardise the nomenclature of OCTA perfusion status. Visual acuity is not an ideal endpoint for DMI clinical trials. New trial endpoints that represent disease progression need to be developed before irreversible vision loss in patients with DMI. Natural history studies are required to determine the course of each vascular and neuronal parameter to define the DMI phenotypes. These DMI phenotypes may also partly explain the development and recurrence of diabetic macular oedema. It is also currently unclear where and how DMI fits into the diabetic retinopathy severity scales, further highlighting the need to better define the progression of diabetic retinopathy and DMI based on both multimodal imaging and visual function. Finally, we discuss a complete set of proposed therapeutic pathways for DMI, including cell-based therapies that may provide restorative potential.