Astigmatism Management in Modern Cataract Surgery.

Astigmatism management is a frequently encountered challenge in the world of modern cataract surgery. This review article investigates the importance of astigmatic correction and seeks to uncover the critical components of preoperative evaluation. With the rapid growth of new technologies and techniques, this article aims to also catalogue and clarify the multitude of astigmatism treatment options available for the cataract surgeon.

Qualitative use of ICG angiography and lymphography in periorbital surgery.

PURPOSE: Open imaging fluorescence devices have been utilized in surgical oncology, vascular and plastic surgery; however, the role of indocyanine green (ICG) in periorbital surgery and lymphatics has not been explored. METHODS: A prospective, single-center diagnostic study was conducted from 2021 to 2022 utilizing ICG to assess both the periorbital vasculature and lymphatics. Fluorescence was captured with open-imaging fluorescent devices. For ICG angiography, a total of 5-10 mg of ICG was given intravenously at various time points to visualize intraoperative blood flow to eyelid flaps, vascular tumors, or extraocular muscles. For ICG lymphography, 0.03-0.06 mg of ICG was injected subcutaneously to visualize the periorbital and facial lymphatic drainage. RESULTS: Twenty-two patients underwent ICG angiography. Periorbital vascular supply was seen in eyelid reconstructions (n = 8), anophthalmic reconstructions (n = 2), lacrimal gland tumors (n = 2), orbital venous malformations (n = 2), tumor metastasis (n = 1) and benign tumors (n = 1). The anterior ciliary arteries were visualized to the extraocular muscles in fracture repairs (n = 3) and muscle biopsies (n = 2). Ten patients underwent ICG lymphangiography highlighting the global periorbital lymphatic system. CONCLUSION: ICG allows for visualization of the vasculature of extraocular muscles and tumors, assessing perfusion of flaps during reconstruction and the global periorbital lymphatic drainage pathways.

Globe Compression by Bone Fragments in Orbital Blow-in Fractures: A Case Series and Systematic Review.

PURPOSE: The purpose of this study was to describe the clinical characteristics, management, and outcomes of orbital blow-in fractures involving compression of the globe by bone fragments. METHODS: A retrospective case series and systematic literature review were performed. RESULTS: Three male patients (mean age 29 years) with orbital blow-in fractures causing globe indentation presented with extraocular movement restriction, choroidal folds, and B-scan ultrasonography demonstrating deformation of the globe contour by a hyperechoic bone fragment. All underwent surgical repair within 1 day of presentation resulting in improved visual outcomes. An additional 10 cases were identified in the literature review. The majority of patients were male (80%) with a mean age of 29 years. Fractures originated primarily from the lateral orbital wall (50%) or the orbital roof (40%). Globe compression was evident on CT of the orbit (100%) and ultrasonography (30%). Common presenting signs included decreased visual acuity (70%), restriction of supraduction (40%) or abduction (40%), choroidal folds (30%), brow laceration (40%), periorbital edema (40%), and hypoglobus (40%). Most patients underwent surgical intervention (80%) involving fracture reduction (50%) or fragment removal (38%). Reported postsurgical outcomes were excellent with resolution of diplopia, motility, and visual acuity. CONCLUSION: Globe indentation from blow-in fractures are rare. Clinicians should be suspicious in cases of high-velocity trauma to the superolateral orbit with hypoglobus, motility limitation, and indentation of the globe upon dilated exam. Prompt diagnosis and early surgical removal of the compressive orbital bone fragments in a multidisciplinary fashion can lead to good visual, functional, and cosmetic outcomes.

A review of surgical management of progressive myogenic ptosis.

PURPOSE: Surgical correction of myogenic ptosis is a sophisticated endeavor, as the disease is progressive and the post-operative course is prone to significant complications. We sought to review the literature for repair techniques in different types of myogenic ptosis. METHODS: A PubMed/MEDLINE literature search of publications pertaining to surgical outcomes of progressive myogenic ptosis repair was performed. Studies included were original retrospective studies with a minimum of four patients. RESULTS: A total of 27 articles were identified and divided by etiology of myogenic ptosis; either chronic progressive external ophthalmoplegia (CPEO), oculopharyngeal muscular dystrophy (OPMD), myasthenia gravis (MG), or mixed. Surgical techniques predominantly involved levator advancement, levator resection, frontalis sling, blepharoplasty, and Fasanella-Servat. Success rates ranged from 60.5% to 100%. Significant postoperative complications included ptosis recurrence, under-correction, over-correction, keratopathy, lagophthalmos, sling exposure, and sling infection. CONCLUSION: Like surgical repair for other forms of ptosis, correction of progressive myogenic ptosis is guided by levator excursion. However, myogenic ptosis is especially challenging as it is characterized by worsening ptosis and the loss of protective corneal mechanisms. The goals of care with myogenic ptosis involves repairing ptosis just sufficiently to alleviate visual obstruction while avoiding adverse post-operative complications. This intentional under-correction subsequently increases susceptibility for ptosis recurrence. Myogenic ptosis repair therefore requires delicate balancing between function, sustained repair, and corneal protection.

Chromatin domain alterations linked to 3D genome organization in a large cohort of schizophrenia and bipolar disorder brains.

Chromosomal organization, scaling from the 147-base pair (bp) nucleosome to megabase-ranging domains encompassing multiple transcriptional units, including heritability loci for psychiatric traits, remains largely unexplored in the human brain. In this study, we constructed promoter- and enhancer-enriched nucleosomal histone modification landscapes for adult prefrontal cortex from H3-lysine 27 acetylation and H3-lysine 4 trimethylation profiles, generated from 388 controls and 351 individuals diagnosed with schizophrenia (SCZ) or bipolar disorder (BD) (n = 739). We mapped thousands of cis-regulatory domains (CRDs), revealing fine-grained, 104-106-bp chromosomal organization, firmly integrated into Hi-C topologically associating domain stratification by open/repressive chromosomal environments and nuclear topography. Large clusters of hyper-acetylated CRDs were enriched for SCZ heritability, with prominent representation of regulatory sequences governing fetal development and glutamatergic neuron signaling. Therefore, SCZ and BD brains show coordinated dysregulation of risk-associated regulatory sequences assembled into kilobase- to megabase-scaling chromosomal domains.

Bilateral Cavernous Sinus Thrombosis in Presumed COVID-19 Infection.

Cavernous sinus thrombosis (CST) is a rare life-threatening condition where a blood clot develops within the cavernous sinus secondary to various etiologies, ranging from infection to aseptic causes (e.g., trauma or surgery). The dural sinuses and the cerebral veins have no valves, which allow retrograde blood flow according to pressure gradients. As a result, cavernous sinuses are vulnerable to septic thrombosis from infection at various sites including sphenoid and ethmoid sinuses. Less commonly, infections of the face, ears, nose, tonsils, soft palate, and teeth may lead to CST if treatment is delayed. Clinical findings of CST extending to the opposite cavernous sinus typically requires 24-48 hours after the initial presentation of orbital signs. However, we present a patient with facial and orbital cellulitis that was immediately treated with high-dose IV antibiotics within one hour of presentation and IV heparin six hours after admission and CST diagnosis. However, the patient developed a rapid progression of bilateral CST within six hours, unresponsive to treatment. Although facial cellulitis may lead to septic CST if untreated, the rapid progression of bilateral CST in the setting of acute hypoxic respiratory failure, renal failure, and coagulation abnormalities suggests a possible underlying infection and complications similar to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

Neuronal and glial 3D chromatin architecture informs the cellular etiology of brain disorders.

Cellular heterogeneity in the human brain obscures the identification of robust cellular regulatory networks, which is necessary to understand the function of non-coding elements and the impact of non-coding genetic variation. Here we integrate genome-wide chromosome conformation data from purified neurons and glia with transcriptomic and enhancer profiles, to characterize the gene regulatory landscape of two major cell classes in the human brain. We then leverage cell-type-specific regulatory landscapes to gain insight into the cellular etiology of several brain disorders. We find that Alzheimer's disease (AD)-associated epigenetic dysregulation is linked to neurons and oligodendrocytes, whereas genetic risk factors for AD highlighted microglia, suggesting that different cell types may contribute to disease risk, via different mechanisms. Moreover, integration of glutamatergic and GABAergic regulatory maps with genetic risk factors for schizophrenia (SCZ) and bipolar disorder (BD) identifies shared (parvalbumin-expressing interneurons) and distinct cellular etiologies (upper layer neurons for BD, and deeper layer projection neurons for SCZ). Collectively, these findings shed new light on cell-type-specific gene regulatory networks in brain disorders.

Ocular surface disease associated with immune checkpoint inhibitor therapy.

Immune-related adverse events (irAEs) is a term used to describe the various toxicities associated with immune checkpoint inhibitor (ICI) use. As this class of cancer immunotherapy grows, the diversity of documented irAEs also continues to expand. Ocular toxicities secondary to ICI use are relatively rare, with dry eye and uveitis as the most frequently reported ocular side effects. This article specifically investigates the relationship between ocular surface disease and ICI therapy through a review of the existing literature. Dry eye disease (DED), conjunctivitis, and keratitis were the most commonly reported irAEs affecting the ocular surface across the 29 studies reviewed. Keratoplasty graft rejection was also described in two case reports. Our review of eight clinical trials found the incidence of DED, the most common ocular surface irAE, to range from 1 to 4%. Nearly all cases of ocular surface irAEs were graded as mild or moderate in severity and were often self-limited or controlled with conservative treatment. Duration of checkpoint inhibitor use prior to onset of ocular surface side effects varied widely, ranging from days to months. Ocular surface toxicities associated with checkpoint immunotherapy appear to be under-reported and under-investigated. Further work remains to be done to investigate the full breadth of ocular surface pathologies and the molecular mechanisms by which these toxicities occur.

Cell-specific histone modification maps in the human frontal lobe link schizophrenia risk to the neuronal epigenome.

Risk variants for schizophrenia affect more than 100 genomic loci, yet cell- and tissue-specific roles underlying disease liability remain poorly characterized. We have generated for two cortical areas implicated in psychosis, the dorsolateral prefrontal cortex and anterior cingulate cortex, 157 reference maps from neuronal, neuron-depleted and bulk tissue chromatin for two histone marks associated with active promoters and enhancers, H3-trimethyl-Lys4 (H3K4me3) and H3-acetyl-Lys27 (H3K27ac). Differences between neuronal and neuron-depleted chromatin states were the major axis of variation in histone modification profiles, followed by substantial variability across subjects and cortical areas. Thousands of significant histone quantitative trait loci were identified in neuronal and neuron-depleted samples. Risk variants for schizophrenia, depressive symptoms and neuroticism were significantly over-represented in neuronal H3K4me3 and H3K27ac landscapes. Our Resource, sponsored by PsychENCODE and CommonMind, highlights the critical role of cell-type-specific signatures at regulatory and disease-associated noncoding sequences in the human frontal lobe.

The epigenomics of schizophrenia, in the mouse.

Large-scale consortia including the Psychiatric Genomics Consortium, the Common Minds Consortium, BrainSeq and PsychENCODE, and many other studies taken together provide increasingly detailed insights into the genetic and epigenetic risk architectures of schizophrenia (SCZ) and offer vast amounts of molecular information, but with largely unexplored therapeutic potential. Here we discuss how epigenomic studies in human brain could guide animal work to test the impact of disease-associated alterations in chromatin structure and function on cognition and behavior. For example, transcription factors such as MYOCYTE-SPECIFIC ENHANCER FACTOR 2C (MEF2C), or multiple regulators of the open chromatin mark, methyl-histone H3-lysine 4, are associated with the genetic risk architectures of common psychiatric disease and alterations in chromatin structure and function in diseased brain tissue. Importantly, these molecules also affect cognition and behavior in genetically engineered mice, including virus-mediated expression changes in prefrontal cortex (PFC) and other key nodes in the circuitry underlying psychosis. Therefore, preclinical and small laboratory animal work could target genomic sequences affected by chromatin alterations in SCZ. To this end, in vivo editing of enhancer and other regulatory non-coding DNA by RNA-guided nucleases including CRISPR-Cas, and designer transcription factors, could be expected to deliver pipelines for novel therapeutic approaches aimed at improving cognitive dysfunction and other core symptoms of SCZ.

The methyltransferase SETDB1 regulates a large neuron-specific topological chromatin domain.

We report locus-specific disintegration of megabase-scale chromosomal conformations in brain after neuronal ablation of Setdb1 (also known as Kmt1e; encodes a histone H3 lysine 9 methyltransferase), including a large topologically associated 1.2-Mb domain conserved in humans and mice that encompasses >70 genes at the clustered protocadherin locus (hereafter referred to as cPcdh). The cPcdh topologically associated domain (TADcPcdh) in neurons from mutant mice showed abnormal accumulation of the transcriptional regulator and three-dimensional (3D) genome organizer CTCF at cryptic binding sites, in conjunction with DNA cytosine hypomethylation, histone hyperacetylation and upregulated expression. Genes encoding stochastically expressed protocadherins were transcribed by increased numbers of cortical neurons, indicating relaxation of single-cell constraint. SETDB1-dependent loop formations bypassed 0.2-1 Mb of linear genome and radiated from the TADcPcdh fringes toward cis-regulatory sequences within the cPcdh locus, counterbalanced shorter-range facilitative promoter-enhancer contacts and carried loop-bound polymorphisms that were associated with genetic risk for schizophrenia. We show that the SETDB1 repressor complex, which involves multiple KRAB zinc finger proteins, shields neuronal genomes from excess CTCF binding and is critically required for structural maintenance of TADcPcdh.

Families with Young Children in California: Findings from the California Health Interview Survey, 2011-2014, by Geography and Home Language.

Using data from the California Health Interview Survey (CHIS) for the years 2011-2014, this report presents findings on families with children ages 0-5 years. It breaks down differences between urban, suburban, and rural families, and it highlights the characteristics of families who speak a language other than English in the home. As more than half of families with young children in California speak a language other than English in the home, the characteristics of dual language households are highlighted. In 1998, California passed the California Children and Families Act to improve development for children from the prenatal stage to five years of age. One goal of this ongoing commitment is to expand our understanding of the social and physical environments that can impact a child's well-being and school readiness.

Practical Guidelines for High-Resolution Epigenomic Profiling of Nucleosomal Histones in Postmortem Human Brain Tissue.

BACKGROUND: The nervous system may include more than 100 residue-specific posttranslational modifications of histones forming the nucleosome core that are often regulated in cell-type-specific manner. On a genome-wide scale, some of the histone posttranslational modification landscapes show significant overlap with the genetic risk architecture for several psychiatric disorders, fueling PsychENCODE and other large-scale efforts to comprehensively map neuronal and nonneuronal epigenomes in hundreds of specimens. However, practical guidelines for efficient generation of histone chromatin immunoprecipitation followed by deep sequencing (ChIP-seq) datasets from postmortem brains are needed. METHODS: Protocols and quality controls are given for the following: 1) extraction, purification, and NeuN neuronal marker immunotagging of nuclei from adult human cerebral cortex; 2) fluorescence-activated nuclei sorting; 3) preparation of chromatin by micrococcal nuclease digest; 4) ChIP for open chromatin-associated histone methylation and acetylation; and 5) generation and sequencing of ChIP-seq libraries. RESULTS: We present a ChIP-seq pipeline for epigenome mapping in the neuronal and nonneuronal nuclei from the postmortem brain. This includes a stepwise system of quality controls and user-friendly data presentation platforms. CONCLUSIONS: Our practical guidelines will be useful for projects aimed at histone posttranslational modification mapping in chromatin extracted from hundreds of postmortem brain samples in cell-type-specific manner.

NeuN+ neuronal nuclei in non-human primate prefrontal cortex and subcortical white matter after clozapine exposure.

Increased neuronal densities in subcortical white matter have been reported for some cases with schizophrenia. The underlying cellular and molecular mechanisms remain unresolved. We exposed 26 young adult macaque monkeys for 6 months to either clozapine, haloperidol or placebo and measured by structural MRI frontal gray and white matter volumes before and after treatment, followed by observer-independent, flow-cytometry-based quantification of neuronal and non-neuronal nuclei and molecular fingerprinting of cell-type specific transcripts. After clozapine exposure, the proportion of nuclei expressing the neuronal marker NeuN increased by approximately 50% in subcortical white matter, in conjunction with a more subtle and non-significant increase in overlying gray matter. Numbers and proportions of nuclei expressing the oligodendrocyte lineage marker, OLIG2, and cell-type specific RNA expression patterns, were maintained after antipsychotic drug exposure. Frontal lobe gray and white matter volumes remained indistinguishable between antipsychotic-drug-exposed and control groups. Chronic clozapine exposure increases the proportion of NeuN+ nuclei in frontal subcortical white matter, without alterations in frontal lobe volumes or cell type-specific gene expression. Further exploration of neurochemical plasticity in non-human primate brain exposed to antipsychotic drugs is warranted.

Epilepsy care and mental health care for people with epilepsy: California Health Interview Survey, 2005.

INTRODUCTION: Epilepsy, which requires complex care, can be further complicated by comorbid mental illness. Evidence indicates deficiencies exist in the care received for both epilepsy-related care and for mental health care in people with epilepsy. Evidence indicates there are deficiencies in both these areas for people with epilepsy. Our objective was to evaluate treatment gaps in epilepsy and mental health care among California adults with epilepsy and to compare the mental health services and treatment received by people with epilepsy to that of the general population. METHODS: We conducted multivariate analyses of data from the 2005 California Health Interview Survey (N = 43,020), which included data from 604 adult participants who said they had been told they had epilepsy, to examine comparisons of interest. RESULTS: Twenty-seven percent of California adults with epilepsy who had had at least 1 seizure in the past 3 months had not seen a neurologist or epilepsy specialist in the past year. Of respondents with psychological distress and epilepsy, 84% perceived a need for mental health care in the past year, but only 57% had seen a mental health provider during that time. Of respondents without epilepsy but with psychological distress, 77% perceived a need for mental health care in the past year, but only 32% had seen a mental health provider during that time. CONCLUSION: California adults with epilepsy appear to have substantial unmet needs in both epilepsy care and mental health care. Adults with epilepsy and psychological distress appeared to have received more mental health treatment than psychologically distressed adults without epilepsy. Efforts should be made to improve access to quality epilepsy care that includes assessment and treatment of mental health disorders.

Children's exposure to secondhand smoke: nearly one million affected in California.

Despite the steady decline of smoking rates in California, over 200,000 children under age 12 live in homes where smoking is allowed, and another 742,000 live with an adult or adolescent smoker. Significant differences in children's exposure to tobacco smoke and risk of exposure are found by race/ethnicity, geographic regions within the state and by poverty level. African-American children were found to have a significantly higher rate of exposure than other racial and ethnic groups, while children in the Northern/Sierra and San Joaquin Valley regions were at the highest risk of exposure to secondhand smoke. Children living in lower-income households were also at higher risk. These findings can aid strategies to decrease children's exposure to tobacco smoke in the home through targeted public health messages and outreach to those enrolled in public programs.

Self-reported HIV testing behaviors among a sample of southeast Asians in an urban setting in the United States.

In light of the abruptness and severity of the HIV/AIDS epidemic in Asia, there has been growing concern in recent years about the HIV/AIDS risks with the steady rate of Asian and Pacific Islander (AAPI) migration to the United States. Little is known, however, about existing HIV risks among non-MSM (men who have sex with men) AAPIs. The purpose of this study was to examine self-reported HIV testing behaviors and their correlates among a sample of 604 Southeast Asians living in a U.S. urban setting. The HIV testing rate among our sample adults is 30.8%, lower than the median HIV testing rate in the U.S. adult population by state, lower than that of the general adult testing rate in the study city, and lower than that of the AAPI MSM population. A low sexually transmitted infection (STI) testing rate as a proxy for low perceived sexual risks and a dearth of HIV knowledge were associated with the low HIV testing rate. Traditional health care access measures, such as availability of medical insurance and a personal doctor, cannot explain the low HIV testing rate in this predominantly immigrant population. Culturally and linguistically appropriate HIV prevention campaigns could increase the awareness of HIV/STI risk in this AAPI population.

Substance use among a sample of foreign- and U.S.-born southeast Asians in an urban setting.

Asian Americans (AA) are thought to have the lowest rates of substance use. This study examined substance use prevalence among 494 urban-dwelling Southeast Asians using snowball techniques. Prevalence estimates were age-adjusted proportionate to the U.S. Asian population. Findings show beer and alcohol consumption approximated the national percentage among 25-44 year olds. U.S.-born were about three times likelier to have past month substance use. Foreign-born Vietnamese were likelier than U.S.-born to use all substances except for beer. U.S.- and foreign-born beer consumption rates were similar. Future research is needed to delineate substance use determinants and patterns in foreign and U.S.-born AA sub-groups.