Review
Ophthalmology
Timothy T. Xu, Justin C. Moser, Lauren A. Dalvin
Summary: Advancements in genetic understanding, diagnosis, prognosis, and treatment of uveal melanoma (UM) include molecularly distinct melanocytic malignancy driven by mutations in GNAQ or GNA11, earlier diagnosis and treatment for improved life prognosis, objective imaging risk factors for prediction of malignant nevus transformation, and novel treatment strategies such as customized radiation fields and nanoparticle therapy. Reliable prediction of metastatic disease risk through gene expression profiling or the Cancer Genome Atlas project classification, combined use of clinical tumor features and molecular data for individualized patient prognosis, and consideration of adjuvant therapy in high-risk UM patients to prevent metastatic disease are important aspects. Additionally, for patients with clinically evident metastasis, combination immunotherapy regimens, T cell-based therapies, and focal adhesion kinase inhibitors offer hope for improved clinical response rates. Improved understanding of UM molecular pathogenesis and clinical trials of targeted therapy for prevention and treatment of metastatic disease may ultimately improve patient survival for this challenging disease.
CURRENT OPINION IN OPHTHALMOLOGY
(2021)
Article
Oncology
Thi Hai Yen Nguyen, Tin Nguyen, Quang-Huy Nguyen, Duc-Hau Le
Summary: In this study, omics profiles were used to explore the associations between CNA, MET, and mRNA in UM. Two novel integrative subgroups were discovered, showing associations with immune-related processes and cellular cation homeostasis. These findings can impact UM patient classification and treatment selection.
FRONTIERS IN ONCOLOGY
(2021)
Review
Oncology
Nuno Jorge Lamas, Arnaud Martel, Sacha Nahon-Esteve, Samantha Goffinet, Adam Macocco, Corine Bertolotto, Sandra Lassalle, Paul Hofman
Summary: Uveal melanoma is the most common cancer that develops inside adult eyes, with a poor prognosis and limited treatment options. There is a need to find methods that can accurately predict the prognosis of the disease and effective therapeutic strategies. This article summarizes the current knowledge and challenges in the field of uveal melanoma research, and discusses potential future directions.
Article
Oncology
Ernesto Rossi, Michela Croce, Francesco Reggiani, Giovanni Schinzari, Marianna Ambrosio, Rosaria Gangemi, Giampaolo Tortora, Ulrich Pfeffer, Adriana Amaro
Summary: Survival rates for metastatic uveal melanoma have not significantly improved over the years, as it differs from cutaneous melanoma and is resistant to current therapies. The main obstacles are the activation of oncogenic signaling pathways that cannot be targeted, the lack of tumor specific neo-antigens for immune response, and the pro-tumorigenic microenvironment that promotes tumor progression. However, new drugs targeting oncogenic pathways, innovative immune therapy approaches, and liver-specific treatments offer hope for improving outcomes.
Review
Oncology
Malgorzata Gajdzis, Radoslaw Kaczmarek, Pawel Gajdzis
Summary: Uveal melanoma is the most common primary intraocular neoplasm in adults with a high rate of distant metastases and no effective treatment in the advanced stage. The search for new prognostic factors is crucial for understanding the disease's biology, monitoring patients effectively, and identifying potential therapeutic targets. Numerous studies have demonstrated the complexity of uveal melanoma biology and the potential for individualized treatment approaches based on protein expression patterns.
Article
Oncology
Mathieu F. Bakhoum, Ellis J. Curtis, Michael H. Goldbaum, Paul S. Mischel
Summary: Assessment of BAP1 methylation is an accurate and readily clinically actionable assay to identify high-risk uveal melanoma patients.
NPJ PRECISION ONCOLOGY
(2021)
Article
Oncology
Mizue Terai, Ayako Shimada, Inna Chervoneva, Liam Hulse, Meggie Danielson, Jeff Swensen, Marlana Orloff, Philip B. Wedegaertner, Jeffrey L. Benovic, Andrew E. Aplin, Takami Sato
Summary: Uveal melanoma is driven by G-protein mutations, with a high recurrence rate even after primary treatment. The mutations in GNA11 and GNAQ are associated with survival rates of metastatic uveal melanoma patients.
Article
Cell Biology
Malgorzata Gajdzis, Stamatios Theocharis, Jerzy Klijanienko, Nathalie Cassoux, Sophie Gardrat, Piotr Donizy, Radoslaw Kaczmarek, Pawel Gajdzis
Summary: This study found that high expression of PARP-1 in uveal melanoma is associated with unfavorable clinicopathological parameters and prognosis.
Article
Cell Biology
Han Zhao, Yun Chen, Peijun Shen, Lan Gong
Summary: This study analyzed the immune cell infiltration landscape of uveal melanoma using CIBERSORT and ESTIMATE algorithms, finding that patients with high ICI scores had poorer prognosis and increased expression levels of immune checkpoint-related genes. The study demonstrated that ICI scores are an independent prognostic biomarker and have value in predicting immunotherapeutic outcomes.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Cell Biology
Yao Chen, Xiaozhen Chen, Xianggui Wang
Summary: This study analyzed 10 CRGs in 80 UVM patients and constructed a prognostic gene model. It was found that the alteration of CRGs is related to UVM patients and can predict their prognosis.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Oncology
Jessica J. J. Waninger, Leslie A. A. Fecher, Christopher Lao, Sarah Yentz, Michael D. D. Green, Hakan Demirci
Summary: Uveal melanoma is a rare but common eye tumor with no standardized treatment for metastatic disease. This study suggests that lactate dehydrogenase and white blood cell ratio could be useful blood markers for determining treatment response.
Article
Multidisciplinary Sciences
Yang Luo, Renhao Ni, Xiaojun Jin, Peipei Feng, Chenyi Dai, Lingjing Jiang, Pingping Chen, Lu Yang, Yabin Zhu
Summary: This study reveals that FOXD1 plays a negative role in the prognosis of uveal melanoma by promoting tumor growth and invasion. Through cell culture and genomic analysis, the biological mechanisms of FOXD1 were explored, and a novel tumor prognostic model was established for disease stratification and clinical treatment.
Article
Multidisciplinary Sciences
Xueying Shi, Shilin Xia, Yingming Chu, Nan Yang, Jingyuan Zheng, Qianyi Chen, Zeng Fen, Yuankuan Jiang, Shifeng Fang, Jingrong Lin
Summary: The study analyzed the prognostic value and immune-related characteristics of CARD11 in Uveal melanoma (UVM) using RNA-sequence data and found that CARD11 expression was significantly correlated with clinical features and overall survival in UVM, and positively correlated with autophagy, cellular senescence, and apoptosis. High CARD11 expression was associated with poor overall survival in UVM and could serve as a potential biomarker.
Article
Oncology
Tianyu Wang, Yuanyuan Zhang, Jianhao Bai, Yawen Xue, Qing Peng
Summary: The study revealed that MMP1, MMP9, and other matrix metalloproteinases were upregulated in UVM tissues and correlated with disease progression and patient survival. Additionally, 18 transcription factors associated with MMPs were identified, potentially providing biomarkers and targets for UVM. Further studies are needed to confirm these findings.
Article
Oncology
Yasemin C. Cole, Yu-Zhi Zhang, Beatrice Gallo, Adam P. Januszewski, Anca Nastase, David J. Essex, Caroline M. H. Thaung, Victoria M. L. Cohen, Mandeep S. Sagoo, Anne M. Bowcock
Summary: A study on 100 uveal melanomas from the UK revealed that loss of nuclear BAP1 (nBAP1) predicts shorter overall survival. Tumors with BAP1 loss of function mutations frequently exhibited heterogeneous BAP1 staining, and tumors with >= 25% loss of nBAP1 were a more reliable prognostic indicator than chromosome 3 loss (LOH3) or chromosome 8q gain. Majority of BAP1 mutations result in loss of nBAP1 and aberrant expression of cBAP1.
Article
Multidisciplinary Sciences
Michael A. Durante, Daniel A. Rodriguez, Stefan Kurtenbach, Jeffim N. Kuznetsov, Margaret I. Sanchez, Christina L. Decatur, Helen Snyder, Lynn G. Feun, Alan S. Livingstone, J. William Harbour
NATURE COMMUNICATIONS
(2020)
Article
Genetics & Heredity
Anna M. Armitage, Monica A. Kundra, Neda Ghiam, Paldeep S. Atwal, Dayna Morel, Kathleen S. Hruska, Rebecca Torene, Irman Forghani
Summary: This case report describes the first instance of blood chimerism involving a pathogenic RB1 variant in naturally conceived monochorionic-dizygotic twins with twin-twin-transfusion syndrome, likely due to stem cell exchange. The affected twin developed bilateral retinoblastoma at 7 months of age, with both twins having a 20% allelic ratio of the RB1 pathogenic variant in their blood. Subsequent genotyping confirmed dizygosity, with the affected twin harboring the variant in skin and blood, while the unaffected twin only had the variant in blood.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2021)
Article
Ophthalmology
Jonathan F. Russell, Victor M. Villegas, Stephen G. Schwartz, Christina Y. Weng, Janet L. Davis, Harry W. Flynn, J. William Harbour
Summary: The study examined 12 patients diagnosed with exophytic JRCH at Bascom Palmer Eye Institute and Baylor College of Medicine. Multimodal imaging is valuable in the diagnosis of JRCH, aiding in ruling out other conditions.
AMERICAN JOURNAL OF OPHTHALMOLOGY
(2021)
Article
Multidisciplinary Sciences
Konstantinos E. Hatzistergos, Michael A. Durante, Krystalenia Valasaki, Amarylis C. B. A. Wanschel, J. William Harbour, Joshua M. Hare
Article
Biology
Stefan Kurtenbach, James J. Dollar, Anthony M. Cruz, Michael A. Durante, Christina L. Decatur, J. William Harbour
Summary: Single-cell RNA sequencing (scRNA-seq) is a transformative technology that is visualized using dimensional reduction techniques like UMAP and tSNE. PieParty enhances this visualization by representing each cell as a pie chart with slices corresponding to gene expression, allowing for the simultaneous visualization of multiple genes and gene networks in an information-dense and intuitive manner.
LIFE SCIENCE ALLIANCE
(2021)
Article
Oncology
J. William Harbour
Summary: Through a synthetic lethal screen, ERK activation was found to mediate resistance to FAK inhibition in GNAQ-mutant uveal melanoma. Combining inhibition of PLCB-PKC-ERK and Trio-FAK-Yap, representing compensatory effectors of mutant Gaq signaling, may be a promising therapeutic strategy in metastatic uveal melanoma.
CLINICAL CANCER RESEARCH
(2021)
Article
Ophthalmology
Sushant Wagley, Peter J. Belin, James J. Dollar, J. William Harbour, Amanda C. Maltry, Prithvi Mruthyunjaya, A. M. Y. C. Schefler, Peter H. Tang
Summary: Unilateral multifocal uveal melanomas in the setting of ocular melanosis may result from the development of genetically independent primary tumors, as indicated by the mutation profiles of each tumor.
AMERICAN JOURNAL OF OPHTHALMOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Stefan Kurtenbach, Anthony M. Cruz, Daniel A. Rodriguez, Michael A. Durante, J. William Harbour
Summary: Uphyloplot2 is an easy-to-use tool that generates phylogenetic plots to depict tumor clonality from scRNA-seq data and other sources. It can directly generate phylogenetic plots from inferred RNA-seq data or any Newick formatted dendrogram file, and is publicly available at https://github.com/harbourlab/UPhyloplot2/.
Article
Oncology
Vivian Chua, Anna Han, Nelisa Bechtel, Timothy J. Purwin, Emily Hunter, Connie Liao, J. William Harbour, Andrew E. Aplin
Summary: Metastatic uveal melanoma with BAP1 alterations show elevated AMPK pathway activation, suggesting a potential therapeutic target. Re-expression of BAP1 reduces phosphorylation levels of AMPK and ACC. The survival function of AMPK in BAP1 mutant UM cells is mediated by CaMKK2 and LKB1.
PIGMENT CELL & MELANOMA RESEARCH
(2022)
Article
Genetics & Heredity
Daniel A. Rodriguez, Jessica Yang, Michael A. Durante, Alexander N. Shoushtari, Stergios J. Moschos, Kazimierz O. Wrzeszczynski, J. William Harbour, Richard D. Carvajal
Summary: The study identified temporal and anatomical complexity in the genetic evolution of metastatic uveal melanoma, including multiple seeding events and the occurrence of late driver variants. This highlights the distinction between early and late phases of UM genetic evolution and has implications for novel therapeutic approaches.
NPJ GENOMIC MEDICINE
(2021)
Article
Oncology
Usman Baqai, Timothy J. Purwin, Nelisa Bechtel, Vivian Chua, Anna Han, Edward J. Hartsough, Jeffim N. Kuznetsoff, J. William Harbour, Andrew E. Aplin
Summary: This study demonstrates that loss of BAP1 in uveal melanoma leads to upregulation of cell adhesion molecules (CAMs), including E-cadherin, CADM1, and SDC2. The reexpression of BAP1 reduces the levels of these molecules and functional experiments show that knockdown of E-cadherin and CADM1 affects spheroid cluster formation and cell growth, respectively.
MOLECULAR CANCER RESEARCH
(2022)
Article
Multidisciplinary Sciences
Matthew G. Field, Jeffim N. Kuznetsoff, Michelle G. Zhang, James J. Dollar, Michael A. Durante, Yoseph Sayegh, Christina L. Decatur, Stefan Kurtenbach, Daniel Pelaez, J. William Harbour
Summary: This study identifies a previously unknown dependency of Rb cells on ESRRG and implicates ESRRG as a potential therapeutic target in Rb.
Article
Oncology
Michelle G. Zhang, Jeffim N. Kuznetsoff, Dawn A. Owens, Ryan A. Gallo, Karthik Kalahasty, Anthony M. Cruz, Stefan Kurtenbach, Zelia M. Correa, Daniel Pelaez, J. William Harbour
Summary: Despite advances in chemotherapy, chemoresistance continues to be a major issue in retinoblastoma. The study showed that carboplatin induced molecular reprogramming, upregulating targets in the PI3K-AKT pathway, including ABC transporters and metabolic regulators. These targets could be potentially inhibited to overcome chemoresistance.
Article
Oncology
Anna Han, Dzmitry Mukha, Vivian Chua, Timothy J. Purwin, Manoela Tiago, Bhavik Modasia, Usman Baqai, Jenna L. Aumiller, Nelisa Bechtel, Emily Hunter, Meggie Danielson, Mizue Terai, Philip B. Wedegaertner, Takami Sato, Solange Landreville, Michael A. Davies, Stefan Kurtenbach, J. William Harbour, Zachary T. Schug, Andrew E. Aplin
Summary: Metastatic uveal melanoma is difficult to treat, but targeting metabolic pathways, such as lipid/fat metabolism and mTOR, may be a potential therapeutic approach. The upregulation of enzymes involved in lipid/fat metabolism, such as FASN, and activation of the mTOR pathway were observed in uveal melanoma cells. Inhibiting FASN and mTOR led to the suppression of uveal melanoma cell growth, suggesting a novel treatment strategy for uveal melanoma.
Article
Oncology
Daniel A. Rodriguez, Margaret Sanchez, Christina L. Decatur, Zelia M. Correa, Eden R. Martin, J. William Harbour
Editorial Material
Ophthalmology
David Cui, Ian J. Saldanha, Gavin Li, Priya M. Mathews, Michael X. Lin, Esen K. Akpek
Summary: This article reports on the heterogeneity in methodology of clinical trials submitted to the US Food and Drug Administration for approval of topical dry eye treatments. Multiple outcome measures were used in these trials, highlighting the need for standardized assessment tools to optimize the evaluation and comparison of therapeutic benefits.
AMERICAN JOURNAL OF OPHTHALMOLOGY
(2024)
Article
Ophthalmology
Adanna Udeh, Dana Huh, Terri Young, O'rese Knight, Fasika Woreta
Summary: This study examines the rates and trends of faculty promotions within the field of ophthalmology, with a focus on the rates of promotion among underrepresented in medicine (URiM) faculty. The results show that Black faculty had lower promotion rates and were more likely to leave academic medicine, highlighting the need for strategies and policies to address equity in promotion rates and retention of URiM faculty in academic ophthalmology.
AMERICAN JOURNAL OF OPHTHALMOLOGY
(2024)
Article
Ophthalmology
Ursula Greferath, Erica Fletcher, Judy Savige, Heather G. Mack
Summary: Retinal drusen are uncommon in IgA nephropathy, but they resemble drusen found in age-related macular degeneration. The IgA-staining deposits in the drusen are likely related to systemic deposition of IgA. The nature of cystic spaces in the drusen is still unknown. Further research on the retinas of people with glomerulonephritis is recommended.
AMERICAN JOURNAL OF OPHTHALMOLOGY
(2024)
Article
Ophthalmology
Andrew Mihalache, Ryan S. Huang, Nikhil S. Patil, Marko M. Popovic, Ashwin Mallipatna, Peter J. Kertes, Rajeev H. Muni, Radha P. Kohly
Summary: This study examines sociodemographic predictors of poor vision in children and adolescents in the US. The findings suggest that factors such as affordability of medical care, public health insurance, age, and parental education level are associated with vision difficulty. Addressing these disparities through public health policies is crucial for achieving equity in vision health.
AMERICAN JOURNAL OF OPHTHALMOLOGY
(2024)
Article
Ophthalmology
Johannes Birtel, Richard Caswell, Samantha R. De Silva, Philipp Herrmann, Salwah Rehman, Andrew J. Lotery, Omar A. Mahroo, Michel Michaelides, Andrew R. Webster, Robert E. Maclaren, Peter Charbel Issa
Summary: The study investigated the phenotype, variability, and penetrance of IMPG2-related maculopathy. The results showed that mono-allelic IMPG2 variants could result in haploinsufficiency manifesting as a maculopathy with variable penetrance and expressivity. Family members of patients with IMPG2-related retinitis pigmentosa may also present with vitelliform lesions. The maculopathy is usually limited to the fovea and is associated with moderate visual impairment.
AMERICAN JOURNAL OF OPHTHALMOLOGY
(2024)
Article
Ophthalmology
Colas Nils Authie, Mylene Poujade, Alireza Talebi, Alexis Defer, Ariel Zenouda, Cecilia Coen, Saddek Mohand-Said, Philippe Chaumet-Riffaud, Isabelle Audo, Jose-Alain Sahel
Summary: MOST has been validated as a reliable mobility test for measuring the movement ability of patients with vision impairments in both real and virtual environments.
AMERICAN JOURNAL OF OPHTHALMOLOGY
(2024)
Article
Ophthalmology
Maria Krisch, Jordan Ueberroth, Neha Gupta, Stephen Merriam, Mark p. Breazzano
Summary: Orbeez-related ocular trauma can lead to severe visual morbidity and various intraocular sequelae. Adolescents may be at higher risk for posterior segment complications. Elevated IOP and hyphema at initial presentation may indicate a need for more aggressive interventions.
AMERICAN JOURNAL OF OPHTHALMOLOGY
(2024)
Article
Ophthalmology
Jaron Pruett, Kelly Ruland, Sean Donahue
Summary: The study aimed to validate or refute the hypothesis that infants with birthweight over 750 g and gestational age over 27 weeks, who did not have retinopathy of prematurity (ROP) at 37 weeks, would not develop treatable ROP. The findings of the study supported the termination of examination at 37 weeks in infants meeting these criteria, as the value of continued screening was minimal.
AMERICAN JOURNAL OF OPHTHALMOLOGY
(2024)
Article
Ophthalmology
Emily Sun, Jing Tian, Loaah Eltemsah, Divya Srikumaran, Grace Sun, Jessica Chow, Fasika Woreta
Summary: This study aims to evaluate the research productivity of ophthalmology residency applicants and identify differences in productivity based on gender and race. The findings reveal that women have similar or higher research outputs compared to men, while self-identified underrepresented in medicine (URiM) students have lower research outputs in ophthalmology. Therefore, greater mentorship and support for URiM students are needed to promote the recruitment of diverse trainees in ophthalmology programs.
AMERICAN JOURNAL OF OPHTHALMOLOGY
(2024)
Article
Ophthalmology
Isaac A. Bernstein, Ann Caroline Fisher, Kuldev Singh, Sophia Y. Wang
Summary: This study aims to investigate the association between visual field loss and frailty in a nationally representative cohort of US adults.
AMERICAN JOURNAL OF OPHTHALMOLOGY
(2024)
