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1. Outcomes of Combination Systemic and Intravitreal Antiviral Therapy for Acute Retinal Necrosis

Author

Aaron Lindeke-Myers, Steven Yeh, G. Baker Hubbard, Jessica G. Shantha, Chris S. Bergstrom, and Matthew R. Debiec

Subjects
Adult, Male, Herpesvirus 3, Human, medicine.medical_specialty, Time Factors, Visual acuity, genetic structures, Visual Acuity, Eye Infections, Viral, Retinitis, medicine.disease_cause, Antiviral Agents, Article, 03 medical and health sciences, 0302 clinical medicine, Ophthalmology, medicine, Humans, Retrospective Studies, 030304 developmental biology, 0303 health sciences, business.industry, Drug Administration Routes, Hazard ratio, Varicella zoster virus, Retinal detachment, Retinal Necrosis Syndrome, Acute, medicine.disease, eye diseases, Confidence interval, DNA, Viral, 030221 ophthalmology & optometry, Optic nerve, Female, sense organs, Acute retinal necrosis, medicine.symptom, business, Follow-Up Studies
Abstract

Purpose Determine the efficacy of combination intravitreal and systemic antiviral therapy for the treatment of acute retinal necrosis (ARN) and risk factors impacting visual acuity (VA) and retinal detachment (RD) outcomes. Design Single-center retrospective case series. Participants Patients with an ARN diagnosis based on clinical features and polymerase chain reaction confirmation who were treated at a tertiary referral, university-based academic practice. Methods Patient records were reviewed for demographic information including age and gender. Snellen VA, disease findings including RD outcomes, optic nerve involvement, and treatments were recorded. Incidence rates of major VA and RD outcomes were calculated based on the number of events and exposure times. Cox proportional hazards regression modeling and survival analyses were used to identify factors related to VA and RD outcomes over time. Main Outcome Measures Logarithm of the minimal angle of resolution VA, 2-line or more VA gain, severe vision loss (SVL) of 20/200 or worse, RD development, and fellow eye involvement. Results Twenty-three eyes of 21 patients (11 male, 10 female) were reviewed. Thirteen patients (62%) had herpes simplex virus and 8 patients (38%) had varicella zoster virus. The event rate for 2-line or more VA gain was 0.49 events/eye-year (95% confidence interval [CI], 0.26–0.86 events/eye-year), whereas the rate of SVL was 0.61 events/eye-year (95% CI, 0.34–1.02 events/eye-year). Retinal detachment development was observed at a rate of 0.59 events/eye-year (95% CI, 0.33–1.00 events/eye-year). Thirteen of 23 eyes (57%) demonstrated RD with a mean time of 120 days after ARN diagnosis. With each additional quadrant of retina involved, a greater risk of RD development over time was observed (hazard ratio, 2.21; 95% CI, 1.12–4.35). Nine percent of eyes progressed with additional quadrantic involvement, despite combination systemic and intravitreal antiviral therapy; however, none of the 19 patients demonstrating unilateral ARN showed fellow-eye involvement after initiation of therapy. Conclusions Combination intravitreal and systemic antiviral therapy for ARN can be effective in improving VA and limiting retinitis progression. Each additional quadrant of retina involved was associated with a 2.2-fold greater risk of RD, which may impact monitoring, timing of intervention, and patient counseling.

Published
2021
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2. Intravitreous Cutaneous Metastatic Melanoma in the Era of Checkpoint Inhibition

Author

Christopher A. Barker, Ivana K. Kim, M. Kurli, Jill R. Wells, Baker Hubbard, Codrin Iacob, Jasmine H. Francis, Jedd D. Wolchok, Hans E. Grossniklaus, Korey Jaben, Hakan Demirci, Michael A. Postow, Chris S. Bergstrom, Duncan E. Berry, Michael Engelbert, and David H. Abramson

Subjects
Melphalan, medicine.medical_specialty, Systemic disease, genetic structures, Bevacizumab, medicine.diagnostic_test, business.industry, Enucleation, Fundus photography, Retinal detachment, Context (language use), medicine.disease, eye diseases, Ophthalmology, Cutaneous melanoma, medicine, sense organs, business, medicine.drug
Abstract

Purpose Cutaneous melanoma metastatic to the vitreous is very rare. This study investigated the clinical findings, treatment, and outcome of patients with metastatic cutaneous melanoma to the vitreous. Most patients received checkpoint inhibition for the treatment of systemic disease, and the significance of this was explored. Design Multicenter, retrospective cohort study. Participants Fourteen eyes of 11 patients with metastatic cutaneous melanoma to the vitreous. Methods Clinical records, including fundus photography and ultrasound results, were reviewed retrospectively, and relevant data were recorded for each patient eye. Main Outcome Measures Clinical features at presentation, ophthalmic and systemic treatments, and outcomes. Results The median age at presentation of ophthalmic disease was 66 years (range, 23–88 years), and the median follow-up from diagnosis of ophthalmic disease was 23 months. Ten of 11 patients were treated with immune checkpoint inhibition at some point in the treatment course. The median time from starting immunotherapy to ocular symptoms was 17 months (range, 4.5–38 months). Half of eyes demonstrated amelanotic vitreous debris. Five eyes demonstrated elevated intraocular pressure, and 4 eyes demonstrated a retinal detachment. Six patients showed metastatic disease in the central nervous system. Ophthalmic treatment included external beam radiation (30–40 Gy) in 6 eyes, intravitreous melphalan (10–20 μg) in 4 eyes, enucleation of 1 eye, and local observation while receiving systemic treatment in 2 eyes. Three eyes received intravitreous bevacizumab for neovascularization. The final Snellen visual acuity ranged from 20/20 to no light perception. Conclusions The differential diagnosis of vitreous debris in the context of metastatic cutaneous melanoma includes intravitreal metastasis, and this seems to be particularly apparent during this era of treatment with checkpoint inhibition. External beam radiation, intravitreous melphalan, and systemic checkpoint inhibition can be used in the treatment of ophthalmic disease. Neovascular glaucoma and retinal detachments may occur, and most eyes show poor visual potential. Approximately one quarter of patients demonstrated ocular disease that preceded central nervous system metastasis. Patients with visual symptoms or vitreous debris in the context of metastatic cutaneous melanoma would benefit from evaluation by an ophthalmic oncologist.

Published
2020
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3. Distribution patterns of torpedo maculopathy: Further evidence of a congenital retinal nerve fiber layer-driven etiology

Author

Sherveen Salek, G. Baker Hubbard, Parker J. Williams, Robert A. Prinzi, and Chris S. Bergstrom

Subjects
Embryology, medicine.medical_specialty, RPE, retinal pigment epithelium, Nerve fiber layer, Distribution, Torpedo, Article, Congenital, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, lcsh:Ophthalmology, Ophthalmology, medicine, 030212 general & internal medicine, Hypopigmentation, CHRPE, congenital hypertrophy of the retinal pigment epithelium, Retinal pigment epithelium, OCT, optical coherence tomography, business.industry, Retinal, medicine.disease, IOP, intraocular pressure, medicine.anatomical_structure, chemistry, lcsh:RE1-994, 030221 ophthalmology & optometry, Etiology, Maculopathy, medicine.symptom, business, BCVA, best corrected visual acuity, Optic disc
Abstract

With fewer than 100 peer-reviewed cases reported in the world to date, the underlying etiology of torpedo maculopathy has remained elusive. In this literature review, we provide new evidence to better support, reject and unify claims regarding cause, diagnosis, and proper clinical management of this disease. We reviewed 44 case reports and case series, which included 77 patients (after exclusions). We additionally introduced 3 new cases from our clinical practice for a total of 80 cases. Ages at presentation ranged from 6 months old to 73 years old (mean: 24.2 years old). The nasal aspects of torpedo maculopathy lesions pointed toward the optic disc and localized to a kite-shaped region of the temporal macula, correlating with the anatomic junction of the superior arcuate, inferior arcuate, and papillomacular bundles of retinal nerve fiber layer distribution. No patterns were observed among the temporal aspects of the lesions. These findings support a congenital etiology of torpedo maculopathy and a possible influence of the retinal nerve fiber layer in the development of mature retinal pigment epithelium. Keywords: Congenital, Distribution, Embryology, Hypopigmentation, Nerve fiber layer, Torpedo

Published
2019

4. Clinical management of an outbreak of nutritionally variant streptococcus endophthalmitis following intravitreal bevacizumab injection

Author

Stephen L. Rathbun, Steven Yeh, Alexander C. Barnes, G. Baker Hubbard, Chris S. Bergstrom, Mohan N. Iyer, and Sanjana Kuthyar

Subjects
Pediatrics, medicine.medical_specialty, Bevacizumab, Disease cluster, 03 medical and health sciences, 0302 clinical medicine, Endophthalmitis, lcsh:Ophthalmology, medicine, Nutritionally-variant streptococcus, 030212 general & internal medicine, Adverse effect, Intravitreal injections, business.industry, Public health, Outbreak, Retrospective cohort study, medicine.disease, Granulicatella, Ophthalmology, lcsh:RE1-994, 030221 ophthalmology & optometry, Vancomycin, Original Article, business, medicine.drug
Abstract

Background The management of an outbreak of endophthalmitis associated with intravitreal bevacizumab represents a challenging real-time process involving identification of cases, treatment and mitigation measures during the outbreak. We summarize the clinical presentation and management of a cluster of endophthalmitis cases from contaminated bevacizumab, in addition to mathematical probabilistic assessment of the number of cases that define an outbreak. Methods A retrospective study was conducted to assess the management of an endophthalmitis outbreak after intravitreal bevacizumab (IVB) administration. Demographic data, clinical information, individual patient management and public health reporting measures were reviewed. Outcomes of patients who received prophylactic antibiotics for endophthalmitis prevention were also reviewed. Binomial tail probability calculations were performed to determine the likelihood of clusters of endophthalmitis that could inform when an outbreak was evolving that would warrant more public health notification measures and communication. Results Forty-five eyes of 42 patients who received IVB from a single batch were reviewed. Four cases of endophthalmitis from Granulicatella adiacens, a nutritionally-variant Streptococcus species, were treated successfully with intravitreal antibiotics ± vitrectomy. Thirty-four of the remaining 41 eyes were treated with prophylactic intravitreal vancomycin with no additional cases of endophthalmitis. Outbreak management also included CDC, ASRS and public health authority notification. Binominal tail probabilities demonstrated the rarity of clusters from a single batch (i.e. ~ 1/10,000 for 2 cases; 1/2 million for 3 cases). However, given the U.S. scale of IVB administration, there is an 87% chance of a cluster ≧ 2 and a 1% chance of a cluster ≧ 3 cases annually, which may guide outbreak management. A process diagram was developed to incorporate patient management and public health measures when an outbreak is suspected. Conclusion Intravitreal antibiotics and vitrectomy were effective in the individual management of cases of endophthalmitis, and no serious adverse events occurred with prophylactic intravitreal vancomycin for at-risk eyes. Best practices for outbreaks should be evaluated, given their likelihood within the U.S. and the sight-threatening consequences of endophthalmitis.

Published
2021
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5. 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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6. 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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7. Comparative outcomes and toxicities for ruthenium-106 versus palladium-103 in the treatment of choroidal melanoma

Author

Hans E. Grossniklaus, Pia R. Mendoza, Matthew J. Ferris, Mohammad K. Khan, H. Danish, Chris S. Bergstrom, Maria M. Choudhary, John H. Suh, Ian R. Crocker, Caroline Craven, Ehsan H. Balagamwala, Arun D. Singh, Thomas M. Aaberg, Kirtesh R. Patel, and Jeffrey M. Switchenko

Subjects
Male, Cancer Research, medicine.medical_specialty, Skin Neoplasms, Visual acuity, Radiation retinopathy, Brachytherapy, Urology, Dermatology, Article, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Melanoma, Aged, Retrospective Studies, Radioisotopes, business.industry, Choroid Neoplasms, Hazard ratio, Retrospective cohort study, Odds ratio, Middle Aged, medicine.disease, Confidence interval, Oncology, 030220 oncology & carcinogenesis, Toxicity, 030221 ophthalmology & optometry, Female, Ruthenium Radioisotopes, medicine.symptom, business, Palladium, Retinopathy
Abstract

PURPOSE: For treatment of choroidal melanoma, Palladium-103 ((103)Pd) and Ruthenium-106 ((106)Ru) plaque brachytherapy demonstrates reduced toxicity compared to the historical standard Iodine-125 ((125)I). No report has directly compared clinical outcomes between (103)Pd and (106)Ru, and reasons for selection of one over the other remain purely theoretical. MATERIALS/METHODS: Patients with choroidal melanoma with apical tumor height ≤ 5 mm were included. Patients from Emory University were treated with (103)Pd between 1993 and 2012. Patients from Cleveland Clinic were treated with (106)Ru between 2005 and 2010. Medical records were retrospectively reviewed. We compared post-treatment visual acuity (VA), toxicity, and oncologic outcomes. RESULTS: (103)Pd patients (n = 124) and (106)Ru patients (n = 42) had median follow up of 4.2 and 5.0 years, respectively. Radiation retinopathy-free survival was similar for both radioisotopes but (106)Ru had lower grades of retinopathy (p=0.006). (103)Pd was associated with worse VA preservation (≥20/40) by year 3 (OR 3.8, 95% CI 1.01–14.31, p=0.048). (103)Pd was associated with higher distant metastases-free survival (DMFS) in multivariate analysis (MVA) (HR 0.10, 95% CI 0.02–0.38, p

Published
2018
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8. Visual acuity, oncologic, and toxicity outcomes with 103 Pd vs. 125 I plaque treatment for choroidal melanoma

Author

Thomas M. Aaberg, Elizabeth Butker, Sahitya Reddy, Chris S. Bergstrom, Jeffrey M. Switchenko, Hans E. Grossniklaus, Mudit Chowdhary, Caroline Craven, Pia R. Mendoza, Kirtesh R. Patel, H. Danish, Roshan S. Prabhu, and Ian R. Crocker

Subjects
Choroidal melanoma, medicine.medical_specialty, Multivariate analysis, Visual acuity, Radiation retinopathy, business.industry, Plaque brachytherapy, Urology, Odds ratio, medicine.disease, Surgery, 03 medical and health sciences, 0302 clinical medicine, Oncology, 030220 oncology & carcinogenesis, Toxicity, Propensity score matching, 030221 ophthalmology & optometry, medicine, Radiology, Nuclear Medicine and imaging, medicine.symptom, business
Abstract

Purpose To evaluate outcomes of choroidal melanoma patients treated with 125I or 103Pd plaque brachytherapy. Methods and Materials From 1993 to 2012, our institution treated 160 patients with 103Pd (56.1%) and 125 patients with 125I (43.9%) plaque brachytherapy. Tumor outcomes, visual acuity (VA), and toxicity were compared. Multivariate analyses (MVAs) and propensity score analysis were used to help address differences in baseline characteristics. Results Median followup was longer for 125I patients, 52.7 vs. 43.5 months (p 90% 3-year overall survival and >93% 5-year secondary enucleation-free survival. On MVA, radionuclide was not predictive for tumor outcomes. A higher percentage maintained vision better than 20/40 with 103Pd (63% vs. 35%, p = 0.007) at 3 years. MVA demonstrated 103Pd radionuclide (odds ratio [OR]: 2.12, p = 0.028) and tumor height ≤5 mm (OR: 2.78, p = 0.017) were associated with VA better than 20/40. Propensity score analysis matched 23 125I with 107 103Pd patients. 103Pd continued to predict better VA at 3 years (OR: 8.10, p = 0.014). On MVA for the development of VA worse than 20/200 or degree of vision loss, radionuclide was not significant. Lower rates of radiation retinopathy were seen with 103Pd than 125I (3 years: 47.3% vs. 63.9%, p = 0.016), with radionuclide significant in MVA. Conclusions Both 125I and 103Pd achieve excellent tumor control. An increased probability of long-term VA better than 20/40 and reduced risk of radiation retinopathy is associated with 103Pd.

Published
2017
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9. SEVERE PANUVEITIS, RETINAL VASCULITIS, AND OPTIC DISK GRANULOMA SECONDARY TO SARCOIDOSIS

Author

Hans E. Grossniklaus, W. Lloyd Clark, John F. Payne, Chris S. Bergstrom, and Michael Patterson

Subjects
Adult, Male, Retinal Vasculitis, Pathology, medicine.medical_specialty, Granuloma, Sarcoidosis, Retinal vasculitis, business.industry, Panuveitis, Optic disk, Caseous necrosis, General Medicine, medicine.disease, Article, Ophthalmology, Optic Nerve Diseases, medicine, Optic nerve, Humans, business, Uveitis
Abstract

Purpose: To report a case of panuveitis, retinal vasculitis, and optic disk granuloma due to sarcoidosis. Methods: Case report and literature review. Results: A 26-year-old previously healthy African American male presented with four months of gradual progressive visual decline in the right eye. Clinical examination revealed severe panuveitis, retinal vasculitis, and large optic nerve mass lesion. Diffuse supraclavicular lymphadenopathy was also present. Histopathologic examination of the lymph node biopsy revealed granulomatous inflammation with some areas of caseous necrosis consistent with sarcoidosis. Conclusion: Sarcoidosis is a common cause of uveitis and retinal vasculitis. In rare cases, an optic disk granuloma may occur and can be treated with immunosuppressive therapy.

Published
2016
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10. Intraocular T-cell Lymphoma: Clinical Presentation, Diagnosis, Treatment, and Outcome

Author

Chris S. Bergstrom, Radgonde Amer, Edoardo Baglivo, Hans E. Grossniklaus, Florence Chaput, Chi-Chao Chan, Bahram Bodaghi, Valérie Touitou, Phuc LeHoang, Alexandra Kozyreff, Dominique Bron, Jacob Pe'er, Laure Caspers, UCL - (SLuc) Service d'ophtalmologie, and UCL - SSS/IREC/SLUC - Pôle St.-Luc

Subjects
Male, genetic structures, medicine.medical_treatment, Visual Acuity, Vitrectomy, Central Nervous System Neoplasms, Tertiary Care Centers, 0302 clinical medicine, Intraocular Lymphoma, Immunology and Allergy, T-cell lymphoma, Injections, Spinal, Aged, 80 and over, medicine.diagnostic_test, T-lymphoma, Middle Aged, Treatment Outcome, Intravitreal Injections, Female, Intraocular lymphoma, Uveitis, Immunosuppressive Agents, Adult, medicine.medical_specialty, Primary vitreoretinal lymphoma, Lymphoma, T-Cell, Eye neoplasm, 03 medical and health sciences, Biopsy, medicine, Humans, Aged, Retrospective Studies, Radiotherapy, business.industry, Eye Neoplasms, medicine.disease, eye diseases, Surgery, Lymphoma, Radiation therapy, Ophthalmology, Methotrexate, 030221 ophthalmology & optometry, sense organs, business, 030217 neurology & neurosurgery
Abstract

Purpose: To report on the clinical data of seven patients with T-cell intraocular lymphoma (IOL). Methods: Retrospective case series. Results: Seven immunocompetent patients, 12 eyes, 6 women, with T-cell-IOL were included from five countries. Mean age was 53.5 years (range: 25–82). Four patients had systemic-ocular lymphoma, two had CNS-ocular lymphoma, and one had systemic-CNS- ocular lymphoma. Vitritis was the most frequent clinical sign, followed by anterior uveitis and serous retinal detachment. Cytopathologic examination was performed on all ocular specimens (vitreous in six and iris mass biopsy in one patient). Adjunctive diagnostic procedures included immunohistochemistry, molecular tests, and cytokine profiling of vitreous samples. Treatment modalities included systemic chemotherapy (five patients), intravitreal methotrexate (three patients), globe radiotherapy, and intrathecal chemotherapy. Mean survival from diagnosis was 21.7 months (range: 2–69). Two patients are still alive. Conclusions: T-cell IOL has variable clinical manifestations and prognosis. Systemic involvement, SRD, and vitreoretinal involvement were frequently observed.

Published
2016

11. Primitive Neuroectodermal Tumor/Ewing Sarcoma of the Retina

Author

Chris S. Bergstrom, Hans E. Grossniklaus, Bahig M. Shehata, G. Baker Hubbard, and Poul H. Sorensen

Subjects
Male, Friend leukemia, Pathology, medicine.medical_specialty, Oncogene Proteins, Fusion, Retinal Neoplasms, Enucleation, CD99, Sarcoma, Ewing, Biology, Pathology and Forensic Medicine, Ciliary body, medicine, Humans, Neuroectodermal Tumors, Primitive, Peripheral, Child, Dense core granule, Proto-Oncogene Protein c-fli-1, Retinoblastoma, General Medicine, medicine.disease, eye diseases, Medical Laboratory Technology, medicine.anatomical_structure, Phosphopyruvate Hydratase, Primitive neuroectodermal tumor, Sarcoma
Abstract

An 11-year-old boy underwent enucleation of his left eye for an intraocular tumor. Examination showed a small, round blue cell tumor arising in the peripheral retina near the ciliary body. Immunohistochemical stain results were positive for neuron-specific enolase, synaptophysin, cluster of differentiation 99 (CD99), Friend leukemia integration 1, and CD56. Ultrastructural findings included occasional intracytoplasmic dense core granules. Polymerase chain reaction of the tumor showed a Ewing sarcoma/Friend leukemia integration gene fusion product. The tumor was classified as a primitive neuroectodermal tumor/Ewing sarcoma of the retina and should be distinguished from retinoblastoma. To our knowledge, this is the first case of primary primitive neuroectodermal tumor of the retina.

Published
2012
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12. Vogt-Koyanagi-Harada-like syndrome after CTLA-4 inhibition with ipilimumab for metastatic melanoma

Author

Chris S. Bergstrom, Matthew R. Debiec, David H. Lawson, Steven Yeh, Jason N. Crosson, and Philip W. Laird

Subjects
Cancer Research, Skin Neoplasms, medicine.medical_treatment, T-Lymphocytes, Immunology, Ipilimumab, Autoimmunity, medicine.disease_cause, Autoantigens, Article, Immune tolerance, Antigen, HLA-A2 Antigen, medicine, Immunology and Allergy, Cytotoxic T cell, Humans, CTLA-4 Antigen, Neoplasm Metastasis, Melanoma, Pharmacology, business.industry, Antibodies, Monoclonal, Immunotherapy, Middle Aged, medicine.disease, eye diseases, CTLA-4, Cancer research, Melanocytes, Female, business, Uveomeningoencephalitic Syndrome, medicine.drug
Abstract

Cytotoxic T-lymphocyte-associated antigen is a naturally occurring inhibitor of T-cell costimulation. Monoclonal antibody inhibition of cytotoxic T-lymphocyte-associated antigen with ipilimumab blocks this negative regulator of costimulation, promoting T-cell activation and survival, and leads to melanoma regression. Findings of the Vogt-Koyanagi-Harada (VKH) syndrome, an uveomeningitic syndrome that features neurological, auditory, ophthalmologic, and cutaneous involvement because of autoimmune targeting of melanocytic antigen, have rarely been described in association with melanoma immunotherapy. We describe a case of VKH-like syndrome in a 45-year-old HLA-A02-positive patient with metastatic melanoma treated with ipilimumab. Disruption of immune tolerance by ipilimumab led to melanoma remission while also inciting systemic and ophthalmic autoimmunity toward melanocytic antigen. These observations provide insight into the pathophysiology of the VKH syndrome, and the balance between tumor-associated tolerance and autoimmunity.

Published
2015

13. Fundus autofluorescence features in the inflammatory maculopathies

Author

Aaron Y. Lee, Jiong Yan, Chris S. Bergstrom, Steven Yeh, Farzin Forooghian, and Cecilia S. Lee

Subjects
Pathology, medicine.medical_specialty, genetic structures, media_common.quotation_subject, Scars, fundus autofluorescence imaging, Foveal, Ophthalmology, medicine, media_common, Original Research, Serpiginous choroiditis, business.industry, Acute posterior multifocal placoid pigment epitheliopathy, Convalescence, Clinical Ophthalmology, medicine.disease, quantification, eye diseases, 3. Good health, Autofluorescence, Maculopathy, Punctate inner choroiditis, posterior uveitis, sense organs, medicine.symptom, business, foveal autofluorescence
Abstract

Cecilia S Lee,1 Aaron Y Lee,2 Farzin Forooghian,3 Chris S Bergstrom,1 Jiong Yan,1 Steven Yeh11Section of Vitreoretinal Disease and Surgery, Department of Ophthalmology, Emory Eye Center, Emory University, Atlanta, GA, USA; 2Department of Ophthalmology and Visual Sciences, Washington University in St Louis, St Louis, MO, USA; 3Department of Ophthalmology and Visual Sciences, University ofBritish Columbia, Vancouver, BC,CanadaPurpose: To describe the fundus autofluorescence (FAF) features of the inflammatory ­maculopathies and develop a quantification method for FAF analysis.Methods: This is a retrospective, consecutive case series of patients with inflammatory maculopathies from two tertiary centers. The clinical findings, demographics, and FAF imaging characteristics were reviewed. Foveal autofluorescence (AF) was analyzed. Median and standard deviation (SD) of foveal AF intensity were measured.Results: Thirty eyes of 15 patients were evaluated with both qualitative and quantitative FAF analysis. In acute macular neuroretinopathy, the active phase showed foveal hypoautofluorescence, which became hypoautofluorescent with resolution. In acute posterior multifocal placoid pigment epitheliopathy, multiple lesions with hypoautofluorescent centers with hyperautofluorescent borders were observed in active disease and became hypoautofluorescent with disease convalescence. In multifocal choroiditis and punctate inner choroiditis, the active hyperautofluorescent lesions progressed to inactive, hypoautofluorescent scars. Active serpiginous choroiditis showed hyperautofluorescent borders adjacent to a helicoid-shaped, hypoautofluorescent scar. Active unilateral acute idiopathic maculopathy (UAIM) showed a complex pattern of hypo- and hyperautoflourescence in the macula. The median foveal AF was the greatest in acute macular neuroretinopathy and UAIM among the maculopathies, while the greatest SD of foveal AF intensity was observed in UAIM.Conclusion: The active phase of the majority of inflammatory maculopathies was characterized by hyperautofluorescent lesions. Increased SD of foveal AF correlated with a mixture of hypo- and hyperautoflourescence. Median and SD may be useful metrics in foveal AF and quantifiable values that may be assessed over time as a disease process evolves. Improvements in quantification methods of FAF imaging may allow us to objectively evaluate posterior uveitis.Keywords: posterior uveitis, foveal autofluorescence, quantification, fundus autofluorescence imaging

Published
2014

14. Diagnostic Vitrectomy for Primary Intraocular Lymphoma: When, Why, How?

Author

Cindy S. Hwang, Steven Yeh, and Chris S. Bergstrom

Subjects
Pars plana, medicine.medical_specialty, genetic structures, medicine.medical_treatment, Vitrectomy, Diagnostic Techniques, Ophthalmological, Article, Diagnosis, Differential, Intraocular Lymphoma, Ophthalmology, medicine, Humans, medicine.diagnostic_test, business.industry, Gene rearrangement, medicine.disease, Fluorescein angiography, eye diseases, medicine.anatomical_structure, Cytopathology, Intraocular lymphoma, sense organs, Differential diagnosis, business, Uveitis
Abstract

Primary intraocular lymphoma (PIOL) can present with uveitis, vitritis, or chorioretinal lesions. While fluorescein angiography, fundus autofluorescence, and optical coherence tomography may aid in the diagnosis of PIOL, a definitive diagnosis can only be achieved with tissue analysis. The specimen may be obtained with a vitreous or aqueous tap, however, a diagnostic pars plana vitrectomy with acquisition of diluted and undilated vitreous fluid or a chorioretinal biopsy is preferable. Once a specimen is obtained, cytopathology, flow cytometry, immunohistochemistry, gene rearrangement studies with polymerase chain reaction, and cytokine analysis can be performed to confirm the diagnosis of PIOL. Treatment is dependent on the presentation of PIOL and may include systemic chemotherapy, local intravitreal chemotherapy, radiation or a combination of therapies.

Published
2014

15. The American Brachytherapy Society consensus guidelines for plaque brachytherapy of uveal melanoma and retinoblastoma

Author

Mark J. Rivard, Virpi Raivio, Walter Choi, Lars Hjelmqvist, John E. Mignano, Ekaterina Semenova, Santosh G Honavar, Stefan Seregard, E. Rand Simpson, Lorenzo Brualla, Chris S. Bergstrom, Marie Lundell, P. Mayles, Charlotta All-Eriksson, S.V. Saakyan, Normand Laperrierre, Holger Geischen, R Doug Errington, Anush Amiryan, Vladimir Valskiy, A. Mazal, Nina Kalach, Naoya Murakami, Rémi Dendale, Hans E. Grossniklaus, Shigenobu Suzuki, Göran Lundell, Laurence Desjardins, Pradeep Patra, Vijay Anand P. Reddy, Norbert Bornfeld, Matthew W. Wilson, Georges Sinclair, Bertil Damato, Wolfgang Sauerwein, Brenda L. Gallie, Ian R. Crocker, Jay S. Duker, Tero Kivelä, Barrett G. Haik, Akbar Beiki-Ardakani, Paul T. Finger, Elizabeth Butker, D. Fluehs, Jorma Heikkonen, and Helen Mayles

Subjects
Uveal Neoplasms, medicine.medical_specialty, Consensus, medicine.medical_treatment, Retinal Neoplasms, Brachytherapy, Medizin, Guidelines, Subspecialty, ABS, medicine, Methods, Humans, Radiology, Nuclear Medicine and imaging, Medical physics, Melanoma, Plaque, Radiation, Retinoblastoma, business.industry, Plaque brachytherapy, medicine.disease, eye diseases, United States, Radiation therapy, medicine.anatomical_structure, Oncology, Radiology Nuclear Medicine and imaging, Practice Guidelines as Topic, Choroid, business, Dose rate
Abstract

Purpose To present the American Brachytherapy Society (ABS) guidelines for plaque brachytherapy of choroidal melanoma and retinoblastoma. Methods and Materials An international multicenter Ophthalmic Oncology Task Force (OOTF) was assembled to include 47 radiation oncologists, medical physicists, and ophthalmic oncologists from 10 countries. The ABS-OOTF produced collaborative guidelines, based on their eye cancer–specific clinical experience and knowledge of the literature. This work was reviewed and approved by the ABS Board of Directors as well as within the journal's peer-reivew process. Results The ABS-OOTF reached consensus that ophthalmic plaque radiation therapy is best performed in subspecialty brachytherapy centers. Quality assurance, methods of plaque construction, and dosimetry should be consistent with the 2012 joint guidelines of the American Association of Physicists in Medicine and ABS. Implantation of plaque sources should be performed by subspecialty-trained surgeons. Although there exist select restrictions related to tumor size and location, the ABS-OOTF agreed that most melanomas of the iris, ciliary body, and choroid could be treated with plaque brachytherapy. The ABS-OOTF reached consensus that tumors with gross orbital extension and blind painful eyes and those with no light perception vision are unsuitable for brachytherapy. In contrast, only select retinoblastomas are eligible for plaque brachytherapy. Prescription doses, dose rates, treatment durations, and clinical methods are described. Conclusions Plaque brachytherapy is an effective eye and vision-sparing method to treat patients with intraocular tumors. Practitioners are encouraged to use ABS-OOTF guidelines to enhance their practice.

Published
2013

16. Short-Term Outcomes of Aflibercept for Neovascular Age-Related Macular Degeneration in Eyes Previously Treated With Other Vascular Endothelial Growth Factor Inhibitors

Author

Chris S. Bergstrom, G. Baker Hubbard, Blaine Cribbs, Vincent Y. Ho, Jiong Yan, Steven Yeh, and Timothy W. Olsen

Subjects
Male, Vascular Endothelial Growth Factor A, Fovea Centralis, medicine.medical_specialty, Visual acuity, genetic structures, Bevacizumab, Recombinant Fusion Proteins, Visual Acuity, Angiogenesis Inhibitors, Antibodies, Monoclonal, Humanized, Article, chemistry.chemical_compound, Ranibizumab, Ophthalmology, medicine, Humans, Aged, Retrospective Studies, Aflibercept, Aged, 80 and over, Drug Substitution, business.industry, Fovea centralis, Middle Aged, Macular degeneration, medicine.disease, eye diseases, Confidence interval, Surgery, Vascular endothelial growth factor, Receptors, Vascular Endothelial Growth Factor, Treatment Outcome, medicine.anatomical_structure, chemistry, Intravitreal Injections, Wet Macular Degeneration, Drug Therapy, Combination, Female, sense organs, medicine.symptom, business, Tomography, Optical Coherence, Follow-Up Studies, medicine.drug
Abstract

Purpose To report results of aflibercept therapy in eyes with neovascular age-related macular degeneration previously treated with bevacizumab, ranibizumab, or both. Design Retrospective, interventional, noncomparative, consecutive case series. Methods Ninety-six eyes from 85 patients with neovascular age-related macular degeneration who previously had received bevacizumab, ranibizumab, or both were treated with aflibercept monthly for 3 months followed by a fourth injection within 2 months. Outcomes were determined 4 ± 1 months after the first aflibercept dose and included: proportion of patients gaining or losing 2 lines or more of best-corrected visual acuity, proportion remaining within a gain or loss of 1 line, mean change in logarithm of the minimal angle of resolution visual acuity, mean change in central foveal thickness, mean change in macular cube volume, and qualitative anatomic response as assessed by spectral-domain optical coherence tomography. Results At baseline, 82 (85%) eyes had signs of active exudation despite a mean of 17 previous anti–vascular endothelial growth factor injections. At final visit, 82 (85%) remained stable within a gain or loss of 1 line, 7 (7%) gained 2 lines or more, and 7 (7%) lost 2 lines or more of best-corrected visual acuity. Mean logarithm of the minimal angle of resolution visual acuity showed minimal change 0.02 (range, −0.46 to 0.70; P = .14). Mean central foveal thickness decreased −18 μm (range, −242 to 198 μm; P = .06). Mean macular volume decreased −0.27 mm 3 (95% confidence interval, −0.4 to −0.1 mm 3 ; P = .004). On qualitative analysis, 4 (5%) eyes had complete resolution of exudative fluid, 40 (49%) showed partial resolution, 26 (32%) remained unchanged, and 12 (14%) showed worsened exudative fluid. Conclusions Aflibercept seems to be an effective alternative for neovascular age-related macular degeneration patients previously treated with bevacizumab, ranibizumab, or both at 4 months of follow-up. Most treated eyes demonstrated stable visual acuity and anatomic improvements by spectral-domain optical coherence tomography.

Published
2013
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17. Multimodality Diagnostic Imaging in Unilateral Acute Idiopathic Maculopathy

Author

Chris S. Bergstrom, John F. Payne, Steven Yeh, G. Baker Hubbard, Cecilia S. Jung, Timothy W. Olsen, Blaine Cribbs, and Jiong Yan

Subjects
Adult, Indocyanine Green, Male, Pathology, medicine.medical_specialty, Visual acuity, genetic structures, Visual Acuity, Article, Ophthalmoscopy, chemistry.chemical_compound, Retinal Diseases, Electroretinography, Humans, Medicine, Macula Lutea, Fluorescein Angiography, Retrospective Studies, Retina, Retinal pigment epithelium, medicine.diagnostic_test, Choroid, business.industry, Middle Aged, Fluorescein angiography, medicine.disease, eye diseases, Ophthalmology, medicine.anatomical_structure, chemistry, Acute Disease, Maculopathy, Female, sense organs, medicine.symptom, business, Indocyanine green, Tomography, Optical Coherence
Abstract

Objective To describe the clinical features and imaging characteristics in unilateral acute idiopathic maculopathy. Methods Retrospective review of 4 patients with a diagnosis of unilateral acute idiopathic maculopathy. Clinical characteristics (age, symptoms, Snellen visual acuity, and funduscopic features) and images from spectral-domain optical coherence tomography, fundus autofluorescence, fluorescein angiography, and indocyanine green angiography were analyzed. Results The median (range) age at presentation was 31 (27-52) years. The median (range) interval between symptom onset and presentation was 4 (1-20) weeks. Associated systemic findings included a viral prodrome (50%), orchitis (50%), hand-foot-mouth disease (25%), and positive coxsackievirus titers (50%). The median (range) visual acuity at initial examination was 20/400 (20/70 to 1/400), which improved to 20/30 (20/20 to 20/60) at final follow-up. The median (range) follow-up time was 8 (8-13) weeks. Early in the disease course, the central macula developed irregular, circular areas of white-gray discoloration. Following recovery, the macula had a stippled retinal pigment epithelium characterized by rarefaction and hyperplasia. Fluorescein angiography demonstrated irregular early hyperfluorescence and late subretinal hyperfluorescence. Spectral-domain optical coherence tomography showed a partially reversible disruption of the outer photoreceptor layer. Fundus autofluorescence initially revealed stippled autofluorescence that eventually became more hypoautofluorescent. Indocyanine green angiography showed “moth-eaten”–appearing choroidal vasculature, suggestive of choroidal inflammation. Conclusions The imaging characteristics highlight the structural changes during the active and resolution phases of unilateral acute idiopathic maculopathy. The visual recovery correlates with structural changes and suggests that the pathogenesis involves inflammation of the inner choroid, retinal pigment epithelium, and outer photoreceptor complex that is partially reversible.

Published
2012
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