Ophthalmology Commons^™

Ophthoevidence Report: Comparative Effects Of Prophylactic Strategies For Post-Intravitreal Injection Endophthalmitis: Protocol For A Systematic Review And Network Meta-Analysis, Maryam Ghadimi, Dena Zeraatkar, João Pedro Lima, Jinhui Ma, Sunir J. Garg, Peter Kaiser, David Steel, Tien Yin Wong, Sobha Sivaprasad, Charles Wykoff, Varun Chaudhary

Wills Eye Hospital Papers

BACKGROUND: Endophthalmitis is a rare but serious complication of intravitreal injections (IVI). To mitigate the risk of post-injection endophthalmitis (PIE), retinal specialists use different strategies, combining various prophylactic measures. However, existing systematic reviews have evaluated the effects of these measures in isolation, which does not consider their concurrent use in practice. A trustworthy systematic review with network meta-analysis (NMA) by providing a framework for simultaneous comparisons of different prophylactic combinations is essential to guide decision-making.

OBJECTIVES: To present a protocol for addressing the comparative effects of different strategies for the prevention of PIE.

METHODS: We will search Medline, EMBASE, Cochrane …

Expert Opinion: Management Of Intraocular Inflammation And Vasculitis After Intravitreal Pegcetacoplan For Geographic Atrophy, Thomas Albini, Steven Yeh, Carl Regillo, Roy Schwartz, Philip Ferrone, Caroline Baumal, Charles Wykoff

Wills Eye Hospital Papers

BACKGROUND AND OBJECTIVE: This expert opinion review is intended to provide guidelines for diagnosis and management of intraocular inflammation (IOI) and vasculitis following pegcetacoplan.

PATIENTS AND METHODS: A case series of all post-marketing reports classified by experts as definite or suspected vasculitis over an 18-month period was assessed.

RESULTS: A total of 306,000 pegcetacoplan intravit real injections were given in the real world between March 1, 2023, and August 31, 2024. Twenty-four eyes from 22 patients (mean age 76 years, 59% female) with definite or suspected vasculitis were evaluated. Comorbidities included hypertension (55%), hypo thyroidism (27%), and recent COVID-19 infection …

Fluocinolone Acetonide Implant As A Baseline Therapy For Diabetic Macular Edema: Results From The Randomized Phase 4 New Day Study, Michael A Singer, Charles C Wykoff, Christopher D Riemann, Victor H Gonzalez, Christina Y Weng, Kamel Alkhatib, Rohit A Amarshi, Scott Moody, Mary Pao

Faculty, Staff and Students Publications

Purpose: The NEW DAY (ClinicalTrials.gov identifier, NCT04469595) study assessed the efficacy and safety of the fluocinolone acetonide (FAc; 0.19 mg) intravitreal implant as baseline therapy in diabetic macular edema (DME).

Design: Prospective, randomized, single-masked, active-controlled, multicenter, 18-month, phase 4 study.

Participants: Adults with type 1 or 2 diabetes and center-involving DME confirmed by central subfield thickness (CST).

Methods: Treatment regimens were FAc implant followed by rescue supplemental injections of aflibercept if needed (2 mg/0.05 ml) for 17 months versus aflibercept loading dose (2 mg every 4 weeks for 5 consecutive doses) followed by rescue supplemental injections of aflibercept if …

Meeting Report From The 2025 Cure Ocular Melanoma (Cure Om) Global Science Meeting, Amsterdam, The Netherlands, October 2025, Andrew E. Aplin, Katherina Alsina, Allison S. Betof, Joseph Birkett, Marcus O. Butler, George Cole, Rizwan Haq, Florian A. Karreth, Vinit B. Mahajan, Rahul Marpadga, Prithvi Mruthyunjaya, Paul Nathan, Jonas A. Nilsson, Gary Palmer, Joseph J. Sacco, Takami Sato, Sarah Stanhope, Pang-Ning Teng, Kyleigh Lipira

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

The 2025 Cure Ocular Melanoma (CURE OM) Global Science Meeting took place in Amsterdam, The Netherlands on October 25th, 2025. Several promising drug candidates are in development; however, there is still an urgent need for better prevention, detection, and treatment of uveal melanoma. The purpose of this meeting was to promote international collaboration and idea exchange between scientists, industry, and patient advocates.

Long Term Evaluation Of The Safety And Efficacy Of Local Cooling Anesthesia During Intravitreal Injections: The Cool-2 Trial, Arshad M. Khanani, Samir N. Patel, Charles C. Wykoff, Gun-Ho Kim, Ajay E. Kuriyan

Wills Eye Hospital Papers

BACKGROUND/OBJECTIVE: To evaluate the safety and effectiveness of a medical device providing cooling anesthesia to the eye as local anesthesia for intravitreal (IVT) injections.

SUBJECTS/METHODS: As a multicenter, open label, dose escalation clinical trial, subjects receiving at least 3 IVT injections in the study eye were recruited to participate. All patients received subconjunctival lidocaine as their anesthesia for previous IVT injections. Subjects receiving IVT injections were assigned (non-randomized) to four groups in which the cooling device was applied to the conjunctiva at the location of the intravitreal injection: Group 1: -10˚C for 20 seconds; Group 2: -15˚C for 10 seconds; …

Investigating The Correlation Between Scleral Spur Angle And Intraocular Lens Tilt, Dylan Mcbee, Karim Kozhaya, Li Wang, Douglas D Koch, Allison J Chen, Mitchell P Weikert

Faculty, Staff and Students Publications

Purpose: To evaluate the correlation between the preoperative vertex-scleral spur angle (Vtx-SSA) and postoperative horizontal intraocular lens (IOL) tilt after routine cataract surgery.

Setting: Cullen Eye Institute, Baylor College of Medicine, Houston, Texas.

Design: Prospective case series.

Methods: This study enrolled patients who underwent uneventful phacoemulsification cataract extraction with IOL implantation. The Anterion and Eyestar 900 swept-source optical coherence tomographers (SS-OCTs) were used to determine Vtx-SSA and lens tilt (crystalline and IOL) measurements, respectively. Tilt vectors were decomposed into orthogonal, vertical, and horizontal components to explore preoperative correlations independently. The Pearson correlation coefficient and linear regression analysis were used to …

Matching-Adjusted Indirect Comparison Of Acoltremon Ophthalmic Solution 0.003% And Cyclosporine 0.05% Ophthalmic Emulsion For Increased Tear Production In Patients With Dry Eye Disease, Stephen Pflugfelder, Tony Okoro, Margaret Ainslie-Garcia, Anja Haltner, Emily K Prentiss, Elizabeth M Salvo-Halloran, Nikethana Srikanth, Michelle Senchyna, Esen K Akpek

Faculty, Staff and Students Publications

No abstract provided.

Multi-Grader Validation Of The Telemedicine Retinopathy Of Prematurity Severity Score, Harrison W. Pratt, Sarthak V. Shah, Cindy S. Zhao, Arthur R. Brant, Caroline R. Baumal, Cagri G. Besirli, Audina M. Berrocal, Kimberley A. Drenser, Anna L. Ells, Clio Armitage Harper, G. Baker Hubbard, Eric D. Nudleman, Polly Quiram, Irena Tsui, Edward Wood, Yoshihiro Yonekawa, Tatiana Rosenblatt, Jochen Kumm, Darius M. Moshfeghi

Wills Eye Hospital Papers

We aimed to statefully validate Retinopathy of Prematurity (ROP) grading by evaluating intergrader variability over age-matched simulated exams. In a prospective retinal photographic grading cohort study, both eyes of twenty patients with five images per eye per visit were graded by twelve expert graders across six weekly visits. For each eye visit, ROP experts graded the Zone, Stage, and Plus, from which the Telemedicine ROP Severity Score (tROP-SS) was calculated. Graders retained knowledge of prior assessments for a given eye and followed International Classification of ROP rules. Intergrader coefficient of variation (CoV) for Zone, Stage, Plus, and tROP-SS remained below …

Systemic Α₂-Agonist Use And Lower Hazard Of Glaucoma Compared With Β-Blockers: A Cohort Study, Ibrahim Abboud, Amin Z. Khudari, Abdelaziz Abdelaal, Amr Almobayed, Subhi J. Al'aref, Jonathan S. Myers, Richard K. Lee, Abdelrahman M. Elhusseiny

Wills Eye Hospital Papers

OBJECTIVE: Systemic antihypertensive medications may influence glaucoma-related outcomes through intraocular pressure-dependent and vascular mechanisms. While topical α₂-agonists are established glaucoma therapies, the association between systemic α₂-agonists and glaucoma hazard remains unexamined; we compared their hazard with systemic β-blockers in adults with hypertension.

METHODS AND ANALYSIS: We conducted a multicentre retrospective cohort study using deidentified electronic health records. Adults aged ≥40 years with hypertension and chronic exposure to systemic α₂-agonists or β-blockers were included. Patients with pre-existing ocular hypertension (OHT), primary open-angle glaucoma (POAG), concomitant comparator use, or inadequate ophthalmic follow-up were excluded. We balanced cohorts using propensity score matching (PSM) …

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 …

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 …

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. …

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 …

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 …

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 …

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 …

Gene-Agnostic Therapeutic Strategies For Inherited Retinal Diseases: Neuroprotection And Immunomodulation, Lucas W. Rowe, S. Patricia Becerra, Robert E. Maclaren, Robert L. Avery, Charles C. Wykoff, Allen C. Ho, Carl D. Regillo, Dean Eliott, Andrew Osborne, Katie M. Binley, Thomas A. Ciulla

Wills Eye Hospital Papers

Background/Objectives: Inherited retinal diseases (IRDs) represent a genetically heterogeneous group of disorders caused by mutations in over 280 genes with more than 3100 identified variants. While gene-specific replacement therapies have achieved landmark success with voretigene neparvovec (Luxturna) for biallelic RPE65-associated retinal dystrophy, developing individual therapies for each genetic subtype remains impractical. This review examines gene-agnostic therapeutic approaches utilizing neuroprotection and immunomodulation that target common pathophysiological mechanisms shared across multiple IRD genotypes. Methods: We reviewed the literature on neuroprotective and immunomodulatory gene therapy strategies for IRDs, focusing on neurotrophic factors and complement system modulation. Results: Neuroprotective approaches delivering neurotrophic factors—including pigment …

Improving Prediction Accuracy Of Radiation-Induced Temporal Lobe Injury In Nasopharyngeal Carcinoma Using Adc-Based Deep Learning And Dosiomics, Li Wang, Yang Li, Ting Qiu, Junyi Liu, Jiawei Zhou, Han Gao, Hongliang Yu, Yinsu Zhu, Baozhou Sun, Guanyu Yang, Shengfu Huang, Lirong Wu, Li Sun, Xia He

Faculty, Staff and Students Publications

Background: To investigate the potential of apparent diffusion coefficient (ADC) map-based deep learning and dose distribution-based dosiomics in predicting radiation-induced temporal lobe injury (RTLI) in nasopharyngeal carcinoma (NPC).

Methods: This retrospective study included 3578 NPC patients from Jiangsu Cancer Hospital receiving intensity-modulated radiation therapy (IMRT). Ninety-four RTLI patients were recruited based on inclusion criteria and matched 1:1 with 97 control subjects using propensity scores. Patients were randomly assigned to the training cohort (n = 135) and the validation cohort (n = 59). Deep transfer learning (DTL) features and dosiomics features were extracted from ADC map and three-dimensional dose distribution, respectively. …

Common And Recurrent Dysregulated Molecular Network Of Placental Hypoxia And Associated Vasculogenesis And Angiogenesis In Fetal Growth Restriction, Wei Li, Xiaoyi Bai, Oi Ka Chan, Maran Bo Wah Leung, So Ling Lau, Chi Chiu Wang, Tak Yeung Leung

Faculty, Staff and Students Publications

Fetuses with fetal growth restriction (FGR) and selective FGR (sFGR) face elevated health risks both before and after birth. Although the underlying pathomechanisms remain unclear, placental dysfunction is recognized as a major contributing factor. By integrating untargeted transcriptomic data from FGR/sFGR placentae, this study identified 69 differentially expressed mRNAs (DEmRs) and eight differentially expressed miRNAs (DEmiRs). Functional enrichment analysis demonstrated significant enrichment in the angiogenesis and vasculogenesis pathways, with the hypoxia-related genes

Non-Congenital Hsv-1 Keratitis In An Immunocompetent 9-Month-Old Infant, Caleb A Casanova, Stephanie Trejo Corona, Stephen F Pflugfelder

Faculty, Staff and Students Publications

Isolated, non-congenital herpes simplex virus type 1 (HSV-1) keratitis in immunocompetent infants is exceedingly rare and may be easily misdiagnosed, leading to delays in appropriate antiviral therapy. This case is unique in that it describes HSV-1 keratitis in a healthy 9-month-old infant presenting without systemic illness, initially treated as bacterial conjunctivitis. The patient presented with unilateral eye pain, redness, and corneal opacification. Subsequent evaluation revealed HSV-1 keratitis, and the patient was treated with intravenous acyclovir in combination with topical moxifloxacin and topical ganciclovir, resulting in complete resolution of symptoms within one week. This case adds to the limited literature on …

Dual-Level Pattern Tree For Visual Field Improves Glaucoma Progression And Polygenic Risk Prediction, Luo Song, Lucy Q. Shen, Louis R. Pasquale, Michael V. Boland, Sarah R. Wellik, Carlos Gustavo De Moraes, Ayellet Segre, Janey L. Wiggs, Constance Turman, Jonathan S. Myers, Tobias Elze, Nazlee Zebardast, David S. Friedman, Jae H. Kang, Mengyu Wang

Wills Eye Hospital Papers

PURPOSE: To develop a dual-level pattern tree to characterize visual field (VF) loss subtypes that can be used to better predict glaucoma progression and glaucoma polygenic risk scores (PRSs).

METHODS: This study included 113,030 patients from three datasets, each used for a specific purpose: (1) model training, (2) progression forecasting, and (3) PRS correlations. We applied archetypal analysis to cluster 24-2 VFs into trunk patterns and their branch patterns. The Cox regression model was used to forecast VF progression using mean deviation (MD) slope, MD-fast slope, total deviation (TD) pointwise slope, and visual field index (VFI) slope. Multivariable regression analyses …

Derivation Of Pluripotent Stem Cell Lines (Rfsci005-A, Rfsci006-A) From Siblings Harboring Identical High-Risk Complement Variants With Discordant Age-Related Macular Degeneration, Naresh Rajendran, Ajeet Singh, Wendy Runyon, Sam Hu, Ritu Kumar, Rinki Ratnapriya, Karl Csaky, Srinivasa R Sripathi

Faculty, Staff and Students Publications

Age-related macular degeneration (AMD) is a complex disease influenced by genetic and environmental factors. Variants in the complement pathway, especially in the CFH gene, increase AMD risk, yet disease severity can differ among individuals with identical high-risk genotypes. We generated induced pluripotent stem cell (iPSC) lines from siblings carrying identical high-risk complement variants but displaying discordant AMD phenotypes. These lines provide a unique platform to study epigenetic, transcriptomic, and environmental factors driving AMD heterogeneity. By comparing differentiated retinal cells, we aim to reveal mechanisms behind variable disease susceptibility and inform personalized therapies for AMD.

Generation Of Ipscs (Rfsci007-A, Rfsci008-A) From A Patient With Early-Onset Bilateral Drusen And A Healthy Sibling For Retinal Disease Modeling, Sonali Singh, Wendy Runyon, Sam Hu, Paige Grona Kennedy, Ajeet Singh, Rinki Ratnapriya, Ritu Kumar, Karl Csaky, Srinivasa R Sripathi

Faculty, Staff and Students Publications

Drusen are extracellular deposits between the retinal pigment epithelium and Bruch's membrane, commonly linked to age-related macular degeneration (AMD). However, their presence in younger individuals offers a unique opportunity to study early disease mechanisms before extensive degeneration. We generated two human induced pluripotent stem cell (hiPSC) lines from siblings' peripheral blood mononuclear cells-one with early-onset bilateral drusen and the other unaffected. This genetically matched iPSC pair enables investigation of early drusen associated pathological changes driving retinal disease development.

Image-Based Meta- And Mega-Analysis (Ibmma): A Unified Framework For Large-Scale, Multi-Site, Neuroimaging Data Analysis, Nick Steele, Ashley A Huggins, Rajendra A Morey, Ahmed Hussain, Courtney Russell, Benjamin Suarez-Jimenez, Elena Pozzi, Hadis Jameei, Lianne Schmaal, Ilya M Veer, Lea Waller, Neda Jahanshad, Sophia I Thomopoulos, Lauren E Salminen, Miranda Olff, Jessie L Frijling, Dick J Veltman, Saskia B J Koch, Laura Nawijn, Mirjam Van Zuiden, Li Wang, Ye Zhu, Gen Li, Dan J Stein, Jonathan Ipser, Yuval Neria, Xi Zhu, Orren Ravid, Sigal Zilcha-Mano, Amit Lazarov, Jennifer S Stevens, Kerry Ressler, Tanja Jovanovic, Sanne J H Van Rooij, Negar Fani, Sven C Mueller, Anna R Hudson, Judith K Daniels, Anika Sierk, Antje Manthey, Henrik Walter, Nic J A Van Der Wee, Steven J A Van Der Werff, Robert R J M Vermeiren, Christian Schmahl, Julia I Herzog, Ivan Rektor, Pavel Říha, Milissa L Kaufman, Lauren A M Lebois, Justin T Baker, Isabelle M Rosso, Elizabeth A Olson, Anthony King, Israel Liberzon, Michael Angstadt, Nicholas D Davenport, Seth G Disner, Scott R Sponheim, Thomas Straube, David Hofmann, Guangming Lu, Rongfeng Qi, Xin Wang, Austin Kunch, Hong Xie, Yann Quidé, Wissam El-Hage, Shmuel Lissek, Hannah Berg, Steven E Bruce, Josh Cisler, Marisa Ross, Ryan J Herringa, Daniel W Grupe, Jack B Nitschke, Richard J Davidson, Christine Larson, Terri A Deroon-Cassini, Carissa W Tomas, Jacklynn M Fitzgerald, Jeremy Elman, Matthew Panizzon, Carol E Franz, Michael J Lyons, William S Kremen, Brandee Feola, Jennifer U Blackford, Bunmi O Olatunji, Geoffrey May, Steven M Nelson, Evan M Gordon, Chadi G Abdallah, Ruth Lanius, Maria Densmore, Jean Théberge, Richard W J Neufeld, Paul M Thompson, Delin Sun

Faculty, Staff and Students Publications

The increasing scale and complexity of neuroimaging datasets aggregated from multiple study sites present substantial analytic challenges, as existing statistical analysis tools struggle to handle missing voxel-data, suffer from limited computational speed and inefficient memory allocation, and are restricted in the types of statistical designs they are able to model. We introduce Image-Based Meta- & Mega-Analysis (IBMMA), a novel software package implemented in R and Python that provides a unified framework for analyzing diverse neuroimaging features, efficiently handles large-scale datasets through parallel processing, offers flexible statistical modeling options, and properly manages missing voxel-data commonly encountered in multi-site studies. IBMMA successfully …

Genomic Profiling Of Intraocular Leiomyomas Reveals Recurrent Copy Number Alterations, Vivian Tang, Yubai Chou, Cuyan Demirkesen, Michele M. Bloomer, Joseph B. Crawford, Ahmet M. Sarici, Carol L. Shields, Ralph C. Eagle Jr., Codrin E. Iacob, Walter P. Devine, Tatyana Milman, Melike Pekmezci

Wills Eye Hospital Papers

PURPOSE: Leiomyomas are benign smooth muscle tumors that commonly present in the uterus, soft tissue, skin, and gastrointestinal tract but in rare cases can also arise within the eye. Notably, intraocular leiomyomas often show slightly different histopathologic and immunohistochemical features, referred to as mesectodermal morphology, given their presumed neural crest origin. Genetic and cytogenetic alterations of intraocular leiomyomas, as well as their association with various clinical and histopathologic features, have not been previously studied.

METHODS: We identified eight patients diagnosed with intraocular leiomyoma and performed targeted next-generation sequencing, whole transcriptome RNA sequencing, and chromosomal copy number analysis on those with …

Ocular Bacterial Microbiome Analysis By Next-Generation Sequencing In Patients With Stevens-Johnson Syndrome And Sjögren’S Disease: Associations With Dry Eye Indices, Luciana Frizon, Talita Trevizani Rocchetti, André Frizon, Rafael Jorge Alves De Alcântara, Ana Luisa Hofling-Lima, Cintia S De Paiva, José Álvaro Pereira Gomes

Faculty, Staff and Students Publications

The ocular surface microbiome plays a crucial role in maintaining immune homeostasis, and its disruption may contribute to mucosal inflammation and autoimmunity. This pilot exploratory study investigated and compared the ocular surface bacterial microbiome in patients with Stevens-Johnson syndrome (SJS), Sjögren's disease (SjD), and healthy controls using next-generation sequencing (NGS) and correlated these findings with dry eye parameters. Conjunctival swabs were collected from sixteen individuals: ten with SJS, three with SjD, and three healthy controls. Dry eye parameters were employed to evaluate the dry eye disease. Microbiome profiles were determined by the NGS of the 16S V3-V4 region and analyzed …

Branch Retinal Artery Occlusion After Covid-19, Danielle Kalberer Od, Mba, Grace Tan Od

Optometric Clinical Practice

Background: A healthy, 39-year-old male patient presented with sudden onset, painless vision loss of the right eye’s superior visual field two months after a mild case of COVID-19.

Case Report: The patient was diagnosed with an acute branch retinal artery occlusion and referred to the emergency department for prompt evaluation. When the emergency workup was unremarkable the patient was referred to cardiology and hematology and follow up with a retinal specialist. The exhaustive systemic work-up was unremarkable other than recent COVID-19. Retinal perfusion to the affected area resumed in the weeks after the incident but irreversible vision loss occurred.

Conclusion: …

Biallelic Loss-Of-Function Variants In C19orf44 Lead To Retinal Degeneration, Hafiz Muhammad Jafar Hussain, Wang Meng, Yumei Li, Sabika Firasat, Mark E Pennesi, Michael B Gorin, Bin Guan, Rebecca Lynn Clark, Emma Fale-Olsen, Ranya Al Rawi, Aime Agather, Laryssa A Huryn, Paul Yang, Anna Matynia, Rui Chen

Faculty, Staff and Students Publications

Background: Inherited retinal diseases (IRDs) are a group of disorders often resulting in progressive vision loss, ultimately leading to blindness. A significant portion of their genetic causes remain unresolved, partly due to undiscovered disease-associated genes or variants. This study aimed to identify novel genetic links to IRDs.

Methods: All patients underwent comprehensive ophthalmological evaluation, including retinal imaging (fundus autofluorescence and macular optical coherence tomography) and electroretinogram testing. Whole exome sequencing and whole genome sequencing were performed on patients with clinically unsolved IRD, and data were analysed using an in-house pipeline to identify causal variants. Subsequently, Sanger sequencing was performed to …

Corneal Sensory Nerve Regulation Of Tear Production Through Stimulation Of Transient Receptor Potential Melastatin 8 (Trpm8) Channel: A Potential New Approach For Treating Dry Eye Disease, Juana Gallar, Stephen Pflugfelder, Anat Galor, Preeya K Gupta, Pedram Hamrah

Faculty, Staff and Students Publications

The lacrimal functional unit (LFU) tightly controls the secretion of all tear components, thus playing a critical role in maintaining ocular surface homeostasis. Forming an exquisitely sensitive neural network across the ocular surface, corneal sensory nerves detect environmental stimuli (e.g., temperature, chemicals, and mechanical pressure) through transient receptor potential (TRP) ion channels. Among these, TRP melastatin 8 (TRPM8) is a key regulator of basal tear production. Stimulated by the small temperature reductions and tear film osmolarity increases that arise due to evaporative cooling, TRPM8 activates the LFU, leading to increased basal tear production. Here, we focus on reviewing the topical …

Molecular And Genetic Landscapes Of Retina And Brain Microglia In Neurodegenerative Diseases, Khang Ma, Rinki Ratnapriya

Faculty, Staff and Students Publications

Microglia-driven dysregulation has emerged as a significant underlying mechanism in many neurodegenerative diseases, such as age-related macular degeneration (AMD) and Alzheimer's disease (AD). Although both brain and retinal microglia originate from the yolk sac, it is uncertain whether they share molecular similarities or genetic and molecular foundations related to neurodegenerative diseases. In this study, we examine the transcriptomic and epigenetic profiles of retina and brain microglia through integrative analyses of single-nucleus RNA sequencing (snRNA-seq) and single-nucleus ATAC sequencing (snATAC-seq) from 97 independent human samples across 11 different studies. Our findings reveal that retina and brain microglia share similar expression and …