CCGI Activities Update FY24

ALAN S. CRANDALL CENTER FOR GLAUCOMA INNOVATION AT THE JOHN A. MORAN EYE CENTER

FY24 ACTIVITIES UPDATE July 1, 2023-June 30, 2024

ALAN S. CRANDALL CENTER FOR GLAUCOMA INNOVATION

CONTENTS

An image of trabecular meshwork cells, which play a critical role in regulating intraocular pressure, taken by the laboratory of David J. Krizaj, PhD.

1

Crandall Center Overview

2

Message from the Director

6

Collaboration Matrix

7

Scientific Advisory Board

13

Clinical Investigators

14

Research Investigators

17

Industry Collaborators

18

Industry-Sponsored Research

20

Research Grants

23

Clinical Research & Trials

25

Publication Highlights

Crandall Center

OVERVIEW Nearly 80 million people are living with glaucoma, a blinding disease that will rob them of their eyesight. That number is projected to rise to 112 million people by 2040.

Directed by Iqbal Ike K. Ahmed, MD, FRCSC, the Alan S. Crandall Center for Glaucoma Innovation, was created to reverse this trend by leveraging unique resources for research found only at the John A. Moran Eye Center. The Crandall Center is organized into four initiatives:

Glaucoma Therapeutics This initiative conducts research to assist companies in developing safe and effective diagnostics and therapeutics and is headed by Crandall Center Director Iqbal Ike K. Ahmed, MD, FRCSC.

Global Care This initiative works to find better ways to diagnose glaucoma and inexpensive yet effective ways to treat it in low-resource nations and is headed by Craig J. Chaya, MD, who also serves as medical director of Moran’s Global Outreach Division.

Neuroprotection-Based Therapies This initiative is conducting research to develop new therapies to protect, restore, or regenerate the optic nerve and is directed by Crandall Center Associate Director of Science David Krizaj, PhD, of the Krizaj Laboratory.

Translational Research This initiative works to understand the biology and genetics of glaucoma to develop new treatments and is headed by Gregory S. Hageman, PhD, who also directs Moran’s Sharon Eccles Steele Center for Translational Medicine.

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ALAN S. CRANDALL CENTER FOR GLAUCOMA INNOVATION

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DIRECTOR’S YEAR IN REVIEW

It is my privilege to share the inaugural Alan S. Crandall Center for Glaucoma Innovation Activities Update.

Three years ago, I embarked on a journey to create a world-class center of excellence that would accelerate breakthroughs in glaucoma care and research. We have much to learn about the disease, and a growing number of patients are counting on us to develop new treatments and cures.

The John A. Moran Eye Center provides an exceptional environment for innovation. It has attracted some of the field’s top investigators and houses unparalleled resources for clinical, basic, and translational research. The Crandall Center has been building on this foundation, and I am thankful to report FY 2024 has been an exciting time of expansion.

I would like to welcome our new investigators who have recently joined the Moran Eye Center, to announce formation of our Scientific Advisory Board, and to highlight some key projects and collaborations that will take us into the future.

ALAN S. CRANDALL CENTER FOR GLAUCOMA INNOVATION

New Investigators Zachary W. Davis, PhD, studies the causal mechanisms underlying visual function in the brain; his work holds great promise for developing new disease models and studying how glaucoma impacts visual perception.

Adam M. Dubis, PhD, is renowned for improving ophthalmic and neurological treatment using cutting-edge imaging, image analytics, and data science tools.

Fiona S. McDonnell, PhD, studies outflow physiology and how nanoparticles called exosomes contribute to the regulation of intraocular pressure.

Ian F. Pitha, MD, PhD, combines his prior training in pharmacology with additional training in models of glaucoma and biomaterials to develop sustained drug delivery methods and surgical device designs.

Scientific Advisory Board I am humbled to share that some of the field’s top minds have generously agreed to serve on the Crandall Center’s newly formed Scientific Advisory Board. They will provide expert guidance, strategic insights, and informed recommendations to help drive our research initiatives.

W. Daniel Stamer, PhD, who serves as Co Vice-Chair of Basic Science Research and the Joseph A.C. Wadsworth Distinguished Professor of Ophthalmology at Duke University, will lead the board as chair. Additional board members are Jonathan Crowston, MD, PhD, C. Ross Ethier, PhD, Sir Peng T. Khaw, MD, PhD, Ingeborg Stalmans, MD, PhD, and Donald J. Zack, MD, PhD. This is a truly esteemed group, and I encourage you to read about their work in detail later in this report.

Key Projects Understanding glaucoma genetics Working with a major pharmaceutical company, Translational Initiative Director Gregory S. Hageman, PhD, has launched a large-scale protein study to discover gene-directed pathways he can use to develop new therapies for glaucoma. This approach, and Dr. Hageman’s exceptional team, led Moran to its first gene therapy for age-related macular degeneration, now in clinical trials.

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ALAN S. CRANDALL CENTER FOR GLAUCOMA INNOVATION

Vetting New Surgical Devices We continue to conduct pre-clinical research with industry for exciting new devices aimed at increasing surgical precision and providing better outcomes. Research has included: The first-in-human clinical study of the Myra Vision Calibreye System, which allows surgeons to implant a drainage device in the eye and later adjust it without the need for additional surgery.

Evaluating a first-generation EyeQ Technologies cyclophotocoagulation laser that targets the ciliary body to lower intraocular pressure.

Documenting histopathological effects on eye tissue following procedures with a new Elios Vision excimer laser that creates microscopic openings in the trabecular network.

In FY25, we will conduct a pre-clinical study with ViaLase, the first femtosecond laser, imageguided, high-precision trabeculotomy (FLigHT) for open-angle glaucoma. We will also be involved in a drainage device material evaluation for Gore.

Increasing Access to Care Moran’s Global Outreach Division, led by Craig J. Chaya, MD, has established a glaucoma fellowship training program in Mwanza, Tanzania, and has started remote surgical mentorship training sessions.

Advancing Neuroprotective Therapies Crandall Center Associate Director David Krizaj, PhD, is preparing to file an investigational new drug application with the FDA for a therapy designed to both lower high intraocular pressure associated with glaucoma and prevent optic nerve death. This therapy is based on his impressive and growing body of work studying the calcium-permeable stretch-activated ion channel TRPV4. Dr. Krizaj has collaborated with the University of Utah Department of Chemistry and the College of Pharmacy on the new drug.

Providing Education We have trained two Crandall Center research fellows, and our current fellows are Michael Jensen, MD, and Meghan Sharma, MD. We hosted a Masterclass in the fall of 2024 that provided mentor-based didactic and hands-on training in interventional glaucoma and inperson wet labs and workshops. The goal is to improve practice patterns and clinical outcomes and significantly grow the number of patients treated in each field. Additionally, the Crandall Center has been proud to host the Interventional Glaucoma Consortium in Salt Lake City for the past two years.

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ALAN S. CRANDALL CENTER FOR GLAUCOMA INNOVATION

Improving Clinical Care Testing throughout one glaucoma patient’s lifetime generates thousands of data points.

Investigator Brian C. Stagg, MD, has developed an analytic system to help physicians sort through the data to decide on the best treatments and timing for follow-up testing. This can allow glaucoma doctors to assess the data more quickly and adapt it to their patients’ needs.

Other investigator-initiated projects are studying minimally invasive glaucoma surgery (MIGS) device outcomes and diurnal rhythms in intraocular pressure.

In closing, I deeply appreciate your interest in our mission at the Crandall Center and our collective goal to change the course of glaucoma worldwide. We can do it together.

Sincerely,

Iqbal Ike K. Ahmed, MD, FRCSC Professor of Ophthalmology and Visual Sciences Director, Alan S. Crandall Center for Glaucoma Innovation Jack R. and Hazel M. Robertson Presidential Endowed Chair John A. Moran Eye Center, University of Utah

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Crandall Center

COLLABORATION MATRIX Randall J Olson, MD CEO, John A. Moran Eye Center Distinguished Professor and Chair, Department of Ophthalmology and Visual Sciences University of Utah

Paul S. Bernstein, MD, PhD Vice Chair, Clinical and Basic Science Research

Iqbal Ike K. Ahmed, MD, FRCSC Director, Alan S. Crandall Center for Glaucoma Innovation Director, Glaucoma Therapeutics Initiative Clinician Scientist

Gregory S. Hageman, PhD Director, Sharon Eccles Steele Center for Translational Medicine Director, Translational Research Initiative Sr. Research Scientist

Amanda Peral-Orantes Administrative Manager

Deborah Harrison Associate Director, Research

Evan Conrad Lab Manager

Craig J. Chaya, MD Director, Global Outreach Division Director, Global Care Initiative Sr. Clinician Investigator

Zachary W. Davis, PhD Cortical Mechanisms of Visual Perception Research Scientist Adam M. Dubis, PhD Artificial Intelligence and Imaging Research Scientist

Bryan W. Jones, PhD Retinal Circuitry & Metabolomics Sr. Research Scientist Fiona S. McDonnell, PhD Glaucoma Physiology & Outflow Research Scientist

Brian C. Stagg, MD Glaucoma Informatics Research Scientist

David Krizaj, PhD Associate Director of Science, Crandall Center Director, Neuroprotection-Based Therapies Initiative Sr. Research Scientist

Ian F. Pitha, MD, PhD Associate Director, Crandall Center Sr. Research Scientist

Clinician Investigators Iqbal Ike K. Ahmed, MD, FRCSC Craig J. Chaya, MD Susan Chortkoff, MD Austin S. Nakatsuka, MD Ian F. Pitha, MD, PhD Rachel G. Simpson, MD Brian C. Stagg, MD Barbara M. Wirostko, MD Norm A. Zabriskie, MD

W. Daniel Stamer, PhD Chair, Scientific Advisory Board

Scientific Advisory Board Iqbal Ike K. Ahmed, MD, FRCSC Paul S. Bernstein, MD, PhD Jonathan Crowston, PhD C. Ross Ethier, PhD Sir Peng T. Khaw, MD, PhD Randall J Olson, MD Ingeborg Stalmans, MD, PhD Donald J. Zack, MD, PhD

Nick Mamalis, MD Director, Ophthalmic Pathology Laboratory Co-Director, Intermountain Ocular Research Center

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Crandall Center

SCIENTIFIC ADVISORY BOARD The Crandall Center has established a Scientific Advisory Board, comprised of Chair W. Daniel Stamer, PhD, Iqbal Ike K. Ahmed, MD, FRCSC, Paul S. Bernstein, MD, PhD, Jonathan Crowston, MD, PhD, C. Ross Ethier, PhD, Sir Peng T. Khaw, MD, PhD, Randall J Olson, MD, Ingeborg Stalmans, MD, PhD, and Donald J. Zack, MD, PhD.

W. Daniel Stamer, PhD, Scientific Advisory Board Chair Joseph A.C. Wadsworth Distinguished Professor of Ophthalmology and Professor of Biomedical Engineering at Duke University Dr. Stamer’s research focuses on understanding the molecular and cellular mechanisms that regulate conventional outflow in health, and the dysregulation that occurs in disease leading to ocular hypertension.

Notable accomplishments include the Rudin Prize for Glaucoma in 2012, the Research to Prevent Blindness Senior Scientific Investigator Award in 2013, and election as Association for Research in Vision and Ophthalmology president in 2018.

He currently holds prominent editorial positions at three premier ophthalmology journals: as editor-in-chief for the “Journal of Ocular Pharmacology and Therapeutics,” as an editorial board member for “Investigative Ophthalmology & Visual Science,” and as executive editor for “Experimental Eye Research.” In addition to 39 collaborative projects with 11 pharmaceutical companies, the National Institutes of Health has continuously funded Dr. Stamer’s research for the past 18 years.

His work is documented in 140 original articles, 27 review articles/book chapters, and 19 editorials.

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ALAN S. CRANDALL CENTER FOR GLAUCOMA INNOVATION

Jonathan Crowston, MD, PhD Professor of Ophthalmology at the University of Sydney Director of the Save Sight Institute at Camperdown Campus Glaucoma Consultant at the Royal Prince Alfred Hospital Dr. Crowston is an ophthalmologist and clinician-scientist conducting lab and clinic-based research to understand how aging increases an individual’s risk of glaucoma and related neurodegenerative diseases of the optic nerve. He has a particular interest in the role of metabolic dysfunction and aging on the optic nerve’s resilience to injury.

Dr. Crowston has been exploring mechanisms of neuro-recovery in injured neurons and how this can be modified by lifestyle interventions, including diet and exercise. He is leading a multicenter clinical trial examining the effect of nicotinamide on glaucoma progression. He cofounded Oculo, which developed a shared care platform for eye care providers that was sold to Revenio in 2021.

Dr. Crowston has received a number of awards for his research and teaching and published widely in the area of glaucoma and neuroprotection.

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ALAN S. CRANDALL CENTER FOR GLAUCOMA INNOVATION

C. Ross Ethier, PhD Lawrence L. Gellerstedt, Jr. and Mary Duckworth Gellerstedt Chair in Bioengineering and a Georgia Research Alliance Eminent Scholar at the Georgia Institute of Technology and Emory University Founding Chair of the Bioengineering Society (UK) Dr. Ethier researches the biomechanics of cells and whole organs, with specific emphasis on ocular biomechanics. His primary focus is on developing treatments for glaucoma and myopia.

His work has attracted more than 18,000 citations and has an h-index of 79, making him currently the world’s most-cited researcher in the field of ocular biomechanics. Dr. Ethier’s research has spawned three books, seven book chapters, more than 230 refereed journal articles, over 500 conference and seminar presentations, four patents, and four invention disclosures. He has received both the Steacie and Humboldt Fellowships, and the Lissner Medal from the American Society of Mechanical Engineers.

Dr. Ethier sits on the editorial boards of four journals, is the co-editor-inchief of the ASME “Journal of Biomechanical Engineering,” serves as chair of the Glaucoma Research Society’s Membership Committee, and is on the Board of Directors of the Association for Research in Vision and Ophthalmology, where he is also chair of the finance committee. He is a member of the BrightFocus Foundation’s Glaucoma Research Scientific Review Committee, and the Finance Committee of the Biomedical Engineering Society.

He chairs the external Advisory Boards for the Departments of Bioengineering at Imperial College London and University of British Columbia. Dr. Ethier is the Founding Chair of the Bioengineering Society (UK) and has also received the title of fellow from the American Society of Mechanical Engineers; American Institute for Medical and Biological Engineering; International Academy for Medical and Biological Engineering; Association for Research in Vision and Ophthalmology; The City and Guilds Institute; and the Biomedical Engineering Society.

He has acted for the Governments of Israel and Singapore, chairing external reviewer committees evaluating Biomedical Engineering programs.

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ALAN S. CRANDALL CENTER FOR GLAUCOMA INNOVATION

Sir Peng T. Khaw, MD, PhD Professor of Glaucoma and Ocular Healing, at the University College of London Institute of Ophthalmology and Consultant Ophthalmic Surgeon at Moorfields Eye Hospital Co-Director of the National Institute for Health Research (NIHR) Biomedical Research Centre in Ophthalmology at Moorfields President of the UK Paediatric Glaucoma Society NIHR Senior Investigator Dr. Khaw has a special interest in the surgical and medical treatment of refractory glaucoma, particularly pediatric glaucoma.

His group undertakes research into new surgical techniques and new treatments to prevent scarring and encourage regeneration of tissues after ocular surgery and disease. They have developed inexpensive single applications of intra-operative antimetabolites that have been tested in clinical trials across the world, and have also developed new surgical techniques, including the Moorfields Safer Surgery System, dramatically reducing bleb-related and other complications, now used worldwide. They are also developing drug delivery systems, stem cell therapies, and new single-application anti-scarring treatments.

Dr. Khaw has delivered over 35 national and international named lectures, and won over 12 prizes and awards, including the first international Association for Research in Vision and Ophthalmology Pfizer Translational Medicine Prize. He was the first UK President of ARVO (20122013). He has raised grants of over £120 million, including funding for the world’s largest Children’s Eye Hospital and translational research clinical center, and was knighted in the Queen’s Birthday Honours in 2013 for services to ophthalmology, one of two ophthalmologists in the last century to be recognized. He passionately believes that scientific research will enable us to achieve new and better treatments to change lives for the better.

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ALAN S. CRANDALL CENTER FOR GLAUCOMA INNOVATION

Ingeborg Stalmans, MD, PhD Director of the Laboratory of Ophthalmology of the Catholic University of Leuven (KUL) Director of the Glaucoma Unit at the University Hospitals Leuven (UZ Leuven) in Belgium Dr. Stalmans’ research at KUL focuses on the eye as a window to the body and the use of retinal imaging to detect and monitor not only eye diseases but also cardiovascular diseases and dementia. In this context, artificial intelligence (AI) is a powerful tool to make optimal use of the multitude of imaging and other metadata.

Dr. Stalmans is part of the Mission Lucidity consortium and the Alzheimer’s Disease Detection Using Multimodal Imaging of the Retina (ADMIRE) consortium, which is working to develop a multimodal retinal imaging tool for the early detection and clinical follow-up of patients with Alzheimer’s.

She is the co-promoter of a PhD project to use AI for the detection of glaucoma and its progression; this has resulted in a convolutional neural network-based algorithm which can reliably detect glaucoma based on photos of the optic disc. Further work is ongoing to explore the potential for the prediction of functional damage based on structural damage as well as the prediction of disease progression. The Leuven Eye Study, a prospective cohort involving about 350 glaucoma patients and healthy controls, was established to investigate the vascular aspects of glaucoma. These data also serve as a source for AI work on prediction of disease progression in glaucoma.

Dr. Stalmans is also developing retinal imaging as a biomarker for cardiovascular diseases. The ENRICH (ENdothelial Retinal Function as Indicator for Vascular Cognitive Health) consortium is a multi-disciplinary team bringing together clinicians, engineers, and basic scientists to explore the potential of retinal vascular parameters to detect and monitor microvascular dysfunction in relation to cognitive health and to explore the fundamentals of microvascular dysfunction by studying senescence, vascular permeability, and pericyte function. AI will be used to exploit the data it generates.

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ALAN S. CRANDALL CENTER FOR GLAUCOMA INNOVATION

Donald J. Zack, MD, PhD Guerrieri Professor of Genetic Engineering and Molecular Ophthalmology at Johns Hopkins University Co-director of the Center for Stem Cells and Ocular Regenerative Medicine at the Wilmer Eye Institute Dr. Zack studies the control of gene expression in retinal ganglion cells, the cells whose death in glaucoma leads to visual loss and potentially blindness. He also studies the mechanisms by which ganglion cells die in glaucoma and is developing novel methods to slow down, and hopefully prevent, ganglion cell death in glaucoma.

Dr. Zack and his colleagues are beginning studies to promote the differentiation of stem cells into retinal ganglion cells, in the hope that someday that might offer the possibility of restoring vision to glaucoma patients who have already lost significant vision due to ganglion cell death.

Dr. Zack has published over 160 peer-reviewed journal articles and has won a number of awards, including the Alcon Research Award.

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Crandall Center

CLINICAL INVESTIGATORS

Iqbal Ike K. Ahmed, MD, FRCSC

Craig J. Chaya, MD

Susan Chortkoff, MD

Austin S. Nakatsuka, MD

Ian F. Pitha, MD, PhD

Rachel G. Simpson, MD

Barbara M. Wirostko, MD

Norm A. Zabriskie, MD

Brian C. Stagg, MD

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Crandall Center

RESEARCH INVESTIGATORS Iqbal Ike K. Ahmed, MD, FRCSC Director, Crandall Center for Glaucoma Innovation Dr. Ahmed directs the center’s research and personally oversees its Glaucoma Therapeutics Initiative. A glaucoma, cataract, and anterior segment surgeon, Dr. Ahmed is recognized as one of the world’s top surgeons for complex eye conditions. He has conducted groundbreaking research in device development that has advanced the surgical treatment of diseases, including glaucoma and surgical complications.

Paul S. Bernstein, MD, PhD Vice Chair for Clinical and Basic Science Research Dr. Bernstein directs research efforts at the Moran Eye Center and studies the biophysics of nutritional interventions against inherited and acquired ocular disorders. He was among the first researchers to test the early diagnostic capabilities of fluorescence lifetime imaging ophthalmoscopy, a new non-invasive retinal imaging technique .

Zachary W. Davis, PhD Dr. Davis studies the mechanisms in the brain whereby visual information collected by the retina is processed and integrated by circuits and systems in the cortex to generate visual perception. He hopes to identify basic science principles underlying the normal healthy function of the visual system to understand how damage or disease can be mitigated or reversed.

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ALAN S. CRANDALL CENTER FOR GLAUCOMA INNOVATION

Adam M. Dubis, PhD Dr. Dubis is a leader in data driven research for health and medicine. He has commercialized several analytical tools while focusing on developing safer, more robust artificial intelligence models to support improved ophthalmic care and to better understand disease progression. His lab applies deep learning techniques to retinal image and data analysis and Dr. Dubis consults worldwide.

Gregory S. Hageman, PhD Director, Sharon Eccles Steele Center for Translational Medicine Director, Translational Research Initiative Dr. Hageman has used a repository of patient and tissue resources to foster a robust understanding of AMD biology and to discover pathways, identify and validate therapeutic targets, and develop therapies for AMD. He is now using these resources to study glaucoma.

Bryan W. Jones, PhD Dr. Jones studies retinal circuitry/connectomics and metabolomics in neural plasticity in retinal disease. His research provided the first understanding of retinal plasticity in diseases like retinitis pigmentosa and AMD. This work is responsible for discovering the substantial clinical significance of negative neuronal remodeling in retinal degenerative disease.

David Krizaj, PhD Associate Director of Science, Alan S. Crandall Center for Glaucoma Innovation Director, Neuroprotection-Based Therapies Initiative Dr. Krizaj studies the relationship between intracellular signaling pathways and neurotransmission in the retina. He has developed a potential neuroprotective therapy from researching how non-conventional signaling pathways, such as intracellular calcium stores, calcium transporters, and store-operated calcium channels, collaborate with voltage-operated signals to modulate graded exocytosis.

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ALAN S. CRANDALL CENTER FOR GLAUCOMA INNOVATION

Nick Mamalis, MD Director, Ophthalmic Pathology Laboratory Co-Director, Intermountain Ocular Research Center Dr. Mamalis evaluates all specimens submitted to the laboratory and performs research in the area of intra-ocular lenses and postoperative inflammation.

Fiona S. McDonnell, PhD Dr. McDonnell studies the physiology and anatomy of the conventional outflow pathway. Her projects include studying nanoparticles called extracellular vesicles and how they contribute to glaucoma, as well as examining the physiology of small vessels in the eye and their role in intraocular pressure regulation. She is an expert in perfusion of eyes to study outflow facility using iPerfusion technology."

Ian F. Pitha, MD, PhD Associate Director, Alan S. Crandall Center for Glaucoma Innovation Dr. Pitha combines his training in pharmacology, models of glaucoma, and biomaterials to develop sustained drug delivery methods with the goal of improving glaucoma treatment. He studies the role of scleral cells in affecting scleral remodeling, with the goal of discovering approaches to alter scleral biomechanics to prevent glaucomatous vision loss.

Brian C. Stagg, MD A glaucoma specialist and public health researcher, Dr. Stagg is a former National Clinician Scholar research fellow. His research focuses on using informatics to personalize glaucoma care and ensure that each patient gets appropriate treatment. Recent projects have included a clinical decision support system to streamline decision-making for clinicians.

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Crandall Center

INDUSTRY COLLABORATORS Aequus Pharmaceuticals Aerie Pharmaceuticals Akorn Alcon Vision, LLC Allergan: AbbVie Apellis Aquea Health, Inc ArcScan Avisi Bausch & Lomb Bausch Health Beaver Visitec Beyeonics Bionode Carl Zeiss Meditec Centricity Vision Ciliatech CorNeat Vision Custom Surgical Elcon Medical Elios Vision ElutiMed Equinox Exhaura eyeFlow Eyelight Innovations

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EyeQ Genentech Glaukos Heidelberg Engineering Heine Heru Hexiris Pharma Iantrek iCare InjectSense Iridex iStar Ivantis Johnson & Johnson Vision Katalyst Surgical Labtician Thea LayerBio Leica Microsystems Liberty Vision LifeLong Vision Long Bridge Medical, Inc. MicroOptx MST Surgical Myra Vision New World Medical

Ocular Instruments Ocular Therapeutix Oculo Oculus Omega Ophthalmics Omni Surgical System Omega Ophthalmics PolyActiva Ripple Therapeutics Sanoculis Santen Science Based Health Sight Sciences Smartlens, Inc. Stroma Thea Pharma ViaLase Vizzario W.L. Gore & Associates

Crandall Center

INDUSTRY-SPONSORED RESEARCH PRECLINICAL

Principal Investigator Iqbal Ike K. Ahmed, MD, FRCSC: Sponsor: Myra Vision Evaluation of the biocompatibility and surgical operability of a new glaucoma drainage device in the rabbit model. (Completed) Sponsor: Elios Vision Morphological changes of the trabecular meshwork and Schlemm’s canal after excimer laser trabeculostomy, goniotomy, and trabeculotomy in human cadaveric eyes.

(Completed) Evaluation of the biocomparibility of glaucoma excimer laser treatment in a rabbit model.

(Completed) Sponsor: EyeQ Side-by-side comparison of EyeQ nano ECP vs Endo Optiks E2 system in a cadaveric model.

(Completed) Sponsor: W.L. Gore & Associates Impact of ePTFE morphology and structure on subconjunctival tissue response in a rabbit model. (Ongoing) Sponsor: ViaLase Optimizing outflow facility with ViaLase femtosecond laser trabeculotomy. (Ongoing)

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ALAN S. CRANDALL CENTER FOR GLAUCOMA INNOVATION

CLINICAL TRIALS

Principal Investigator Iqbal Ike K. Ahmed, MD, FRCSC: Sponsor: Allergan Xen 63 Prospective Study (Ongoing) Sponsor: Alcon Vision, LLC Vivity for Patients Post Refractive Surgery (Ongoing) Sponsor: Glaukos iStent INFINITE in Adults with Primary Open Angle Glaucoma (Ongoing) Sponsor: iStar Miniject in Subjects with Open Angle Glaucoma (Ongoing) Principal Investigator Craig J. Chaya, MD: Sponsor: Iantrek An observational registry study of safety and effectiveness outcomes through 24 months postoperatively following Cyclopen Micro-interventional Cyclodialysis System procedures in patients with POAG: the CREST Registry. (Ongoing) Sponsor: AbbVie AbbVie XEN Ab Ex - A prospective, multicenter clinical study to evaluate the safety and effectiveness of ab externo implantation of Glaucoma Gel Stent. (Ongoing) Principal Investigator Austin S. Nakatsuka, MD: Sponsor: Elios Vision A prospective, multicenter, non-randomized clinical trial designed to evaluate the safety and feasibility of the ELIOS System to reduce IOP in patients with primary open-angle glaucoma as a standalone procedure. (Ongoing)

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Crandall Center

RESEARCH GRANTS INVESTIGATOR-INITIATED CLINICAL RESEARCH GRANTS

Principal Investigator Craig J. Chaya, MD: Funding Sponsor: Iantrek Diurnal Evaluation of Intraocular Pressure in Patients Receiving Rndoscleral Supraciliary Biostent (Ongoing) Funding Sponsor: Alcon Vision, LLC Learning Curve Associated with Hydrus Microstent Implantation (Ongoing) Principal Investigator Rachel G. Simpson, MD: Funding Sponsor: Alcon Vision, LLC Post-Operative Anterior Segment OCT Evaluation of Trabecular Microstent Positioning and the Impact on IOP (Ongoing) Principal Investigator Brian C. Stagg, MD: Funding Sponsor: PeriVision, Inc. VR Visual Field Usability Testing (Completed) Funding Sponsor: University of Michigan Sight Outcomes Research (SOURCE) Multicenter Ophthalmology EHR Repository (Completed) Funding Sponsor: Carl Zeiss Meditec Comparing OCT Acquisition Efficiency (Ongoing)

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ALAN S. CRANDALL CENTER FOR GLAUCOMA INNOVATION

INVESTIGATOR-INITIATED NON-CLINICAL GRANTS

Principal Investigator Zachary W. Davis, PhD: Funding Sponsor: Whitehall Foundation The Role of Spatiotemporal Cortical Interactions in Visual Perception Principal Investigator Bryan W. Jones, PhD: Funding Sponsor: University of Texas at Austin NEURONEX2 Funding Sponsor: NIH National Eye Institute Core Imaging Funding Sponsor: University of Colorado Cell-Based Therapies Funding Sponsor: Research to Prevent Blindness Retinal Plasticity and Neurodegenerative Disease Funding Sponsor: Research to Prevent Blindness Connectome Evaluation of Muller Cell Connectivity in the Inner Retina (Rebecca Pfeiffer, PhD) Funding Sponsor: University of Southern California Mesoscale Correlative Light-Electron Microscopy (Clem) Computational Pathoconnectomes of Degenerated Retinas Funding Sponsor: NIH National Eye Institute Retinal Circuitry

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ALAN S. CRANDALL CENTER FOR GLAUCOMA INNOVATION

Principal Investigator David Krizaj, PhD: Funding Sponsor: NIH National Eye Institute Core Physiology Funding Sponsor: NIH National Eye Institute T32 Vision Training Grant Funding Sponsor: NIH National Eye Institute Mechanobiology of Glauxoma-2 Funding Sponsor: NIH National Eye Institute Molecular/Cellular Mechanisms Principal Investigator Fiona S. McDonnell, PhD: Funding Sponsor: NIH National Eye Institute Exosomes and Conv Outflow Principal Investigator Brian C. Stagg, MD: Funding Sponsor: NIH National Eye Institute Improving Glaucoma Care Using a Scalable Decision Support System

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Crandall Center

CLINICAL RESEARCH & TRIALS INVESTIGATOR-INITIATED RESEARCH

Principal Investigator Iqbal Ike K. Ahmed, MD, FRCSC: Glaucoma Drainage Device and Endothelial Cell Loss Compare Trial (DECLARE) Early Surgeon Experiences of the 63-μm Gelatin Microstent versus the 45-μm Gelatin Microstent: An International Multicenter Study Principal Investigator Craig J. Chaya, MD: The Effectiveness of Various MIGS at the University of Utah: A Retrospective Review Retrospective Review of Cataract Surgery Outcomes Multi-Center GATT Retrospective Review Patterns of Blindness in the Navajo Nation Glaucoma Surgery in Patients with Uveitis Principal Investigator Fiona McDonnell, PhD: Collecting Trabecular Meshwork Tissue Discarded from Trabeculectomy to Study Open-Angle Glaucoma Principal Investigator Austin S. Nakatsuka, MD: Anterior Capsule Polishing and Negative Dysphotopsia

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ALAN S. CRANDALL CENTER FOR GLAUCOMA INNOVATION

Principal Investigator Rachel G. Simpson, MD: The Inequitable Burden of Presentation Topics on Female Conference Speakers Statistical Analysis of Applicant Demographics and Performance on the Altus Situational Judgment Test Principal Investigator Brian C. Stagg, MD: Secondary Analysis of Electronic Medical Record Data to Improve Eyecare Improving Glaucoma Care Using a Scalable Decision Support System Preliminary Design & Evaluation of Glaucoma Disease Manager Evaluation of the Moran Eye Center Tele-Retinal Diabetic Retinopathy Screening Program at Community Health Centers, Inc. Clinics Surveying User Experience with a Novel Head-Mounted Visual Field Perimeter Principal Investigator Barbara M. Wirostko, MD: Diurnal Evaluation of IOP in Patients Receiving Selective Laser Trabeculoplasty Pseudoexfoliation and Co-Morbidities Diurnal Evaluation of Intraocular Pressure in Patients Receiving Selective Laser Trabeculoplasty iCARE Home: Diurnal Rhythms in Intraocular Pressure Collecting Surgical Waste from Cataract Surgeries to Study Pseudoexfoliation (XFS) Altered Proteins in the Eye

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Crandall Center

PUBLICATION HIGHLIGHTS Below is a list of select collaborator publications between July 1, 2023, and June 30, 2024.

Iqbal Ike K. Ahmed, MD, FRCSC The Evolving Surgical Paradigm of Scleral Allograft Bio-Tissue Use in Ophthalmic Surgery: Techniques and Clinical Indications for Ab-Externo and Ab-Interno Scleral Reinforcement Mitomycin C 0.2 mg/ml vs. Mitomycin C 0.4mg/ml during the implantation of an ab externo SIBS microshunt: A mega-analysis Risk communication in cataract surgery Intraocular Pressure While Using Gonioscopy, SLT, and Laser Iridotomy Lenses: An Ex Vivo Study Minimally invasive micro sclerostomy (MIMS) procedure in the treatment of open-angle glaucoma Validation of a Wearable Virtual Reality Perimeter for Glaucoma Staging, The NOVA Trial: Novel Virtual Reality Field Assessment Association Between Sociodemographic Factors and Self-reported Glaucoma in the National Health Interview Survey: A Population-Based Analysis Bilaterally subluxed diffractive intraocular lenses: big expectations and even bigger comorbidities Prophylaxis against intraocular pressure spikes following uncomplicated phacoemulsification: a systematic-review and meta-analysis

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ALAN S. CRANDALL CENTER FOR GLAUCOMA INNOVATION

Difficult decisions, filtration surgery, and the heartbreak of the numerator Two-Year Performance and Safety Results of the MINIject Supraciliary Implant in Patients With Primary Open-Angle Glaucoma: Meta-Analysis of the STAR-I, II, III Trials Corneal endothelial safety profile in minimally invasive glaucoma surgery Preservative-Free versus Benzalkonium Chloride-Preserved Latanoprost Ophthalmic Solution in Patients with Primary Open-Angle Glaucoma or Ocular Hypertension: A Phase 3 US Clinical Trial Surgical Augmentation of the Suprachoroidal Space: A Novel Material and Implant New Devices in Glaucoma Multi-center validation of Catquest-9SF visual function questionnaire in Ontario, Canada Craig J. Chaya, MD A Health-Related Quality of Life Measure for Patients Who Undergo Minimally Invasive Glaucoma Surgery Managing primary open-angle glaucoma in the setting of suboptimal surgical outcomes in the fellow eye Micropulse cyclophotocoagulation compared to continuous wave cyclophotocoagulation for the management of refractory pediatric glaucoma The usage of CustomFlex iris prosthesis for uveitis-induced iris defects Managing primary open-angle glaucoma in the setting of suboptimal surgical outcomes in the fellow eye

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ALAN S. CRANDALL CENTER FOR GLAUCOMA INNOVATION

Zachary W. Davis, PhD Acute Neuropixels Recordings in the Marmoset Monkey Horizontal cortical connections shape intrinsic traveling waves into feature-selective motifs that regulate perceptual sensitivity The double-drift illusion biases the marmoset oculomotor system Adam M. Dubis, PhD Deep Density Estimation for Cone Counting and Diagnosis of Genetic Eye Diseases from Adaptive Optics Scanning Light Ophthalmoscope Images Reduced Cone Density Is Associated with Multiple Sclerosis Gregory S. Hageman, PhD Replenishing IRAK-M expression in retinal pigment epithelium attenuates outer retinal degeneration Levels of the HtrA1 Protein in Serum and Vitreous Humor Are Independent of Genetic Risk for Age-Related Macular Degeneration at the 10q26 Locus The vascular geometry of the choriocapillaris is associated with spatially heterogeneous molecular exchange with the outer retina Vitreomacular interface abnormalities in the Ghanaian African Levels of complement factor H-related 4 protein do not influence susceptibility to age-related macular degeneration or its course of progression Retinal and Choroidal Thickness in an Indigenous Population from Ghana: Comparison with Individuals with European or African Ancestry

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ALAN S. CRANDALL CENTER FOR GLAUCOMA INNOVATION

Replenishing Age-Related Decline of IRAK-M Expression in Retinal Pigment Epithelium Attenuates Outer Retinal Degeneration Transcriptomic analysis of the ocular posterior segment completes a cell atlas of the human eye Bryan W. Jones, PhD Distinctive synaptic structural motifs link excitatory retinal interneurons to diverse postsynaptic partner types Impact of Retinal Degeneration on Response of ON and OFF Cone Bipolar Cells to Electrical Stimulation Metabolic changes and retinal remodeling in Heterozygous CRX mutant cats (CRXRDY/+) Unbalanced redox status network as an early pathological event in congenital cataracts NUDC is critical for rod photoreceptor function, maintenance, and survival Modeling complex age-related eye disease Retinal connectomics: towards complete, accurate networks Retinal Pathoconnectomics: A Window into Neurodegeneration Elastin Layer in Bruch’s Membrane as a Target for Immunization or Tolerization to Modulate Pathology in the Mouse Model of Smoke-Induced Ocular Injury David Krizaj, PhD TRPV4 and chloride channels mediate volume sensing in trabecular meshwork cells Regulation of Corneal Stromal Cell Behavior by Modulating Curvature Using a Hydraulically Controlled Organ Chip Array Retinal ganglion cell repopulation for vision restoration in optic neuropathy: a roadmap from the RReSTORe Consortium PAGE | 28

ALAN S. CRANDALL CENTER FOR GLAUCOMA INNOVATION

Nick Mamalis, MD ASCRS clinical advisory on intracameral moxifloxacin injection for injection prophylaxis Explantation of a light-adjustable intraocular lens: case report with laboratorial analyses Rotational stability of a new hydrophobic acrylic intraocular lens platform - Journal of Cataract and Refractive Surgery Complications of foldable intraocular lenses requiring explantation or secondary intervention: 2022 survey with update of long-term trends Fiona S. McDonnell, PhD Modeling complex age-related eye disease Greater Outflow Facility Increase After Targeted Trabecular Bypass in Angiographically Determined Low-low Regions Comparison of the extracellular vesicle proteome between glaucoma and non-glaucoma trabecular meshwork cells Austin S. Nakatsuka, MD The lens that would not stay put Randall J Olson, MD Efficiency of a polymer-coated phacoemulsification tip in cataract surgery Effect of Modified Peristaltic Phacoemulsification Device on Efficiency and Post-Occlusion Pressure Surge Temperature Change of Ophthalmic Viscosurgical Devices in a Bi-Chamber Set-Up at a Flow of 0 and 20mL/min Effect of low and passive flow on OVD thermal properties during phacoemulsification PAGE | 29

ALAN S. CRANDALL CENTER FOR GLAUCOMA INNOVATION

The effect of increasing power when grooving using phacoemulsification A comparison of venturi and peristaltic based phacoemulsification efficiency in routine femtosecond laser cataract surgery Subgroup Analysis from a Phase 1/2 Randomized Clinical Trial of 2.6% EDTA Ophthalmic Solution in Patients with Age-Related Cataract The effect of patient age on some new and older IOL power calculation formulas Mortality and Causes of Death Among Individuals with Keratoconus Ian F. Pitha, MD, PhD IOP and glaucoma damage: The essential role of optic nerve head and retinal mechanosensors Cyclic strain alters the transcriptional and migratory response of scleral fibroblasts to TGFbeta A new era in posterior segment ocular drug delivery: translation of systemic, cell-targeted, dendrimer-based therapies Nanofiber-based glaucoma drainage implant improves surgical outcomes by modulating fibroblast behavior Brian C. Stagg, MD Uveitis-Glaucoma-Hyphema Syndrome from Subtle Malposition of a Hydrus Microstent Vision Loss in Children from Immigrant and Nonimmigrant Households: Evidence from the National Survey of Children's Health 2018-2020 The Digital Divide in Eye Health Care Delivery Association between vision impairment and increased prevalence of falls in older US adults

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ALAN S. CRANDALL CENTER FOR GLAUCOMA INNOVATION

Using Natural Language Processing to Identify Different Lens Pathology in Electronic Health Records Incident glaucoma and ocular hypertension after periocular and intravitreal steroid injections: a claims-based analysis Association Between Health Insurance and Primary Care Vision Testing Among Children and Adolescents Using Technology to Address Ophthalmic Technician Shortages in Glaucoma Clinics A scoping review of patients' barriers to eye care for glaucoma and keratitis Systematic User-centered Design of a Prototype Clinical Decision Support System for Glaucoma Barbara M. Wirostko, MD Glucagon-Like Peptide 1 Receptor Agonists: A Role in Glaucoma?

Incident glaucoma and ocular hypertension after periocular and intravitreal steroid injections: a claims-based analysis The Use of ChatGPT to Assist in Diagnosing Glaucoma Based on Clinical Case Reports Preclinical Pharmacokinetic Profile of Topical Ophthalmic and Intravenous Delivery of QLS-101, a Novel ATP-Sensitive Potassium Channel Opening Ocular Hypotensive Agent Abdominal aortic aneurysm and exfoliation syndrome in Utah Use of Home Tonometry for Clinical Management of Unilateral Glaucoma Secondary to ICE Syndrome Lifting the Patient's Voice in Ophthalmology

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