Ophthalmology Commons^™

Light Scattering By Vitreous Of Humans With Vision Degrading Myodesopsia From Floaters, Alba M Paniagua-Diaz, Justin H Nguyen, Pablo Artal, Wei Gui, J Sebag

Faculty, Staff and Student Publications

PURPOSE: Vision-degrading myodesopsia (VDM) from vitreous floaters significantly degrades vision and impacts visual quality of life (VQOL), but the relationship to light scattering is poorly understood. This study compared in vitro measures of light scatter and transmission in surgically excised human vitreous to preoperative indexes of vitreous structure, visual function, and VQOL.

METHODS: Pure vitreous collected during vitrectomy from 8 patients with VDM had wide-angle straylight measurements and dark-field imaging, performed within 36 hours of vitrectomy. Preoperative VQOL assessment with VFQ-25, contrast sensitivity (CS) measurements with Freiburg acuity contrast testing, and quantitative ultrasonography were compared to light scattering and transmission …

The Variety Of Mechanosensitive Ion Channels In R/Etinal Neurons, Ji-Jie Pang

Faculty, Staff and Students Publications

Alterations in intraocular and external pressure critically involve the pathogenesis of glaucoma, traumatic retinal injury (TRI), and other retinal disorders, and retinal neurons have been reported to express multiple mechanical-sensitive channels (MSCs) in recent decades. However, the role of MSCs in visual functions and pressure-related retinal conditions has been unclear. This review will focus on the variety and functional significance of the MSCs permeable to K+, Na+, and Ca2+, primarily including the big potassium channel (BK); the two-pore domain potassium channels TRAAK and TREK; Piezo; the epithelial sodium channel (ENaC); and the transient receptor potential channels vanilloid TRPV1, TRPV2, and …

Eye Infection Risks From Pseudomonas Aeruginosa Via Hand Soap And Eye Drops, Anna Gitter, Kristina D Mena, Karla S Mendez, Fuqing Wu, Charles P Gerba

Faculty, Staff and Student Publications

Eye infections from bacterial contamination of bulk-refillable liquid soap dispensers and artificial tear eye drops continue to occur, resulting in adverse health outcomes that include impaired vision or eye enucleation. Pseudomonas aeruginosa (P. aeruginosa), a common cause of eye infections, can grow in eye drop containers and refillable soap dispensers to high numbers. To assess the risk of eye infection, a quantitative microbial risk assessment for P. aeruginosa was conducted to predict the probability of an eye infection for two potential exposure scenarios: (i) individuals using bacteria-contaminated eye drops and (ii) contact lens wearers washing their hands with …

Ic3d Classification Of Corneal Dystrophies-Edition 3, Jayne Weiss, Christopher Rapuano, Berthold Seitz, Massimo Busin, Tero Kivelä, Nacim Bouheraoua, Cecilie Bredrup, Ken Nischal, Harshvardhan Chawla, Vincent Borderie, Kenneth Kenyon, Eung Kweon Kim, Hans Ulrik Møller, Francis Munier, Tim Berger, Walter Lisch

Wills Eye Hospital Papers

PURPOSE: The International Committee for the Classification of Corneal Dystrophies (IC3D) was created in 2005 to develop a new classification system integrating current information on phenotype, histopathology, and genetic analysis. This update is the third edition of the IC3D nomenclature.

METHODS: Peer-reviewed publications from 2014 to 2023 were evaluated. The new information was used to update the anatomic classification and each of the 22 standardized templates including the level of evidence for being a corneal dystrophy [from category 1 (most evidence) to category 4 (least evidence)].

RESULTS: Epithelial recurrent erosion dystrophies now include epithelial recurrent erosion dystrophy, category 1 ( …

Immunologic Basis For Development Of Keratoconjunctivitis Sicca In Systemic Autoimmune Diseases: Role Of Innate Immune Sensors, Michael E Stern, Argyrios N Theofilopoulos, Philipp Steven, Jerry Y Niederkorn, Robert Fox, Margarita Calonge, Christof Scheid, Stephen C Pflugfelder

Faculty, Staff and Students Publications

The literature is filled with citations reporting an increased incidence of chronic dry eye disease, also known as keratoconjunctivitis sicca, in patients with systemic autoimmune diseases such as rheumatoid arthritis, Sjögren's Syndrome, systemic sclerosis and lupus. As the most environmentally exposed mucosal surface of the body, the conjunctiva constantly responds to environmental challenges which are typically self limited, but when persistent and unresolved may provoke pathogenic innate and adaptive immune reactions. Our understanding of the pathophysiological mechanisms by which systemic autoimmune diseases cause dry eye inducing ocular surface inflammation continues to evolve. Conjunctival immune tone responds to self or foreign …

A Double-Blind, Randomized Controlled Study Of The Effects Of Celecoxib On Clinical Symptoms And Cognitive Impairment In Patients With Drug-Naïve First Episode Schizophrenia: Pharmacogenetic Impact Of Cyclooxygenase-2 Functional Polymorphisms, Dong-Mei Wang, Da-Chun Chen, Mei-Hong Xiu, Li Wang, Thomas R Kosten, Xiang-Yang Zhang

Faculty, Staff and Students Publications

Chronic low-grade peripheral and central nervous system inflammation may have a role in the pathogenesis of schizophrenia (SCZ). Inhibition of cyclooxygenase-2 (COX2), the arachidonic acid pathway, may inhibit cytokine responses and minimize inflammation. In this study, we added the COX2 inhibitor celecoxib to risperidone monotherapy to examine its efficacy on clinical symptoms and cognitive deficits in drug-naïve first episode (DNFE) SCZ patients. First, we genotyped two polymorphisms (rs5275 and rs689466) in the COX-2 gene in a case-control study of 353 SCZ patients and 422 healthy controls. Ninety patients participated in a 12-week, double-blind, randomized, placebo-controlled trial of celecoxib 400 mg/day. …

Functional Vision In Patients With Biallelic Ush2a Variants, Elise Heon, Michele Melia, Laura E Bocchino, Lassana Samarakoon, Jacque L Duncan, Allison R Ayala, Isabelle Audo, Chris Bradley, Janet K Cheetham, Gislin Dagnelie, Todd A Durham, Carel B Hoyng, Nieraj Jain, Kanishka T Jayasundera, Mark E Pennesi, Christina Y Weng, Foundation Fighting Blindness Consortium Investigator Group

Faculty, Staff and Students Publications

Purpose: To describe functional vision (FV) and investigate the relationship between FV, visual acuity (VA), and hill of vision (VTOT) at baseline in patients with biallelic USH2A variants.

Design: Multicenter, international, cross-sectional study.

Methods: In individuals with biallelic disease-causing variants in USH2A, clinical diagnosis of Usher syndrome type 2 (USH2) or autosomal recessive nonsyndromic retinitis pigmentosa (ARRP) was based on history of hearing loss and audiology examinations. The VALVVFQ-48 was administered verbally to participants ≥18 years old. VA was measured in both eyes; VTOT was determined from static perimetry in the study eye (better VA). FV scores were calculated using …

Visual Outcome And Ocular Complications In Patients With Lacrimal Gland Carcinoma After Eye-Sparing Surgery And Adjuvant Radiation Therapy, Zhenyang Zhao, Steven Jay Frank, Jing Ning, Jiawei Zhao, Xinyang Jiang, Xin A Wang, Amy C Schefler, Ehab Hanna, Amy Moreno, Brandon Gunn, Renata Ferrarotto, Bita Esmaeli

Faculty, Staff and Student Publications

Background: We report visual outcomes and ocular complications in patients with lacrimal gland carcinoma who had eye-sparing surgery followed by radiotherapy.

Methods: This review included consecutive patients with lacrimal gland carcinoma who underwent eye-sparing surgery and adjuvant radiotherapy or concurrent chemoradiation therapy between 2007 and 2018. Clinical data, including details of ophthalmological examinations and radiation treatment were reviewed.

Results: The study included 23 patients, 15 males and 8 females, with median age 51 years. Twenty patients (87%) received intensity-modulated proton therapy; 3 (13%) received intensity-modulated radiotherapy. Nineteen patients (83%) received concurrent chemotherapy. After a median follow-up time of 37 months …

Strabismus Management In Retinoblastoma Survivors, Babak Masoomian, Carol L. Shields, Hamid Riazi Esfahani, Atefeh Khalili, Fariba Ghassemi, Pukhraj Rishi, Mohammad Reza Akbari, Masoud Khorrami-Nejad

Wills Eye Hospital Papers

PURPOSE: To report the result of strabismus surgery in eye-salvaged retinoblastoma (Rb) patients.

METHODS: A retrospective case series including 18 patients with Rb and strabismus who underwent strabismus surgery after completing tumor treatment by a single pediatric ophthalmologist.

RESULTS: A total of 18 patients (10 females and 8 males) were included with a mean age of 13.3 ± 3.0 (range, 2-39) months at the time tumor presentation and 6.0 ± 1.5 (range, 4-9) years at the time of strabismus surgery. Ten (56%) patients had unilateral and 8(44%) had bilateral involvement and the most common worse eye tumor's group was D …

Inactivation Of Adenosine Receptor 2a Suppresses Endothelial-To-Mesenchymal Transition And Inhibits Subretinal Fibrosis In Mice, Qiuhua Yang, Yongfeng Cai, Qian Ma, Albert Xiong, Peishan Xu, Zhidan Zhang, Jiean Xu, Yaqi Zhou, Zhiping Liu, Dingwei Zhao, John Asara, Wei Li, Huidong Shi, Ruth B Caldwell, Akrit Sodhi, Yuqing Huo

Faculty, Staff and Students Publications

Anti–vascular endothelial growth factor therapy has had a substantial impact on the treatment of choroidal neovascularization (CNV) in patients with neovascular age-related macular degeneration (nAMD), the leading cause of vision loss in older adults. Despite treatment, many patients with nAMD still develop severe and irreversible visual impairment because of the development of subretinal fibrosis. We recently reported the anti-inflammatory and antiangiogenic effects of inhibiting the gene encoding adenosine receptor 2A (Adora2a), which has been implicated in cardiovascular disease. Here, using two mouse models of subretinal fibrosis (mice with laser injury–induced CNV or mice with a deficiency in the …

Unraveling The Intraday Variations In The Tear Fluid Proteome, Garrett Jones, Jeremy Altman, Saleh Ahmed, Tae Jin Lee, Wenbo Zhi, Shruti Sharma, Ashok Sharma

Faculty, Staff and Student Publications

PURPOSE: Tear fluid is a complex and dynamic biological fluid that plays essential roles in maintaining ocular homeostasis and protecting against the external environment. Owing to the small sample volume, studying the tear proteome is challenging. However, advances in high-resolution mass spectrometry have expanded tear proteome profiling, revealing >500 unique proteins. Tears are emerging as a noninvasive source of biomarkers for both ocular and systemic diseases; nevertheless, intraday variability of proteins in tear fluid remains questionable. This study investigates intraday variations in the tear fluid proteome to identify stable proteins that could act as candidate biomarkers.

METHODS: Tear samples from …

High Clinical Exome Sequencing Diagnostic Rates And Novel Phenotypic Expansions For Nonisolated Microphthalmia, Anophthalmia, And Coloboma, Bhavana Kunisetty, Bailey A Martin-Giacalone, Xiaonan Zhao, Pamela N Luna, Brian P Brooks, Robert B Hufnagel, Chad A Shaw, Jill A Rosenfeld, A J Agopian, Philip J Lupo, Daryl A Scott

Faculty, Staff and Student Publications

PURPOSE: A molecular diagnosis is only made in a subset of individuals with nonisolated microphthalmia, anophthalmia, and coloboma (MAC). This may be due to underutilization of clinical (whole) exome sequencing (cES) and an incomplete understanding of the genes that cause MAC. The purpose of this study is to determine the efficacy of cES in cases of nonisolated MAC and to identify new MAC phenotypic expansions.

METHODS: We determined the efficacy of cES in 189 individuals with nonisolated MAC. We then used cES data, a validated machine learning algorithm, and previously published expression data, case reports, and animal models to determine …

Reply: Efficacy Of Segmented Axial Length And Artificial Intelligence Approaches To Intraocular Lens Power Calculation In Short Eyes, Karim Kozhaya, Peter I Kenny, Li Wang, Mitchell P Weikert, Douglas D Koch

Faculty, Staff and Students Publications

No abstract provided.

Centriole And Transition Zone Structures In Photoreceptor Cilia Revealed By Cryo-Electron Tomography, Zhixian Zhang, Abigail R Moye, Feng He, Muyuan Chen, Melina A Agosto, Theodore G Wensel

Faculty, Staff and Students Publications

Primary cilia mediate sensory signaling in multiple organisms and cell types but have structures adapted for specific roles. Structural defects in them lead to devastating diseases known as ciliopathies in humans. Key to their functions are structures at their base: the basal body, the transition zone, the "Y-shaped links," and the "ciliary necklace." We have used cryo-electron tomography with subtomogram averaging and conventional transmission electron microscopy to elucidate the structures associated with the basal region of the "connecting cilia" of rod outer segments in mouse retina. The longitudinal variations in microtubule (MT) structures and the lumenal scaffold complexes connecting them …

Risk Of Alzheimer's Disease And Related Dementias In Persons With Glaucoma: A National Cohort Study, Casey Crump, Jan Sundquist, Weiva Sieh, Kristina Sundquist

Faculty, Staff and Student Publications

PURPOSE: Glaucoma is a heterogeneous group of optic neuropathies that potentially may be associated with other cerebral neurodegenerative processes leading to dementia. However, prior studies have been inconsistent. We examined dementia risks after glaucoma diagnosis in a large population-based cohort.

DESIGN: National matched cohort study.

PARTICIPANTS: A total of 324 730 persons diagnosed with glaucoma during 1995-2017 in Sweden and 3 247 300 age- and sex-matched population-based controls without prior dementia.

METHODS: Cox regression was used to compute hazard ratios (HRs) for Alzheimer's disease (AD), vascular dementia (VaD), and all-cause dementia in persons with glaucoma compared with controls, adjusting for …

Smaller Total And Subregional Cerebellar Volumes In Posttraumatic Stress Disorder: A Mega-Analysis By The Enigma-Pgc Ptsd Workgroup, Ashley A Huggins, C Lexi Baird, Melvin Briggs, Sarah Laskowitz, Ahmed Hussain, Samar Fouda, Courtney Haswell, Delin Sun, Lauren E Salminen, Neda Jahanshad, Sophia I Thomopoulos, Dick J Veltman, Jessie L Frijling, Miranda Olff, Mirjam Van Zuiden, Saskia B J Koch, Laura Nawjin, Li Wang, Ye Zhu, Gen Li, Dan J Stein, Jonathan Ipser, Soraya Seedat, Stefan Du Plessis, Leigh L Van Den Heuvel, Benjamin Suarez-Jimenez, Xi Zhu, Yoojean Kim, Xiaofu He, Sigal Zilcha-Mano, Amit Lazarov, Yuval Neria, Jennifer S Stevens, Kerry J Ressler, Tanja Jovanovic, Sanne J H Van Rooij, Negar Fani, Anna R Hudson, Sven C Mueller, Anika Sierk, Antje Manthey, Henrik Walter, Judith K Daniels, Christian Schmahl, Julia I Herzog, Pavel Říha, Ivan Rektor, Lauren A M Lebois, Milissa L Kaufman, Elizabeth A Olson, Justin T Baker, Isabelle M Rosso, Anthony P King, Isreal Liberzon, Mike Angstadt, Nicholas D Davenport, Scott R Sponheim, Seth G Disner, Thomas Straube, David Hofmann, Rongfeng Qi, Guang Ming Lu, Lee A Baugh, Gina L Forster, Raluca M Simons, Jeffrey S Simons, Vincent A Magnotta, Kelene A Fercho, Adi Maron-Katz, Amit Etkin, Andrew S Cotton, Erin N O'Leary, Hong Xie, Xin Wang, Yann Quidé, Wissam El-Hage, Shmuel Lissek, Hannah Berg, Steven Bruce, Josh Cisler, Marisa Ross, Ryan J Herringa, Daniel W Grupe, Jack B Nitschke, Richard J Davidson, Christine L Larson, Terri A Deroon-Cassini, Carissa W Tomas, Jacklynn M Fitzgerald, Jennifer Urbano Blackford, Bunmi O Olatunji, William S Kremen, Michael J Lyons, Carol E Franz, Evan M Gordon, Geoffrey May, Steven M Nelson, Chadi G Abdallah, Ifat Levy, Ilan Harpaz-Rotem, John H Krystal, Emily L Dennis, David F Tate, David X Cifu, William C Walker, Elizabeth A Wilde, Ian H Harding, Rebecca Kerestes, Paul M Thompson, Rajendra Morey

Faculty, Staff and Students Publications

Although the cerebellum contributes to higher-order cognitive and emotional functions relevant to posttraumatic stress disorder (PTSD), prior research on cerebellar volume in PTSD is scant, particularly when considering subregions that differentially map on to motor, cognitive, and affective functions. In a sample of 4215 adults (PTSD n = 1642; Control n = 2573) across 40 sites from the ENIGMA-PGC PTSD working group, we employed a new state-of-the-art deep-learning based approach for automatic cerebellar parcellation to obtain volumetric estimates for the total cerebellum and 28 subregions. Linear mixed effects models controlling for age, gender, intracranial volume, and site were used to …

Treatment Strategies For Anti-Vegf Resistance In Neovascular Age-Related Macular Degeneration By Targeting Arteriolar Choroidal Neovascularization, Yingbin Fu, Zhao Zhang, Keith A Webster, Yannis M Paulus

Faculty, Staff and Students Publications

Despite extensive use of intravitreal anti-vascular endothelial growth factor (anti-VEGF) biologics for over a decade, neovascular age-related macular degeneration (nAMD) or choroidal neovascularization (CNV) continues to be a major cause of irreversible vision loss in developed countries. Many nAMD patients demonstrate persistent disease activity or experience declining responses over time despite anti-VEGF treatment. The underlying mechanisms of anti-VEGF resistance are poorly understood, and no effective treatment strategies are available to date. Here we review evidence from animal models and clinical studies that supports the roles of neovascular remodeling and arteriolar CNV formation in anti-VEGF resistance. Cholesterol dysregulation, inflammation, and ensuing …

Collagen Type Xii Is Undetectable In Keratoconus Bowman’S Layer, Mohammed Rigi, Hyeck-Soo Son, Loren Moon, Mario Matthaei, Divya Srikumaran, Albert S Jun, Charles G Eberhart, Uri S Soiberman

Faculty, Staff and Student Publications

PURPOSE: Corneal biomechanical failure is the hallmark of keratoconus (KC); however, the cause of this failure remains elusive. Collagen type XII (

METHODS: TaqMan quantitative PCR was performed on 31 corneal epithelium samples of progressive KC and myopic control eyes. Tissue microarrays were constructed using full-thickness corneas from 61 KC cases during keratoplasty and 18 non-KC autopsy eyes and stained with an antibody specific to COL12A1. Additionally,

RESULTS: COL12A1 expression was reduced at transcript levels in KC epithelium compared to controls (ratio: 0.58, p<0.03). Immunohistochemical studies demonstrated that COL12A1 protein expression in BL was undetectable, with reduced expression in KC epithelium, basement membrane, and stroma.

CONCLUSIONS: The apparent absence of COL12A1 in KC BL, together with the functional importance that

Orbital And Periocular Complications In Patients With Sinonasal Tumours With Orbital Invasion, Jiawei Zhao, Xinyang Jiang, Ehab Hanna, Shirley Y Su, Amy Moreno, Brandon Gunn, Steven Jay Frank, Renata Ferrarotto, Jing Ning, Bita Esmaeli

Faculty, Staff and Student Publications

Aims: The purpose of this study was to determine the frequency and associated risk factors of orbital/periocular complications in patients with sinonasal tumour with orbital invasion managed with eye-sparing treatments.

Methods: A retrospective case series of patients with primary sinonasal tumour with orbital invasion from January 2008 to December 2018. Patient factors were compared between the following groups: (1)patients with orbital/periocular complications versus those who did not and (2) patients who needed secondary oculoplastic surgical procedures versus those who did not.

Results: Out of 80 patients, 48 had eye-sparing surgery, 8 had orbital exenteration and 24 were managed non-surgically. The …

Efficacy And Safety Of Artificial Tears Containing Lipidure And Hypromellose For The Treatment Of Moderate Dry Eye Disease In Contact Lens Wearers, Caterina Gagliano, Marco Zeppieri, Antonio Longo, Giovanni Rubegni, Roberta Amato, Roberta Foti, Francesco Cappellani, Massimiliano Cocuzza, Federico Visalli, Ludovica Cannizzaro, Alessandro Avitabile, Giuseppe Gagliano, Lucia Lapenna, Fabiana D'Esposito

Wills Eye Hospital Papers

Background and Objectives: Dry eye disease (DED) affects 5–50% of the global population and deeply influences everyday life activities. This study compared the efficacy, tolerability, and safety of novel Respilac artificial tears containing lipidure and hypromellose (HPMC) with the widely used Nextal artificial tears, which are also HPMC-based, for the treatment of moderate DED in contact lenses (CL) wearers.

Materials and Methods: In a prospective, single-center, randomized investigation, 30 patients aged ≥18 years, diagnosed with moderate DED, and wearing CL were randomly assigned to the Respilac (n = 15) or Nextal group (n = 15). Patients self-administrated one drop of …

Phenotypic Features Determining Visual Acuity In Albinism And The Role Of Amblyogenic Factors., Frank A Proudlock, Rebecca J Mclean, Viral Sheth, Sarim Ather, Irene Gottlob

Cooper Medical School of Rowan University Departmental Research

Albinism is a spectrum disorder causing foveal hypoplasia, nystagmus, and hypopigmentation of the iris and fundus along with other visual deficits, which can all impact vision. Albinism is also associated with amblyogenic factors which could affect monocular visual acuity. The foveal appearance in albinism can range from mild foveal hypoplasia to that which is indistinguishable from the peripheral retina. The appearance can be quickly and easily graded using the Leicester Grading System in the clinic. However, interquartile ranges of 0.3 logMAR for the grades associated with albinism limit the accuracy of the grading system in predicting vision. Here, we discuss …

Visual Field Deficits In Albinism In Comparison To Idiopathic Infantile Nystagmus., Viral Sheth, Rebecca J Mclean, Zhanhan Tu, Sarim Ather, Irene Gottlob, Frank A Proudlock

Cooper Medical School of Rowan University Departmental Research

PURPOSE: This is the first systematic comparison of visual field (VF) deficits in people with albinism (PwA) and idiopathic infantile nystagmus (PwIIN) using static perimetry. We also compare best-corrected visual acuity (BCVA) and optical coherence tomography measures of the fovea, parafovea, and circumpapillary retinal nerve fiber layer in PwA.

METHODS: VF testing was performed on 62 PwA and 36 PwIIN using a Humphrey Field Analyzer (SITA FAST 24-2). Mean detection thresholds for each eye were calculated, along with quadrants and central measures. Retinal layers were manually segmented in the macular region.

RESULTS: Mean detection thresholds were significantly lower than normative …

Examining The Association Between Posttraumatic Stress Disorder And Disruptions In Cortical Networks Identified Using Data-Driven Methods, Jin Yang, Ashley A Huggins, Delin Sun, C Lexi Baird, Courtney C Haswell, Jessie L Frijling, Miranda Olff, Mirjam Van Zuiden, Saskia B J Koch, Laura Nawijn, Dick J Veltman, Benjamin Suarez-Jimenez, Xi Zhu, Yuval Neria, Anna R Hudson, Sven C Mueller, Justin T Baker, Lauren A M Lebois, Milissa L Kaufman, Rongfeng Qi, Guang Ming Lu, Pavel Říha, Ivan Rektor, Emily L Dennis, Christopher R K Ching, Sophia I Thomopoulos, Lauren E Salminen, Neda Jahanshad, Paul M Thompson, Dan J Stein, Sheri M Koopowitz, Jonathan C Ipser, Soraya Seedat, Stefan Du Plessis, Leigh L Van Den Heuvel, Li Wang, Ye Zhu, Gen Li, Anika Sierk, Antje Manthey, Henrik Walter, Judith K Daniels, Christian Schmahl, Julia I Herzog, Israel Liberzon, Anthony King, Mike Angstadt, Nicholas D Davenport, Scott R Sponheim, Seth G Disner, Thomas Straube, David Hofmann, Daniel W Grupe, Jack B Nitschke, Richard J Davidson, Christine L Larson, Terri A Deroon-Cassini, Jennifer U Blackford, Bunmi O Olatunji, Evan M Gordon, Geoffrey May, Steven M Nelson, Chadi G Abdallah, Ifat Levy, Ilan Harpaz-Rotem, John H Krystal, Rajendra A Morey, Aristeidis Sotiras

Faculty, Staff and Students Publications

Posttraumatic stress disorder (PTSD) is associated with lower cortical thickness (CT) in prefrontal, cingulate, and insular cortices in diverse trauma-affected samples. However, some studies have failed to detect differences between PTSD patients and healthy controls or reported that PTSD is associated with greater CT. Using data-driven dimensionality reduction, we sought to conduct a well-powered study to identify vulnerable networks without regard to neuroanatomic boundaries. Moreover, this approach enabled us to avoid the excessive burden of multiple comparison correction that plagues vertex-wise methods. We derived structural covariance networks (SCNs) by applying non-negative matrix factorization (NMF) to CT data from 961 PTSD …

Biallelic Creld1 Variants Cause A Multisystem Syndrome, Including Neurodevelopmental Phenotypes, Cardiac Dysrhythmias, And Frequent Infections, Lauren Jeffries, Emily K Mis, Kirsty Mcwalter, Sandra Donkervoort, Nina N Brodsky, Jean-Marie Carpier, Weizhen Ji, Cristian Ionita, Bhaskar Roy, Jon S Morrow, Armine Darbinyan, Krishna Iyer, Ritu B Aul, Siddharth Banka, Katherine R Chao, Laura Cobbold, Stacey Cohen, Helena M Custodio, Margaret Drummond-Borg, Frances Elmslie, Erika Finanger, Bryan E Hainline, Ingo Helbig, Stacy Hewson, Ying Hu, Adam Jackson, Dragana Josifova, Monica Konstantino, Meganne E Leach, Bryan Mak, David Mccormick, Elisabeth Mcgee, Stanley Nelson, Joanne Nguyen, Kimberly Nugent, Lucy Ortega, Howard P Goodkin, Elizabeth Roeder, Sani Roy, Katie Sapp, Dimah Saade, Sanjay M Sisodiya, Karen Stals, Shelley Towner, William Wilson, Deciphering Developmental Disorders, Genomics England Research Consortium, Undiagnosed Disease Network, Mustafa K Khokha, Carsten G Bönnemann, Carrie L Lucas, Saquib A Lakhani

Faculty, Staff and Students Publications

PURPOSE: We sought to delineate a multisystem disorder caused by recessive cysteine-rich with epidermal growth factor-like domains 1 (CRELD1) gene variants.

METHODS: The impact of CRELD1 variants was characterized through an international collaboration utilizing next-generation DNA sequencing, gene knockdown, and protein overexpression in Xenopus tropicalis, and in vitro analysis of patient immune cells.

RESULTS: Biallelic variants in CRELD1 were found in 18 participants from 14 families. Affected individuals displayed an array of phenotypes involving developmental delay, early-onset epilepsy, and hypotonia, with about half demonstrating cardiac arrhythmias and some experiencing recurrent infections. Most harbored a frameshift in trans with a missense …

Integrating Genetic Regulation And Single-Cell Expression With Gwas Prioritizes Causal Genes And Cell Types For Glaucoma, Andrew R Hamel, Wenjun Yan, John M Rouhana, Aboozar Monovarfeshani, Xinyi Jiang, Puja A Mehta, Jayshree Advani, Yuyang Luo, Qingnan Liang, Skanda Rajasundaram, Arushi Shrivastava, Katherine Duchinski, Sreekar Mantena, Jiali Wang, Tavé Van Zyl, Louis R Pasquale, Anand Swaroop, Puya Gharahkhani, Anthony P Khawaja, Stuart Macgregor, Rui Chen, Veronique Vitart, Joshua R Sanes, Janey L Wiggs, Ayellet V Segrè

Faculty, Staff and Students Publications

Primary open-angle glaucoma (POAG), characterized by retinal ganglion cell death, is a leading cause of irreversible blindness worldwide. However, its molecular and cellular causes are not well understood. Elevated intraocular pressure (IOP) is a major risk factor, but many patients have normal IOP. Colocalization and Mendelian randomization analysis of >240 POAG and IOP genome-wide association study (GWAS) loci and overlapping expression and splicing quantitative trait loci (e/sQTLs) in 49 GTEx tissues and retina prioritizes causal genes for 60% of loci. These genes are enriched in pathways implicated in extracellular matrix organization, cell adhesion, and vascular development. Analysis of single-nucleus RNA-seq …

Psychological Distress And Social Support Among Community Paediatric Palliative Care Programme Caregivers: Longitudinal Analysis, Esther Chui Yan Wong, Phillip Lung Wai Au-Doung, Yvonne Yuen Ling Chu, Sandy Sin Yuet Wong, Chi Kong Li, Yin Ting Cheung

Faculty, Staff and Students Publications

No abstract provided.

Biallelic Variants In Rbm42 Cause A Multisystem Disorder With Neurological, Facial, Cardiac, And Musculoskeletal Involvement, Yiyao Chen, Bingxin Yang, Xiaoyu Merlin Zhang, Songchang Chen, Minhui Wang, Liya Hu, Nina Pan, Shuyuan Li, Weihui Shi, Zhenhua Yang, Li Wang, Yajing Tan, Jian Wang, Yanlin Wang, Qinghe Xing, Zhonghua Ma, Jinsong Li, He-Feng Huang, Jinglan Zhang, Chenming Xu

Faculty, Staff and Students Publications

Here, we report a previously unrecognized syndromic neurodevelopmental disorder associated with biallelic loss-of-function variants in the RBM42 gene. The patient is a 2-year-old female with severe central nervous system (CNS) abnormalities, hypotonia, hearing loss, congenital heart defects, and dysmorphic facial features. Familial whole-exome sequencing (WES) reveals that the patient has two compound heterozygous variants, c.304C>T (p.R102*) and c.1312G>A (p.A438T), in the RBM42 gene which encodes an integral component of splicing complex in the RNA-binding motif protein family. The p.A438T variant is in the RRM domain which impairs RBM42 protein stability in vivo. Additionally, p.A438T disrupts the interaction of …

A Proposal For The Use Of A Fixed Low-Energy Selective Laser Trabeculoplasty For Open Angle Glaucoma, Zachary Sacks, L. Jay Katz, Gus Gazzard, Sarah H. Van Tassel, Eytan Z. Blumenthal, Fabian S. Lerner, Augusto Azuara-Blanco, Gregory John Roy Spooner, Yoram Solberg, Thomas Samuelson, Michael Belkin

Wills Eye Hospital Papers

Selective laser trabeculoplasty (SLT) has been in routine clinical use for over 20 years with millions of patients successfully treated and a low rate of clinically significant complications. The procedure requires the clinician to manually position the laser beam on the trabecular meshwork using a gonioscopy lens and to titrate the SLT laser energy based on the amount of pigmentation in the angle, as well as the observation of small bubbles produced by the laser effect. We propose that SLT energy titration is unnecessary either to achieve intraocular pressure (IOP) reduction or to minimize potential side effects. Ample evidence to …

Ginkgo Biloba For Tardive Dyskinesia And Plasma Mnsod Activity: Association With Mnsod Ala-9val Variant: A Randomized, Double-Blind Trial, Dongmei Wang, Yang Tian, Jiajing Chen, Rongrong Zhu, Jiaxin Li, Huixia Zhou, Dachun Chen, Li Wang, Thomas R Kosten, Xiang-Yang Zhang

Faculty, Staff and Students Publications

Background: Excessive free radicals are implicated in the pathophysiology of tardive dyskinesia (TD), and Ginkgo biloba extract (EGb761) scavenges free radicals, thereby enhancing antioxidant enzymes such as mitochondrial manganese superoxide dismutase (MnSOD). This study examined whether EGb761 treatment would improve TD symptoms and increase MnSOD activity, particularly in TD patients with specific MnSOD Val-9Ala genotype.

Methods: An EGb761 (240 mg/day) 12-week double-blind clinical trial with 157 TD patients was randomized. The severity of TD was measured by the Abnormal Involuntary Movement Scale (AIMS) and plasma MnSOD activity was assayed before and after 12 weeks of treatment. Further, in an expanded …

Gaze Transition Entropy As A Measure Of Attention Allocation In A Dynamic Workspace Involving Automation, Zixin Cui, Tetsuya Sato, Austin Jackson, Sampath Jayarathna, Makoto Itoh, Yusuke Yamani

Psychology Faculty Publications

Real-world work environments require operators to perform multiple tasks with continual support from an automated system. Eye movement is often used as a surrogate measure of operator attention, yet conventional summary measures such as percent dwell time do not capture dynamic transitions of attention in complex visual workspace. This study analyzed eye movement data collected in a controlled a MATB-II task environment using gaze transition entropy analysis. In the study, human subjects performed a compensatory tracking task, a system monitoring task, and a communication task concurrently. The results indicate that both gaze transition entropy and stationary gaze entropy, measures of …