Eye Diseases Commons^™

Diabetic Retinopathy: A Pathophysiological Discussion, Nathanael C. Nicholls

Senior Honors Theses

Diabetic retinopathy is a severe complication of diabetes that is capable of causing vision loss or blindness. As a result of hyperglycemia, the disease increases oxidative stress and activates biochemical processes such as the Hippo pathway and the complement system to cause significant damage to the retina. Overexpression of BTG1 and microRNA-183 enables activation of biochemical pathways that lead to negative effects on the retinal vascular endothelium including angiogenesis and inflammation. Conventional methods of diagnosis for diabetic retinopathy include fundus examination, nucleoside detection, and optical coherence tomography angiography. Photocoagulation and hormonal intravitreal injection are the most popular current treatments, while …

Comparison Between Maia And Mp-3 In Healthy Subjects And Patients With Diabetes, Diabetic Retinopathy, And Age-Related Macular Degeneration, Anna Marmalidou, Haleema Siddiqui, Muhammad Usman Jamil, Kwang Min Woo, Antonio Yaghy, A. Yasin Alibhai, Hiroyuki Takahashi, Stephanie Kaiser, Keith Effert, Peter Zhao, Shilpa Desai, Christopher Robinson, Jay Duker, Nadia Waheed

SKMC Student Presentations and Publications

PURPOSE: The purpose of this study was to assess the comparability of mean sensitivity (MS) values obtained using the Macular Integrity Assessment (MAIA; CenterVue S.p.A. [iCare], Padova, Italy) and Microperimeter-3 (MP-3; NIDEK CO., Ltd., Gamagori, Japan) microperimetry (MP) devices.

METHODS: This cross-sectional study includes subjects with healthy eyes, eyes with diabetes mellitus without diabetic retinopathy (DM no DR), diabetic retinopathy (DR), and non-exudative age-related macular degeneration (AMD). Patients underwent testing on both MAIA and MP-3 MP devices, using a 10-2 macular grid with 68 stimuli and identical parameters. A diagnosis-adjusted linear regression model and mixed modeling mapped MP-3 MS to …

Hyperglycemia Causes Differential Change In Macrophage Population In The Lacrimal Gland, Conjunctiva And Cornea, Saleh Alfuraih, Amy Tran, Lois Kim, Rais Ansari, Ajay Sharma

Pharmacy Faculty Articles and Research

Background: Due to its location, the ocular surface is exposed to environmental microbes. Innate immune cells including macrophages are first line defense against infections. In vitro exposure to high glucose as well as diabetes-associated hyperglycemia has been shown to affect innate immune cell function and population. The present study was designed to examine the effect of diabetes-associated hyperglycemia on the lacrimal gland, conjunctiva and cornea macrophage population, phenotypic changes and cytokines/chemokines.

Methods: Mouse model of Streptozotocin-induced diabetes was used to induce hyperglycemia. Immunostaining for CD11b and F4/80 was performed to stain macrophages in whole mount cornea, conjunctiva and 50 µm …

Tgf-Β Signaling Pathways In The Development Of Diabetic Retinopathy, Andrew Callan, Sonal Jha, Laura Valdez, Lois Baldado, Andrew Tsin

Central & West Texas GME Research Day 2024

No abstract provided.

Diabetes-Associated Hyperglycemia Causes Rapid-Onset Ocular Surface Damage, Judy Weng, Christopher Ross, Jacob Baker, Saleh Alfuraih, Kiumars Shamloo, Ajay Sharma

Pharmacy Faculty Articles and Research

Purpose: The metabolic alterations due to chronic hyperglycemia are well-known to cause diabetes-associated complications. Short-term hyperglycemia has also been shown to cause many acute changes, including hemodynamic alterations and osmotic, oxidative, and inflammatory stress. The present study was designed to investigate whether diabetes-associated hyperglycemia can cause rapid-onset detrimental effects on the tear film, goblet cells, and glycocalyx and can lead to activation of an inflammatory cascade or cellular stress response in the cornea.

Methods: Mouse models of type 1 and type 2 diabetes were used. Tear film volume, goblet cell number, and corneal glycocalyx area were measured on …

Reversal Of Dual Epigenetic Repression Of Non-Canonical Wnt-5a Normalises Diabetic Corneal Epithelial Wound Healing And Stem Cells, Ruchi Shah, Tanya M Spektor, Daniel J Weisenberger, Hui Ding, Rameshwar Patil, Cynthia Amador, Xue-Ying Song, Steven T Chun, Jake Inzalaco, Sue Turjman, Sean Ghiam, Jiho Jeong-Kim, Sasha Tolstoff, Sabina V Yampolsky, Onkar B Sawant, Yaron S Rabinowitz, Ezra Maguen, Pedram Hamrah, Clive N Svendsen, Mehrnoosh Saghizadeh, Julia Y Ljubimova, Andrei A Kramerov, Alexander V Ljubimov

Faculty, Staff and Student Publications

AIMS/HYPOTHESIS: Diabetes is associated with epigenetic modifications including DNA methylation and miRNA changes. Diabetic complications in the cornea can cause persistent epithelial defects and impaired wound healing due to limbal epithelial stem cell (LESC) dysfunction. In this study, we aimed to uncover epigenetic alterations in diabetic vs non-diabetic human limbal epithelial cells (LEC) enriched in LESC and identify new diabetic markers that can be targeted for therapy to normalise corneal epithelial wound healing and stem cell expression.

METHODS: Human LEC were isolated, or organ-cultured corneas were obtained, from autopsy eyes from non-diabetic (59.87±20.89 years) and diabetic (71.93±9.29 years) donors. The …

Accuracy Of Artificial Intelligence In Estimating Best-Corrected Visual Acuity From Fundus Photographs In Eyes With Diabetic Macular Edema, William Paul, Philippe Burlina, Rohita Mocharla, Neil Joshi, Zhuolin Li, Sophie Gu, Onnisa Nanegrungsunk, Kira Lin, Susan B Bressler, Cindy X Cai, Jun Kong, T Y Alvin Liu, Hadi Moini, Weiming Du, Fouad Amer, Karen Chu, Robert Vitti, Farshid Sepehrband, Neil M Bressler

Faculty, Staff and Students Publications

IMPORTANCE: Best-corrected visual acuity (BCVA) is a measure used to manage diabetic macular edema (DME), sometimes suggesting development of DME or consideration of initiating, repeating, withholding, or resuming treatment with anti-vascular endothelial growth factor. Using artificial intelligence (AI) to estimate BCVA from fundus images could help clinicians manage DME by reducing the personnel needed for refraction, the time presently required for assessing BCVA, or even the number of office visits if imaged remotely.

OBJECTIVE: To evaluate the potential application of AI techniques for estimating BCVA from fundus photographs with and without ancillary information.

DESIGN, SETTING, AND PARTICIPANTS: Deidentified color fundus …

Improving Diabetic Retinopathy Screening Practices With Qi Methodology In Family Medicine Offices, Rea Isaac, Anne Jones

Rowan-Virtua Research Day

Early detection and treatment of diabetic retinopathy (DR) is crucial in preventing vision loss and blindness in vulnerable diabetics. With around 7.7 million patients having DR, and the target population being 20 -75 years old, the potential for improving their quality of life is substantial (WHO, 2022). Despite the importance of timely and routine eye exams, 45% of diabetic patients do not complete an exam despite physicians recommendations (Lu, 2014). This project aims to standardize eye exams, improve process flow, and improve patient understanding of the urgency of timely and comprehensive eye exams for DR. Multiple PDSA cycles and QI …

Evaluation Of Retinal Nerve Fibre Layer Thickness As A Possible Measure Of Diabetic Retinal Neurodegeneration In The Epic-Norfolk Eye Study, Sidra Zafar, Kristen A Staggers, Jie Gao, Yao Liu, Praveen J Patel, Paul J Foster, Benjamin J Frankfort, Michael Abramoff, Charles G Minard, Alasdair Warwick, Anthony P Khawaja, Roomasa Channa

Faculty, Staff and Students Publications

BACKGROUND/AIMS: Markers to clinically evaluate structural changes from diabetic retinal neurodegeneration (DRN) have not yet been established. To study the potential role of peripapillary retinal nerve fibre layer (pRNFL) thickness as a marker for DRN, we evaluated the relationship between diabetes, as well as glycaemic control irrespective of diabetes status and pRNFL thickness.

METHODS: Leveraging data from a population-based cohort, we used general linear mixed models (GLMMs) with a random intercept for patient and eye to assess the association between pRNFL thickness (measured using GDx) and demographic, systemic and ocular parameters after adjusting for typical scan score. GLMMs were also …

Patient And Provider Experience With Artificial Intelligence Screening Technology For Diabetic Retinopathy In A Rural Primary Care Setting, Brian M. Nolan, Emma R. Daybranch, Kerri Barton, Neil Korsen

Journal of Maine Medical Center

Introduction: The development of autonomous artificial intelligence for interpreting diabetic retinopathy (DR) images has allowed for point-of-care testing in the primary care setting. This study describes patient and provider experiences and perceptions of the artificial intelligence DR screening technology called EyeArt by EyeNuk during implementation of the tool at Western Maine Primary Care in Norway, Maine.

Methods: This non-randomized, single-center, prospective observational study surveyed 102 patients and 13 primary care providers on their experience of the new screening intervention.

Results: All surveyed providers agreed that the new screening tool would improve access and annual screening rates. Some providers also identified …

Barriers To Screening For Diabetic Retinopathy: A Scoping Review, Amy Cooper Rn, Bsn, Lajerica Bates Rn, Bsn, Julie Bridges Rn, Bsn, Laura Reed Dnp, Fnp-Bc

Doctor of Nursing Practice Projects

Purpose/Background

More than 34 million people in the United States have diabetes. Diabetic retinopathy (DR) is a major complication of diabetes and a leading cause of vision loss. Risk factors for diabetic retinopathy include Type 1 and Type 2 Diabetes, hypertension, smoking, and being African American or Hispanic/Latino. This scoping review seeks to analyze the current research on ways to increase vision screenings, thus reducing cases of diabetic retinopathy in adults.

Methods

Between September 2020 and November 2021, a search was conducted using PubMed, EBSCOhost, Medline, and CINAHL to identify articles using keywords such as diabetic retinopathy and ophthalmology. This …

The Circadian E3 Ligase Fbxl21 Regulates Myoblast Differentiation And Sarcomere Architecture Via Myoz1 Ubiquitination And Nfat Signaling, Bo Hu, Jian-Xing Ma, Adam S Duerfeldt

Faculty, Staff and Student Publications

Diabetic retinopathy and age-related macular degeneration are common retinal diseases with shared pathophysiology, including oxidative stress-induced inflammation. Cellular mechanisms responsible for converting oxidative stress into retinal damage are ill-defined but have begun to clarify. One common outcome of retinal oxidative stress is mitochondrial damage and subsequent release of mitochondrial DNA into the cytosol. This leads to activation of the cGAS-STING pathway, resulting in interferon release and disease-amplifying inflammation. This review summarizes the evolving link between aberrant cGAS-STING signaling and inflammation in common retinal diseases and provides prospective for targeting this system in diabetic retinopathy and age-related macular degeneration. Further defining …

Conjunctival And Lingual Mucosal Neuromas Without Multiple Endocrine Neoplasia Type 2b, Talia N. Shoshany, Christopher J. Rapuano, Tatyana Milman

Wills Eye Hospital Papers

Purpose: To report a patient with conjunctival and buccal neuromas and enlarged corneal nerves without Multiple Endocrine Neoplasia 2B (MEN2B).

Observations: A 28-year-old female presented with progressively enlarging bilateral limbal conjunctival growths. Slit lamp examination was notable for enlarged corneal nerves and well-circumscribed gelatinous subepithelial limbal nodules. Systemic examination revealed similar lesions on the tongue. Conjunctival biopsy demonstrated a mucosal neuroma. The patient underwent endocrine workup for MEN2B and genetic testing for the RET-proto oncogene mutations, all of which were negative.

Conclusions and Importance: The findings in our patient may be compatible with pure mucosal neuroma syndrome. The pattern of …

Examining The Effects Of Hyperglycemia On Retinal Regeneration, Emmanuella Ec Kyllians

Theses and Dissertations--Biology

Diabetes is a disease that affects how the body processes glucose, leading to a cascade of other complications, one of which is diabetic retinopathy (DR). DR is a neurovascular disease that affects the retina and research has revealed the role of retinal neurodegeneration in its development. Animal models like zebrafish have emerged as important tools for studying the molecular and cellular mechanisms underlying DR. On the other hand, retinitis pigmentosa (RP) is a degenerative disease that involves the progressive degeneration of rods and cones, and hyperglycemia has been found to impair regeneration. Therefore, this study aims to examine the effects …

Interventions To Improve Adherence To Recommended Diabetic Retinopathy Screening In Adult Patients With Diabetes Mellitus: A Scoping Review, Clare Anderson Bsn, Rn, Dnp, Fnp, Sarah May Bsn, Rn, Dnp, Fnp, Diana Dedmon Dnp, Aprn, Fnp-Bc

Doctor of Nursing Practice Projects

Purpose/Background Diabetic retinopathy (DR) is the leading cause of blindness in adults. Current guidelines recommend that all patients with type 2 diabetes mellitus (T2DM) have a DR screening (DRS) upon diagnosis of T2DM and then annually, but the adherence rate is only approximately 60%. This scoping review aims to evaluate the effectiveness of primary care providers (PCPs) employing strategies to increase compliance with annual DRS among adult patients with T2DM.

Methods Between September 2021 and January 2022, a literature review was performed to collect studies evaluating interventions to increase adherence to DRS. Individual searches of PubMed, SCOPUS, and CINAHL were …

Secretogranin Iii Stringently Regulates Pathological But Not Physiological Angiogenesis In Oxygen-Induced Retinopathy, Chang Dai, Prabuddha Waduge, Liyang Ji, Chengchi Huang, Ye He, Hong Tian, Elizabeth Zuniga-Sanchez, Amit Bhatt, Iok-Hou Pang, Guanfang Su, Keith A Webster, Wei Li

Faculty, Staff and Students Publications

Conventional angiogenic factors, such as vascular endothelial growth factor (VEGF), regulate both pathological and physiological angiogenesis indiscriminately, and their inhibitors may elicit adverse side effects. Secretogranin III (Scg3) was recently reported to be a diabetes-restricted VEGF-independent angiogenic factor, but the disease selectivity of Scg3 in retinopathy of prematurity (ROP), a retinal disease in preterm infants with concurrent pathological and physiological angiogenesis, was not defined. Here, using oxygen-induced retinopathy (OIR) mice, a surrogate model of ROP, we quantified an exclusive binding of Scg3 to diseased versus healthy developing neovessels that contrasted sharply with the ubiquitous binding of VEGF. Functional immunohistochemistry visualized …

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 …

Hyperglycemia During The First Three Days Of Life Increases The Risk Of Retinopathy Of Prematurity In Extremely Low Birth Weight Infants, Jihan M. Esmail, Ramasubbareddy Dhanireddy Md

Longitudinal Scholar's Project

Background: The association between hyperglycemia and ROP has been inconsistent in previous studies. Extremely low birth weight (ELBW) infants are at high risk for ROP. They also experience hypoglycemia initially and hyperglycemia while receiving IV glucose infusion. The effect of initial hypoglycemia on hyperglycemia associated ROP risk is unknown.

Objective: To study the effect of initial hypoglycemia and subsequent hyperglycemia during the first three days of life on the incidence of ROP and severe ROP in ELBW (birth weight ≤1000g) infants.

Methods: Clinical and demographic data were collected from 227 ELBW infants born during the years 2017-2019 at the Regional …

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 …

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 …

Assessing Disease Severity Of Diabetic Retinopathy Using Novel Graphical Interpretation Of Flicker Electroretinogram, Anjalee Choudhury, Jonas Moses, Victor Gonzalez

MEDI 9331 Scholarly Activities Clinical Years

Purpose: To assess the clinical value of reporting full-field electroretinogram (eg, flicker ERG) findings graphically to determine the severity of diabetic retinopathy (DR) within an office-based setting.

Methods: Patients with type 2 diabetes mellitus were included and classified into varying degrees of DR based on presence and severity. Flicker ERG responses were recorded and compared between groups.

Results: Between the varying disease stages, significant differences in the mean magnitude and phase values were found. There was also a significant difference between the proportions of the magnitude and phase color-coded frequencies between groups of severity and threat to …

Effect Of High Glucose On Ocular Surface Epithelial Cell Barrier And Tight Junction Proteins, Saleh M. Alfuraih, Ashley Barbarino, Christopher Ross, Kiumars Shamloo, Vishal Jhanji, Miao Zhang, Ajay Sharma

Pharmacy Faculty Articles and Research

PURPOSE. Patients with diabetes mellitus are reported to have ocular surface defects, impaired ocular surface barrier function, and a higher incidence of corneal and conjunctival infections. Tight junctions are critical for ocular surface barrier function. The present study was designed to investigate the effect of high glucose exposure on human corneal and conjunctival epithelial cell barrier function and tight junction proteins.

METHODS. Human corneal and conjunctival epithelial cells were exposed to 15 mM and 30 mM glucose for 24 and 72 hours. The barrier function was measured using transepithelial electrical resistance (TEER). The cell migration was quantified using scratch assay. …

Modulation Of Inflammatory Pathway By Inflammatory Inhibitor Jsh-23 Mitigates Diabetic Retinopathy., Rubens Petit Homme

Electronic Theses and Dissertations

Diabetic retinopathy (DR) is the most common microvascular complication of diabetes mellitus (DM). Its pathology is consisted of the breakdown of the blood-retinal barrier (BRB), particularly the inner blood-retinal barrier (iBRB). The exact mechanism that leads to the iBRB impairment and the development of DR has not been elucidated yet. However, chronic inflammation that is hallmark of the type I DM has recently become a key focus in DR study. Hyperglycemia causes dysregulation of nuclear factor-kappa B (NF-kB); and its constant activation increases the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and intercellular adhesion molecule-1 (ICAM-1) in the …

Observing Growth Effects Of Pigment Epithelium-Derived Factor On Human Retinal Pericytes In Vitro, Anjalee Choudhury, Andrew Tsin, Zachary Perez, Fransisco Elisarraras

School of Medicine Publications

The purpose of this study is to investigate and determine the role of PEDF in the pathogenesis of diabetic retinopathy as induced by advanced glycation end-products (AGEs). Human retinal pericytes were isolated from donors and will be measured for cell proliferation under the influence of PEDF both in the presence and absence of AGEs. Expected outcomes involve both the maintenance and increased survival of HRPs after treatment with PEDF under stimulated hyperglycemic conditions.

Characterization Of Extracellular Vesicles From Human Diabetic Retinopathy Retinal Tissue In Vitro And From Urine Of Human Patients With Diabetic Retinopathy, Jason Mighty

Dissertations, Theses, and Capstone Projects

Diabetic Retinopathy (DR) is a neurovascular complication associated with diabetes mellitus that affects approximately 120 million people worldwide and its prevalence is expected to reach 190 million by 2030. DR diagnosis is accomplished with fundus ophthalmoscopy often when retinal damage and vision loss have already occurred. A group of biomarker being explored for early detection of diseases are extracellular vesicles (EVs), which are nanometer diameter lipid enclosed vesicles, released from all cell types and containing genetic cargo reflective of releasing cell state. EV biomarkers are currently being explored to help monitor disease predisposition, pathogenesis and response to treatment. While an …

A Process Improvement Project To Increase Referral And Documentation Rates For Diabetic Retinopathy Screening, Debra Ann Bryant Taylor

DNP Projects

Abstract

Background: Approximately 5.3 million Americans, aged 18 and over, carry a diagnosis of diabetic retinopathy (DR). By the year 2050 this number is expected to triple without effective healthcare intervention. Approximately 4.8% of the global blindness is attributable to DR, a silent, progressive, microvascular complication of diabetes. Best practice dictates immediate screening at time of diagnosis of Type II Diabetes Mellitus (T2DM) and biennial screenings thereafter, yet this need is often unmet.

Purpose: This study is a continuation of a process put into place by Dr. Michelle Campbell in October 2017 at the Norton Community Medical Associates Mount Washington …

Does Ranibizumab Improve Best Corrected Visual Acuity In Adults With Diabetic Macular Edema Compared To Those Without Ranibizumab?, James E. Huang

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective evidence based medicine (EBM) review is to determine whether or not ranibizumab improves best corrected visual acuity (BCVA) in adults with diabetic macular edema compared to patients who do not receive ranibizumab.

STUDY DESIGN: The selective review examined best corrected visual acuity values reported from published, primary literature sources that examined the efficacy of ranibizumab in diabetic macular edema.

DATA SOURCES: Two double blind randomized controlled trials and one case control study were selected and reviewed.

OUTCOMES MEASURED: Best corrected visual acuity (BCVA) as measured from Early Treatment Diabetic Retinopathy Study visual …

Beta-2-Adrenergic Receptor Regulates Insulin Signaling To Reduce Cell Death In Müller Cells, Robert Jason Walker

Theses and Dissertations (ETD)

No abstract provided.