Myeloid cell reprogramming alleviates immunosuppression and promotes clearance of metastatic lesions.

Suppressive myeloid cells, including monocyte and neutrophil populations, play a vital role in the metastatic cascade and can inhibit the anti-tumor function of cytotoxic T-cells. Cargo-free polymeric nanoparticles (NPs) have been shown to modulate innate immune cell responses in multiple pathologies of aberrant inflammation. Here, we test the hypothesis that the intravenous administration of drug-free NPs in the 4T1 murine model of metastatic triple-negative breast cancer can reduce metastatic colonization of the lungs, the primary metastatic site, by targeting the pro-tumor immune cell mediators of metastatic progression. In vivo studies demonstrated that NP administration reprograms the immune milieu of the lungs and reduces pulmonary metastases. Single-cell RNA sequencing of the lungs revealed that intravenous NP administration alters myeloid cell phenotype and function, skewing populations toward inflammatory, anti-tumor phenotypes and away from pro-tumor phenotypes. Monocytes, neutrophils, and dendritic cells in the lungs of NP-treated mice upregulate gene pathways associated with IFN signaling, TNF signaling, and antigen presentation. In a T-cell deficient model, NP administration failed to abrogate pulmonary metastases, implicating the vital role of T-cells in the NP-mediated reduction of metastases. NPs delivered as an adjuvant therapy, following surgical resection of the primary tumor, led to clearance of established pulmonary metastases in all treated mice. Collectively, these results demonstrate that the in vivo administration of cargo-free NPs reprograms myeloid cell responses at the lungs and promotes the clearance of pulmonary metastases in a method of action dependent on functional T-cells.

Implications of TGFß Signaling and CDK Inhibition for the Treatment of Breast Cancer.

TGFß signaling enacts tumor-suppressive functions in normal cells through promotion of several cell regulatory actions including cell-cycle control and apoptosis. Canonical TGFß signaling proceeds through phosphorylation of the transcription factor, SMAD3, at the C-terminus of the protein. During oncogenic progression, this tumor suppressant phosphorylation of SMAD3 can be inhibited. Overexpression of cyclins D and E, and subsequent hyperactivation of cyclin-dependent kinases 2/4 (CDKs), are often observed in breast cancer, and have been associated with poor prognosis. The noncanonical phosphorylation of SMAD3 by CDKs 2 and 4 leads to the inhibition of tumor-suppressive function of SMAD3. As a result, CDK overactivation drives oncogenic progression, and can be targeted to improve clinical outcomes. This review focuses on breast cancer, and highlights advances in the understanding of CDK-mediated noncanonical SMAD3 phosphorylation. Specifically, the role of aberrant TGFß signaling in oncogenic progression and treatment response will be examined to illustrate the potential for therapeutic discovery in the context of cyclins/CDKs and SMAD3.

Utility of IOLMaster 700 Swept-Source Optical Coherence Tomography in Detecting Macular Disease for Preoperative Cataract Surgery Patients.

PURPOSE: To assess the efficacy of IOLMaster 700 (IOLM) biometer swept-source optical coherence tomography (SS-OCT) in detecting macular pathology before cataract surgery and to compare IOLM SS-OCT characteristics of foveal pathology with a widely used spectral-domain OCT (SD-OCT) system. PATIENTS AND METHODS: Retrospective analysis of 1156 consecutive eyes with IOLMaster 700 SS-OCT undergoing cataract surgery from January to June 2017 was performed. Approximately a third of these eyes (327 eyes) also had a SD-OCT scan performed previously. A single reviewer assessed each SS-OCT scan and identified them as "normal" or "abnormal." SS-OCT sensitivity and specificity in identifying foveal pathology was assessed using findings on Spectralis SD-OCT scans as the gold standard. RESULTS: Of 327 eyes with both IOLM SS-OCT and Spectralis SD-OCT scans, 121 eyes (37.0%) had abnormal SS-OCT scans. Of these 121 eyes, SD-OCT scans confirmed pathology in 104 eyes (86.0%). Of the remaining 206 eyes graded to have normal SS-OCT scans, 84 eyes (40.8%) had normal SD-OCT scans, and 122 eyes (59.2%) had pathologic findings on SD-OCT scans. For each pathologic condition, subtle but definitive differences existed in the appearance of the IOLM SS-OCT and SD-OCT images. CONCLUSION: Using a normal or abnormal Spectralis SD-OCT scan as confirmation of absence or presence of foveal pathology respectively, we found a high positive predictive value (86.0%) of an abnormal IOLM SS-OCT scan and a high specificity (83.2%) but low sensitivity (46.0%) and negative predictive value (40.8%) of a normal-appearing SS-OCT scan. These results suggest that an abnormal IOLM SS-OCT scan in an eye without known pathology is a strong indicator of an abnormal macula and should prompt further evaluation of the retina to identify pathology prior to cataract surgery. Importantly, IOLM SS-OCT scans do not detect all macular pathology and cannot be used as a screening test for identifying macular pathology.

Cargo-free immunomodulatory nanoparticles combined with anti-PD-1 antibody for treating metastatic breast cancer.

The presence of immunosuppressive innate immune cells such as myeloid derived suppressor cells (MDSCs), Ly6C-high monocytes, and tumor-associated macrophages (TAMs) at a tumor can inhibit effector T cell and NK cell function. Immune checkpoint blockade using anti-PD-1 antibody aims to overcome the immune suppressive environment, yet only a fraction of patients responds. Herein, we test the hypothesis that cargo-free PLG nanoparticles administered intravenously can divert circulating immune cells from the tumor microenvironment to enhance the efficacy of anti-PD-1 immunotherapy in the 4T1 mouse model of metastatic triple-negative breast cancer. In vitro studies demonstrate that these nanoparticles decrease the expression of MCP-1 by 5-fold and increase the expression of TNF-α by more than 2-fold upon uptake by innate immune cells. Intravenous administration of particles results in internalization by MDSCs and monocytes, with particles detected in the liver, lung, spleen, and primary tumor. Nanoparticle delivery decreased the abundance of MDSCs in circulation and in the lung, the latter being the primary metastatic site. Combined with anti-PD-1 antibody, nanoparticles significantly slowed tumor growth and resulted in a survival benefit. Gene expression analysis by GSEA indicated inflammatory myeloid cell pathways were downregulated in the lung and upregulated in the spleen and tumor. Upregulation of extrinsic apoptotic pathways was also observed in the primary tumor. Collectively, these results demonstrate that cargo-free PLG nanoparticles can reprogram immune cell responses and alter the tumor microenvironment in vivo to overcome the local immune suppression attributed to myeloid cells and enhance the efficacy of anti-PD-1 therapy.

Disease-induced immunomodulation at biomaterial scaffolds detects early pancreatic cancer in a spontaneous model.

Pancreatic cancer has the worst prognosis of all cancers due to disease aggressiveness and paucity of early detection platforms. We developed biomaterial scaffolds that recruit metastatic tumor cells and reflect the immune dysregulation of native metastatic sites. While this platform has shown promise in orthotopic breast cancer models, its potential in other models is untested. Herein, we demonstrate that scaffolds recruit disseminated pancreatic cells in the KPCY model of spontaneous pancreatic cancer prior to adenocarcinoma formation (3-fold increase in scaffold YFP + cells). Furthermore, immune cells at the scaffolds differentiate early- and late-stage disease with greater accuracy (0.83) than the natural metastatic site (liver, 0.50). Early disease was identified by an approximately 2-fold increase in monocytes. Late-stage disease was marked by a 1.5-2-fold increase in T cells and natural killer cells. The differential immune response indicated that the scaffolds could distinguish spontaneous pancreatic cancer from spontaneous breast cancer. Collectively, our findings demonstrate the utility of scaffolds to reflect immunomodulation in two spontaneous models of tumorigenesis, and their particular utility for identifying early disease stages in the aggressive KPCY pancreatic cancer model. Such scaffolds may serve as a platform for early detection of pancreatic cancer to improve treatment and prognosis.

Longitudinal Retinal Layer Changes and Clinical Outcome in Patients with Multiple Evanescent White Dot Syndrome.

Purpose: To evaluate longitudinal changes in retinal layer thickness and clinical outcome in patients with MEWDS.Methods: In 20 patients with MEWDS, SD-OCT images and BCVA were assessed at baseline, and at months 1, 3, and 12. SD-OCTs were segmented and measurements were performed within the fovea and a MEWDS lesion. Baseline and follow-up values in the affected eye were compared to measurements performed at the corresponding location in the fellow eye.Results: ONL thickness was 4.7% thicker in MEWDS-eyes compared with the baseline, with a significant decrease of 9% at 3 months. Within the lesion, INL thickness was 7.9% increased at baseline and decreased significantly over the follow-up of 12 months. BCVA was decreased at baseline (0.2 ± 0.18logMAR) and at the 3 months but after 12 months had increased to 0.01 ± 0.04 logMAR.Conclusion: MEWDS shows the involvement of different retinal layers and characteristic changes over the disease course.

Management of Patients With Glomerulonephritis During the COVID-19 Pandemic: Recommendations From the Canadian Society of Nephrology COVID-19 Rapid Response Team.

PURPOSE OF PROGRAM: This article will provide guidance on how to best manage patients with glomerulonephritis (GN) during the COVID-19 pandemic. SOURCES OF INFORMATION: We reviewed relevant published literature, program-specific documents, and guidance documents from international societies. An informal survey of Canadian nephrologists was conducted to identify practice patterns and expert opinions. We hosted a national webinar with invited input and feedback after webinar. METHODS: The Canadian Society of Nephrology (CSN) Board of Directors invited physicians with expertise in GN to contribute. Specific COVID-19-related themes in GN were identified, and consensus-based recommendations were made by this group of nephrologists. The recommendations received further peer input and review by Canadian nephrologists via a CSN-sponsored webinar. This was attended by 150 kidney health care professionals. The final consensus recommendations also incorporated review by Editors of the Canadian Journal of Kidney Health and Disease. KEY FINDINGS: We identified 9 areas of GN management that may be affected by the COVID-19 pandemic: (1) clinic visit scheduling, (2) clinic visit type, (3) provision of multidisciplinary care, (4) blood and urine testing, (5) home-based monitoring essentials, (6) immunosuppression, (7) other medications, (8) patient education and support, and (9) employment. LIMITATIONS: These recommendations are expert opinion, and are subject to the biases associated with this level of evidence. To expedite the publication of this work, a parallel review process was created that may not be as robust as standard arm's length peer review processes. IMPLICATIONS: These recommendations are intended to provide optimal care during the COVID-19 pandemic. Our recommendations may change based on the evolving evidence.

DIAGNOSTIC IMAGE QUALITY ASSESSMENT AND CLASSIFICATION IN MEDICAL IMAGING: OPPORTUNITIES AND CHALLENGES.

Magnetic Resonance Imaging (MRI) suffers from several artifacts, the most common of which are motion artifacts. These artifacts often yield images that are of non-diagnostic quality. To detect such artifacts, images are prospectively evaluated by experts for their diagnostic quality, which necessitates patient-revisits and rescans whenever non-diagnostic quality scans are encountered. This motivates the need to develop an automated framework capable of accessing medical image quality and detecting diagnostic and non-diagnostic images. In this paper, we explore several convolutional neural network-based frameworks for medical image quality assessment and investigate several challenges therein.

Cyclin E overexpression confers resistance to trastuzumab through noncanonical phosphorylation of SMAD3 in HER2+ breast cancer.

The efficacy of trastuzumab, a treatment for HER2+ breast cancer, can be limited by the development of resistance. Cyclin E (CCNE) overexpression has been implicated in trastuzumab resistance. We sought to uncover a potential mechanism for this trastuzumab resistance and focused on a model of CCNE overexpressing HER2+ breast cancer and noncanonical phosphorylation of the TGF-ß signaling protein, SMAD3. Network analysis of transcriptional activity in a HER2+, CCNE overexpressing, trastuzumab-resistant cell line (BT474R2) identified decreased SMAD3 activity was associated with treatment resistance. Immunoblotting showed SMAD3 expression was significantly downregulated in BT474R2 cells (p < .01), and noncanonical phosphorylation of SMAD3 was increased in these CCNE-overexpressing cells. Also, in response to CDK2 inhibition, expression patterns linked to restored canonical SMAD3 signaling, including decreased cMyc and increased cyclin-dependent inhibitor, p15, were identified. The BT474R2 cell line was modified through overexpression of SMAD3 (BT474R2-SMAD3), a mutant construct resistant to CCNE-mediated noncanonical phosphorylation of SMAD3 (BT474R2-5M), and a control (BT474R2-Blank). In vitro studies examining the response to trastuzumab showed increased sensitivity to treatment for BT474R2-5M cells. These findings were then validated in NSG mice inoculated with BT474R2-5M cells or BT474R2 control cells. After treatment with trastuzumab, the NSG mice inoculated with BT474R2-5M cells developed significantly lower tumor volumes (p < .001), when compared to mice inoculated with BT474R2 cells. Taken together, these results indicate that for patients with HER2+ breast cancer, a mechanism of CCNE-mediated trastuzumab resistance, regulated through noncanonical SMAD3 phosphorylation, could be treated with CDK2 inhibition to help enhance the efficacy of trastuzumab therapy.

Quality of life and satisfaction among physicians after wavefront-optimized vs topography-guided laser vision correction.

PURPOSE: To assess satisfaction, quality of life, occupational impact, and clinical outcomes of physicians who have undergone laser vision correction (LVC) using either wavefront-optimized (WFO) or topography-guided (TG) excimer laser ablation profile with femtosecond laser flap creation. SETTING: Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio, USA. DESIGN: Retrospective survey study. METHODS: A 12-question survey was sent to all physicians who underwent laser in situ keratomileusis or photorefractive keratectomy at the Cole Eye Institute between 2011 and 2018 on the WaveLight Allegretto Wave Eye-Q Laser (Alcon Laboratories, Inc.). Visual outcomes were obtained from patient charts. RESULTS: Two hundred thirty-five physicians (454 eyes) met the study's inclusion criteria, including 181 physicians (353 eyes) who underwent WFO LVC and 54 physicians (101 eyes) who underwent TG LVC. One hundred seventeen physicians (49.8%) responded to the survey and reported an overall satisfaction rate of 98.3% among all physicians receiving LVC with 96.6% reporting they would have the procedure again. Visual outcomes showed a high level of surgical predictability, efficacy, and safety among WFO and TG eyes, with a higher percentage of eyes that received TG ablation achieving 20/10 vision (22% vs 4%, P < .0001) and 20/15 vision (87% vs 69%, P < .01) when compared with WFO eyes. CONCLUSIONS: Physicians who had undergone LVC with either WFO or TG excimer laser ablation reported high satisfaction and quality-of-life improvements. Both groups achieved excellent visual outcomes, with a higher percentage of TG eyes achieving 20/10 and 20/15 vision.

Toward Continuous Social Phenotyping: Analyzing Gaze Patterns in an Emotion Recognition Task for Children With Autism Through Wearable Smart Glasses.

BACKGROUND: Several studies have shown that facial attention differs in children with autism. Measuring eye gaze and emotion recognition in children with autism is challenging, as standard clinical assessments must be delivered in clinical settings by a trained clinician. Wearable technologies may be able to bring eye gaze and emotion recognition into natural social interactions and settings. OBJECTIVE: This study aimed to test: (1) the feasibility of tracking gaze using wearable smart glasses during a facial expression recognition task and (2) the ability of these gaze-tracking data, together with facial expression recognition responses, to distinguish children with autism from neurotypical controls (NCs). METHODS: We compared the eye gaze and emotion recognition patterns of 16 children with autism spectrum disorder (ASD) and 17 children without ASD via wearable smart glasses fitted with a custom eye tracker. Children identified static facial expressions of images presented on a computer screen along with nonsocial distractors while wearing Google Glass and the eye tracker. Faces were presented in three trials, during one of which children received feedback in the form of the correct classification. We employed hybrid human-labeling and computer vision-enabled methods for pupil tracking and world-gaze translation calibration. We analyzed the impact of gaze and emotion recognition features in a prediction task aiming to distinguish children with ASD from NC participants. RESULTS: Gaze and emotion recognition patterns enabled the training of a classifier that distinguished ASD and NC groups. However, it was unable to significantly outperform other classifiers that used only age and gender features, suggesting that further work is necessary to disentangle these effects. CONCLUSIONS: Although wearable smart glasses show promise in identifying subtle differences in gaze tracking and emotion recognition patterns in children with and without ASD, the present form factor and data do not allow for these differences to be reliably exploited by machine learning systems. Resolving these challenges will be an important step toward continuous tracking of the ASD phenotype.

Plaque herniation after stenting the culprit lesion with myocardial bridging in ST elevation myocardial infarction: A case report.

BACKGROUND: Myocardial bridging (MB) is increasingly recognized to stimulate atherogenesis, which may contribute to an acute coronary syndrome. Stenting the coronary segment with MB has been recognized to have an increased risk of in-stent restenosis, stent fracture and coronary perforation. The safety and efficacy of stenting the culprit lesion with overlaying MB in ST elevation myocardial infarction (STEMI) as primary reperfusion therapy has not been established. CASE SUMMARY: We reported a patient who presented with inferior STEMI with a culprit lesion of an acute thrombotic occlusion in the right coronary artery and thrombolysis and thrombin inhibition in myocardial infarction 0 flow. After the stent placement during primary percutaneous coronary intervention, intravascular ultrasound revealed MB overlying the stented segment where heavy atherosclerotic plaque were present. Likely due to the combination of plaque herniation or prolapse caused by MB, as well as local increased inflammation and thrombogenicity, acute stent thrombosis occurred at this region, which led to acute stent failure. The patient required an emergent repeated cardiac catheterization and placing a second layer of stent to enhance the radial strength and reduce the inter-strut space. CONCLUSION: Plaque herniation or prolapse after stenting a MB segment in STEMI is a potential etiology for acute stent failure.

Severe bilateral descemetoceles in Alpha-1 antitrypsin deficiency.

PURPOSE: To report a case of severe bilateral descemetoceles in a patient with alpha-1 antitrypsin (A1AT) deficiency during intensive care unit hospitalization. OBSERVATIONS: A 42-year-old male presented with sub-acute bilateral vision loss during an intensive care unit hospitalization following liver and kidney transplantations. On exam, this patient's best-corrected visual acuity was 20/80 in both eyes. There were bilateral descemetoceles inferotemporally in both eyes with overlying epithelial defects and dense surrounding punctate epithelial staining. The patient was initially treated with gatifloxacin drops and frequent lubricating ointment. Given the concern for impending perforation, cyanoacrylate glue with bandage contact lens was applied to both eyes. His best corrected visual acuity remained unchanged in the right eye and improved to 20/30 in the left eye. Upon medical stabilization, anterior lamellar graft was performed in the right eye, with plans for the same treatment in the left eye in the future. CONCLUSIONS: As A1AT is found in the tear film and is believed to play a role in regulating protease activity in the cornea, we hypothesize that this patient's A1AT deficiency exacerbated the progression of corneal ulceration leading to severe descemetocele formation.

Electrodeposition of pure phase SnSb exhibiting high stability as a sodium-ion battery anode.

Electrodeposition of pure phase SnSb is reported for the first time. The purity of the product is important, as the impure phase is found to be detrimental to the material's lifetime as a sodium-ion anode. The directly deposited electrode was able to retain 95% capacity after 300 cycles, and only fall below 80% capacity retention after 800 cycles when cycled versus sodium.

Combinatorial, Microparticle-Based Delivery of Immune Modulators Reprograms the Dendritic Cell Phenotype and Promotes Remission of Collagen-Induced Arthritis in Mice.

Safe, effective, antigen-specific therapy for rheumatoid arthritis (RA) remains an elusive clinical goal with a few lasting, viable options on the horizon. Existing therapeutic interventions are indiscriminate and inconsistently immunosuppressive, often leaving patients susceptible to infection. Herein, we investigate the use of a dual-sized, microparticle "regulatory vaccine" (REGvac) that passively targets dendritic cells for antigen-specific biomaterial-based immunotherapy of RA. This REGvac employs poly(d,l-lactic-co-glycolic-acid) (PLGA) microparticles (MPs) encapsulating (i) a dendritic cell chemoattractant, (ii) potent immunosuppressive molecules, (iii) and an RA-relevant autoantigen to provide a multifaceted approach for the treatment of collagen-induced arthritis (CIA), the primary mouse model of RA. Subcutaneous administrations of the REGvac after mice had developed moderate clinical symptoms markedly diminished overt inflammation in the paws, halted cartilage degradation, and restored gait parameters within 56 days after initial treatment. Positron emission tomography imaging corroborated reduction of inflammation in the paws of REGvac-treated mice. In-depth immunological assessments showed a decreased expression of CD80, CD86, and MHC II on CD11c+ dendritic cells in joint-associated lymph nodes. Further, we observed significant increases in conventional regulatory CD25+FOXP3+ T cells, as well as programmed cell death protein-1 (PD-1)-expressing CD4+ T cells in joint-proximal lymph nodes and the spleen. Real-time PCR analysis of joint tissues from treated mice revealed significant decreases in inflammatory cytokine expression (IL-6), while IL-10 mRNA levels were significantly increased. These observations strongly hint toward the induction of multiple tolerogenic mechanisms by administration of this MP regulatory vaccine. With regards to antigen specificity, ex vivo antigen recall assays revealed a lack of response to collagen by CD4+ T cells from the popliteal and inguinal lymph nodes of REGvac-treated mice, contrasting with the proliferative response of CD4+ T cells from CIA+ mice. Taken altogether, our results strongly support the application of this MP regulatory vaccine as a potent, biomaterial-based, antigen-specific therapy for RA.

Latent, Immunosuppressive Nature of Poly(lactic-co-glycolic acid) Microparticles.

Use of biomaterials to spatiotemporally control the activation of immune cells is at the forefront of biomedical engineering research. As more biomaterial strategies are employed for immunomodulation, understanding the immunogenicity of biodegradable materials and their byproducts is paramount in tailoring systems for immune activation or suppression. Poly(D,L-lactic-co-glycolic acid) (PLGA), one of the most commonly studied polymers in tissue engineering and drug delivery, has been previously described on one hand as an immune adjuvant, and on the other as a nonactivating material. In this study, the effect of PLGA microparticles (MPs) on the maturation status of murine bone marrow-derived dendritic cells (DCs), the primary initiators of adaptive immunity, was investigated to decipher the immunomodulatory properties of this biomaterial. Treatment of bone marrow-derived DCs from C57BL/6 mice with PLGA MPs led to a time dependent decrease in the maturation level of these cells, as quantified by decreased expression of the positive stimulatory molecules MHCII, CD80, and CD86 as well as the ability to resist maturation following challenge with lipopolysaccharide (LPS). Moreover, this immunosuppression was dependent on the molecular weight of the PLGA used to fabricate the MPs, as higher molecular weight polymers required longer incubation to produce comparable dampening of maturation molecules. These phenomena were correlated to an increase in lactic acid both intracellularly and extracellularly during DC/PLGA MP coculture, which is postulated to be the primary agent behind the observed immune inhibition. This hypothesis is supported by our results demonstrating that resistance to LPS stimulation may be due to the ability of PLGA MP-derived lactic acid to inhibit the phosphorylation of TAK1 and therefore prevent NF-κB activation. This work is significant as it begins to elucidate how PLGA, a prominent biomaterial with broad applications ranging from tissue engineering to pharmaceutics, could modulate the local immune environment and offers insight on engineering PLGA to exploit its evolving immunogenicity.

MEK/CDK4,6 co-targeting is effective in a subset of NRAS, BRAF and 'wild type' melanomas.

Targeted therapy has become a cornerstone for the treatment of melanoma patients. Targeting NRAS function is particularly challenging. To date, only single MEK inhibitor treatment was able to show minimal clinical efficacy. The discovery that co-targeting of MEK and CDK4,6 has antitumor activity created excitement for patients and clinicians; however, it is largely unknown if only NRAS mutant patients might benefit from MEK/CDK4,6 blockade. In this study we investigate response patterns of NRAS, BRAF mutant and 'wild type' melanoma cells in vitro and in vivo when challenged with inhibitors of MEK, CDK4,6 and the combination of both. Data revealed, that in vitro growth response patterns of cells treated with the MEK/CDK4,6 combination correspond to in vivo efficacy of MEK/CDK4,6 co-targeting in melanoma xenograft models. Strikingly, this was consistently observed in NRAS and BRAF mutant, as well as in 'wild type' melanoma cells. Additionally, cells displaying elevated p-Rb levels after single MEK inhibition, showed more effective growth reduction with MEK/CDK4,6 co-targeting compared to single MEK inhibitor treatment in vivo. Findings indicate that combined MEK/CDK4,6 inhibition could offer an effectively therapeutic modality in a subset of BRAF and NRAS mutant, as well as 'wild type' melanoma patients.

Calcified amorphous tumor: A rare cause of central retinal artery occlusion.

PURPOSE: We report the case of a central retinal artery occlusion secondary to presumed embolus from a calcified amorphous tumor of the heart, a very rare non-neoplastic cardiac mass. OBSERVATIONS: A 60-year-old female presented with acute unilateral vision loss of the left eye. Examination revealed hand motion visual acuity of the left eye and a left relative afferent pupillary defect. Fundoscopy showed whitening of the macula with a cherry red spot, consistent with a central retinal artery occlusion. Initial workup was unremarkable, including hypercoagulability labs, magnetic resonance imaging of the brain, and magnetic resonance angiography of the head and neck. Transthoracic echocardiogram (TTE) showed calcification of the mitral valve but no masses. Subsequently, transesophageal echocardiogram (TEE) was performed, which revealed a mobile calcified amorphous tumor of the heart. CONCLUSIONS: Calcified amorphous tumor of the heart is a very rare cardiac mass that may cause retinal artery occlusion. TEE is a more sensitive imaging modality to assess for potential cardio-embolic sources if TTE is unrevealing.

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.