Eye Diseases Commons^™

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 …

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

Targeting Cyp51 In The Treatment Of Acanthamoeba Keratitis, Ashkan Hassani, Vineet Sadarangani, Brad Haubrich

Annual Research Symposium

Acanthamoeba castellanii causes a rare but serious ocular infection called Acanthamoeba keratitis. Risk factors for infection include contact with contaminated water and poor hygiene of contact lenses. The first-line treatment is comprised of a months-long schedule of antibiotics. However, in cases where pharmacological interventions fail to address the infection, surgery may be necessary, with the continued risk of potential vision loss. Consequently, new treatments are needed, whether new pharmacological agents or new combination therapies with current agents. As an aerobic parasite, Acanthamoeba synthesizes ergosterol as a cell membrane insert, and ergosterol biosynthesis inhibitors (EBIs), common in antifungal pharmaceuticals, could potentially …

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 …

Effect Of Suprachoroidal Triamcinolone On Intraocular Pressure: A Systematic Review And Meta-Analysis, Altamash Shahriyar Ghazanfar, Aly Hamza Khowaja, Haroon Tayyab

Department of Ophthalmology & Visual Sciences

Background: Triamcinolone acetonide is a synthetic corticosteroid with multiple ocular uses. Like other corticosteroids, it too is associated with ocular side effects such as increased intraocular pressure (IOP), glaucoma and cataracts. Suprachoroidal administration of triamcinolone is hoped to reduce the ocular side effects of the drug, especially rises in IOP. Our systematic review and meta-analysis aims to study this phenomenon.
Objectives: The purpose of this study was to evaluate the effect of suprachoroidal triamcinolone injections on IOP.
Design: Systematic review and meta-analysis.
Methods: We utilized the Medline, Scopus and Cochrane databases for this review. Studies published till June 2023, which …

Ectoine, From A Natural Bacteria Protectant To A New Treatment Of Dry Eye Disease, Xin Chen, Na Lin, Jin-Miao Li, Haixia Liu, Anmar Abu-Romman, Ebru Yaman, Fang Bian, Cintia S De Paiva, Stephen C Pflugfelder, De-Quan Li

Faculty, Staff and Students Publications

Ectoine, a novel natural osmoprotectant, protects bacteria living in extreme environments. This study aimed to explore the therapeutic effect of ectoine for dry eye disease. An experimental dry eye model was created in C57BL/6 mice exposed to desiccating stress (DS) with untreated mice as controls (UT). DS mice were dosed topically with 0.5-2.0% of ectoine or a vehicle control. Corneal epithelial defects were detected via corneal smoothness and Oregon Green dextran (OGD) fluorescent staining. Pro-inflammatory cytokines and chemokines were evaluated using RT-qPCR and immunofluorescent staining. Compared with UT mice, corneal epithelial defects were observed as corneal smoothness irregularities and strong …

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 …

Rates Of Reoperation In Duane Retraction Syndrome, Han Woong Lim, Bryce Hwang, Cyril Archambault, Scott Lambert

Wills Eye Hospital Papers

PURPOSE: To investigate the types of strabismus surgeries performed and the reoperation rate in patients with Duane retraction syndrome (DRS).

DESIGN: Retrospective cohort analysis.

PARTICIPANTS: An insurance claims data set was used to identify patients diagnosed with DRS between 2007 and 2021.

METHODS: We recorded the type of strabismus surgery performed and the timing and frequency of reoperations. The hazard ratios (HRs) for reoperation were estimated according to the surgical methods using Cox regression analysis.

RESULTS: Of the 9435 patients diagnosed with DRS, 1023 (10.8%) underwent ≥ 1 strabismus operation. The median age at surgery was 5.0 years, and patients …

Long-Term Surgical Outcomes Of Glaucoma Drainage Implants In Eyes With Preoperative Intraocular Pressure Less Than 19 Mmhg, Shahin Hallaj, Jae-Chiang Wong, Lauren E. Hock, Natasha Nayak Kolomeyer, Aakriti G. Shukla, Michael J. Pro, Marlene R. Moster, Jonathan S. Myers, Reza Razeghinejad, Daniel Lee

Wills Eye Hospital Papers

BACKGROUND: This retrospective review reports on patients who underwent glaucoma drainage implant (GDI) surgery and had baseline intraocular pressure (IOP) of ≤18 mmHg with at least one year of follow-up.

METHODS: Clinical data of 67 eyes of 67 patients were collected from patients' charts, and the outcomes of GDI were evaluated until 7 years. GDI failure was defined as IOP reduction of less than 20% from the baseline at two consecutive visits three months after surgery, decline to no light perception, or if additional glaucoma surgery was performed.

RESULTS: The average age was 65.9 ± 13.2 years. Most cases were …

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 Case Of Persistent Ophthalmic Artery Occlusion After Migraine In The Setting Of Cerebral Vascular Anomalies, Khaled Moumneh, Austin Bach

West Florida Division GME Research Day 2024

No abstract provided.

Phase 1 Trial Of Tpi 287, A Microtubule Stabilizing Agent, In Combination With Bevacizumab In Adults With Recurrent Glioblastoma, Samuel A Goldlust, Louis B Nabors, Sigmund Hsu, Nimish Mohile, Paul J Duic, Tara Benkers, Samuel Singer, Mayank Rao, Lori Cappello, Sandra L Silberman, George Farmer

Faculty, Staff and Student Publications

BACKGROUND: Recurrent glioblastoma (rGBM) has limited treatment options. This phase 1 protocol was designed to study the safety and preliminary efficacy of TPI 287, a central nervous system penetrant microtubule stabilizer, in combination with bevacizumab (BEV) for the treatment of rGBM.

METHODS: GBM patients with up to 2 prior relapses without prior exposure to anti-angiogenic therapy were eligible. A standard 3 + 3 design was utilized to determine the maximum tolerated dose (MTD) of TPI 287. Cohorts received TPI 287 at 140-220 mg/m

RESULTS: Twenty-four patients were enrolled at 6 centers. Treatment was generally well tolerated. Fatigue, myelosuppression, and peripheral …

Genotypes Of Snps Of Key Genes Regulate Susceptibility And Drug Sensitivity To Neovascular Amd, Jinglin Cui

Theses and Dissertations (ETD)

Age-related macular degeneration (AMD), particularly its neovascular form, stands as a leading cause of blindness globally, with its prevalence in our country on a steady rise. This underscores the critical impact of neovascular AMD (nAMD) management on patient quality of life and societal burden. Current optimal treatments hinge on anti-vascular endothelial growth factor (anti-VEGF) therapies, though their efficacy varies across different drugs and individuals, highlighting the importance of precise drug selection in clinical outcomes. Research suggests that factors such as baseline vision, age, disease duration, lesion size, central retina thickness, neovascularization type, and demographic differences influence nAMD prognosis. In addition, …

Patients With Floaters: Answers From Virtual Assistants And Large Language Models, Gloria Wu, Weichen Zhao, Adrial Wong, David A Lee

Faculty, Staff and Student Publications

OBJECTIVES: "Floaters," a common complaint among patients of all ages, was used as a query term because it affects 30% of all people searching for eye care. The American Academy of Ophthalmology website's "floaters" section was used as a source for questions and answers (www.aao.org). Floaters is a visual obstruction that moves with the movement of the eye. They can be associated with retinal detachment, which can lead to vision loss. With the advent of large language model (LLM) chatbots ChatGPT, Bard versus virtual assistants (VA), Google Assistant, and Alexa, we analyzed their responses to "floaters."

METHODS: Using AAO.org, "Public …

Optical Coherence Elastography Measures The Biomechanical Properties Of The Ex Vivo Porcine Cornea After Lasik, Achuth Nair, Fernando Zvietcovich, Manmohan Singh, Mitchell P Weikert, Salavat R Aglyamov, Kirill V Larin

Faculty, Staff and Students Publications

SIGNIFICANCE: The biomechanical impact of refractive surgery has long been an area of investigation. Changes to the cornea structure cause alterations to its mechanical integrity, but few studies have examined its specific mechanical impact.

AIM To quantify how the biomechanical properties of the cornea are altered by laser assisted in situ keratomileusis (LASIK) using optical coherence elastography (OCE) in ex vivo porcine corneas.

APPROACH: Three OCE techniques, wave-based air-coupled ultrasound (ACUS) OCE, heartbeat (Hb) OCE, and compression OCE were used to measure the mechanical properties of paired porcine corneas, where one eye of the pair was left untreated, and the …

Editorial: Managing Cancer Metastasis By Tackling Anticancer Drug Resistance, Erxi Wu, Zhongzhi Wu, Chao-Yie Yang, Dan Qi, Xiaoxiao Hu, Wei Li

Faculty, Staff and Students Publications

No abstract provided.

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 …

Altered Outer Retinal Structure, Electrophysiology And Visual Perception In Parkinson's Disease, Katie K N Tran, Pei Ying Lee, David I Finkelstein, Allison M Mckendrick, Bao N Nguyen, Bang V Bui, Christine T O Nguyen

Faculty, Staff and Student Publications

BACKGROUND: Visual biomarkers of Parkinson's disease (PD) are attractive as the retina is an outpouching of the brain. Although inner retinal neurodegeneration in PD is well-established this has overlap with other neurodegenerative diseases and thus outer retinal (photoreceptor) measures warrant further investigation.

OBJECTIVE: To examine in a cross-sectional study whether clinically implementable measures targeting outer retinal function and structure can differentiate PD from healthy ageing and whether these are sensitive to intraday levodopa (L-DOPA) dosing.

METHODS: Centre-surround perceptual contrast suppression, macular visual field sensitivity, colour discrimination, light-adapted electroretinography and optical coherence tomography (OCT) were tested in PD participants (n = …

Neuroimaging-Based Classification Of Ptsd Using Data-Driven Computational Approaches: A Multisite Big Data Study From The Enigma-Pgc Ptsd Consortium, Xi Zhu, Yoojean Kim, Orren Ravid, Xiaofu He, Benjamin Suarez-Jimenez, Sigal Zilcha-Mano, Amit Lazarov, Seonjoo Lee, Chadi G Abdallah, Michael Angstadt, Christopher L Averill, C Lexi Baird, Lee A Baugh, Jennifer U Blackford, Jessica Bomyea, Steven E Bruce, Richard A Bryant, Zhihong Cao, Kyle Choi, Josh Cisler, Andrew S Cotton, Judith K Daniels, Nicholas D Davenport, Richard J Davidson, Michael D Debellis, Emily L Dennis, Maria Densmore, Terri Deroon-Cassini, Seth G Disner, Wissam El Hage, Amit Etkin, Negar Fani, Kelene A Fercho, Jacklynn Fitzgerald, Gina L Forster, Jessie L Frijling, Elbert Geuze, Atilla Gonenc, Evan M Gordon, Staci Gruber, Daniel W Grupe, Jeffrey P Guenette, Courtney C Haswell, Ryan J Herringa, Julia Herzog, David Bernd Hofmann, Bobak Hosseini, Anna R Hudson, Ashley A Huggins, Jonathan C Ipser, Neda Jahanshad, Meilin Jia-Richards, Tanja Jovanovic, Milissa L Kaufman, Mitzy Kennis, Anthony King, Philipp Kinzel, Saskia B J Koch, Inga K Koerte, Sheri M Koopowitz, Mayuresh S Korgaonkar, John H Krystal, Ruth Lanius, Christine L Larson, Lauren A M Lebois, Gen Li, Israel Liberzon, Guang Ming Lu, Yifeng Luo, Vincent A Magnotta, Antje Manthey, Adi Maron-Katz, Geoffery May, Katie Mclaughlin, Sven C Mueller, Laura Nawijn, Steven M Nelson, Richard W J Neufeld, Jack B Nitschke, Erin M O'Leary, Bunmi O Olatunji, Miranda Olff, Matthew Peverill, K Luan Phan, Rongfeng Qi, Yann Quidé, Ivan Rektor, Kerry Ressler, Pavel Riha, Marisa Ross, Isabelle M Rosso, Lauren E Salminen, Kelly Sambrook, Christian Schmahl, Martha E Shenton, Margaret Sheridan, Chiahao Shih, Maurizio Sicorello, Anika Sierk, Alan N Simmons, Raluca M Simons, Jeffrey S Simons, Scott R Sponheim, Murray B Stein, Dan J Stein, Jennifer S Stevens, Thomas Straube, Delin Sun, Jean Théberge, Paul M Thompson, Sophia I Thomopoulos, Nic J A Van Der Wee, Steven J A Van Der Werff, Theo G M Van Erp, Sanne J H Van Rooij, Mirjam Van Zuiden, Tim Varkevisser, Dick J Veltman, Robert R J M Vermeiren, Henrik Walter, Li Wang, Xin Wang, Carissa Weis, Sherry Winternitz, Hong Xie, Ye Zhu, Melanie Wall, Yuval Neria, Rajendra A Morey

Faculty, Staff and Students Publications

Background: Recent advances in data-driven computational approaches have been helpful in devising tools to objectively diagnose psychiatric disorders. However, current machine learning studies limited to small homogeneous samples, different methodologies, and different imaging collection protocols, limit the ability to directly compare and generalize their results. Here we aimed to classify individuals with PTSD versus controls and assess the generalizability using a large heterogeneous brain datasets from the ENIGMA-PGC PTSD Working group.

Methods: We analyzed brain MRI data from 3,477 structural-MRI; 2,495 resting state-fMRI; and 1,952 diffusion-MRI. First, we identified the brain features that best distinguish individuals with PTSD from controls …

The Atoh1-Cre Knock-In Allele Ectopically Labels A Subpopulation Of Amacrine Cells And Bipolar Cells In Mouse Retina, Sih-Rong Wu, Huda Y Zoghbi

Duncan NRI Faculty and Staff Publications

The retina has diverse neuronal cell types derived from a common pool of retinal progenitors. Many molecular drivers, mostly transcription factors, have been identified to promote different cell fates. In Drosophila, atonal is required for specifying photoreceptors. In mice, there are two closely related atonal homologs, Atoh1 and Atoh7. While Atoh7 is known to promote the genesis of retinal ganglion cells, there is no study on the function of Atoh1 in retinal development. Here, we crossed Atoh1^Cre/+ mice to mice carrying a Cre-dependent TdTomato reporter to track potential Atoh1-lineage neurons in retinas. We characterized a heterogeneous …

Autosomal Dominant Optic Atrophy Plus Syndrome, Aaron W. Case Od, Lovelee E. Sayomac Od, Matthew J. Anderson Od

Optometric Clinical Practice

Background: Dominant optic atrophy (DOA) is the most commonly encountered hereditary optic neuropathy in clinical practice and is the result of a mutation in the OPA1 or OPA3 genes encoding mitochondrial membrane proteins. The resultant mitochondrial dysfunction causes a distinct set of ophthalmic findings and may progress to extra-ocular systems known as OPA plus syndrome. We present a case of late-onset OPA plus syndrome encompassing both typical ophthalmic findings and the rarer extra-ocular findings. Case Report: A 41 year-old Caucasian male presents for a second opinion regarding a previously diagnosed traumatic optic neuropathy. Examination revealed decreased best-corrected acuities, …

The Neuroimmune Regulation And Potential Therapeutic Strategies Of Optic Pathway Glioma, Khushboo Irshad, Yu-Kai Huang, Paul Rodriguez, Jung Lo, Benjamin E Aghoghovwia, Yuan Pan, Kun-Che Chang

Faculty, Staff and Student Publications

Optic pathway glioma (OPG) is one of the causes of pediatric visual impairment. Unfortunately, there is as yet no cure for such a disease. Understanding the underlying mechanisms and the potential therapeutic strategies may help to delay the progression of OPG and rescue the visual morbidities. Here, we provide an overview of preclinical OPG studies and the regulatory pathways controlling OPG pathophysiology. We next discuss the role of microenvironmental cells (neurons, T cells, and tumor-associated microglia and macrophages) in OPG development. Last, we provide insight into potential therapeutic strategies for treating OPG and promoting axon regeneration.

Conditional Deletion Of Cd25 In The Corneal Epithelium Reveals Sex Differences In Barrier Disruption, Anmar Abu-Romman, Kaitlin K Scholand, Sonali Pal-Ghosh, Zhiyuan Yu, Yashaswini Kelagere, Ghasem Yazdanpanah, Winston W-Y Kao, Vivien J Coulson-Thomas, Mary Ann Stepp, Cintia S De Paiva

Faculty, Staff and Students Publications

PURPOSE: IL-2 promotes activation, clonal expansion, and deletion of T cells. IL-2 signals through its heterotrimeric receptor (IL-2R) consisting of the CD25, CD122 and CD132 chains. CD25 knockout (KO) mice develop Sjögren Syndrome-like disease. This study investigates whether corneal CD25/IL-2 signaling is critical for ocular health.

METHODS: Eyes from C57BL/6 mice were collected and prepared for immunostaining or in-situ hybridization. Bulk RNA sequencing was performed on the corneal epithelium from wild-type and CD25KO mice. We generated a conditional corneal-specific deletion of CD25 in the corneal epithelium (CD25

RESULTS: In C57BL/6 mice, CD25 mRNA was expressed in ocular tissues. Protein expression …

Clinical Trials Submissions To The Ocular Surface, Gary D Novack, Cintia S De Paiva

Faculty, Staff and Students Publications

No abstract provided.

Clinical Diagnosis And Management Of Demodex Blepharitis: The Demodex Expert Panel On Treatment And Eyelid Health (Depth), Brandon D Ayres, Eric Donnenfeld, Marjan Farid, Ian Benjamin Gaddie, Preeya K Gupta, Edward Holland, Paul M Karpecki, Richard Lindstrom, Kelly K Nichols, Stephen C Pflugfelder, Christopher E Starr, Elizabeth Yeu

Faculty, Staff and Students Publications

Background: Twelve ocular surface disease experts convened to achieve consensus about Demodex blepharitis (DB) using a modified Delphi panel process.

Methods: Online surveys were administered using scaled, open-ended, true/false, and multiple-choice questions. Consensus for questions using a 1 to 9 Likert scale was predefined as median scores of 7-9 and 1-3. For other question types, consensus was achieved when 8 of 12 panellists agreed. Questions were randomized, and results of each survey informed the following survey.

Results: Twelve practitioners comprised the Demodex Expert Panel on Treatment and Eyelid Health (DEPTH). Following 3 surveys, experts agreed that DB is chronic (n …

Single Cell Analysis Of Short-Term Dry Eye Induced Changes In Cornea Immune Cell Populations, Brandon D Ayres, Eric Donnenfeld, Marjan Farid, Ian Benjamin Gaddie, Preeya K Gupta, Edward Holland, Paul M Karpecki, Richard Lindstrom, Kelly K Nichols, Stephen C Pflugfelder, Christopher E Starr, Elizabeth Yeu

Faculty, Staff and Students Publications

BACKGROUND: Twelve ocular surface disease experts convened to achieve consensus about Demodex blepharitis (DB) using a modified Delphi panel process.

METHODS: Online surveys were administered using scaled, open-ended, true/false, and multiple-choice questions. Consensus for questions using a 1 to 9 Likert scale was predefined as median scores of 7-9 and 1-3. For other question types, consensus was achieved when 8 of 12 panellists agreed. Questions were randomized, and results of each survey informed the following survey.

RESULTS: Twelve practitioners comprised the Demodex Expert Panel on Treatment and Eyelid Health (DEPTH). Following 3 surveys, experts agreed that DB is chronic (n …

Tnf Is A Critical Cytokine In Age-Related Dry Eye Disease, Yashaswini Kelagere, Kaitlin K Scholand, Erica N Dejong, Andrea I Boyd, Zhiyuan Yu, Roger A Astley, Michelle C Callegan, Dawn Me Bowdish, Helen P Makarenkova, Cintia S De Paiva

Faculty, Staff and Students Publications

Aging is a complex biological process that is characterized by low-grade inflammation, called inflammaging. Aging affects multiple organs including eye and lacrimal gland. Tumor necrosis factor (TNF) is a pleiotropic cytokine that participates in inflammation, activation of proteases such as cathepsin S, and formation of ectopic lymphoid organs. Using genetic and pharmacological approaches, we investigated the role of TNF in age-related dry eye disease, emphasizing the ocular surface and lacrimal gland inflammation. Our results show the increased protein and mRNA levels of TNF in aged lacrimal glands, accompanied by increased TNF, IL1β, IL-18, CCL5, CXCL1, IL-2, IL-2 receptor alpha (CD25), …

Nlrp3 Selectively Drives Il-1Β Secretion By Pseudomonas Aeruginosa Infected Neutrophils And Regulates Corneal Disease Severity, Martin S Minns, Karl Liboro, Tatiane S Lima, Serena Abbondante, Brandon A Miller, Michaela E Marshall, Jolynn Tran Chau, Alicia Roistacher, Arne Rietsch, George R Dubyak, Eric Pearlman

Faculty, Staff and Student Publications

Macrophages infected with Gram-negative bacteria expressing Type III secretion system (T3SS) activate the NLRC4 inflammasome, resulting in Gasdermin D (GSDMD)-dependent, but GSDME independent IL-1β secretion and pyroptosis. Here we examine inflammasome signaling in neutrophils infected with Pseudomonas aeruginosa strain PAO1 that expresses the T3SS effectors ExoS and ExoT. IL-1β secretion by neutrophils requires the T3SS needle and translocon proteins and GSDMD. In macrophages, PAO1 and mutants lacking ExoS and ExoT (ΔexoST) require NLRC4 for IL-1β secretion. While IL-1β release from ΔexoST infected neutrophils is also NLRC4-dependent, infection with PAO1 is instead NLRP3-dependent and driven by the ADP ribosyl transferase activity …

Bilateral Severe Iatrogenic Pigmentary Glaucoma Following Laser Treatment For Cosmetic Iris Color Change, Jiaru Liu, Salim Korban, Marlene R. Moster, Marc-André Rhéaume, Qianqian Wang

Wills Eye Hospital Papers

PURPOSE: We report a case of bilateral severe pigmentary glaucoma and paracentral acute middle maculopathy (PAMM) following laser treatment for iris color change.

OBSERVATIONS: A 32-year-old female presented to our emergency clinic after having undergone 4 sessions of bilateral cosmetic iris laser treatment in Turkey to lighten the color of her dark brown irides. Visual acuity was 20/150 in the right eye (OD) and counting fingers in the left eye (OS) at presentation. Intraocular pressures (IOP) were 50 mmHg in the right eye and 42 mmHg in the left eye, with 4+ free-floating pigmented cells in the anterior chamber. The …

Cultivated Autologous Limbal Epithelial Cell (Calec) Transplantation: Development Of Manufacturing Process And Clinical Evaluation Of Feasibility And Safety, Ula V Jurkunas, Jia Yin, Lynette K Johns, Sanming Li, Helene Negre, Kit L Shaw, Lassana Samarakoon, Allison R Ayala, Ahmad Kheirkhah, Kishore Katikireddy, Alex Gauthier, Stephan Ong Tone, Aaron R Kaufman, Stacey Ellender, Diego E Hernandez Rodriguez, Heather Daley, Reza Dana, Myriam Armant, Jerome Ritz

Faculty, Staff and Student Publications

To treat unilateral limbal stem cell (LSC) deficiency, we developed cultivated autologous limbal epithelial cells (CALEC) using an innovative xenobiotic-free, serum-free, antibiotic-free, two-step manufacturing process for LSC isolation and expansion onto human amniotic membrane with rigorous quality control in a good manufacturing practices facility. Limbal biopsies were used to generate CALEC constructs, and final grafts were evaluated by noninvasive scanning microscopy and tested for viability and sterility. Cultivated cells maintained epithelial cell phenotype with colony-forming and proliferative capacities. Analysis of LSC biomarkers showed preservation of "stemness." After preclinical development, a phase 1 clinical trial enrolled five patients with unilateral LSC …