California Stress, Trauma, and Resilience Study (CalSTARS) protocol: A multiomics-based cross-sectional investigation and randomized controlled trial to elucidate the biology of ACEs and test a precision intervention for reducing stress and enhancing resilience.

Adverse Childhood Experiences (ACEs) are very common and presently implicated in 9 out of 10 leading causes of death in the United States. Despite this fact, our mechanistic understanding of how ACEs impact health is limited. Moreover, interventions for reducing stress presently use a one-size-fits-all approach that involves no treatment tailoring or precision.

Axonal Energy Crisis and Calcium Phosphate Dysregulation as Pathogenesis of Optic Disc Drusen.

Soft tissue ectopic calcification is due to abnormal accumulation of calcium and phosphate outside the bone. It is the result of the failure of a complex, active, and highly regulated process - much of which is still not well understood. Some of our understanding of ectopic calcification come from studies on diseases such as atherosclerosis, aortic valve disease and kidney stone disease.

Siponimod-associated cystoid macular edema without known risk factors.

Purpose: This case report highlights the importance of monitoring ocular health for patients starting on siponimod treatment, a sphingosine-1-phosphate receptor modulator, for relapsing-remitting multiple sclerosis. By showing how medication adverse events present in patients, we can revisit the current guidelines on ophthalmic evaluation recommendations.

Observations: We report a 60-year-old patient who presented with unilateral blurry vision upon initiating siponimod therapy for the treatment of relapsing-remitting multiple sclerosis.

Development of a novel SupraChoroidal-to-Optic-NervE (SCONE) drug delivery system.

Purpose: Targeted drug delivery to the optic nerve head may be useful in the preclinical study and later clinical management of optic neuropathies, however, there are no FDA-approved drug delivery systems to achieve this. The purpose of this work was to develop an optic nerve head drug delivery technique.

Methods: Different strategies to approach the optic nerve head were investigated, including standard intravitreal and retroorbital injections.

Perivascular neurons instruct 3D vascular lattice formation via neurovascular contact.

The vasculature of the central nervous system is a 3D lattice composed of laminar vascular beds interconnected by penetrating vessels. The mechanisms controlling 3D lattice network formation remain largely unknown. Combining viral labeling, genetic marking, and single-cell profiling in the mouse retina, we discovered a perivascular neuronal subset, annotated as Fam19a4/Nts-positive retinal ganglion cells (Fam19a4/Nts-RGCs), directly contacting the vasculature with perisomatic endfeet.

Therapeutic benefit of idebenone in patients with Leber hereditary optic neuropathy: The LEROS nonrandomized controlled trial.

Leber hereditary optic neuropathy (LHON) is a mitochondrial disease leading to rapid and severe bilateral vision loss. Idebenone has been shown to be effective in stabilizing and restoring vision in patients treated within 1 year of onset of vision loss. The open-label, international, multicenter, natural history-controlled LEROS study (ClinicalTrials.

Compartmentalized ciliation changes of oligodendrocytes in aged mouse optic nerve.

Primary cilia are microtubule-based sensory organelles that project from the apical surface of most mammalian cells, including oligodendrocytes, which are myelinating cells of the central nervous system (CNS) that support critical axonal function. Dysfunction of CNS glia is associated with aging-related white matter diseases and neurodegeneration, and ciliopathies are known to affect CNS white matter. To investigate age-related changes in ciliary profile, we examined ciliary length and frequency in the retinogeniculate pathway, a white matter tract commonly affected by diseases of aging but in which expression of cilia has not been characterized.

Peripapillary and macular microvasculature features of non-arteritic anterior ischemic optic neuropathy.

Purpose: The hallmark of non-arteritic anterior ischemic optic neuropathy (NAION) is vascular compromise to the anterior optic nerve and thinning of the retinal nerve fiber layer (RNFL) and secondary degeneration of the retinal ganglion cell body or thinning of the ganglion cell complex (GCC). This study investigates optical coherence tomography (OCT) and OCT Angiography (OCTA) changes in chronic NAION and identifies imaging biomarkers that best predict disease.

Methods: We performed a retrospective case-control study of 24 chronic NAION eyes (18 patients) and 70 control eyes (45 patients) to compare both whole-eye and regional OCT, OCTA, static perimetry measurements.

High Altitude as a Risk Factor for the Development of Nonarteritic Anterior Ischemic Optic Neuropathy.

Background: Episodic high-altitude exposure leads to optic disc edema and retinopathy. It is uncertain whether high-altitude exposure is a risk factor for nonarteritic anterior ischemic optic neuropathy (NAION).

Methods: We performed a single-center, retrospective, cross-sectional case study of 5 patients with high-altitude-associated NAION (HA-NAION) from April 2014 to April 2019.

Association of left ventricular diastolic function with coronary artery calcium score: A Project Baseline Health Study.

Background: Coronary artery calcium (CAC) and left ventricular diastolic dysfunction (LVDD) are strong predictors of cardiovascular events and share common risk factors. However, their independent association remains unclear.

Methods: In the Project Baseline Health Study (PBHS), 2082 participants underwent cardiac-gated, non-contrast chest computed tomography (CT) and echocardiography.

Upregulation of retinal VEGF and connexin 43 in murine nonarteritic anterior ischemic optic neuropathy induced with 577 nm laser.

Nonarteritic anterior ischemic optic neuropathy (NAION) is a common acute optic neuropathy and cause of irreversible vision loss in those older than 50 years of age. There is currently no effective treatment for NAION and the biological mechanisms leading to neuronal loss are not fully understood. Promising novel targets include glial cells activation and intercellular communication mediated by molecules such as gap junction protein Connexin 43 (Cx43), which modulate neuronal fate in central nervous system disorders.

Multicolor Imaging of Optic Disc Drusen.

Optic disc drusen (ODD) are calcified deposits at the anterior optic nerve that are often detectable by ophthalmic imaging, including optical coherence tomography and fundus autofluorescence imaging. Multicolor (MC) imaging is a novel modality that captures reflectance of blue, green, and near-infrared laser lights with confocal scanning laser ophthalmoscopy to rapidly acquire high-resolution reflectance images of the optic disc and retina. Here, we show an eye with 3 MC imaging features of ODD, including prominent green hyperreflectance of the optic disc, green sheathing of the papillary and peripapillary vasculature (arterioles > venules), and presence of orange superficial ODD.

Predicting Visuo-Motor Diseases From Eye Tracking Data.

Eye tracking, or oculography, provides insight into where a person is looking. Recent advances in camera technology and machine learning have enabled prevalent devices like smart-phones to track gaze and visuo-motor behavior at near clinical-quality resolution. A critical gap in using oculography to diagnose visuo-motor dysfunction on a large scale is in the design of visual task paradigms, algorithms for diagnosis, and sufficiently large datasets.

Variation in Evolving Optic Neuritis.

Background: The typical natural history of optic neuritis is subjected to important exceptions. Recognition of these exceptions has led to valuable insights regarding specific etiologies of optic neuritis. Exceptions to the natural history of recovering optic neuritis are well-defined (e.

Immunoprofiling of Nonarteritic Anterior Ischemic Optic Neuropathy.

Purpose: Nonarteritic anterior ischemic optic neuropathy (NAION) is a common acute optic neuropathy in those older than 50 years. There is no blood diagnostic test or efficient treatment for NAION. We investigated the suitability of blood inflammatory proteins as biomarkers and therapeutic targets of NAION.

Freezing of saccades in dopa-responsive parkinsonian syndrome.

Purpose: Ocular motor abnormalities such as abnormal saccades are common in idiopathic Parkinson's disease (PD) and atypical parkinsonian syndrome, such as progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). In this study, we describe a case of patient with PD and show a video illustrating severe delay of reflexive saccades.

Observations: A 68-year-old Caucasian woman with diagnosis of PD presented for evaluation of diplopia.

Topographic Quadrant Analysis of Peripapillary Superficial Microvasculature in Optic Disc Drusen.

Limited information is known about the topographic effect of optic disc drusen (ODD) on peripapillary retinal nerve fibers and microvasculature. This study aims to understand the structural and functional impact of ODD in different quadrants of the optic disc. We performed a retrospective case-control study of 22 ODD patients (34 eyes) and 26 controls (33 eyes) to compare optical coherence tomography (OCT) retinal nerve fiber layer (RNFL), OCT angiography (OCTA), and corresponding static perimetry mean deviation (MD) calculated using the modified Garway-Heath map in different quadrants of the optic disc.

Hypoxia-induced inflammation: Profiling the first 24-hour posthypoxic plasma and central nervous system changes.

Central nervous system and visual dysfunction is an unfortunate consequence of systemic hypoxia in the setting of cardiopulmonary disease, including infection with SARS-CoV-2, high-altitude cerebral edema and retinopathy and other conditions. Hypoxia-induced inflammatory signaling may lead to retinal inflammation, gliosis and visual disturbances. We investigated the consequences of systemic hypoxia using serial retinal optical coherence tomography and by assessing the earliest changes within 24h after hypoxia by measuring a proteomics panel of 39 cytokines, chemokines and growth factors in the plasma and retina, as well as using retinal histology.

Multimodal Imaging Features of Optic Disc Drusen.

Purpose: To identify key en face multimodal imaging features of optic disc drusen (ODD).

Design: Retrospective cross-sectional study.

Methods: Setting: a single academic center.

Updates on ophthalmic imaging features of optic disc drusen, papilledema, and optic disc edema.

Purpose Of Review: Optic nerve head elevation can be associated with vision loss. This review provides an update regarding key features of optic disc drusen (ODD) compared with papilledema from increased intracranial pressure and optic disc edema from other causes.

Recent Findings: Clinical history and funduscopic examination are not sufficient to correctly diagnose different causes of optic nerve head elevation.

Dual Specific Phosphatase 14 Deletion Rescues Retinal Ganglion Cells and Optic Nerve Axons after Experimental Anterior Ischemic Optic Neuropathy.

Purpose: Understanding molecular changes is essential for designing effective treatments for nonarteritic anterior ischemic optic neuropathy (AION), the most common acute optic neuropathy in adults older than 50 years. We investigated changes in the mitogen-activated protein kinase (MAPK) pathway after experimental AION and focused on dual specificity phosphatase 14 (Dusp14), an atypical MAPK phosphatase that is downstream of Krüppel-like transcription factor (KLF) 9-mediated inhibition of retinal ganglion cell (RGC) survival and axonal regeneration.

Materials And Methods: We induced severe AION in a photochemical thrombosis model in adult C57BL/6 wild-type and Dusp14 knockout mice.

The Project Baseline Health Study: a step towards a broader mission to map human health.

The Project Baseline Health Study (PBHS) was launched to map human health through a comprehensive understanding of both the health of an individual and how it relates to the broader population. The study will contribute to the creation of a biomedical information system that accounts for the highly complex interplay of biological, behavioral, environmental, and social systems. The PBHS is a prospective, multicenter, longitudinal cohort study that aims to enroll thousands of participants with diverse backgrounds who are representative of the entire health spectrum.