Peripapillary hyperreflective ovoid mass-like structures-a novel entity as frequent cause of pseudopapilloedema in children.

BACKGROUND: Optic nerve head drusen (ONHD) are considered the most common cause for pseudopapilloedema in children. We aimed to investigate and further characterize a new type of optic nerve head lesion on enhanced depth imaging optical coherence tomography (EDI-OCT) named peripapillary hyperreflective ovoid mass-like structures (PHOMS), and ONHD in asymptomatic children with pseudopapilloedema. METHODS: Retrospective cohort study including 64 eyes from 32 patients with pseudopapilloedema due to PHOMS and/or ONHD. Mean age was 9.0 ± 3.1 years. PHOMS and ONHD were identified and classified on EDI-OCT and infrared images. Ultrasound images were classified for the presence of hyperechogenic structures of the optic nerve head. RESULTS: On EDI-OCT, PHOMS were detected in 63 out of 64 eyes (98.4%). In 60 eyes (93.8%), small hyperreflective foci inside the PHOMS were present. In all cases, we identified a new ring sign visible on infrared images, corresponding clearly to the edge of the PHOMS as seen on EDI-OCT. On ultrasound, we describe a new feature of PHOMS appearing as small hyperechogenic structures without posterior shadowing. In 13 eyes (20.3%), ONHD were present on EDI-OCT and ultrasound. CONCLUSION: This is the first study showing that PHOMS are the most common cause for pseudopapilloedema in children. PHOMS is a new entity of optic nerve head lesions. It might be a precursor of buried optic nerve head drusen, which can lead to visual field defects, haemorrhages and CNV. This study offers new tools to identify and follow-up these lesions early in childhood using EDI-OCT.

The identification of nuclear αvß3 integrin in ovarian cancer: non-paradigmal localization with cancer promoting actions.

Nuclear translocation of transmembrane proteins was reported in high-grade serous ovarian cancer (HGSOC), a highly aggressive gynecological malignancy. Although the membrane receptor αvß3 integrin is amply expressed in HGSOC and involved in disease progression, its nuclear localization was never demonstrated. Nuclear αvß3 was explored in HGSOC cells (OVCAR3, KURAMOCHI, and JHOS4), nuclear localization signal (NLS) modified ß3 OVCAR3, Chinese hamster ovaries (CHO-K1) and human embryonic kidney (HEK293) before/after transfections with ß3/ß1 integrins. We used the ImageStream technology, Western blots (WB), co immunoprecipitations (Co-IP), confocal immunofluorescence (IF) microscopy, flow cytometry for cell counts and cell cycle, wound healing assays and proteomics analyses. Fresh/archived tumor tissues were collected from nine HGSOC patients and normal ovarian and fallopian tube (FT) tissues from eight nononcological patients and assessed for nuclear αvß3 by WB, confocal IF microscopy and immunohistochemistry (IHC). We identified nuclear αvß3 in HGSOC cells and tissues, but not in normal ovaries and FTs. The nuclear integrin was Tyr 759 phosphorylated and functionally active. Nuclear αvß3 enriched OVCAR3 cells demonstrated induced proliferation and oncogenic signaling, intact colony formation ability and inhibited migration. Proteomics analyses revealed a network of nuclear αvß3-bound proteins, many of which with key cancer-relevant activities. Identification of atypical nuclear localization of the αvß3 integrin in HGSOC challenges the prevalent conception that the setting in which this receptor exerts its pleiotropic actions is exclusively at the cell membrane. This discovery proposes αvß3 moonlighting functions and may improve our understanding of the molecular basis of ovarian cancer pathogenesis.