Optometry Commons^™

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

Faculty, Staff and Students Publications

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

A Reliable Diabetic Retinopathy Grading Via Transfer Learning And Ensemble Learning With Quadratic Weighted Kappa Metric, Sai Venkatesh Chilukoti, Liqun Shan, Vijay Srinivas Tida, Anthony S. Maida, Xiali Hei

Computer Science Faculty Publications

The most common eye infection in people with diabetes is diabetic retinopathy (DR). It might cause blurred vision or even total blindness. Therefore, it is essential to promote early detection to prevent or alleviate the impact of DR. However, due to the possibility that symptoms may not be noticeable in the early stages of DR, it is difficult for doctors to identify them. Therefore, numerous predictive models based on machine learning (ML) and deep learning (DL) have been developed to determine all stages of DR. However, existing DR classification models cannot classify every DR stage or use a computationally heavy …

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 …

Counterfeit Contact Lenses, Claire E. Mcdonnell

Articles

This article covers how counterfeit cosmetic and corrective contact lenses potentially reach the end user and the dangers of counterfeit lenses.

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

Faculty, Staff and Students Publications

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

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

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

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

Faculty, Staff and Students Publications

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

The Ocular Sequelae Of Eyelash And Eyebrow Fashions, Claire E. Mcdonnell

Articles

This is an article on the possible adverse side effects of eyelash and eyebrow fashions e.g. fake eyelashes, eyelash tinting, eyebrow lamination, microblading. Advice is given to eyecare practitioners discussing these treatments with patients.

Aligning Eye Care Provider Beliefs With Behaviors: Exploring And Improving Ocular Surface Disease Decision-Making In A Cataract Surgery Clinic, Amy Hellem

Communication (PhD) Dissertations

Millions of cataract surgeries are performed every year in the United States, yet both surgeon reports and patient reports indicate that practices are not utilizing the diagnostic tests and treatments that are advocated in the medical literature to identify and manage ocular surface disease prior to surgery. As a result, patients risk suffering several significant consequences with regard to their vision, comfort and safety. Personal observations from my 25 years of experience working with ophthalmologists and optometrists led to curiosity regarding the root cause of undertreatment of ocular surface disease. Specifically, I had the impression that eye care providers held …

Exploring The Impact Of Caffeine, Alcohol, And Opioids On Intraocular Pressure: A Comprehensive Analysis Of Short-Term And Long-Term Effects On Vision, Jake Prieto

CMC Senior Theses

Coffee, alcohol, and opioids are addictive drugs commonly used in modern society, yet their impact on ocular health remains ambiguous. This systematic review aims to elucidate this ambiguity by examining their effects on intraocular pressure (IOP). Utilizing IOP as a metric, both short-term and long-term effects are evaluated across individuals with irregular IOP levels and healthy subjects. Furthermore, the study analyzes choroidal thickness as an additional measure to reinforce or challenge the findings regarding IOP, leveraging the inverse relationship between the two metrics concerning elevated IOP-related illnesses, such as open-angle glaucoma (OAG).

A comprehensive literature search was performed through Google …

Analysis Of Macular Pigment Carotenoids In Human Blood Serum Of Glaucoma Patients As A Measure Of Ocular Health: A Raman Spectroscopic Study., Joy Udensi, Ekaterina Loskutova, James Loughman, Hugh J. Byrne

Datasets

Carotenoids are a major component of the human diet and have been widely studied for their antioxidant, and vision protection roles in the human body, and dietary supplementation is promoted in particular for ocular health. An initial trial (European Nutrition in Glaucoma Management (ENIGMA)), which assessed macular pigment optical density (MPOD) as well as ocular structural, functional and perceptual parameters before and after the 18-month supplementation of glaucoma patients with macular pigment (MP) carotenoids (lutein, zeaxanthin, meso-zeaxanthin), confirmed supplementation significantly improved the clinical ocular health of participants. Blood contains all major dietary carotenoids, presenting it as a suitable and efficient …

Raman Microspectroscopy For Detection Of Oral Potentially Malignant Disorders Using Minimally Invasive Brush Biopsy Samples, Isha Behl

Doctoral

Oral cancer is one of the most common cancers worldwide. The current gold standard for screening and diagnosis of oral premalignant and cancerous lesions is histopathological examination. Subjectivity is a major limitation of this technique, however. Other diagnostic methods exist, but they are not sensitive enough for early detection of potentially malignant disorders (PMDs), as these methods are based on morphological changes, which can occur late in malignant transformation. Raman spectroscopy, on the other hand, can provide molecular level information of the biological sample, through unique vibrational fingerprints of molecules. This is advantageous over the gold standard method, as molecular …

Myopia Progression Patterns Among Paediatric Patients In A Clinical Setting, Michael Moore, Gareth Lingham, Daniel Ian Flitcroft, James Loughman

Articles

Purpose

This retrospective analysis of electronic medical record (EMR) data investigated the natural history of myopic progression in children from optometric practices in Ireland.

Methods

The analysis was of myopic patients aged 7–17 with multiple visits and not prescribed myopia control treatment. Sex- and age-specific population centiles for annual myopic progression were derived by fitting a weighted cubic spline to empirical quantiles. These were compared to progression rates derived from control group data obtained from 17 randomised clinical trials (RCTs) for myopia. Linear mixed models (LMMs) were used to allow comparison of myopia progression rates against outputs from a predictive …

Quantitative Raman Analysis Of Human Blood Serum Of Glaucoma Patients Supplemented With Macular Pigment Carotenoids., Joy Udensi, Ekaterina Loskutova, James Loughman, Hugh J. Byrne

Datasets

Carotenoids have been widely studied for their high dietary, antioxidant, and vision protection roles in the human body. Blood contains all major dietary carotenoids and hence presents as a suitable and efficient substrate for the estimation of dietary carotenoids in vivo. Following the 18-month supplementation of open angle glaucoma patients with macula pigment carotenoids (Lutein, Zeaxanthin and Meso-Zeaxanthin) in the European Nutrition in Glaucoma Management (ENIGMA) trial, Raman spectroscopic analysis of the pre-supplementation baseline and 18-month supplemented blood serum carotenoids from participants was carried out, to investigate the systemic impact of supplementation in the blood and explore a more direct …

Trpv4 Affects Visual Signals In Photoreceptors And Rod Bipolar Cells, Ye Long, Maxim Kozhemyakin, Samuel M Wu, Ji-Jie Pang

Faculty, Staff and Students Publications

INTRODUCTION: Mechanical sensitive channels expressed in mammalian retinas are effectors of elevated pressure stresses, but it is unclear how their activation affects visual function in pressure-related retinal disorders.

METHODS: This study investigated the role of the transient potential channel vanilloid TRPV4 in photoreceptors and rod bipolar cells (RBCs) with immunohistochemistry, confocal microscopy, electroretinography (ERG), and patch-clamp techniques.

RESULTS: TRPV4 immunoreactivity (IR) was found in the outer segments of photoreceptors, dendrites and somas of PKCα-positive RBCs and other BCs, plexiform layers, and retinal ganglion cells (RGCs) in wild-type mice. TRPV4-IR was largely diminished in the retinas of homozygous TRPV4 transgenic mice. …

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 …

The Co-Expression Of The Depolarizing And Hyperpolarizing Mechanosensitive Ion Channels In Mammalian Retinal Neurons, Vivian Y Pang, Zhuo Yang, Samuel M Wu, Ji-Jie Pang

Faculty, Staff and Students Publications

Introduction

The elevation of the intraocular and extraocular pressures is associated with various visual conditions, including glaucoma and traumatic retinal injury. The retina expresses mechanosensitive channels (MSCs), but the role of MSCs in retinal physiology and pathologies has been unclear.

Methods

Using immunocytochemistry, confocal microscopy, and patch-clamp recording techniques, we studied the co-expression of K⁺-permeable (K-MSCs) TRAAK and big potassium channel BK with the epithelial sodium channel ENaC and transient receptor potential channel vanilloid TPRV4 and TRPV2 favorably permeable to Ca²⁺ than Na⁺ (together named N-MSCs), and TRPV4 activity in the mouse retina.

Results

TRAAK immunoreactivity …

The Utility Of Software-Detected Non-Invasive Tear Break-Up In Comparison To Fluorescein Tear Break-Up Measurements, Stephen C Pflugfelder, Yasushi Kikukawa, Shin Tanaka, Takuya Kosugi

Faculty, Staff and Students Publications

PURPOSE: The purpose of this study is to characterize and discuss the difference between software-detected non-invasive tear break-up time (NIBUT) and the traditional clinical method of fluorescein break-up time (FBUT).

METHODS: Tear interferometry with the KOWA DR-1α (Kowa, Japan) and a standardized comprehensive ocular surface/tear evaluation were performed in 307 eyes. Software-detected NIBUT in the KOWA DR-1α images and the investigator-detected FBUT were compared.

RESULTS: Software-detected NIBUT was significantly shorter than investigator-measured FBUT. NIBUT was 3.1 ± 2.5 s (mean ± SD), whereas FBUT was 4.8 ± 3.0 s. This difference was due to three different patterns or conditions: a …

Atypical Haemorrhagic Presentation Of Neuro-Retinitis And Serous Retinal Detachment Secondary To Cat-Scratch Disease, Henry C Skrehot, Amer F Alsoudi, Ryan P Nolan, Adam J Cantor, Asad Loya, Rod Foroozan

Faculty, Staff and Students Publications

Cat-scratch disease (CSD) is a self-limited disease caused by Bartonella henselae, a fastidious gram-negative intracellular bacillus bacterium. Neuroretinitis, a form of optic neuropathy characterised clinically by optic disc swelling and a macular star, is an uncommon manifestation of CSD occurring in approximately 1-2% of cases. We report a case of a 14-year-old female who presented to the emergency department with a chief complaint of acute painless vision loss described as a large black spot in the centre of her right eye vision 2 weeks after being scratched by cats. Fundus examination revealed Frisen grade 5 disc oedema with an …

Single Cell Analysis Of Short-Term Dry Eye Induced Changes In Cornea Immune Cell Populations, Jehan Alam, Ebru Yaman, Gerda Cristal Villalba Silva, Rui Chen, Cinita S De Paiva, Mary Ann Stepp, Stephen C Pflugfelder

Faculty, Staff and Students Publications

BACKGROUND: Dry eye causes corneal inflammation, epitheliopathy and sensorineural changes. This study evaluates the hypothesis that dry eye alters the percentages and transcriptional profiles of immune cell populations in the cornea.

METHODS: Desiccating stress (DS) induced dry eye was created by pharmacologic suppression of tear secretion and exposure to drafty low humidity environment. Expression profiling of corneal immune cells was performed by single-cell RNA sequencing (scRNA-seq). Cell differentiation trajectories and cell fate were modeled through RNA velocity analysis. Confocal microscopy was used to immunodetect corneal immune cells. Irritation response to topical neurostimulants was assessed.

RESULTS: Twelve corneal immune cell populations …

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 = …