Eye Diseases Commons^™

Spatial Transcriptomics Of The Lacrimal Gland Features Macrophage Activity And Epithelium Metabolism As Key Alterations During Chronic Inflammation, Olivier Mauduit, Vanessa Delcroix, Takeshi Umazume, Cintia S De Paiva, Darlene A Dartt, Helen P Makarenkova

Faculty, Staff and Students Publications

The lacrimal gland (LG) is an exocrine gland that produces the watery part of the tear film that lubricates the ocular surface. Chronic inflammation, such as Sjögren’s syndrome (SS), is one of the leading causes of aqueous-deficiency dry eye (ADDE) disease worldwide. In this study we analyzed the chronic inflammation in the LGs of the NOD.B10Sn-H2b/J (NOD.H-2b) mice, a mouse model of SS, utilizing bulk RNAseq and Visium spatial gene expression. With Seurat we performed unsupervised clustering and analyzed the spatial cell distribution and gene expression changes in all cell clusters within the LG sections. Moreover, for the …

New, Potent, Small Molecule Agonists Of Tyrosine Kinase Receptors Attenuate Dry Eye Disease, Zhiyuan Yu, Shaon Joy, Tianxiong Mi, Ghasem Yazdanpanah, Kevin Burgess, Cintia S De Paiva

Faculty, Staff and Students Publications

Nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin3 (NT-3) bind to tyrosine kinase (Trk) receptors, TrkA, TrkB, and TrkC, respectively. This study investigated the efficacy of novel molecule agonists of Trk receptors in an in vivo model of dry eye disease (DED). Small molecule TrkC agonist (C1) and a pan-Trk agonist (pan) were synthesized for this. C57BL/6J mice were subjected to desiccating stress (DS) and received bilateral eye drops of C1, pan, or vehicle (2x/day). Dry eye signs, inflammation and expression of corneal barrier function, and conjunctival goblet cell (GC) densities were measured as part of the DED …

Gut Microbiota From Sjögren Syndrome Patients Causes Decreased T Regulatory Cells In The Lymphoid Organs And Desiccation-Induced Corneal Barrier Disruption In Mice, Laura Schaefer, Claudia M Trujillo-Vargas, Firas S Midani, Stephen C Pflugfelder, Robert A Britton, Cintia S De Paiva

Faculty, Staff and Students Publications

Sjögren syndrome (SS) is an autoimmune inflammatory disorder characterized by secretory dysfunction in the eye and mouth; in the eye, this results in tear film instability, reduced tear production, and corneal barrier disruption. A growing number of studies show that homeostasis of the ocular surface is impacted by the intestinal microbiome, and several 16S sequencing studies have demonstrated dysbiosis of the intestinal microbiota in SS patients. In this study, we utilized metagenomic sequencing to perform a deeper analysis of the intestinal microbiome using stools collected from sex- and age-matched healthy (n = 20), dry eye (n = 4) …

Review Of Evidence For Environmental Causes Of Uveal Coloboma, Evan B Selzer, Delphine Blain, Robert B Hufnagel, Philip J Lupo, Laura E Mitchell, Brian P Brooks

Faculty, Staff and Student Publications

Uveal coloboma is a condition defined by missing ocular tissues and is a significant cause of childhood blindness. It occurs from a failure of the optic fissure to close during embryonic development and may lead to missing parts of the iris, ciliary body, retina, choroid, and optic nerve. Because there is no treatment for coloboma, efforts have focused on prevention. While several genetic causes of coloboma have been identified, little definitive research exists regarding the environmental causes of this condition. We review the current literature on environmental factors associated with coloboma in an effort to guide future research and preventative …

Sibling Concordance In Symptom Onset And Atrophy Growth Rates In Stargardt Disease Using Ultra-Widefield Fundus Autofluorescence, Rachael C. Heath Jeffery, Jennifer A. Thompson, Johnny Lo, Tina M. Lamey, Terri L. Mclaren, John N. De Roach, Dimitar N. Azamanov, Ian L. Mcallister, Ian J. Constable, Fred K. Chen

Research outputs 2022 to 2026

Purpose: To investigate concordance in symptom onset, area of dark autofluorescence (DAF), and growth rate (GR) between Stargardt disease siblings at an age-matched time point. Methods: In this retrospective longitudinal study of sibling pairs with identical biallelic ABCA4 variants, age at symptom onset, best-corrected visual acuity, atrophy area, and effective radius of DAF on ultra-widefield fundus autofluorescence were recorded. Absolute intersibling differences for both eyes were compared with absolute interocular differences using the Mann-Whitney test. Results: Overall 39 patients from 19 families were recruited. In 16 families, age-matched best-corrected visual acuity and DAF were compared between siblings. In 8 families, …

Role Of Meibum And Tear Phospholipids In The Evaporative Water Loss Associated With Dry Eye., Samiyyah M. Sledge

Electronic Theses and Dissertations

It is generally believed that the tear film lipid surface film inhibits the rate of evaporation (Revap) of the underlying tear aqueous. It is also generally believed that changes in the composition of the tear film lipid layer is responsible for an increase in Revap in patients with dry eye. Both of these ideas have never been proven. The purpose of the current studies was to test these ideas. Revap was measured in vitro gravimetrically. Lipid spreading was measured using Raman spectroscopy and microscopy. The influence of the following surface films on the Revap of the sub phase of physiologically …

Frequency Of Hepatitis B, Hepatitis C And Human Immunodeficiency Virus In Patients Undergoing Cataract Surgery, Mahfouth Abdalla Bamashmus, Ahmed Mousa Abdulrahim

Hadhramout University Journal of Natural & Applied Sciences

The aim of this study is to assess the frequency of Hepatitis B (HBV), Hepatitis C (HCV) and Human Immunodeficiency (HIV) viral infections in patients undergoing cataract surgery. This study was conducted among 1,203 patients above the age of 17 years who were scheduled for cataract surgery at Yemen Magrabi Hospital from January 1st, through December 31st, 2012. Patients had investigations for HBV, HCV and HIV and findings were analyzed. The total number of patients screened was 1,203 including 603 (51.1%) males and 600 (49.9%) females. The mean (+SD) age was 59.96 + 12.39 years. Out of the 1,203 cataract …

Super-Resolution Microscopy Reveals Photoreceptor-Specific Subciliary Location And Function Of Ciliopathy-Associated Protein Cep290, Valencia L Potter, Abigail R Moye, Michael A Robichaux, Theodore G Wensel

Faculty, Staff and Students Publications

Mutations in the cilium-associated protein CEP290 cause retinal degeneration as part of multiorgan ciliopathies or as retina-specific diseases. The precise location and the functional roles of CEP290 within cilia and, specifically, the connecting cilia (CC) of photoreceptors, remain unclear. We used super-resolution fluorescence microscopy and electron microscopy to localize CEP290 in the CC and in the primary cilia of cultured cells with subdiffraction resolution and to determine effects of CEP290 deficiency in 3 mutant models. Radially, CEP290 localizes in close proximity to the microtubule doublets in the region between the doublets and the ciliary membrane. Longitudinally, it is distributed throughout …

Klebsiella Pneumoniae Cryptogenic Liver Abscess And Endophthalmitis – A Case Report And Review Of Literature, Mihai Leonard Grecescu, Monica Grecescu, Andreea Smarandache Maria, Cristian Mihai Branescu, Anca Anghelache, Anca Silvia Dumitriu, Stana Paunica, Andreea Cristina Costea

Journal of Mind and Medical Sciences

Klebsiella pneumoniae has emerged as the predominant pathogenic agent of liver abscess in Asia, and the incidence is increasing worldwide. Hypervirulent strains are associated with septic metastatic dissemination in the eyes, lungs, and central nervous system, causing severe morbidity. We present the case of a 54year old man, with no previous comorbidities, admitted in emergency for the blind red painful eye. Further investigation documented septic endophthalmitis with transscleral extension and orbital cellulitis. Thoraco-abdominal computed tomography evidenced a hepatic abscess as the locus of the primary infection. Intravenous antibiotherapy with cefuroxime, followed by meropenem and vancomycin were efficient for managing the …

Optical Coherence Tomography Based Indices In Predicting Functional Outcome Of Macular Hole Surgery: A Retrospective Chart Review, Haroon Tayyab, Rehman Siddiqui, Sana Jahangir, Shiraz Hashmi

Section of Ophthalmology

Objectives: The objective of this study was to assess the utility of novel macular hole indices of Optical Coherence Tomography (OCT) and predicting the functional outcome of surgery.
Methods: This was a retrospective chart review of 28 eyes who underwent surgery for idiopathic Full Thickness Macular Hole (FTMH) at The Aga Khan University Hospital (AKUH), Karachi from January 2016 to March 2020. Data of preoperative OCTs were recovered from data server of OCT machine. Measurements of the pre-operative OCTs were calculated using caliper function of OCT software by two independent technicians. Parameters included Macular Hole Index (MHI), Traction Hole Index …

Spontaneous Closure Of Full Thickness Macular Hole In The Presence Of An Epiretinal Membrane In A Vitrectomised Eye: A Case Report, Rehman Siddiqui, Muhammad Umar Fawad, Nida Ahsan

Section of Ophthalmology

We report the case of a spontaneous closure of full thickness macular hole (FTMH) in the presence of an epiretinal membrane (ERM) in a previously vitrectomised eye. The patient had undergone vitrectomy for rhegmatogenous retinal detachment and developed an ERM two weeks after the surgery, which converted into a FTMH after one week. Eight months after the vitrectomy, spontaneous closure of FTMH was observed with an improvement in best-corrected visual acuity (BCVA) from 20/200 to 20/40. The patient was followed up for four years, and the FTMH remained closed. Spontaneous closure of FTMH is possible even in the presence of …

Structure And Dynamics Of Photoreceptor Sensory Cilia, Theodore G Wensel, Valencia L Potter, Abigail Moye, Zhixian Zhang, Michael A Robichaux

Faculty, Staff and Students Publications

The rod and cone photoreceptor cells of the vertebrate retina have highly specialized structures that enable them to carry out their function of light detection over a broad range of illumination intensities with optimized spatial and temporal resolution. Most prominent are their unusually large sensory cilia, consisting of outer segments packed with photosensitive disc membranes, a connecting cilium with many features reminiscent of the primary cilium transition zone, and a pair of centrioles forming a basal body which serves as the platform upon which the ciliary axoneme is assembled. These structures form a highway through which an enormous flux of …

Frequency Of Retinopathy Of Prematurity (Rop) In Infants Screened For Rop: Two Years Follow-Up Results Of A Single Center In Turkey, Adem Ugurlu

BioMedicine

Aim: The aim of this retrospective study was to determine the incidence of retinopathy of prematurity (ROP) in infants referred to our clinic for screening ROP.

Material and Method: The data of 729 infants who were referred to the ROP outpatient clinic of the Ophthalmology Unit of Erzincan Binali Yildirim University, Turkey between April 2018 and March 2020 were analyzed retrospectively. The gestational age and weight of the infants, stay in the neonatal intensive care unit, duration of oxygen therapy, and detailed ophthalmologic examination findings were recorded in the study.

Findings and Results: Of the 729 babies screened for ROP,122 …

Use Of Intravitreal Methotrexate Infusion In Complicated Retinal Detachment For Prevention Of Proliferative Vitreoretinopathy In A Pilot Study, Sana Jahangir, Tehmina Jahangir, Muhammad H. Ali, Qasim Lateef, Uzma Hamza, Haroon Tayyab

Section of Ophthalmology

Objective: The objective of this pilot study was to evaluate the efficacy and safety of per-operative intravitreal methotrexate (MTX) infusion during vitrectomy in patients of retinal detachment (RD) with advanced grade proliferative vitreoretinopathy (PVR).
Methods: In this prospective interventional case series, we included patients with Grade C PVR, recurrent RD, and open globe trauma. All patients underwent standard single surgeon operated 23-gauge pars plana vitrectomy (PPV) with 80mg of MTX in 1000mL of irrigation fluid. All patients were followed up after four months to assess the final status of retinal attachment and visual acuity. Ethical review board permission was sought …

Neurovascular Regulation In Diabetic Retinopathy And Emerging Therapies, Liyang Ji, Hong Tian, Keith A Webster, Wei Li

Faculty, Staff and Students Publications

Diabetic retinopathy (DR) is the leading cause of vision loss in working adults in developed countries. The disease traditionally classified as a microvascular complication of diabetes is now widely recognized as a neurovascular disorder resulting from disruption of the retinal neurovascular unit (NVU). The NVU comprising retinal neurons, glia and vascular cells coordinately regulates blood flow, vascular density and permeability to maintain homeostasis. Disturbance of the NVU during DR can lead to vision-threatening clinical manifestations. A limited number of signaling pathways have been identified for intercellular communication within the NVU, including vascular endothelial growth factor (VEGF), the master switch for …

Predicting The Environmental Suitability For Onchocerciasis In Africa As An Aid To Elimination Planning, Elizabeth A. Cromwell, Joshua C P. Osborne, Thomas R. Unnasch, Maria-Gloria Basáñez, Katherine M. Gass, Kira A. Barbre, Elex Hill, Kimberly B. Johnson, Katie M. Donkers, Zulfiqar Ahmed Bhutta

Centre of Excellence in Women and Child Health

Recent evidence suggests that, in some foci, elimination of onchocerciasis from Africa may be feasible with mass drug administration (MDA) of ivermectin. To achieve continental elimination of transmission, mapping surveys will need to be conducted across all implementation units (IUs) for which endemicity status is currently unknown. Using boosted regression tree models with optimised hyperparameter selection, we estimated environmental suitability for onchocerciasis at the 5 × 5-km resolution across Africa. In order to classify IUs that include locations that are environmentally suitable, we used receiver operating characteristic (ROC) analysis to identify an optimal threshold for suitability concordant with locations where …

Comprehensive Review And Update Of Burning Eye Syndrome, Stephen Giacomazzi, Ivan Urits, Briggs Hoyt, Ashley Hubble, Elyse M. Cornett, Kyle Gress, Karina Charipova, Amnon A. Berger, Hisham Kassem, Alan D. Kaye, Omar Viswanath

Journal of Patient-Centered Research and Reviews

Keratoconjunctivitis sicca (“dry eye”) is a common (14%–30% of adults over age 48) though difficult to treat condition that causes both discomfort and disability with associated dryness, pain, and visual disturbances. Etiology is not clearly understood but is likely varied, with a subset of patients suffering from chronic neuropathic pain referred to as “burning eye syndrome.” This review of existing literature summarizes the clinical presentation, natural history, pathophysiology, and treatment modalities of burning eye syndrome.

Chronicity of burning eye syndrome is likely secondary to increased nociception from the cornea, decrease in inhibitory signals, and nerve growth factor expression alterations. Treatment …

Preventing Ocular Surface Disease In The Pediatric Intensive Care Unit, Emily Mallette

Dissertations

Preventing Ocular Surface Disease in the Pediatric Intensive Care Unit

Problem: Ocular surface disease in the Pediatric Intensive Care Unit is a significant problem in intubated patients due to altered eye protective mechanics, leading to exposure of the eye surface and dry eye. The purpose of this quality improvement project was to evaluate how an eye care protocol affected the frequency of artificial tear ointment administration.

Method: A descriptive, cohort design utilizing a retrospective chart review with convenience sampling of intubated children in the PICU from two cohorts was used. Comparisons were made between the preintervention cohort in 2020 and …

Platelet And Erythrocyte Extravasation Across Inflamed Corneal Venules Depend On Cd18, Neutrophils, And Mast Cell Degranulation, Angie De La Cruz, Aubrey Hargrave, Sri Magadi, Justin A Courson, Paul T Landry, Wanyu Zhang, Fong W Lam, Monica A Bray, C Wayne Smith, Alan R Burns, Rolando E Rumbaut

Faculty, Staff and Student Publications

Platelet extravasation during inflammation is under-appreciated. In wild-type (WT) mice, a central corneal epithelial abrasion initiates neutrophil (PMN) and platelet extravasation from peripheral limbal venules. The same injury in mice expressing low levels of the β2-integrin, CD18 (CD18hypo mice) shows reduced platelet extravasation with PMN extravasation apparently unaffected. To better define the role of CD18 on platelet extravasation, we focused on two relevant cell types expressing CD18: PMNs and mast cells. Following corneal abrasion in WT mice, we observed not only extravasated PMNs and platelets but also extravasated erythrocytes (RBCs). Ultrastructural observations of engorged limbal venules showed platelets and RBCs …

Retinal Regeneration In A Genetic Mouse Model Of Glaucoma, Joshua Paris

Masters Theses

Glaucoma is a degenerative retinal disease characterized by progressive loss of retinal ganglion cells (RGCs). Previous studies have shown that application of a specific α7 nicotinic acetylcholine receptor agonist, PNU-282987 (PNU), onto the murine retina induces neurogenesis of numerous retinal cell types, including RGCs. The aim of this study is to characterize the short-term and long-term effects of PNU in a glaucoma model. The effects of PNU were analyzed in a DBA/2J mouse model that auto-induces a glaucoma-like condition in adulthood. These mice manifest an elevated intraocular pressure (IOP) starting at 6 months, followed by loss of RGCs. To assess …