Optometry Commons^™

Il-17 Producing Lymphocytes Cause Dry Eye And Corneal Disease With Aging In Rxrα Mutant Mouse, Jehan Alam, Ghasem Yazdanpanah, Rinki Ratnapriya, Nicholas Borcherding, Cintia S De Paiva, Dequan Li, Rodrigo Guimaraes De Souza, Zhiyuan Yu, Stephen C Pflugfelder

Faculty, Staff and Students Publications

PURPOSE: To investigate IL-17 related mechanisms for developing dry eye disease in the Pinkie mouse strain with a loss of function RXRα mutation.

METHODS: Measures of dry eye disease were assessed in the cornea and conjunctiva. Expression profiling was performed by single-cell RNA sequencing (scRNA-seq) to compare gene expression in conjunctival immune cells. Conjunctival immune cells were immunophenotyped by flow cytometry and confocal microscopy. The activity of RXRα ligand 9-cis retinoic acid (RA) was evaluated in cultured monocytes and γδ T cells.

RESULTS: Compared to wild type (WT) C57BL/6, Pinkie has increased signs of dry eye disease, including decreased tear …

Problems In Csf And Ophthalmic Disease Research, Ryan Machiele, Benjamin Jay Frankfort, Hanspeter Esriel Killer, David Fleischman

Faculty, Staff and Students Publications

There has been significant interest and progress in the understanding of cerebrospinal fluid pressure and its relationship to glaucoma and other ophthalmic diseases. However, just as every physiologic fluid pressure fluctuates, cerebrospinal fluid pressure (CSFP) is similarly dynamic. Coupling this with the difficulty in measuring the pressure, there are many obstacles in furthering this field of study. This review highlights some of the difficulties in CSFP research, including fluid compartmentalization, estimation equations, and pressure fluctuation. Keeping these limitations in mind will hopefully improve the quality and context of this burgeoning field.

Systematic Profiling Of Dnmt3a Variants Reveals Protein Instability Mediated By The Dcaf8 E3 Ubiquitin Ligase Adaptor, Yung-Hsin Huang, Chun-Wei Chen, Venkatasubramaniam Sundaramurthy, Mikołaj Słabicki, Dapeng Hao, Caroline J Watson, Ayala Tovy, Jaime M Reyes, Olga Dakhova, Brielle R Crovetti, Christina Galonska, Minjung Lee, Lorenzo Brunetti, Yubin Zhou, Katrina Tatton-Brown, Yun Huang, Xiaodong Cheng, Alexander Meissner, Peter J M Valk, Lionel Van Maldergem, Mathijs A Sanders, Jamie R Blundell, Wei Li, Benjamin L Ebert, Margaret A Goodell

Faculty, Staff and Students Publications

Clonal hematopoiesis is a prevalent age-related condition associated with a greatly increased risk of hematologic disease; mutations in DNA methyltransferase 3A (DNMT3A) are the most common driver of this state. DNMT3A variants occur across the gene with some particularly associated with malignancy, but the functional relevance and mechanisms of pathogenesis of the majority of mutations are unknown. Here, we systematically investigated the methyltransferase activity and protein stability of 253 disease-associated DNMT3A mutations, and found that 74% were loss-of-function mutations. Half of these variants exhibited reduced protein stability and, as a class, correlated with greater clonal expansion and acute …

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) …

Selective Vulnerability Of The Intermediate Retinal Capillary Plexus Precedes Retinal Ganglion Cell Loss In Ocular Hypertension, Priyamvada M Pitale, Guofu Shen, Rohini R Sigireddi, Maria Polo-Prieto, Yong H Park, Solomon E Gibson, Peter D Westenskow, Roomasa Channa, Benjamin J Frankfort

Faculty, Staff and Students Publications

Introduction: Glaucoma, a disease of retinal ganglion cell (RGC) injury and potentially devastating vision loss, is associated with both ocular hypertension (OHT) and reduced ocular blood flow. However, the relationship between OHT and retinal capillary architecture is not well understood. In this project, we studied microvasculature damage in mice exposed to mild levels of induced OHT.

Methods: Mild OHT was induced with the microbead model for 2 weeks. At this time point, some retinas were immunostained with CD31 (endothelium), Collagen IV (basement membrane), and RBPMS (RGCs) for z-stack confocal microscopy. We processed these confocal images to distinguish the three retinal …

Selectively Targeting Disease-Restricted Secretogranin Iii To Alleviate Choroidal Neovascularization, Liyang Ji, Prabuddha Waduge, Lili Hao, Avinash Kaur, Wencui Wan, Yan Wu, Hong Tian, Jinsong Zhang, Keith A Webster, Wei Li

Faculty, Staff and Students Publications

Choroidal neovascularization (CNV), a leading cause of blindness in the elderly, is routinely treated with vascular endothelial growth factor (VEGF) inhibitors that have limited efficacy and potentially adverse side effects. An unmet clinical need is to develop novel therapies against other angiogenic factors for alternative or combination treatment to improve efficacy and safety. We recently described secretogranin III (Scg3) as a disease-selective angiogenic factor, causally linked to diabetic retinopathy and acting independently of the VEGF pathway. An important question is whether such a disease-selective Scg3 pathway contributes to other states of pathological angiogenesis beyond diabetic retinopathy. By applying a novel …

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 …

Cathepsin S Is A Novel Target For Age-Related Dry Eye, Zhiyuan Yu, Jinmiao Li, Gowthaman Govindarajan, Sarah F Hamm-Alvarez, Jehan Alam, De-Quan Li, Cintia S De Paiva

Faculty, Staff and Students Publications

Cathepsin S (CTSS) is a protease that is proinflammatory on epithelial cells. The purpose of this study was to investigate the role of CTSS in age-related dry eye disease. Ctss−/− mice [in a C57BL/6 (B6) background] of different ages were compared to B6 mice. CTSS activity in tears and lacrimal gland (LG) lysates was measured. The corneal barrier function was investigated in naïve mice or after topical administration of CTSS eye drops 5X/day for two days. Eyes were collected, and conjunctival goblet cell density was measured in PAS-stained sections. Immunoreactivity of the tight junction proteins, ZO-1 and occludin, was …

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 …

Understanding Blue Light Retinal Damages And The Methods Of Prevention, Amelia Lee

Senior Honors Theses

Light emitting diode (LED) lights that comprise television screens, phone displays, laptops, and tablets have been studied by scientists in order to understand the implications of blue light radiation and the effects that it has on the human body—especially the retina of the eye. The retina is comprised of highly metabolic cells, and when those cells are placed under oxidative stress, death occurs causing ocular disease. Additionally, excess blue light exposure causes shifts in biological rhythms that govern patterns of alertness and sleep. Recently scientists began studying the methods of blue light prevention. Some studies show that blue light radiation …

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 …

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 …

Transitional Vocational Program For Persons With Low Vision And Other Visual Impairments, Andria Lubben, Karen Park, Susan Macdermott, Becki Cohill

Summer 2021 Virtual OTD Capstone Symposium

Background: Low Vision is a life-altering visual disability (CDC, 2015). OTs work with individuals with low vision and work in the workplace and education, however, there is no research on OTs working with individuals with low vision in work or post educational settings (Butler, 2016). Vocational and educational needs are often not being met for individuals with low vision (Barbieri et al., 2019).

Problem: OTs have a limited role in adolescent transition to the workplace and higher education in individuals with low vision and other visual impairments.

Purpose: To understand transitional programs that support vocational and educational development of individuals …

Evaluation Of The Spot™ Photoscreener’S Efficacy For Detecting Amblyopia Risk Factors Compared To Optometrists’ Examinations In 305 South Dakota Children, Jeremy J. Kudrna Md, Eric Habbe Md, Andrea Bordewyk Md, Hadly Carson Eisenbeisz Ms-Iv, Ryan Scarborough Od, Terrence Spencer Md

Aesculapius Journal (Health Sciences & Medicine)

Purpose: This study sought to further validate the efficacy of the SPOT^TM photoscreener version (v) 3.0.0500 as a screening device for amblyopia risk factors (ARF).

Methods: This was a cross-sectional study from five different western South Dakota outpatient clinics. Data from 610 eyes of 305 children aged 6 months to 13.5 years collected between July 2018 to September 2018 were analyzed, using both the out-of-box referral criteria and the 2013 American Association for Pediatric Ophthalmology and Strabismus (AAPOS) referral criteria. Optometrist (eye care provider or ECP) cycloplegia practice patterns were deferred to each clinics’ specific protocols. Power vector and …

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 …

Interdisciplinary Practice For Occupational Therapy And Low Vision Rehabilitation, Priscilla Gim, Karen Park, Becki Cohill, Susan Macdermott

Spring 2021 Virtual OTD Capstone Symposium

The purpose of this capstone project was to advocate occupational therapy in low vision rehabilitation for improved access to low vision rehabilitation (LVR) for the adult population. However, due to COVID-19 pandemic, this capstone project shifted to a research study assessing limiting factors for occupational therapy collaboration with low vision services and exploring eye physician’s perception on low vision occupational therapy.

A mixed-methods survey was conducted to explore 54 eye physicians including Doctor of Medicine (MD) specialized in ophthalmology and Doctor of Optometry (OD)’s perception on the role of low vision occupational therapy, benefit of low vision occupational therapy, current …

Single-Cell Transcriptomics Identifies Limbal Stem Cell Population And Cell Types Mapping Its Differentiation Trajectory In Limbal Basal Epithelium Of Human Cornea, De-Quan Li, Sangbae Kim, Jin-Miao Li, Qianmiao Gao, Jongsu Choi, Fang Bian, Jiaoyue Hu, Yun Zhang, Jin Li, Rong Lu, Yumei Li, Stephen C Pflugfelder, Hongyu Miao, Rui Chen

Faculty, Staff and Students Publications

PURPOSE: This study aimed to uncover novel cell types in heterogenous basal limbus of human cornea for identifying LSC at single cell resolution.

METHODS: Single cells of human limbal basal epithelium were isolated from young donor corneas. Single-cell RNA-Sequencing was performed using 10x Genomics platform, followed by clustering cell types through the graph-based visualization method UMAP and unbiased computational informatic analysis. Tissue RNA in situ hybridization with RNAscope, immunofluorescent staining and multiple functional assays were performed using human corneas and limbal epithelial culture models.

RESULTS: Single-cell transcriptomics of 16,360 limbal basal cells revealed 12 cell clusters belonging to three lineages. …

Addressing Artificial Intelligence Bias In Retinal Diagnostics, Philippe Burlina, Neil Joshi, William Paul, Katia D Pacheco, Neil M Bressler

Faculty, Staff and Students Publications

PURPOSE: This study evaluated generative methods to potentially mitigate artificial intelligence (AI) bias when diagnosing diabetic retinopathy (DR) resulting from training data imbalance or domain generalization, which occurs when deep learning systems (DLSs) face concepts at test/inference time they were not initially trained on.

METHODS: The public domain Kaggle EyePACS dataset (88,692 fundi and 44,346 individuals, originally diverse for ethnicity) was modified by adding clinician-annotated labels and constructing an artificial scenario of data imbalance and domain generalization by disallowing training (but not testing) exemplars for images of retinas with DR warranting referral (DR-referable) from darker-skin individuals, who presumably have greater …

Application Of Big-Data For Epidemiological Studies Of Refractive Error, Michael Moore, James Loughman, John Butler, Arne Ohlendorf, Siegfried Wahl, Daniel Ian Flitcroft

Articles

Purpose

To examine whether data sourced from electronic medical records (EMR) and a large industrial spectacle lens manufacturing database can estimate refractive error distribution within large populations as an alternative to typical population surveys of refractive error.

Subjects

A total of 555,528 patient visits from 28 Irish primary care optometry practices between the years 1980 and 2019 and 141,547,436 spectacle lens sales records from an international European lens manufacturer between the years 1998 and 2016.

Methods

Anonymized EMR data included demographic, refractive and visual acuity values. Anonymized spectacle lens data included refractive data. Spectacle lens data was separated into lenses …

Application Of Big-Data For Epidemiological Studies Of Refractive Error, James Loughman

Articles

To examine whether data sourced from electronic medical records (EMR) and a large industrial spectacle lens manufacturing database can estimate refractive error distribution within large populations as an alternative to typical population surveys of refractive error.

Identification Of Deep-Intronic Splice Mutations In A Large Cohort Of Patients With Inherited Retinal Diseases, Xinye Qian, Jun Wang, Meng Wang, Austin D Igelman, Kaylie D Jones, Yumei Li, Keqing Wang, Kerry E Goetz, David G Birch, Paul Yang, Mark E Pennesi, Rui Chen

Faculty, Staff and Students Publications

High throughput sequencing technologies have revolutionized the identification of mutations responsible for a diverse set of Mendelian disorders, including inherited retinal disorders (IRDs). However, the causal mutations remain elusive for a significant proportion of patients. This may be partially due to pathogenic mutations located in non-coding regions, which are largely missed by capture sequencing targeting the coding regions. The advent of whole-genome sequencing (WGS) allows us to systematically detect non-coding variations. However, the interpretation of these variations remains a significant bottleneck. In this study, we investigated the contribution of deep-intronic splice variants to IRDs. WGS was performed for a cohort …

Loss Of Class Iii Phosphoinositide 3-Kinase Vps34 Results In Cone Degeneration, Ammaji Rajala, Feng He, Robert E Anderson, Theodore G Wensel, Raju V S Rajala

Faculty, Staff and Students Publications

The major pathway for the production of the low-abundance membrane lipid phosphatidylinositol 3-phosphate (PI(3)P) synthesis is catalyzed by class III phosphoinositide 3-kinase (PI3K) Vps34. The absence of Vps34 was previously found to disrupt autophagy and other membrane-trafficking pathways in some sensory neurons, but the roles of phosphatidylinositol 3-phosphate and Vps34 in cone photoreceptor cells have not previously been explored. We found that the deletion of Vps34 in neighboring rods in mouse retina did not disrupt cone function up to 8 weeks after birth, despite diminished rod function. Immunoblotting and lipid analysis of cones isolated from the cone-dominant retinas of the …

Optic Disc Pits: A Case Report And Review, Jeffrey A. Sterling Od, Faao, Fsls

Optometric Clinical Practice

Background: Congenital optic disc pits (ODP) are a rare clinical finding affecting approximately 1 in 11,000 people. Affected individuals are generally asymptomatic unless fluid accumulates in the macula resulting in severe vision loss. The management of ODPs depends mostly on clinical findings and can range from observation to surgery. Optometrists need to be aware of clinical presentations and possible complications of ODPs.

Case Report: This report will review a case of an asymptomatic optic disc pit and discuss the potential treatment options if complications arise.

Conclusion: Although rare, congenital optic disc pits need to be accurately assessed and diagnosed. Symptoms …

Mtor-Initiated Metabolic Switch And Degeneration In The Retinal Pigment Epithelium, Young-Mi Go, Jing Zhang, Jolyn Fernandes, Christopher Litwin, Rui Chen, Theodore G Wensel, Dean P Jones, Jiyang Cai, Yan Chen

Faculty, Staff and Students Publications

The retinal pigment epithelium (RPE) is a particularly vulnerable tissue to age-dependent degeneration. Over the life span, the RPE develops an expanded endo-lysosomal compartment to maintain the high efficiency of phagocytosis and degradation of photoreceptor outer segments (POS) necessary for photoreceptor survival. As the assembly and activation of the mechanistic target of rapamycin complex 1 (mTORC1) occur on the lysosome surface, increased lysosome mass with aging leads to higher mTORC1 activity. The functional consequences of hyperactive mTORC1 in the RPE are unclear. In the current study, we used integrated high-resolution metabolomic and genomic approaches to examine mice with RPE-specific deletion …

Pterygium Recurrence And Corneal Stabilization Point After Pterygium Excision Using The Controlled Partial Avulsion Fibrin Glue Technique, Mohd Radzi Hilmi, Khairidzan Mohd Kamal, Mohd Zulfaezal Che Azemin

Makara Journal of Health Research

Background: This study aimed to evaluate the pterygium recurrence rate and corneal stabilization point after pterygium excision via the controlled partial avulsion fibrin glue technique using multiple corneal parameters.

Methods: One hundred eyes of 100 patients who had undergone primary pterygium excision surgery via the controlled partial avulsion fibrin glue technique were retrospectively reviewed. Corneal stabilization points were determined over four follow-up sessions (i.e., the 1st, 3rd, 6th, and 12th months after surgery) based on changes in Simulated-K, corneal irregularity measurement, shape factor, and toric mean keratometry. Post-operative courses were followed for 12 months after surgery. Recurrence was …

Access To Eye Care Before And After Vision Loss: A Qualitative Study Investigating Eye Care Among Persons Who Have Become Blind, Tosha Zaback, Stephanie Lam, Joan Randall, Teresa Field, Mitchell V. Brinks

The Qualitative Report

Navigating access to eye care requires that patients recognize the need for screening and care, employ limited financial and social resources, manage complex health insurance policies, and access specialty clinical care. We investigated the experience of patients through the progression of vision loss to blindness, utilizing qualitative methods. We conducted structured telephone interviews with 28 persons with blindness throughout Oregon. Utilizing closed and open-ended questions, we explored patient experience on the events preceding avoidable blindness. Coding for emergent themes was conducted independently by two researchers using a constant comparative method. Participants described important barriers to accessing eye care: at the …

A Comparison Of Emoji Characters To Picture Optotypes, Simran Brar

Research Days

No abstract provided.

The Efficacy Of Warm Compresses In The Treatment Of Meibomian Gland Dysfunction And Demodex Folliculorum Blepharitis, Orla Murphy, Veronica O'Dwyer, Aoife Lloyd-Mckernan

Articles

Purpose: To investigate and compare the effect of warm compresses on meibomian gland dysfunction and Demodex folliculorum blepharitis.

Methods: Forty-two subjects (13 males, 29 females; mean age of 56.45 years) enrolled and completed the two-month warm compress treatment study. Three warm compress therapies were compared: Warm face cloth, MGDRx EyeBag® and OPTASETM Moist Heat Mask. Subjects attended for four visits: baseline, two weeks, four weeks, and eight weeks. Subjective symptoms, osmolarity, non-invasive tear break-up time, ocular surface staining, Schirmer I test, meibum expressibility and clarity, and eyelash manipulation and epilation to assess for the presence of Demodex folliculorum, …

Quality Improvement Initiative To Increase Comprehensive Eye Exams In Patients With Diabetes, Julia Khoury

Doctor of Nursing Practice

Diabetic retinopathy is the most common microvascular complication associated with poorly controlled diabetes. Yet, only 60% of the diabetic population receives an annual eye examination by an eye specialist. Retinal imaging increases surveillance of retinopathy, however, it does not take the place of a comprehensive eye examination by an ophthalmologist or optometrist. The aim of this quality improvement project was to increase comprehensive eye examinations in patients with diabetes aged 18 to 75 years in a family practice that recently purchased a retinal imager. This quality improvement project occurred over a 10-week period. Project objectives included increasing comprehensive dilated eye …

Anterior Subcapsular Cataract Secondary To Black Mold Exposure, Katherine B. Lynch Od, Bruce A. Teitelbaum Od

Optometric Clinical Practice

A case report of a 31-year-old woman who developed anterior subacapsular cataracts, and associated dermatological signs, after exposure to black mold. While atopic illness is commonly seen in childhood, a growing body of literature supports adult onset atopic dermatitis. Anterior subcapsular cataracts are pathognomonic for atopic illness, and can support a definitive and expedited dermatologic diagnosis of adult onset disease.