A Phase 1, Open-Label, Dose-Escalation Trial to Investigate Safety and Tolerability of Single Intravitreous Injections of ICON-1 Targeting Tissue Factor in Wet AMD.

Background And Objective: This phase 1 study evaluated the safety and tolerability of single intravitreous injections (IVIs) of ICON-1 (Iconic Therapeutics, South San Francisco, CA) in patients with neovascular age-related macular degeneration (nAMD). ICON-1 is a modified factor VIIa protein linked with the Fc portion of a human immunoglobulin G1. The molecule binds tissue factor overexpressed on choroidal neovascularization (CNV) in AMD.

In-Vivo Detection and Tracking of T Cells in Various Organs in a Melanoma Tumor Model by 19F-Fluorine MRS/MRI.

Background: 19F-MRI and 19F-MRS can identify specific cell types after in-vitro or in-vivo 19F-labeling. Knowledge on the potential to track in-vitro 19F-labeled immune cells in tumor models by 19F-MRI/MRS is scarce.

Aim: To study 19F-based MR techniques for in-vivo tracking of adoptively transferred immune cells after in-vitro 19F-labeling, i.

Cardiomyocyte Lineage Specification in Adult Human Cardiac Precursor Cells Via Modulation of Enhancer-Associated Long Noncoding RNA Expression.

The mechanisms controlling differentiation in adult cardiac precursor cells (CPCs) are still largely unknown. In this study, CPCs isolated from the human heart were found to produce predominantly smooth muscle cells but could be redirected to the cardiomyocyte fate by transient activation followed by inhibition of NOTCH signaling. NOTCH inhibition repressed expression, and blocked smooth muscle differentiation.

Characterization of perfluorocarbon relaxation times and their influence on the optimization of fluorine-19 MRI at 3 tesla.

Purpose: To characterize and optimize F MRI for different perfluorocarbons (PFCs) at 3T and quantify the loss of acquisition efficiency as a function of different temperature and cellular conditions.

Methods: The T and T relaxation times of the commonly used PFCs perfluoropolyether (PFPE), perfluoro-15-crown-5-ether (PFCE), and perfluorooctyl bromide (PFOB) were measured in phantoms and in several different conditions (cell types, presence of fixation agent, and temperatures). These relaxation times were used to optimize pulse sequences through numerical simulations.

CARMEN, a human super enhancer-associated long noncoding RNA controlling cardiac specification, differentiation and homeostasis.

Long noncoding RNAs (lncRNAs) are emerging as important regulators of developmental pathways. However, their roles in human cardiac precursor cell (CPC) remain unexplored. To characterize the long noncoding transcriptome during human CPC cardiac differentiation, we profiled the lncRNA transcriptome in CPCs isolated from the human fetal heart and identified 570 lncRNAs that were modulated during cardiac differentiation.

Fluorine MR Imaging of Inflammation in Atherosclerotic Plaque in Vivo.

Purpose: To preliminarily test the hypothesis that fluorine 19 ((19)F) magnetic resonance (MR) imaging enables the noninvasive in vivo identification of plaque inflammation in a mouse model of atherosclerosis, with histologic findings as the reference standard.

Materials And Methods: The animal studies were approved by the local animal ethics committee. Perfluorocarbon (PFC) emulsions were injected intravenously in a mouse model of atherosclerosis (n = 13), after which (19)F and anatomic MR imaging were performed at the level of the thoracic aorta and its branches at 9.

Functional importance of cardiac enhancer-associated noncoding RNAs in heart development and disease.

The key information processing units within gene regulatory networks are enhancers. Enhancer activity is associated with the production of tissue-specific noncoding RNAs, yet the existence of such transcripts during cardiac development has not been established. Using an integrated genomic approach, we demonstrate that fetal cardiac enhancers generate long noncoding RNAs (lncRNAs) during cardiac differentiation and morphogenesis.

Selective in vivo visualization of immune-cell infiltration in a mouse model of autoimmune myocarditis by fluorine-19 cardiac magnetic resonance.

Background: The goal of this study was to characterize the performance of fluorine-19 ((19)F) cardiac magnetic resonance (CMR) for the specific detection of inflammatory cells in a mouse model of myocarditis. Intravenously administered perfluorocarbons are taken up by infiltrating inflammatory cells and can be detected by (19)F-CMR. (19)F-labeled cells should, therefore, generate an exclusive signal at the inflamed regions within the myocardium.

Macular infarction secondary to Staphylococcus epidermidis infection.

Purpose: To describe a patient with macular infarction caused by Staphylococcus epidermidis-induced endophthalmitis.

Methods: Case report.

Results: An 88-year-old woman was referred to our clinic for endophthalmitis after cataract extraction.

Antibacterial role for natural killer cells in host defense to Bacillus anthracis.

Natural killer (NK) cells have innate antibacterial activity that could be targeted for clinical interventions for infectious disease caused by naturally occurring or weaponized bacterial pathogens. To determine a potential role for NK cells in immunity to Bacillus anthracis, we utilized primary human and murine NK cells, in vitro assays, and in vivo NK cell depletion in a murine model of inhalational anthrax. Our results demonstrate potent antibacterial activity by human NK cells against B.

Isolation of cardiovascular precursor cells from the human fetal heart.

Weakening of cardiac function in patients with heart failure results from a loss of cardiomyocytes in the damaged heart. Cell replacement therapies as a way to induce myocardial regeneration in humans could represent attractive alternatives to classical drug-based approaches. However, a suitable source of precursor cells, which could produce a functional myocardium after transplantation, remains to be identified.

Exudative retinal detachment and angle closure glaucoma as the presenting signs of primary pulmonary hypertension.

Background: Primary pulmonary arterial hypertension is a rare systemic condition that may present with distinct ocular findings.

Purpose: To report a patient whose ophthalmic manifestations led to a diagnosis of pulmonary arterial hypertension.

Results: A 58-year-old woman presented with bilateral serous detachments, angle closure, dilated episcleral blood vessels, subretinal drusenoid-like deposits, and intraretinal hemorrhages.

Recombinant tissue plasminogen activator in the treatment of suprachoroidal hemorrhage.

Background: Suprachoroidal hemorrhages are a vision-threatening complication, and poor visual outcome is correlated with increasing hemorrhage complexity. The recommended time of surgical drainage is 10-14 days after the hemorrhage begins to liquefy. We describe a case in which recombinant tissue plasminogen activator (r-tPA), alteplase, is injected within the suprachoroidal space before surgery to assist in the drainage of an organized clot prior to liquefaction.

Midlenticular Optic Opacification af a Hydrophobic Acrylic Intraocular Lens in Association with Retained Perfluorocarbon Liquid Following Vitreoretinal Surgery.

The postoperative course of a patient who underwent retinal detachment repair using perfluoro-n-octane (PFO) and perfluoropropane (C(3)F(8)) gas endotamponade is described in which midlenticular optic opacification of a hydrophobic acrylic intraocular lens was noted. Mechanisms for optic opacification are proposed, which include dystrophic calcification and PFO-induced optic degeneration. The case presents a novel case of midlenticular intraocular lens optic opacification in the setting of retained perfluorocarbon liquid following retinal detachment repair.

Pegaptanib sodium for macular edema secondary to branch retinal vein occlusion.

Purpose: To assess the efficacy and safety of intravitreous pegaptanib sodium (Macugen; EyeTech Pharmaceuticals/Pfizer Inc, New York, New York, USA) for macular edema secondary to branch retinal vein occlusion (BRVO).

Design: Prospective, randomized, dose-finding study.

Methods: Twenty subjects from three clinical practices in the United States with BRVO of more than 1 month's and fewer than 6 months' duration; best-corrected visual acuity (BCVA) 70 to 25 Early Treatment Diabetic Retinopathy Study letters inclusive (approximately 20/40 to 20/320 Snellen); and central foveal thickness of 250 microm or more were included.

Progenitor cell therapy for heart disease.

Many cell types are currently being studied as potential sources of cardiomyocytes for cell transplantation therapy to repair and regenerate damaged myocardium. The question remains as to which progenitor cell represents the best candidate. Bone marrow-derived cells and endothelial progenitor cells have been tested in clinical studies.

Comparative antimicrobial activity of granulysin against bacterial biothreat agents.

Granulysin is a cationic protein produced by human T cells and natural killer cells that can kill bacterial pathogens through disruption of microbial membrane integrity. Herein we demonstrate antimicrobial activity of the granulysin peptide derived from the active site against Bacillus anthracis, Yersinia pestis, Francisella tularensis, and Burkholderia mallei, and show pathogen-specific differences in granulysin peptide effects. The susceptibility of Y.

Endophthalmitis after pars plana vitrectomy a 20- and 25-gauge comparison.

Objective: Recent retrospective analyses have suggested that postoperative endophthalmitis may be more frequent with 25- than 20-gauge pars plana vitrectomy (PPV). Because the infection risk may depend on the suturing status of the sclerotomy, and the perioperative anti-infection protocol, we compared the incidence rate of endophthalmitis after sutureless 25-gauge versus sutured 20-gauge PPV on a large cohort of patients operated with a standardized perioperative anti-infection protocol.

Design: Retrospective comparative case series.

Submacular combination treatment for management of acute, massive submacular hemorrhage in age-related macular degeneration.

A surgical technique is described combining submacular anti-vascular endothelial growth factor (anti-VEGF) and recombinant tissue plasminogen activator (r-TPA) with pneumatic displacement of massive submacular hemorrhage in age-related macular degeneration. An 84-year-old man with a large, acute submacular hemorrhage secondary to age-related macular degeneration underwent combination vitrectomy, submacular anti-VEGF and r-TPA injection with pneumatic displacement of the hemorrhage. At the last follow-up visit, 7 months after surgery, visual acuity was 20/80 with a small fibrovascular pigment epithelial detachment and atrophic retinal pigment epithelial changes.

Association of systemic risk factors with the progression of laser-treated retinopathy of prematurity to retinal detachment.

Purpose: To identify systemic risk factors associated with treatment failure of diode laser photocoagulation for threshold or prethreshold retinopathy of prematurity (ROP).

Methods: Consecutive infants treated with laser at our institution and infants referred from outside centers with progression to stage 4 or 5 ROP after laser treatment were included in this retrospective study. Two groups were identified: those with regression of ROP after laser (LT group; 196 eyes of 98 infants) and those with progression to stage 4 or 5 ROP after laser (ST group; 134 eyes of 80 infants).

Pediatric rhegmatogenous retinal detachment: clinical features and surgical outcomes.

Objective: To describe the characteristics of and surgical outcomes for primary pediatric rhegmatogenous retinal detachment (RRD) and to evaluate whether specific characteristics impact anatomical outcomes after surgical intervention.

Methods: Data for consecutive patients (18 years of age or younger) with RRD who required surgery over a 5-year period were studied retrospectively. Patients with recurrent retinal detachment or active retinopathy of prematurity were excluded.

Traumatic macular hole in shaken baby syndrome successfully treated with pars plicata vitrectomy and gas tamponade.

Purpose: To describe an infant with shaken baby syndrome and a traumatic macular hole treated with pars plana vitrectomy and gas tamponade.

Design: Case report.

Methods: A 4-month-old infant with suspected shaken baby syndrome presented with intraretinal and premacular hemorrhages.

Suprachoroidal hemorrhage as an intraoperative complication of 25-gauge pars plana vitrectomy.

Purpose: To describe a case of suprachoroidal hemorrhage occurring during 25-gauge vitrectomy.

Methods: Retrospective case review.

Results: An 80-year old pseudophakic man developed intraoperative suprachoroidal hemorrhage during a vitreous biopsy procedure for chronic intraocular inflammation.

Syphilitic scleritis and choroidal malignant melanoma of the same eye.

A 42-year-old Italian homosexual presented with a red painful eye associated with exudative retinal detachment that was subsequently attributed to syphilitic posterior scleritis. These findings all resolved with intravenous penicillin therapy. However, choroidal mass lesion persisted and subsequent ancillary imaging including B scan and ultrasonography confirmed the presence of a choroidal melanoma, which was treated with radioactive plaque therapy.