Ophthalmology Commons^™

Purine Metabolic Adaptation Protects The Endothelium From Disturbed Flow-Induced Dna Damage And Atherosclerosis, Qian Ma, Yongfeng Cai, Zhidan Zhang, Dingwei Zhao, Yuan Zhao, Peishan Xu, Tammy Lu, Wendy Zhang, Qiuhua Yang, Yaqi Zhou, Varadarajan Sudhahar, Tohru Fukai, Hanjoong Jo, Yiming Xu, Yuqing Huo

Faculty, Staff and Students Publications

Despite effective lipid-lowering therapies, atherosclerosis continues to be a leading cause of death, with considerable residual cardiovascular risk. Atherosclerotic lesions develop preferentially at arterial regions exposed to disturbed flow (d-flow), which induces genomic stress, endothelial injury, and barrier dysfunction. Hemodynamic forces are known to reprogram endothelial metabolism, but the role of de novo purine synthesis (DNPS), which supplies nucleotides for genome maintenance and whose terminal steps are catalyzed by the bifunctional enzyme ATIC, remains undefined in atherosclerosis. By integrating bulk and single-cell multiomics with in vitro flow systems and in vivo models, we show that d-flow upregulates DNPS and ATIC …

Mogad Is The Most Common Cause Of Isolated Optic Neuritis In Children, Chaitanya Aduru, Akansha Chandrasekar, Kyla Blasingame, Jonathan Rosen, Jesse M Levine, Karla Salazar, Madhuri Chilakapati, Rod Foroozan, Victoria Hardwick, Jonathan M Yarimi, Nikita Shukla, Timothy E Lotze, Kristen S Fisher, Alexander J Sandweiss

Faculty, Staff and Students Publications

Objectives: The study aimed to characterize the clinical features, etiologies, and outcomes of isolated, first-time pediatric ON in the post-MOG-IgG era.

Methods: This was a single-center retrospective cohort study at Texas Children's Hospital of patients diagnosed with first-time ON between 2018-2024, with follow-up data collected through 2025. Inclusion criteria required monocular or binocular subacute vision loss with supportive paraclinical signs. Subjects were excluded if they had a prior history of demyelinating disease or extra-orbital demyelinating lesions on initial brain/spine MRI. Primary outcomes were the proportion of MOG-IgG seropositivity, retinal nerve fiber layer thickness, and visual acuity at onset and most …

Tropomyosin-Related Kinase Receptor Type B Agonism In Geographic Atrophy-The Translational Challenges From Preclinical Data To A First-In-Human Trial, David Brown, Oliver Zeitz, Clare Bailey, Sunir J. Garg, Karl Csaky, James Talks, Sobha Sivaprasad, Peter M. Benz, Rolf Herrmann, Remko A. Bakker, Sebastian Bandholtz, Ankit Mittal, Qihong Huang, Serge Kosobokovs, Gudrun Simons, Andrea Giani, Jochen Huber, Martin Gliem

Wills Eye Hospital Papers

OBJECTIVE: To report results of the first-in-human trial of intravitreal tropomyosin-related kinase receptor type B (TrkB) agonist BI 754132 in participants with geographic atrophy (GA). To discuss BI 754132 clinical data in the context of the preclinical findings and their translation into human data.

DESIGN: An open-label, uncontrolled, nonrandomized phase I trial (NCT04002310) assessing the safety, tolerability, and pharmacokinetics of BI 754132 in participants with GA supported by preclinical data.

PARTICIPANTS: Participants with GA recruited between July 2019 and August 2022 in the United States and UK.

METHODS: Clinical trial comprising a single rising dose (SRD) part (n = 15) …

Assessment Of Correctness, Content Omission, And Risk Of Harm In Large Language Model Responses To Ophthalmology Continuing Medical Education Questions, Jacqueline L. Chen, Amanda J. Lu, Rohan Verma, Li Wang, Douglas D. Koch, Allison J. Chen

SKMC Student Presentations and Publications

PURPOSE: To evaluate the accuracy and prose responses of 2 large language models (LLMs) to ophthalmology continuing medical education questions.

DESIGN: Question prompts and multiple choice (MC) answer options were input into the 2 LLMs, and responses were analyzed for accuracy and assessed for evidence of correctness, completeness, bias, and potential harm using a previously reported standardized rubric.

SUBJECTS: Basic and Clinical Science Course questions and MC answer options from the American Academy of Ophthalmology question bank were used as inputs into the 2 LLMs (ChatGPT-4 and Google Vertex's Gemini Pro 1.5).

METHODS: The MC responses were assessed for accuracy …

Convergence And Divergence Of Opinion About Treatment Of Binocular Vision Disorders Among Vision Care Professionals, Sonia Young

Dissertations

There are three distinct professions prominent in the field of pediatric vision care. They are ophthalmology, optometry and orthoptics. All professions are integral to the detection and treatment of pediatric binocular vision disorders. However, distinct schools of thought exist to describe the best approach to pediatric binocular vision disorders and their treatments. Literature often highlights two opposing schools of thought represented by the “medical” and “behavioral” approaches. While there is academic debate about the merits and pitfalls of either approach, there is a paucity of nuanced perspectives which more closely resemble the ways in which pediatric ocular clinicians approach diagnosis …

Immune Checkpoint Inhibitor-Associated Perioptic Neuritis, Neud Kiros, Alina Sinha, Anant Krishnan

Conference Presentation Abstracts

Clinical History A 47-year-old male with history of stage IV gastric cancer on nivolumab presented with blurry vision worse at close distances. Binocular horizontal diplopia was found on exam. Fundus exam demonstrated 4+ disc edema and hemorrhage bilaterally. Recent head MRI was negative for leptomeningeal enhancement. MR venogram and MRI orbits with contrast were ordered as well as lumbar puncture. The patient’s next dose of immunotherapy was held. Opening pressure was normal, and MRV showed no evidence of dural sinus thrombosis. MRI of the orbits was positive for perioptic neuritis bilaterally, and the patient was started on a steroid taper …

Assessment Of Correctness, Content Omission, And Risk Of Harm In Large Language Model Responses To Ophthalmology Continuing Medical Education Questions, Jacqueline L Chen, Amanda J Lu, Rohan Verma, Li Wang, Douglas D Koch, Allison J Chen

Faculty, Staff and Students Publications

Purpose: To evaluate the accuracy and prose responses of 2 large language models (LLMs) to ophthalmology continuing medical education questions.

Design: Question prompts and multiple choice (MC) answer options were input into the 2 LLMs, and responses were analyzed for accuracy and assessed for evidence of correctness, completeness, bias, and potential harm using a previously reported standardized rubric.

Subjects: Basic and Clinical Science Course questions and MC answer options from the American Academy of Ophthalmology question bank were used as inputs into the 2 LLMs (ChatGPT-4 and Google Vertex's Gemini Pro 1.5).

Methods: The MC responses were assessed for accuracy …

Extrapulmonary Small Cell Carcinoma Presenting As Bilateral Papilledema, Hyponatremia, Encephalitis, Seizures, Crmp5-Igg Reactivity, And Prominent Anterior Tubular Perivascular Spaces, Ramsis Benjamin, Drew Thomas, Nina Mourao, J. Judd Fite, Brianna Woodliff, Shubhank Goyal

School of Medicine Publications

Background: Paraneoplastic syndromes that affect both the optic disc and the brain parenchyma typically harbor antibodies directed toward CV2/collapsin response-mediator protein 5 (anti-CRMP5), amphiphysin, Ma antigen 2 (Ma2/Ta), and Yo. The most common cancers linked to anti-CRMP5 antibodies include small-cell lung carcinoma (SCLC), followed by thymoma, renal cell carcinoma, and thyroid papillary carcinoma. A long-held belief explains papilledema as related to increased pressure within the subarachnoid space or the microvascular capillaries, but intracranial pressures within the normal standard range may exist in a person with a paraneoplastic syndrome and papilledema. The glymphatic system, a central waste-clearance conduit, may play a …

Deep Learning And Experimental Validation Of Brca1-Associated Protein-1 Missense Variant Pathogenicity In Uveal Melanoma, Nikhil Davé, David J. Taylor Gonzalez, Mak B. Djulbegovic, Linda A. Cernichiaro-Espinosa, Benjamin A. King, Carol L. Shields, Matthew W. Wilson

Wills Eye Hospital Papers

OBJECTIVE: To benchmark the pathogenicity predictions of AlphaMissense, a deep learning model, against high-throughput functional scores from saturation genome editing (SGE) for all experimentally tested BRCA1-associated protein-1 (BAP1) missense variants in uveal melanoma (UM).

DESIGN: Cross-sectional analytical study comparing computational predictions with experimentally derived functional classifications and clinical annotations.

SUBJECTS PARTICIPANTS AND/OR CONTROLS:  ClusteredAll 4619 BAP1 single amino acid substitutions profiled in a published Regularly Interspaced Short Palindromic Repeats-Cas9 SGE viability assay. No separate control cohort was required. Clinical Variant Database (ClinVar)-annotated variants within this set served as an independent reference.

METHODS: Saturation genome editing log₂-fitness …

Lotilaner Ophthalmic Solution 0.25% In The Treatment Of Demodex Blepharitis: A Case Report, Paul Karpecki, Brandon Ayres, Eric Donnenfeld, Marjan Farid, Ian Benjamin Gaddie, Preeya K Gupta, Cecelia Koetting, Richard Lindstrom, Selina Mcgee, Kelly K Nichols, Laura M Periman, Stephen Pflugfelder, Christopher Starr, Nandini Venkateswaran, Elizabeth Yeu

Faculty, Staff and Students Publications

Demodex blepharitis is a chronic inflammatory ocular condition caused by Demodex mite infestation of the eyelid that can negatively impact quality of life. Currently, lotilaner ophthalmic solution 0.25% is the only FDA-approved treatment for Demodex blepharitis. The Demodex Expert Panel on Treatment and Eyelid Health has established consensus that lotilaner ophthalmic solution 0.25% should be considered the preferred first-line treatment for Demodex blepharitis. We report a patient who presented with collarettes, the pathognomonic sign of Demodex blepharitis, meibomian gland dysfunction, and poor visual acuity. The patient also had a history of neovascular age-related macular degeneration. Consistent with the Demodex Expert …

Dapk2 Regulates Pkm2 Phosphorylation At Threonine 45 To Facilitate Disturbed Flow-Induced Atherosclerosis, Shuai Guo, Long Xu, Yixin Chen, Yuan Zhao, Yuting Zhang, Runfa Yu, Kaixiang Cao, Litao Wang, Wenjia Ai, Jiang-Yun Luo, Lu Lu, Jun He, Yuan Zhou, Li Wang, Andrew H Baker, Yuqing Huo, Yiming Xu

Faculty, Staff and Students Publications

Background: Oscillatory shear stress (OSS), resulting from disturbed blood flow, is implicated in atherosclerotic plaque formation by incompletely understood mechanisms. This study aims to elucidate the involvement of death-associated protein kinase (DAPK) 2 in OSS-induced endothelial cell (EC) activation and atherosclerosis.

Methods: Publicly available resources, including genome-wide microarray, RNA sequencing, and single-cell RNA sequencing, were utilized to identify key OSS-sensitive regulatory factors. Techniques such as mass spectrometry, immunoprecipitation, proximity ligation assay, and RNA sequencing were employed to identify pyruvate kinase M2 (PKM2) as the binding protein of DAPK2 and determine the specific site of PKM2 phosphorylation by DAPK2. To assess …

Evaluating The Efficacy Of Dry Lab Cataract Simulation For Medical Students, Ashley Choi, Andrew Chen, Miel Sundararajan, Karine D. Bojikian, Anthony Chung, Shu Feng

Journal of Academic Ophthalmology

Background: Cataract surgery is a major component of ophthalmologic surgical training. However, medical students often lack early exposure to intraocular surgery, limiting their ability to assess their interest in the field.

Purpose: To evaluate the educational impact of a cataract surgery dry lab workshop for medical students using the Kitaro Anterior Segment Dry Lab Kit.

Methods: The workshop included a faculty-led presentation on eye anatomy, cataract formation, and cataract surgery, followed by hands-on practice. Pre- and post-workshop questionnaires were conducted to evaluate students’ knowledge in cataract surgery, interest in ophthalmology, interest in microsurgery, and evaluation of the …

Effect Of Pre-Training Patients Using A Self-Directed Slideshow Presentation On Visual Field Reliability In First-Time Test Takers, Lillian M. Centlivre B.S., Derek Zahnleuter B.S., Rahul Babu B.S., Chaesik Kim, Kaitlin Ziadeh Md, Hanna Simmons Md, Vivian Rajeswaren Md, Aleskey Parker Williams Do, Jacob Im Md, Aleksey Mishulin Md, Faisal Ridha Al-Timimi Md, Hassan Tokko

Medical Student Research Symposium

Title: Effect of Pre-Training Patients Using a Self-Directed Slideshow Presentation on Visual Field Reliability in First-Time Test Takers

Authors: Lillian Centlivre BS, Derek Zahnleuter BS, Rahul Babu BS, Chaesik Kim BSEE, Kaitlin Ziadeh MD, Hanna Simmons MD, Vivian Rajeswaren MD, Aleksey Parker Williams DO, Jacob Im MD, Aleksey Mishulin MD, Faisal Ridha Al-Timimi MD, Hassan Tokko MD

Background: Visual field (VF) testing is essential for detecting glaucoma, but reliability is limited by patient inexperience and poor fixation. Prior studies report VF test reliability around 59%, primarily attributed to increased fixation loss (FL). Other studies note 75.9% reliability using training videos …

Eating For Healthy Eyes: The Role Of Nutrition In Ocular Health, Brianna Stroh

Honors Program: Senior Projects (Public)

The central research question of this thesis asks: How does nutrition influence ocular health overall and the impact of nutrition on the development or progression of common eye diseases? Building upon existing research in optometry/ophthalmology, nutrition science, and public health, this project examines the physiological mechanisms linking diet to eye health and evaluates how specific nutrients and dietary patterns contribute to disease prevention and visual function. This thesis employs a comprehensive review of peer-reviewed literature to evaluate the relationship between nutrition and ocular disease. Key areas of focus include the role of oxidative stress in eye disease development, the protective …

A Comprehensive Review Of Tear Fluid Proteome Alterations In Dry Eye Disease: Insights Into Pathophysiology And Biomarker Potential, Saleh Ahmed, Steven Safille, Victoria Clifton, Shruti Sharma, Cintia S De Paiva, Ashok Sharma

Faculty, Staff and Students Publications

Tear fluid is a highly specialized and dynamic biofluid composed of proteins, lipids, mucins, and electrolytes that is essential for maintaining ocular surface integrity, immune defense, and tear film stability. Growing evidence from tear proteomic studieshas revealed extensive alterations in protein composition in dry eye disease (DED), reflecting a complex interplay between local ocular surface pathology and systemic inflammatory influences. This review summarizes proteomic findings from 50 published studies to identify tear proteins that are consistently upregulated or downregulated in DED and to interpret their biological relevance in the context of ocular surface homeostasis. Across studies, proteins upregulated in DED …

Rexinoid Net-3ib Promotes Resident Macrophage Gene Expression And Mitigates Desiccation-Induced Ocular Surface Disease, Jehan Alam, Yangluowa Qu, Jianming Shao, Ebru Yaman, Karen Zheng, Hiroki Kakuta, Stephen C Pflugfelder

Faculty, Staff and Students Publications

Purpose: To evaluate the effects of rexinoid NEt-3IB on desiccating stress-induced dry eye, as well as monocyte/macrophage gene expression and cellular trajectory.

Methods: Eyes were topically treated with rexinoid NEt-3IB (5 µM) or vehicle three times a day for 5 days of desiccating stress-induced dry eye. Single-cell RNA sequencing (RNA-seq) profiled gene expression in conjunctival immune cells. RNA-seq was also used to evaluate gene expression in lipopolysaccharide (LPS)-stimulated, dexamethasone-treated (Dex, 1 µM), or NEt-3IB-treated (1-1000 nM) cultured monocytes. Cellular state trajectory and latent time were inferred with scVelo, and latent-time-associated genes were identified using Monocle 3. Permeability to Oregon Green-labeled …

Avacincaptad Pegol For Geographic Atrophy Secondary To Age-Related Macular Degeneration: Two-Year Efficacy And Safety Results From The Gather2 Phase 3 Trial, Arshad M Khanani, Carl J Danzig, Jeffrey S Heier, Glenn J Jaffe, Peter K Kaiser, David R Lally, Sunil S Patel, Lejla Vajzovic, Christina Y Weng, Hersh Patel, Julie Clark, Dhaval Desai, Don Luo, Erin Henry, Frank G Holz

Faculty, Staff and Students Publications

Purpose: Avacincaptad pegol (ACP) is a pegylated RNA aptamer that inhibits complement C5. The efficacy and safety of ACP 2 mg was investigated in GATHER2, with positive year 1 results published. Herein, 2-year results are reported.

Design: Phase 3, randomized, sham-controlled study (ClinicalTrials.gov identifier, NCT04435366).

Participants: Patients with non-center point-involving geographic atrophy (GA).

Methods: Eligible patients were randomized 1:1 to receive monthly ACP 2 mg (n = 225) or sham (n = 222) for 1 year. At month 12, patients who received ACP 2 mg were randomized again 1:1 to dosing every month (EM; n = 96) or every …

Comprehensive Profiling Of The Human Tear Fluid Mirnome Using Small Rna Sequencing, Garrett Jones, Drew Mayernik, Saleh Ahmed, Eliza Williams, Jeremy Altman, Tae Jin Lee, Amy Estes, Cintia S De Paiva, Pamela Martin, Shruti Sharma, Ashok Sharma

Faculty, Staff and Students Publications

Purpose: To generate a comprehensive profile of microRNAs (miRNAs) present in human tear fluid using next-generation sequencing (NGS), establish a reference miRNome for healthy human tear fluid, and investigate whether miRNA expression varies by sex, race, or age.

Methods: Tear samples were collected from 32 adults using Schirmer strips. RNA was isolated using the miRNeasy Serum/Plasma Kit, and cDNA libraries were prepared using the QIAseq miRNA Library Kit. Barcoded libraries were sequenced on the NovaSeq 6000 platform. Bioinformatic analyses included adapter trimming, alignment to miRBase, normalization with DESeq2, and functional annotation using multiMiR and clusterProfiler. Differential expression analysis was performed …

Results Of A Randomized, Double-Masked, Placebo-Controlled Phase 1/2 Study Of A Trpv1 Antagonist Sjp-0132 In Participants With Dry Eye Disease, Tomoyuki Wada, Kazunori Omatsu, Stephen C Pflugfelder

Faculty, Staff and Students Publications

Purpose: To investigate the safety, tolerability, pharmacokinetic profile, and efficacy of SJP-0132 in participants with dry eye disease (DED).

Design: Phase 1/2, randomized, double-masked, single-center, placebo-controlled single and multiple ascending dose study.

Participants: Generally healthy adults aged ≥18 years with a patient-reported history of DED for ≥6 months, eye dryness visual analog scale (VAS: 0-100) ≥40 mm, 5-item dry eye questionnaire (DEQ-5) ≥6, and central corneal fluorescein staining (CFS) of 2 to 4 (Baylor scale: 0-5 for each of five zones).

Methods: This study consisted of Part A and Part B, containing four single- and two multiple-ascending dose cohorts, respectively. …

Epidemiological Analysis Of Pediatric Ocular Trauma In Sports And Recreational Activities, Zachary Goodrich, Michael Foster, Cameron Dean, Jody He, Shambhawi Thakur, Lauren Mason, John Gote, Eric Crouch

Knowledge and Creativity Expo

Purpose: To characterize sports- and recreational activity- related orbital and ocular trauma presenting to a pediatric emergency department over an 11-year period.

Methods: Data from the electronic medical record of a Level 1 Pediatric Trauma Center was used to identify all cases of orbital and ocular trauma that occurred during sports or recreational activities between 1/1/2010 and 3/1/2021 in patients age 0 to 18 years old. Variables collected included activity type, age, sex, race, injured region, diagnosis, and treatment plan. Activities were categorized as contact sports, non-contact sports, or recreational activities. Comparative analyses used chi-square, ANOVA, t-tests, and Fisher exact …