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1. CONE PHOTORECEPTOR INTEGRITY ASSESSED WITH ADAPTIVE OPTICS IMAGING AFTER LASER POINTER-INDUCED RETINAL INJURY

Author: Frederick H. Davidorf, Carol Vitellas, Elaine Wells-Gray, Nayanika Challa, Stacey S. Choi, and Nathan Doble
Subjects: Optics and Photonics, medicine.medical_specialty, genetic structures, law.invention, chemistry.chemical_compound, Eye Injuries, Retinal Diseases, Optical coherence tomography, law, Foveal, Ophthalmology, Humans, Medicine, Adaptive optics, Retina, medicine.diagnostic_test, business.industry, Lasers, Fundus photography, Retinal, General Medicine, Laser, eye diseases, Ophthalmoscopy, medicine.anatomical_structure, chemistry, Retinal Cone Photoreceptor Cells, Laser pointer, sense organs, business, Tomography, Optical Coherence
Abstract: PURPOSE To examine the three-dimensional foveal cone photoreceptor structure in a patient who had suffered laser pointer induced retinal injury. METHODS Patient underwent standard fundus photography and clinical spectral domain optical coherence tomography (SD-OCT) imaging. High-resolution imaging was performed using an Adaptive Optics-OCT-Scanning Laser Ophthalmoscope (AO-OCT-SLO). RESULTS AO imaging revealed loss of inner and outer segments of cone photoreceptors while the anterior retinal layers appeared healthy. Analysis of cone topology showed an increase in Voronoi domain area and a less regular hexagonal packing structure closer to the lesion site. CONCLUSION Exposure to laser pointer radiation, however brief, can result in damage to the retina. Here, repeated imaging nine months later showed a decrease in the size of the lesions (ranging from 3.7 to 23.9%) compared to the first time point. However, the longer-term prognosis is likely permanent scarring.
Published: 2022
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2. Prediction for 2-Year Vision Outcomes Using Early Morphologic and Functional Responses in the Comparison of Age-related Macular Degeneration Treatments Trials

Author: Katie Xue, Peiying Hua, Maureen G. Maguire, Ebenezer Daniel, Glenn J. Jaffe, Juan E. Grunwald, Gui-shuang Ying, David F. Williams, Sara Beardsley, Steven Bennett, Herbert Cantrill, Carmen Chan-Tram, Holly Cheshier, Kathyrn Damato, John Davies, Sundeep Dev, Julianne Enloe, Gennaro Follano, Peggy Gilbert, Jill Johnson, Tori Jones, Lisa Mayleben, Robert Mittra, Martha Moos, Ryan Neist, Neal Oestreich, Polly Quiram, Robert Ramsay, Edwin Ryan, Stephanie Schindeldecker, John Snater, Trenise Steele, Dwight Selders, Jessica Tonsfeldt, Shelly Valardi, Gary Edd Fish, Hank A. Aguado, Sally Arceneaux, Jean Arnwine, Kim Bell, Tina Bell, Bob Boleman, Patricia Bradley, David Callanan, Lori Coors, Jodi Creighton, Timothy Crew, Kimberly Cummings, Christopher Dock, Karen Duignan, Dwain Fuller, Keith Gray, Betsy Hendrix, Nicholas Hesse, Diana Jaramillo, Bradley Jost, Sandy Lash, Laura Lonsdale, Michael Mackens, Karin Mutz, Michael Potts, Brenda Sanchez, William Snyder, Wayne Solley, Carrie Tarter, Robert Wang, Patrick Williams, Stephen L. Perkins, Nicholas Anderson, Ann Arnold, Paul Blais, Joseph Googe, Tina T. Higdon, Cecile Hunt, Mary Johnson, James Miller, Misty Moore, Charity K. Morris, Christopher Morris, Sarah Oelrich, Kristina Oliver, Vicky Seitz, Jerry Whetstone, Bernard H. Doft, Jay Bedel, Robert Bergren, Ann Borthwick, Paul Conrad, Amanda Fec, Christina Fulwylie, Willia Ingram, Shawnique Latham, Gina Lester, Judy Liu, Louis Lobes, Nicole M. Lucko, Holly Mechling, Lori Merlotti, Keith McBroom, Karl Olsen, Danielle Puskas, Pamela Rath, Maria Schmucker, Lynn Schueckler, Christina Schultz, Heather Shultz, David Steinberg, Avni Vyas, Kim Whale, Kimberly Yeckel, David H. Orth, Linda S. Arredondo, Susan Brown, Barbara J. Ciscato, Joseph M. Civantos, Celeste Figliulo, Sohail Hasan, Belinda Kosinski, Dan Muir, Kiersten Nelson, Kirk Packo, John S. Pollack, Kourous Rezaei, Gina Shelton, Shannya Townsend-Patrick, Marian Walsh, H. Richard McDonald, Nina Ansari, Amanda Bye, Arthur D. Fu, Sean Grout, Chad Indermill, Robert N. Johnson, J. Michael Jumper, Silvia Linares, Brandon J. Lujan, Ames Munden, Meredith Persons, Rosa Rodriguez, Jennifer M. Rose, Brandi Teske, Yesmin Urias, Stephen Young, Richard F. Dreyer, Howard Daniel, Michele Connaughton, Irvin Handelman, Stephen Hobbs, Christine Hoerner, Dawn Hudson, Marcia Kopfer, Michael Lee, Craig Lemley, Joe Logan, Colin Ma, Christophe Mallet, Amanda Milliron, Mark Peters, Harry Wohlsein, Joel A. Pearlman, Margo Andrews, Melissa Bartlett, Nanette Carlson, Emily Cox, Robert Equi, Marta Gonzalez, Sophia Griffin, Fran Hogue, Lance Kennedy, Lana Kryuchkov, Carmen Lopez, Danny Lopez, Bertha Luevano, Erin McKenna, Arun Patel, Brian Reed, Nyla Secor, Iris R. Sison, Tony Tsai, Nina Varghis, Brooke Waller, Robert Wendel, Reina Yebra, Daniel B. Roth, Jane Deinzer, Howard Fine, Flory Green, Stuart Green, Bruce Keyser, Steven Leff, Amy Leviton, Amy Martir, Kristin Mosenthine, Starr Muscle, Linda Okoren, Sandy Parker, Jonathan Prenner, Nancy Price, Deana Rogers, Linda Rosas, Alex Schlosser, Loretta Studenko, Thea Tantum, Harold Wheatley, Michael T. Trese, Thomas Aaberg, Denis Bezaire, Craig Bridges, Doug Bryant, Antonio Capone, Michelle Coleman, Christina Consolo, Cindy Cook, Candice DuLong, Bruce Garretson, Tracy Grooten, Julie Hammersley, Tarek Hassan, Heather Jessick, Nanette Jones, Crystal Kinsman, Jennifer Krumlauf, Sandy Lewis, Heather Locke, Alan Margherio, Debra Markus, Tanya Marsh, Serena Neal, Amy Noffke, Kean Oh, Clarence Pence, Lisa Preston, Paul Raphaelian, Virginia R. Regan, Peter Roberts, Alan Ruby, Ramin Sarrafizadeh, Marissa Scherf, Sarita Scott, Scott Sneed, Lisa Staples, Brad Terry, Matthew T. Trese, Joan Videtich, George Williams, Mary Zajechowski, Daniel P. Joseph, Kevin Blinder, Lynda Boyd, Sarah Buckley, Meaghan Crow, Amanda Dinatale, Nicholas Engelbrecht, Bridget Forke, Dana Gabel, Gilbert Grand, Jennifer Grillion-Cerone, Nancy Holekamp, Charlotte Kelly, Ginny Nobel, Kelly Pepple, Matt Raeber, P. Kumar Rao, Tammy Ressel, Steven Schremp, Merrilee Sgorlon, Shantia Shears, Matthew Thomas, Cathy Timma, Annette Vaughn, Carolyn Walters, Rhonda Weeks, Jarrod Wehmeier, Tim Wright, Daniel M. Berinstein, Aida Ayyad, Mohammed K. Barazi, Erica Bickhart, Tracey Brady, Lisa Byank, Alysia Cronise, Vanessa Denny, Courtney Dunn, Michael Flory, Robert Frantz, Richard A. Garfinkel, William Gilbert, Michael M. Lai, Alexander Melamud, Janine Newgen, Shamekia Newton, Debbie Oliver, Michael Osman, Reginald Sanders, Manfred von Fricken, Pravin Dugel, Sandra Arenas, Gabe Balea, Dayna Bartoli, John Bucci, Jennifer A. Cornelius, Scheleen Dickens, Don Doherty, Heather Dunlap, David Goldenberg, Karim Jamal, Norma Jimenez, Nicole Kavanagh, Derek Kunimoto, John Martin, Jessica Miner, Sarah Mobley, Donald Park, Edward Quinlan, Jack Sipperley, Carol Slagle, Danielle Smith, Miguelina Yafchak, Rohana Yager, Christina J. Flaxel, Steven Bailey, Peter Francis, Chris Howell, Thomas Hwang, Shirley Ira, Michael Klein, Andreas Lauer, Teresa Liesegang, Ann Lundquist, Sarah Nolte, Susan K. Nolte, Scott Pickell, Susan Pope, Joseph Rossi, Mitchell Schain, Peter Steinkamp, Maureen D. Toomey, Debora Vahrenwald, Kelly West, Baker Hubbard, Stacey Andelman, Chris Bergstrom, Judy Brower, Blaine Cribbs, Linda Curtis, Jannah Dobbs, Lindreth DuBois, Jessica Gaultney, Deborah Gibbs, Debora Jordan, Donna Leef, Daniel F. Martin, Robert Myles, Timothy Olsen, Bryan Schwent, Sunil Srivastava, Rhonda Waldron, Andrew N. Antoszyk, Uma Balasubramaniam, Danielle Brooks, Justin Brown, David Browning, Loraine Clark, Sarah Ennis, Susannah Held, Jennifer V. Helms, Jenna Herby, Angie Karow, Pearl Leotaud, Caterina Massimino, Donna McClain, Michael McOwen, Jennifer Mindel, Candace Pereira, Rachel Pierce, Michele Powers, Angela Price, Jason Rohrer, Jason Sanders, Robert L. Avery, Kelly Avery, Jessica Basefsky, Liz Beckner, Alessandro Castellarin, Stephen Couvillion, Jack Giust, Matthew Giust, Maan Nasir, Dante Pieramici, Melvin Rabena, Sarah Risard, Robert See, Jerry Smith, Lisha Wan, Sophie J. Bakri, Nakhleh Abu-Yaghi, Andrew Barkmeier, Karin Berg, Jean Burrington, Albert Edwards, Shannon Goddard, Shannon Howard, Raymond Iezzi, Denise Lewison, Thomas Link, Colin A. McCannel, Joan Overend, John Pach, Margaret Ruszczyk, Ryan Shultz, Cindy Stephan, Diane Vogen, Reagan H. Bradford, Vanessa Bergman, Russ Burris, Amanda Butt, Beth Daniels, Connie Dwiggins, Stephen Fransen, Tiffany Guerrero, Darin Haivala, Amy Harris, Sonny Icks, Ronald Kingsley, Lena Redden, Rob Richmond, Brittany Ross, Kammerin White, Misty Youngberg, Trexler M. Topping, Steve Bennett, Sandy Chong, Mary Ciotti, Tina Cleary, Emily Corey, Dennis Donovan, Albert Frederick, Lesley Freese, Margaret Graham, Natalya Gud, Taneika Howard, Mike Jones, Michael Morley, Katie Moses, Jen Stone, Robin Ty, Torsten Wiegand, Lindsey Williams, Beth Winder, Carl C. Awh, Michelle Amonette, Everton Arrindell, Dena Beck, Brandon Busbee, Amy Dilback, Sara Downs, Allison Guidry, Gary Gutow, Jackey Hardin, Sarah Hines, Emily Hutchins, Kim LaCivita, Ashley Lester, Larry Malott, MaryAnn McCain, Jayme Miracle, Kenneth Moffat, Lacy Palazzotta, Kelly Robinson, Peter Sonkin, Alecia Travis, Roy Trent Wallace, Kelly J. Winters, Julia Wray, April E. Harris, Mari Bunnell, Katrina Crooks, Rebecca Fitzgerald, Cameron Javid, Corin Kew, Erica Kill, Patricia Kline, Janet Kreienkamp, Maricruz Martinez, Roy Ann Moore, Egbert Saavedra, LuAnne Taylor, Mark Walsh, Larry Wilson, Thomas A. Ciulla, Ellen Coyle, Tonya Harrington, Charlotte Harris, Cindi Hood, Ingrid Kerr, Raj Maturi, Dawn Moore, Stephanie Morrow, Jennifer Savage, Bethany Sink, Tom Steele, Neelam Thukral, Janet Wilburn, Joseph P. Walker, Jennifer Banks, Debbie Ciampaglia, Danielle Dyshanowitz, Jennifer Frederick, A. Tom Ghuman, Richard Grodin, Cheryl Kiesel, Eileen Knips, Jonathan McCue, Maria Ortiz, Crystal Peters, Paul Raskauskas, Etienne Schoeman, Ashish Sharma, Glenn Wing, Rebecca Youngblood, Suresh R. Chandra, Michael Altaweel, Barbara Blodi, Kathryn Burke, Kristine A. Dietzman, Justin Gottlieb, Gene Knutson, Denise Krolnik, T. Michael Nork, Shelly Olson, John Peterson, Sandra Reed, Barbara Soderling, Guy Somers, Thomas Stevens, Angela Wealti, Srilaxmi Bearelly, Brenda Branchaud, Joyce W. Bryant, Sara Crowell, Sharon Fekrat, Merritt Gammage, Cheala Harrison, Sarah Jones, Noreen McClain, Brooks McCuen, Prithvi Mruthyunjaya, Jeanne Queen, Neeru Sarin, Cindy Skalak, Marriner Skelly, Ivan Suner, Ronnie Tomany, Lauren Welch, Susanna S. Park, Allison Cassidy, Karishma Chandra, Idalew Good, Katrina Imson, null Sashi, null Kaur, Helen Metzler, Lawrence Morse, Ellen Redenbo, Marisa Salvador, David Telander, Mark Thomas, Cindy Wallace, Charles C. Barr, Amanda Battcher, Michelle Bottorff, Mary Chasteen, Kelly Clark, Diane Denning, Debra Schoen, Amy Schultz, Evie Tempel, Lisa Wheeler, Greg K. Whittington, Thomas W. Stone, Todd Blevins, Michelle Buck, Lynn Cruz, Wanda Heath, Diana Holcomb, Rick Isernhagen, Terri Kidd, John Kitchens, Cathy Sears, Ed Slade, Jeanne Van Arsdall, Brenda VanHoose, Jenny Wolfe, William Wood, John Zilis, Carol Crooks, Larry Disney, Mimi Liu, Stephen Petty, Sandra Sall, James C. Folk, Tracy Aly, Abby Brotherton, Douglas Critser, Connie J. Hinz, Stefani Karakas, Valerie Kirschner, Cheyanne Lester, Cindy Montague, Stephen Russell, Heather Stockman, Barbara Taylor, Randy Verdick, Jean Walshire, John T. Thompson, Barbara Connell, Maryanth Constantine, John L. Davis, null Gwen Holsapple, Lisa Hunter, C. Nicki Lenane, Robin Mitchell, Leslie Russel, Raymond Sjaarda, David M. Brown, Matthew Benz, Llewellyn Burns, JoLene G. Carranza, Richard Fish, Debra Goates, Shayla Hay, Theresa Jeffers, Eric Kegley, Dallas Kubecka, Stacy McGilvra, Beau Richter, Veronica Sneed, Cary Stoever, Isabell Tellez, Tien Wong, Ivana Kim, Christopher Andreoli, Leslie Barresi, Sarah Brett, Charlene Callahan, Karen Capaccioli, William Carli, Matthew Coppola, Nicholas Emmanuel, Claudia Evans, Anna Fagan, Marcia Grillo, John Head, Troy Kieser, Elaine Lee, Ursula Lord, Edward Miretsky, Kate Palitsch, Todd Petrin, Liz Reader, Svetlana Reznichenko, Mary Robertson, Justin Smith, Demetrios Vavvas, John Wells, Cassie Cahill, W. Lloyd Clark, Kayla Henry, David Johnson, Peggy Miller, LaDetrick Oliver, Robbin Spivey, Tiffany Swinford, Mallie Taylor, Michael Lambert, Kris Chase, Debbie Fredrickson, Joseph Khawly, Valerie Lazarte, Donald Lowd, Pam Miller, Arthur Willis, Philip J. Ferrone, Miguel Almonte, Rachel Arnott, Ingrid Aviles, Sheri Carbon, Michael Chitjian, Kristen DAmore, Christin Elliott, David Fastenberg, Barry Golub, Kenneth Graham, AnnMarie Lavorna, Laura Murphy, Amanda Palomo, Christina Puglisi, David Rhee, Juan Romero, Brett Rosenblatt, Glenda Salcedo, Marianne Schlameuss, Eric Shakin, Vasanti Sookhai, Richard Kaiser, Elizabeth Affel, Gary Brown, Christina Centinaro, Deborah Fine, Mitchell Fineman, Michele Formoso, Sunir Garg, Lisa Grande, Carolyn Herbert, Allen Ho, Jason Hsu, Maryann Jay, Lisa Lavetsky, Elaine Liebenbaum, Joseph Maguire, Julia Monsonego, Lucia O’Connor, Lisa Pierce, Carl Regillo, Maria Rosario, Marc Spirn, James Vander, Jennifer Walsh, Frederick H. Davidorf, Amanda Barnett, Susie Chang, John Christoforidis, Joy Elliott, Heather Justice, Alan Letson, Kathryne McKinney, Jeri Perry, Jill A. Salerno, Scott Savage, Stephen Shelley, Lawrence J. Singerman, Joseph Coney, John DuBois, Kimberly DuBois, Gregg Greanoff, Dianne Himmelman, Mary Ilc, Elizabeth McNamara, Michael Novak, Scott Pendergast, Susan Rath, Sheila Smith-Brewer, Vivian Tanner, Diane E. Weiss, Hernando Zegarra, Lawrence Halperin, Patricia Aramayo, Mandeep Dhalla, Brian Fernandez, Cindy Fernandez, Jaclyn Lopez, Monica Lopez, Jamie Mariano, Kellie Murphy, Clifford Sherley, Rita Veksler, Firas Rahhal, Razmig Babikian, David Boyer, Sepideh Hami, Jeff Kessinger, Janet Kurokouchi, Saba Mukarram, Sarah Pachman, Eric Protacio, Julio Sierra, Homayoun Tabandeh, Adam Zamboni, Michael Elman, Jennifer Belz, Tammy Butcher, Theresa Cain, Teresa Coffey, Dena Firestone, Nancy Gore, Pamela Singletary, Peter Sotirakos, JoAnn Starr, Travis A. Meredith, Cassandra J. Barnhart, Debra Cantrell, RonaLyn Esquejo-Leon, Odette Houghton, Harpreet Kaur, Fatoumatta NDure, Ronald Glatzer, Leonard Joffe, and Reid Schindler
Subjects: Ophthalmology
Published: 2023
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3. Atypical choroidal nevus in a subject with a germline PALB2 pathogenic variant

Author: Mohamed H. Abdel-Rahman, Frederick H. Davidorf, Matthew D Karl, Robert Pilarski, Colleen M. Cebulla, and Timothy W. Grosel
Subjects: Uveal Neoplasms, 0301 basic medicine, Cancer Research, Pathology, medicine.medical_specialty, PALB2, 030105 genetics & heredity, Article, Germline, Lesion, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Genetics, Humans, Medicine, Genetic Predisposition to Disease, Family history, Melanoma, Nevus, Genetics (clinical), Aged, business.industry, Cancer, medicine.disease, eye diseases, Choroidal nevus, Oncology, 030220 oncology & carcinogenesis, Female, sense organs, medicine.symptom, Fanconi Anemia Complementation Group N Protein, business
Abstract: INTRODUCTION: Recent evidence suggests that PALB2 variants may increase risk for the development of uveal melanoma and uveal melanocytic neoplasms. Here we report a case of an atypical choroidal nevus in a patient with a personal history of cancer and pathogenic PALB2 germline variant. MATERIALS AND METHODS: Retrospective case report of a patient with an atypical choroidal nevus and pathogenic PALB2 germline variant RESULTS: A 75-year-old white female presented with an elevated predominantly amelanotic choroidal lesion OS. On examination and ophthalmic imaging, the mass measured 8.8 mm x 6.5 mm x 1.5mm. The mass showed predominantly medium to high reflectivity on diagnostic A-scan and acoustic hollowing on B-scan. OCT over the lesion showed no subretinal fluid. The patient has a personal history of breast cancer and gastric adenoma and a strong family history of cancer. The patient was found to have a pathogenic truncating variant in PALB2 (rs118203998 c.3549C>A, p.Y1183*). CONCLUSION: Together with our previous findings of pathogenic PALB2 variants in uveal melanoma patients, this new finding of an atypical choroidal nevus in a patient with a pathogenic PALB2 germline variant suggests that pathogenic PALB2 variants may be a risk factor for uveal melanocytic neoplasms. This finding warrants further assessment of the prevalence and progression of uveal melanocytic neoplasms in PALB2 pathogenic variants carriers.
Published: 2021
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4. Whole Exome Sequencing Identifies Candidate Genes Associated with Hereditary Predisposition to Uveal Melanoma

Author: Lynn Schoenfield, Silvia Casadei, Meghan J DeBenedictis, Mohamed H. Abdel-Rahman, Ben Kelly, Peter White, Frederick H. Davidorf, Andrew W. Stacey, Daniel D. Kinnamon, Mary Claire King, David M Gordon, Arun D. Singh, James B. Massengill, T. Walsh, Nicholas K. Hayward, Getachew Boru, Klarke M. Sample, James Scarth, Timothy W. Grosel, Ellie Fewings, Colleen M. Cebulla, Peter Johansson, Marc Tischkowitz, and Robert Pilarski
Subjects: Adult, Male, Uveal Neoplasms, Oncology, Candidate gene, medicine.medical_specialty, Adolescent, MLH1, Article, 03 medical and health sciences, 0302 clinical medicine, Germline mutation, Internal medicine, Exome Sequencing, medicine, Humans, Genetic Predisposition to Disease, Child, Melanoma, Germ-Line Mutation, Exome sequencing, Aged, Retrospective Studies, 030304 developmental biology, Genetic testing, Aged, 80 and over, 0303 health sciences, medicine.diagnostic_test, Reverse Transcriptase Polymerase Chain Reaction, business.industry, Tumor Suppressor Proteins, Infant, Cancer, DNA, Neoplasm, Odds ratio, Middle Aged, medicine.disease, Immunohistochemistry, Neoplasm Proteins, 3. Good health, MSH6, Ophthalmology, Child, Preschool, 030221 ophthalmology & optometry, Female, business, Ubiquitin Thiolesterase, Genes, Neoplasm
Abstract: To identify susceptibility genes associated with hereditary predisposition to uveal melanoma (UM) in patients with no detectable germline BAP1 alterations.Retrospective case series from academic referral centers.Cohort of 154 UM patients with high risk of hereditary cancer defined as patients with 1 or more of the following: (1) familial UM, (2) young age (35 years) at diagnosis, (3) personal history of other primary cancers, and (4) family history of 2 or more primary cancers with no detectable mutation or deletion in BAP1 gene.Whole exome sequencing, a cancer gene panel, or both were carried out. Probands included 27 patients with familial UM, 1 patient with bilateral UM, 1 patient with congenital UM, and 125 UM patients with strong personal or family histories, or both, of cancer. Functional validation of variants was carried out by immunohistochemistry, reverse-transcriptase polymerase chain reaction, and genotyping.Clinical characterization of UM patients with germline alterations in known cancer genes.We identified actionable pathogenic variants in 8 known hereditary cancer predisposition genes (PALB2, MLH1, MSH6, CHEK2, SMARCE1, ATM, BRCA1, and CTNNA1) in 9 patients, including 3 of 27 patients (11%) with familial UM and 6 of 127 patients (4.7%) with a high risk for cancer. Two patients showed pathogenic variants in CHEK2 and PALB2, whereas variants in the other genes each occurred in 1 patient. Biallelic inactivation of PALB2 and MLH1 was observed in tumors from the respective patients. The frequencies of pathogenic variants in PALB2, MLH1, and SMARCE1 in UM patients were significantly higher than the observed frequencies in noncancer controls (PALB2: P = 0.02; odds ratio, 8.9; 95% confidence interval, 1.5-30.6; MLH1: P = 0.04; odds ratio, 25.4; 95% confidence interval, 1.2-143; SMARCE1: P = 0.001; odds ratio, 2047; 95% confidence interval, 52-4.5e15, respectively).The study provided moderate evidence of gene and disease association of germline mutations in PALB2 and MLH1 with hereditary predisposition to UM. It also identified several other candidate susceptibility genes. The results suggest locus heterogeneity in predisposition to UM. Genetic testing for hereditary predisposition to cancer is warranted in UM patients with strong personal or family history of cancers, or both.
Published: 2020
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5. Use and Perceptions of Advanced Driver Assistance Systems by Older Drivers With and Without Age-Related Macular Degeneration

Author: Rebecca A, Deffler, Jing, Xu, Ava K, Bittner, Alex R, Bowers, Shirin E, Hassan, Nicole, Ross, San-San L, Cooley, Aprile, Doubt, Frederick H, Davidorf, and Bradley E, Dougherty
Subjects: Ophthalmology, Automobile Driving, Macular Degeneration, Surveys and Questionnaires, Biomedical Engineering, Accidents, Traffic, Humans, Aged
Abstract: Advanced driver assistance systems (ADAS) have been reported to improve the safety of elderly and normally sighted drivers. The purpose of this study was to assess exposure to, perceived safety of, comfort level with, and interest in using ADAS among drivers with age-related macular degeneration (AMD).Current drivers aged 60+ years were recruited at four US sites to complete a survey about ADAS and driving habits. Frequency of use and/or perceptions of eight ADAS were investigated. An avoidance score was generated using questions about difficult driving situations.The survey was completed by 166 participants (80 with AMD vs. 86 without). Participants with AMD had worse self-rated vision than those without (34% vs. 2% poor or fair rating), and drove fewer weekly miles (median [interquartile range [IQR] 30 [15 to 75] vs. 60 [30 to 121] miles, P = 0.002). Participants with AMD reported more avoidance of difficult driving situations (P0.001). There was no difference in the number of ADAS used by AMD status (median [IQR for AMD = 2.5 [1 to 5] vs. 3 [2 to 4] without, P = 0.87). Greater reported number of ADAS used was associated with less avoidance of difficult situations (P = 0.02). The majority perceived improved safety with most ADAS.Many drivers with AMD utilize common ADAS, which subjectively improve their road safety and may help to reduce self-imposed restrictions for difficult situations and mileage.Drivers with AMD are adopting readily available ADAS, for which they reported potential benefits, such as safety and less restrictive driving.
Published: 2022

6. BAP1 Tumor Predisposition Syndrome

Author: Sarah Smith, Mohamed H. Abdel-Rahman, Robert Pilarski, Frederick H. Davidorf, and Colleen M. Cebulla
Subjects: BAP1, Tumor suppressor gene, business.industry, Renal cell carcinoma, Melanoma, Cutaneous melanoma, medicine, Cancer research, Basal cell carcinoma, Mesothelioma, medicine.disease, business, Haploinsufficiency
Abstract: The BAP1 tumor predisposition syndrome results from autosomal dominant haploinsufficiency of the BAP1 tumor suppressor gene. The syndrome was identified through the findings of three independent centers researching predisposition for each of their tumors of interest. BAP1 variants have now been confirmed to be associated, in order of decreasing frequency, with BAP1-inactivated melanocytic tumors, uveal melanoma, malignant mesothelioma, cutaneous melanoma, renal cell carcinoma, and basal cell carcinoma. There are several additional unconfirmed tumors, such as hepatocellular carcinoma, cholangiocarcinoma, and meningioma that may ultimately prove to be related. The syndrome is now being more rapidly characterized as centers worldwide are pooling data on patients and their families through the BAP1 Interest Group Consortium. Knowledge of this condition may allow for prevention, early detection, and appropriate treatment of related malignancies.
Published: 2021
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7. Heterogeneity in Mitogen-Activated Protein Kinase (MAPK) Pathway Activation in Uveal Melanoma With Somatic GNAQ and GNA11 Mutations

Author: Mohamed H. Abdel-Rahman, Getachew Boru, Klarke M. Sample, Frederick H. Davidorf, James B. Massengill, and Colleen M. Cebulla
Subjects: 0301 basic medicine, MAPK/ERK pathway, Uveal Neoplasms, Blotting, Western, DNA Mutational Analysis, GNA11, Biology, medicine.disease_cause, Transfection, Targeted therapy, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, GNAQ, Cell Line, Tumor, medicine, Humans, Melanoma, Mutation, MEK inhibitor, Wild type, Sequence Analysis, DNA, medicine.disease, Immunohistochemistry, GTP-Binding Protein alpha Subunits, 3. Good health, 030104 developmental biology, 030220 oncology & carcinogenesis, Mitogen-activated protein kinase, Cancer research, biology.protein, GTP-Binding Protein alpha Subunits, Gq-G11, Anatomy and Pathology/Oncology, uveal melanoma, Mitogen-Activated Protein Kinases, MAP Kinase, Polymorphism, Restriction Fragment Length, Plasmids, Signal Transduction
Abstract: Purpose The activation of the mitogen-activated protein kinase (MAPK) pathway has been suggested as the major downstream target when GNAQ and GNA11 (GNAQ/11) are mutated in uveal melanoma (UM). However, clinical trials with single agent MEK inhibitor showed no clinical significance in altering the overall outcome of the disease in UM; therefore, we investigated the correlation between naturally occurring mutations in GNAQ/11 and activation of MAPK pathway in vivo in primary UM. Methods Screening for activating mutations in codons 183 and 209 of GNAQ/11 was carried out by sequencing and restriction fragment length polymorphism (RFLP) in a cohort of 42 primary UM. Activation of the MAPK pathway and other potential downstream signals was assessed by immunohistochemistry and/or Western blot analysis. Potential downstream signaling of mutant and wild type GNAQ/11 was studied by transient transfection assay in nonmutant cell lines. Results Somatic mutations in GNAQ/11 were observed in 35/42 (83.3%) of primary UM. Tumors with GNAQ/11 mutations showed variations in the activation of ERK1/2 with significant tumor heterogeneity. Weak and undetectable ERK1/2 activation was observed in 4/35 (11.4%) and 8/35 (22.9%) of the GNAQ/11 mutant UM, respectively. Tumor heterogeneity of GNAQ/11 mutations was also observed in a subset of tumors. Conclusions Our results indicate that there is marked variation in MAPK activation in UM with GNAQ/11 mutations. Thus, GNAQ/11 mutational status is not a sufficient biomarker to adequately predict UM patient responses to single-agent selective MEK inhibitor therapy.
Published: 2019

8. Analysis of the exome aggregation consortium (ExAC) database suggests that the BAP1- tumor predisposition syndrome is underreported in cancer patients

Author: James B. Massengill, Klarke M. Sample, Mohamed H. Abdel-Rahman, Joseph P. McElroy, Frederick H. Davidorf, Robert Pilarski, and Colleen M. Cebulla
Subjects: Male, 0301 basic medicine, Proband, Cancer Research, Population, Biology, computer.software_genre, Polymorphism, Single Nucleotide, Article, Germline, 03 medical and health sciences, 0302 clinical medicine, Neoplasms, Databases, Genetic, Genetics, Humans, Missense mutation, Exome, Genetic Predisposition to Disease, education, Exome sequencing, education.field_of_study, BAP1, Database, Tumor Suppressor Proteins, Pedigree, Exact test, Phenotype, 030104 developmental biology, 030220 oncology & carcinogenesis, Female, Ubiquitin Thiolesterase, computer
Abstract: The BAP1-tumor predisposition syndrome (BAP1-TPDS) has been recently identified to predispose patients to a variety of cancers and preneoplastic lesions. About 130 unrelated probands have been identified worldwide; however, the impact of the syndrome is suspected to be much larger given the diversity of the cancer phenotype. To evaluate the frequency of germline BAP1 mutations in the general and cancer populations, we analyzed the Exome Aggregation Consortium (ExAC), a database that contains 53105 exomes of unrelated individuals unaffected by cancer (general population) and exomes of 7601 unrelated individuals affected by cancer provided by the Cancer Genome Atlas (TCGA, cancer subjects). BAP1 null variants were seen at much higher frequency in the cancer subjects (0.0526%) compared to the general population (0.00188%) with a relative risk of 27.93 and (P = 0.0011, [95% CI: 3.122-249.883], Fisher's exact test). We also studied a reported BAP1 null variant, c.1203T > G, p.T401* (rs200156887), observed commonly in the general population. Sequencing and restriction fragment polymorphism of the RT-4 cell line that contains this variant revealed that it is in fact a 3bp deletion/insertion, c.1201_1203delinsGAG, a likely benign missense alteration p.Y401E explaining the relative high frequency of this variant in the general population. In conclusion, germline null mutations in BAP1 have a significantly higher frequency in cancer patients than the general population. Given the low frequency of reported families with BAP1-TPDS, our results suggest that the syndrome is underreported especially in patients with cancer.
Published: 2018
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9. Plasma Vascular Endothelial Growth Factor Concentrations after Intravitreous Anti–Vascular Endothelial Growth Factor Therapy for Diabetic Macular Edema

Author: Lee M. Jampol, Adam R. Glassman, Danni Liu, Lloyd Paul Aiello, Neil M. Bressler, Elia J. Duh, Susan Quaggin, John A. Wells, Charles C. Wykoff, David Browning, Andrew N. Antoszyk, Angela K. Price, Sherry L. Fredenberg, Jenna T. Herby, Christina J. Fleming, Ashley A. McClain, Sarah A. Ennis, Kelly R. Gallagher, Angella S. Karow, Autumn C. Grupp, Danielle Puskas, Lynn Watson, Swann J. Bojaj, Uma M. Balasubramaniam, Donna McClain, Donna R. Styles, Jeff A. Kuopus, Kathryn Kimrey, Loraine M. Clark, Lisa A. Jackson, Michael D. McOwen, Matt Dunlap, Susannah J. Held, Dante J. Pieramici, Ma'an A. Nasir, Alessandro A. Castellarin, Dilsher Dhoot, Sarah Fishbein, Jack Giust, Lisha Wan, Michelle S. Hanna, Melvin D. Rabena, Jerry Smith, Layne J. Bone, Kelly Avery, Matthew Giust, Aimee Walker, Aimee H. Shook, Sara Esau, Nitce L. Ruvalcaba, W. Lloyd Clark, David L. Johnson, John F. Payne, Tiffany R. Swinford, Mallie M. Taylor, Cassandra L. Garrison, Peggy D. Miller, Amber R. Houlahan, Charlotte A. O'Neill, Ashley Floyd, Crystal C. Parker, Courtney Sease, Tara Graham, Robin Spencer, Tiffany N. Ogbuewu, Ashley Studebaker, Tyler Huggins, Robbin Spivey, Brian Jones, Ashley Williams, Ron Petty, Erin L. Poston, G. Michael Ward, Carl W. Baker, Ron H. Tilford, Tracey M. Caldwell, Lynnette F. Lambert, Mary J. Palmer, Tracey R. Martin, Tana R. Williams, Samantha Kettler, Alecia B. Camp, Paolo S. Silva, Paul G. Arrigg, George S. Sharuk, Sabera T. Shah, Jennifer K. Sun, Corey Westerfeld, Christopher Michael Andreoli, Deborah Schlossman, Timothy Murtha, Hanna Kwak, Flor M. Flores, Margaret E. Stockman, Troy Kieser, Michael N. Krigman, Leila Bestourous, Elizabeth S. Weimann, Jerry D. Cavallerano, Kristen M. Hock, Mary Ann Robertson, Rita K. Kirby, Steve L. Papaconstantinou, Kylie M. Madigan, Robert W. Cavicchi, Kate A. Palitsch, Taygan Yilmaz, Brian B. Berger, Chirag D. Jhaveri, Tori Moore, Ginger J. Manhart, Rachel A. Walsh, Ivana Gunderson, Dietrich Riepen, Chelsey A. Bravenec, Ryan M. Reid, Yong Ren, Ben Ostrander, Christopher C. Stovall, Michael J. Elman, Robert A. Liss, Henry A. Leder, JoAnn Starr, Jennifer L. Belz, Charlene K. Putzulo, Dallas R. Sandler, Jennifer L. Simmons, Pamela V. Singletary, Ashley Davis, Perel M. Simpson, Teresa Coffey, Daniel J. Ketner, Terri Cain, Ashley M. Metzger, Peter Sotirakos, Dennis M. Marcus, Harinderjit Singh, Courtney N. Roberts, Geri L. Floyd, Siobhan O. Ortiz, Virginia Mims, L. Allison Foster, Christy Coursey, Jared C. Gardner, Ken Ivey, John Stewart O'Keefe, Juan A. Astruc, Bryan J. Schwent, Ali R. Tabassian, Suzette A. Rosen, David C. Vaughan, Jeffrey Michaels, Natalie J. Arndt, John J. Maziarz, Scott M. Friedman, Nader Moinfar, Kimberly A. Williamson, Damanda F. Fagan, Katrina L. Dawson, Paige N. Walters, Allen McKinney, Steve Carlton, Robert C. Kwun, Victoria L. Knudsen, Kirk E. Winward, Mano Swartz, James G. Howard, Michelle Riley, Gena Taylor, Michelle Holt, Jason G. Winward, Adam Walsh, Teresa Taylor, Daniel Walsh, G. Robert Hampton, Jamin S. Brown, Rajeev K. Seth, Laurie J. Sienkiewycz, Deborah A. Appleton, Cindy J. Grinnell, Charity A. Cowley, Lynn M. Kwasniewski, Michelle L. Manley, Nicole E. Robarge, Stefanie R. DeSantis, Peter B. Hay, Teresa M. DeForge, Tien P. Wong, Eric Chen, David M. Brown, Rosa Y. Kim, James C. Major, Amy C. Schefler, Richard H. Fish, Matthew S. Benz, Meredith Lipman, Amy Hutson, Nubia Landaverde, Ashley E. Chancey, Cassie Cone, Tressa Royse, Veronica A. Sneed, Belinda A. Almanza, Brenda Dives, Beau A. Richter, Eric N. Kegley, Andreas K. Lauer, Christina J. Flaxel, Steven T. Bailey, Mitchell Schain, Ann D. Lundquist, Shelley A. Hanel, Shirley D. Ira, Susan K. Nolte, Peter N. Steinkamp, Dawn M. Ryan, Scott R. Pickell, Jocelyn T. Hui, Michelle Brix, Jordan Barth, Chris S. Howell, Gregory M. Fox, Blake A. Cooper, Ivan R. Batlle, Lexie R. Manning, Karla A. Batlle, Holly Wyrick, Katherine Pippin, Samantha Perkins, Frank T. Yeager, Ryan B. Rush, Glenn R. Gardner, Christi Rush, Johnathan R. Hawkins, Brenda Dumas, Ben Ysasaga, Chirag P. Shah, Michael G. Morley, Torsten W. Wiegand, Tina S. Cleary, Trexler M. Topping, Lindsey Colegrove, Katharine Bechtel, Britta Johnson, Lisa Lebedew, Natacha Lorius, Sandy G. Chong, Jennifer L. Stone, Michael Cullen Jones, Dennis Donovan, Sherry Malone, Margie Graham, Audrey Santos, Steve A. Bennett, Kevin J. Blinder, Bradley T. Smith, Ginny S. Nobel, Rhonda F. Weeks, Erika A. Hoehn, Maria A. Stuart, Kelly E. Pepple, Lynda K. Boyd, Brook G. Pulliam, Steve A. Schremp, Stephanie L. Guevara, Jarrod Wehmeier, Timothy L. Wright, Dana L. Gabel, David G. Miller, Jerome P. Schartman, Lawrence J. Singerman, Joseph M. Coney, Michael A. Novak, Llewelyn J. Rao, Susan C. Rath, Elizabeth McNamara, Larraine Stone, Veronica A. Smith, Cecelia Rykena, Kimberly A. DuBois, Mary A. Ilc, Vivian Tanner, Kim Drury, Trina M. Nitzsche, Gregg A. Greanoff, John C. DuBois, Stuart K. Burgess, Tirso M. Lara, Noel H. Pereda, Cindy V. Fernandez, Deborah Davis, Evelyn Quinchia, Karen Workman, Jared S. Nielsen, Jeong-Hyeon Sohn, Kyle J. Alliman, David D. Saggau, Marianne Parker, Bethany George, Carrie L. Eastvold, Kristin Sells, Tami Jo Woehl, Marilyn A. Johnson, Holly Keenan, Jennifer L. Coleman, Jamie Spillman, Shannon Freeman, Leigh S. Schmidt, Lisa M. Boender, Jill L. Partin, Bailey R. Bennett, Jay Rostvold, Cameron McLure Stone, Lea R. Raymer, Andrea K. Menzel, Leslie D. Rickman, Barbara Campbell, Lorraine P. Sherlin, Lisa H. Hawkins, Melissa L. Buckner, Olesya N. Matsipura, Paula A. Price, A. Thomas Ghuman, Paul A. Raskauskas, Ashish G. Sharma, Glenn Wing, Joseph P. Walker, Eileen Knips, Cheryl Kiesel, Crystal Y. Peters, Cheryl Ryan, Laura Greenhoe, Natalie N. Torres, Rebecca J. Youngblood, Danielle Turnbo, Anita H. Leslie, Etienne C. Schoeman, Raymond K. Kiesel, Ronald M. Kingsley, Vinay A. Shah, Robert E. Leonard, Heather R. Miller, Sonny Icks, Vanessa A. Bergman, Vanessa K. Drummond, Brittany L. Ross, Reshial D. Ellis, Tina R. Whittington, Shannon R. Almeida, Amanda M. Butt, Russ Burris, Mark A. Peters, Michael S. Lee, Paul S. Tlucek, Colin Ma, Stephen Hobbs, Amanda C. Milliron, Stephanie L. Ho, Marcia Kopfer, Joe Logan, Christine Hoerner, Joseph A. Khawly, Hassan T. Rahman, Diana Abdelgani, Pam S. Miller, Debbie Fredrickson, Erica Pineda, Desiree Lopez, Donald K. Lowd, Colin Blank, Lorena R. Martinez, Jason E. Muniz, Justin Gottlieb, Michael S. Ip, Barbara A. Blodi, Kristine A. Dietzman, Kathryn F. Burke, Christopher M. Smith, Shelly R. Olson, Angela M. Wealti, Sandie L. Reed, Denise A. Krolnik, John C. Peterson, Victor Hugo Gonzalez, Roberto Diaz-Rohena, Juan G. Santiago, Rohit Adyanthaya, Nehal R. Patel, Deyla Anaya, Dina Garcia, Edna E. Cruz, Crystal A. Alvarez, Ruth Iracheta, Jessica Rodriguez, Monica R. Cantu, Rebecca R. Flores, Hector Jasso, Rachel Rodriguez, Karina Miranda, Krystle R. Lozano, Maricela Garza, Lazaro Aguero, Amanda L. Sandoval, Monique Montemayor, Samuel Alonso, Santos Garza, David Allen DiLoreto, Rajeev S. Ramchandran, David M. Kleinman, George W. O'Gara, Andrea M. Czubinski, Peter MacDowell, Kari M. Steinmetz, Dan A. Castillo, Yvonne F. Yu, Salina M. Tongue, Melissa S. Keim, Rachel Hollar, Brandi N. Deats, Brittany S. Richardson, Lynn Singer, Taylor A. Pannell, Stewart A. Daniels, Tushar M. Ranchod, Craig J. Leong, Stacey Touson, Shannon R. Earl, Melissa C. Bartlett, Christine Fernando, Djorella Factor, Jessica Garcia, Anna K. Nguyen, Betty Hom, Cathy Walker, Grace M. Marudo, Jose Carlos Suazo, Leah M. McNeil, Fred Hanamoto, Matthew D. Hughes, Robin D. Ross, Susan M. Sanford, Nicole Martini Markiewicz, Tracy M. Utley, Shannon Henderson, Joanie H. Lippincott, Patricia Streasick, Louis C. Glazer, Frank W. Garber, Jeffrey D. Zheutlin, Angela D. Listerman, Christine E. Feehan, Heather L. Cruz, Donald E. Kuitula, Olivia P. Rainey, Sue Weatherbee, Joseph M. Googe, R. Keith Shuler, Nicholas G. Anderson, Stephen L. Perkins, Kristina Oliver, Nicole Grindall, Ann Arnold, Jennifer Beerbower, Cecile Hunt, Kathy L. Schulz, Sarah M. Oelrich, Jerry K. Whetstone, Justin Walsh, Chris Morris, Robert W. Wong, Peter A. Nixon, Jeni L. Leon, Chris A. Montesclaros, Carrie E. Leung, Phill Le, Codey L. Harborth, Margaret A. Rodriguez, Cory Mangham, Thomas M. Aaberg, Scott J. Westhouse, Holly L. Vincent, Rebecca Malone, Kathy L. Karsten, Raj K. Maturi, Ashley M. Harless, Carolee K. Novak, Laura A. Bleau, Thomas Steele, Charlotte Harris, Alisha Bildner, Abby Maple, Thomas W. Stone, Rick D. Isernhagen, John W. Kitchens, Diana M. Holcomb, Jeanne Van Arsdall, Michelle Buck, Edward A. Slade, Mark T. Chiu, Ashok K. Reddy, Frank W. Wyant, Mary M. Montano-Niles, Lorraine J. Carter, Shirley Maerki, Laura Tartaglia, Paul P. Gomez, Stephen A. Maestas, Camille Shanta, Lisbrenda M. Jimenez, Robert A. Stoltz, Stephanie L. Vanderveldt, Scott I. Lampert, Leslie G. Marcus, Shelly Fulbright, James P. Martin, Roger L. Novack, David S. Liao, Tammy Eileen Lo, Janet Kurokouchi, Richard Ngo, Connie V. Hoang, Julio Sierra, Adam Zamboni, Eric G. Protacio, Jeff Kessinger, Seema Garg, Odette M. Houghton, Jan Niklas Ulrich, Sai H. Chavala, Elizabeth L. DuBose, Cassandra J. Barnhart, Megha Karmalkar, Pooja D. Jani, Justin Goble, Debra Cantrell, Rona Lyn Esquejo, Sandeep N. Shah, Natasha Harmon, Mandeep S. Dhalla, Mario R. del Cid, Lawrence S. Halperin, Jaclyn A. Brady, Monica Hamlin, Monica L. Lopez, Jamie Mariano, Candace M. Neale, Rita R. Veksler, Angelica Mannarelli, Robert E. Coffee, Petros Euthymiou Carvounis, Pejman Hemati, Cindy J. Dorenbach, Annika S. Joshi, April Leger, Dana B. Barnett, Joseph F. Morales, Sam E. Mansour, Cathy Choyce, Aissa L. Dirawatun, Emma A. Nagy, Jamie C. Kerkstra, Joseph T. Fan, Mukesh Bhogilal Suthar, Michael E. Rauser, Gisela Santiago, Liel Marvyn Cerdenio, Brandi J. Perez, Kara E. Halsey, William H. Kiernan, Jesse Knabb, Rachel Catren, Michel Shami, Brenda K. Arrington, Keri S. Neuling, Ashaki Meeks, Natalie R. Garcia, Kayla Blair, Ginger K. Rhymes, Janet Medrano, Judy E. Kim, David V. Weinberg, Kimberly E. Stepien, Thomas B. Connor, Vesper V. Williams, Tracy L. Kaczanowski, Krissa L. Packard, Judy Flanders, Vicki Barwick, Pat A. Winter, Joseph R. Beringer, Kathy J. Selchert, John T. Lehr, Elaine Rodriguez-Roman, Teri Jones, Martha Eileen Haddox, Mark Pena, Brenda Hernandez, Clement K. Chan, Maziar Lalezary, Steven G. Lin, Kimberly S. Walther, Tiana Gonzales, Lenise E. Myers, Kenneth M. Huff, Richard Chace, Sunny Kallay, Kirsten Stevens, Nicole Dolbec, Ronda Baker-Hill, Janea Surette, Steven J. Rose, Brian P. Connolly, Ernest G. Guillet, Edward F. Hall, Margaret M. Yagoda, Mary Jo Doran, Mindy Burgess, Ann Reynard, Margaret Powers, Joe Territo, Calvin E. Mein, Moises A. Chica, R. Gary Lane, Sarah Elizabeth Holy, Lita Kirschbaum, Vanessa D. Martinez, Jaynee Baker, Christa G. Kincaid, Elaine Castillo, Christopher Sean Wienecke, Sara L. Schlichting, Brenda Nakoski, Kenneth R. Diddie, Deborah M. Cadwell, Louise Van Arsdale, Taryn F. Boisvert, Joyce Galonsky, Susie O'Hayer, Melissa L. Johnson, Frank J. McCabe, Brad J. Baker, Melvyn H. Defrin, Marie V. Lampson, Heather Pratte, Selena A. Baron, Aundrea S. Borelli, Frederick H. Davidorf, Michael B. Wells, Susie Chang, John Byron Christoforidis, Alan D. Letson, Jill A. Salerno, Jerilyn G. Perry, Stephen E. Shelley, Patrick J. Fish, Michael H. Scott, James A. Dixon, Shannon R. Walsh, Philomina M. Ozpirincci, Brenda L. Tebon, Marcia J. Moyle, Michael R. Pavlica, Noelle S. Matta, Cristina M. Brubaker, Alyson B. Backer, Neelakshi Bhagat, Catherine Fay, Tatiana Mikheyeva, Michael Lazar, Janie D. Ellenberger, Beth Malpica, Alexander J. Brucker, Benjamin J. Kim, Brian L. VanderBeek, Sheri Drossner, Joan C. DuPont, Rebecca Salvo, Stephanie B. Engelhard, Jim M. Berger, Sara Morales, Beth Serpentine, Paul L. Kaufman, Jessica D. McCluskey, Kathy T. Wynne, Julian Jordan, Brandun Watson, Robert S. Wirthlin, Eric S. Guglielmo, Eileen A. Dittman, Dylan C. Waidelich, Cristofer J. Garza, Adeline M. Stone, Ashley Nicole Oakes, Ivan J. Suner, Mark E. Hammer, Marc C. Peden, Janet R. Traynom, Rochelle DenBoer, Heidi Vargo, Susan Ramsey, Anita Kim Malzahn, Debra Jeffres, Nauman A. Chaudhry, Sumit P. Shah, Gregory M. Haffner, Emiliya German, Shannan Moreau, Laura A. Fox, Jennifer M. Matteson, JoAnna L. Pelletier, Alison Fontecchio, Emily Morse, Greg McNamara, Marie Grace Laglivia, Marissa L. Scherf, Angela LaPre, Justin A. Cocilo, Arup Das, Linda Friesen, Michele Franco, Johnny Lucero, Melissa Frazier, Robert Laviolette, Umar Khalil Mian, Rebecca L. Riemer, Evelyn Koestenblatt, Louise V. Wolf, Christine Kim, Irina Katkovskaya, Erica Otoo, Kevin A. Ellerbe, Kenneth Boyd, Caroline Costa, Paul Andrew Edwards, Hua Gao, Thomas Hessburg, Uday Desai, Janet Murphy, Mary K. Monk, Julianne Hall, Melina Mazurek, Katie M. Ventimiglia, Brian A. Rusinek, Bradley A. Stern, Kris Brouhard, Katie M. Weier, Megan Allis, Jenny Shaken, Nicole M. Massu, Tracy A. Troszak, David Burley, Abdhish R. Bhavsar, Geoffrey G. Emerson, Jacob M. Jones, Tracy A. Anderson, Andrea Gilchrist, Matt D. Peloquin, Gaid Gaid, Yang Vang, Samantha Ryan, Denise Vang, Alanna C. Evans, Tonja Scherer, Howard S. Lazarus, Debra Paige Bunch, Liana C. Davis, Kelly Booth, Margaret Trimble, Mary A. Bledsaw, Jay Moore, Daniel F. Rosberger, Sandra Groeschel, Miriam A. Madry, Nikoletta DiGirolamo, Dustin Pressley, Robert Santora, Yenelda M. Gomez, Karl R. Olsen, Robert L. Bergren, P. William Conrad, Pamela P. Rath, Avni Patel Vyas, Judy C. Liu, Lori A. Merlotti, Jennifer L. Chamberlin, Holly M. Mechling, Mary E. Kelly, Kellianne Marfisi, Kimberly A. Yeckel, Veronica L. Bennett, Christina M. Schultz, Grace A. Rigoni, Julie Walter, Missy A. Forish, Amanda Fec, Courtney L. Foreman, David Steinberg, Keith D. McBroom, Melvin C. Chen, Marc H. Levy, Waldemar Torres, Peggy Jelemensky, Tara L. Raphael, Joann Rich, Mark Sneath, James L. Kinyoun, Gurunadh Atmaram Vemulakonda, Susan A. Rath, Patricia K. Ernst, Juli A. Pettingill, Ronald C. Jones, Brad C. Clifton, James D. Leslie, Sharon D. Solomon, Lisa K. Levin, Deborah Donohue, Mary Frey, Lorena Larez, Keisha Murray, Rita L. Denbow, Janis Graul, David Emmert, Charles Herring, Nick Rhoton, Joe Belz, Alice T. Lyon, Rukhsana G. Mirza, Amanda M. Krug, Carmen Ramirez, Lori Kaminski, Anna Liza M. Castro-Malek, Amber N. Mills, Zuzanna Rozenbajgier, Marriner L. Skelly, Evica Simjanoski, Andrea R. Degillio, Jennifer I. Lim, Felix Y. Chau, Marcia Niec, Tametha Johnson, Yesenia Ovando, Mark Janowicz, Catherine Carroll, Jeffrey G. Gross, Barron C. Fishburne, Amy M. Flowers, Riley Stroman, Christen Ochieng, Angelique S.A. McDowell, Ally M. Paul, Randall L. Price, John H. Drouilhet, Erica N. Lacaden, Deborah J. Nobler, Howard L. Cummings, Deanna Jo Long, Ben McCord, Jason Robinson, Jamie Swift, Julie P. Maynard, Patricia J. Pahk, Hannah Palmer-Dwore, Dipali H. Dave, Mariebelle Pacheco, Barbara A. Galati, Eneil Simpson, Andrew J. Barkmeier, Diane L. Vogen, Karin A. Berg, Shannon L. Howard, Jean M. Burrington, Jessica Ann Morgan, Joan T. Overend, Shannon Goddard, Denise M. Lewison, Jaime L. Tesmer, Craig Michael Greven, Joan Fish, Cara Everhart, Mark D. Clark, David T. Miller, George Baker Hubbard, Jiong Yan, Blaine E. Cribbs, Linda T. Curtis, Judy L. Brower, Jannah L. Dobbs, Debora J. Jordan, Baseer U. Ahmad, Suber S. Huang, Hillary M. Sedlacek, Cherie L. Hornsby, Lisa P. Ferguson, Kathy Carlton, Kelly A. Sholtis, Peggy Allchin, Claudia Clow, Mark A. Harrod, Geoffrey Pankhurst, Irit Baum-Rawraway, Stacie A. Hrvatin, Ronald C. Gentile, Alex Yang, Wanda Carrasquillo-Boyd, Robert Masini, Chander N. Samy, Robert J. Kraut, Kathy Shirley, Linsey Corso, Karen Ely, Elizabeth Scala, Stewart Gross, Vanessa Alava, Eyal Margalit, Donna G. Neely, Maria Blaiotta, Lori Hagensen, April E. Harris, Rita L. Lennon, Denice R. Cota, Larry Wilson, Lloyd P. Aiello, Roy W. Beck, Susan B. Bressler, Kakarla V. Chalam, Ronald P. Danis, Bambi J. Arnold-Bush, Frederick Ferris, Talat Almukhtar, Brian B. Dale, Alyssa Baptista, Crystal Connor, Jasmine Conner, Sharon R. Constantine, Kimberly Dowling, Simone S. Dupre, Allison R. Ayala, Meagan L. Huggins, Seidu Inusah, Paula A. Johnson, Brenda L. Loggins, Shannon L. McClellan, Michele Melia, Eureca Battle, Cynthia R. Stockdale, Danielle Stanley, Glenn Jaffe, Brannon Balsley, Michael Barbas, Russell Burns, Dee Busian, Ryan Ebersohl, Cynthia Heydary, Sasha McEwan, Justin Myers, Amanda Robertson, Kelly Shields, Garrett Thompson, Katrina Winter, Ellen Young, Matthew D. Davis, Yijun Huang, Barbara Blodi, Amitha Domalpally, James Reimers, Pamela Vargo, Hugh Wabers, Dawn Myers, Daniel Lawrence, James Allan, Andrew Antoszyk, Scott Friedman, Ingrid U. Scott, Eleanor Schron, Donald F. Everett, Päivi H. Miskala, John Connett, Gary Abrams, Deborah R. Barnbaum, Harry Flynn, Ruth S. Weinstock, Charles P. Wilkinson, Stephen Wisniewski, Saul Genuth, Robert Frank, Frederick L. Ferris, Glenn J. Jaffe, Abdhish Bhavsar, Joseph Googe, Andreas Lauer, and Ashley McClain
Subjects: Male, Vascular Endothelial Growth Factor A, medicine.medical_specialty, Visual acuity, genetic structures, Bevacizumab, Recombinant Fusion Proteins, Visual Acuity, 030232 urology & nephrology, Angiogenesis Inhibitors, Enzyme-Linked Immunosorbent Assay, Gastroenterology, Macular Edema, Article, law.invention, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Randomized controlled trial, law, Ranibizumab, Internal medicine, medicine, Humans, Stroke, Aflibercept, Diabetic Retinopathy, business.industry, Middle Aged, medicine.disease, Confidence interval, Vascular endothelial growth factor, Ophthalmology, Receptors, Vascular Endothelial Growth Factor, Treatment Outcome, chemistry, Intravitreal Injections, Retreatment, 030221 ophthalmology & optometry, Female, medicine.symptom, business, Tomography, Optical Coherence, Follow-Up Studies, medicine.drug
Abstract: PURPOSE: Assess systemic vascular endothelial growth factor-A (VEGF) levels after treatment with intravitreous aflibercept, bevacizumab or ranibizumab. DESIGN: Comparative-effectiveness trial with participants randomly assigned to 2-mg aflibercept, 1.25-mg bevacizumab, or 0.3-mg ranibizumab following a retreatment algorithm. PARTICIPANTS: Participants with available plasma samples (N=436) METHODS: Plasma samples were collected before injections at baseline, 4-week, 52-week and 104-week visits. In a pre-planned secondary analysis, systemic free-VEGF levels from an ELISA immunoassay were compared across anti-VEGF agents and correlated with systemic side effects. MAIN OUTCOME MEASURES: Changes in the natural log (ln) of plasma VEGF levels. RESULTS: Baseline free-VEGF levels were similar across all 3 groups. At 4 weeks, mean ln(VEGF) changes were −0.30±0.61, −0.31±0.54, −0.02±0.44 pg/ml for the aflibercept, bevacizumab, and ranibizumab groups, respectively. The adjusted differences between treatment groups (adjusted CI; P-value) were −0.01 (−0.12, +0.10; P=0.89), −0.31 (−0.44, −0.18; P
Published: 2018
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10. Measurement of Perceived Stress in Age-Related Macular Degeneration

Author: Bradley E Dougherty, San-San Cooley, and Frederick H. Davidorf
Subjects: Male, medicine.medical_specialty, Visual acuity, Psychometrics, genetic structures, Visual Acuity, Vision, Low, Perceived Stress Scale, Anxiety, Article, Macular Degeneration, 03 medical and health sciences, 0302 clinical medicine, Quality of life, Sickness Impact Profile, Surveys and Questionnaires, Ophthalmology, medicine, Humans, 030212 general & internal medicine, Depression (differential diagnoses), Aged, Aged, 80 and over, Psychiatric Status Rating Scales, Rasch model, Depression, Macular degeneration, medicine.disease, humanities, eye diseases, stomatognathic diseases, Quality of Life, 030221 ophthalmology & optometry, Optometry, Female, sense organs, medicine.symptom, Psychology, Stress, Psychological
Abstract: To validate the Perceived Stress Scale (PSS) in patients with age-related macular degeneration (AMD) using Rasch analysis.Study participants with AMD were recruited from the retina service of the Department of Ophthalmology at the Ohio State University during clinical visits for treatment or observation. Visual acuity with habitual distance correction was assessed. A 10-item version of the PSS was administered in large print or by reading the items to the patient. Rasch analysis was used to investigate the measurement properties of the PSS, including fit to the model, ability to separate between people with different levels of perceived stress, category response structure performance, and unidimensionality.A total of 137 patients with a diagnosis of AMD were enrolled. The mean (±SD) age of participants was 82 ± 9 years. Fifty-four percent were female. Median Early Treatment of Diabetic Retinopathy Study (ETDRS) visual acuity of the better eye was 65 letters (Snellen 20/50), with a range of approximately 20/800 to 20/15. Forty-seven percent of participants were receiving an anti-VEGF injection on the day of the study visit. The response category structure was appropriate. One item, "How often have you felt confident in your ability to handle your personal problems?" was removed due to poor fit statistics. The remaining nine items showed good fit to the model, acceptable measurement precision as assessed by the Rasch person separation statistic, and unidimensionality. There was some evidence of differential item functioning by age and visual acuity.The Perceived Stress Scale demonstrated acceptable measurement properties and may be useful for the measurement of perceived stress in patients with AMD.
Published: 2017
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11. Hereditary predisposition to uveal melanoma

Author: Robert Pilarski, Mohamed H. Abdel-Rahman, Kavin Fatehchand, Colleen M. Cebulla, and Frederick H. Davidorf
Subjects: medicine.medical_specialty, business.industry, Melanoma, Disease, Malignancy, medicine.disease, Dermatology, Environmental risk, Cutaneous melanoma, Eye color, Etiology, Medicine, business, Green iris
Abstract: Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. Known risk factors for the risk of UM development include white race, blue/green iris eye color, older age, and some environmental risk, in particular arc welding. UM represent 3%–5% of all melanomas but it is biologically and genetically different from cutaneous melanoma. Based on the rarity of familial UM (about 1%), characterized by more than one individual with UM in the family, the contribution of genetics to the etiology of UM has been considered minimal in the traditional ophthalmology literature. However, multiple lines of evidence suggest that genetics contribute much more to the etiology of UM tumor predisposition. In the following chapter, we summarize the evidence of a genetic contribution to UM predisposition and discuss current genes suspected to be associated with the disease.
Published: 2020
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12. Contributors

Author: Mohamed H. Abdel-Rahman, Elizabeth D. Au, Milam A. Brantley, Kinga M. Bujakowska, Colleen M. Cebulla, Rui Chen, Jessica N. Cooke Bailey, Frederick H. Davidorf, Eiko K. de Jong, Anneke I. den Hollander, Rachayata Dharmat, Patty P.A. Dhooge, Michael H. Farkas, Kavin Fatehchand, John H. Fingert, Xiaoyi Raymond Gao, Maartje J. Geerlings, Jonathan L. Haines, Carel B. Hoyng, Robert P. Igo, Hacer Isildak, Tadeusz J. Kaczynski, Mariam Lotfy Khaled, Yutao Liu, Leighanne R. Main, Matthew A Miller, Matthew P. Ohr, Robert Pilarski, Emily Place, Claudio Punzo, Riccardo Sangermano, Stephen G. Schwartz, Hilary Scott, Ruifang Sui, Dyon Valkenburg, Carly J. van der Heide, Naomi Wagner, Andrea R. Waksmunski, Hui Wang, Katie Weihbrecht, and Hannah Youngblood
Published: 2020
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13. Germline large deletion ofBAP1and decreased expression in non‐tumor choroid in uveal melanoma patients with high risk for inherited cancer

Author: Frederick H. Davidorf, Robert Pilarski, Joseph P. McElroy, James B. Massengill, Timothy W. Grosel, Meredith Stautberg, Mohamed H. Abdel-Rahman, Arun D. Singh, Joanne M. Jeter, Colleen M. Cebulla, Meghan J Marino, and Getachew Boru
Subjects: Adult, Male, Uveal Neoplasms, Cancer Research, Adolescent, Biology, Article, Germline, 03 medical and health sciences, 0302 clinical medicine, Gene duplication, Genetics, medicine, Humans, RNA, Messenger, Family history, Child, Melanoma, Germ-Line Mutation, Aged, Aged, 80 and over, BAP1, Choroid, Tumor Suppressor Proteins, Infant, Cancer, Middle Aged, medicine.disease, medicine.anatomical_structure, Child, Preschool, 030220 oncology & carcinogenesis, DNA methylation, Cancer research, Female, Age of onset, Ubiquitin Thiolesterase, Gene Deletion
Abstract: Uveal melanoma (UM) is the most common phenotype in patients with germline BAP1 mutation. This study aimed to identify selection criteria for BAP1 germline testing and assessed the role of large deletion/duplication and epigenetic inactivation. One hundred seventy-two UM patients with high risk of hereditary cancer were included. Germline variants in BAP1 were assessed by direct sequencing and large deletion/duplication by multiplex ligation-dependent probe amplification. BAP1 expression in unaffected choroid tissue from a patient with UM was assessed by quantitative RT-PCR and methylation by pyrosequencing. Twenty-eight patients had one or more germline sequence variants in BAP1; seven of these were pathogenic. One hundred forty patients were assessed for large deletion/duplication and in one BAP1 whole gene deletion was detected. In total, eight patients (4.7%) had pathogenic alterations in BAP1 with the highest frequencies of in patients with a personal/family history of ≥2 BAP1-related cancers 6/16 (38%), age of onset
Published: 2019
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14. GermlineBAP1alterations in familial uveal melanoma

Author: Karan Rai, Muneeb Rehman, Ahmad H Saqr, Getachew Boru, Robert Pilarski, Colleen M. Cebulla, Arun D. Singh, Frederick H. Davidorf, James B. Massengill, Mohamed H. Abdel-Rahman, and Meghan J Marino
Subjects: 0301 basic medicine, Untranslated region, Genetics, Cancer Research, BAP1, Biology, Germline, 03 medical and health sciences, Exon, 030104 developmental biology, 0302 clinical medicine, Germline mutation, Gene duplication, 030221 ophthalmology & optometry, Multiplex ligation-dependent probe amplification, Gene
Abstract: Uveal melanoma (UM) is the most commonly diagnosed primary intraocular tumor in adults. Familial UM (FUM), defined as two or more family members diagnosed with UM, is rare and estimated at less than 1% of all UM. Currently, BAP1 is the only gene known to contribute significant risk for UM. In this study we aimed to estimate the frequency of BAP1 mutation in FUM and to characterize the family and personal histories of other cancers in these families. We identified 32 families with FUM, including seven families previously reported by our group. BAP1 mutation testing was carried out by direct sequencing of the coding exons and the adjacent untranslated regions of the gene. Germline deletion and duplication analysis of BAP1 was assessed by multiplex ligation-dependent probe amplification (MLPA). Germline BAP1 mutations were found in 6/32 (19%) families. No deletions or duplications were identified in any of the 24 samples tested by MLPA. Combined with published studies, the frequency of BAP1 mutations was 14/64 (22%) in FUM. FUM families without BAP1 mutations have distinct family histories with high rates of prostate cancer in first- and second-degree relatives. It is likely that additional genes conferring risk for FUM exist. It is important to understand key shared features of FUM to focus future research on identifying these additional tumor predisposition syndromes. Though BAP1 should be tested first in these families, FUM families without BAP1 mutation should be explored for additional predisposition genes. © 2016 Wiley Periodicals, Inc.
Published: 2016
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15. MIF promoter polymorphisms are associated with epiretinal membrane but not retinal detachment with PVR in an american population

Author: Heather Van Law, C. Ellis Wisely, Jay P. Mathias, Michael B. Wells, John B Allen, Fatoumata Yanoga, Bongsu Kim, Rania Kusibati, Robert Pilarski, William Stevenson, Elena Geraymovych, Mohd Hussain Shah, Demarcus Williams, Andrea Inman, Daniel M. Miller, Soledad Fernandez, Mohamed H. Abdel-Rahman, Tyler Heisler-Taylor, Niraj Shah, Dino D. Klisovic, Srinivas Kondapalli, Susie Chang, William Terrell, Frederick H. Davidorf, Beatrice Y. Brewington, Matthew Ohr, Colleen M. Cebulla, Sumaya Hamadmad, Ahmad B. Tarabishy, and Yildiz Vedat
Subjects: Adult, Male, medicine.medical_specialty, Genotyping Techniques, Biology, Polymerase Chain Reaction, Polymorphism, Single Nucleotide, Article, Cellular and Molecular Neuroscience, Young Adult, Ophthalmology, medicine, American population, Humans, Promoter Regions, Genetic, Macrophage Migration-Inhibitory Factors, Aged, Aged, 80 and over, Vitreoretinopathy, Proliferative, Retinal Detachment, Retinal detachment, Epiretinal Membrane, Middle Aged, medicine.disease, Sensory Systems, United States, Intramolecular Oxidoreductases, Female, Epiretinal membrane
Published: 2019

16. Comprehensive Study of the Clinical Phenotype of Germline BAP1 Variant-Carrying Families Worldwide

Author: Carla Daniela Robles-Espinoza, Hilary Racher, Luca Mastracci, Robert Pilarski, Frederick H. Davidorf, Saleem Taibjee, William Glasson, Martine J. Jager, Jo Burke, Ivana K. Kim, Lisa Golmard, Rajmohan Murali, Hayley Hamilton, Giulia Ciccarese, Jane M. Palmer, Madeleine Howlie, Arnaud de la Fouchardière, David J. Adams, Tero Kivelä, Sonika Dahiya, Peter Johansson, Lorenza Pastorino, Sebastian Walpole, Annelies de Klein, Bruna Dalmasso, Anne Marie Lane, Marina Marinkovic, William Bruno, Judith Symmons, Sonja Klebe, Julia Newton-Bishop, Marc-Henri Stern, Michael R. Speicher, Joni A. Turunen, Colleen M. Cebulla, Dominique Stoppa-Lyonnet, Carsten Bergmann, Hildur Helgadottir, Mohamed H. Abdel-Rahman, S.J. O’Shea, Meredith Stautberg, Ching-Ni Njauw, Jens Folke Kiilgaard, Pauliina Repo, Erin M. Garfield, Paola Queirolo, Rana'a T. Al-Jamal, Remco van Doorn, Antonia L. Pritchard, Gregorius P M Luyten, Michael L. Nickerson, Mitchell Cheung, Pedram Gerami, Miriam Potrony, Paola Ghiorzo, Odile Cabaret, Julian Adlard, Veronica Höiom, Hensin Tsao, Cindy Chau, J. William Harbour, Irma Dianzani, Joseph R. Testa, Brigitte Bressac-de Paillerets, Sunil K Warrier, Maartje Nielsen, Marta Betti, Susana Puig, Emine Kilic, Sandro Santagata, Karin Wadt, Nicholas K. Hayward, Virginia Andreotti, Raul Ossio, Natasha M. van Poppelen, Nicola K. Poplawski, Reetta Stiina Järvinen, Clinical Genetics, and Ophthalmology
Subjects: Male, 0301 basic medicine, Cancer Research, Genotype, Reviews, Biology, Risk Assessment, Germline, Age of Onset, Alleles, Female, Gene Frequency, Humans, Neoplastic Syndromes, Hereditary, Phenotype, Tumor Suppressor Proteins, Ubiquitin Thiolesterase, Genetic Association Studies, Genetic Predisposition to Disease, Germ-Line Mutation, Loss of heterozygosity, 03 medical and health sciences, 0302 clinical medicine, Genotype-phenotype distinction, Germline mutation, Missense mutation, Neoplastic Syndromes, Allele, BAP1, 3. Good health, Hereditary, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Cutaneous melanoma, Cancer research
Abstract: BACKGROUND: The BRCA1-associated protein-1 (BAP1) tumor predisposition syndrome (BAP1-TPDS) is a hereditary tumor syndrome caused by germline pathogenic variants in BAP1 encoding a tumor suppressor associated with uveal melanoma, mesothelioma, cutaneous melanoma, renal cell carcinoma, and cutaneous BAP1-inactivated melanocytic tumors. However, the full spectrum of tumors associated with the syndrome is yet to be determined. Improved understanding of the BAP1-TPDS is crucial for appropriate clinical management of BAP1 germline variant carriers and their families, including genetic counseling and surveillance for new tumors. METHODS: We collated germline variant status, tumor diagnoses, and information on BAP1 immunohistochemistry or loss of somatic heterozygosity on 106 published and 75 unpublished BAP1 germline variant-positive families worldwide to better characterize the genotypes and phenotypes associated with the BAP1-TPDS. Tumor spectrum and ages of onset were compared between missense and null variants. All statistical tests were two-sided. RESULTS: The 181 families carried 140 unique BAP1 germline variants. The collated data confirmed the core tumor spectrum associated with the BAP1-TPDS and showed that some families carrying missense variants can exhibit this phenotype. A variety of noncore BAP1-TPDS -associated tumors were found in families of variant carriers. Median ages of onset of core tumor types were lower in null than missense variant carriers for all tumors combined (P
Published: 2018
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17. Known and novel ocular toxicities of biologics, targeted agents, and traditional chemotherapeutics

Author: Andrew J Hendershot, Elaine M Binkley, Dimosthenis Mantopoulos, Colleen M. Cebulla, Anne L Kunkler, Matthew P Ohr, Frederick H. Davidorf, and Kari Kendra
Subjects: Adult, Male, medicine.medical_specialty, genetic structures, Side effect, Adolescent, Drug-Related Side Effects and Adverse Reactions, Eye Diseases, medicine.medical_treatment, Blepharospasm, Visual Acuity, Ipilimumab, 03 medical and health sciences, Cellular and Molecular Neuroscience, Young Adult, 0302 clinical medicine, FOLFOX, Branch retinal artery occlusion, Neoplasms, Medicine, Humans, Adverse effect, Aged, Retrospective Studies, Chemotherapy, Biological Products, business.industry, Middle Aged, medicine.disease, Dermatology, eye diseases, Sensory Systems, Ophthalmology, Docetaxel, 030220 oncology & carcinogenesis, 030221 ophthalmology & optometry, Female, sense organs, medicine.symptom, business, medicine.drug
Abstract: Increases in cancer with an aging population and the rapid development of new chemotherapeutics underscore the need for ophthalmologists to identify and manage potential ocular toxicities. This retrospective case series reports the ocular side effects of traditional and novel chemotherapeutic agents from a large center. The medical records of 3537 adult patients 18 years and older who presented to an academic ophthalmology department on high-risk medications identified by ICD-9 search between January 2010 and February 2015 were reviewed. A cancer diagnosis, as well as a temporal association with chemotherapeutic use and ocular side effect, was deemed necessary for inclusion in the study. The main measures were ocular side effects in cancer patients taking chemotherapy, ocular imaging abnormalities, and the outcome of each side effect. Of the 161 oncology patients referred to the ophthalmology clinic for chemotherapeutic screening or ocular side effect, 31 (19.3%) were identified as having an ocular adverse reaction due to a novel or traditional chemotherapeutic medication. A novel flattening of the corneal curvature with hyperopic shift and corneal microcysts was identified in a patient taking the antibody–drug conjugate mirvetuximab soravtansine and was reversible with topical steroids. A bilateral medium-vessel choroidal vasculopathy with serous retinal detachment was seen with ipilimumab. The most frequent medication with ocular toxicity was interferon-α(2b) (IFN-α(2b)) (6/31, 19.4%); headache was typical in these patients (83.3%). Ibrutinib ocular toxicity was second most common (5/31, 16.1%), usually causing red or dry eye, while one patient developed branch retinal artery occlusion. Retinal abnormalities documented on OCT imaging occurred with IFN-α(2b), ipilimumab, binimetinib, and docetaxel, while rod-cone ERG abnormality was seen with cisplatin. Inflammatory conditions included anterior scleritis with zoledronic acid, focal eyelid inflammation with veliparib, bilateral chemosis with R-CHOP, iritis, and blepharospasm with IFN-α(2b). AION occurred with pemetrexed, and transient vision loss with hyperemic disc OS was seen with FOLFOX. Two patients (2/31, 6.5%) developed permanent vision loss. Six patients were lost to follow-up, and the clinical course was unknown (6/31, 19.4%). Cases of permanent visual loss were observed; yet, in the majority of side effects, they improved with topical therapy and/or holding the medication. Further research is needed to elucidate the incidence and the pathophysiology of these side effects and maximize patient quality of life.
Published: 2018

18. Brachytherapy for patients with uveal melanoma: historical perspectives and future treatment directions

Author: Yusra F Shao, Beatrice Y. Brewington, Frederick H. Davidorf, and Colleen M. Cebulla
Subjects: medicine.medical_specialty, molecular markers, genetic prognostic testing, medicine.medical_treatment, Enucleation, Brachytherapy, Ocular Melanoma, brachytherapy, Review, 03 medical and health sciences, 0302 clinical medicine, Ophthalmology, Biopsy, medicine, fine-needle-aspiration biopsy, medicine.diagnostic_test, business.industry, UM, Melanoma, medicine.disease, eye diseases, 3. Good health, Radiation therapy, 030220 oncology & carcinogenesis, 030221 ophthalmology & optometry, Primary treatment, Radiology, uveal melanoma, business
Abstract: Surgical management with enucleation was the primary treatment for uveal melanoma (UM) for over 100 years. The Collaborative Ocular Melanoma Study confirmed in 2001 that globe-preserving episcleral brachytherapy for UM was safe and effective, demonstrating no survival difference with enucleation. Today, brachytherapy is the most common form of radiotherapy for UM. We review the history of brachytherapy in the treatment of UM and the evolution of the procedure to incorporate fine-needle-aspiration biopsy techniques with DNA-and RNA-based genetic prognostic testing.
Published: 2018

19. Endogenous endophthalmitis and osteomyelitis associated with interleukin 17 inhibitor treatment for psoriasis in a patient with diabetes

Author: John B Allen, Frederick H. Davidorf, Christine E. Martinez, and Colleen M. Cebulla
Subjects: Male, Methicillin-Resistant Staphylococcus aureus, medicine.medical_specialty, genetic structures, Pain, Vision, Low, Bacteremia, medicine.disease_cause, Antibodies, Monoclonal, Humanized, Eye, Eye Infections, Bacterial, Article, Diabetes Complications, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Endophthalmitis, Psoriasis, Diabetes mellitus, medicine, Humans, Immunologic Factors, business.industry, Osteomyelitis, Interleukin-17, Type 2 Diabetes Mellitus, Antibodies, Monoclonal, General Medicine, Middle Aged, Staphylococcal Infections, medicine.disease, Dermatology, Surgery, Anti-Bacterial Agents, Diabetes Mellitus, Type 2, Staphylococcus aureus, 030221 ophthalmology & optometry, Secukinumab, Interleukin 17, business
Abstract: A 64-year-old man with type 2 diabetes mellitus and plaque psoriasis presented to the emergency room with 3 days of progressive right eye pain and decreased vision. After extensive workup and multidisciplinary team effort, the patient was diagnosed with and treated for unilateral endogenous methicillin-sensitive Staphylococcus aureus endophthalmitis, bacteraemia and osteomyelitis of the foot. The patient had been started on the interleukin 17 (IL-17) inhibitor secukinumab for his treatment-resistant plaque psoriasis 4 weeks prior to presentation. After treatment, his final vision was light perception and the foot infection resolved without sequelae. To our knowledge, this is the first reported case of both endogenous endophthalmitis and osteomyelitis associated with an IL-17 inhibitor.
Published: 2017

20. SOCIOECONOMIC STATUS AND MISSED CLINICAL APPOINTMENTS IN AGE-RELATED MACULAR DEGENERATION

Author: San-San Cooley, Bradley E Dougherty, Rebecca A Deffler, and Frederick H. Davidorf
Subjects: Gerontology, Health (social science), genetic structures, business.industry, Macular degeneration, medicine.disease, Health Professions (miscellaneous), eye diseases, Abstracts, Age related, Medicine, Life-span and Life-course Studies, business, Socioeconomic status
Abstract: Age-related macular degeneration (AMD) is a leading cause of blindness in older adults. We have previously found that socioeconomic status (SES), as represented by educational achievement, is inversely related to visual acuity in people being treated for AMD. The purpose of this study was to evaluate possible mechanisms for this relationship in patients with AMD, specifically attendance at scheduled clinical appointments with a retina specialist, access to transportation, and having had a low vision rehabilitation examination. Methods: Visual acuity with habitual correction was measured via ETDRS chart with letter-by-letter scoring. SES was represented as highest level of education. Visual function and social support scales were administered and scored using Rasch analysis. ANOVA and Fisher’s Exact Tests were used to examine the relationships among SES, VA, and clinical and transportation variables. Results: 42 people with AMD (37% female, mean±SD age of 77 ± 10 years) were recruited from The Ohio State University retina service. 54% of subjects missed at least one appointment that was not rescheduled within a month. Missed clinical appointments were more common among low SES groups (p=0.42). Having missed an appointment was associated with older age (p=0.032) and worse self-reported visual function (p=0.029). Only 7% of subjects reported difficulty finding transportation to appointments. Conclusion: Lower SES was related to an increased likelihood of missed appointments in people with AMD, as well as poorer visual functioning. Attendance at clinical appointments may be a factor in explaining the relationship between lower SES and poor vision in people with age-related macular degeneration.
Published: 2018
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21. Significant upregulation of small heat shock protein αA-crystallin in retinal detachment

Author: Sumaya Hamadmad, Mohd Hussain Shah, Rania Kusibati, Bongsu Kim, Brandon Erickson, Tyler Heisler-Taylor, Sanjoy K. Bhattacharya, Mohamed H. Abdel-Rahman, Colleen M. Cebulla, Heather Van Law, Frederick H. Davidorf, Matthew Ohr, Michael Wells, Fatoumata Yanoga, Susie Chang, William Terrell, Daniel M. Miller, Dino Klisovic, John B. Allen, Niraj Shah, Elena Geraymovych, Ahmad B. Tarabishy, Srinivas S. Kondapalli, Beatrice Y. Brewington, Andrea Inman, Demarcus Williams, Jay Mathias, C. Ellis Wisely, and Robert Pilarski
Subjects: Male, Blotting, Western, alpha-Crystallin A Chain, Article, Retina, Mice, Cellular and Molecular Neuroscience, Downregulation and upregulation, Crystallin, Heat shock protein, medicine, Animals, Humans, Aged, Aged, 80 and over, Regulation of gene expression, Extramural, Chemistry, Retinal Detachment, Retinal detachment, Middle Aged, medicine.disease, Immunohistochemistry, Sensory Systems, Heat-Shock Proteins, Small, Up-Regulation, Cell biology, Blot, Ophthalmology, Gene Expression Regulation, RNA, Female
Published: 2019
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22. Expanding the clinical phenotype of hereditaryBAP1cancer predisposition syndrome, reporting three new cases

Author: Frederick H. Davidorf, Mary Jill Asrat, Louise C. Strong, James B. Massengill, Mohamed H. Abdel-Rahman, Colleen M. Cebulla, Karan Rai, Thereasa A. Rich, Barbara Mcgillivray, and Robert Pilarski
Subjects: Oncology, Cancer Research, medicine.medical_specialty, BAP1, Candidate gene, Biology, medicine.disease, Germline, Germline mutation, Renal cell carcinoma, Internal medicine, Immunology, Genetics, Carcinoma, medicine, Mesothelioma, Family history, neoplasms
Abstract: The clinical phenotype of BAP1 hereditary cancer predisposition syndrome (MIM 614327) includes uveal melanoma (UM), cutaneous melanoma (CM), renal cell carcinoma (RCC), and mesothelioma. However, the frequency of the syndrome in patients with UM and the association with other cancers are still not clear. In this study, we screened 46 previously untested, unrelated UM patients with high risk for hereditary cancer for germline mutation in BAP1. We also studied four additional patients with a personal or family history suggestive of BAP1 hereditary cancer syndrome. We identified three patients with germline pathogenic mutations (c.2050 C>T, pGln684*; c.1182C>G, p.Tyr394*, and c.1882_1885delTCAC, p. Ser628Profs*8) in BAP1. Two of these three patients presented with UM and the third with a metastatic adenocarcinoma likely from a hepatic cholangiocarcinoma. Reported family histories included UM, mesothelioma, RCC, CM, and several other internal malignancies. The results of this study confirm the association between germline BAP1 mutation and predisposition to UM, mesothelioma, CM and RCC. However, other cancers, such as cholangiocarcinoma and breast carcinoma may be part of the phenotype of this hereditary cancer predisposition syndrome. In addition, the results support the existence of other candidate genes in addition to BAP1 contributing to hereditary predisposition to UM.
Published: 2013
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23. Dynamic Contrast-Enhanced Magnetic Resonance Imaging of Ocular Melanoma as a Tool to Predict Metastatic Potential

Author: Guang Jia, Hendrik von Tengg-Kobligk, Michael V. Knopp, Johannes T. Heverhagen, John B. Christoforidis, Mohamed H. Abdel-Rahman, Frederick H. Davidorf, Lai Wei, and Wenbo Wei
Subjects: Choroidal melanoma, Gadolinium DTPA, Male, Pathology, medicine.medical_specialty, Ocular Melanoma, Contrast Media, 610 Medicine & health, 030218 nuclear medicine & medical imaging, Metastasis, Diagnosis, Differential, 03 medical and health sciences, 0302 clinical medicine, Blood plasma, medicine, Humans, Radiology, Nuclear Medicine and imaging, Neoplasm Metastasis, Melanoma, Aged, medicine.diagnostic_test, business.industry, Choroid Neoplasms, Magnetic resonance imaging, Histology, medicine.disease, Image Enhancement, Magnetic Resonance Imaging, Dynamic contrast, 030221 ophthalmology & optometry, Female, business, Nuclear medicine, Preclinical imaging
Abstract: PURPOSE This study explores the capability of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to differentiate tumor characteristics of metastatic and nonmetastatic choroidal melanoma as a potential tool for patient management. MATERIALS AND METHODS A total of 13 patients (69 ± 9 years) with choroidal melanoma were imaged using DCE-MRI on a 3-T MRI system with a 16-channel head coil. The Tofts 2-compartment model was chosen for quantification, and parameters K (the transfer constant from the blood plasma to the extracellular space) and Kep (the transfer constant from the extracellular space to the blood plasma) were calculated and compared. Metastasis was excluded by subsequent clinical work-up or confirmed by histology after targeted biopsy. RESULTS Six patients were diagnosed with metastatic melanoma and 7 without. All orbital tumors were at least larger than 2 mm. A significant difference was identified in K between patients with (0.73 ± 0.18/min) and without (1.00 ± 0.21/min) metastatic melanoma (P = 0.03), whereas the difference was not significantly shown in Kep (2.58 ± 1.54/min of metastatic patients vs 2.98 ± 1.83/min of nonmetastatic patients, P = 0.67). CONCLUSIONS Dynamic contrast-enhanced magnetic resonance imaging has the potential to differentiate orbital melanomas with metastatic and nonmetastatic spread. Thus, DCE-MRI has the potential to be an in vivo imaging technique to predict early which patients are prone to metastatic disease.
Published: 2017
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24. Genetic markers of pigmentation are novel risk loci for uveal melanoma

Author: Matjaz Vogelsang, Justin Rendleman, Khagay Nagdimov, Karan Rai, Mohamed H. Abdel-Rahman, Tomas Kirchhoff, Esther Kazlow, Iman Osman, Robert Ferguson, Frederick H. Davidorf, Robert Pilarski, Esma Ucisik-Akkaya, Carlos N Martinez, Robert J. Klein, and Colleen M. Cebulla
Subjects: Adult, Male, Uveal Neoplasms, 0301 basic medicine, Adolescent, Population, Single-nucleotide polymorphism, Genome-wide association study, Biology, Polymorphism, Single Nucleotide, Article, 03 medical and health sciences, Risk Factors, Biomarkers, Tumor, Eye color, Genetic predisposition, Humans, education, Melanoma, Aged, Genetic association, Aged, 80 and over, Genetics, education.field_of_study, Multidisciplinary, Pigmentation, Middle Aged, 030104 developmental biology, Genetic Loci, Genetic marker, Cutaneous melanoma, Female, Genome-Wide Association Study
Abstract: While the role of genetic risk factors in the etiology of uveal melanoma (UM) has been strongly suggested, the genetic susceptibility to UM is currently vastly unexplored. Due to shared epidemiological risk factors between cutaneous melanoma (CM) and UM, in this study we have selected 28 SNPs identified as risk variants in previous genome-wide association studies on CM or CM-related host phenotypes (such as pigmentation and eye color) and tested them for association with UM risk. By logistic regression analysis of 272 UM cases and 1782 controls using an additive model, we identified five variants significantly associated with UM risk, all passing adjustment for multiple testing. The three most significantly associated variants rs12913832 (OR = 0.529, 95% CI 0.415–0.673; p = 8.47E-08), rs1129038 (OR = 0.533, 95% CI 0.419–0.678; p = 1.19E-07) and rs916977 (OR = 0.465, 95% CI 0.339–0.637; p = 3.04E-07) are correlated (r2 > 0.5) and map at 15q12 in the region of HERC2/OCA2, which determines eye-color in the human population. Our data provides first evidence that the genetic factors associated with pigmentation traits are risk loci of UM susceptibility.
Published: 2016
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25. Germline BAP1 alterations in familial uveal melanoma

Author: Karan, Rai, Robert, Pilarski, Getachew, Boru, Muneeb, Rehman, Ahmad H, Saqr, James B, Massengill, Arun, Singh, Meghan J, Marino, Frederick H, Davidorf, Colleen M, Cebulla, and Mohamed, H Abdel-Rahman
Subjects: Adult, Male, Uveal Neoplasms, Adolescent, Tumor Suppressor Proteins, Middle Aged, Prognosis, Article, Pedigree, Young Adult, Biomarkers, Tumor, Humans, Female, Genetic Predisposition to Disease, Melanoma, Ubiquitin Thiolesterase, Germ-Line Mutation, Aged, Follow-Up Studies, Neoplasm Staging
Abstract: Uveal melanoma (UM) is the most commonly diagnosed primary intraocular tumor in adults. Familial UM (FUM), defined as two or more family members diagnosed with UM, is rare and estimated at less than 1% of all UM. Currently, BAP1 is the only gene known to contribute significant risk for UM. In this study we aimed to estimate the frequency of BAP1 mutation in FUM and to characterize the family and personal histories of other cancers in these families. We identified 32 families with FUM, including seven families previously reported by our group. BAP1 mutation testing was carried out by direct sequencing of the coding exons and the adjacent untranslated regions of the gene. Germline deletion and duplication analysis of BAP1 was assessed by multiplex ligation-dependent probe amplification (MLPA). Germline BAP1 mutations were found in 6/32 (19%) families. No deletions or duplications were identified in any of the 24 samples tested by MLPA. Combined with published studies, the frequency of BAP1 mutations was 14/64 (22%) in FUM. FUM families without BAP1 mutations have distinct family histories with high rates of prostate cancer in first- and second-degree relatives. It is likely that additional genes conferring risk for FUM exist. It is important to understand key shared features of FUM to focus future research on identifying these additional tumor predisposition syndromes. Though BAP1 should be tested first in these families, FUM families without BAP1 mutation should be explored for additional predisposition genes. © 2016 Wiley Periodicals, Inc.
Published: 2016

26. Monosomy 3 status of uveal melanoma metastases is associated with rapidly progressive tumors and short survival

Author: Colleen M. Cebulla, William E. Carson, Vishal Verma, Benjamin N. Christopher, Frederick H. Davidorf, Mohamed H. Abdel-Rahman, and Thomas Olencki
Subjects: Adult, Male, Uveal Neoplasms, Monosomy, Pathology, medicine.medical_specialty, Lung Neoplasms, Genotype, DNA Mutational Analysis, Biology, Eye neoplasm, Article, Cellular and Molecular Neuroscience, medicine, Humans, Codon, Melanoma, Molecular Biology, Survival rate, Aged, BAP1, GNA11, Liver Neoplasms, DNA, Neoplasm, Middle Aged, medicine.disease, GTP-Binding Protein alpha Subunits, Sensory Systems, Survival Rate, Ophthalmology, Disease Progression, GTP-Binding Protein alpha Subunits, Gq-G11, Female, Chromosomes, Human, Pair 3, Polymorphism, Restriction Fragment Length, Progressive disease, GNAQ, Microsatellite Repeats
Abstract: The aim of the study was to investigate the molecular genetics of uveal melanoma (UM) metastases and correlate it with disease progression. Twelve pathologically confirmed UM metastases from 11 patients were included. Molecular genetic alterations in chromosomes 3 (including the BAP1 region), 8q, 6p, and 1p were investigated by microsatellite genotyping. Mutations in codon 209 of GNAQ and GNA11 genes were studied by restriction-fragment length polymorphism (RFLP). We identified monosomy of chromosome 3 in tumors from four patients with an average survival of 5 months (range 1-8 months) from time of diagnosis of metastatic disease. In contrast, tumors with either disomy or partial chromosome 3 alterations showed significantly slower metastatic disease progression with an average survival of 69 months (range 40-123 months, p = 0.003). Alterations in chromosomal arms 1p, 6p, and 8q and mutations in either GNAQ or GNA11 showed no association with disease progression. Prominent mononuclear inflammatory infiltrate was observed in tumors from patients with slowly progressive disease. In conclusion, in UM metastases, monosomy 3 is associated with highly aggressive, rapidly progressive disease while disomy or partial change of 3 and prominent mononuclear inflammatory infiltrate in the tumor is associated with better prognosis. These findings should be considered when designing clinical trials testing effectiveness of various therapies of metastatic UM.
Published: 2012
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27. Long-Term Survivors with Metastatic Uveal Melanoma

Author: Mohamed H. Abdel-Rahman, Dominic M. Buzzacco, Frederick H. Davidorf, Thomas Olencki, Colleen M. Cebulla, and Stanley Park
Subjects: Sorafenib, medicine.medical_specialty, Tumor, Isolated hepatic perfusion, Sunitinib, business.industry, medicine.medical_treatment, Melanoma, Brachytherapy, Enucleation, medicine.disease, Primary tumor, Article, transpupillary thermal therapy and chemotherapy, Surgery, Metastasis, Ophthalmology, medicine, metastasis, alanine transaminase, Radiology, uveal melanoma, business, medicine.drug
Abstract: Background: To report the tumor, patient, and treatment characteristics of long-term metastatic uveal melanoma survivors. Methods: A non-comparative, retrospective case series of patients from a single institution surviving >24 months with metastatic uveal melanoma (UM). Results: Nine patients met the study criteria and their charts were reviewed. The mean age at diagnosis of UM was 44.1 years (SD +/- 14.4 years). Initial treatment modalities included enucleation (67%), brachytherapy (22%), and proton beam radiation (11%). The average time from primary tumor diagnosis to detection of metastasis was 125.9 months (SD +/- 95 months). The most common location for initial metastasis was the liver. All patients underwent treatment for metastatic disease including systemic therapy, surgical resection, and isolated hepatic perfusion. The majority of patients received treatment with a tyrosine kinase inhibitor (sorafenib, sunitinib, and/or imatinib). The median survival with metastasis was 51 months (range 27-123 months). Patients had a long disease-free interval before presentation of metastatic disease. Conclusions: A small subset of patients with metastatic UM has prolonged survival. Identification of these patients may be helpful for future clinical trial design.
Published: 2012
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28. Comparison of 16 mm OSU-Nag and COMS eye plaques

Author: Frederick H. Davidorf, Yujin Qi, and Hualin Zhang
Subjects: 131 Cs, genetic structures, medicine.medical_treatment, Brachytherapy, Dose distribution, Iodine Radioisotopes, Comparable size, medicine, Radiation Oncology Physics, Humans, Radiology, Nuclear Medicine and imaging, OSU‐NAG eye plaque, Melanoma, Instrumentation, Radiation, COMS eye plaque, business.industry, Eye Neoplasms, Radiotherapy Planning, Computer-Assisted, Plaque brachytherapy, 125 I, Silastic, eye diseases, Sclera, medicine.anatomical_structure, Cesium Radioisotopes, sense organs, Nuclear medicine, business, Monte Carlo Method
Abstract: OSU‐NAG eye plaques use fewer sources than COMS‐plaques of comparable size, and do not employ a Silastic seed carrier insert. Monte Carlo modeling was used to calculate 3D dose distributions for a 16 mm OSU‐NAG eye plaque and a 16 mm COMS eye plaque loaded with either Iodine‐125 or Cesium‐131 brachytherapy sources. The OSU‐NAG eye plaque was loaded with eight sources forming two squares, whereas the COMS eye plaque was loaded with thirteen sources approximating three isocentric circles. A spherical eyeball 24.6 mm in diameter and an ellipsoid‐like tumor 6 mm in height and 12 mm in the major and minor axes were used to evaluate the doses delivered. To establish a fair comparison, a water seed carrier was used instead of the Silastic seed carrier designed for the traditional COMS eye plaque. Calculations were performed on the dose distributions along the eye plaque axis and the DVHs of the tumor, as well as the 3D distribution. Our results indicated that, to achieve a prescription dose of 85 Gy at 6 mm from the inner sclera edge for a six‐day treatment, the OSU‐NAG eye plaque will need 6.16 U/source and 6.82 U/source for 125I and 131Cs, respectively. The COMS eye plaque will require 4.02 U/source and 4.43 U/source for the same source types. The dose profiles of the two types of eye plaques on their central axes are within 9% difference for all applicable distances. The OSU‐NAG plaque delivers about 10% and 12% more dose than the COMS for 125I and 131Cs sources, respectively, at the inner sclera edge, but 6% and 3% less dose at the opposite retina. The DVHs of the tumor for two types of plaques were within 6% difference. In conclusion, the dosimetric quality of the OSU‐NAG eye plaque used in eye plaque brachytherapy is comparable to the COMS eye plaque. PACS number: 87.56B, 87.55k, 87.55kh
Published: 2012
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29. In vitro anti-uveal melanoma activity of phenolic compounds from the Egyptian medicinal plant Acacia nilotica

Author: Mohamed H. Abdel-Rahman, Manar M. Salem, and Frederick H. Davidorf
Subjects: Uveal Neoplasms, Uterine Cervical Neoplasms, Biology, Catechin, Retina, law.invention, chemistry.chemical_compound, Phenols, law, Cell Line, Tumor, Drug Discovery, Digallic acid, Humans, Gallocatechin, Gallic acid, Methyl gallate, Melanoma, Pharmacology, Plants, Medicinal, Molecular Structure, Plant Extracts, Acacia, General Medicine, Antineoplastic Agents, Phytogenic, chemistry, Biochemistry, Polyphenol, Fruit, Cutaneous melanoma, Egypt, Female, sense organs, Glioblastoma, Phytotherapy
Abstract: Anti-uveal melanoma activity-guided fractionation of the MeOH extract of Acacia nilotica pods resulted in the isolation of the new compound gallocatechin 5-O-gallate in addition to methyl gallate, gallic acid, catechin, catechin 5-O-gallate, 1-O-galloyl-β-D-glucose, 1,6-di-O-galloyl-β-D-glucose and digallic acid. The structures of the isolated compounds were elucidated on the basis of HRESIMS, NMR spectroscopy and CD data. In addition to uveal melanoma, the antiproliferative activities of the isolated compounds and the related compound epigallocatechin 3-O-gallate (EGCG) were evaluated against cutaneous melanoma, ovarian cancer, glioblastoma and normal retinal pigmented cells.
Published: 2011
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30. Molecular genetic testing of uveal melanoma from routinely processed and stained cytology specimens

Author: Benjamin N. Christopher, Paul E. Wakely, Mohamed H. Abdel-Rahman, Frederick H. Davidorf, and Colleen M. Cebulla
Subjects: Uveal Neoplasms, Pathology, medicine.medical_specialty, Genotype, Genotyping Techniques, DNA Mutational Analysis, Biology, Article, Cellular and Molecular Neuroscience, Tumor Cells, Cultured, medicine, Humans, Melanoma, Genotyping, Histocytological Preparation Techniques, GNA11, DNA, Neoplasm, DNA extraction, Molecular biology, GTP-Binding Protein alpha Subunits, Sensory Systems, Ophthalmology, Molecular Diagnostic Techniques, Feasibility Studies, GTP-Binding Protein alpha Subunits, Gq-G11, Microsatellite, Chromosomes, Human, Pair 6, Chromosomes, Human, Pair 3, Restriction fragment length polymorphism, Polymorphism, Restriction Fragment Length, GNAQ, Chromosomes, Human, Pair 8, Microsatellite Repeats
Abstract: In the following study we investigated the utility of molecular genetic testing of the DNA extracted from routinely stained and processed smears from uveal melanoma (UM). Smears from five uveal melanoma cell lines and 12 primary tumors were prepared and stained with Papanicolaou and Romanowsky stains. Genotyping was carried out utilizing 14 microsatellite markers on chromosomes 3, 6 and 8. Mutational screening for alterations in GNAQ and GNA11 genes was carried out by restriction fragment length polymorphism. The results were compared to those obtained through direct sequencing of frozen tumor tissues. High quality DNA was extracted from the stained slides with no difference in the efficiency of DNA extraction between the two staining techniques. The extracted DNA was of adequate quality for genotyping and mutational screening. DNA extracted from approximately 200 tumor cells is sufficient for reproducible testing of allelic imbalances and for studying the common somatic mutations in GNAQ and GNA11 genes. In conclusion, we presented the feasibility of utilizing routinely stained cytology smears from UM for molecular genetic testing. The DNA obtained is of sufficient quality to carry out genotyping for markers on chromosome 3, 6 and 8, as well as screening for somatic mutations in GNAQ and GNA11 genes.
Published: 2011
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31. Frequency, molecular pathology and potential clinical significance of partial chromosome 3 aberrations in uveal melanoma

Author: Mohammed F. Faramawi, Abhik Ray-Chaudhury, Nyla A. Heerema, Carol Cole, Khaled Said-Ahmed, Andrew McFaddin, Benjamin N. Christopher, Frederick H. Davidorf, and Mohamed H. Abdel-Rahman
Subjects: Adult, Male, Uveal Neoplasms, Pathology, medicine.medical_specialty, Monosomy, Genotype, Uveal Neoplasm, Kaplan-Meier Estimate, Biology, Polymerase Chain Reaction, Article, Pathology and Forensic Medicine, History, 17th Century, Loss of heterozygosity, medicine, Humans, Neoplasm Invasiveness, Melanoma, Aged, Aged, 80 and over, Chromosome Aberrations, Comparative Genomic Hybridization, Cytogenetics, Karyotype, medicine.disease, Chromosome 3, Karyotyping, Female, Chromosomes, Human, Pair 3, Comparative genomic hybridization
Abstract: The clinical significance of partial chromosome 3 alteration in uveal melanoma is still not clear. Also, the reported frequencies vary considerably in the published literature from 0 to 48%. The aims of the following study were to identify the frequency, molecular pathology and potential clinical significance of partial chromosome 3 alteration in uveal melanoma. We studied 47 uveal melanomas with an average follow-up of 36 months. Of these, 14 had confirmed metastasis. Allelic imbalance/loss of heterozygosity was studied using microsatellite markers on chromosome 3 enriched in markers located in the previously reported smallest regions of deletion overlap. Chromosomal alterations were assessed by conventional cytogenetics or comparative genomic hybridization (CGH) in a subset of patients. Utilizing genotyping, partial chromosome 3 alteration was detected in 14/47 tumors (30%). In the 23 tumors with available cytogenetic/CGH, partial chromosome 3 alteration was detected in 8/23 (38%) and was caused by both gains (4/8) and losses (4/8) of chromosome 3 with high frequency of complex chromosome 3 aberrations detected by cytogenetics. Out of the 14 tumors with confirmed metastasis, only 1 showed partial chromosome 3 alteration and the remaining showed monosomy 3. By limiting the aggressive disease marker to monosomy 3, genotyping showed 93% sensitivity and 67% specificity for detection of aggressive uveal melanoma. In conclusion, partial chromosome 3 alterations are common in uveal melanoma and mostly caused by complex cytogenetic changes leading to partial gains and/or partial losses of chromosome 3. Partial chromosome 3 alteration is not likely to be associated with highly aggressive uveal melanoma that metastasizes within the first 3 years after treatment. Microsatellite-based genotyping of chromosome 3 is highly sensitive for detection of aggressive uveal melanoma.
Published: 2011
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32. Melanoma candidate genes CDKN2A/p16/INK4A, p14ARF, and CDK4 sequencing in patients with uveal melanoma with relative high-risk for hereditary cancer predisposition

Author: James B. Massengill, Benjamin N. Christopher, Mohamed H. Abdel-Rahman, Frederick H. Davidorf, Ryan Noss, and Robert Pilarski
Subjects: Adult, Male, Uveal Neoplasms, Cancer Research, Candidate gene, Dermatology, Germline, Exon, Germline mutation, CDKN2A, Tumor Suppressor Protein p14ARF, medicine, Humans, Genetic Predisposition to Disease, Family history, Melanoma, Cyclin-Dependent Kinase Inhibitor p16, Germ-Line Mutation, Aged, Aged, 80 and over, business.industry, Genes, p16, Cyclin-Dependent Kinase 4, Middle Aged, medicine.disease, Oncology, Cutaneous melanoma, Cancer research, Female, business, Polymorphism, Restriction Fragment Length
Abstract: The reported frequencies of germline mutations in the melanoma candidate genes are low in patients with uveal melanoma (UM). However, the number of families studied is limited and the majority of the published reports used low-sensitivity techniques for mutational screening. Identifying the frequency of alterations in any of the melanoma genes in patients with UM with increased hereditary cancer risk is important for proper counseling of these patients. We studied a total of 47 patients with UM including three with a family history of UM, 18 with a family and/or personal history of cutaneous melanoma (CM), three with early age at diagnosis (30), 11 with increased risk for a known familial cancer syndrome, and 12 with a second primary tumor. Germline screening for mutations in CDKN2A, p14ARF, and exon 2 of CDK4 was carried out by direct sequencing. We identified a variant (IVS1-69 CT) of uncertain significance in exon 1b of p14ARF in one of the patients with UM and his mother who also had UM. The variant was neither detected in any of the other patients with UM nor in 146 controls. We did not identify pathogenic mutations in CDKN2A nor exon 2 of CDK4 gene. Our study supports the low frequency of germline mutation of the CM candidate genes in patients with UM with family histories suggestive of a high risk for hereditary cancer. Germline testing for CDKN2A might be reserved for patients with UM with a family history of two or more CM.
Published: 2011
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33. Investigation of the potential utility of a linomide analogue for treatment of choroidal neovascularization

Author: Yong Yang, P.-K. Li, James B. Massengill, Frederick H. Davidorf, Mohamed H. Abdel-Rahman, S. Meadows, and M.M. Salem
Subjects: Male, Vascular Endothelial Growth Factor A, Umbilical Veins, medicine.medical_treatment, Blotting, Western, Angiogenesis Inhibitors, Retinal Pigment Epithelium, Quinolones, Umbilical vein, Cellular and Molecular Neuroscience, chemistry.chemical_compound, Epidermal growth factor, Rats, Inbred BN, medicine, Animals, Humans, Fluorescein Angiography, Phosphorylation, Cells, Cultured, Cell Proliferation, Mitogen-Activated Protein Kinase 1, Platelet-Derived Growth Factor, Mitogen-Activated Protein Kinase 3, biology, Reverse Transcriptase Polymerase Chain Reaction, Growth factor, Vascular Endothelial Growth Factor Receptor-2, Choroidal Neovascularization, Sensory Systems, Rats, Vascular endothelial growth factor, Endothelial stem cell, Disease Models, Animal, Ophthalmology, Choroidal neovascularization, chemistry, Immunology, Cancer research, Systemic administration, biology.protein, Fibroblast Growth Factor 2, Endothelium, Vascular, medicine.symptom, Platelet-derived growth factor receptor
Abstract: The aim of this study was to test the selectivity, in-vivo effectiveness, and potential mechanism of action of a linomide analogue (N-phenyl-1,2-dihydro-4-hydroxyl-2-oxo-quinoline-3-carboxamide, Lin05) for inhibition of choroidal neovascularization. The selectivity of Lin05 was tested in cell proliferation assays with human umbilical vein endothelial cells (HUVEC) and a retinal pigmented epithelial cell line(ARPE-19). In-vivo anti-angiogenic effect of Lin05 was investigated utilizing an experimental laser-induced choroidal neovascularization (ECNV) model in adult Brown Norway rats. Western blot and/or reverse transcriptase-PCR was used to test the effect of Lin05 on potential targets. Our results indicate that Lin05 is at least an 8-fold more selective inhibitor of endothelial cell proliferation compared to RPE cells. Systemic administration of Lin05 in an ECNV model was associated with a significant decrease in both vascular leakage on fluorescein angiography and lesion size by histopathology (p = 0.02). No systemic toxicity was detected for Lin05 in major organs such as the liver, lung and kidneys. Lin05 did not inhibit VEGF-induced VEGFR2 (KDR) phosphorylation in HUVEC nor was associated with decreased VEGF gene expression. Also it did not inhibit insulin-like growth factor (IGF-1) and Epidermal Growth Factor (EGF) induced activation of p42/p44 MAPK activation. It inhibited both PDGF- and bFGF-induced p42/p44 MAPK phosphorylation. However, the effect on PDGF was variable in different HUVEC cells. In conclusion, Lin05 is a potential anti-angiogenic agent for the treatment of eye diseases associated with pathological neovascularization. The anti-angiogenic effect of Lin05 is likely through inhibition of bFGF but not through inhibition of the VEGF/KDR pathway.
Published: 2010
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34. Germline BAP1 mutations misreported as somatic based on tumor-only testing

Author: Robert Pilarski, Mohamed H. Abdel-Rahman, Karan Rai, Colleen M. Cebulla, and Frederick H. Davidorf
Subjects: 0301 basic medicine, Male, Uveal Neoplasms, Cancer Research, Somatic cell, Genetic counseling, Germline mosaicism, Breast Neoplasms, Biology, Germline, Article, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Germline mutation, Genetics, medicine, Humans, Genetic Predisposition to Disease, Melanoma, Genetics (clinical), Germ-Line Mutation, BAP1, Tumor Suppressor Proteins, Cancer, DNA, Neoplasm, Middle Aged, medicine.disease, Pedigree, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Female, Ubiquitin Thiolesterase
Abstract: We present three unrelated patients with germline mutations in BAP1 misreported as somatic mutations. All had strong family histories of cancer. One of these patients presented with an invasive breast cancer with the tumor tissue showing partial loss of the mutant rather than the wild type allele, suggesting that the germline BAP1 mutation didn't contribute to breast cancer development in this patient. This data highlights the importance of sequencing matching germline and tumor DNA for proper assessment of somatic versus germline mutation status. In patients with somatic mutations reported from laboratories carrying out tumor-only genomic testing, the possibility that a variant may be a germline mutation should be considered, especially if the personal and/or family history suggests hereditary cancer predisposition. Since tumor-only testing can reveal germline mutations, ethical issues for patients being tested should be considered including proper consent and genetic counseling.
Published: 2016

35. Subretinal Hyperreflective Material in the Comparison of Age-Related Macular Degeneration Treatments Trials

Author: Alex S. Willoughby, Gui-shuang Ying, Cynthia A. Toth, Maureen G. Maguire, Russell E. Burns, Juan E. Grunwald, Ebenezer Daniel, Glenn J. Jaffe, David F. Williams, Sara Beardsley, Steven Bennett, Herbert Cantrill, Carmen Chan-Tram, Holly Cheshier, Kathyrn Damato, John Davies, Sundeep Dev, Julianne Enloe, Gennaro Follano, Peggy Gilbert, Jill Johnson, Tori Jones, Lisa Mayleben, Robert Mittra, Martha Moos, Ryan Neist, Neal Oestreich, Polly Quiram, Robert Ramsay, Edwin Ryan, Stephanie Schindeldecker, John Snater, Trenise Steele, Dwight Selders, Jessica Tonsfeldt, Shelly Valardi, Gary Edd Fish, Hank A. Aguado, Sally Arceneaux, Jean Arnwine, Kim Bell, Tina Bell, Bob Boleman, Patricia Bradley, David Callanan, Lori Coors, Jodi Creighton, Timothy Crew, Kimberly Cummings, Christopher Dock, Karen Duignan, Dwain Fuller, Keith Gray, Betsy Hendrix, Nicholas Hesse, Diana Jaramillo, Bradley Jost, Sandy Lash, Laura Lonsdale, Michael Mackens, Karin Mutz, Michael Potts, Brenda Sanchez, William Snyder, Wayne Solley, Carrie Tarter, Robert Wang, Patrick Williams, Stephen L. Perkins, Nicholas Anderson, Ann Arnold, Paul Blais, Joseph Googe, Tina T. Higdon, Cecile Hunt, Mary Johnson, James Miller, Misty Moore, Charity K. Morris, Christopher Morris, Sarah Oelrich, Kristina Oliver, Vicky Seitz, Jerry Whetstone, Bernard H. Doft, Jay Bedel, Robert Bergren, Ann Borthwick, Paul Conrad, Amanda Fec, Christina Fulwylie, Willia Ingram, Shawnique Latham, Gina Lester, Judy Liu, Louis Lobes, Nicole M. Lucko, Holly Mechling, Lori Merlotti, Keith McBroom, Karl Olsen, Danielle Puskas, Pamela Rath, Maria Schmucker, Lynn Schueckler, Christina Schultz, Heather Shultz, David Steinberg, Avni Vyas, Kim Whale, Kimberly Yeckel, David H. Orth, Linda S. Arredondo, Susan Brown, Barbara J. Ciscato, Joseph M. Civantos, Celeste Figliulo, Sohail Hasan, Belinda Kosinski, Dan Muir, Kiersten Nelson, Kirk Packo, John S. Pollack, Kourous Rezaei, Gina Shelton, Shannya Townsend-Patrick, Marian Walsh, H. Richard McDonald, Nina Ansari, Amanda Bye, Arthur D. Fu, Sean Grout, Chad Indermill, Robert N. Johnson, J. Michael Jumper, Silvia Linares, Brandon J. Lujan, Ames Munden, Meredith Persons, Rosa Rodriguez, Jennifer M. Rose, Brandi Teske, Yesmin Urias, Stephen Young, Richard F. Dreyer, Howard Daniel, Michele Connaughton, Irvin Handelman, Stephen Hobbs, Christine Hoerner, Dawn Hudson, Marcia Kopfer, Michael Lee, Craig Lemley, Joe Logan, Colin Ma, Christophe Mallet, Amanda Milliron, Mark Peters, Harry Wohlsein, Joel A. Pearlman, Margo Andrews, Melissa Bartlett, Nanette Carlson, Emily Cox, Robert Equi, Marta Gonzalez, Sophia Griffin, Fran Hogue, Lance Kennedy, Lana Kryuchkov, Carmen Lopez, Danny Lopez, Bertha Luevano, Erin McKenna, Arun Patel, Brian Reed, Nyla Secor, Iris R. Sison, Tony Tsai, Nina Varghis, Brooke Waller, Robert Wendel, Reina Yebra, Daniel B. Roth, Jane Deinzer, Howard Fine, Flory Green, Stuart Green, Bruce Keyser, Steven Leff, Amy Leviton, Amy Martir, Kristin Mosenthine, Starr Muscle, Linda Okoren, Sandy Parker, Jonathan Prenner, Nancy Price, Deana Rogers, Linda Rosas, Alex Schlosser, Loretta Studenko, Thea Tantum, Harold Wheatley, Michael T. Trese, Thomas Aaberg, Denis Bezaire, Craig Bridges, Doug Bryant, Antonio Capone, Michelle Coleman, Christina Consolo, Cindy Cook, Candice DuLong, Bruce Garretson, Tracy Grooten, Julie Hammersley, Tarek Hassan, Heather Jessick, Nanette Jones, Crystal Kinsman, Jennifer Krumlauf, Sandy Lewis, Heather Locke, Alan Margherio, Debra Markus, Tanya Marsh, Serena Neal, Amy Noffke, Kean Oh, Clarence Pence, Lisa Preston, Paul Raphaelian, Virginia R. Regan, Peter Roberts, Alan Ruby, Ramin Sarrafizadeh, Marissa Scherf, Sarita Scott, Scott Sneed, Lisa Staples, Brad Terry, Matthew T. Trese, Joan Videtich, George Williams, Mary Zajechowski, Daniel P. Joseph, Kevin Blinder, Lynda Boyd, Sarah Buckley, Meaghan Crow, Amanda Dinatale, Nicholas Engelbrecht, Bridget Forke, Dana Gabel, Gilbert Grand, Jennifer Grillion-Cerone, Nancy Holekamp, Charlotte Kelly, Ginny Nobel, Kelly Pepple, Matt Raeber, P. Kumar Rao, Tammy Ressel, Steven Schremp, Merrilee Sgorlon, Shantia Shears, Matthew Thomas, Cathy Timma, Annette Vaughn, Carolyn Walters, Rhonda Weeks, Jarrod Wehmeier, Tim Wright, Daniel M. Berinstein, Aida Ayyad, Mohammed K. Barazi, Erica Bickhart, Tracey Brady, Lisa Byank, Alysia Cronise, Vanessa Denny, Courtney Dunn, Michael Flory, Robert Frantz, Richard A. Garfinkel, William Gilbert, Michael M. Lai, Alexander Melamud, Janine Newgen, Shamekia Newton, Debbie Oliver, Michael Osman, Reginald Sanders, Manfred von Fricken, Pravin Dugel, Sandra Arenas, Gabe Balea, Dayna Bartoli, John Bucci, Jennifer A. Cornelius, Scheleen Dickens, Don Doherty, Heather Dunlap, David Goldenberg, Karim Jamal, Norma Jimenez, Nicole Kavanagh, Derek Kunimoto, John Martin, Jessica Miner, Sarah Mobley, Donald Park, Edward Quinlan, Jack Sipperley, Carol Slagle, Danielle Smith, Miguelina Yafchak, Rohana Yager, Christina J. Flaxel, Steven Bailey, Peter Francis, Chris Howell, Thomas Hwang, Shirley Ira, Michael Klein, Andreas Lauer, Teresa Liesegang, Ann Lundquist, Sarah Nolte, Susan K. Nolte, Scott Pickell, Susan Pope, Joseph Rossi, Mitchell Schain, Peter Steinkamp, Maureen D. Toomey, Debora Vahrenwald, Kelly West, Baker Hubbard, Stacey Andelman, Chris Bergstrom, Judy Brower, Blaine Cribbs, Linda Curtis, Jannah Dobbs, Lindreth DuBois, Jessica Gaultney, Deborah Gibbs, Debora Jordan, Donna Leef, Daniel F. Martin, Robert Myles, Timothy Olsen, Bryan Schwent, Sunil Srivastava, Rhonda Waldron, Andrew N. Antoszyk, Uma Balasubramaniam, Danielle Brooks, Justin Brown, David Browning, Loraine Clark, Sarah Ennis, Susannah Held, Jennifer V. Helms, Jenna Herby, Angie Karow, Pearl Leotaud, Caterina Massimino, Donna McClain, Michael McOwen, Jennifer Mindel, Candace Pereira, Rachel Pierce, Michele Powers, Angela Price, Jason Rohrer, Jason Sanders, Robert L. Avery, Kelly Avery, Jessica Basefsky, Liz Beckner, Alessandro Castellarin, Stephen Couvillion, Jack Giust, Matthew Giust, Maan Nasir, Dante Pieramici, Melvin Rabena, Sarah Risard, Robert See, Jerry Smith, Lisha Wan, Sophie J. Bakri, Nakhleh Abu-Yaghi, Andrew Barkmeier, Karin Berg, Jean Burrington, Albert Edwards, Shannon Goddard, Shannon Howard, Raymond Iezzi, Denise Lewison, Thomas Link, Colin A. McCannel, Joan Overend, John Pach, Margaret Ruszczyk, Ryan Shultz, Cindy Stephan, Diane Vogen, Reagan H. Bradford, Vanessa Bergman, Russ Burris, Amanda Butt, Beth Daniels, Connie Dwiggins, Stephen Fransen, Tiffany Guerrero, Darin Haivala, Amy Harris, Sonny Icks, Ronald Kingsley, Lena Redden, Rob Richmond, Brittany Ross, Kammerin White, Misty Youngberg, Trexler M. Topping, Steve Bennett, Sandy Chong, Mary Ciotti, Tina Cleary, Emily Corey, Dennis Donovan, Albert Frederick, Lesley Freese, Margaret Graham, Natalya Gud, Taneika Howard, Mike Jones, Michael Morley, Katie Moses, Jen Stone, Robin Ty, Torsten Wiegand, Lindsey Williams, Beth Winder, Carl C. Awh, Michelle Amonette, Everton Arrindell, Dena Beck, Brandon Busbee, Amy Dilback, Sara Downs, Allison Guidry, Gary Gutow, Jackey Hardin, Sarah Hines, Emily Hutchins, Kim LaCivita, Ashley Lester, Larry Malott, MaryAnn McCain, Jayme Miracle, Kenneth Moffat, Lacy Palazzotta, Kelly Robinson, Peter Sonkin, Alecia Travis, Roy Trent Wallace, Kelly J. Winters, Julia Wray, April E. Harris, Mari Bunnell, Katrina Crooks, Rebecca Fitzgerald, Cameron Javid, Corin Kew, Erica Kill, Patricia Kline, Janet Kreienkamp, Maricruz Martinez, Roy Ann Moore, Egbert Saavedra, LuAnne Taylor, Mark Walsh, Larry Wilson, Thomas A. Ciulla, Ellen Coyle, Tonya Harrington, Charlotte Harris, Cindi Hood, Ingrid Kerr, Raj Maturi, Dawn Moore, Stephanie Morrow, Jennifer Savage, Bethany Sink, Tom Steele, Neelam Thukral, Janet Wilburn, Joseph P. Walker, Jennifer Banks, Debbie Ciampaglia, Danielle Dyshanowitz, Jennifer Frederick, A. Tom Ghuman, Richard Grodin, Cheryl Kiesel, Eileen Knips, Jonathan McCue, Maria Ortiz, Crystal Peters, Paul Raskauskas, Etienne Schoeman, Ashish Sharma, Glenn Wing, Rebecca Youngblood, Suresh R. Chandra, Michael Altaweel, Barbara Blodi, Kathryn Burke, Kristine A. Dietzman, Justin Gottlieb, Gene Knutson, Denise Krolnik, T. Michael Nork, Shelly Olson, John Peterson, Sandra Reed, Barbara Soderling, Guy Somers, Thomas Stevens, Angela Wealti, Srilaxmi Bearelly, Brenda Branchaud, Joyce W. Bryant, Sara Crowell, Sharon Fekrat, Merritt Gammage, Cheala Harrison, Sarah Jones, Noreen McClain, Brooks McCuen, Prithvi Mruthyunjaya, Jeanne Queen, Neeru Sarin, Cindy Skalak, Marriner Skelly, Ivan Suner, Ronnie Tomany, Lauren Welch, Susanna S. Park, Allison Cassidy, Karishma Chandra, Idalew Good, Katrina Imson, Sashi Kaur, Helen Metzler, Lawrence Morse, Ellen Redenbo, Marisa Salvador, David Telander, Mark Thomas, Cindy Wallace, Charles C. Barr, Amanda Battcher, Michelle Bottorff, Mary Chasteen, Kelly Clark, Diane Denning, Debra Schoen, Amy Schultz, Evie Tempel, Lisa Wheeler, Greg K. Whittington, Thomas W. Stone, Todd Blevins, Michelle Buck, Lynn Cruz, Wanda Heath, Diana Holcomb, Rick Isernhagen, Terri Kidd, John Kitchens, Cathy Sears, Ed Slade, Jeanne Van Arsdall, Brenda VanHoose, Jenny Wolfe, William Wood, John Zilis, Carol Crooks, Larry Disney, Mimi Liu, Stephen Petty, Sandra Sall, James C. Folk, Tracy Aly, Abby Brotherton, Douglas Critser, Connie J. Hinz, Stefani Karakas, Valerie Kirschner, Cheyanne Lester, Cindy Montague, Stephen Russell, Heather Stockman, Barbara Taylor, Randy Verdick, Jean Walshire, John T. Thompson, Barbara Connell, Maryanth Constantine, John L. Davis, Gwen Holsapple, Lisa Hunter, C. Nicki Lenane, Robin Mitchell, Leslie Russel, Raymond Sjaarda, David M. Brown, Matthew Benz, Llewellyn Burns, JoLene G. Carranza, Richard Fish, Debra Goates, Shayla Hay, Theresa Jeffers, Eric Kegley, Dallas Kubecka, Stacy McGilvra, Beau Richter, Veronica Sneed, Cary Stoever, Isabell Tellez, Tien Wong, Ivana Kim, Christopher Andreoli, Leslie Barresi, Sarah Brett, Charlene Callahan, Karen Capaccioli, William Carli, Matthew Coppola, Nicholas Emmanuel, Claudia Evans, Anna Fagan, Marcia Grillo, John Head, Troy Kieser, Elaine Lee, Ursula Lord, Edward Miretsky, Kate Palitsch, Todd Petrin, Liz Reader, Svetlana Reznichenko, Mary Robertson, Justin Smith, Demetrios Vavvas, John Wells, Cassie Cahill, W. Lloyd Clark, Kayla Henry, David Johnson, Peggy Miller, LaDetrick Oliver, Robbin Spivey, Tiffany Swinford, Mallie Taylor, Michael Lambert, Kris Chase, Debbie Fredrickson, Joseph Khawly, Valerie Lazarte, Donald Lowd, Pam Miller, Arthur Willis, Philip J. Ferrone, Miguel Almonte, Rachel Arnott, Ingrid Aviles, Sheri Carbon, Michael Chitjian, Kristen DAmore, Christin Elliott, David Fastenberg, Barry Golub, Kenneth Graham, AnnMarie Lavorna, Laura Murphy, Amanda Palomo, Christina Puglisi, David Rhee, Juan Romero, Brett Rosenblatt, Glenda Salcedo, Marianne Schlameuss, Eric Shakin, Vasanti Sookhai, Richard Kaiser, Elizabeth Affel, Gary Brown, Christina Centinaro, Deborah Fine, Mitchell Fineman, Michele Formoso, Sunir Garg, Lisa Grande, Carolyn Herbert, Allen Ho, Jason Hsu, Maryann Jay, Lisa Lavetsky, Elaine Liebenbaum, Joseph Maguire, Julia Monsonego, Lucia O'Connor, Lisa Pierce, Carl Regillo, Maria Rosario, Marc Spirn, James Vander, Jennifer Walsh, Frederick H. Davidorf, Amanda Barnett, Susie Chang, John Christoforidis, Joy Elliott, Heather Justice, Alan Letson, Kathryne McKinney, Jeri Perry, Jill A. Salerno, Scott Savage, Stephen Shelley, Lawrence J. Singerman, Joseph Coney, John DuBois, Kimberly DuBois, Gregg Greanoff, Dianne Himmelman, Mary Ilc, Elizabeth Mcnamara, Michael Novak, Scott Pendergast, Susan Rath, Sheila Smith-Brewer, Vivian Tanner, Diane E. Weiss, Hernando Zegarra, Lawrence Halperin, Patricia Aramayo, Mandeep Dhalla, Brian Fernandez, Cindy Fernandez, Jaclyn Lopez, Monica Lopez, Jamie Mariano, Kellie Murphy, Clifford Sherley, Rita Veksler, Firas Rahhal, Razmig Babikian, David Boyer, Sepideh Hami, Jeff Kessinger, Janet Kurokouchi, Saba Mukarram, Sarah Pachman, Eric Protacio, Julio Sierra, Homayoun Tabandeh, Adam Zamboni, Michael Elman, Jennifer Belz, Tammy Butcher, Theresa Cain, Teresa Coffey, Dena Firestone, Nancy Gore, Pamela Singletary, Peter Sotirakos, JoAnn Starr, Travis A. Meredith, Cassandra J. Barnhart, Debra Cantrell, RonaLyn Esquejo-Leon, Odette Houghton, Harpreet Kaur, Fatoumatta NDure, Ronald Glatzer, Leonard Joffe, Reid Schindler, Stuart L. Fine, Marilyn Katz, Mary Brightwell-Arnold, Ruchira Glaser, Judith Hall, Sandra Harkins, Jiayan Huang, Alexander Khvatov, Kathy McWilliams, Ellen Peskin, Maxwell Pistilli, Susan Ryan, Allison Schnader, Gui-Shuang Ying, Glenn Jaffe, Jennifer Afrani-Sakyi, Brannon Balsley, Linda S. Bennett, Adam Brooks, Adrienne Brower-Lingsch, Lori Bruce, Russell Burns, Dee Busian, John Choong, Lindsey Cloaninger, Francis Char DeCroos, Emily DuBois, Mays El-Dairi, Sarah Gach, Katelyn Hall, Terry Hawks, ChengChenh Huang, Cindy Heydary, Alexander Ho, Shashi Kini, Michelle McCall, Daaimah Muhammad, Jayne Nicholson, Pamela Rieves, Kelly Shields, Adam Specker, Sandra Stinnett, Sujatha Subramaniam, Patrick Tenbrink, Cynthia Toth, Aaron Towe, Kimberly Welch, Natasha Williams, Katrina Winter, Ellen Young, Judith Alexander, Elisabeth Flannagan, E. Revell Martin, Candace Parker, Krista Sepielli, Tom Shannon, Claressa Whearry, Maryann Redford, Marcia R. Kopfer, Frederick L. Ferris, Joan DuPont, Lawrence M. Friedman, Susan B. Bressler, David L. DeMets, Martin Friedlander, Mark W. Johnson, Anne Lindblad, Douglas W. Losordo, and Franklin G. Miller
Subjects: Vascular Endothelial Growth Factor A, medicine.medical_specialty, Visual acuity, genetic structures, Visual Acuity, Angiogenesis Inhibitors, Retinal Pigment Epithelium, Antibodies, Monoclonal, Humanized, Retina, Article, Cicatrix, Ophthalmology, Geographic Atrophy, Ranibizumab, Medicine, Humans, Prospective Studies, Fluorescein Angiography, External limiting membrane, Prospective cohort study, medicine.diagnostic_test, business.industry, Fundus photography, Macular degeneration, Middle Aged, medicine.disease, Fluorescein angiography, eye diseases, Bevacizumab, Choroidal neovascularization, medicine.anatomical_structure, Intravitreal Injections, Wet Macular Degeneration, sense organs, medicine.symptom, business, Tomography, Optical Coherence, medicine.drug
Abstract: To evaluate the association of subretinal hyperreflective material (SHRM) with visual acuity (VA), geographic atrophy (GA), and scar in the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT).Prospective cohort study within a randomized clinical trial.The 1185 CATT participants.Masked readers graded scar and GA on fundus photography and fluorescein angiography and graded SHRM on time-domain and spectral-domain (SD) optical coherence tomography (OCT) throughout 104 weeks. Measurements of SHRM height and width in the fovea, within the center 1 mm(2), or outside the center 1mm(2) were obtained on SD OCT images at 56 (n = 76) and 104 (n = 66) weeks.Presence of SHRM, as well as location and size, and associations with VA, scar, and GA.Among CATT participants, the percentage with SHRM at enrollment was 77%, decreasing to 68% at 4 weeks after treatment and to 54% at 104 weeks. At 104 weeks, scar was present more often in eyes with persistent SHRM than in eyes with SHRM that resolved (64% vs. 31%; P0.0001). Among eyes with detailed evaluation of SHRM at weeks 56 (n = 76) and 104 (n = 66), mean VA letter score was 73.5 (standard error [SE], 2.8), 73.1 (SE, 3.4), 65.3 (SE, 3.5), and 63.9 (SE, 3.7) when SHRM was absent, present outside the central 1 mm(2), present within the central 1 mm(2) but not the foveal center, or present at the foveal center (P = 0.02), respectively. When SHRM was present, the median maximum height under the fovea, within the central 1 mm(2) including the fovea and anywhere within the scan, was 86 μm, 120 μm, and 122 μm, respectively. Visual acuity was decreased with greater SHRM height and width (P0.05).In eyes with neovascular age-related macular degeneration (AMD), SHRM is common and often persists after anti-vascular endothelial growth factor treatment. At 2 years, eyes with scar were more likely to have SHRM than other eyes. Greater SHRM dimensions were associated with worse VA. In eyes with neovascular AMD, SHRM is an important morphologic biomarker.
Published: 2015

36. Expression of Vascular Endothelial Growth Factor in Uveal Melanoma Is Independent of 6p21-Region Copy Number

Author: Mohamed H. Abdel-Rahman, Elson L. Craig, Frederick H. Davidorf, and Charis Eng
Subjects: Cancer Research, Oncology
Abstract: Purpose: Overexpression of vascular endothelial growth factor (VEGF) and overrepresentation of the 6p region have been reported with a wide variation in uveal melanoma. The aim of the current study is to identify the frequency of copy number alteration in the 6p21 region and its correlation with the expression of VEGF in uveal melanoma. Experimental Design: We studied 88 uveal melanomas for copy number change in the 6p region by comparative genomic hybridization and/or chromogenic in situ hybridization. Expression of VEGF protein was estimated by immunohistochemistry. In 15 tumors, VEGF mRNA expression was also studied by quantitative reverse transcription–PCR (RT-PCR) and VEGF splice variants were detected by RT-PCR. Results: Copy number of the 6p21 region was successfully estimated in 37 tumors. In 10 (27%) of those, overrepresentation of the 6p21 region was detected. There was no statistically significant difference in VEGF expression between tumors with and without gain of 6p21 (P = 0.82). VEGF expression was not confined to the tumors and was also detected in the surrounding normal tissue. Expression of VEGF, detected by quantitative RT-PCR, was concordant with expression of VEGF protein. Different VEGF isoforms were expressed in different tumors with no obvious correlation with disease status. Conclusion: VEGF is overexpressed in a significant number of uveal melanomas. It should be noted that VEGF is not a candidate oncogene in uveal melanoma with 6p gain/amplification. VEGF overexpression other than structural amplification is probably significant in the pathogenesis of uveal melanomas, and its mechanism must be sought.
Published: 2005
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37. JUXTAFOVEAL TELANGIECTASIS–A NAME CHANGE?

Author: Robert B. Chambers, Melissa D Pressman, and Frederick H. Davidorf
Subjects: Fovea Centralis, medicine.medical_specialty, medicine.diagnostic_test, business.industry, MEDLINE, Retinal Vessels, General Medicine, Middle Aged, Fluorescein angiography, Ophthalmology, Retinal Diseases, Terminology as Topic, Microscopy, Electron, Scanning, medicine, Humans, Female, Telangiectasis, Fluorescein Angiography, business
Published: 2004
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38. Multifocal choroiditis following simultaneous hepatitis A, typhoid, and yellow fever vaccination

Author: Frederick H. Davidorf, Sarah Escott, and Ahmad B. Tarabishy
Subjects: Pathology, medicine.medical_specialty, business.industry, Yellow fever, Hepatitis A, Case Report, Fundus (eye), medicine.disease, vaccination, Dermatology, Multifocal choroiditis, Typhoid fever, eye diseases, yellow fever, Vaccination, Ophthalmology, Yellow fever vaccination, medicine, sense organs, multifocal choroiditis, business, hepatitis A, typhoid, Sudden onset
Abstract: The paper describes the first reported case of multifocal choroiditis following simultaneous hepatitis-A, typhoid, and yellow fever vaccinations. A 33-year-old male developed sudden onset of flashing lights and floaters in his right eye 3 weeks following hepatitis A, typhoid, and yellow fever vaccinations. Fundus examination and angiography confirmed the presence of multiple peripheral chorioretinal lesions. These lesions demonstrated characteristic morphologic changes over a period of 8 weeks which were consistent with a diagnosis of self-resolving multifocal choroiditis. Vaccine-induced intraocular inflammation has been described infrequently. We demonstrate the first case of self-resolving multifocal choroiditis following simultaneous administration of hepatitis A, yellow fever, and typhoid immunizations.
Published: 2013

39. Custom-made 'nag' eye plaques for 125i brachytherapy

Author: Constance J. Bauer, Frederick H. Davidorf, Hong Wu, Robert B. Chambers, Subir Nag, and Dian Wang
Subjects: Male, Choroidal melanoma, Cancer Research, medicine.medical_specialty, Visual acuity, genetic structures, medicine.medical_treatment, Brachytherapy, Iodine Radioisotopes, Ophthalmology, medicine, Humans, Radiology, Nuclear Medicine and imaging, Melanoma, Radiation, business.industry, Choroid Neoplasms, medicine.disease, eye diseases, Short distance, Sclera, Surgery, Radiation therapy, medicine.anatomical_structure, Oncology, Female, medicine.symptom, business, Follow-Up Studies, Retinopathy, Optic disc
Abstract: Purpose To report our experience in treating medium-size ocular melanomas with custom-made "Nag" eye plaques. Method Seventy-eight patients with medium-size ocular melanomas were treated with plaques of 0.6-mm-thick, 18k gold with a radius of curvature of 12 mm to conform to the curvature of the eyeball. These plaques were custom-made in various sizes and shapes to encompass the base of the tumor and a 1-mm margin on all sides. Apertures in three wings of these plaques allowed sutures to be easily placed to hold the plaques onto the sclera. A dose of 100 Gy (before TG-43) or 85 Gy (after TG-43) was delivered with 125 I in 4 days. The dose was prescribed to the periphery of tumor at the level of tumor apex to ensure that the entire tumor volume received at least this dose. Results The median follow-up was 49 months (range 8–112 months). The progression-free survival (Kaplan-Meier method), overall survival, and disease-specific survival at 5 years were 93%, 86%, and 97%, respectively. Fifty of 78 (64%) patients retained useful visual acuity (20/200 or better). Thirty-one of 78 (40%) patients developed retinopathy or papillopathy. In the subgroup of 22 patients with tumor distance ≤2 mm from optic disc or macula, 12 patients (54%) developed retinopathy or papillopathy. Only 7 of these patients (32%) had useful vision (20/200 or better). Short distance to optic disc or macula was associated with significantly poor visual acuity and moderate to severe retinopathy or papillopathy (ANOVA, p = 0.004 and p = 0.002, respectively). Conclusion Our experience suggests that custom-made Nag plaque brachytherapy can control medium-size choroidal melanoma and that a 1-mm, rather than the standard 2-mm, minimum margin is sufficient when this plaque and prescription methods are used. Patients with tumors close (≤2 mm) to optic disc or macula have a significantly poorer visual outcome.
Published: 2003
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40. Lack of GNAQ germline mutations in uveal melanoma patients with high risk for hereditary cancer predisposition

Author: Frederick H. Davidorf, Robert Pilarski, Mohamed H. Abdel-Rahman, Benjamin B. Christopher, and James B. Massengill
Subjects: Uveal Neoplasms, Cancer Research, Candidate gene, Cancer, Biology, medicine.disease, Eye neoplasm, GTP-Binding Protein alpha Subunits, Introns, Germline, Germline mutation, Oncology, Cutaneous melanoma, Genetics, medicine, Cancer research, GTP-Binding Protein alpha Subunits, Gq-G11, Humans, Genetic Predisposition to Disease, Family history, Melanoma, Germ-Line Mutation, Genetics (clinical), GNAQ
Abstract: A high frequency of somatic mutation in GNAQ has been reported in uveal melanoma (UM). GNAQ is located in the chromosomal band 9q21, the same chromosomal band that harbors a putative candidate gene for hereditary UM. We investigated the frequency of germline sequence alterations in the GNAQ gene in UM patients with increased predisposition to hereditary cancer. A total of 44 high risk UM patients were studied including three patients with a family history of UM, 15 patients with a family history of cutaneous melanoma (CM), three patients with early age at onset of their UM (
Published: 2010
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41. RAPID IMPROVEMENT OF RUBEOSIS IRIDIS FROM A SINGLE BEVACIZUMAB (AVASTIN) INJECTION

Author: Derick Rj, Mouser Jg, and Frederick H. Davidorf
Subjects: Male, Vascular Endothelial Growth Factor A, medicine.medical_specialty, Visual acuity, Bevacizumab, Visual Acuity, Iris, Glaucoma, Antibodies, Monoclonal, Humanized, Fluorophotometry, Injections, Text mining, Ophthalmology, medicine, Humans, Fluorescein Angiography, Melanoma, Rubeosis iridis, medicine.diagnostic_test, business.industry, Choroid Neoplasms, Antibodies, Monoclonal, General Medicine, Middle Aged, medicine.disease, Fluorescein angiography, Glaucoma, Neovascular, Vitreous Body, Iris Diseases, Monoclonal, medicine.symptom, business, medicine.drug
Published: 2006
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42. The Endophthalmitis Vitrectomy Study

Author: Mark W. Johnson, Bernard H. Doft, Sheryl F. Kelsey, Michael Barza, Louis A. Wilson, Charles C. Barr, Stephen R. Wisniewski, Andrew K. Vine, Barbara A. Blodi, Susan G. Elner, Laurie M. Jessup, Sharad Khanderia, Carl L. Pierson, Julie Willis, Frances McIver, Sally Stanley, Scott R. Sneed, Antonio Capone, Thomas M. Aaberg, Jennifer I. Lim, Paul Sternberg, Diana S. Coffman, Cameile N. Moore, Susanne K. Gardner, Frederick S. Nolte, Ann Fremstad, Deborah Gibbs, James Gilman, Ray Swords, H.Edith Aguilar, Travis A. Meredith, Vinod Lakhanpal, Faith D. Christian, A. Hood, Richard S. Schwalbe, Emery E. Billings, William Buie, James J. Mallonee, Mary Ann Millar, Sharon Verbeek, Peter A. Campochiaro, Carol B. Palardy, Lois Reynolds, James D. Dick, Dennis Cain, Donald J. D'Amico, Albert R. Frederick, Michael G. Morley, Richard D. Pesavento, Carmen A. Puliafito, Trexler M. Topping, Susan M. Finn, Laura A. Raymond, Ann Sullivan Baker, Barbara Paton, Claudia Evans, Jeffrey Napoli, Christine Kierman, Kathryn Makris, Tom McInnes, Wini T. Reidy, Ruth White, Richard A. Garfinkel, A.Raymond Pilkerton, Robert A. Frantz, Gill B. Abernathy, Jay G. Barbaccia, H.Russell Ensey, Carol A. Ormes, Choong H. Park, Joel Caplan, Kathryn Russell, Robert Toma, Kirk H. Packo, Serge de Bustros, Timothy P. Flood, Louis Glazer, Maggie DeAlba, Evangeline Evanich, Michael A. Montwill, Jeri J. Rothman, Gail Ruderman, Melodie Beard, William Landau, Min H. Shen, Martha Gordon, Sharon Graff, Kathy Kwiatkowski, Loreen Pappas, Douglas Bryant, Don Doherty, Frank Morini, Linda Arredondo, Bruce R. Garretson, Carlos Gerena, Maureen Hunt, Sharon M. Kinnaird, Toni Neri, Thomas A. Rice, Michael A. Novak, Pamela S. Rowe, Scott Jamieson, Deborah Newberry, Glenn R. Rech, Michael J. Dul, Livia Kinser, Krystyna Strozewski, Susan Clark-Rath, Marty DeLisio, David L. Dempsey, Donna Kukula, Anne Pinter-Smith, Sheila Smith-Brewer, Tracey Ludwig, Robert B. Chambers, Frederick H. Davidorf, Cindy S. Taylor, Karen N. Hale, William J. Buesching, Chhanda Chaudhuri, Nanci J. Cover, Gail R. Shortlidge, Michael J. Keating, Scott J. Savage, Paula Andrzejewska, Susan Cometet, Jill D. Milliron, Rob Richmond, Lori Schneider, Debra Weisenberger, Herbert L. Cantrill, Robert C. Ramsay, Amy B. Brallier, Timothy P. Johnson, Edith E. Rossing, Kathleen A. Knauth, Martha M. Monahan, Neal W. Oestreich, Kenneth F. Clark, Anita M. Glennen, David L. Yarian, Stuart N. Green, Steven R. Leff, Leo Masciulli, Margaret M. Lucido, Edward J. Ludwig, Charlotte L. Marano, Linda Peters, Kim Joho, Doris C. Volkert, Finn Andersen, Donna Coffey, Alex Schlosser, Ann Honeywell, Robert N. Mames, William T. Driebe, George A. Stern, Amye Francis, Z.Suzanne Zam, Rhonda Cooper, Darla Gaskins, Diana J. Shamis, Melinda Willingham, Kay Barker, Harry Rosa, Scott M. Friedman, Thomas W. Gardner, George W. Blankenship, Carole J. Coyle, Christopher J. Bero, Cindy Halas, Suzanne Schick, Jean Walker, Denise Cunningham, H.Michael Lambert, Pamela S. Clogston, Pamela M. Frady, S.Neal Gardner, Michael S. Osato, Louise Carr, James Shigley, Pedro F. Lopez, Lawrence P. Chong, Donald A. Frambach, Lupe CisnerosMargaret^Padilla, Edmond Ming Yee, Tamako Nakamura, A.Frances Walonker, Ronald Morales, Tracy Nichols, Maria E. Huete, Peter E. Liggett, Richard R. Ober, Beth Quillen-Thomas, Mark Williams, Steven M. Bloom, Pamela J. Greene, Greg K. Whittington, Mark E. Martin, Glen Watson, Betty Jenkins-Curry, Leigh A. Gilkey, Steven Huelsman, Dennis P. Han, Thomas C. Burton, William F. Mieler, Jose S. Pulido, Frederick H. Reeser, Janet L. Newman, Kathy A. Werner, Paul J. Pisarzewicz, Nina A. Reinerio, Mary Lee K. Walloch, Zuzana Wilmer, Jan Laabs, Ruth Picchiottino, Jim Phillips, Walter Wipplinger, Gary W. Abrams, Dale T. Jurkiewicz, Margaret L. Leet, Paul Mandel, Kim Metzger, Lori Suchla, Denise Zarling, Mark W. Balles, Edwin H. Ryan, William H. Knobloch, Sally M. Cook, Darlette G. Luke, Patricia Ferrieri, Norynne M. Schiminsky, Anne Genia, David A. Philiph, Elizabeth K. Stinson, Linda M. Wright, William C. McMichael, Sandy J. Mielke, Lisa J. Ponwith, Peter Reed Pavan, Scott E. Pautler, Marion L. Coats, Nancy M. Kirk, Sharon M. Millard, Frank C. Castellano, Charlotte R. Edwards, Angela Marquardt, Amy J. McCormack, Michael T. McCormick, Bernard Renshaw, Angela Restuccia, Monica Campbell, Nell Christopher, L.Scott Garrett, Demetrios G. Halkias, Kim Hothersall, Karen Mickler, Thomas S. Minnick, Cheryl Burr, Wyatt Saxon, Miguel A. Arcacha, Steve Carlton, Sonya K. Edison, Marc J. Mallis, Tamre L. Sayers, Thomas W. Sudds, Robert J. Tiberia, Sherry Wolabaugh, Reagan H. Bradford, David W. Parke, Thomas C. Wolf, Janie M. Shofner, Lee E. Tobey, Harold G. Jensen, Dinah Sanchez, Janie Shofner, Russell Burris, Kellie K. Drake, Kay R. Grissom, J.James Rowsey, Charles P. Wilkinson, Gary C. Brown, William E. Benson, Jay L. Federman, Alfred C. Lucier, Joseph I. Maguire, Lov K. Sarin, Eric P. Shakin, Arunan Sivalingam, William Tasman, James F. Vander, Nancy Ward, Clement A. Weisbecker, Caroline L. Agnew, Richard Lambert, Terrance Torner, Kathy Carlson, Gerrie Franchine, Michelle S. Serfass, Robert L. Bergren, Louis A. Lobes, Karl R. Olsen, Jeffrey S. Rinkoff, Donna J. Metz, Margaret N. Leonard, Lisa M. Karenchak, Regis P. Kowalski, Lynn A. Wellman, Linda A. Wilcox, Alan F. Campbell, David R. Steinberg, Gary L. Vagstad, Kimberly A. Flook, Mary M. Good, Beverly J. Keenen, Kim A. Mellinger, Raymond R. Margherio, Morton S. Cox, Patrick L. Murphy, Michael T. Trese, Jane C. Werner, George A. Williams, Patricia E. Manatrey, Janet L. Prote, Richard Lucarotti, Susan Martin, Jeff Band, Grace Bostic, Kristi Gumming, Beth Mitchell, Virginia S. Regan, Craig Bridges, Sam Cox, Gary Houston, John Johnson, Pat Streasik, Betty Wood, Mark S. Blumenkranz, Lisa Cayo, Virginia Kaye, Carmen Luz Valenzuela, Ira K. Orgel, Lon S. Poliner, Paul E. Tornambe, Sarah V. Cannon, Janet L. Nielsen, Anne Carlson, Pauline Chan, Lynne Drake, Martha Grim, Corky Peterson, Lynn A. Borg, Joann Gillyatt, Conny Beyer, Mark E. Hammer, W.Sanderson Grizzard, Theresa L. Shannon, Janet R. Traynom, Melinda J. Collado, Dennis W. McManus, Daniel E. Sweeney, Donald H. Adams, Thomas T. Watson, Michael V. Antworth, Johanna Glacy Araos, Mark A. Greenwald, Mohsen Habib, Sandra K. Myers, Karen M. Ockers, Judy-Ann Thibodeau, Brett Watkins, Philip T. Nelsen, J.Gregory Rosenthal, Fay V. Mintz, Michael Biedenbach, Nicholas J. Leonardy, Sue M. Lawniczak, Chuck Bork, George Hageage, Evelyn B. Hunter, MarLynn J. Marshall, Patricia Roman, Rick Hill, Thomas Hofbauer, Jack Lemanowicz, Howard P. Cupples, Gladys I. Guzman, Richard J. Brodeur, Donald Yee, Edward C. Delaha, Stanley L. Geyer, Stacey Slovis, William J. Shields, Susan Lauber, Karl Michelitsch, Aaron Kassoff, Sharon Watling, JoAnne C. Buehler, Jeffrey McVay, Gale K. Podobinski, Robert L. Sillett, Shirley Groer, Brian Avery, Steven H. Belle, James Boles, Linda Henry, Sarah J. Shema, Linda Titus-Emstoff, Matthew Davis, Yvonne L. Magli, Larry Hubbard, Suzanne Thomas, Donald F. Everett, Richard Mowery, Donald Everett, Kathryn Davis, Stanley Azen, Preston Covey, Brooks McCuen, Andrew Packer, and Jeffrey Robin
Subjects: medicine.medical_specialty, business.industry, medicine.medical_treatment, Eye disease, Vitrectomy, Intraocular lens, Eye infection, medicine.disease, Surgery, law.invention, Clinical trial, Ophthalmology, Endophthalmitis, Randomized controlled trial, law, medicine, Complication, business
Abstract: Purpose: The authors determine if specific features of the clinical presentation of acute postoperative endophthalmitis correlate with the microbiologic culture results. Methods: A total of 420 patients who had clinical evidence of endophthalmitis within 6 weeks after cataract surgery or secondary intraocular lens implantation were evaluated as part of a randomized clinical trial. Results of cultures performed on aqueous and vitreous specimens obtained at presentation were categorized as follows: gram-positive coagulase-negative micrococci, "other" gram-positive, gram-negative, and equivocal/no growth. Results: Eleven features of the initial clinical presentation were associated with significant differences in the microbiologic spectrum ( P Conclusions: The presenting characteristics of acute endophthalmitis after cataract surgery may be helpful in predicting the most likely culture results. Such predictions do not appear sufficiently strong to guide the initial empiric choice of intravitreal antibiotics.
Published: 1997
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43. Optic Disc Edema From Remote Uveal Melanoma

Author: Martin Lubow, Sireesha A. Clark, Abhik Ray-Chaudhury, Colleen M. Cebulla, Frederick H. Davidorf, and Mohamed H. Abdel-Rahman
Subjects: Intraocular pressure, medicine.medical_specialty, Visual acuity, medicine.diagnostic_test, business.industry, Melanoma, Retinal detachment, medicine.disease, Fluorescein angiography, Article, Ophthalmoscopy, Ophthalmology, medicine, medicine.symptom, Papilledema, business, Optic Disc Edema
Published: 2013

44. The identification of novel genetic risk loci in uveal melanoma

Author: Tomas Kirchhoff, Esther Kazlow, Colleen M. Cebulla, Robert Pilarski, Matjaz Vogelsang, Robert Ferguson, Mohamed H. Abdel-Rahman, Carlos N Martinez, Frederick H. Davidorf, Karan Rai, Esma Ucisik-Akkaya, and Iman Osman
Subjects: Genetics, Cancer Research, business.industry, Melanoma, Bioinformatics, medicine.disease, eye diseases, Oncology, Etiology, Genetic predisposition, Medicine, Identification (biology), sense organs, Intraocular tumor, Genetic risk, business
Abstract: 1543Background: Uveal melanoma (UM) is the most common primary intraocular tumor in adult, but its etiology for the most part remains unclear. It has been suggested that the genetic susceptibility ...
Published: 2016
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45. Atypical cat scratch disease with vitritis, serous macular detachment, neuroretinitis, and retrobulbar optic neuritis

Author: Martin Lubow, Dominic M. Buzzacco, Colleen M. Cebulla, and Frederick H. Davidorf
Subjects: Pathology, medicine.medical_specialty, medicine.diagnostic_test, business.industry, medicine.medical_treatment, Serous macular detachment, Vitrectomy, Cat-scratch disease, Eye infection, Fluorescein angiography, medicine.disease, Sensory Systems, Retrobulbar optic neuritis, Article, Cellular and Molecular Neuroscience, Ophthalmology, Medicine, business
Published: 2012

46. Germline BAP1 mutation predisposes to uveal melanoma, lung adenocarcinoma, meningioma, and other cancers

Author: Frederick H. Davidorf, Benjamin N. Christopher, Peter Hovland, Mohamed H. Abdel-Rahman, Getachew Boru, Robert Pilarski, Colleen M. Cebulla, and James B. Massengill
Subjects: Proband, Adult, Male, Uveal Neoplasms, Candidate gene, Lung Neoplasms, EIF1AX, DNA Mutational Analysis, Loss of Heterozygosity, Adenocarcinoma of Lung, Biology, Adenocarcinoma, Germline, Article, Loss of heterozygosity, Germline mutation, Genetics, medicine, Meningeal Neoplasms, Humans, Genetic Predisposition to Disease, Gene Silencing, Genetic Testing, Melanoma, Genetics (clinical), Germ-Line Mutation, BAP1, Tumor Suppressor Proteins, Genetic Diseases, Inborn, Middle Aged, medicine.disease, Pedigree, Gene Expression Regulation, Neoplastic, Cancer research, Female, Chromosomes, Human, Pair 3, Meningioma, Ubiquitin Thiolesterase, Microsatellite Repeats
Abstract: Objective To investigate the potential contribution of germline sequence alterations in the BAP1 gene in uveal melanoma (UM) patients with possible predisposition to hereditary cancer. Design A total of 53 unrelated UM patients with high risk for hereditary cancer and five additional family members of one proband were studied. Mutational screening was carried out by direct sequencing. Results Of the 53 UM patients studied, a single patient was identified with a germline BAP1 truncating mutation, c. 799 C→T (p.Q267X), which segregated in several family members and was associated with UM and other cancers. Biallelic inactivation of BAP1 and decreased BAP1 expression were identified in the UM, lung adenocarcinoma and meningioma tumours from three family members with this germline BAP1 mutation. Germline BAP1 variants of uncertain significance, likely non-pathogenic, were also identified in two additional UM patients. Conclusion This study reports a novel hereditary cancer syndrome caused by a germline BAP1 mutation that predisposes patients to UM, lung carcinoma, meningioma, and possibly other cancers. The results indicate that BAP1 is the candidate gene in only a small subset of hereditary UM, suggesting the contribution of other candidate genes.
Published: 2011

47. Diabetic Retinopathy During Pregnancy

Author: Frederick H. Davidorf and Robert B. Chambers
Subjects: medicine.medical_specialty, Fetus, Pregnancy, Obstetrics, business.industry, Eye disease, Obstetrics and Gynecology, Diabetic retinopathy, medicine.disease, Surgery, Diabetes mellitus, Pediatrics, Perinatology and Child Health, Epidemiology, medicine, Gestation, business, Retinopathy
Abstract: This article outlines the pathophysiology of diabetic retinopathy, its epidemiology, and its diagnosis. Recommendations for management of the pregnant diabetic patient through the team approach has resulted in a dramatic improvement in maternal and fetal complications during pregnancy. By including a retinal specialist in the team during each trimester, the effects of pregnancy on the progression of diabetic retinopathy should be nearly identical to that of the non-pregnant patient.
Published: 1993
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48. Cancer family history characterization in an unselected cohort of 121 patients with uveal melanoma

Author: J. L. Sexton, Mohamed H. Abdel-Rahman, Frederick H. Davidorf, Robert Pilarski, and Sameera Ezzat
Subjects: Oncology, Adult, Male, Uveal Neoplasms, Cancer Research, medicine.medical_specialty, Population, Eye neoplasm, Cancer syndrome, Cohort Studies, Neoplasms, Multiple Primary, Young Adult, Neoplastic Syndromes, Hereditary, Risk Factors, Internal medicine, Genetics, medicine, Familial predisposition, Cancer Family, Humans, Genetic Predisposition to Disease, Young adult, Family history, education, Melanoma, Genetics (clinical), Aged, Gynecology, Aged, 80 and over, education.field_of_study, business.industry, Cancer, Middle Aged, medicine.disease, Pedigree, Female, business
Abstract: Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. The extent of the contribution of familial/hereditary predisposition to the development of uveal melanoma is largely unknown. Thus we sought to ascertain the frequency of cancers in patients with UM and their family members to identify the prevalence of hereditary/familial predisposition to cancer in these patients. An unselected series of 121 patients with UM seen in a university-based tertiary referral program were consented to the study. Cancer histories (site and age of diagnosis) were obtained for all first- and second-degree relatives. Patients/families were classified as being potentially at high risk for hereditary predisposition if they met any of the following criteria: (1) Diagnosis of UM at age 30 or under, (2) Two or more cases of UM in the family, (3) UM plus at least one other primary cancer in the same patient (excluding non-melanoma skin and cervix cancers due to their strong environmental etiological link). (4) Family history meeting high risk criteria for a known hereditary cancer predisposition syndrome as defined by Hampel et al. (J Med Genet 41(2): 81-91, 2004). One patient had a family history of UM (0.8%). Ten patients (8.3%) had a personal and/or family history consistent with predisposition to a known hereditary cancer syndrome including six with possible hereditary breast, two with hereditary colon and two with hereditary melanomas. Twenty three patients (19%) had a personal history of a second cancer after exclusion of non-melanoma skin and cervical cancers. The frequency of cutaneous melanomas was significantly higher in UM patients than the general population (RR: 2.97, 95% CI: 1.00-6.94). Patients with a family history suggestive of a high risk predisposition to a known cancer syndrome had a significantly higher risk for having a second cancer than the remaining UM patients (P = 0.02). Our results indicate that the frequency of UM patients with high risk for a hereditary cancer predisposition is much higher than earlier estimates (0.6%) and that it could be as high as 11.6%. Our results suggest that cancer phenotypes in these patients are diverse and include cancers other than UM. Thus, alerting ophthalmologists to the need for expanding their cancer family history intake to include other cancers is warranted. It also suggests that patients with a hereditary predisposition to UM have a higher risk for the development of other cancers and that characterization of the germline genetic alterations in these patients is highly warranted.
Published: 2010

49. Treatment of Iris Melanoma With Photodynamic Therapy

Author: Frederick H. Davidorf and Jonathan M. Davidorf
Subjects: Hematoporphyrin, Pathology, medicine.medical_specialty, business.industry, Eye disease, medicine.medical_treatment, Melanoma, Iris melanoma, Photodynamic therapy, medicine.disease, chemistry.chemical_compound, chemistry, Total dose, Medicine, Tumor necrosis factor alpha, Photosensitizer, business
Abstract: Photodynamic therapy was used to treat four patients with iris melanoma. Hematoporphyrin derivative was used as a sensitizing agent. The tumors were exposed to a total dose of 1.72 x 10 p 6 J/cm p 2 of 630-nanometer laser light. The eye of the first patient, enucleated after treatment, histopathologically showed significant tumor necrosis. The tumors in the three subsequent patients were almost completely ablated, with no evidence of regrowth.
Published: 1992
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50. Systemic immunostimulation after retinal laser treatment in retinitis pigmentosa

Author: Robert B. Chambers, Barry T. Shannon, Frederick H. Davidorf, Lowell L. Williams, and Lawrence E. Leguire
Subjects: Adult, medicine.medical_specialty, Adolescent, Lymphocyte, Immunology, Inflammation, Light Coagulation, Antibodies, Viral, medicine.disease_cause, Pathology and Forensic Medicine, Interferon-gamma, Leukocyte Count, chemistry.chemical_compound, Immune system, Retinitis pigmentosa, medicine, Humans, Immunology and Allergy, Immunity, Cellular, Retina, business.industry, Lasers, Receptors, Interleukin-2, Retinal, Rubella virus, Middle Aged, Flow Cytometry, medicine.disease, Antigens, Differentiation, Surgery, medicine.anatomical_structure, Solubility, chemistry, Antibody Formation, medicine.symptom, business, Retinitis Pigmentosa, Retinopathy
Abstract: Systemic immunostimulation followed an experimental treatment trial of scatter argon laser photocoagulation directed to the retina of one eye of 10 patients with heredo-degenerative retinitis pigmentosa (RP). Significantly increased RP lymphocyte CD25, CD26, and CD4/CD26 activation epitope expressions over prelaser values and controls were found with a normalization of soluble interleukin-2 receptor secretion after laser treatment. Serum interferon-gamma was low both pre- and postlaser. Interestingly, when a panel of viral antibodies was tested, only those to rubella virus were elevated in the early postlaser period. The character of RP immunostimulation after laser-induced inflammation could be consistent with an antigenic stimulus from laser-released retinal proteins which might be of autoimmune or latent infectious origin. Enhanced immune responses may be a common but unrecognized sequellae of retinal laser.
Published: 1992
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