Optical Coherence Tomographic Angiography Imaging in Age-Related Macular Degeneration.

Optical coherence tomographic angiography (OCTA) is emerging as a rapid, noninvasive imaging modality that can provide detailed structural and flow information on retinal and choroidal vasculature. This review contains an introduction of OCTA and summarizes the studies to date on OCTA imaging in age-related macular degeneration

Use of Fundus Autofluorescence Combined with Optical Coherence Tomography for Diagnose of Geographic Atrophy in Age-Related Macular Degeneration

The aim of this study was to demonstrate the sensitivity of Optical coherence tomography (OCT) in detection of geographic atrophy (GA) secondary to exudative age related macular degeneration (AMD). In this retrospective case series study 77 patients (53% female, with mean ± standard deviation [SD] of 82.6±9.3 years) with 97 eyes (45 OS [left eyes]/52 OD [right eyes]) were included. This was a retrospective review of the charts of patients who presented with exudative AMD at the Pitié Salpetrière Hospital, Paris, France, between December 2016 and August 2017 that received intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) therapies. At baseline, following biomicroscopy examination, multimodal imaging was performed including, fluorescein angiography (FA), fundus auto-fluorescence (FAF), spectral domain optical coherence tomography (SD-OCT) and indocyanine green angiography (ICGA). During the follow-up, SD-OCT with/without FAF and FA were performed for each patient at 6, 12 and 18 months. For investigation of the prevalence of GA in eyes undergoing intravitreal injections with anti-VEGF therapy, FAF and SD-OCT images were qualitatively reviewed by four independent observers (two graders per group). Kappa coefficient of Cohen was calculated to determine agreement between the graders. The kappa coefficient of Cohen, for inter-rater agreement in the evaluation of FAF images was 0.468, indicating a moderate agreement between the first and second raters. Thus, the sensitivity and specificity of FAF for the diagnosis of GA were 70% and 57%, respectively. If atrophy was assessed with SD-OCT image analysis, the kappa coefficient for inter-rater agreement was 0.846, implying an acceptable agreement between both readers. The sensitivity and specificity of SD-OCT were 93% and 58% respectively. In conclusion, SD-OCT image analysis was more sensitive than FAF for identifying GA in patients treated for exudative AMD. Epub: October 1, 2019

Acute Kidney Injury in Patients with COVID – 19 Infection: Α Tertiary Referral Hospital Experience

The emersion of the new coronavirus SARS COV 2 (Severe Acute Respiratory SyndromeCoronavirus 2) was rapidly characterized as a pandemic by WHO. The majormanifestation of the virus is respiratory distress; however, the involvement of other organsshould not be overlooked. The kidney is one of the most important target organsof the specific virus with acute kidney injury (AKI) described in 5-36% of COVIDpositive patients and an average 25% within the severely ill.Purp ose: The purpose of this study was to consider the incidence of AKI in patientswith COVID 19 in our cohort and to better understand risk factors associated withAKI. Further, we wanted to investigate the impact of AKI on survival and in hospitalmortality.Methods: Patients admitted to Evagelismos General Hospital with confirmed COVID-19 infection from 11th March until 22th May were investigated. Patients 18 yearsold as well as transplanted patients were excluded from this study. AKI was definedaccording to the AKI criteria.Results : From 99 patients with COVID-19 infection, AKI occurred in 41 (41.4%).A total of 44 patients (44.4%) were admitted to Intensive Care Unit (ICU) and 31 ofthem (70.5%) developed AKI. Of the 44 patients with AKI, 16 (39%) required renalreplacement therapy. Hospital mortality, in total, was 16.2% (37% among patientswith AKI versus 0.02% among those without AKI, p=0.000).Conclusion: AKI was common among patients hospitalized with COVID 19. AKIwas associated with older age, clinical severity and existing CKD

Μοριακοί παράγοντες φλεγμονής στη διαβητική αμφιβληστροειδοπάθεια: ο ρόλος της azurocidin

PURPOSE. Azurocidin, released by neutrophils during leukocyte-endothelial interaction, is a main cause of leukocyte-evoked vascular leakage. Its role in the retina, however, is unknown.METHODS. Brown Norway rats received intravitreal injections of azurocidin and vehicle control. Blood-retinal barrier (BRB) breakdown was quantified using the Evans blue (EB) dye technique 1, 3, and 24 hours after intravitreal injection. To block azurocidin, aprotinin was injected intravenously before the intravitreal injections. To investigate if azurocidin increases retinal leukostasis, number of adherent leukocytes in the retina 2 hours and 24 hours after azurocidin injection were quantified using the Concanavalin A perfusion technique. To investigate whether azurocidin plays a role in vascular endothelial growth factor (VEGF)-induced BRB breakdown, rats were treated intravenously with aprotinin, followed by intravitreal injection of VEGF164. BRB breakdown was quantified 24 hours later. To investigate whether azurocidin may mediate BRB breakdown in early diabetes, aprotinin or vehicle was injected intravenously each day for 10 days to streptozotocin-induced diabetic rats, and BRB breakdown was quantified. To investigate whether azurocidin may mediate BRB breakdown in endotoxin induced uveitis (EIU) as another model of leukocyte mediated retinal vascular leakage , EIU rats were treated with aprotinin or vehicle and BRB breakdown was quantified 24 hours after the EIU induction.RESULTS. Intravitreal injection of azurocidin (20 μg) induced a 6.8-fold increase in vascular permeability compared with control at 1–3 hours (P < 0.05), a 2.7-fold increase at 3-5 hours (P < 0.01), and a 1.7-fold increase at 24 hours (P < 0.05). Azurocidin did not increase static retinal leukostasis at 2 hours after the intravitreal injection or 24 hours after the intravitreal injection. Aprotinin inhibited azurocidin-induced BRB breakdown by 98% (P < 0.05). Furthermore, treatment with aprotinin significantly suppressed VEGF-induced BRB breakdown by 93% (P < 0.05) , BRB breakdown in early experimental diabetes by 40.6% (P < 0.05) and BRB breakdown in EIU by 73% (P<0.05)CONCLUSIONS. Azurocidin increases retinal vascular permeability and is effectively blocked by aprotinin. The inhibition of VEGF-induced, early diabetic BRB breakdown and EIU retinal vascular leakage with aprotinin indicates that azurocidin may be an important mediator of leukocyte-dependent BRB breakdown especially in a disease model like diabetes that leukostasis is crucial in pathogenesis. Azurocidin may become a new therapeutic target in the treatment of retinal vascular leakage, diabetic retinopathy and diabetic macular edema.ΣΚΟΠΟΣ.Η Azurocidin, μετά την εκκρισή της από τα ουδετερόφιλα λευκοκύτταρα κατα την διάρκεια της αλληλεπίδρασης λευκοκυττάρων -αγγειακών ενδοθηλιακών κυτταρων είναι η κύρια αιτία αυξημένης αγγειακής διαπερατότητας σαν αποτέλεσμα της προσκόλλησης των λευκοκυττάρων. Ο ρόλος της στον αμφιβληστροειδή, όμως, παραμένει άγνωστος.ΜΕΘΟΔΟΙ. Η azurocidin δόθηκε με ενδουαλοειδικές ενέσεις σε Brown Norway αρουραίους. Η ποσοτικοποίηση της ρήξης του αιματο-αμφιβληστροειδικού φραγμού (ΑΑΦ) έγινε με την τεχνική Evans Blue (EB) 1, 3, and 24 ώρες μετά την ενδουαλοειδική ένεση. Για να μελετήσουμε αν η azurocidin προκαλεί αυξημένη προσκόλληση λευκοκυττάρων στα αγγεία του αμφιβληστροειδή, ο αριθμός των προσκολλημένων λευκοκυττάρων μετρήθηκε με την μέθοδο της Concanavalin A 2 ώρες και 24 ώρες μετά την ενδουαλοειδική ένεση με azurocidin. Για την απενεργοποίηση της azurocidin, απροτινίνη δόθηκε ενδοφλέβια πριν την ενδουαλοειδική ένεση της azurocidin. Για να μελετήσουμε αν η azurocidin παίζει ρόλο στην ρήξη του ΑΑΦ που προκαλει ο αγγειακός αυξητικός ενδοθηλιακός παράγοντας (vascular endothelial growth factor-VEGF), οι αρουραίοι παρέλαβαν ενδοφλέβια θεραπεία με απροτινίνη και το VEGF δώθηκε ενδουαλοειδικά και η ρήξη του ΑΑΦ ποσοτικοποιήθηκε 24 ώρες αργότερα. Για να μελετήσουμε αν η azurocidin παίζει ρόλο στην ρήξη του ΑΑΦ στα αρχικά στάδια του διαβήτη, απροτινίνη δωθηκε ενδοφλέβια καθημερινά για 10 μέρες σε αρουραίους που είχαν γίνει διαβητικοί με ενδοπεριτοναική ένεση streptozotocin και η ρήξη του ΑΑΦ μετρήθηκε 2 εβδομάδες μετά την έναρξη του διαβήτη. Για να μελετήσουμε αν η azurocidin παιζει ρόλο στην ρήξη του ΑΑΦ στην ραγοειδίτιδα λόγω ενδοτοξίνης (endotoxin induced uveitis, EIU) ως μοντέλο ρήξης του ΑΑΦ με την μεσολάβηση προσκόλλημένων λευκοκυττάρων, θεραπεία με απροτινίνη δωθηκε σε αρουραιους με πειραματική ραγοειδιτιδα EIU και η ρήξη του ΑΑΦ μετρήθηκε 24 ώρες μετά την έναρξη της ραγοειδίτιδας. ΑΠΟΤΕΛΕΣΜΑΤΑ. Ενδουαλοειδική ένεση azurocidin (20 μg) αύξησε την αγγειακή διαπερατότητα του αμφιβληστροειδούς κατα 6.8 φορές σε σύγκριση με την ομάδα ελέγχου 1-3 ώρες μετά την ένεση (P < 0.05), κατά 2.7-φορές στις 3-5 ώρες (P < 0.01) και κατά 1.7 φορές στις 24 ώρες (P < 0.05). H azurocidin δεν αύξησε τον αριθμό προσκολλημένων λευκοκυττάρων στα αγγεία του αμφιβληστροειδή 2 ώρες και 24 ώρες μετά την ενδουαολειδίκη ένεση. Η απροτινίνη ανέστειλε την αύξηση της διαπερατότητας μετά απο την ενδαυαλοειδική ένεση της azurocidin κατα 98% (P < 0.05). Επίσης , η απροτινίνη ανέστειλε την ρήξη του ΑΑΦ μετά απο την ενδoυαλοειδική ένεση VEGF κατα 93% (P < 0.05), μείωσε την ρήξη του ΑΑΦ σε διαβητικούς αρουραίους κατά 40.6% (P < 0.05) και μειώσε την αγγειακή διαπερατότητα του αμφιβληστροειδούς στην πειραματική ραγοειδίτιδα κατα 73% (P<0.05). ΣΥΜΠΕΡΑΣΜΑΤΑ. Η αzurocidin αυξάνει την αγγειακή διαπερατότητα του αμφιβληστροειδή και η απροτινίνη ειναι αποτελεσματικός αναστολέας της δράσης της αzurocidin στην διαπερατότητα των αγγείων του αμφιβληστροειδή. Η αναστολή της ρήξης του ΑΑΦ με την απροτινίνη στο μοντέλο διαβητικής αμφιβληστροειδοπάθειας, μετά απο ένεση VEGF και στο μοντέλο ραγοειδίτιδας είναι ένδειξη πως η azurocidin είναι πιθανό να έχει σημαντικό ρόλο στην ρήξη του ΑΑΦ μέσω προσκόλλησης λευκοκυττάρων στα αγγειακά ενδοθηλιακά κύτταρα ειδικά στον διαβήτη όπου η προσκόλληση των λευκοκυττάρων εινια κρίσιμη στην παθογένεση του διαβητικού οιδήματος της ωχράς. Η αzurocidin μπορεί να αποτέλεσει ένα καινούριο θεραπευτικό στόχο για την διαβητική αμφιβληστροεδοπάθεια και το διαβητικό οίδημα της ωχράς

Review of OCT Angiography Findings in Diabetic Retinopathy: Insights and Perspectives

Diabetes mellitus (DM), a disorder rapidly growing in prevalence, is linked to the retinal microvasculature complication diabetic retinopathy (DR). As one of the leading global causes of vision impairment and loss, imaging techniques to detect and monitor DR must continue to improve in order to address this growing burden. Optical coherence tomography angiography (OCTA) is a nascent imaging modality that generates three-dimensional visualizations of the retinal and choroidal microvasculature. Compared to fluorescein angiography, the gold-standard imaging modality for retinal vessels, OCTA offers the advantages of being non-invasive, quick, and able to resolve the multiple plexuses within the retina. Quantitative OCTA studies have explored parameters such as vessel density (VD), foveal avascular zone (FAZ), acircularity index, vessel tortuosity (VT), and fractal dimension (FD) amongst DR patients. This review synthesizes the main trends emerging from quantitative OCTA-based studies of DR and interrogates them within the context of DR pathophysiology. We offer a glimpse into how analysis techniques have shifted in the years since OCTA came into existence, while speculating on its future role in clinical practice

A Review of the Role of the Intestinal Microbiota in Age-Related Macular Degeneration

Blindness from age-related macular degeneration (AMD) is an escalating problem, yet AMD pathogenesis is incompletely understood and treatments are limited. The intestinal microbiota is highly influential in ocular and extraocular diseases with inflammatory components, such as AMD. This article reviews data supporting the role of the intestinal microbiota in AMD pathogenesis. Multiple groups have found an intestinal dysbiosis in advanced AMD. There is growing evidence that environmental factors associated with AMD progression potentially work through the intestinal microbiota. A high-fat diet in apo-E-/- mice exacerbated wet and dry AMD features, presumably through changes in the intestinal microbiome, though other independent mechanisms related to lipid metabolism are also likely at play. AREDS supplementation reversed some adverse intestinal microbial changes in AMD patients. Part of the mechanism of intestinal microbial effects on retinal disease progression is via microbiota-induced microglial activation. The microbiota are at the intersection of genetics and AMD. Higher genetic risk was associated with lower intestinal bacterial diversity in AMD. Microbiota-induced metabolite production and gene expression occur in pathways important in AMD pathogenesis. These studies suggest a crucial link between the intestinal microbiota and AMD pathogenesis, thus providing a novel potential therapeutic target. Thus, the need for large longitudinal studies in patients and germ-free or gnotobiotic animal models has never been more pressing

Effects of Systemic Drugs on the Development and Progression of Age-Related Macular Degeneration

Age-related macular degeneration (AMD) is the leading cause of severe loss of central vision among people over 50. The pathophysiology of the disease is multifactorial and can be attributed to genetics, aging, inflammation, environmental factors, and lifestyle factors including smoking, diet, obesity, and alcohol consumption. While there is no treatment for dry AMD, the current standard treatment for wet AMD is an intraocular injection of anti-vascular endothelial growth factor-an effective, yet expensive, therapy that requires ongoing treatment. As the aging population continues to grow, and AMD diagnoses continue to rise, new treatments should be explored to reduce vision complications and decrease treatment burdens. Many systemic conditions have progressive pathological changes that may affect AMD, particularly those affecting systemic vasculature like diabetes and cardiovascular status. Consequently, systemic drugs used to treat coexistent systemic diseases may influence some of the pathogenic mechanisms of AMD and lead its progression or delay. In this review we explore the current literature to summarize the findings of the reported effects of antihypertensive, immunosuppressants, cholesterol lowering agents, nonsteroidal anti-inflammatory drugs, dopamine precursors, hypoglycemic agents, and anticoagulants on AMD

Racial differences in quantitative optical coherence tomography angiography findings between older non-diabetics with co-morbidities

This cross-sectional study compared optical coherence tomography angiography (OCTA) parameters between older Black and White adults with systemic comorbidities in an effort to further understand racial differences in the retinal microvasculature. We analyzed vessel density at the superficial (SCP), intermediate (ICP), and deep capillary plexuses (DCP), foveal avascular zone (FAZ) parameters, and blood flow area (BFA) at the choriocapillaris. We used a mixed-effects linear regression model, controlling for hypertension and two eyes from the same subject, to compare OCTA parameters. Black subjects had lower foveal vessel density at the SCP and ICP, while no differences were observed at the parafovea or 3x3 mm macular area of any capillary layer. Black subjects had greater FAZ area, perimeter, and FD-300, a measurement of vessel density in a 300 μm wide ring around the FAZ. Black subjects also had lower BFA at the choriocapillaris. Within a cohort of subjects without hypertension, these differences remained statistically significant, with the exception of foveal vessel density at the SCP and foveal BFA of the choriocapillaris. These findings suggest that normative databases of OCTA parameters must strive to be diverse in nature to adequately capture differences across patient populations. Further study is required to understand if baseline differences in OCTA parameters contribute to epidemiological disparities in ocular diseases

Using Computational Drug-Gene Analysis to Identify Novel Therapeutic Candidates for Retinal Neuroprotection

Retinal cell death is responsible for irreversible vision loss in many retinal disorders. No commercially approved treatments are currently available to attenuate retinal cell loss and preserve vision. We seek to identify chemicals/drugs with thoroughly-studied biological functions that possess neuroprotective effects in the retina using a computational bioinformatics approach. We queried the National Center for Biotechnology Information (NCBI) to identify genes associated with retinal neuroprotection. Enrichment analysis was performed using ToppGene to identify compounds related to the identified genes. This analysis constructs a Pharmacome from multiple drug-gene interaction databases to predict compounds with statistically significant associations to genes involved in retinal neuroprotection. Compounds with known deleterious effects (e.g., asbestos, ethanol) or with no clinical indications (e.g., paraquat, ozone) were manually filtered. We identified numerous drug/chemical classes associated to multiple genes implicated in retinal neuroprotection using a systematic computational approach. Anti-diabetics, lipid-lowering medicines, and antioxidants are among the treatments anticipated by this analysis, and many of these drugs could be readily repurposed for retinal neuroprotection. Our technique serves as an unbiased tool that can be utilized in the future to lead focused preclinical and clinical investigations for complex processes such as neuroprotection, as well as a wide range of other ocular pathologies