Sonographic Retrobulbar Spot Sign in Diagnosis of Central Retinal Artery Occlusion: A Case Report.

Central retinal artery occlusion (CRAO) is a rare emergency department presentation with high morbidity and potential for long-term vision loss. Additionally, this finding requires an expeditious embolic workup for possible systemic pathology (i.e., stroke). The gold standard for diagnosis is visualization of a pale retina with a "cherry-red spot" on the fovea seen under dilated fundoscopic examination. However, performing a dilated fundoscopic exam is often not practical and technically challenging in the emergency room setting. Alternatively, point of care ultrasound is an inexpensive, non-invasive tool that is already highly utilized in the emergency department and can aid in diagnosis. In the case described in this report, a 66-year-old female presented to the emergency department with painless, monocular vision loss. Ultrasound showed a hyperechoic density on the distal aspect of the optic nerve ("retrobulbar spot sign") and dilated fundoscopic exam showed right eye pale macula with cherry red spot, all consistent with CRAO. Here we present a case that suggests an opportunity for improvement in evaluation of monocular vision loss in the emergency department by adding bedside ocular ultrasound to aid in more rapid diagnosis of CRAO. Topics: Central retinal occlusion, vision loss, point-of-care ultrasound, ocular ultrasound, emboli.

Wide-Field In Vivo Confocal Microscopy of Meibomian Gland Acini and Rete Ridges in the Eyelid Margin.

Purpose: In vivo confocal microscopy (IVCM) has been widely used to evaluate changes in the meibomian glands (MGs) in response to age and disease. This study examined the structures described as MGs using wide-field IVCM and laser scanning confocal microscopy (LSCM) in situ and characterized their spatial distribution and localization relevant to the eyelid margin. Methods: IVCM was performed on 30 subjects aged 18 to 38 to visualize structures in the eyelid margin. Size, shape, and distribution characteristics were measured, and individual frames were montaged into wide-field images. Structures observed on IVCM were then visualized using LSCM of whole-mount and cryosectioned cadaver eyelids stained with Nile red, mucin-1 (MUC1), laminin-5, and 4',6-diamidine-2'-phenylindole dihydrochloride. Results: The size, distribution, and staining patterns of the reflective structures seen on IVCM did not correspond to the MGs in cadaver eyelids. Instead, staining profiles indicated that these structures corresponded to the rete ridges present at the dermal-epidermal junction. Wide-field imaging showed a densely populated field of rete ridges with distinct size and shape characteristics depending on their location relative to the meibomian orifices. A distal shift of the mucocutaneous junction (MCJ) was evident in some eyelids. Conclusions: IVCM is unable to visualize MGs in the human eyelid margin due to light attenuation at that tissue depth. LSCM confirms that these structures are rete ridges located at the dermal-epidermal junction. Alterations in the structure of the dermal-epidermal junction within the eyelid margin indicate a shifting of the MCJ and may impact tear film dynamics.

Two classes of matrix metalloproteinases reciprocally regulate synaptogenesis.

Synaptogenesis requires orchestrated intercellular communication between synaptic partners, with trans-synaptic signals necessarily traversing the extracellular synaptomatrix separating presynaptic and postsynaptic cells. Extracellular matrix metalloproteinases (Mmps) regulated by secreted tissue inhibitors of metalloproteinases (Timps), cleave secreted and membrane-associated targets to sculpt the extracellular environment and modulate intercellular signaling. Here, we test the roles of Mmp at the neuromuscular junction (NMJ) model synapse in the reductionist Drosophila system, which contains just two Mmps (secreted Mmp1 and GPI-anchored Mmp2) and one secreted Timp. We found that all three matrix metalloproteome components co-dependently localize in the synaptomatrix and show that both Mmp1 and Mmp2 independently restrict synapse morphogenesis and functional differentiation. Surprisingly, either dual knockdown or simultaneous inhibition of the two Mmp classes together restores normal synapse development, identifying a reciprocal suppression mechanism. The two Mmp classes co-regulate a Wnt trans-synaptic signaling pathway modulating structural and functional synaptogenesis, including the GPI-anchored heparan sulfate proteoglycan (HSPG) Wnt co-receptor Dally-like protein (Dlp), cognate receptor Frizzled-2 (Frz2) and Wingless (Wg) ligand. Loss of either Mmp1 or Mmp2 reciprocally misregulates Dlp at the synapse, with normal signaling restored by co-removal of both Mmp classes. Correcting Wnt co-receptor Dlp levels in both Mmp mutants prevents structural and functional synaptogenic defects. Taken together, these results identify an Mmp mechanism that fine-tunes HSPG co-receptor function to modulate Wnt signaling to coordinate synapse structural and functional development.