Recovery From Homonymous Hemianopia in Hyperglycemia-Induced Occipital Lobe Electroclinical Seizures Following Glycemic Control.

BACKGROUND: Visual changes due to hyperglycemia in diabetes are not uncommon. While blurred vision is a well-established sequela of chronic hyperglycemia, homonymous hemianopia with or without electroclinical seizures is much rarer and can be mistaken for migraine, temporal arteritis, or ischemia of the central nervous system. METHODS: This article analyzed case studies for 3 patients (67M, 68M, 52F) presenting with complex visual phenomena, from 3 to 42 days duration, including pathogenesis, clinical findings, management, and follow-up. RESULTS: Examinations demonstrated dense left homonymous hemianopias in 2 patients and a left inferior homonymous quadrantanopia in one, with no other abnormalities. Patients described vivid, nonstereotyped intermittent hallucinations in the affected fields. Blood glucose levels ranged from 13.5 to 35.0 mmol/L (243-630 mg/dL) without ketosis and HbA1c from 14.6% to 16.8%. Computed tomography of the brain showed no acute intracranial pathology. MRI of the brain either detected no abnormalities or demonstrated changes consistent with seizure activity. Electroencephalogram (EEG) demonstrated seizures over the right occipital region in each patient. EEG seizures coincided with patients' hallucinations, while they remained otherwise conscious. Oral hypoglycemic and antiepileptic medications were commenced with rapid and complete reversal of the seizures and visual field deficits, confirmed by repeat Automated 30-2 and MRI. CONCLUSIONS: Hyperglycemia-induced occipital lobe seizures with visual hallucinations and interictal homonymous visual field defects represent a rare but clinically important diagnosis. This article highlights the importance of prompt recognition and treatment to facilitate recovery.

Spontaneous Extrusion of a Conjunctivolith Containing Herpes Virus Confirmed by Electron Microscopy and Energy Dispersive Spectroscopy.

: This report describes the spontaneous extrusion from between the eyelids of a presumed conjunctivolith in a patient with resolving severe herpes zoster ophthalmicus. A 57-year-old man presented for ophthalmologic assessment and management due to severe left herpes zoster ophthalmicus. At one subsequent ophthalmologic assessment, a conjunctivolith spontaneously egressed the lateral commissure of the OS when the lateral fornix was inspected. The conjunctivolith was retrieved from the floor of the consulting room. Electron microscopic analysis and energy dispersive spectroscopy was undertaken to determine its composition. Scanning electron microscopy showed that the conjunctivolith was composed of carbon, calcium, and oxygen. Transmission electron microscopy diagnosed Herpes virus within the conjunctivolith. Conjunctivoliths, or possible lacrimal gland stones, are a very rare phenomenon, and their etiology is currently unclear. In this case, there was likely to have been an association between herpes zoster ophthalmicus and the conjunctivolith.

Lacrimal gland sinus generated by a retained cilium: case report and literature review.

Lacrimal gland stone(s) (LGSs) are rare and usually asymptomatic. LGSs should be distinguished from dacryoliths, as the former arise in the lacrimal gland. The aetiology of LGSs in many cases is likely related to a reaction to a hair within the palpebral lobe of lacrimal gland. Eye rubbing may contribute to the migration of the hair into the lacrimal gland. This case report describes the rare occurrence of an LGS with a central hair shaft (cilium) and associated sinus formation in a 39-year-old male presenting with persistent redness of, and discharge from the right eye for 4 weeks. Examination revealed a sinus opening onto the inferonasal surface of the palpebral lobe of the right lacrimal gland. The patient was treated with surgical excision of the sinus, with rapid and complete resolution of his symptoms.

Acute angle closure glaucoma misdiagnosed as sinusitis.

A 69-year-old woman developed severe right suprabulbar pain with blurred right-sided vision. There were no haloes around lights, photophobia, nausea or vomiting. Investigations in the emergency department excluded a posterior communicating/internal carotid artery aneurysm. However, she did not have an ophthalmological assessment and the initial diagnosis was of sinusitis-related headache. An urgent ear, nose and throat assessment found no abnormality, but a local ophthalmologist subsequently diagnosed and managed the patient's acute angle closure crisis. Periocular pain always deserves detailed assessment with an accurate history, visual acuity assessment and intraocular pressure measurement.

Enhanced hepatic respiratory capacity and altered lipid metabolism support metabolic homeostasis during short-term hypoxic stress.

BACKGROUND: Tissue hypoxia is a key feature of several endemic hepatic diseases, including alcoholic and non-alcoholic fatty liver disease, and organ failure. Hypoxia imposes a severe metabolic challenge on the liver, potentially disrupting its capacity to carry out essential functions including fuel storage and the integration of lipid metabolism at the whole-body level. Mitochondrial respiratory function is understood to be critical in mediating the hepatic hypoxic response, yet the time-dependent nature of this response and the role of the respiratory chain in this remain unclear. RESULTS: Here, we report that hepatic respiratory capacity is enhanced following short-term exposure to hypoxia (2 days, 10% O2) and is associated with increased abundance of the respiratory chain supercomplex III2+IV and increased cardiolipin levels. Suppression of this enhanced respiratory capacity, achieved via mild inhibition of mitochondrial complex III, disrupted metabolic homeostasis. Hypoxic exposure for 2 days led to accumulation of plasma and hepatic long chain acyl-carnitines. This was observed alongside depletion of hepatic triacylglycerol species with total chain lengths of 39-53 carbons, containing palmitic, palmitoleic, stearic, and oleic acids, which are associated with de novo lipogenesis. The changes to hepatic respiratory capacity and lipid metabolism following 2 days hypoxic exposure were transient, becoming resolved after 14 days in line with systemic acclimation to hypoxia and elevated circulating haemoglobin concentrations. CONCLUSIONS: The liver maintains metabolic homeostasis in response to shorter term hypoxic exposure through transient enhancement of respiratory chain capacity and alterations to lipid metabolism. These findings may have implications in understanding and treating hepatic pathologies associated with hypoxia.

Aromatic Higher Alcohols in Wine: Implication on Aroma and Palate Attributes during Chardonnay Aging.

The higher alcohols 2-phenylethanol, tryptophol, and tyrosol are a group of yeast-derived compounds that have been shown to affect the aroma and flavour of fermented beverages. Five variants of the industrial wine strain AWRI796, previously isolated due to their elevated production of the 'rose-like aroma' compound 2-phenylethanol, were characterised during pilot-scale fermentation of a Chardonnay juice. We show that these variants not only increase the concentration of 2-phenylethanol but also modulate the formation of the higher alcohols tryptophol, tyrosol, and methionol, as well as other volatile sulfur compounds derived from methionine, highlighting the connections between yeast nitrogen and sulfur metabolism during fermentation. We also investigate the development of these compounds during wine storage, focusing on the sulfonation of tryptophol. Finally, the sensory properties of wines produced using these strains were quantified at two time points, unravelling differences produced by biologically modulating higher alcohols and the dynamic changes in wine flavour over aging.

Assessment of Saccadic Velocity at the Bedside.

Saccades are a key component for the assessment and diagnosis of Neuro-ophthalmological disorders. Traditionally, clinicians have been taught to use large amplitude saccades (LAS) to assess saccadic velocity (SV), when small amplitude saccades (SAS) may be more effective. This study aimed to evaluate the advantages of SAS over LAS by presenting a video to 108 clinicians where both methods were used to assess a patient with a unilateral partial 6th nerve palsy. SAS was the preferred method in identifying the 6th nerve palsy by 43/55 (78.2%) of Neurologists, and 36/53 (67.9%) of Ophthalmologists. These findings indicate that SAS may be a more effective method than LAS for determining SV.

Floppy eyelid syndrome "plasty" procedure: Employment of a periosteal transposition flap for surgery of floppy eyelid syndrome.

IMPORTANCE: Floppy eyelid syndrome "plasty" (FESplasty) is a surgical technique that addresses underlying superior tarsal plate and lateral canthal instability in floppy eyelid syndrome (FES) and aims to restore normal anatomical and physiological function to the upper eyelid. BACKGROUND: To describe the use of FESplasty in the surgical management of FES, and to report outcomes in an initial patient cohort. DESIGN: Retrospective study. PARTICIPANTS: Seven patients (nine eyelids) with FES undergoing FESplasty. METHODS: A single surgeon (G.W.) performed all procedures. FESplasty utilizes a periosteal flap based at the inferolateral orbital rim, and applied to the anterior surface of the upper tarsal plate. It is combined with a titrated shortening procedure of the upper eyelid. Patient demographics, comorbidities and ocular symptoms and signs were recorded preoperatively. Pre- and postoperative upper eyelid distractibility were graded and documented. MAIN OUTCOME MEASURES: Postoperative improvement in upper eyelid distractibility and symptomatology, operative complications and FES recurrence. RESULTS: FES symptoms and upper eyelid laxity improved at last follow-up (average 24 weeks) in all patients, with no FES recurrences after a maximum follow-up of 36 weeks. One patient, in whom FESplasty exacerbated his pre-existing aponeurotic ptosis, required definitive ptosis surgery subsequently. There was one case of postoperative wound infection. Obstructive sleep apnoea was present in four of the seven patients. The remaining three patients were awaiting assessment. CONCLUSIONS AND RELEVANCE: FESplasty is likely to confer long-term effective stabilization of the lateral canthal tendon, lateral commissure and superior tarsal plate. Anatomical and functional results appeared to have been successfully achieved.

Five cases of orbital extramedullary plasmacytoma: diagnosis and management of an aggressive malignancy.

Purpose: Multiple myeloma is an insidious haematological malignancy characterised by monoclonal proliferation of plasma cells in the bone marrow. Extramedullary plasmacytoma is a rare manifestation of multiple myeloma and usually occurs in the upper respiratory tract. Orbital involvement is particularly uncommon, but may be associated with devastating visual impairment and poor clinical outcomes. Therefore, this article aims to highlight the need for multidisciplinary management of orbital extramedullary plasmacytoma. Methods: This is a retrospective observational case series of five patients. All presented to the authors for management of orbital extramedullary plasmacytomas from 2004 to 2015 at Prince of Wales and Mater Hospitals in Sydney, Australia. Medical records were reviewed for pertinent information including demographics, disease features, management strategy, and clinical progress. The study met Medical Ethics Board standards and is in accordance with the Helsinki Agreements. Results: This case series of five patients underscores the poor prognosis of orbital extramedullary plasmacytoma. Despite aggressive multidisciplinary management, four of these five patients succumbed to their illness during the study period. However, multidisciplinary management did manage to minimise symptoms and preserve quality of life. Conclusions: On a case-by-case basis, patients may derive palliative benefit from orbital surgery in conjunction with radiotherapy and chemotherapy. Orbital surgeons are encouraged to work within a multidisciplinary framework of medical specialists, including haematologists and radiation oncologists, when determining the optimal management plan in cases of orbital extramedullary plasmacytoma.

Intracranial Arterial Compression of the Anterior Visual Pathway.

Compression of anterior visual pathway (AVP) structures by intracranial arteries is observed not infrequently on neuroimaging. Whether or not such compression results in damage to these structures, however, remains unclear. This information is important to define as AVP compression by intracranial arteries may be a causative factor in patients with otherwise unexplained visual dysfunction. In a single centre, 37 patients with evidence of intracranial artery AVP compression demonstrated on magnetic resonance imaging were identified by retrospective review of case records over the period 2011-2017. Variables were collected, including patient demographics, visual acuity, visual fields, pupillary reactions and optic disc appearance for patients in the case series. Visual field deficits correlated with compression sites in the 37 patients examined. Internal carotid artery-optic nerve compression was the most frequent (unilateral compression n = 9, bilateral compression n = 14), followed by chiasmal compression by the anterior cerebral artery (n = 8) and a combination of optic nerve and chiasmal compression (n = 5). Visual acuity and visual fields were stable on follow-up (mean 4 years) in 24 of 26 cases (93%). We conclude that AVP compression by intracranial arteries may be a causative factor in unexplained visual dysfunction. The visual defects are largely non-progressive.

Specific Binding to Differentially Expressed Human Carcinoembryonic Antigen-Related Cell Adhesion Molecules Determines the Outcome of Neisseria gonorrhoeae Infections along the Female Reproductive Tract.

The gonococcal Opa proteins are an antigenically variable family of surface adhesins that bind human carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), CEACAM3, CEACAM5, and/or CEACAM6, cell surface glycoproteins that are differentially expressed on a broad spectrum of human cells and tissues. While they are presumed to be important for infection, the significance of various Opa-CEACAM-mediated cellular interactions in the context of the genital tract has remained unclear. Here, we observed that CEACAM1 and CEACAM5 are differentially expressed on epithelia lining the upper and lower portions of the human female genital tract, respectively. Using transgenic mouse lines expressing human CEACAMs in a manner that reflects this differential pattern, we considered the impact of Opa-CEACAM interactions during uncomplicated lower genital tract infections versus during pelvic inflammatory disease. Our results demonstrate that Opa-CEACAM5 binding on vaginal epithelia facilitates the long-term colonization of the lower genital tract, while Opa protein binding to CEACAM1 on uterine epithelia enhances gonococcal association and penetration into these tissues. While these Opa-dependent interactions with CEACAM-expressing epithelial surfaces promote infection, Opa binding by neutrophil-expressed CEACAMs counterbalances this by facilitating more effective gonococcal clearance. Furthermore, during uterine infections, CEACAM-dependent tissue invasion aggravates disease pathology by increasing the acute inflammatory response. Together, these findings demonstrate that the outcome of infection is determined by both the cell type-specific expression of human CEACAMs and the CEACAM specificity of the Opa variants expressed, which combine to determine the level of gonococcal association with the genital mucosa versus the extent of CEACAM-dependent inflammation and gonococcal clearance by neutrophils.

Murine host response to Neisseria gonorrhoeae upper genital tract infection reveals a common transcriptional signature, plus distinct inflammatory responses that vary between reproductive cycle phases.

BACKGROUND: The emergence of fully antimicrobial resistant Neisseria gonorrhoeae has led global public health agencies to identify a critical need for next generation anti-gonococcal pharmaceuticals. The development and success of these compounds will rely upon valid pre-clinical models of gonorrhoeae infection. We recently developed and reported the first model of upper genital tract gonococcal infection. During initial characterization, we observed significant reproductive cycle-based variation in infection outcome. When uterine infection occurred in the diestrus phase, there was significantly greater pathology than during estrus phase. The aim of this study was to evaluate transcriptional profiles of infected uterine tissue from mice in either estrus or diestrus phase in order to elucidate possible mechanisms for these differences. RESULTS: Genes and biological pathways with phase-independent induction during infection showed a chemokine dominant cytokine response to Neisseria gonorrhoeae. Despite general induction being phase-independent, this common anti-gonococcal response demonstrated greater induction during diestrus phase infection. Greater activity of granulocyte adhesion and diapedesis regulators during diestrus infection, particularly in chemokines and diapedesis regulators, was also shown. In addition to a greater induction of the common anti-gonococcal response, Gene Set Enrichment Analysis identified a diestrus-specific induction of type-1 interferon signaling pathways. CONCLUSIONS: This transcriptional analysis of murine uterine gonococcal infection during distinct points in the natural reproductive cycle provided evidence for a common anti-gonococcal response characterized by significant induction of granulocyte chemokine expression and high proinflammatory mediators. The basic biology of this host response to N. gonorrhoeae in estrus and diestrus is similar at the pathway level but varies drastically in magnitude. Overlaying this, we observed type-1 interferon induction specifically in diestrus infection where greater pathology is observed. This supports recent work suggesting this pathway has a significant, possibly host-detrimental, function in gonococcal infection. Together these findings lay the groundwork for further examination of the role of interferons in gonococcal infection. Additionally, this work enables the implementation of the diestrus uterine infection model using the newly characterized host response as a marker of pathology and its prevention as a correlate of candidate vaccine efficacy and ability to protect against the devastating consequences of N. gonorrhoeae-associated sequelae.

Sharpening the focus on ophthalmology teaching: perceptions of medical students and junior medical officers.

IMPORTANCE: Worldwide, ophthalmology teaching is being reduced or eliminated from medical school curricula. The current state of ophthalmic teaching in Australia is unknown. BACKGROUND: To evaluate the perceptions of junior medical officers (JMOs) and medical students on ophthalmology teaching in Australian medical schools. DESIGN: Survey-based cross-sectional study. PARTICIPANTS: A total of 838 JMOs and medical students from across Australia. METHODS: Fifty-six hospitals and 20 medical schools across Australia were contacted. Hardcopy and online surveys were distributed to participants at consenting institutions, evaluating the characteristics of ophthalmology teaching received during medical school and participant confidence in basic ophthalmological clinical skills and knowledge. Factor analysis was performed on confidence scores. MAIN OUTCOME MEASURES: Likert scale confidence ratings, teaching methods encountered versus preferred. RESULTS: Four hundred and thirty-two (51.6%) surveys were received from JMOs and 406 (48.4%) from medical students. The most common form of teaching received were lectures (71.3% JMOs, 65.5% medical students), while the most preferred type were hospital tutorials (37.7% JMOs, 61.6% medical students). Mean confidence in ophthalmology-specific skills and knowledge topics were not high for medical students (skills: 2.66/5, 95% confidence interval [CI] = 2.55-2.76; knowledge: 2.88/5, 95% CI = 2.80-2.96) and JMOs (skills: 2.52/5, 95% CI = 2.43-2.60; knowledge: 2.84/5, 95% CI = 2.77-2.91). Many participants voiced the need for more ophthalmology teaching, particularly clinically oriented opportunities. CONCLUSIONS AND RELEVANCE: JMOs and medical students do not show high levels of confidence in basic ophthalmological clinical skills and knowledge, and report inadequate emphasis on ophthalmology during medical school.

Intracellular Drug Uptake-A Comparison of Single Cell Measurements Using ToF-SIMS Imaging and Quantification from Cell Populations with LC/MS/MS.

ToF-SIMS is a label-free imaging method that has been shown to enable imaging of amiodarone in single rat macrophage (NR8383) cells. In this study, we show that the method extends to three other cell lines relevant to drug discovery: human embryonic kidney (HEK293), cervical cancer (HeLa), and liver cancer (HepG2). There is significant interest in the variation of drug uptake at the single cell level, and we use ToF-SIMS to show that there is great diversity between individual cells and when comparing each of the cell types. These single cell measurements are compared to quantitative measurements of cell-associated amiodarone for the population using LC/MS/MS and cell counting with flow cytometry. NR8383 and HepG2 cells uptake the greatest amount of amiodarone with an average of 2.38 and 2.60 pg per cell, respectively, and HeLa and Hek 293 have a significantly lower amount of amiodarone at 0.43 and 0.36 pg per cell, respectively. The amount of cell-associated drug for the ensemble population measurement (LC/MS/MS) is compared with the ToF-SIMS single cell data: a similar amount of drug was detected per cell for the NR8383, and HepG2 cells at a greater level than that for the HEK293 cells. However, the two techniques did not agree for the HeLa cells, and we postulate potential reasons for this.