Vascular and haematopoietic cells organize into specialized tissues during early embryogenesis to supply essential nutrients to all organs and thus play critical roles in development and disease. At the top of the haemato-vascular specification cascade lies cloche, a gene that when mutated in zebrafish leads to the striking phenotype of loss of most endothelial and haematopoietic cells and a significant increase in cardiomyocyte numbers. Although this mutant has been analysed extensively to investigate mesoderm diversification and differentiation and continues to be broadly used as a unique avascular model, the isolation of the cloche gene has been challenging due to its telomeric location. Here we used a deletion allele of cloche to identify several new cloche candidate genes within this genomic region, and systematically genome-edited each candidate. Through this comprehensive interrogation, we succeeded in isolating the cloche gene and discovered that it encodes a PAS-domain-containing bHLH transcription factor, and that it is expressed in a highly specific spatiotemporal pattern starting during late gastrulation. Gain-of-function experiments show that it can potently induce endothelial gene expression. Epistasis experiments reveal that it functions upstream of etv2 and tal1, the earliest expressed endothelial and haematopoietic transcription factor genes identified to date. A mammalian cloche orthologue can also rescue blood vessel formation in zebrafish cloche mutants, indicating a highly conserved role in vertebrate vasculogenesis and haematopoiesis. The identification of this master regulator of endothelial and haematopoietic fate enhances our understanding of early mesoderm diversification and may lead to improved protocols for the generation of endothelial and haematopoietic cells in vivo and in vitro.

Consensus guidelines were developed based on published literature, expert opinion, and practical experience to bridge the gap between clinical needs and medical evidence to support the treatment of patients with noninfectious uveitis with noncorticosteroid immunomodulatory agents.

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Cosmetic injection of hyaluronic acid (HA) and other fillers is increasingly common, and the late complications of these relatively new procedures are now coming to medical attention. Three patients with delayed periocular swelling that began years after injection of HA are described, with CT, MRI, and histopathologic characterization. While HA fillers are marketed as having a temporary effect of several months, the authors demonstrate that they may persist in the body for up to 9 years. Unlike most previous reports, there was no inflammatory reaction or encapsulation, simply infiltration into more superficial subcutaneous layers. All cases improved after surgical biopsy and hyaluronidase injections. Delayed periocular swelling after filler injections from several years prior can mimic serious medical conditions. With a detailed history and high index of suspicion, one may avoid a costly and invasive workup.

Approximately half of the treated eyes had resolution of intraocular inflammation at 3 months after corticosteroid injection.

IMPORTANCE Idiopathic disease is the most frequent diagnosis in a uveitis clinic. The need to distinguish sarcoidosis from idiopathic uveitis is controversial. However, cardiac involvement in sarcoidosis can be life-threatening. OBJECTIVE To report a series of patients with uveitis and cardiac sarcoidosis to illustrate the importance of categorizing the causes of uveitis.

Purpose of review Ocular involvement in sarcoidosis is present in up to 80 percent of patients and is frequently manifested before diagnosis of the underlying systemic disease. Considering the therapeutic consequences, early diagnosis of the underlying disease is advantageous in patients presenting with ocular inflammation. There are several ocular findings suggestive of underlying sarcoidosis, such as granulomatous keratic precipitates, iris nodules, cells in the vitreous humor known as snowballs and snowbanks, and retinal periphlebitis. High suspicion is crucial for the diagnosis of sarcoidosis. This review on ocular sarcoidosis will mainly focus on new diagnostic and treatment modalities. Recent findings Recent studies found possible new diagnostic indicators for the diagnosis of ocular sarcoidosis which include not only serum profiles but also vitreous sample analysis. Ophthalmologic imaging techniques have improved to investigate the ocular structure in detail. Results from recent uveitis clinical trials have included sarcoidosis as an underlying cause and have reported positive results. Summary The diagnosis of ocular sarcoidosis can be challenging in some cases. High suspicion is important to diagnose ocular sarcoidosis with various laboratory and ophthalmic tools. There are many possible options for the treatment of ocular sarcoidosis including various biologic agents.