Optometry Commons^™

Enhancing Cataract Surgery Outcomes: Optimal Use Of Pre- And Post-Operative Eye Drops, Keith Skolnick M.D., Anu Valiaveedu

Mako: NSU Undergraduate Student Journal

Many preoperative and postoperative cataract patients struggle with comprehending the use of prescription medication as directed. Language barriers and low health literacy levels are major factors contributing to improper use of prescriptions. To increase patients comprehension, the Fort Lauderdale Eye Institute employed an educational intervention consisting of a live presentation and an instructional video. Results found that 44% of patients were hesitant to ask questions to clinical staff, 32% felt overwhelmed, and nearly 70% lacked confidence in using their prescribed eye drops. Following the intervention, 91% of patients reported increased confidence in their medications, and most indicated that the video …

Non-Isolated Tetralogy Of Fallot (Tof+): Exome Sequencing Efficacy And Phenotypic Expansions, Julia Volpi, Xiaonan Zhao, Nichole Owen, Tia Evans, Muriel Holder-Espinasse, Nayana Lahiri, Eleanor Sherlock, Gemma Poke, Jeroen Breckpot, Koen Devriendt, Bjorn Cools, Alfredo Brusco, Giovanni Battista Ferrero, Enrico Grosso, Pradeep Vasudevan, Sara Loddo, Antonio Novelli, Maria Cristina Digilio, Aafke Engwerda, Marrit Hitzert, Alison Male, Lucy Bownass, Ruth Newbury-Ecob, Zosia Miedzybrodzka, Ruth Armstrong, Sally Ann Lynch, Gunnar Houge, Shiyi Xiong, Seema R Lalani, Jill A Rosenfeld, Pamela N Luna, Chad A Shaw, Daryl A Scott

Faculty, Staff and Students Publications

Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart defect (CHD). TOF may present in isolation or in conjunction with one or more non-cardiac congenital anomalies or neurodevelopmental disorders (TOF+). Uncertainty regarding the efficacy of various genetic testing strategies, and an incomplete understanding of the genetic causes of TOF+, may lead to hesitancy in recommending genetic testing, particularly, clinical exome sequencing (cES). Here, we analyzed cES data from 131 individuals with TOF+. A definitive or probable diagnosis was made for 31 individuals, yielding a diagnostic rate of 23.6% (31/131). One individual received three diagnoses. Commercially available CHD panels …

Oculomics: Current Concepts And Evidence, Zhuoting Zhu, Yueye Wang, Ziyi Qi, Wenyi Hu, Xiayin Zhang, Siegfried K Wagner, Yujie Wang, An Ran Ran, Joshua Ong, Ethan Waisberg, Mouayad Masalkhi, Alex Suh, Yih Chung Tham, Carol Y Cheung, Xiaohong Yang, Honghua Yu, Zongyuan Ge, Wei Wang, Bin Sheng, Yun Liu, Andrew G Lee, Alastair K Denniston, Peter Van Wijngaarden, Pearse A Keane, Ching-Yu Cheng, Mingguang He, Tien Yin Wong

Faculty, Staff and Student Publications

The eye provides novel insights into general health, as well as pathogenesis and development of systemic diseases. In the past decade, growing evidence has demonstrated that the eye's structure and function mirror multiple systemic health conditions, especially in cardiovascular diseases, neurodegenerative disorders, and kidney impairments. This has given rise to the field of oculomics-the application of ophthalmic biomarkers to understand mechanisms, detect and predict disease. The development of this field has been accelerated by three major advances: 1) the availability and widespread clinical adoption of high-resolution and non-invasive ophthalmic imaging ("hardware"); 2) the availability of large studies to interrogate associations …

Characterizing The Genetic Basis For Inherited Retinal Disease: Lessons Learned From The Foundation Fighting Blindness Clinical Consortium's Gene Poll, Kari Branham, Lassana Samarakoon, Isabelle Audo, Allison R Ayala, Janet K Cheetham, Stephen P Daiger, Patty Dhooge, Jacque L Duncan, Todd A Durham, Abigail T Fahim, Rachel M Huckfeldt, Robert B Hufnagel, Susanne Kohl, Ramiro S Maldonado, Michele Melia, Michel Michaelides, Mark E Pennesi, José-Alain Sahel, Juliana M Ferraz Sallum, Mandeep S Singh, Dror Sharon, Kimberly Stepien, Kaylie Jones, Christina Y Weng

Faculty, Staff and Students Publications

PURPOSE: The Foundation Fighting Blindness (FFB) Consortium is a collaboration of 41 international clinical centers that manage patients affected with inherited retinal diseases (IRDs). The annual Consortium gene poll was initiated in 2020 to capture the genetic cause of disease in patients with IRD and associated clinical practices of Consortium sites. Data from the 2022 gene poll are reported here.

METHODS: In 2022, academic, private practice, and government ophthalmology clinics that are members of the Consortium centers were polled to identify per-case IRD genetic causality from a list of 387 syndromic and nonsyndromic IRD genes. The survey also assessed how …

Dna Methylation Profiling At Base-Pair Resolution Reveals Unique Epigenetic Features Of Early-Onset Colorectal Cancer In Underrepresented Populations, Jason Sheng Li, Karen Riggins, Li Yang, Chaorong Chen, Patricia Castro, Wedad Alfarkh, Neda Zarrin-Khameh, Michael E Scheurer, Chad J Creighton, Benjamin Musher, Wei Li, Lanlan Shen

Faculty, Staff and Students Publications

BACKGROUND: The incidence of early-onset colorectal cancer (EOCRC) has been rising at an alarming rate in the USA, and EOCRC disproportionately affects racial/ethnic minorities. Here, we construct comprehensive profiles of EOCRC DNA methylomes at base-pair resolution for a cohort of Hispanic and African American patients.

RESULTS: We show the epigenetic landscape of these EOCRC patients differs from that of late-onset colorectal cancer patients, and methylation canyons in EOCRC tumor tissue preferentially overlapped genes in cancer-related pathways. Furthermore, we identify epigenetic alterations in metabolic genes that are specific to our racial/ethnic minority EOCRC cohort but not Caucasian patients from TCGA. Top …

Spatial Organization Of The Mouse Retina At Single Cell Resolution By Merfish, Jongsu Choi, Jin Li, Salma Ferdous, Qingnan Liang, Jeffrey R Moffitt, Rui Chen

Faculty, Staff and Students Publications

The visual signal processing in the retina requires the precise organization of diverse neuronal types working in concert. While single-cell omics studies have identified more than 120 different neuronal subtypes in the mouse retina, little is known about their spatial organization. Here, we generated the single-cell spatial atlas of the mouse retina using multiplexed error-robust fluorescence in situ hybridization (MERFISH). We profiled over 390,000 cells and identified all major cell types and nearly all subtypes through the integration with reference single-cell RNA sequencing (scRNA-seq) data. Our spatial atlas allowed simultaneous examination of nearly all cell subtypes in the retina, revealing …

Anti-Scg3 Gene Therapy To Treat Choroidal Neovascularization In Mice, Chengchi Huang, Liyang Ji, Avinash Kaur, Hong Tian, Prabuddha Waduge, Keith A Webster, Wei Li

Faculty, Staff and Students Publications

Neovascular age-related macular degeneration (nAMD) with choroidal neovascularization (CNV) is a leading cause of blindness in the elderly in developed countries. The disease is currently treated with anti-angiogenic biologics, including aflibercept, against vascular endothelial growth factor (VEGF) but with limited efficacy, treatment resistance and requirement for frequent intravitreal injections. Although anti-VEGF gene therapy may provide sustained therapy that obviates multiple injections, the efficacy and side effects related to VEGF pathway targeting remain, and alternative strategies to block angiogenesis independently of VEGF are needed. We recently reported that secretogranin III (Scg3) induces only pathological angiogenesis through VEGF-independent pathways, and Scg3-neutralizing antibodies …

Review Of Gene Therapies For Age-Related Macular Degeneration, Arshad M Khanani, Mathew J Thomas, Aamir A Aziz, Christina Y Weng, Carl J Danzig, Glenn Yiu, Szilárd Kiss, Nadia K Waheed, Peter K Kaiser

Faculty, Staff and Students Publications

Gene therapies aim to deliver a therapeutic payload to specified tissues with underlying protein deficiency. Since the 1990s, gene therapies have been explored as potential treatments for chronic conditions requiring lifetime care and medical management. Ocular gene therapies target a range of ocular disorders, but retinal diseases are of particular importance due to the prevalence of retinal disease and the current treatment burden of such diseases on affected patients, as well as the challenge of properly delivering these therapies to the target tissue. The purpose of this review is to provide an update on the most current data available for …

3’Aqtl-Atlas: An Atlas Of 3’Utr Alternative Polyadenylation Quantitative Trait Loci Across Human Normal Tissues, Ya Cui, Fanglue Peng, Dan Wang, Yumei Li, Jason Sheng Li, Lei Li, Wei Li

Faculty, Staff and Students Publications

Genome-wide association studies (GWAS) have identified thousands of non-coding single-nucleotide polymorphisms (SNPs) associated with human traits and diseases. However, functional interpretation of these SNPs remains a significant challenge. Our recent study established the concept of 3' untranslated region (3'UTR) alternative polyadenylation (APA) quantitative trait loci (3'aQTLs), which can be used to interpret ∼16.1% of GWAS SNPs and are distinct from gene expression QTLs and splicing QTLs. Despite the growing interest in 3'aQTLs, there is no comprehensive database for users to search and visualize them across human normal tissues. In the 3'aQTL-atlas (https://wlcb.oit.uci.edu/3aQTLatlas), we provide a comprehensive list of 3'aQTLs containing …

Electroacupuncture Ameliorates Inflammatory Response Induced By Retinal Ischemia-Reperfusion Injury And Protects The Retina Through The Dor-Bdnf/Trkb Pathway, Runjie Guo, Yongjie Zhang, Yue Geng, Ping Chen, Tiantian Fu, Yong Xia, Ren Zhang, Yuan Zhu, Jingling Jin, Nange Jin, Hong Xu, Xuesong Tian

Faculty, Staff and Student Publications

Objectives: Retinal ischemia-reperfusion injury (RIRI) is the common pathological basis of many ophthalmic diseases in the later stages, and inflammation is the primary damage mechanism of RIRI. Our study aimed to assess whether electroacupuncture (EA) has a protective effect against RIRI and to elucidate its related mechanisms.

Methods: A high-intraocular pressure (HIOP) model was used to simulate RIRI in Wistar rats. EA was applied to the EA1 group [Jingming (BL1) + Shuigou (GV26)] and the EA2 group [Jingming (BL1) + Hegu (LI4)] respectively for 30 min starting immediately after the onset of reperfusion and repeated (30 min/time) at 12 h …

Super-Resolution Microscopy Reveals Photoreceptor-Specific Subciliary Location And Function Of Ciliopathy-Associated Protein Cep290, Valencia L Potter, Abigail R Moye, Michael A Robichaux, Theodore G Wensel

Faculty, Staff and Students Publications

Mutations in the cilium-associated protein CEP290 cause retinal degeneration as part of multiorgan ciliopathies or as retina-specific diseases. The precise location and the functional roles of CEP290 within cilia and, specifically, the connecting cilia (CC) of photoreceptors, remain unclear. We used super-resolution fluorescence microscopy and electron microscopy to localize CEP290 in the CC and in the primary cilia of cultured cells with subdiffraction resolution and to determine effects of CEP290 deficiency in 3 mutant models. Radially, CEP290 localizes in close proximity to the microtubule doublets in the region between the doublets and the ciliary membrane. Longitudinally, it is distributed throughout …

Identification Of Deep-Intronic Splice Mutations In A Large Cohort Of Patients With Inherited Retinal Diseases, Xinye Qian, Jun Wang, Meng Wang, Austin D Igelman, Kaylie D Jones, Yumei Li, Keqing Wang, Kerry E Goetz, David G Birch, Paul Yang, Mark E Pennesi, Rui Chen

Faculty, Staff and Students Publications

High throughput sequencing technologies have revolutionized the identification of mutations responsible for a diverse set of Mendelian disorders, including inherited retinal disorders (IRDs). However, the causal mutations remain elusive for a significant proportion of patients. This may be partially due to pathogenic mutations located in non-coding regions, which are largely missed by capture sequencing targeting the coding regions. The advent of whole-genome sequencing (WGS) allows us to systematically detect non-coding variations. However, the interpretation of these variations remains a significant bottleneck. In this study, we investigated the contribution of deep-intronic splice variants to IRDs. WGS was performed for a cohort …

Targeted Aav5-Smad7 Gene Therapy Inhibits Corneal Scarring In Vivo, Suneel Gupta, Jason T. Rodier, Ajay Sharma, Elizabeth A. Giuliano, Prashant R. Sinha, Nathan P. Hesemann, Arkasubhra Ghosh, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

Corneal scarring is due to aberrant activity of the transforming growth factor β (TGFβ) signaling pathway following traumatic, mechanical, infectious, or surgical injury. Altered TGFβ signaling cascade leads to downstream Smad (Suppressor of mothers against decapentaplegic) protein-mediated signaling events that regulate expression of extracellular matrix and myogenic proteins. These events lead to transdifferentiation of keratocytes into myofibroblasts through fibroblasts and often results in permanent corneal scarring. Hence, therapeutic targets that reduce transdifferentiation of fibroblasts into myofibroblasts may provide a clinically relevant approach to treat corneal fibrosis and improve long-term visual outcomes. Smad7 protein regulates the functional effects of TGFβ signaling …