Vision Loss from Metastatic Colon Cancer to the Planum Sphenoidale and Optic Nerves.

An 80-year-old man was seen in urgent neuro-ophthalmology consultation for bilateral vision loss. He had a past medical history of hypertension and metastatic stage IV colorectal adenocarcinoma. Four months prior to presentation, he developed gradual onset, painless blurred vision in his right eye. He underwent cataract surgery in that eye, but his vision continued to decline to the point of no light perception. He developed new onset, painless, blurred vision in his left eye 3 weeks prior to presentation and woke up with no light perception in his left eye one day prior to presentation.

Differential roles for cryptochromes in the mammalian retinal clock.

Cryptochromes 1 and 2 (CRY1/2) are key components of the negative limb of the mammalian circadian clock. Like many peripheral tissues, Cry1 and -2 are expressed in the retina, where they are thought to play a role in regulating rhythmic physiology. However, studies differ in consensus as to their localization and function, and CRY1 immunostaining has not been convincingly demonstrated in the retina. Here we describe the expression and function of CRY1 and -2 in the mouse retina in both sexes. Unexpectedly, we show that CRY1 is expressed throughout all retinal layers, whereas CRY2 is restricted to the photoreceptor layer. Retinal period 2::luciferase recordings from CRY1-deficient mice show reduced clock robustness and stability, while those from CRY2-deficient mice show normal, albeit long-period, rhythms. In functional studies, we then investigated well-defined rhythms in retinal physiology. Rhythms in the photopic electroretinogram, contrast sensitivity, and pupillary light response were all severely attenuated or abolished in CRY1-deficient mice. In contrast, these physiological rhythms are largely unaffected in mice lacking CRY2, and only photopic electroretinogram rhythms are affected. Together, our data suggest that CRY1 is an essential component of the mammalian retinal clock, whereas CRY2 has a more limited role.-Wong, J. C. Y., Smyllie, N. J., Banks, G. T., Pothecary, C. A., Barnard, A. R., Maywood, E. S., Jagannath, A., Hughes, S., van der Horst, G. T. J., MacLaren, R. E., Hankins, M. W., Hastings, M. H., Nolan, P. M., Foster, R. G., Peirson, S. N. Differential roles for cryptochromes in the mammalian retinal clock.

Integrating AI with tele-ophthalmology in Canada: a review.

The field of ophthalmology is rapidly advancing, with technological innovations enhancing the diagnosis and management of eye diseases. Tele-ophthalmology, or the use of telemedicine for ophthalmology, has emerged as a promising solution to improve access to eye care services, particularly for patients in remote or underserved areas. Despite its potential benefits, tele-ophthalmology faces significant challenges, including the need for high volumes of medical images to be analyzed and interpreted by trained clinicians. Artificial intelligence (AI) has emerged as a powerful tool in ophthalmology, capable of assisting clinicians in diagnosing and treating a variety of conditions. Integrating AI models into existing tele-ophthalmology infrastructure has the potential to revolutionize eye care services by reducing costs, improving efficiency, and increasing access to specialized care. By automating the analysis and interpretation of clinical data and medical images, AI models can reduce the burden on human clinicians, allowing them to focus on patient care and disease management. Available literature on the current status of tele-ophthalmology in Canada and successful AI models in ophthalmology was acquired and examined using the Arksey and O'Malley framework. This review covers literature up to 2022 and is split into 3 sections: 1) existing Canadian tele-ophthalmology infrastructure, with its benefits and drawbacks; 2) preeminent AI models in ophthalmology, across a variety of ocular conditions; and 3) bridging the gap between Canadian tele-ophthalmology and AI in a safe and effective manner.

Primary Vitreoretinal Lymphoma Presenting Solely with Asymptomatic Peripheral Drusenoid Lesions.

Introduction: Primary vitreoretinal lymphoma (PVRL) is a rare malignant tumor that typically involves the retina, vitreous, or optic nerve head. PVRL often occurs concurrently with central nervous system lymphoma. Here, we present the first report of a patient with biopsy-confirmed PVRL presenting solely with asymptomatic peripheral drusenoid lesions. Case Presentation: A woman in her 70s presented with new elevated amelanotic yellow lesions with overlying pigment in both of her eyes not previously seen prior to cataract surgery. Over the next 4 months, there was waxing and waning of lesions which resolved and first appeared in the right eye and then the left. A diagnostic vitrectomy of the left eye revealed B-cell lymphoma. The patient elected for initial treatment with radiation therapy of both orbits. A new lesion was identified in her right eye nearly 18 months after starting maintenance therapy with ibrutinib, following which systemic chemotherapy with methotrexate was initiated. Conclusion: Elevated clinical suspicion for a malignant process is needed for patients with progressive new retinal lesions in older age. Local radiation therapy to the orbits alone may not be sufficient to prevent progression despite initial presentation showing confinement of disease to the intraocular space.

Pre-term Familial Exudative Vitreoretinopathy: A Novel Nonsense LRP5 Mutation.

PURPOSE: This case report details the diagnosis and management of a pre-term infant with aggressive bilateral retinal pathology. METHODS: A 4-week-old preterm baby girl, born at 28 weeks and 6 days to consanguineous parents, was referred for suspected aggressive posterior retinopathy of prematurity (ROP). She had a family history of bilateral retinal detachments and intellectual disability in an older sister. Clinical assessment included retinal examination, fluorescein angiography, optical coherence tomography, dual-energy X-ray absorptiometry (DEXA), and genetic testing. The genetic testing involved sequence analysis and copy number variation analysis of 25 genes related to vitreoretinopathy. RESULTS: Retinal examination and fluorescein angiography revealed extensive non-perfusion and telangiectatic vessels in both eyes, and a macula-involving tractional retinal detachment in the left eye. Despite treatment with intravitreal bevacizumab and laser photocoagulation, they progressed to total retinal detachment and no light perception in both eyes. Genetic testing revealed a pathogenic homozygous nonsense mutation in the LRP5 gene (c.3259C>T, p.(Gln1087*)), a mutation not previously reported in association with familial exudative vitreoretinopathy (FEVR). At 10 months of age, DEXA demonstrated normal bone density, diverging from the typical presentation of osteoporosis pseudoglioma syndrome associated with LRP5 mutations. CONCLUSION: This case describes a novel mutation in a complex retinal disease and underscores the necessity of considering pre-term FEVR in the differential diagnosis of atypical or aggressive ROP in preterm infants. The overlap in clinical features between ROP and FEVR highlights the complexity of diagnosis and management and the importance of genetic testing in preterm infants with retinal vascular abnormalities.

Ensemble of deep convolutional neural networks is more accurate and reliable than board-certified ophthalmologists at detecting multiple diseases in retinal fundus photographs.

AIMS: To develop an algorithm to classify multiple retinal pathologies accurately and reliably from fundus photographs and to validate its performance against human experts. METHODS: We trained a deep convolutional ensemble (DCE), an ensemble of five convolutional neural networks (CNNs), to classify retinal fundus photographs into diabetic retinopathy (DR), glaucoma, age-related macular degeneration (AMD) and normal eyes. The CNN architecture was based on the InceptionV3 model, and initial weights were pretrained on the ImageNet dataset. We used 43 055 fundus images from 12 public datasets. Five trained ensembles were then tested on an 'unseen' set of 100 images. Seven board-certified ophthalmologists were asked to classify these test images. RESULTS: Board-certified ophthalmologists achieved a mean accuracy of 72.7% over all classes, while the DCE achieved a mean accuracy of 79.2% (p=0.03). The DCE had a statistically significant higher mean F1-score for DR classification compared with the ophthalmologists (76.8% vs 57.5%; p=0.01) and greater but statistically non-significant mean F1-scores for glaucoma (83.9% vs 75.7%; p=0.10), AMD (85.9% vs 85.2%; p=0.69) and normal eyes (73.0% vs 70.5%; p=0.39). The DCE had a greater mean agreement between accuracy and confident of 81.6% vs 70.3% (p<0.001). DISCUSSION: We developed a deep learning model and found that it could more accurately and reliably classify four categories of fundus images compared with board-certified ophthalmologists. This work provides proof-of-principle that an algorithm is capable of accurate and reliable recognition of multiple retinal diseases using only fundus photographs.

Evaluating smartphone fundoscopy as a pedagogical tool in medical education: a narrative review.

Direct ophthalmoscopy continues to be the "gold standard" method for retinal and optic nerve evaluation despite known challenges for learners to acquire this clinical skill and minimal opportunities for patient-facing practice. Here we review current literature regarding smartphone fundoscopy (SF) as an alternative learning tool that remains underutilized in Canadian medical schools. SF has significant advantages over direct ophthalmoscopy, such as enhanced learner visualization of ocular structure and pathologies, greater learner usability in comparison, and improved fundus assessment during more difficult ocular examinations such as with pediatric patients. Furthermore, SF provides opportunities for instructor exchange and feedback, group learning, increased learner confidence, and most important, an improved patient experience. Yet challenges remain with SF, including patient confidentiality during data capture and sharing and meaningful integration into an already limited and saturated curriculum. Our review finds SF to be a pedagogic tool with the potential to reinvigorate fundoscopy learning to improve competency in this important clinical skill.

Insulin in the ventral tegmental area reduces hedonic feeding and suppresses dopamine concentration via increased reuptake.

Mesolimbic dopamine (DA) signaling has been implicated in the incentive, reinforcing and motivational aspects of food intake. Insulin receptors are expressed on dopaminergic neurons of the ventral tegmental area (VTA), and insulin may act in the VTA to suppress feeding. However, the neural mechanisms underlying insulin effects in the VTA are poorly understood. Here, we measured the effects of insulin on evoked DA concentration in the VTA using fast-scan cyclic voltammetry. Insulin concentration-dependently reduced evoked somatodendritic DA in the VTA, requiring activation of phosphoinositol 3-kinase and mTOR signaling. Insulin depression of somatodendritic DA was abolished in the presence of a selective DA transporter (DAT) inhibitor, GBR 12909, as well as in VTA slices of DAT knockout mice, suggesting that insulin upregulated the number or function of DAT to reduce DA concentration. Finally, insulin administered to the VTA depressed sated feeding of sweetened high-fat food. Taken together, these results indicate that insulin depresses DA concentration in the VTA via increased reuptake of DA through DAT. Insulin-mediated decrease of DA in the VTA may suppress salience of food once satiety is reached.

Magnetic resonance or computed tomography venography in the evaluation of young overweight women with papilledema.

BACKGROUND/OBJECTIVES: To compare the yield of magnetic resonance venography (MRV)/computed tomography venography (CTV) in a group of overweight women with incidentally-discovered papilledema and symptomatic intracranial hypertension (IC-HTN) patients without risk factors for dural venous sinus thrombosis (DVST). DESIGN: Retrospective cohort study. METHODS: Retrospective cohort study of female patients between ages 16 and 50 with papilledema, body mass index >25 kg/m2 and MRV/CTV imaging. Patients were excluded if they had risk factors for DVST. The incidence of DVST and clinical features were retrieved. Patients were divided into those with incidentally-discovered papilledema (Group-1) and those who presented due to symptoms of IC-HTN (Group-2). RESULTS: One hundred three patients (45 Group-1, 58 Group-2) were included in the study. Group-2 patients were more likely to have pulsatile tinnitus (p = 0.017), transient visual obscurations, and showed a trend towards increased headache (p = 0.058). Group-2 was also more likely to have been treated with acetazolamide (p < 0.01) and undergo lumbar puncture (p = 0.02). DVST was initially reported in four patients (one in Group-1, three in Group-2), but after further review, two cases (one from Group-1, one from Group-2) were found to be false positives. The final two DVST diagnoses were in Group-2 and presented with significant neurological symptoms. CONCLUSIONS: DVST was not found among a group of 45 young, overweight women with incidentally-discovered papilledema and without DVST risk factors. We therefore believe it is reasonable practice to perform MRI alone, without dedicated MRV/CTV, in the investigation of young, overweight women with incidentally-discovered papilledema without risk factors for DVST.

Novel techniques for intraoperative parathyroid gland identification: a comprehensive review.

INTRODUCTION: The parathyroid glands (PGs) are critical for calcium regulation and homeostasis. The preservation of PGs during neck surgery is crucial to avoid postoperative hypoparathyroidism. There are no existing guidelines for intraoperative PG identification, and the current approach relies heavily on the experience of the operating surgeon. A technique that accurately and rapidly identifies PGs would represent a useful intraoperative adjunct. AREAS COVERED: This review aims to assess common dye and fluorescence-based PG imaging techniques and examine their utility for intraoperative PG identification. A literature search of published data on methylene blue (MB), indocyanine green (ICG) angiography, near-infrared autofluorescence (NIRAF), and the PGs between 1971 and 2020 was conducted on PubMed. EXPERT OPINION: NIRAF and near-infrared (NIR) parathyroid angiography have emerged as promising and reliable techniques for intraoperative PG identification. NIRAF may aid with real-time identification of both normal and diseased PGs and reduce the risk of postoperative complications such as hypocalcemia. Further large prospective multicenter studies should be conducted in thyroid and parathyroid surgical patient populations to confirm the clinical efficacy of these intraoperative NIR-based PG detection techniques.

Cocaine disinhibits dopamine neurons by potentiation of GABA transmission in the ventral tegmental area.

Drug-evoked synaptic plasticity in the mesolimbic system reshapes circuit function and drives drug-adaptive behavior. Much research has focused on excitatory transmission in the ventral tegmental area (VTA) and the nucleus accumbens (NAc). How drug-evoked synaptic plasticity of inhibitory transmission affects circuit adaptations remains unknown. We found that medium spiny neurons expressing dopamine (DA) receptor type 1 (D1R-MSNs) of the NAc project to the VTA, strongly preferring the GABA neurons of the VTA. Repeated in vivo exposure to cocaine evoked synaptic potentiation at this synapse, occluding homosynaptic inhibitory long-term potentiation. The activity of the VTA GABA neurons was thus reduced and DA neurons were disinhibited. Cocaine-evoked potentiation of GABA release from D1R-MSNs affected drug-adaptive behavior, which identifies these neurons as a promising target for novel addiction treatments.

Insulin induces long-term depression of ventral tegmental area dopamine neurons via endocannabinoids.

The prevalence of obesity has markedly increased over the past few decades. Exploration of how hunger and satiety signals influence the reward system can help us understand non-homeostatic feeding. Insulin may act in the ventral tegmental area (VTA), a critical site for reward-seeking behavior, to suppress feeding. However, the neural mechanisms underlying insulin effects in the VTA remain unknown. We demonstrate that insulin, a circulating catabolic peptide that inhibits feeding, can induce long-term depression (LTD) of mouse excitatory synapses onto VTA dopamine neurons. This effect requires endocannabinoid-mediated presynaptic inhibition of glutamate release. Furthermore, after a sweetened high-fat meal, which elevates endogenous insulin, insulin-induced LTD is occluded. Finally, insulin in the VTA reduces food anticipatory behavior in mice and conditioned place preference for food in rats. Taken together, these results suggest that insulin in the VTA suppresses excitatory synaptic transmission and reduces anticipatory activity and preference for food-related cues.