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1. Retinal vasculitis with Chronic Recurrent Multifocal Osteomyelitis: a case report and review of the literature

Author

Victoria K. Shanmugam, Marc Phillpotts, Timothy Brady, Monica Dalal, Shawn Haji-Momenian, Esma Akin, Kavita Nataranjan, Sean McNish, and Donald S. Karcher

Subjects
Case report, Retinal Vasculitis, Sternoclavicular, Chronic recurrent multifocal osteomyelitis, CRMO, SAPHO, Diseases of the musculoskeletal system, RC925-935
Abstract

Abstract Background Concurrent presentation of retinal vasculitis with mixed sclerotic and lytic bone lesions is rare. Case presentation We present the case of a 37-year old woman with a several year history of episodic sternoclavicular pain who presented for rheumatologic evaluation due to a recent diagnosis of retinal vasculitis. We review the differential diagnosis of retinal vasculitis, along with the differential diagnosis of mixed sclerotic and lytic bone lesions. Ultimately, bone marrow biopsy confirmed diagnosis of chronic recurrent multifocal osteomyelitis (CRMO). Concurrent presentation of CRMO with retinal vasculitis is extremely rare but important to recognize. The patient demonstrated clinical response to prednisone and tumor necrosis factor-alpha inhibition (TNF-i). Conclusion This case reports and unusual presentation of CRMO spectrum disease involving the sternum and sternoclavicular joint with concurrent retinal vasculitis.

Published
2019
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2. Sympathetic Ophthalmia Two Weeks After 23-Gauge Vitrectomy

Author

Marena Patronas, H. Nida H.N.S. Sen, Alexander A.H. Hacopian, Bahaeddin B.E. El Khatib, Menka S.M.P. Patel, and Monica Dalal

Subjects
Ophthalmology, medicine.medical_specialty, Infectious Diseases, lcsh:Ophthalmology, lcsh:RE1-994, business.industry, Sympathetic ophthalmia, Brief Report, medicine, medicine.disease, business, 23 gauge vitrectomy
Published
2020

3. Natural History of Drusenoid Pigment Epithelial Detachment Associated with Age-Related Macular Degeneration

Author

Jeannette J. Yu, Elvira Agrón, Traci E. Clemons, Amitha Domalpally, Freekje van Asten, Tiarnan D. Keenan, Catherine Cukras, Emily Y. Chew, Frederick L. Ferris, John Paul SanGiovanni, Traci Clemons, Anne Lindblad, Robert Lindblad, Nilay Shah, Robert Sperduto, Wendy McBee, Gary Gensler, Molly Harrington, Alice Henning, Katrina Jones, Kumar Thotapally, Diana Tull, Valerie Watson, Kayla Williams, Christina Gentry, Francine Kaufman, Chris Morrison, Elizabeth Saverino, Sherrie Schenning, Barbara Blodi, Ronald P. Danis, Matthew Davis, Kathy Glander, Gregory Guilfoil, Larry D. Hubbard, Kristine Johnson, Ronald Klein, Barbara Nardi, Michael Neider, Nancy Robinson, Eileen Rosensteel, Hugh Wabers, Grace Zhang, Alan J. Ruby, Antonio Capone, Bawa Dass, Kimberly Drenser, Bruce R. Garretson, Tarek S. Hassan, Michael Trese, George A. Williams, Jeremy Wolfe, Tina Bell, Mary Zajechowski, Dennis Bezaire, Fran McIver, Anthony Medina, Jackie Pagett, Stephanie Hatch Smith, Lynn Swartz, Tom Treuter, Andrew Antoszyk, Justin Brown, David J. Browning, Walter Holland, Angella Karow, Kelly Stalford, Angela Price, Sarah Ennis, Sherry Fredenberg, Jenna Herby, Uma Balasubramaniam, Loraine Clark, Donna McClain, Michael McOwen, Lynn Watson, Michael Klein, Steven T. Bailey, Thomas J. Hwang, Andreas Lauer, J. Timothy Stout, Patty McCollum, Milt Johnson, Patrick B. Rice, Ivana Kim, John Loewenstein, Joan Miller, Lucia Sobrin, Lucy Young, Jacqueline Sullivan, Patricia Houlihan, Linda Merry, Ann Marie Lane, Ursula Lord Bator, Claudia Evans, Sarah Brett, Charleen Callahan, Marcia Grillo, David Walsh, Kamella Lau Zimmerman, Gary Edd Fish, Rajiv Anand, Lori E. Coors, Dwain G. Fuller, Rand Spencer, Robert C. Wang, Karen Duignan, Sally Arceneaux, Hank Aguado, Nicholas Hesse, Michael Mackens, Brian Swan, Wai T. Wong, Monica Dalal, Naima Jacobs-El, Catherine Meyerle, Benjamin Nicholson, Henry Wiley, Katherine Hall Shimel, Angel Garced, Janice Oparah, Greg Short, Alana Temple, Babilonia Ayukawa, Guy Foster, Darryl Hayes, Dessie Koutsandreas, Roula Nashwinter, John Rowan, Michael Bono, Denise Cunningham, Marilois Palmer, Alicia Zetina, David H. Orth, Kourous Rezaei, Joseph Civantos, Sohail Hasan, Kirk Packo, Celeste Figliulo, Pam Stanberry, Tara Farmer, Kiersten Nelson, Shannya Townsend-Patrick, Philip Rosenfeld, Royce Chen, Rishi Doshi, Sander Dubovy, Brian T. Kim, Matthew Lowrance, Andrew Moshfeghi, Zayna Nahas, Gary Schienbaum, John Vishak, Christina Weng, Zohar Yehoshua, Belen Rodriguez, Jose Rebimbas, Jane Gleichauf, Mike Kicak, Jason Mena, Tim Odem, Elizabeth Sferza-Camp, Alicia Disgdiertt, Jim Oramas, Isabel Rams, Stephanie Thatcher, Susan B. Bressler, Neil M. Bressler, Daniel Finkelstein, Steven H. Sherman, Sharon Solomon, Howard S. Ying, Rita Denbow, Deborah Phillips, Elizabeth Radcliffe, Judy Belt, Dennis Cain, David Emmert, Mark Herring, Jacquelyn McDonald, G. Baker Hubbard, Chris S. Bergstrom, Blaine Cribbs, Andrew Hendrick, Brandon Johnson, Philip Laird, Sonia Mehta, Timothy Olsen, Justin Townsend, Jion Yan, Steven Yeh, Linda Curtis, Judy Brower, Hannah Yi, Jannah Rutter Dobbs, Debbie Jordan, Michael J. Elman, Robert A. Liss, JoAnn Starr, Jennifer Belz, Charlene Putzulo, Teresa Coffey, Ashley Davis, Pamela Singletary, Giorya Shabi Andreani, Theresa Cain, Daniel Ketner, Peter Sotirakos, Suresh Chandra, Barbara A. Blodi, Michael M. Altaweel, Justin L. Gottlieb, Michael Ip, T. Michael Nork, Thomas S. Stevens, Kathryn Burke, Shelly Olson, Kristine Dietzman, Barbara Soderling, Guy Somers, Angie Wealti, Denise Krolnik, John Peterson, Sandra Reed, Thomas Friberg, Andrew Eller, Denise Gallagher, Leanne Labriola, Melissa Pokrifka, Aron Gedansky, Natalie Anthony, Cassandra Grzybowski, Dawn Matthews, Sharon Murajda-Jumba, Jessica Toro, David G. Callanan, Wayne A. Solley, Patrick Williams, Sandy Lash, Bob Boleman, Chris Dock, Michel Shami, Brenda Arrington, Ashaki Meeks, Alan R. Margherio, Paul Raphaelian, Debra Markus, Justin Langdon, Elizabeth Truax, Sandy Lewis, Brad Terry, Amy Noffke, Kean Oh, Ramin Sarrafizadeh, Scott Sneed, Julie Hammersley, Serena Neal, Mary Doran, Nan Jones, Lisa Preston, Heather Jessick, Tanya Tracy Marsh, Michael Tolentino, Adam Berger, Richard Hamilton, David Misch, Suk Jin Moon, Dawn Sutherland, Vera Dilts, Sara Henderson, Esmeralda Medina, Donald Trueman, Laura Holm, Jason Strickland, Darmakusuma Ie, Jeffrey L. Lipkowitz, Kekul B. Shah, Susan Geraghty, Beverly Sannazzaro, Morgan Harper, Krista Bayer, Mary B. Lansing, Lauren B. Fox, Rebecca Lee, Jay B. Stallman, Michael Jacobson, Sean Koh, Scott Lampert, John Miller, Mark Rivellese, Atul Sharma, Robert A. Stoltz, Stephanie Vanderveldt, Leslie Marcus, Starr Hendricks, Ryan Hollman, Grethel Betanzos, Leslie Ellorin, Shelly Fulbright, Debbie McCormick, Paul A. Edwards, Julianne Hall, Mary Monk, Melanie Gutkowski, Melina Mazurek, Janet Murphy, Katherine Gusas, Crystal Moffett, David Burley, Nicole Chesney, Katie Kilgo, Brian Rusinek, Bradley Stern, Tracy Troszak, Rhonda Baker-Levingston, Carl W. Baker, Tracey Caldwell, Tammy Walker, Lynnette F. Lambert, Tracey Martin, Mary Jill Palmer, Tana Williams, Michael A. Novak, Joseph Coney, David G. Miller, Scott Pendergast, Lawrence Singerman, Nicholas Zakov, Hernando Zegarra, Kim DuBois, Susan Rath, Lori Revella, Tammy Brink, Kim Drury, Lisa Hogue, Mary Ilc, Connie Keller, Elizabeth McNamara, Vivian Tanner, Tamara Cunningham, John DuBois, Gregg Greanoff, Trina Nitzsche, Sheila Smith-Brewer, Ricky D. Isernhagen, John W. Kitchens, Thomas W. Stone, William J. Wood, Diana Holcomb, Virginia Therrien, Michelle Buck, Jeanne Van Arsdall, Edward Slade, Todd E. Schneiderman, David J. Spinak, Jackie Gaedke, Heather Davis Brown, Dan Helgren, Jenifer Garrison Pangelinan, Lawrence Halperin, Scott Anagnoste, Mandeep Dhalla, Krista Rosenberg, Barry Taney, W. Scott Thompson, Jaclyn Lopez, Monica Hamlin, Monica Lopez, Jamie Mariano, Evelyn Quinchia, Patricia Aramayo, Rita Veksler, Michael Lee, Richard Dreyer, Irvin Handelman, Colin Ma, Mark Peters, Stephen Hobbs, Amanda Milliron, Marcia Kopfer, Michele Connaughton, A. Christine Hoerner, R. Joseph Logan, Harry J. Wohlsein, David Boyer, Thomas G. Chu, Pouya Dayani, David Liao, Roger L. Novack, Firas M. Rahhal, Richard Roe, Homayoun Tabandeh, Janet Bayramyan, Tammy Gasparyan, Connie Hoang, Janet Kurokouchi, Tammy Eileen Lo, Richard Ngo, Mary Ann Nguyen, Michael Peyton, Charles Yoon, Julio Sierra, Adam Zamboni, Jeff Kessinger, Eric Protacio, Adam Smucker, Pamela Rath, Robert Bergren, Bernard Doft, Judy Liu, Karl Olsen, Lori Merlotti, Willia Ingram, Kellianne Marfisi, Kimberly Yeckel, Heather Schultz Carmelo, Amanda Fec, Keith McBroom, David Steinberg, Marc Levy, Jody Abrams, Melvin Chen, Waldemar Torres, Peggy Jelemensky, Mark Prybylski, Tara Raphael, Diana Appleby, Charlotte Rodman, Mark Sneath, Robert H. Rosa, Vanessa Hoelscher, Adelia Castano, Jocelyn Parker, John Hoskins, Nicholas Anderson, Joseph Googe, Tod A. McMillan, James Miller, Stephen Perkins, Kristina Oliver, Jennifer Beerbower, Bruce Gilliland, Cecile Hunt, Mike Jacobus, Raul Lince, Christopher Morris, Sarah Oelrich, Jerry Whetstone, Clement K. Chan, Steven Lin, Kim Walther, Tiana Gonzales, Lenise Myers, Kenneth Huff, David M. Brown, Eric Chen, Matthew S. Benz, Richard H. Fish, Rosa Y. Kim, James Major, Tien Pei Wong, Charles Wycoff, Cassandra Cone, Debbie Goates Gilaspia, Nubia Landaverde, Robert Smith, Deneva Zamora, Veronica Sneed, Melina Vela, Eric Kegley, Craig Greven, Shree Kurup, Charles Richards, Madison Slusher, Cara Everhart, Joan Fish, Mark Clark, David Miller, Marshall Tyler, J. Michael Jumper, Arthur D. Fu, Robert N. Johnson, Brandon Lujan, H. Richard McDonald, Rosa Rodriguez, Nina Ansari, Jeanifer Joaquin, Silvia Linares, Lizette Lopez, Jessica Sabio, Sean Grout, Chad Indermill, Yesmin Urias, Roberto Zimmerman, Linda Margulies, Sara J. Schmidt, Joy L. Meier, Sherry L. Hadley, William Rosenthal, Barbara Johnson, Lois Swafford, Richard Shields, R. Scott Varner, Richard Rosen, Ronald Gentile, Melissa Rivas, Katy W. Tai, Wanda Carrasquillo-Boyd, Robert Masini, Glenn Stoller, Ken Carnevale, Diane M. LaRosa, Barbara Burger, Tereza Conway, Carla Del Castillo, Julissa Diaz, Susan Jones, Nina Mondoc, Charlene Balfour, C.H. Vitha, Jennifer Lutz, Barbara McGinley, Fadi El Baba, Ann Marie Lavorna, Renee Jones, Jean Lewis, Ruth Tenzler, Mary Salvas-Mladek, Diane Van Kesteren, W. Copley McLean, W. Zachery Bridges, Cameron Stone, Denise Ammons, Mary Lamy, Andrea Menzel, Lea Doll Raymer, Barbara Campbell, Lisa Hawkins, Leslie Rickman, Lorraine Sherlin, Paula Price, Albert Sinyai, Ronald Kingsley, Reagan H. Bradford, Robert E. Leonard, Sonny Icks, Vanessa Bergman, Brittany Ross, Russ Burris, Amanda Butt, Rob Richmond, Alice Lyon, Manjot Gill, Lee Jampol, Rukhsana Mizra, Zuzanna Rozenbajgier, Jeremy Chapman, Lori Kaminski, Andrea Degillio, Evica Simjanoski, Jeffrey Heier, Hyung Cho, Tina Scheufele Cleary, Darin Goldman, Chirag Shah, Trexler Topping, Marissa Weber, Torsten Wiegand, Jeremy Schindelheim, Joy Bankert, Jennifer Stone, Alison Nowak, Sandy Chong, Lindsay Williams, Steven Bennett, Dennis Donovan, Margaret Graham, Cullen Jones, Anne Fung, Jan-Kristine Bayabo, Razelda Bosch, Esperanza Cruz, Ashley Emerson, Alycia Fleming, Denice Barsness, Jorge Rodriguez, Marina Soboleva, Ingrid U. Scott, Esther Bowie, Kimberly A. Neely, David A. Quillen, Laura Walter, Timothy Bennett, James Strong, John Wells, Lloyd Clark, David Johnson, Peggy Miller, Mallie Taylor, Tiffany Swinford, Robbin Spivey, Michael Banach, Lawrence Ho, Richard Lanning, Thomas R. Pheasant, Jay G. Prensky, Steven Truong, Julia Teatsworth, Michelle Dietrich, Ann Wasilus, Ann Miller, Megan Rakes, Teresa Slagle, Michelle Richards, Patricia Schuessler, Lacy Stover, Paul Beer, Naomi S. Falk, Mary Beth Shannon, Jeannie Olmeda, Don Berdeen, Joseph F. Fisher, James Folk, Stephen Russell, Barbara Taylor, Connie Hinz, Jean Walshire, Heather Stockman, Bruce Critser, Stefani Karakas, Cindy Montague, Randy Verdick, Omesh Gupta, Joseph Maguire, Christopher Brady, Francis Char DeCroos, Michael Dollin, Sunir Garg, Adam Gerstenblith, Julia Haller, Allen C. Ho, Jason Hsu, Richard Kaiser, John Pitcher, Carl Regillo, Rajiv Shah, Marc Spirn, William Tasman, James Vander, Noga Senderowitsch, Michele Formoso, Michelle Markun, Cedric George, Christina Centinaro, Lisa Grande, Stefanie Carey, Elaine Liebenbaum, SriniVas Sadda, Mark Humayun, Rachel Sierra, Elizabeth Corona, Margaret Padilla, Moonseok Nu, Sylvia Ramos, Cullen Barnett, Glenn Currie, Cornelia Gottlieb, Richard Garfinkel, Daniel Berinstein, Marcus Colyer, William Deegan, Michael Min-Shyue Lai, Robert Murphy, Michael Osman, Michael Rivers, Reginald Sanders, Manfred A. von Fricken, Debbie Oliver, Jeanne Kirshon, Tanya Alexander Snowden, Thomas Blondo, Alysia Cronise, Vanessa Denny, Kylie Mendez, Janine Newgen, Justin Davis, Mike Flory, Robert Frantz, Bryan Murphy, Steve Rauch, Judy E. Kim, Jane Bachman, Thomas B. Connor, Dennis P. Han, Kimberly Stepian, David V. Weinberg, William J. Wirostko, Krissa Packard, Tracy Kaczanowski, Vesper Williams, Vicki Barwick, Judy Flanders, Dennis Backes, Joe Beringer, Kristy Keller, Kathy Selchert, Paul Bernstein, Michael Teske, Albert Vitale, Susan Allman, Bonnie Carlstrom, Kimberley Wegner, Anne Haroldsen, Deborah Harrison, Cyrie Fry, James Gilman, Glen Jenkins, Paula Morris, Michael Rauser, Joseph Fan, Mukesh Suthar, Gisela Santiago, Kara Rollins Halsey, Christy Quesada, William Kiernan, Jesse Knabb, Richard Alan Lewis, Cindy Dorenbach, Steven Spencer, Dana Barnett, Joseph Morales, Barron C. Fishburne, Jeffrey G. Gross, Michael A. Magee, Amy Flowers, Angie McDowell, Randall Price, Suber Huang, Johnny Tang, Shawn Wilker, Cherie Hornsby, Lisa Ferguson, Kirk Krogstad, Riva Adamovsky, Peggy Allchin, Kathleen Carlton, Claudia Clow, Kelly Sholtis, Stephanie Burke, Mark Harrod, Stacie Hrvatin, Geoffrey Pankhurst, Nelson R. Sabates, Michael Cassell, Komal Desai, Abraham Poulose, Felix Sabates, Yin Chen, Gary Gallimore, Yolanda Konior, Nicola Kim, Sami Uwaydat, Deborah Troillett, Karen Aletter, Robert N. Frank, Gary Abrams, James Puklin, Asheesh Tewari, Cheryl Milanovic, Melanie Bailey, David Griffith, Dena McDonald, Kit Morehead, Zlatan Sadikovic, Lisa Schillace, Elizabeth Silvis, Brian Joondeph, Nancy Christmas, Alan Kimura, Mimi Liu, Stephen Petty, John Zilis, Jenny Benitez, Cassandra Berryman Catlett, Eric Fluegel, Shane Mowry, Hoang Nguyen, David Reflow, Odette M. Houghton, Seema Garg, Maurice B. Landers, Travis Meredith, Sandy Barnhart, Megha Karmalkar, Debra Cantrell, Rona Lyn Esquejo-Leon, Linda Manor, Sue Pope, David Stines, Amelia Stokely, Dean Hainsworth, Dyann Helming, Debbie Eichelberger, Mary Paige Leaton, Chuck Hamm, Edward Chaum, Alessandro Iannaccone, Barbara Jennings, Tracy Murray, Joe Mastellone, Robert Millay, Brian Kim, Theresa Goddard, Liza Jarrett Beaudette, Nina Changelian-Aitken, Fernando Corrada, Jason Dubuque, Raymond Iezzi, Sophie J. Bakri, Jose S. Pulido, Diane Vogen, Rebecca Nielsen, Karin Berg, Jean Burrington, Shannon Howard, Joan Overend, Zbigniew Krason, Denise Lewison, Thomas Link, Kevin J. Blinder, Nicholas E. Engelbrecht, M. Gilbert Grand, Daniel P. Joseph, Gaurav K. Shah, Bradley Smith, Matthew Thomas, Rhonda Weeks, Lynda Boyd, Dana Gabel, Ron Adelman, John Huang, James Kempton, Aaron Parnes, Jennifer Dupont, Elizabeth Perotti, Victoria Donaldson, Kenneth Fong, Pamela Ossorio, Anita Agarwal, Paul Sternberg, Sandy Owings, Tony Adkins, Elaine Lok, Garvin Munn, Buddy Skellie, Neelakshi Bhagat, Monique S. Roy, Marco Zarbin, Catherine Fay, Michael Lazar, Beth Malpica, Tatiana Mikheyav, Lawrence Ulanski, Jennifer Lim, Marcia Niec, Tametha Johnson, Yesenia Ovando, Catherine Nail Carroll, Mark Janowicz, Steven Schwartz, David Cupp, Michael Gorin, Gad Heilweil, Hamid Hosseini, Jean-Pierre Hubschman, Allan Kreiger, Tara Young McCannel, Carolyn Pan, David Sarraf, Irena Tsui, Joshua Udoetek, Vinad Voleti, Logan Hitchcock, Rosaleen Ostrick, Melissa Chun, Jennie Kageyama, Nilo Davila, Kristin Lipka, Christina Shin, Cynthia Owsley, Michael Albert, Richard Feist, John Mason, Martin Thomley, Angelia Johnson, Tracy Emond, Joanna Hamela, Angela Marsh, Karen Searcey, Kia Rookard, Yu-Guang He, Rafael L. Ufret-Vincenty, Mike Molai, William Anderson, John Horna, Alan Letson, Colleen Cebulla, Susie Chang, Fred Davidorf, Jill Salerno, Laura Sladoje, Christina Stetson, Jeri Perry, Scott Savage, Cynthia Toth, Glenn Jaffe, Stefanie Schuman, Neeru Sarin, Jim Crowell, Tiffanie Keaton, Michael Kelly, Brian Lutman, Marriner Skelly, Lauren Welch, Lawrence Morse, Allan Hunter, Susanna Soon-Chun Park, Cynthia Wallace, Ember Dhillon, Marisa Salvador, Barbara Holderreed, Karishma Chandra, Sashi Kaur, Ellen Redenbo, Smiley Hom, Michael Cooney, Irene Barbazetto, James M. Klancnik, John A. Sorenson, Lawrence Yannuzzi, Maria Scolaro, Eugene Agresta, Nancy Gonzalez, Sandeep Grover, K.V. Chalam, Shailesh Gupta, Christopher Lyons, Wenhua Li, Chirag Patel, Jose Carrion, Henry Ferreyra, Amberly Rodriguez, Iliana Molina, Gabriel Balea, Pam Emory, Marlene Rico, Giorgio Siqueiros, Alexander J. Brucker, Joshua Dunaief, Juan Grunwald, Benjamin Kim, Albert M. Maguire, Brian VanderBeek, Sheri Drossner, Joan DuPont, Rebecca Salvo, Jim Berger, Cheryl Devine, Bill Nyberg, Laurel Weeney, David DiLoreto, Mina Chung, Valerie Davis, Peter MacDowell, George O. Gara, Daniel Castillo, Andrea Czubinski, Melissa Keim, Brandi Hardy, Rachel Grunhaus Hollar, Lynn Schueckler, Alice T. Lyon, Aaron Weinberg, Mira Shiloach, Nicole Pelkofer, Qin Zhou, Laura McPoland, Rajendra Apte, P. Kumar Rao, Sam Pistorius, Jamie Kambarian, Eve Adcock, Sarah Gould, Melanie Quinn, Rhonda Curtis, Amy Frost, Charla Meyer, and Greg Rathert

Subjects
0303 health sciences, medicine.medical_specialty, Visual acuity, genetic structures, business.industry, Eye disease, Hazard ratio, Age-Related Eye Disease Study, Retrospective cohort study, Fundus (eye), Macular degeneration, medicine.disease, eye diseases, 03 medical and health sciences, Ophthalmology, 0302 clinical medicine, 030221 ophthalmology & optometry, medicine, sense organs, medicine.symptom, Prospective cohort study, business, 030304 developmental biology
Abstract

Purpose To investigate the natural history and genetic associations of drusenoid pigment epithelial detachment (DPED) associated with age-related macular degeneration (AMD). Design Retrospective analysis of a prospective cohort study. Participants Of the 4203 Age-Related Eye Disease Study 2 (AREDS2) participants, 391 eyes (325 participants) had DPED without late AMD at the time of DPED detection. Genetic analyses included 120 white AREDS2 participants and 145 Age-Related Eye Disease Study (AREDS) participants with DPED. Methods Baseline and annual stereoscopic fundus photographs were graded centrally to detect DPED, a well-defined yellow elevated mound of confluent drusen ≥433 μm in diameter, and to evaluate progression rates to late AMD: geographic atrophy (GA) and neovascular (NV)-AMD. Five single nucleotide polymorphisms (CFH [rs10611670], C3 [rs2230199], CFI [rs10033900], C2/CFB [rs114254831], ARMS2 [rs10490924]) and genetic risk score (GRS) group were investigated for association with DPED development. Kaplan–Meier analyses and multivariable proportional hazard regressions were performed. Main Outcome Measures Progression rates to late AMD and decrease of ≥3 lines in visual acuity (VA) from the time of DPED detection; association of rate of DPED development with genotype. Results Mean (standard deviation [SD]) follow-up time from DPED detection was 4.7 (0.9) years. DPED was associated with increased risk of progression to late AMD (hazard ratio [HR], 2.36; 95% confidence interval [CI], 1.98–2.82; P Conclusions This study replicates the results of previous natural history studies of eyes with DPED including the high rates of progression to late AMD and vision loss (regardless of progression to late AMD). The genetic associations are consistent with genes associated with AMD progression.

Published
2019
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4. Progression of Geographic Atrophy in Age-related Macular Degeneration

Author

Tiarnan D. Keenan, Elvira Agrón, Amitha Domalpally, Traci E. Clemons, Freekje van Asten, Wai T. Wong, Ronald G. Danis, SriniVas Sadda, Philip J. Rosenfeld, Michael L. Klein, Rinki Ratnapriya, Anand Swaroop, Frederick L. Ferris, Emily Y. Chew, John Paul SanGiovanni, Traci Clemons, Anne Lindblad, Robert Lindblad, Nilay Shah, Robert Sperduto, Wendy McBee, Gary Gensler, Molly Harrington, Alice Henning, Katrina Jones, Kumar Thotapally, Diana Tull, Valerie Watson, Kayla Williams, Christina Gentry, Francine Kaufman, Chris Morrison, Elizabeth Saverino, Sherrie Schenning, Barbara Blodi, Ronald P. Danis, Matthew Davis, Kathy Glander, Gregory Guilfoil, Larry D. Hubbard, Kristine Johnson, Ronald Klein, Barbara Nardi, Michael Neider, Nancy Robinson, Eileen Rosensteel, Hugh Wabers, Grace Zhang, Alan J. Ruby, Antonio Capone, Bawa Dass, Kimberly Drenser, Bruce R. Garretson, Tarek S. Hassan, Michael Trese, George A. Williams, Jeremy Wolfe, Tina Bell, Mary Zajechowski, Dennis Bezaire, Fran McIver, Anthony Medina, Jackie Pagett, Stephanie Hatch Smith, Lynn Swartz, Tom Treuter, Andrew Antoszyk, Justin Brown, David J. Browning, Walter Holland, Angella Karow, Kelly Stalford, Angela Price, Sarah Ennis, Sherry Fredenberg, Jenna Herby, Uma Balasubramaniam, Loraine Clark, Donna McClain, Michael McOwen, Lynn Watson, Michael Klein, Steven T. Bailey, Thomas J. Hwang, Andreas Lauer, J. Timothy Stout, Patty McCollum, Milt Johnson, Patrick B. Rice, Ivana Kim, John Loewenstein, Joan Miller, Lucia Sobrin, Lucy Young, Jacqueline Sullivan, Patricia Houlihan, Linda Merry, Ann Marie Lane, Ursula Lord Bator, Claudia Evans, Sarah Brett, Charleen Callahan, Marcia Grillo, David Walsh, Kamella Lau Zimmerman, Gary Edd Fish, Rajiv Anand, Lori E. Coors, Dwain G. Fuller, Rand Spencer, Robert C. Wang, Karen Duignan, Sally Arceneaux, Hank Aguado, Nicholas Hesse, Michael Mackens, Brian Swan, Catherine Cukras, Monica Dalal, Naima Jacobs-El, Catherine Meyerle, Benjamin Nicholson, Henry Wiley, Katherine Hall Shimel, Angel Garced, Janice Oparah, Greg Short, Alana Temple, Babilonia Ayukawa, Guy Foster, Darryl Hayes, Dessie Koutsandreas, Roula Nashwinter, John Rowan, Michael Bono, Denise Cunningham, Marilois Palmer, Alicia Zetina, David H. Orth, Kourous Rezaei, Joseph Civantos, Sohail Hasan, Kirk Packo, Celeste Figliulo, Pam Stanberry, Tara Farmer, Kiersten Nelson, Shannya Townsend-Patrick, Philip Rosenfeld, Royce Chen, Rishi Doshi, Sander Dubovy, Brian T. Kim, Matthew Lowrance, Andrew Moshfeghi, Zayna Nahas, Gary Schienbaum, John Vishak, Christina Weng, Zohar Yehoshua, Belen Rodriguez, Jose Rebimbas, Jane Gleichauf, Mike Kicak, Jason Mena, Tim Odem, Elizabeth Sferza-Camp, Alicia Disgdiertt, Jim Oramas, Isabel Rams, Stephanie Thatcher, Susan B. Bressler, Neil M. Bressler, Daniel Finkelstein, Steven H. Sherman, Sharon Solomon, Howard S. Ying, Rita Denbow, Deborah Phillips, Elizabeth Radcliffe, Judy Belt, Dennis Cain, David Emmert, Mark Herring, Jacquelyn McDonald, G. Baker Hubbard, Chris S. Bergstrom, Blaine Cribbs, Andrew Hendrick, Brandon Johnson, Philip Laird, Sonia Mehta, Timothy Olsen, Justin Townsend, Jion Yan, Steven Yeh, Linda Curtis, Judy Brower, Hannah Yi, Jannah Rutter Dobbs, Debbie Jordan, Michael J. Elman, Robert A. Liss, JoAnn Starr, Jennifer Belz, Charlene Putzulo, Teresa Coffey, Ashley Davis, Pamela Singletary, Giorya Shabi Andreani, Theresa Cain, Daniel Ketner, Peter Sotirakos, Suresh Chandra, Barbara A. Blodi, Michael M. Altaweel, Justin L. Gottlieb, Michael Ip, T. Michael Nork, Thomas S. Stevens, Kathryn Burke, Shelly Olson, Kristine Dietzman, Barbara Soderling, Guy Somers, Angie Wealti, Denise Krolnik, John Peterson, Sandra Reed, Thomas Friberg, Andrew Eller, Denise Gallagher, Leanne Labriola, Melissa Pokrifka, Aron Gedansky, Natalie Anthony, Cassandra Grzybowski, Dawn Matthews, Sharon Murajda-Jumba, Jessica Toro, David G. Callanan, Wayne A. Solley, Patrick Williams, Sandy Lash, Bob Boleman, Chris Dock, Michel Shami, Brenda Arrington, Ashaki Meeks, Alan R. Margherio, Paul Raphaelian, Debra Markus, Justin Langdon, Elizabeth Truax, Sandy Lewis, Brad Terry, Amy Noffke, Kean Oh, Ramin Sarrafizadeh, Scott Sneed, Julie Hammersley, Serena Neal, Mary Doran, Nan Jones, Lisa Preston, Heather Jessick, Tanya Tracy Marsh, Michael Tolentino, Adam Berger, Richard Hamilton, David Misch, Suk Jin Moon, Dawn Sutherland, Vera Dilts, Sara Henderson, Esmeralda Medina, Donald Trueman, Laura Holm, Jason Strickland, Darmakusuma Ie, Jeffrey L. Lipkowitz, Kekul B. Shah, Susan Geraghty, Beverly Sannazzaro, Morgan Harper, Krista Bayer, Mary B. Lansing, Lauren B. Fox, Rebecca Lee, Jay B. Stallman, Michael Jacobson, Sean Koh, Scott Lampert, John Miller, Mark Rivellese, Atul Sharma, Robert A. Stoltz, Stephanie Vanderveldt, Leslie Marcus, Starr Hendricks, Ryan Hollman, Grethel Betanzos, Leslie Ellorin, Shelly Fulbright, Debbie McCormick, Paul A. Edwards, Julianne Hall, Mary Monk, Melanie Gutkowski, Melina Mazurek, Janet Murphy, Katherine Gusas, Crystal Moffett, David Burley, Nicole Chesney, Katie Kilgo, Brian Rusinek, Bradley Stern, Tracy Troszak, Rhonda Baker-Levingston, Carl W. Baker, Tracey Caldwell, Tammy Walker, Lynnette F. Lambert, Tracey Martin, Mary Jill Palmer, Tana Williams, Michael A. Novak, Joseph Coney, David G. Miller, Scott Pendergast, Lawrence Singerman, Nicholas Zakov, Hernando Zegarra, Kim DuBois, Susan Rath, Lori Revella, Tammy Brink, Kim Drury, Lisa Hogue, Mary Ilc, Connie Keller, Elizabeth McNamara, Vivian Tanner, Tamara Cunningham, John DuBois, Gregg Greanoff, Trina Nitzsche, Sheila Smith-Brewer, Ricky D. Isernhagen, John W. Kitchens, Thomas W. Stone, William J. Wood, Diana Holcomb, Virginia Therrien, Michelle Buck, Jeanne Van Arsdall, Edward Slade, Todd E. Schneiderman, David J. Spinak, Jackie Gaedke, Heather Davis Brown, Dan Helgren, Jenifer Garrison Pangelinan, Lawrence Halperin, Scott Anagnoste, Mandeep Dhalla, Krista Rosenberg, Barry Taney, W. Scott Thompson, Jaclyn Lopez, Monica Hamlin, Monica Lopez, Jamie Mariano, Evelyn Quinchia, Patricia Aramayo, Rita Veksler, Michael Lee, Richard Dreyer, Irvin Handelman, Colin Ma, Mark Peters, Stephen Hobbs, Amanda Milliron, Marcia Kopfer, Michele Connaughton, A. Christine Hoerner, R. Joseph Logan, Harry J. Wohlsein, David Boyer, Thomas G. Chu, Pouya Dayani, David Liao, Roger L. Novack, Firas M. Rahhal, Richard Roe, Homayoun Tabandeh, Janet Bayramyan, Tammy Gasparyan, Connie Hoang, Janet Kurokouchi, Tammy Eileen Lo, Richard Ngo, Mary Ann Nguyen, Michael Peyton, Charles Yoon, Julio Sierra, Adam Zamboni, Jeff Kessinger, Eric Protacio, Adam Smucker, Pamela Rath, Robert Bergren, Bernard Doft, Judy Liu, Karl Olsen, Lori Merlotti, Willia Ingram, Kellianne Marfisi, Kimberly Yeckel, Heather Schultz Carmelo, Amanda Fec, Keith McBroom, David Steinberg, Marc Levy, Jody Abrams, Melvin Chen, Waldemar Torres, Peggy Jelemensky, Mark Prybylski, Tara Raphael, Diana Appleby, Charlotte Rodman, Mark Sneath, Robert H. Rosa, Vanessa Hoelscher, Adelia Castano, Jocelyn Parker, John Hoskins, Nicholas Anderson, Joseph Googe, Tod A. McMillan, James Miller, Stephen Perkins, Kristina Oliver, Jennifer Beerbower, Bruce Gilliland, Cecile Hunt, Mike Jacobus, Raul Lince, Christopher Morris, Sarah Oelrich, Jerry Whetstone, Clement K. Chan, Steven Lin, Kim Walther, Tiana Gonzales, Lenise Myers, Kenneth Huff, David M. Brown, Eric Chen, Matthew S. Benz, Richard H. Fish, Rosa Y. Kim, James Major, Tien Pei Wong, Charles Wycoff, Cassandra Cone, Debbie Goates Gilaspia, Nubia Landaverde, Robert Smith, Deneva Zamora, Veronica Sneed, Melina Vela, Eric Kegley, Craig Greven, Shree Kurup, Charles Richards, Madison Slusher, Cara Everhart, Joan Fish, Mark Clark, David Miller, Marshall Tyler, J. Michael Jumper, Arthur D. Fu, Robert N. Johnson, Brandon Lujan, H. Richard McDonald, Rosa Rodriguez, Nina Ansari, Jeanifer Joaquin, Silvia Linares, Lizette Lopez, Jessica Sabio, Sean Grout, Chad Indermill, Yesmin Urias, Roberto Zimmerman, Linda Margulies, Sara J. Schmidt, Joy L. Meier, Sherry L. Hadley, William Rosenthal, Barbara Johnson, Lois Swafford, Richard Shields, R. Scott Varner, Richard Rosen, Ronald Gentile, Melissa Rivas, Katy W. Tai, Wanda Carrasquillo-Boyd, Robert Masini, Glenn Stoller, Ken Carnevale, Diane M. LaRosa, Barbara Burger, Tereza Conway, Carla Del Castillo, Julissa Diaz, Susan Jones, Nina Mondoc, Charlene Balfour, C.H. Vitha, Jennifer Lutz, Barbara McGinley, Fadi El Baba, Ann Marie Lavorna, Renee Jones, Jean Lewis, Ruth Tenzler, Mary Salvas-Mladek, Diane Van Kesteren, W. Copley McLean, W. Zachery Bridges, Cameron Stone, Denise Ammons, Mary Lamy, Andrea Menzel, Lea Doll Raymer, Barbara Campbell, Lisa Hawkins, Leslie Rickman, Lorraine Sherlin, Paula Price, Albert Sinyai, Ronald Kingsley, Reagan H. Bradford, Robert E. Leonard, Sonny Icks, Vanessa Bergman, Brittany Ross, Russ Burris, Amanda Butt, Rob Richmond, Alice Lyon, Manjot Gill, Lee Jampol, Rukhsana Mizra, Zuzanna Rozenbajgier, Jeremy Chapman, Lori Kaminski, Andrea Degillio, Evica Simjanoski, Jeffrey Heier, Hyung Cho, Tina Scheufele Cleary, Darin Goldman, Chirag Shah, Trexler Topping, Marissa Weber, Torsten Wiegand, Jeremy Schindelheim, Joy Bankert, Jennifer Stone, Alison Nowak, Sandy Chong, Lindsay Williams, Steven Bennett, Dennis Donovan, Margaret Graham, Cullen Jones, Anne Fung, Jan-Kristine Bayabo, Razelda Bosch, Esperanza Cruz, Ashley Emerson, Alycia Fleming, Denice Barsness, Jorge Rodriguez, Marina Soboleva, Ingrid U. Scott, Esther Bowie, Kimberly A. Neely, David A. Quillen, Laura Walter, Timothy Bennett, James Strong, John Wells, Lloyd Clark, David Johnson, Peggy Miller, Mallie Taylor, Tiffany Swinford, Robbin Spivey, Michael Banach, Lawrence Ho, Richard Lanning, Thomas R. Pheasant, Jay G. Prensky, Steven Truong, Julia Teatsworth, Michelle Dietrich, Ann Wasilus, Ann Miller, Megan Rakes, Teresa Slagle, Michelle Richards, Patricia Schuessler, Lacy Stover, Paul Beer, Naomi S. Falk, Mary Beth Shannon, Jeannie Olmeda, Don Berdeen, Joseph F. Fisher, James Folk, Stephen Russell, Barbara Taylor, Connie Hinz, Jean Walshire, Heather Stockman, Bruce Critser, Stefani Karakas, Cindy Montague, Randy Verdick, Omesh Gupta, Joseph Maguire, Christopher Brady, Francis Char DeCroos, Michael Dollin, Sunir Garg, Adam Gerstenblith, Julia Haller, Allen C. Ho, Jason Hsu, Richard Kaiser, John Pitcher, Carl Regillo, Rajiv Shah, Marc Spirn, William Tasman, James Vander, Noga Senderowitsch, Michele Formoso, Michelle Markun, Cedric George, Christina Centinaro, Lisa Grande, Stefanie Carey, Elaine Liebenbaum, Mark Humayun, Rachel Sierra, Elizabeth Corona, Margaret Padilla, Moonseok Nu, Sylvia Ramos, Cullen Barnett, Glenn Currie, Cornelia Gottlieb, Richard Garfinkel, Daniel Berinstein, Marcus Colyer, William Deegan, Michael Min-Shyue Lai, Robert Murphy, Michael Osman, Michael Rivers, Reginald Sanders, Manfred A. von Fricken, Debbie Oliver, Jeanne Kirshon, Tanya Alexander Snowden, Thomas Blondo, Alysia Cronise, Vanessa Denny, Kylie Mendez, Janine Newgen, Justin Davis, Mike Flory, Robert Frantz, Bryan Murphy, Steve Rauch, Judy E. Kim, Jane Bachman, Thomas B. Connor, Dennis P. Han, Kimberly Stepian, David V. Weinberg, William J. Wirostko, Krissa Packard, Tracy Kaczanowski, Vesper Williams, Vicki Barwick, Judy Flanders, Dennis Backes, Joe Beringer, Kristy Keller, Kathy Selchert, Paul Bernstein, Michael Teske, Albert Vitale, Susan Allman, Bonnie Carlstrom, Kimberley Wegner, Anne Haroldsen, Deborah Harrison, Cyrie Fry, James Gilman, Glen Jenkins, Paula Morris, Michael Rauser, Joseph Fan, Mukesh Suthar, Gisela Santiago, Kara Rollins Halsey, Christy Quesada, William Kiernan, Jesse Knabb, Richard Alan Lewis, Cindy Dorenbach, Steven Spencer, Dana Barnett, Joseph Morales, Barron C. Fishburne, Jeffrey G. Gross, Michael A. Magee, Amy Flowers, Angie McDowell, Randall Price, Suber Huang, Johnny Tang, Shawn Wilker, Cherie Hornsby, Lisa Ferguson, Kirk Krogstad, Riva Adamovsky, Peggy Allchin, Kathleen Carlton, Claudia Clow, Kelly Sholtis, Stephanie Burke, Mark Harrod, Stacie Hrvatin, Geoffrey Pankhurst, Nelson R. Sabates, Michael Cassell, Komal Desai, Abraham Poulose, Felix Sabates, Yin Chen, Gary Gallimore, Yolanda Konior, Nicola Kim, Sami Uwaydat, Deborah Troillett, Karen Aletter, Robert N. Frank, Gary Abrams, James Puklin, Asheesh Tewari, Cheryl Milanovic, Melanie Bailey, David Griffith, Dena McDonald, Kit Morehead, Zlatan Sadikovic, Lisa Schillace, Elizabeth Silvis, Brian Joondeph, Nancy Christmas, Alan Kimura, Mimi Liu, Stephen Petty, John Zilis, Jenny Benitez, Cassandra Berryman Catlett, Eric Fluegel, Shane Mowry, Hoang Nguyen, David Reflow, Odette M. Houghton, Seema Garg, Maurice B. Landers, Travis Meredith, Sandy Barnhart, Megha Karmalkar, Debra Cantrell, Rona Lyn Esquejo-Leon, Linda Manor, Sue Pope, David Stines, Amelia Stokely, Dean Hainsworth, Dyann Helming, Debbie Eichelberger, Mary Paige Leaton, Chuck Hamm, Edward Chaum, Alessandro Iannaccone, Barbara Jennings, Tracy Murray, Joe Mastellone, Robert Millay, Brian Kim, Theresa Goddard, Liza Jarrett Beaudette, Nina Changelian-Aitken, Fernando Corrada, Jason Dubuque, Raymond Iezzi, Sophie J. Bakri, Jose S. Pulido, Diane Vogen, Rebecca Nielsen, Karin Berg, Jean Burrington, Shannon Howard, Joan Overend, Zbigniew Krason, Denise Lewison, Thomas Link, Kevin J. Blinder, Nicholas E. Engelbrecht, M. Gilbert Grand, Daniel P. Joseph, Gaurav K. Shah, Bradley Smith, Matthew Thomas, Rhonda Weeks, Lynda Boyd, Dana Gabel, Ron Adelman, John Huang, James Kempton, Aaron Parnes, Jennifer Dupont, Elizabeth Perotti, Victoria Donaldson, Kenneth Fong, Pamela Ossorio, Anita Agarwal, Paul Sternberg, Sandy Owings, Tony Adkins, Elaine Lok, Garvin Munn, Buddy Skellie, Neelakshi Bhagat, Monique S. Roy, Marco Zarbin, Catherine Fay, Michael Lazar, Beth Malpica, Tatiana Mikheyav, Lawrence Ulanski, Jennifer Lim, Marcia Niec, Tametha Johnson, Yesenia Ovando, Catherine Nail Carroll, Mark Janowicz, Steven Schwartz, David Cupp, Michael Gorin, Gad Heilweil, Hamid Hosseini, Jean-Pierre Hubschman, Allan Kreiger, Tara Young McCannel, Carolyn Pan, David Sarraf, Irena Tsui, Joshua Udoetek, Vinad Voleti, Logan Hitchcock, Rosaleen Ostrick, Melissa Chun, Jennie Kageyama, Nilo Davila, Kristin Lipka, Christina Shin, Cynthia Owsley, Michael Albert, Richard Feist, John Mason, Martin Thomley, Angelia Johnson, Tracy Emond, Joanna Hamela, Angela Marsh, Karen Searcey, Kia Rookard, Yu-Guang He, Rafael L. Ufret-Vincenty, Mike Molai, William Anderson, John Horna, Alan Letson, Colleen Cebulla, Susie Chang, Fred Davidorf, Jill Salerno, Laura Sladoje, Christina Stetson, Jeri Perry, Scott Savage, Cynthia Toth, Glenn Jaffe, Stefanie Schuman, Neeru Sarin, Jim Crowell, Tiffanie Keaton, Michael Kelly, Brian Lutman, Marriner Skelly, Lauren Welch, Lawrence Morse, Allan Hunter, Susanna Soon-Chun Park, Cynthia Wallace, Ember Dhillon, Marisa Salvador, Barbara Holderreed, Karishma Chandra, Sashi Kaur, Ellen Redenbo, Smiley Hom, Michael Cooney, Irene Barbazetto, James M. Klancnik, John A. Sorenson, Lawrence Yannuzzi, Maria Scolaro, Eugene Agresta, Nancy Gonzalez, Sandeep Grover, K.V. Chalam, Shailesh Gupta, Christopher Lyons, Wenhua Li, Chirag Patel, Jose Carrion, Henry Ferreyra, Amberly Rodriguez, Iliana Molina, Gabriel Balea, Pam Emory, Marlene Rico, Giorgio Siqueiros, Alexander J. Brucker, Joshua Dunaief, Juan Grunwald, Benjamin Kim, Albert M. Maguire, Brian VanderBeek, Sheri Drossner, Joan DuPont, Rebecca Salvo, Jim Berger, Cheryl Devine, Bill Nyberg, Laurel Weeney, David DiLoreto, Mina Chung, Valerie Davis, Peter MacDowell, George O. Gara, Daniel Castillo, Andrea Czubinski, Melissa Keim, Brandi Hardy, Rachel Grunhaus Hollar, Lynn Schueckler, Alice T. Lyon, Aaron Weinberg, Mira Shiloach, Nicole Pelkofer, Qin Zhou, Laura McPoland, Rajendra Apte, P. Kumar Rao, Sam Pistorius, Jamie Kambarian, Eve Adcock, Sarah Gould, Melanie Quinn, Rhonda Curtis, Amy Frost, Charla Meyer, and Greg Rathert

Subjects
0301 basic medicine, medicine.medical_specialty, genetic structures, business.industry, Eye disease, Incidence (epidemiology), Fundus (eye), Macular degeneration, medicine.disease, eye diseases, Confidence interval, Geographic atrophy, 03 medical and health sciences, Ophthalmology, 030104 developmental biology, 0302 clinical medicine, Age related, 030221 ophthalmology & optometry, medicine, sense organs, Prospective cohort study, business
Abstract

Purpose To analyze the prevalence, incidence, and clinical characteristics of eyes with geographic atrophy (GA) in age-related macular degeneration (AMD), including clinical and genetic factors affecting enlargement. Design Prospective cohort study within a controlled clinical trial. Participants Age-Related Eye Disease Study 2 (AREDS2) participants, aged 50–85 years. Methods Baseline and annual stereoscopic color fundus photographs were evaluated for GA presence and area. Analyses included GA prevalence and incidence rates, Kaplan-Meier rates, mixed-model regression, and multivariable analysis of the square root of GA, area adjusted for covariates, including clinical/imaging characteristics and genotype. Main Outcome Measures (1) Presence or development of GA; (2) change in the square root of GA area over time. Results At baseline, 517 eyes (6.2%) of 411 participants (9.8%) had pre-existing GA (without neovascular AMD), with the following characteristics: 33% central, 67% noncentral; and the following configurations: 36% small, 26% solid/unifocal, 24% multifocal, 9% horseshoe/ring, and 6% indeterminate. Of the remaining 6530 eyes at risk, 1099 eyes (17.3%) of 883 participants developed incident GA without prior neovascular disease during mean follow-up of 4.4 years. The Kaplan-Meier rate of incident GA was 19% of eyes at 5 years. In eyes with incident GA, 4-year risk of subsequent neovascular AMD was 29%. In eyes with incident noncentral GA, 4-year risk of central involvement was 57%. GA enlargement rate (following square root transformation) was similar in eyes with pre-existing GA (0.29 mm/year; 95% confidence interval 0.27–0.30) and incident GA (0.28 mm/year; 0.27–0.30). In the combined group, GA enlargement was significantly faster with noncentrality, multifocality, intermediate baseline size, and bilateral GA (P Conclusions Analyses of AREDS2 data on natural history of GA provide representative data on GA evolution and enlargement. GA enlargement, which was influenced by lesion features, was relentless, resulting in rapid central vision loss. The genetic variants associated with faster enlargement were partially distinct from those associated with risk of incident GA. These findings are relevant to further investigations of GA pathogenesis and clinical trial planning.

Published
2018
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5. Sympathetic Ophthalmia Two Weeks After 23-Gauge Vitrectomy

Author

Bahaeddin El Khatib, Menka S. Patel, Alexander Hacopian, Monica Dalal, H. Nida Sen, and Marena Patronas

Subjects
genetic structures, eye diseases
Abstract

Sympathetic Ophthalmia (SO) is a rare disease that presents as a bilateral, diffuse, granulomatous panuveitis. Sympathetic Ophthalmia is a clinical diagnosis with history of penetrating ocular injury in the inciting eye and presence of panuveitis in the sympathizing eye. Though early enucleation is believed to minimize the risk, there have been reports of SO even after enucleation of inciting eyes. The possible association between vitrectomy and SO has been initially proposed by Gass [9] and later studied extensively in a large cohort in the UK with an estimated SO risk of 1 in 799 vitrectomies [11]. There have been several case series and reports of SO following vitrectomy, however only three documented cases of SO following vitrectomy without use of silicone oil. These cases demonstrated an onset of SO ranging between 4 weeks to 2 months. We present a patient with SO in the sympathizing eye presenting 16 days after an uncomplicated 23-gauge (23G) sutureless pars plana vitrectomy (PPV) without the use of silicone oil.

Published
2020
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6. Ophthalmic Issues in Chronic Kidney Disease

Author

Marc L. Weber, Andrew Kummer, Monica Dalal, and Emily Y. Chew

Subjects
medicine.medical_specialty, Kidney, education.field_of_study, business.industry, Population, Renal function, Disease, medicine.disease, Ophthalmic pathology, Surgery, medicine.anatomical_structure, Diabetes mellitus, medicine, business, Intensive care medicine, education, Retinopathy, Kidney disease
Abstract

Ophthalmic pathology and kidney diseases are intricately linked. Patients with CKD encounter well-known ophthalmic diseases such as retinopathy at a rate that exceeds the general population, particularly those with diabetic kidney disease. Furthermore, ophthalmic disease in patients with CKD tends to manifest with greater severity compared to those with normal kidney function. Beyond diabetes, there are a host of inherited and acquired diseases with both kidney and ophthalmic phenotypes. Often, a thorough ophthalmic evaluation can solidify or unify a diagnosis in a timely fashion and may even prevent unnecessary invasive procedures. Given the complexity and severity of these diseases, it appears prudent to involve the care of ophthalmology in the care of many more CKD patients, extending beyond the relationship ophthalmologists already have with diabetic patients. Future studies are clearly needed to better define the relationship and treatment of ophthalmic complications in the setting of CKD.

Published
2020
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7. Neoplastic Masquerade Syndromes in Patients With Uveitis

Author

H. Nida Sen, Robert B. Nussenblatt, Landon Grange, Susan Vitale, Chi-Chao Chan, Monica Dalal, and Amr Kouchouk

Subjects
medicine.medical_specialty, Visual acuity, business.industry, Retrospective cohort study, medicine.disease, Eye neoplasm, Dermatology, Surgery, Lymphoma, Posterior segment of eyeball, Ophthalmology, Cohort, Medicine, Young adult, medicine.symptom, business, Uveitis
Abstract

Purpose To identify the demographic and clinical characteristics, along with the frequency, of neoplastic masquerade syndromes in a tertiary uveitis clinic. Design A retrospective observational cohort. Methods Demographic and clinical data on all patients presenting to the National Eye Institute (NEI) with uveitis between 2004 and 2012 were used to compare neoplastic masquerade syndromes and uveitis. Results A total of 853 patients presenting with uveitis were identified. Of these, 21 (2.5%) were diagnosed with neoplastic masquerade syndromes. The average age at presentation of masquerade syndrome patients was 57 years (median, 55; range, 38–78); for uveitis, 42 years (median, 43; range, 3-98) ( P = 0.0003). There were 48% females in the masquerade syndromes group, compared with 59% females in the uveitis group. African American patients represented 9% of the masquerade syndrome patients and 36% of uveitis patients ( P = 0.01). Mean worse eye visual acuity was 0.89 (20/160) in neoplastic masquerade syndromes, and 0.66 (20/100) in the uveitis group ( P = 0.21). Of masquerade syndrome patients, 90% had posterior inflammation, compared with 63% of uveitis patients ( P = 0.006). Of those with masquerade syndromes, 48% of patients had unilateral disease, compared with 27% of the uveitis patients ( P = 0.04). Conclusions Patients with neoplastic masquerade syndromes were more likely to be older, male, or non-African American and to have posterior segment inflammation and unilateral disease. Patients with masquerade syndromes also had worse visual acuity than did uveitis patients. These differences in clinical characteristics may help to raise the suspicion for neoplastic masquerade syndromes.

Published
2014
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8. Comparison of Wide-Field Fluorescein Angiography and 9-Field Montage Angiography in Uveitis

Author

Elvira Agrón, Monica Dalal, Denise Cunningham, H. Nida Sen, Robert B. Nussenblatt, Breno R Lima, Divya Nigam, Darby Miller, Naima Jacobs-El, and Benjamin P. Nicholson

Subjects
Adult, medicine.medical_specialty, Adolescent, Posterior pole, Vascular leakage, Article, Fundus camera, Capillary Permeability, Young Adult, chemistry.chemical_compound, Retinal Diseases, Ophthalmology, medicine, Humans, Fluorescein Angiography, Child, Retrospective Studies, medicine.diagnostic_test, business.industry, Retinal Vessels, Uveitis, Posterior, Retinal, Middle Aged, medicine.disease, Fluorescein angiography, Wide field, Surgery, chemistry, Angiography, business, Uveitis
Abstract

To compare qualitatively and quantitatively Optos fundus camera fluorescein angiographic images of retinal vascular leakage with 9-field montage Topcon fluorescein angiography (FA) images in patients with uveitis. We hypothesized that Optos images reveal more leakage in patients with uveitis.Retrospective, observational case series.Images of all patients with uveitis imaged with same-sitting Optos FA and 9-field montage FA during a 9-month period at a single institution (52 eyes of 31 patients) were graded for the total area of retinal vascular leakage. The main outcome measure was area of fluorescein leakage.The area of apparent FA leakage was greater in Optos images than in 9-field montage images (median 22.5 mm(2) vs 4.8 mm(2), P0.0001). Of the 49 (45%) eyes with gradable photos, 22 had at least 25% more leakage in the Optos image than in the montage image; 2 (4.1%) had at least 25% less leakage in Optos; and 25 (51%) were similar in the 2 modalities. There were 2 eyes that had no apparent retinal vascular leakage in 9-field montage but were found to have apparent leakage in Optos images. Of the 49 eyes, 23 had posterior pole leakage, and of these, 17 (73.9%) showed more posterior pole leakage in the Optos image. A single 200-degree Optos FA image captured a mean 1.50× the area captured by montage photography.More retinal vascular pathology, in both the periphery and the posterior pole, is seen with Optos FA in patients with uveitis when compared with 9-field montage. The clinical implications of Optos FA findings have yet to be determined.

Published
2014
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9. Diagnostic Procedures in Vitreoretinal Lymphoma

Author

Monica Dalal, Emily Moriarty, Chi-Chao Chan, Robert B. Nussenblatt, H. Nida Sen, Megan Casady, and Lisa J. Faia

Subjects
Adult, Male, Pars plana, medicine.medical_specialty, Lymphoma, Biopsy, Retinal Neoplasms, medicine.medical_treatment, Vitrectomy, Diagnosis, Differential, Cerebrospinal fluid, Cytology, medicine, Humans, Immunology and Allergy, Invasive Procedure, Aged, Retrospective Studies, medicine.diagnostic_test, Lumbar puncture, business.industry, Brain biopsy, Middle Aged, Flow Cytometry, Surgery, Vitreous Body, Ophthalmology, medicine.anatomical_structure, Female, business, Follow-Up Studies
Abstract

Purpose: To evaluate the type and number of diagnostic interventions needed to confirm the presence of vitreoretinal lymphoma. Method: Chart review of interventions performed for diagnosis of vitreoretinal lymphoma. Results: Of the 27 cases, diagnosis was made by pars plana vitrectomy in 13 (48.1%), vitreous tap in 2 (7.4%), anterior chamber tap in 1 (3.7%), chorioretinal biopsy in 2 (7.4%), brain biopsy in 5 (18.5%), and cerebrospinal fluid cytology via lumbar puncture in 4 (14.8%). Ten (37%) had definitive results on the first procedure, and 17 (63%) had at least one false negative. Vitrectomy was the most common procedure performed. Patients required a mean of 2.1 procedures. Average time from onset of symptoms to confirmed histopathologic diagnosis was 13.9 months. Conclusion: Vitreoretinal lymphoma is difficult to recognize and requires a high degree of clinical suspicion. It often takes more than one invasive procedure to make the diagnosis.

Published
2013
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10. Diagnosis of Occult Melanoma Using Transient Receptor Potential Melastatin 1 (TRPM1) Autoantibody Testing

Author

Elizabeth A. Gamboa, Robert M. Duvoisin, Chi-Chao Chan, Brett G. Jeffrey, Catherine W. Morgans, Sunir J. Garg, H. Nida Sen, and Monica Dalal

Subjects
Pathology, medicine.medical_specialty, genetic structures, Axillary lymph nodes, medicine.diagnostic_test, business.industry, Melanoma, Autoantibody, medicine.disease, Fluorescein angiography, Occult, eye diseases, Ophthalmology, medicine.anatomical_structure, medicine, sense organs, business, TRPM1, Retinopathy, Electroretinography
Abstract

Purpose To report the first case of melanoma-associated retinopathy (MAR) and underlying occult melanoma diagnosed based on the presence of serum transient receptor potential melastatin 1 (TRPM1) autoantibodies. Design Interventional case report with basic science correlation. Participants One patient with MAR. Intervention Testing for the presence of serum TRPM1 autoantibodies. Main Outcome Measures Diagnosis of an occult melanoma involving the axillary lymph nodes (unknown primary site) and MAR based on the presence of TRPM1 autoantibodies in the patient's serum. Results The patient's clinical exam was remarkable for mild intraocular inflammation in both eyes and retinal hemorrhages with an apparent choroidal neovascularization in the left eye, which was confirmed by fluorescein angiography and indocyanine green angiography testing. Humphrey visual field 30-2 SITA-fast (Humphrey Visual Field Analyzer, Carl Zeiss Meditec, Inc, Dublin, CA) demonstrated diffuse depression in both eyes out of proportion to the clinical exams, prompting electroretinography testing that revealed an electronegative response. Dark-adapted thresholds were markedly elevated and mediated by cones. Due to concern for MAR, a systemic work-up for melanoma was performed by the primary care physician that was unrevealing. Given our continued clinical suspicion for MAR, the patient's serum was sent for evaluation for TRPM1 autoantibodies. The patient's serum applied to normal human retina exhibited positivity in the inner nuclear layer. Application of the patient's serum to wild-type and TRPM1 knockout mouse retina revealed strongly labeled bipolar cells in the wild-type retina, but not in the TRPM1 knockout retina, indicating TRPM1-dependent immunoreactivity. The antigen was confirmed as TRPM1 by labeling of TRPM1-transfected human embryonic kidney 293 cells. Additional systemic work-up prompted by this finding resulted in identification of an occult metastatic melanoma involving the axillary lymph nodes with an unknown primary site. The patient underwent surgical excision of the occult melanoma without evidence of other sites of metastases. He also received intravenous immunoglobulin therapy and his vision has stabilized. Conclusions This is the first reported case of a melanoma-associated retinopathy diagnosed utilizing the innovative approach of testing for serum TRPM1 autoantibodies. Financial Disclosure(s) Proprietary or commercial disclosure may be found after the references.

Published
2013
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11. Subconjunctival Palomid 529 in the treatment of neovascular age-related macular degeneration

Author

Monica Dalal, Benjamin P. Nicholson, Jingsheng Tuo, Catherine B. Meyerle, Chi-Chao Chan, Emily Y. Chew, Naima Jacobs-El, Robert B. Nussenblatt, and Frederick L. Ferris

Subjects
Indocyanine Green, Male, medicine.medical_specialty, Visual acuity, genetic structures, Visual Acuity, Pilot Projects, Mechanistic Target of Rapamycin Complex 2, mTORC1, Mechanistic Target of Rapamycin Complex 1, Article, Cellular and Molecular Neuroscience, Ophthalmology, medicine, Humans, Benzopyrans, Prospective Studies, Enzyme Inhibitors, Fluorescein Angiography, Coloring Agents, PI3K/AKT/mTOR pathway, Aged, Aged, 80 and over, medicine.diagnostic_test, business.industry, TOR Serine-Threonine Kinases, Macular degeneration, medicine.disease, Fluorescein angiography, Palomid 529, eye diseases, Sensory Systems, Surgery, Clinical trial, Treatment Outcome, Choroidal neovascularization, Multiprotein Complexes, Wet Macular Degeneration, Female, sense organs, medicine.symptom, business, Conjunctiva, Tomography, Optical Coherence
Abstract

Recent evidence suggests that neovascular age-related macular degeneration (AMD) may have an immune mediated component. Palomid 529, an investigational medication involving the immune Akt/mTOR pathway, is unique in dissociating both targets of rapamycin complexes TORC1 and TORC2. This small short-term pilot study assesses the safety of subconjunctival Palomid 529 in the treatment of neovascular AMD, with some limited efficacy information.In this 12-week phase I open-label prospective pilot study, five participants with neovascular age-related macular degeneration that were refractory to intravitreal anti-vascular endothelial growth factor (VEGF) received three serial monthly subconjunctival doses of 1.9 mg Palomid 529. All participants were also offered concomitant monthly intravitreal anti-VEGF injections. Safety was monitored via adverse events recording. Additional outcome measures included visual acuity, optical coherence tomography, fluorescein angiography, indocyanine green angiography and fundus photography.The study drug was well-tolerated by all participants. There were no drug-related adverse events and no serious adverse events. A depot formed at the injection site, which persisted at the end of the study. In these anti-VEGF refractory patients, no clinically important changes in best-corrected visual acuity, fluorescein leakage pattern, choroidal neovascularization size on indocyanine green angiography, or autofluorescence pattern on fundus autofluorescence were observed compared to baseline. The fluid status, assessed with optical coherence tomography showed that central retinal thickness and macular volume remained stable in three participants, while the other two participants clinically progressed.Serial subconjunctival injections of Palomid 529 were well-tolerated and resulted in depot formation. There were no concerns for any ocular or systemic toxicity during this small short-term study. Larger randomized studies are required to determine efficacy.

Published
2013
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12. Consensus on the Diagnosis and Management of Nonparaneoplastic Autoimmune Retinopathy Using a Modified Delphi Approach

Author

Austin Fox, Grazyna Adamus, Careen Y. Lowder, Catherine W. Morgans, Barbara Detrick, Wendy M. Smith, Richard W J Lee, Robert B. Nussenblatt, Thiran Jayasundera, John R. Heckenlively, H. Nida Sen, Monica Dalal, John J. Hooks, Lynn K. Gordon, Janet L. Davis, Debra A. Goldstein, Nicholas J. Butler, and Chi-Chao Chan

Subjects
Pathology, medicine.medical_specialty, Consensus, Delphi Technique, Paraneoplastic Syndromes, Clinical Sciences, Modified delphi, Delphi method, MEDLINE, Ophthalmology & Optometry, Autoimmune retinopathy, Autoantigens, Article, Retina, Autoimmune Diseases, 03 medical and health sciences, 0302 clinical medicine, Retinal Diseases, Clinical Research, Opthalmology and Optometry, Ocular diagnosis, Ocular, medicine, Humans, Intensive care medicine, Eye Disease and Disorders of Vision, Autoantibodies, business.industry, medicine.disease, Ophthalmology, 030221 ophthalmology & optometry, Public Health and Health Services, business, 030217 neurology & neurosurgery, Antiretinal antibodies, Retinopathy, Antibody detection
Abstract

© 2016 PUBLISHED BY ELSEVIER INC. Purpose To develop diagnostic criteria for nonparaneoplastic autoimmune retinopathy (AIR) through expert panel consensus and to examine treatment patterns among clinical experts. Design Modified Delphi process. Methods A survey of uveitis specialists in the American Uveitis Society, a face-to-face meeting (AIR Workshop) held at the National Eye Institute, and 2 iterations of expert panel surveys were used in a modified Delphi process. The expert panel consisted of 17 experts, including uveitis specialists and researchers with expertise in antiretinal antibody detection. Supermajority consensus was used and defined as 75% of experts in agreement. Results There was unanimous agreement among experts regarding the categorization of autoimmune retinopathies as nonparaneoplastic and paraneoplastic, including cancer-associated retinopathy and melanoma-associated retinopathy. Diagnostic criteria and tests essential to the diagnosis of nonparaneoplastic AIR and multiple supportive criteria reached consensus. For treatment, experts agreed that corticosteroids and conventional immunosuppressives should be used (prescribed) as first- or second-line treatments, though a consensus agreed that biologics and intravenous immunoglobulin were considered appropriate in the treatment of nonparaneoplastic AIR patients regardless of the stage of disease. Experts agreed that more evidence is needed to treat nonparaneoplastic AIR patients with long-term immunomodulatory therapy and that there is enough equipoise to justify randomized, placebo-controlled trials to determine if nonparaneoplastic AIR patients should be treated with long-term immunomodulatory therapy. Regarding antiretinal antibody detection, consensus agreed that a standardized assay system is needed to detect serum antiretinal antibodies. Consensus agreed that an ideal assay should have a 2-tier design and that Western blot and immunohistochemistry should be the methods used to identify antiretinal antibodies. Conclusions Consensus was achieved using a modified Delphi process to develop diagnostic criteria for nonparaneoplastic AIR. There is enough equipoise to justify randomized, placebo-controlled trials to determine whether patients with nonparaneoplastic AIR should be treated with long-term immunomodulatory therapy. Efforts to develop a standardized 2-tier assay system for the detection of antiretinal antibodies have been initiated as a result of this study.

Published
2016
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13. Reply

Author

Austin R. Fox, Lynn K. Gordon, John R. Heckenlively, Janet L. Davis, Debra A. Goldstein, Careen Y. Lowder, Robert B. Nussenblatt, Nicholas J. Butler, Monica Dalal, Thiran Jayasundera, Wendy M. Smith, Richard W. Lee, Grazyna Adamus, Chi-Chao Chan, John J. Hooks, Catherine W. Morgans, Barbara Detrick, and H. Nida Sen

Subjects
Ophthalmology
Published
2016
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14. List of Contributors

Author

Farsad Afshinnia, Anupam Agarwal, Gerald B. Appel, Susan P. Bagby, James L. Bailey, George L. Bakris, Brendan J. Barrett, Carolyn A. Bauer, Tomas Berl, Jeffrey S. Berns, Andrew Bomback, Anirban Bose, Frank C. Brosius, Lee K. Brown, David A. Bushinsky, Laurence W. Busse, Ruth C. Campbell, Helen Cathro, Lakhmir S. Chawla, Sheldon Chen, Glenn M. Chertow, Emily Chew, Michel Chonchol, David M. Clive, Debbie L. Cohen, Lewis M. Cohen, Scott D. Cohen, Ashte’ K. Collins, Sara Combs, Ricardo Correa-Rotter, Daniel Cukor, Monica Dalal, Tavis Dancik, Andrew Davenport, Sara Davison, Dick de Zeeuw, Pierre Delanaye, Sushma M. Dharia, Mirela A. Dobre, Paul Drawz, Albert W. Dreisbach, Michael Emmett, John H. Fanton, Arnold J. Felsenfeld, Hilda Fernandez, Michael F. Flessner, Barry I. Freedman, Yvette Fruchter, Susan L. Furth, Guillermo García-García, Michael J. Germain, Gregory G. Germino, Michael S. Goligorsky, Arthur Greenberg, Lisa M. Guay-Woodford, Katrina Hawkins, Charles A. Herzog, Jean L. Holley, Thomas H. Hostetter, Andrew A. House, Keith A. Hruska, Yonghong Huan, Hassan N. Ibrahim, Nashat Imran, Jonathan Chávez Iñiguez, Robert T. Isom, Kristen L. Jablonski, Kenar D. Jhaveri, Kirsten Johansen, Richard J. Johnson, Milind Y. Junghare, Duk-Hee Kang, Feras F. Karadsheh, Jameela Kari, Bertram L. Kasiske, Charbel C. Khoury, Paul L. Kimmel, Jeffrey B. Kopp, Andrew Kummer, Hiddo J.Lambers Heerspink, Lilach O. Lerman, Adeera Levin, Barton S. Levine, Susie Q. Lew, Sreedhar Mandayam, Tej K. Mattoo, Sharon E. Maynard, Timothy W. Meyer, William E. Mitch, Alvin H. Moss, Marva Moxey-Mims, Paul Muntner, Anne M. Murray, Karl A. Nath, Joel Neugarten, Gloria No, Madeleine V. Pahl, Mark S. Paller, Biff F. Palmer, Patrick S. Parfrey, Samir S. Patel, Roberto Pecoits-Filho, Steven J. Peitzman, Aldo J. Peixoto, Phuong-Chi T. Pham, Phuong-Thu T. Pham, Ton J. Rabelink, Jai Radhakrishnan, Anas Raed, Dominic S. Raj, Juan Carlos Ramirez-Sandoval, Jane F. Reckelhoff, Claudio Ronco, Mark E. Rosenberg, Mitchell H. Rosner, Brad Rovin, Prabir Roy-Chaudhury, Rebecca Ruebner, Andrew D. Rule, Jeff M. Sands, Steven J. Scheinman, Lynn E. Schlanger, Michael E. Seifert, Stephen Seliger, Ajay K. Singh, John C. Stendahl, Kameswaran Surendran, Stephen C. Textor, Ravi I. Thadhani, Raymond R. Townsend, Mark L. Unruh, Joseph A. Vassalotti, Nosratola D. Vaziri, Manuel T. Velasquez, Nisha Ver Halen, Connie J. Wang, Christoph Wanner, Marc Weber, Matthew R. Weir, Maria R. Wing, Michelle P. Winn, David C. Wymer, Jerry Yee, and Fuad N. Ziyadeh

Published
2015
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15. Subconjunctival sirolimus in the treatment of autoimmune non-necrotizing anterior scleritis: results of a phase I/II clinical trial

Author

Monica Dalal, H. Nida Sen, Robert B. Nussenblatt, Nirali Bhatt, William R Tucker, and Dominic Obiyor

Subjects
Adult, Male, medicine.medical_specialty, Intraocular pressure, Visual acuity, genetic structures, Visual Acuity, Pilot Projects, Article, Autoimmune Diseases, Anterior Eye Segment, Ophthalmology, Medicine, Humans, Prospective Studies, Adverse effect, Prospective cohort study, Intraocular Pressure, Aged, Sirolimus, business.industry, Middle Aged, Surgery, Clinical trial, Tolerability, Concomitant, Female, medicine.symptom, Injections, Intraocular, Complication, business, Conjunctiva, Immunosuppressive Agents, Scleritis
Abstract

Purpose To investigate the safety, tolerability and efficacy of subconjunctival sirolimus injections as a treatment for active, autoimmune, non-necrotizing anterior scleritis. Design Phase I/II, single-center, open-label, nonrandomized, prospective pilot study. Methods Five participants with active, autoimmune, non-necrotizing anterior scleritis with scleral inflammatory grade of ≥1+ in at least 1 quadrant with a history of flares were enrolled. A baseline injection was given, with the primary outcome measure of at least a 2-step reduction or reduction to grade zero in the study eye by 8 weeks. Secondary outcomes included changes in visual acuity and intraocular pressure, ability to taper concomitant immunosuppressive regimen, and number of participants who experienced a disease flare requiring reinjection. Safety outcomes included the number and severity of systemic and ocular toxicities, and vision loss ≥15 ETDRS letters. The study included 6 visits over 4 months with an extension phase to 1 year for participants who met the primary outcome. Results All participants (N = 5, 100%; 95% CI [0.60, 1.00]) met the primary outcome in the study eye by the week 8 visit. There was no significant change in mean visual acuity or intraocular pressure. Three out of 5 patients (60%) experienced flares requiring reinjection. No systemic toxicities were observed. Two participants (40%) experienced a localized sterile inflammatory reaction at the site of the injection, which resolved without complication. Conclusions Subconjunctival sirolimus leads to a short-term reduction in scleral inflammation, though relapses requiring reinjection do occur. There were no serious adverse events, though a local sterile conjunctival inflammatory reaction was observed.

Published
2014

16. Ocular Disease

Author

H. Nida Sen, Monica Dalal, and Robert B. Nussenblatt

Subjects
Cellular immunity, business.industry, Inflammation, Disease, medicine.disease, Ciliary body, medicine.anatomical_structure, Immune system, Antigen, Immunology, Medicine, Choroid, medicine.symptom, business, Uveitis
Abstract

Uveitis consists of inflammation of the iris, ciliary body, and choroid. Anatomical location, type of inflammation, and demographic features are important factors for elucidating the underlying etiology. The presence of uveitogenic antigens in the human eye have been established, and are thought to incite disease in conjunction with disarray of the immune system. Several elements including genetics, hormones, and environmental influences are thought to play a role in the development of uveitis. Experimental autoimmune uveitis (EAU) has been important for studying the molecular mechanisms involved, including the role of cellular immunity and cytokines. While many treatment options for uveitis exist, the continued understanding of the disease process allows for more tailored therapies.

Published
2014
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17. Ulnar Nerve Abscess and Relapse in a Patient with Indeterminate Leprosy 1 Year after Completion of Multidrug Therapy

Author

Monica Dalal, J.H. Makkannavar, Amit Agrawal, and Jayaprakash Shetty

Subjects
Male, medicine.medical_specialty, Adolescent, Prednisolone, Leprostatic Agents, Recurrence, Leprosy, Humans, Medicine, Abscess, Ulnar nerve, Glucocorticoids, Ulnar Nerve, biology, business.industry, Anti-Inflammatory Agents, Non-Steroidal, General Medicine, biology.organism_classification, medicine.disease, Surgery, Pediatrics, Perinatology and Child Health, Indeterminate leprosy, Drug Therapy, Combination, Neurology (clinical), business, Mycobacterium
Abstract

The introduction of multidrug therapy has efficiently controlled leprosy in developing countries. However, Mycobacterium laprae may survive and cause relapse despite adequate treatment with antileprosy drugs. Relapse may be characterized by a combination of new signs or symptoms and presence of acid-fast bacilli on skin or nerve biopsy samples. We report a case of a child in whom ulnar abscess developed 12 months after successful completion of multidrug therapy with clinical and histopathological evidence of relapse.

Published
2005
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18. Neurological manifestations of Hansen's disease and their management

Author

Amit Agrawal, Jayaprakash Shetty, Monica Dalal, and Lekha Pandit

Subjects
medicine.medical_specialty, Pathology, Biopsy, Leprostatic Agents, Disease, Pharmacotherapy, Leprosy, medicine, Humans, Peripheral Nerves, Mycobacterium leprae, LEPRA REACTIONS, Skin, Neurologic Examination, Nerve biopsy, medicine.diagnostic_test, biology, business.industry, Public health, Peripheral Nervous System Diseases, General Medicine, medicine.disease, biology.organism_classification, Prognosis, Dermatology, Bacterial Vaccines, Surgery, Drug Therapy, Combination, Neurology (clinical), business
Abstract

Hansen's disease is almost eliminated from developed countries but in developing countries of Africa, Asia and Latin America leprosy is still considered to be a public health problem. Mycobacterium leprae have the affinity for peripheral nerves and neuropathy is a cardinal manifestation of the disease. The nerve damage affects sensory, motor, and autonomic fibers resulting in the physical impairments and limitation of physical activities and social participation. Leprosy is a curable disease and treatment provided in the early stages will avert the disabilities. Approach to the neuritic leprosy depends on its clinical characteristics, nerve biopsy, and histological appearance of dermatological and neurological lesions. In this article we review the literature and discuss the pathology, clinical features, diagnosis and management of neurological manifestations of leprosy.

Published
2004

19. CLAVATA1 dominant-negative alleles reveal functional overlap between multiple receptor kinases that regulate meristem and organ development

Author

Frans E. Tax, Steven E. Clark, Jianming Li, Monica Dalal, Alison K. Huttly, Anne Dievart, and Alexzandria D. Lacey

Subjects
DNA, Bacterial, Recombinant Fusion Proteins, MAPK7, Meristem, Arabidopsis, F62 - Physiologie végétale - Croissance et développement, Plant Science, Protein Serine-Threonine Kinases, MAP2K7, Gene Expression Regulation, Plant, c-Raf, Alleles, Genes, Dominant, Genetics, G protein-coupled receptor kinase, biology, Cyclin-dependent kinase 4, Arabidopsis Proteins, Cyclin-dependent kinase 2, fungi, Gene Expression Regulation, Developmental, Receptor Protein-Tyrosine Kinases, Cell Biology, Plants, Genetically Modified, Phenotype, Mutation, biology.protein, Janus kinase, Protein Kinases, Proto-oncogene tyrosine-protein kinase Src, Signal Transduction, Research Article
Abstract

The CLAVATA1 (CLV1) receptor kinase controls stem cell number and differentiation at the Arabidopsis shoot and flower meristems. Other components of the CLV1 signaling pathway include the secreted putative ligand CLV3 and the receptor-like protein CLV2. We report evidence indicating that all intermediate and strong clv1 alleles are dominant negative and likely interfere with the activity of unknown receptor kinase(s) that have functional overlap with CLV1. clv1 dominant-negative alleles show major differences from dominant-negative alleles characterized to date in animal receptor kinase signaling systems, including the lack of a dominant-negative effect of kinase domain truncation and the ability of missense mutations in the extracellular domain to act in a dominant-negative manner. We analyzed chimeric receptor kinases by fusing CLV1 and BRASSINOSTEROID INSENSITIVE1 (BRI1) coding sequences and expressing these in clv1 null backgrounds. Constructs containing the CLV1 extracellular domain and the BRI1 kinase domain were strongly dominant negative in the regulation of meristem development. Furthermore, we show that CLV1 expressed within the pedicel can partially replace the function of the ERECTA receptor kinase. We propose the presence of multiple receptors that regulate meristem development in a functionally related manner whose interactions are driven by the extracellular domains and whose activation requires the kinase domain.

Published
2003

20. Autoimmune Retinopathy

Author

Landon, Grange, Monica, Dalal, Robert B, Nussenblatt, and H Nida, Sen

Subjects
Ophthalmology, Retinal Diseases, Paraneoplastic Syndromes, Ocular, Practice Guidelines as Topic, Humans, Autoantigens, Retina, Article, Autoantibodies, Autoimmune Diseases
Abstract

To provide a detailed review of current clinical guidelines for the diagnosis, work-up and treatment of autoimmune retinopathy and to preview briefly possible future therapies.Perspective based on literature review and clinical expertise.Interpretation of current literature, relying on the authors' clinical experience.Autoimmune retinopathy is a rare immunologic disease characterized by the presence of circulating antiretinal antibodies along with electroretinographic and visual field abnormalities. An ophthalmic examination can be normal or show minimal findings. The diagnosis of autoimmune retinopathy is made difficult by diagnostic criteria that are both limited and nonstandardized. Currently, the diagnosis is made based on the demonstration of serum antiretinal antibodies and the presence of clinical manifestations (including abnormal electroretinographic findings). The mere presence of these antibodies is not diagnostic. Lack of an accepted gold standard for antiretinal antibodies detection and poor interlaboratory concordance make the diagnosis challenging. There are anecdotal reports of immunosuppressive therapy in autoimmune retinopathy; however, the response to treatment is variable, with more favorable results achieved in paraneoplastic retinopathy, particularly cancer-associated retinopathy, with a combination of chemotherapy and immunosuppression. Whether an earlier attempt to treat nonparaneoplastic autoimmune retinopathy would be more beneficial is unknown. Early treatment attempts are limited by lack of sensitive and specific assays and definitive clinical criteria.Little is known about the clinical course, prognosis and treatment of autoimmune retinopathy. Additional studies should examine the specificity and pathogenicity of antiretinal antibodies and screen for biomarkers, and they should be conducted concurrently with studies seeking to identify appropriate treatment.

Published
2014
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21. Bullous variant of acral erythema due to methotrexate

Author

Monica Dalal, Sheela Kuruvila, and B Sivanesan

Subjects
Adult, Male, Antimetabolites, Antineoplastic, medicine.medical_specialty, Acral erythema, Erythema, medicine.medical_treatment, Dermatology, Biopsy, lcsh:Dermatology, Carcinoma, medicine, Mucositis, Humans, skin and connective tissue diseases, Stomatitis, Chemotherapy, integumentary system, medicine.diagnostic_test, Foot, business.industry, lcsh:RL1-803, Hand, medicine.disease, Methotrexate, Infectious Diseases, Injections, Intravenous, Carcinoma, Squamous Cell, Macular Rash, Cytarabine, Mouth Neoplasms, Drug Eruptions, medicine.symptom, business, medicine.drug
Abstract

Chemotherapy-induced acral erythema is a painful erythema of the palms and soles which occurs following chemotherapy. It is usually seen due to cytarabine, doxorubicin and fluorouracil. We present a 40-year-old male patient, a biopsy proven case of squamous cell carcinoma of the floor of the mouth, who developed a bullous variant of acral erythema after a single intravenous dose of methotrexate. He also had fever, buccal mucositis, leucopenia, thrombocytopenia and hyperpigmented macular rash on the face and upper trunk. The bullous variant of acral erythema due to methotrexate has rarely been reported.

Published
2006
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