Faculty Bibliography

SIGNIFICANCE/CONCLUSIONS:This case highlights ocular side effects of a rare, potentially life-threatening complication from coronavirus disease (COVID-19). Papilledema can occur due to increased intracranial pressure caused by cerebral venous sinus thrombosis, the incidence of which may be more likely in patients with a history of COVID-19 due to an induced hypercoagulable state. PURPOSE/OBJECTIVE:This case report presents a case of papilledema secondary to cerebral venous sinus thrombosis in a patient with a recent history of severe coronavirus disease (COVID-19). CASE REPORT/METHODS:A 29-year-old male hospitalized with a complicated course of coronavirus disease (COVID-19) was referred to the ophthalmology department for episodic blurry vision of both eyes and intermittent binocular diplopia. Clinical examination revealed diffuse bilateral optic disc edema. Magnetic resonance venography of the brain during his admission revealed subtotal occlusion of the right transverse sinus by thrombosis. At the time of diagnosis, the patient was already taking systemic anti-coagulation therapy for treatment of a recent pulmonary embolism also thought to be induced by COVID-19. After additional treatment with acetazolamide there was improvement in his optic nerve edema. CONCLUSIONS:Cerebral venous sinus thrombosis, a serious and potentially life-threatening condition, can occur as a rare complication of COVID-19. In such cases, patients may develop increased intracranial pressure, papilledema, and subsequent vison loss. Magnetic resonance venography should be ordered in patients with suspected papilledema to help rule out the presence of cerebral venous sinus thrombosis.

Patent foramen ovale might cause cryptogenic strokes, including retinal artery occlusion. Herein, we describe a previously healthy young man who presented with central retinal artery occlusion in the setting of patent foramen ovale and explore the need for transesophageal echocardiogram for its diagnosis. Cardiovascular workup and neuroimaging were unremarkable. Transthoracic echocardiogram bubble study revealed a right to left atrial shunt and subsequent transesophageal echocardiogram disclosed patent foramen ovale. This congenital cardiac anomaly was the likely conduit for a thrombo-embolic central retinal artery occlusion. We identified seven patients with patent foramen ovale associated with central retinal artery occlusion in the literature. Transthoracic echocardiogram was diagnostic in only one patient (14.3%), whereas transesophageal echocardiogram was required to reveal patent foramen ovale in the remaining six (85.7%). Our case and the previous reports support the link between central retinal artery occlusion and patent foramen ovale. Therefore, providers should consider the more sensitive transesophageal echocardiogram during the initial evaluation of young patients without immediately identifiable causes of retinal artery occlusion.

Paranasal sinus mucoceles are benign lesions that commonly present with orbital signs due to their anatomic proximity. We are reporting a case of bilateral frontal sinus mucocele presenting with spontaneous eyelid ecchymosis. To our knowledge this is the first case report of eyelid ecchymosis as the initial sign of this condition. In addition, our patient lacked commonly described symptoms such as diplopia or pain. This report highlights the importance of including frontal sinus mucocele in the differential diagnosis of spontaneous periorbital ecchymosis.

PURPOSE/OBJECTIVE:We present here a patient with choroidal metastases of choriocarcinoma; her clinical and pathologic findings are described. METHODS:Retrospective case study with fundus photographs. A 23-year-old woman presented with a dense vitritis, retinal detachment, and underlying chorioretinal lesions. Systemic workup revealed choriocarcinoma with disseminated metastases. RESULTS:This patient's underlying malignancy was unrecognized at initial presentation to ophthalmology. This case reaffirms the importance of thorough systemic investigation for atypical intraocular lesions. CONCLUSION/CONCLUSIONS:Adult intraocular neoplasms are most commonly metastases from distal primary malignancies. The same holds true for uveal malignancies. In many uveal malignancies, the intraocular lesion is a harbinger for an, as yet, undiscovered underlying systemic malignancy.

Protein kinase M zeta (PKM zeta) is a newly described form of PKC that is necessary and sufficient for the maintenance of hippocampal long term potentiation (LTP) and the persistence of memory in Drosophila. PKM zeta is the independent catalytic domain of the atypical PKC zeta isoform and produces long term effects at synapses because it is persistently active, lacking autoinhibition from the regulatory domain of PKC zeta. PKM has been thought of as a proteolytic fragment of PKC. Here we report that brain PKM zeta is a new PKC isoform, synthesized from a PKM zeta mRNA encoding a PKC zeta catalytic domain without a regulatory domain. Multiple zeta-specific antisera show that PKM zeta is expressed in rat forebrain as the major form of zeta in the near absence of full-length PKC zeta. A PKC zeta knockout mouse, in which the regulatory domain was disrupted and catalytic domain spared, still expresses brain PKM zeta, indicating that this form of PKM is not a PKC zeta proteolytic fragment. Furthermore, the distribution of brain PKM zeta does not correlate with PKC zeta mRNA but instead with an alternate zeta RNA transcript thought incapable of producing protein. In vitro translation of this RNA, however, generates PKM zeta of the same molecular weight as that in brain. Metabolic labeling of hippocampal slices shows increased de novo synthesis of PKM zeta in LTP. Because PKM zeta is a kinase synthesized in an autonomously active form and is necessary and sufficient for maintaining LTP, it serves as an example of a link coupling gene expression directly to synaptic plasticity.

Synaptic stimulation activates signal transduction pathways, producing persistently active protein kinases. PKMzeta is a truncated, persistently active isoform of atypical protein kinase C-zeta (aPKCzeta), which lacks the N-terminal pseudosubstrate regulatory domain. Using a Pavlovian olfactory learning task in Drosophila, we found that induction of the mouse aPKMzeta (MaPKMzeta) transgene enhanced memory. The enhancement required persistent kinase activity and was temporally specific, with optimal induction at 30 minutes after training. Induction also enhanced memory after massed training and corrected the memory defect of radish mutants, but did not improve memory produced by spaced training. The 'M' isoform of the Drosophila homolog of MaPKCzeta (DaPKM) was present and active in fly heads. Chelerythrine, an inhibitor of PKMzeta, and the induction of a dominant-negative MaPKMzeta transgene inhibited memory without affecting learning. Finally, induction of DaPKM after training also enhanced memory. These results show that atypical PKM is sufficient to enhance memory in Drosophila and suggest that it is necessary for normal memory maintenance.

Long-term potentiation (LTP) and long-term depression (LTD) are persistent modifications of synaptic strength that have been implicated in learning, memory, and neuronal development. Despite their opposing effects, both forms of plasticity can be triggered by the activation of NMDA receptors. One mechanism proposed for this bidirectional response is that the specific patterns of afferent stimulation producing LTP and LTD activate to different degrees a uniform receptor population. A second possibility is that these patterns activate separate receptor subpopulations composed of different NMDA receptor (NR) subunits. To test this hypothesis we examined the inhibition of LTP and LTD by a series of competitive NMDA receptor antagonists that varied in their affinities for NR2A/B and NR2C/D subunits. The potency for the inhibition of LTP compared with inhibition of LTD varied widely among the agents. Antagonists with higher affinity for NR2A/B subunits relative to NRC/D subunits showed more potent inhibition of LTP than of LTD. D-3-(2-carboxypiperazine-4-yl)-1-propenyl-1-phosphonic acid, which binds to NR2A/B with very high affinity relative to NR2C/D, showed an approximately 1000-fold higher potency for LTP than for LTD. These results show that distinct subpopulations of NMDA receptors characterized by different NR2 subunits contribute to the induction mechanisms of potentiation and depression.