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1. Randomized trial of bilateral gene therapy injection for m.11778G>A MT-ND4 Leber optic neuropathy

Author

Newman, Nancy J, Yu-Wai-Man, Patrick, Subramanian, Prem S, Moster, Mark L, Wang, An-Guor, Donahue, Sean P, Leroy, Bart P, Carelli, Valerio, Biousse, Valerie, Vignal-Clermont, Catherine, Sergott, Robert C, Sadun, Alfredo A, Rebolleda Fernández, Gema, Chwalisz, Bart K, Banik, Rudrani, Bazin, Fabienne, Roux, Michel, Cox, Eric D, Taiel, Magali, Sahel, José-Alain, Giulia, Amore, Shweta, Anand, Rudrani, Banik, Piero, Barboni, Valérie, Biousse, Hayley, Boston, Asma, Burale, Michele, Carbonelli, Valerio, Carelli, Celia, Chen, Hui-Chen, Cheng, Steve, Cho, Manuela, Contin, Pietro, D’Agati, DeBusk, Adam A, Julie, De Zaeytijd, Jannah, Dobbs, Lindreth, DuBois, Simona, Esposti, Alcides, Fernandes Filho, Elizabeth, Fortin, Sapna, Gangaputra, Deborah, Gibbs, François, Girmens Jean, Rabih, Hage, Haller, Julia A, Gad, Heilweil, George Baker, Hubbard III, Jeong-Min, Hwang, Laia, Jaumendreu Urquijo, Neringa, Jurkute, Rustum, Karanjia, Wahiba, Khemliche, La Chiara, Morgia, Maria, Massini, Marc, Mathias, Memon, Muhammad A, Susan, Mohamed, Muñoz Negrete, Francisco J, Ghazala, O’Keefe, Shriji, Patel, Paula, Pecen, Peragallo, Jason H, Lise, Plaine, Mary, Preston, Gema, Rebolleda Fernández, Martina, Romagnoli, José-Alain, Sahel, Melissa, SantaMaria, Chuanbin, Sun, Katy, Tai, Heather, Tollis, Irena, Tsui, Tucker, William R, Catherine, Vignal-Clermont, An-Guor, Wang, Saige, Wilkins, and Patrick, Yu-Wai-Man

Subjects
Biomedical and Clinical Sciences, Ophthalmology and Optometry, Clinical Research, Genetics, Neurosciences, Clinical Trials and Supportive Activities, Eye Disease and Disorders of Vision, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Eye, Humans, DNA, Mitochondrial, Genetic Therapy, Inflammation, Mutation, Optic Atrophy, Hereditary, Leber, LHON REFLECT Study Group, NADH dehydrogenase 4, leber hereditary optic neuropathy, lenadogene nolparvovec, mitochondrial DNA, recombinant adeno-associated virus vector 2, Medical and Health Sciences, Psychology and Cognitive Sciences, Neurology & Neurosurgery, Biomedical and clinical sciences, Health sciences, Psychology
Abstract

Leber hereditary optic neuropathy (LHON) is an important example of mitochondrial blindness with the m.11778G>A mutation in the MT-ND4 gene being the most common disease-causing mtDNA variant worldwide. The REFLECT phase 3 pivotal study is a randomized, double-masked, placebo-controlled trial investigating the efficacy and safety of bilateral intravitreal injection of lenadogene nolparvovec in patients with a confirmed m.11778G>A mutation, using a recombinant adeno-associated virus vector 2, serotype 2 (rAAV2/2-ND4). The first-affected eye received gene therapy; the fellow (affected/not-yet-affected) eye was randomly injected with gene therapy or placebo. The primary end point was the difference in change from baseline of best-corrected visual acuity (BCVA) in second-affected/not-yet-affected eyes treated with lenadogene nolparvovec versus placebo at 1.5 years post-treatment, expressed in logarithm of the minimal angle of resolution (LogMAR). Forty-eight patients were treated bilaterally and 50 unilaterally. At 1.5 years, the change from baseline in BCVA was not statistically different between second-affected/not-yet-affected eyes receiving lenadogene nolparvovec and placebo (primary end point). A statistically significant improvement in BCVA was reported from baseline to 1.5 years in lenadogene nolparvovec-treated eyes: -0.23 LogMAR for the first-affected eyes of bilaterally treated patients (P < 0.01); and -0.15 LogMAR for second-affected/not-yet-affected eyes of bilaterally treated patients and the first-affected eyes of unilaterally treated patients (P < 0.05). The mean improvement in BCVA from nadir to 1.5 years was -0.38 (0.052) LogMAR and -0.33 (0.052) LogMAR in first-affected and second-affected/not-yet-affected eyes treated with lenadogene nolparvovec, respectively (bilateral treatment group). A mean improvement of -0.33 (0.051) LogMAR and -0.26 (0.051) LogMAR was observed in first-affected lenadogene nolparvovec-treated eyes and second-affected/not-yet-affected placebo-treated eyes, respectively (unilateral treatment group). The proportion of patients with one or both eyes on-chart at 1.5 years was 85.4% and 72.0% for bilaterally and unilaterally treated patients, respectively. The gene therapy was well tolerated, with no systemic issues. Intraocular inflammation, which was mostly mild and well controlled with topical corticosteroids, occurred in 70.7% of lenadogene nolparvovec-treated eyes versus 10.2% of placebo-treated eyes. Among eyes treated with lenadogene nolparvovec, there was no difference in the incidence of intraocular inflammation between bilaterally and unilaterally treated patients. Overall, the REFLECT trial demonstrated an improvement of BCVA in LHON eyes carrying the m.11778G>A mtDNA mutation treated with lenadogene nolparvovec or placebo to a degree not reported in natural history studies and supports an improved benefit/risk profile for bilateral injections of lenadogene nolparvovec relative to unilateral injections.

Published
2023

2. A Multicenter Analysis of Nucleic Acid Quantification Using Aqueous Humor Liquid Biopsy in Retinoblastoma

Author

Deborah H. Im, BS, Sarah Pike, BA, Mark W. Reid, PhD, Chen-Ching Peng, PhD, Shreya Sirivolu, BA, Hans E. Grossniklaus, MD, MBA, G. Baker Hubbard, 3rd, MD, Alison H. Skalet, MD, PhD, Kellyn N. Bellsmith, MD, Carol L. Shields, MD, Sara E. Lally, MD, Andrew W. Stacey, MD, Bibiana J. Reiser, MD, Aaron Nagiel, MD, PhD, Rachana Shah, MD, Liya Xu, PhD, and Jesse L. Berry, MD

Subjects
Aqueous humor, Liquid biopsy, Circulating analytes, Retinoblastoma, Multicenter, Ophthalmology, RE1-994
Abstract

Purpose: Retinoblastoma (RB) is most often diagnosed with clinical features and not diagnosed with tumor biopsy. This study describes tumor-derived analyte concentrations from aqueous humor (AH) liquid biopsy and its use in clinical assays. Design: Case series study. Participants: Sixty-two RB eyes from 55 children and 14 control eyes from 12 children from 4 medical centers. Methods: This study included 128 RB AH samples including: diagnostic (DX) samples, samples from eyes undergoing treatment (TX), samples after completing treatment (END), and during bevacizumab injection for radiation therapy after completing RB treatment (BEV). Fourteen-control AH were analyzed for unprocessed analytes (double-stranded DNA [dsDNA], single-stranded DNA [ssDNA], micro-RNA [miRNA], RNA, and protein) with Qubit fluorescence assays. Double-stranded DNA from 2 RB AH samples underwent low-pass whole-genome sequencing to detect somatic copy number alterations. Logistic regression was used to predict disease burden given analyte concentrations. Main Outcome Measures: Unprocessed analyte (dsDNA, ssDNA, miRNA, RNA and protein) concentrations. Results: Results revealed dsDNA, ssDNA, miRNA, and proteins, but not RNA, were quantifiable in most samples (up to 98%) with Qubit fluorescence assays. Median dsDNA concentration was significantly higher in DX (3.08 ng/μl) compared to TX (0.18 ng/μl; P

Published
2023
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3. Machine Learning OCT Predictors of Progression from Intermediate Age-Related Macular Degeneration to Geographic Atrophy and Vision Loss

Author

Eleonora M. Lad, MD, PhD, Karim Sleiman, MD, David L. Banks, PhD, Sanjay Hariharan, MS, Traci Clemons, PhD, Rolf Herrmann, PhD, Daniyar Dauletbekov, MD, PhD, Andrea Giani, MD, Victor Chong, MD, MBA, Emily Y. Chew, MD, Cynthia A. Toth, MD, Cynthia A. Toth, Wai Wong, Thomas Huang, G. Baker Hubbard, Sunil Srivastava, Michelle McCall, Katrina Winter, Neeru Sarin, Katherine Hall, Patti McCollum, Linda Curtis, Stefanie Schuman, Stephanie J. Chiu, Sina Farsiu, Vincent Tai, Traci Clemons, and Emily Chew

Subjects
Classification trees, Geographic atrophy, Machine learning, Prediction, Random forest, Ophthalmology, RE1-994
Abstract

Purpose: To describe spectral-domain OCT (SD-OCT) features, age, gender, and systemic variables that may be used in machine/deep learning studies to identify high-risk patient subpopulations with high risk of progression to geographic atrophy (GA) and visual acuity (VA) loss in the short term. Design: Prospective, longitudinal study. Participants: We analyzed imaging data from patients with intermediate age-related macular degeneration (iAMD) (N = 316) enrolled in the Age-Related Eye Disease Study 2 (AREDS2) Ancillary SD-OCT with adequate SD-OCT imaging for repeated measures. Methods: Qualitative and quantitative multimodal variables from the database were derived at each yearly visit over 5 years. Based on statistical analyses developed in the field of cardiology, an algorithm was developed and used to select person-years without GA on color fundus photography or SD-OCT at baseline. The analysis used machine learning approaches to generate classification trees. Eyes were stratified as low, average, above average, and high risk in 1 or 2 years, based on OCT and demographic features by the risk of GA development or decreased VA by 5+ and 10+ letters. Main Outcome Measures: New onset of SD-OCT–determined GA and VA loss. Results: We identified multiple retinal and subretinal SD-OCT and demographic features from the baseline visit, each of which independently conveyed low to high risk of new-onset GA or VA loss on each of the follow-up visits at 1 or 2 years. Conclusions: We propose a risk-stratified classification of iAMD based on the combination of OCT-derived retinal features, age, gender, and systemic variables for progression to OCT-determined GA or VA loss. After external validation, the composite early end points may be used as exclusion or inclusion criteria for future clinical studies of iAMD focused on prevention of GA progression or VA loss.

Published
2022
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4. Clinical management of an outbreak of nutritionally variant streptococcus endophthalmitis following intravitreal bevacizumab injection

Author

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

Subjects
Intravitreal injections, Endophthalmitis, Outbreak, Disease cluster, Nutritionally-variant streptococcus, Granulicatella, Ophthalmology, RE1-994
Abstract

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. Comparison in Retreatments between Bevacizumab and Ranibizumab Intravitreal Injections for Retinopathy of Prematurity

Author

Nimesh A. Patel, Luis A. Acaba-Berrocal, Sandra Hoyek, Kenneth C. Fan, Maria Ana Martinez-Castellanos, Caroline R. Baumal, C. Armitage Harper, Audina M. Berrocal, Wu Wei-Chi, Rand Spencer, Shunji Kusaka, Polly Quiram, Jose Asilis, Michael P. Blair, Swati Agarwal, Anna Ells, Cagri G. Besirli, Irena Tsui, Thomas C. Lee, Aaron Nagiel, Andres Kychenthal, Jessica Kovarik, Anton Orlin, Janet Alexander, Vaidehi S. Dedania, Sengul Ozdek, Michel J. Shami, Cornelius Regan, Shilpa Desai, Moran Roni Levin, Deborah Y. Chong, Mrinali Gupta, Adam Pflugrath, Ashkan Abbey, Christopher G. Fuller, Lori E. Coors, Nicolas Yannuzzi, Catherine Negron, Hasenin Al-khersan, Paul Runge, Huseyin Baran Ozdemir, Tugce Kucukbalci, Chiharu Iwahashi, Mark Solinski, David Sutter, Jonathan Sears, Christine Sonnie, David Portney, Jake Duker, Tamara Lenis, Andreas Di-Luciano, Pablo Chamartin, Nikisha Kothari, Grecia Yael Ortiz-Ramirez, Gabriela Patricia Amadeo Oreggioni, Ameay V. Naravane, Peter J. Belin, Nahomy Ledesma Vicioso, Demetrios Vavvas, M. Elizabeth Hartnett, Robinson V.P. Chan, Eric Nudleman, Darius M. Moshfeghi, Atchara Amphornphruet, Michael Chiang, Michael J. Shapiro, J. Peter Campbell, Lejla Vajzovic, Mario Capecchi, G. Baker Hubbard, Jason Horowtiz, Rabia Karani, Rosina Negrin Martin, and Emmanuel Chang

Subjects
Ophthalmology
Published
2023

6. The Prevalence of Retinal Disease and Associated CNS Disease in Young Patients with Incontinentia Pigmenti

Author

Ian D. Danford, Brittni A. Scruggs, Antonio Capone, Michael T. Trese, Kim A. Drenser, Aristomenis Thanos, Eric Nudleman, Atchara Amphornphruet, Boontip Tipsuriyaporn, G. Baker Hubbard, Anna Ells, C. Armitage Harper, Jessica Goldstein, Charles Calvo, Chris Wallace-Carrete, Duncan Berry, Emmanuel Chang, Lisa Leishman, Michael Shapiro, Michael Blair, Mikel Mikhail, Carol L. Shields, Rachel Schwendeman, Yoshihiro Yonekawa, Mrinali P. Gupta, Anton Orlin, Supalert Prakhunhungsit, Shizuo Mukai, Audina Berrocal, M. Elizabeth Hartnett, and J. Peter Campbell

Subjects
Ophthalmology, Retinal Diseases, Central Nervous System Diseases, Prevalence, Humans, Infant, Vascular Diseases, Incontinentia Pigmenti, Child, Article, Retina, Retrospective Studies
Abstract

PURPOSE: To evaluate the prevalence of retinal disease on fluorescein angiography (FA) in patients with incontinentia pigmenti (IP) and to compare the severity of retinal disease in those with and without known central nervous system (CNS) disease. DESIGN: Multi-institutional consecutive retrospective case series. SUBJECTS: New patients with a diagnosis of IP were seen at the Casey Eye Institute at the Oregon Health and Science University (OHSU), Moran Eye Center, University of Utah, or Bascom Palmer Eye Institute, University of Miami from December 2011 to September 2018. METHODS: Detailed ophthalmoscopic examination and FA were recommended for all new patients and performed on every patient who had parental consent. Ophthalmoscopic findings and FA images were graded for severity by 2 masked graders on a 3-point scale: 0 = no disease, 1 = vascular abnormalities without leakage, 2 = leakage or neovascularization, and 3 = retinal detachment. The presence of known CNS disease was documented. Additional cases were obtained from a pediatric retina listserv for examples of phenotypic variation. MAIN OUTCOME MEASURES: The proportion of eyes noted to have disease on ophthalmoscopy compared with FA and the severity of retinal disease in those with and without known CNS disease. RESULTS: Retinal pathology was detected in 18 of 35 patients (51%) by indirect ophthalmoscopy and 26 of 35 patients (74%) by FA (P = 0.048) in a predominantly pediatric population (median age, 9 months). Ten patients (29%) had known CNS disease at the time of the eye examination. A Wilcoxon rank-sum test indicated that the retinal severity scores for patients with CNS disease (median, 2) were significantly higher than the retinal severity scores for patients without CNS disease (median, 1), z = −2.12, P = 0.034. CONCLUSIONS: Retinal disease is present in the majority of patients with IP, and ophthalmoscopic examination is less sensitive than FA for detection of disease. There may be a correlation between the severity of retinal and CNS disease.

Published
2022

7. PROLIFERATIVE RETINOPATHY IN A 13-YEAR-OLD WITH ADAMS–OLIVER SYNDROME

Author

Benjamin I. Meyer, G. Baker Hubbard, Phoebe D. Lenhart, Adam M. Hanif, Nieraj Jain, and Parker J. Williams

Subjects
medicine.medical_specialty, Visual acuity, Adolescent, genetic structures, Neovascularization, chemistry.chemical_compound, Retinal Diseases, Ophthalmology, medicine, Humans, Fluorescein Angiography, Laser Coagulation, medicine.diagnostic_test, business.industry, Vitreoretinopathy, Proliferative, Retinal, Retinopathy of prematurity, General Medicine, medicine.disease, Fluorescein angiography, Optic disc drusen, eye diseases, chemistry, Familial exudative vitreoretinopathy, sense organs, medicine.symptom, business, Adams–Oliver syndrome
Abstract

PURPOSE Adams-Oliver syndrome is a rare, inherited disorder of embryologic development that affects multiple systems. Ocular manifestations have been poorly characterized due to the low prevalence and high mortality of the disease when it is associated with internal organ and/or ophthalmic manifestations. We present a case of Adams-Oliver syndrome in a 13-year-old patient whose multimodal retinal imaging findings helped direct management. METHODS Case report reviewing medical records and imaging. PATIENTS Single patient. RESULTS Visual acuity upon presentation was 20/40 in each eye. Ultra-widefield fluorescein angiography revealed peripheral non-perfusion with terminal vascular bulbs, as well as leakage from a temporal fibrovascular complex in the left eye. Fundus autofluorescence imaging showed hyperautofluorescence associated with optic disc drusen and the fibrovascular complex. Treatment with targeted laser photocoagulation was associated with regression of the neovascularization. CONCLUSIONS Retinal manifestations of Adams-Oliver syndrome as observed with ultra-widefield fundus imaging may resemble those of familial exudative vitreoretinopathy and retinopathy of prematurity. Treatment of avascular retina with panretinal photocoagulation can be considered.

Published
2022

8. MRI Features for Identifying MYCN-amplified RB1 Wild-type Retinoblastoma

Author

Robin W. Jansen, Christiaan M. de Bloeme, Liesbeth Cardoen, Sophia Göricke, Sabien van Elst, Jaime Lyn Jessen, Aparna Ramasubramanian, Alison H. Skalet, Audra K. Miller, Philippe Maeder, Ogul E. Uner, G. Baker Hubbard, Hans Grossniklaus, H. Culver Boldt, Kim E. Nichols, Rachel C. Brennan, Saugata Sen, Selma Sirin, Hervé J. Brisse, Paolo Galluzzi, Charlotte J. Dommering, Jonas A. Castelijns, Paul van der Valk, Ronald Boellaard, Josephine Dorsman, Annette C. Moll, Marcus C. de Jong, Pim de Graaf, University of Zurich, Radiology and nuclear medicine, Human genetics, CCA - Cancer biology and immunology, Pathology, Amsterdam Neuroscience - Neuroinfection & -inflammation, Amsterdam Neuroscience - Brain Imaging, CCA - Imaging and biomarkers, Amsterdam Reproduction & Development (AR&D), Ophthalmology, ACS - Diabetes & metabolism, APH - Health Behaviors & Chronic Diseases, APH - Quality of Care, CCA - Cancer Treatment and quality of life, and AII - Cancer immunology

Subjects
10036 Medical Clinic, Radiology, Nuclear Medicine and imaging, 610 Medicine & health
Abstract

Background MYCN-amplified RB1 wild-type (MYCNARB1+/+) retinoblastoma is a rare but clinically important subtype of retinoblastoma due to its aggressive character and relative resistance to typical therapeutic approaches. Because biopsy is not indicated in retinoblastoma, specific MRI features might be valuable to identify children with this genetic subtype. Purpose To define the MRI phenotype of MYCNARB1+/+ retinoblastoma and evaluate the ability of qualitative MRI features to help identify this specific genetic subtype. Materials and Methods In this retrospective, multicenter, case-control study, MRI scans in children with MYCNARB1+/+ retinoblastoma and age-matched children with RB1-/- subtype retinoblastoma were included (case-control ratio, 1:4; scans acquired from June 2001 to February 2021; scans collected from May 2018 to October 2021). Patients with histopathologically confirmed unilateral retinoblastoma, genetic testing (RB1/MYCN status), and MRI scans were included. Associations between radiologist-scored imaging features and diagnosis were assessed with the Fisher exact test or Fisher-Freeman-Halton test, and Bonferroni-corrected P values were calculated. Results A total of 110 patients from 10 retinoblastoma referral centers were included: 22 children with MYCNARB1+/+ retinoblastoma and 88 control children with RB1-/- retinoblastoma. Children in the MYCNARB1+/+ group had a median age of 7.0 months (IQR, 5.0-9.0 months) (13 boys), while children in the RB1-/- group had a median age of 9.0 months (IQR, 4.6-13.4 months) (46 boys). MYCNARB1+/+ retinoblastomas were typically peripherally located (in 10 of 17 children; specificity, 97%; P < .001) and exhibited plaque or pleomorphic shape (in 20 of 22 children; specificity, 51%; P = .011) with irregular margins (in 16 of 22 children; specificity, 70%; P = .008) and extensive retina folding with vitreous enclosure (specificity, 94%; P < .001). MYCNARB1+/+ retinoblastomas showed peritumoral hemorrhage (in 17 of 21 children; specificity, 88%; P < .001), subretinal hemorrhage with a fluid-fluid level (in eight of 22 children; specificity, 95%; P = .005), and strong anterior chamber enhancement (in 13 of 21 children; specificity, 80%; P = .008). Conclusion MYCNARB1+/+ retinoblastomas show distinct MRI features that could enable early identification of these tumors. This may improve patient selection for tailored treatment in the future. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Rollins in this issue.

Published
2023

9. Prediction for 2-Year Vision Outcomes Using Early Morphologic and Functional Responses in the Comparison of Age-related Macular Degeneration Treatments Trials

Author

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

Subjects
Ophthalmology
Published
2023

10. A Novel Approach to Subretinal Fluid Drainage in Coats'-Related Exudative Retinal Detachment

Author

K'Mani, Blyden, David A, Levine, Caroline, Craven, and G Baker, Hubbard

Subjects
Laser Coagulation, Subretinal Fluid, Retinal Detachment, Drainage, Humans, Retinal Telangiectasis, Angiogenesis Inhibitors, Cataract
Abstract

Laser is effective at treating exudative retinal detachment (ERD) in Coats' disease. However, with severe ERD, the retina may be in contact with the lens. In such cases, laser can result in cataract formation. This case report of two patients treated at an academic medical center for Coats'-related ERD describes a technique of minimally invasive subretinal fluid drainage to create space between the lens and retina to avoid cataract. Transconjunctival unguarded needle drainage allowed for complete treatment of telangiectatic vessels and resulted in favorable anatomical outcomes in the patients. Transconjunctival unguarded needle drainage is a useful technique for treating severe, Coats'-related ERD, when a bullously detached retina is in contact with the lens. [ Ophthalmic Surg Lasers Imaging Retina 2022; 53:407–409.]

Published
2022

11. Surgical Outcomes of Progressive Retinoschisis-Related Retinal Detachments: A 17-Year Survey From a Large Academic Center

Author

Albert, Liao, Joshua, Barnett, Ibraheem, Rehman, Daeja, Hamm, Blaine E, Cribbs, Andrew M, Hendrick, Nieraj, Jain, Steven, Yeh, G Baker, Hubbard, and Jiong, Yan

Subjects
Scleral Buckling, Treatment Outcome, Retinoschisis, Vitrectomy, Retinal Detachment, Visual Acuity, Humans, Prospective Studies, Retina, Retrospective Studies
Abstract

BACKGROUND AND OBJECTIVE: To provide an overview of progressive retinoschisis-related retinal detachment (RSRD) management at a tertiary referral center. MATERIALS AND METHODS: Single-institution retrospective case series from January 1, 2003, to May 1, 2020. RESULTS: Progressive RSRD occurred in 0.9% of patients with retinoschisis. Mean (range) age at time of surgery was 58.7 years (40.0 to 74.0). Ten eyes were initially treated with scleral buckle, three eyes with vitrectomy, and three eyes with combined scleral buckle and vitrectomy. Overall reattachment rate was 100.0%; single-surgery success was 56.2%. Proliferative vitreoretinopathy developed in 10.0% of scleral buckles, 33.3% of vitrectomies, and 33.3% of combined surgeries. CONCLUSIONS: Progressive RSRD is rare and poses surgical management challenges. Final retinal attachment can be achieved successfully but often requires secondary and staged surgeries. Localization of outer retinal breaks may help guide surgical management. Further research—such as a large-scale, prospective, multicenter, randomized trial—would be needed to determine the optimal surgical technique. [ Ophthalmic Surg Lasers Imaging Retina . 2022;53:132–138.]

Published
2022

12. Referable Macular Hemorrhage—A Clinically Meaningful Screening Target in Newborn Infants. Position Statement of the Association of Pediatric Retina Surgeons

Author

Edward H. Wood, Antonio Capone, Kimberly A. Drenser, Audinal Berrocal, G. Baker Hubbard, Natalia F. Callaway, Andres Kychenthal, Anna Ells, Clio A. Harper, Cagri Giray Besirli, Caroline R. Baumal, Demetrios G. Vavvas, Emmanuel Y. Chang, Eric D. Nudleman, Irena Tsui, Jonathan Sears, Lejla Vajzovic, Mary E. Hartnett, Michael J. Shapiro, Polly A. Quiram, Sengul Ozdek, Shunjil Kusaka, Wei-Chi Wu, and Michael T. Trese

Subjects
Surgeons, Neonatal Screening, Eye Diseases, Infant, Newborn, Humans, Infant, Retinal Hemorrhage, Child, Retina
Abstract

Universal newborn eye screening facilitates early diagnosis of ocular abnormalities and mitigates vision loss. “Referral warranted” eye disease is present at birth in about 5.5% of term infants, with “macular hemorrhage impinging on the fovea” representing about 50% of referral warranted disease. The Association of Pediatric Retina Surgeons held a symposium on February 9, 2021 that culminated in a position statement on “referable macular hemorrhage” (RMH) in newborn infants. RMH is meaningful in that in can cause amblyopia through deprivation, can be readily captured with wide-angle photography in a safe and efficient manner, and may lead to early intervention with mitigation of vision loss. [ Ophthalmic Surg Lasers Imaging Retina . 2022;53:3–6.]

Published
2022

13. Outcomes of Infectious Endophthalmitis in Patients with Systemic Antibiotic Allergies to Penicillins, Cephalosporins, or Vancomycin

Author

Duncan E. Berry, Ghazala O'Keefe, Jiong Yan, Benjamin I. Meyer, Prethy Rao, Jessica G. Shantha, Nieraj Jain, Steven Yeh, Blaine Cribbs, Andrew Hendrick, Purnima Patel, and G. Baker Hubbard

Subjects
Male, medicine.medical_specialty, medicine.drug_class, Population, Antibiotics, Ceftazidime, Penicillins, Eye Infections, Bacterial, Drug Hypersensitivity, 03 medical and health sciences, 0302 clinical medicine, Endophthalmitis, Vancomycin, Internal medicine, Ophthalmology, medicine, Humans, education, Contraindication, Aged, Retrospective Studies, 030304 developmental biology, 0303 health sciences, education.field_of_study, business.industry, Retrospective cohort study, Middle Aged, medicine.disease, Anti-Bacterial Agents, Cephalosporins, Penicillin, Treatment Outcome, 030221 ophthalmology & optometry, Female, business, Follow-Up Studies, medicine.drug
Abstract

Purpose The mainstay empiric treatments of bacterial endophthalmitis are intravitreal vancomycin and ceftazidime. In the United States, up to 10% of the general population has a reported penicillin (PCN) allergy. Despite low cross-reactivity between PCN and later-generation cephalosporins, some providers alter the intravitreal antibiotic choice for endophthalmitis because of concern for allergic reactions. We evaluated the management strategies of infectious endophthalmitis in the setting of self-reported systemic antibiotic allergies and the association with adverse reactions after standard intravitreal antibiotic administration. Design Single-center, retrospective cohort study. Participants All patients with endophthalmitis between 2005 and 2019 and documented PCN, PCN-analog, cephalosporin, or vancomycin allergy who received intravitreal antibiotics on the basis of International Classification of Diseases 9th and 10th Revisions, and Current Procedural Terminology codes. Methods Retrospective chart review. Main Outcome Measures Any allergic reaction after intravitreal injection, additional surgical interventions required for treatment, and visual function at last recorded visit. Results Of the 65 patients included in this cohort, the most common causes of endophthalmitis were postcataract extraction surgery (n = 23, 35.4%) and postintravitreal injection (n = 11, 16.9%). All patients (65/65) received intravitreal vancomycin, and 81.5% (53/65) received intravitreal ceftazidime. Of the 53 patients who received intravitreal ceftazidime, 46 (86.8%) had allergies to PCNs alone, 5 (9.4%) had a cephalosporin allergy alone, and 2 (3.8%) had reported allergies to both PCN and cephalosporin antibiotics. Two patients (3.1%) with a documented vancomycin allergy received intravitreal vancomycin without complication. No patients exhibited any systemic or local allergic reactions or complications after intravitreal injection. Conclusions There were no documented allergic reactions in this cohort of patients with systemic antibiotic allergies who were treated for infectious endophthalmitis. Our findings are consistent with previous reports of a low allergic cross-reactivity between PCN and later-generation cephalosporins. Ophthalmologists should use evidence-based practices and a careful informed consent process when choosing intravitreal antibiotics for patients with specific antibiotic allergies. In the routine patient with suspected bacterial endophthalmitis, PCN allergy may not be an absolute contraindication to intravitreal cephalosporin use.

Published
2021

14. Complications of retinopathy of prematurity treatment

Author

Joshua M Barnett and G. Baker Hubbard

Subjects
Vascular Endothelial Growth Factor A, Pediatrics, medicine.medical_specialty, genetic structures, Bevacizumab, Angiogenesis Inhibitors, Article, law.invention, Treatment complications, Randomized controlled trial, law, Late Recurrence, medicine, Humans, Retinopathy of Prematurity, General anaesthesia, Laser Coagulation, business.industry, Infant, Newborn, High myopia, Retinopathy of prematurity, General Medicine, medicine.disease, eye diseases, Clinical trial, Ophthalmology, Treatment Outcome, Intravitreal Injections, business, medicine.drug
Abstract

Purpose of review The purpose of this review is to summarize complications of treatment for retinopathy of prematurity (ROP) and to compare complications of laser and intravitreal antivascular endothelial growth factor (VEGF) injections. Recent findings Poor structural outcomes and myopia are more common with laser for severe ROP than with anti-VEGF. Clinical trial data show unfavourable outcomes in 9.1-9.5% of laser treated, and 1.4-3.6% of anti-VEGF treated eyes. Additional randomized trial data show risk for very high myopia (≥-8.00D) to be 3.8 and 51.4% for zone I eyes treated with bevacizumab and laser, respectively. However, anti-VEGF may be complicated by late recurrence and is more likely to require retreatment than laser. Laser often necessitates general anaesthesia with its attendant risks, including worse short-term respiratory outcomes. Neurodevelopmental complications have been reported with anti-VEGF, but existing studies are subject to bias. Summary Treatment complications are substantially different for the two modalities in common use today. In more severe cases, risk of poor structural outcome and myopia favour treatment with anti-VEGF. In less severe ROP, risk of recurrence and the need for additional treatments may favour laser. Additional data are needed to establish comparative risks of neurodevelopmental complications.

Published
2021

15. Atypical Late-Onset Exudative Retinal Detachment in a Treatment-Naïve Infant With Retinopathy of Prematurity

Author

G. Baker Hubbard, Lauren R. Schaffer, Prethy Rao, and Krishna Mukkamala

Subjects
Male, medicine.medical_specialty, genetic structures, Gestational Age, Late onset, Therapy naive, Neovascularization, Ophthalmology, medicine, Humans, Retinopathy of Prematurity, Retina, Laser Coagulation, business.industry, Infant, Newborn, Retinal Detachment, Postmenstrual Age, Infant, Retinopathy of prematurity, Exudative retinal detachment, Infant, Low Birth Weight, medicine.disease, eye diseases, medicine.anatomical_structure, Gestation, sense organs, medicine.symptom, business
Abstract

A male infant born at 23 weeks gestation with a birthweight of 660 grams presented with retinopathy of prematurity (ROP) that began progressing at 44 weeks. He subsequently developed Zone III, Stage 3, pre-plus disease in both eyes (OU), as well as scattered exudates in the macula, dragged vessels temporally, and an exudative retinal detachment temporally in the left eye after a period of regressing and stable ROP. After bilateral laser photocoagulation, there was regression of the neovascularization, resolution of the exudative detachment, and eventual stabilization of disease OU by 12 months postmenstrual age. [ Ophthalmic Surg Lasers Imaging Retina . 2021;52:403–406.]

Published
2021

16. Iodine-125 plaque brachytherapy for diffuse choroidal hemangioma

Author

Corrina P. Azarcon, Richard L.J. Qiu, Ethan K. Sobol, G. Baker Hubbard, Caroline M. Craven, Chris S. Bergstrom, and Jill R. Wells

Subjects
Ophthalmology, General Medicine
Abstract

To report 6 cases of diffuse choroidal hemangioma (DCH) in children treated with iodine-125 plaque brachytherapy at a single tertiary care center.Retrospective case series.Six pediatric patients diagnosed with DCH were included in the study. Pre-plaque visual acuity (VA) ranged from 20/150 to no light perception (NLP). All patients had extensive serous retinal detachment at presentation. An iodine-125 radioactive plaque was placed on the affected eye to administer a dose of 34.2-42.1 Gy to the tumor apex over a median of 4 days. Tumor regression and subretinal fluid resolution were observed in all eyes within 17 months of treatment. Visual acuity improved in 2 patients. Radiation-induced cataract and subretinal fibrosis were documented in 1 case, and 1 patient developed radiation retinopathy. No patients developed neovascular glaucoma within a follow-up range of 12-65 months.Iodine-125 plaque radiotherapy is an effective option for DCH, although there is a risk for radiation-induced complications.

Published
2022

17. Unilateral Xanthocoria and Retinal Vascular Anomalies in a 3-Year-Old Boy: Retinoblastoma or Coats Disease?

Author

Samera, Ahmad, Corrina P, Azarcon, G Baker, Hubbard, and Jill R, Wells

Subjects
Diagnosis, Differential, Male, Ophthalmology, Pupil Disorders, Child, Preschool, Retinal Neoplasms, Pediatrics, Perinatology and Child Health, Retinal Detachment, Retinoblastoma, Humans, Retinal Telangiectasis, General Medicine, Child
Abstract

The authors describe a challenging case of unilateral retinoblastoma in a patient referred for xanthocoria. A 3-year-old boy was referred for unilateral xanthocoria and disordered retinal vasculature, suggestive of Coats disease. Further investigation revealed diffuse subretinal tumor seeding and areas of calcification, consistent with retinoblastoma. Enucleation was performed and histopathology confirmed exophytic retinoblastoma. This case highlights that xanthocoria, although often encountered in patients with Coats disease, can sometimes be associated with retinoblastoma. As such, retinoblastoma should be considered in the differential diagnosis for children with both leukocoria and xanthocoria. [ J Pediatr Ophthalmol Strabismus. 2022;59(X):e32–e34.]

Published
2022

18. 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

19. Visual and Anatomic Outcomes of Premacular Hemorrhage in Non-Accidental Trauma Infants Managed With Observation or Vitrectomy

Author

G. Baker Hubbard, Christopher R. Stelton, Prethy Rao, and Ogul E. Uner

Subjects
medicine.medical_specialty, genetic structures, medicine.medical_treatment, Visual Acuity, Vitrectomy, Retina, 03 medical and health sciences, 0302 clinical medicine, Interquartile range, medicine, Humans, Strabismus, Retrospective Studies, business.industry, Infant, Retinal Hemorrhage, Mean age, Limiting, medicine.disease, eye diseases, Surgery, Median time, Accidental, Vitreous hemorrhage, 030221 ophthalmology & optometry, business
Abstract

BACKGROUND AND OBJECTIVE: The management of premacular hemorrhage secondary to non-accidental trauma (NAT) is unclear. The authors describe the outcomes of NAT infants referred for surgical evaluation of premacular hemorrhage. PATIENTS AND METHODS: Retrospective institutional review board-approved case series between 2000 and 2019 of vision-threatening premacular hemorrhage (sub-hyaloid or sub-internal limiting membrane hemorrhage without vitreous hemorrhage) in NAT infants. Time to hemorrhage resolution, vision, and comorbidities were collected. RESULTS: Thirty-six patients (62 eyes) with mean age of 5.4 months (range: 2–10 months) were included. Nine eyes (14.5%) underwent vitrectomy. Median time to hemorrhage resolution by observation was 75 days (interquartile range [IQR]: 60–120 days), and time to vitrectomy was 54.5 days (IQR: 47.8–58.5 days). Eight eyes (12.9%) had amblyopia, which was not significantly different between groups. Despite hemorrhage clearance, a higher proportion of eyes in the vitrectomy group had pigmentary changes ( P = .04) and strabismus ( P = .002) at follow-up. CONCLUSIONS: Most cases of NAT-related premacular hemorrhage resolve within 3 months without surgical intervention. Comorbidities may limit visual prognosis. [ Ophthalmic Surg Lasers Imaging Retina. 2020;51:715–722.]

Published
2020

20. Low- and Very Low-Dose Bevacizumab for Retinopathy of Prematurity: Reactivations, Additional Treatments, and 12-Month Outcomes

Author

Sharon F, Freedman, Amra, Hercinovic, David K, Wallace, Raymond T, Kraker, Zhuokai, Li, Amit R, Bhatt, Charline S, Boente, Eric R, Crouch, G Baker, Hubbard, David L, Rogers, Deborah, VanderVeen, Michael B, Yang, Nathan L, Cheung, Susan A, Cotter, Jonathan M, Holmes, and Lawrence, Tychsen

Subjects
Bevacizumab, Laser Coagulation, Intravitreal Injections, Infant, Newborn, Humans, Infant, Angiogenesis Inhibitors, Gestational Age, Retinopathy of Prematurity, Retrospective Studies
Abstract

Low-dose and very low-dose intravitreal bevacizumab (IVB) have been reported to be successful in short-term treatment of type 1 retinopathy of prematurity (ROP), down to an initial dose of 0.004 mg. We now report 12-month outcomes for these infants.Masked, multicenter, dose de-escalation study.One hundred twenty prematurely born infants with type 1 ROP.A cohort of 120 infants with type 1 ROP in at least 1 eye from 2 sequential dose de-escalation studies of low-dose IVB (0.25 mg, 0.125 mg, 0.063 mg, and 0.031 mg) or very low-dose IVB (0.016 mg, 0.008 mg, 0.004 mg, and 0.002 mg) to the study eye; the fellow eye (if also type 1) received 1 dose level higher of IVB. After primary success or failure at 4 weeks, clinical management was at investigator discretion, including all additional treatment.Reactivation of severe ROP by 6 months corrected age, additional treatments, retinal and other ocular structural outcomes, and refractive error at 12 months corrected age.Sixty-two of 113 study eyes (55%) and 55 of 98 fellow eyes (56%) received additional treatment. Of the study eyes, 31 (27%) received additional ROP treatment, and 31 (27%) received prophylactic laser therapy for persistent avascular retina. No trend toward a higher risk of additional ROP treatment related to initial IVB doses was found. However, time to reactivation among study eyes was shorter in eyes that received very low-dose IVB (mean, 76.4 days) than in those that received low-dose IVB (mean, 85.7 days). At 12 months, poor retinal outcomes and anterior segment abnormalities both were uncommon (3% and 5%, respectively), optic atrophy was noted in 10%, median refraction was mildly myopic (-0.31 diopter), and strabismus was present in 29% of infants.Retinal structural outcomes were very good after low- and very low-dose IVB as initial treatment for type 1 ROP, although many eyes received additional treatment. The rate of reactivation of severe ROP was not associated with dose; however, a post hoc data-driven analysis suggested that reactivation was sooner with very low doses.

Published
2022

21. 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

23. Risk Factors for Retinal Detachment in Acute Retinal Necrosis

Author

J. Clay Bavinger, Casey L. Anthony, Aaron T. Lindeke-Myers, Stephanie Lynch, Lucy T. Xu, Joshua Barnett, David Levine, Purnima Patel, Rachel Shah, Nieraj Jain, Prethy Rao, Andrew Hendrick, Blaine E. Cribbs, Jiong Yan, G. Baker Hubbard, Jessica G. Shantha, Ghazala D. O’Keefe, and Steven Yeh

Subjects
Inflammation, Male, Ophthalmology, Herpesvirus 3, Human, Risk Factors, Retinal Detachment, Eye Infections, Viral, Humans, Female, Herpes Simplex, Retinal Necrosis Syndrome, Acute, Retrospective Studies
Abstract

Retinal detachment (RD) is associated with poor visual outcomes in patients with acute retinal necrosis (ARN). This research was undertaken to assess the risk factors for RD in ARN.Retrospective cohort study.Patients diagnosed with ARN at a tertiary referral center from 2010 to 2020.A chart review was performed for all clinical and surgical encounters. Univariate and multivariate logistic analyses of demographic and clinical variables associated with RD were performed. Survival analyses with Kaplan-Meier estimates were performed to compare the time to RD in herpes simplex virus (HSV)- and varicella zoster virus (VZV)-associated ARN.Demographic information, clinical information (including visual acuity [VA]), intraocular pressure (IOP), intraocular inflammation level, the extent of retinitis, incidence and timing of retinal detachment, date of diagnosis, and treatments performed (including intravitreal injections of antiviral medications).Fifty-four eyes of 47 patients who were diagnosed with ARN were included, with equal proportions of eyes (n = 27; 50%) with VZV-ARN and HSV-ARN. Patients with VZV-ARN were, on average, older, more likely to be men, and more likely to be immunosuppressed compared with patients with HSV-ARN. The clinical characteristics, including the initial VA, initial IOP, anterior segment inflammation, clock hours, and posterior extent of retinitis, were similar between eyes with VZV- and HSV-ARN. In the univariate analysis of clinical and demographic variables associated with the development of RD, initial VA (P = 0.0083) and greater clock hours of retinitis (P = 0.009) were significantly associated with RD. These 2 variables remained significant in the multivariate logistic regression; worse VA at presentation had an odds ratio of 2.34 (95% confidence interval [CI], 1.01-5.44; P = 0.042), and greater clock hours of retinitis had an odds ratio of 1.23 (95% CI, 1.02-1.47; P = 0.025). A Kaplan-Meier survival analysis demonstrated no statistical difference in RD-free survival between HSV- and VZV-ARN.Patients with VZV-ARN were more likely to be older, male, and immunosuppressed compared with those with HSV-ARN, although no clear difference was observed in RD by viral etiology. Poor initial VA and clock hours of retinitis were significantly associated with RD development and may be relevant for patient counseling and prognosis.

Published
2021

25. Efficacy and Safety of Intravitreal Gene Therapy for Leber Hereditary Optic Neuropathy Treated within 6 Months of Disease Onset

Author

Irena Tsui, Claudia B. Catarino, Piero Barboni, Günther Rudolph, Nancy J. Newman, Sara Silvestri, Alfredo A. Sadun, Michael Dattilo, Neringa Jurkute, Jean-François Girmens, Cosima Schertler, Magali Taiel, Rustum Karanjia, Claudia Priglinger, Maria K Gemenetzi, Armin Wolf, Manuela Contin, Jasmina Al-Tamami, Thomas Klopstock, James Acheson, Robert C. Sergott, Deborah Gibbs, Rabih Hage, Stephan R. Thurau, Adam A. DeBusk, Lidia Di Vito, Mark L. Moster, Valérie Biousse, Med Lindreth DuBois, Valerio Carelli, Gad Heilweil, Chiara La Morgia, Michele Carbonelli, Andrew Hendrick, Patrick Yu-Wai-Man, Jason H. Peragallo, Gerard Smits, Angelika Pressler, Martin Hildebrandt, Alcides Fernandes Filho, Michael Neuenhahn, Bettina von Livonius, Barrett Katz, Daniel R Muth, Siegfried G. Priglinger, Lauren Leitch-Devlin, Susan Mohamed, William R. Tucker, Maria Massini, Maria Eleftheriadou, Laure Blouin, Catherine Vignal-Clermont, Eman Hawy, Simona Degli Esposti, Heather Tollis, G. Baker Hubbard, Jannah Rutter Dobbs, José-Alain Sahel, Catherine Vignal, Melissa SantaMaria, Julie A. Haller, Emory University School of Medicine, Emory University [Atlanta, GA], Addenbrooke's Hospital, Cambridge University NHS Trust, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), University of Bologna, Jefferson (Philadelphia University + Thomas Jefferson University), Fondation Ophtalmologique Adolphe de Rothschild [Paris], Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts (CHNO), Ludwig-Maximilians-Universität München (LMU), University of California [Los Angeles] (UCLA), University of California, Ludwig Maximilian University [Munich] (LMU), Institut de la Vision, Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Pittsburgh School of Medicine, Pennsylvania Commonwealth System of Higher Education (PCSHE), Institut Hospitalo-Universitaire FOReSIGHT, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts (CHNO)-Sorbonne Université (SU), Newman, NJ, Yu-Wai-Man, P, Carelli, V, Moster, ML, Biousse, V, Vignal-Clermont, C, Sergott, RC, Klopstock, T, Sadun, AA, Barboni, P, DeBusk, AA, Girmens, JF, Rudolph, G, Karanjia, R, Taiel, M, Blouin, L, Smits, G, Katz, B, Sahel, J-A, Vignal, C, Hage, R, Catarino, CB, Priglinger, C, Priglinger, S, Thurau, S, von Livonius, B, Muth, D, Wolf, A, Al-Tamami, J, Pressler, A, Schertler, C, Hildebrandt, M, Neuenhahn, M, Heilweil, G, Tsui, I, Hubbard, GB, Hendrick, A, Dattilo, M, Peragallo, J, Hawy, E, DuBois, Med L, Gibbs, D, Filho, AF, Dobbs, J, Carbonelli, M, Di Vito, L, Contin, M, Mohamed, S, La Morgia, C, Silvestri, S, Acheson, J, Eleftheriadou, M, Esposti, S, Gemenetzi, M, Leitch-Devlin, L, Tucker, WR, Jurkute, N, SantaMaria, M, Tollis, H, Haller, JA, and Massini, M.

Subjects
Male, Time Factors, Visual acuity, genetic structures, physiology [Visual Fields], [SDV]Life Sciences [q-bio], efficacy, Visual Acuity, Phases of clinical research, genetics [Dependovirus], chemistry.chemical_compound, 0302 clinical medicine, Visual Field Test, Quality of life, Clinical endpoint, Contrast (vision), intravitreal gene therapy, media_common, 0303 health sciences, physiology [Visual Acuity], Diabetic retinopathy, Dependovirus, Middle Aged, Dependoviru, genetics [DNA, Mitochondrial], Phase 3 randomized double-masked clinical trial, Treatment Outcome, Intravitreal Injections, diagnosis [Optic Atrophy, Hereditary, Leber], Female, Genetic Vector, medicine.symptom, Human, Adult, safety, LEBER HEREDITARY OPTIC NEUROPATHY, medicine.medical_specialty, retinal anatomic measures, Time Factor, Adolescent, media_common.quotation_subject, psychology [Optic Atrophy, Hereditary, Leber], Genetic Vectors, Visual Field, Humphrey visual field perimetry, Optic Atrophy, Hereditary, Leber, therapy [Optic Atrophy, Hereditary, Leber], DNA, Mitochondrial, bilateral visual improvement, Follow-Up Studie, Leber Hereditary Optic Neuropathy, Young Adult, 03 medical and health sciences, Double-Blind Method, Ophthalmology, psychology [Quality of Life], Electroretinography, medicine, Humans, ddc:610, Aged, 030304 developmental biology, contrast sensitivity, business.industry, Intravitreal Injection, Retinal, Genetic Therapy, retinal anatomic measure, medicine.disease, eye diseases, genetics [Optic Atrophy, Hereditary, Leber], chemistry, Mutation, 030221 ophthalmology & optometry, Visual Field Tests, sense organs, Visual Fields, business, Follow-Up Studies, best-corrected visual acuity
Abstract

International audience; Purpose: To evaluate the efficacy of a single intravitreal injection of rAAV2/2-ND4 in subjects with visual loss from Leber hereditary optic neuropathy (LHON).Design: RESCUE is a multicenter, randomized, double-masked, sham-controlled, phase 3 clinical trial.Participants: Subjects with the m.11778G>A mitochondrial DNA mutation and vision loss ≤6 months from onset in 1 or both eyes were included.Methods: Each subject's right eye was randomly assigned (1:1) to treatment with rAAV2/2-ND4 (single injection of 9 × 1010 viral genomes in 90 μl) or to sham injection. The left eye received the treatment not allocated to the right eye.Main outcome measures: The primary end point was the difference of the change from baseline in best-corrected visual acuity (BCVA) between rAAV2/2-ND4-treated and sham-treated eyes at week 48. Other outcome measures included contrast sensitivity, Humphrey visual field perimetry, retinal anatomic measures, and quality of life. Follow-up extended to week 96.Results: Efficacy analysis included 38 subjects. Mean age was 36.8 years, and 82% were male. Mean duration of vision loss at time of treatment was 3.6 months and 3.9 months in the rAAV2/2-ND4-treated eyes and sham-treated eyes, respectively. Mean baseline logarithm of the minimum angle of resolution (logMAR) BCVA (standard deviation) was 1.31 (0.52) in rAAV2/2-ND4-treated eyes and 1.26 (0.62) in sham-treated eyes, with a range from -0.20 to 2.51. At week 48, the difference of the change in BCVA from baseline between rAAV2/2-ND4-treated and sham-treated eyes was -0.01 logMAR (P = 0.89); the primary end point of a -0.3 logMAR (15-letter) difference was not met. The mean BCVA for both groups deteriorated over the initial weeks, reaching the worst levels at week 24, followed by a plateau phase until week 48, and then an improvement of +10 and +9 Early Treatment Diabetic Retinopathy Study letters equivalent from the plateau level in the rAAV2/2-ND4-treated and sham-treated eyes, respectively.Conclusions: At 96 weeks after unilateral injection of rAAV2/2-ND4, LHON subjects carrying the m.11778G>A mutation treated within 6 months after vision loss achieved comparable visual outcomes in the injected and uninjected eyes.

Published
2021

27. Rhegmatogenous Retinal Detachment in Children

Author

Blaine Cribbs, Andrew Hendrick, Steven Yeh, Jesse M. Smith, G. Baker Hubbard, Justin H. Townsend, Nieraj Jain, Laura T. Ward, and Jiong Yan

Subjects
Pars plana, 0303 health sciences, medicine.medical_specialty, Visual acuity, business.industry, medicine.medical_treatment, Retinal detachment, Vitrectomy, Retrospective cohort study, Odds ratio, medicine.disease, Scleral buckle, eye diseases, Surgery, 03 medical and health sciences, Ophthalmology, 0302 clinical medicine, medicine.anatomical_structure, 030221 ophthalmology & optometry, medicine, medicine.symptom, Risk factor, business, 030304 developmental biology
Abstract

Purpose To describe presenting clinical features and surgical techniques that are associated with successful surgical repair of pediatric rhegmatogenous retinal detachment (RRD). Design Retrospective interventional case series. Participants Two hundred twelve eyes of 191 patients 0 to 18 years of age undergoing surgical repair for RRD between 2001 and 2015 with a minimum follow-up of 3 months. Methods Patients were divided into 3 age groups (0–6 years, 7–12 years, and 13–18 years) and comparisons were made using bivariate and multivariate generalized estimating equation models. A mixed means model was used to examine visual acuity in each age group over time. Main Outcome Measures Complete reattachment of the retina at final follow-up. Results Of 212 eyes, 166 (78%) achieved total reattachment at final follow-up. Mean follow-up was 36.3 months. Rhegmatogenous retinal detachment associated with Stickler syndrome was more likely to occur in the younger cohorts (odds ratio [OR], 0.45; 95% confidence interval [CI], 0.22–0.91), whereas RRD associated with blunt trauma was more likely to occur in the oldest cohort (OR, 2.3; 95% CI, 1.2–4.4). Subtotal RRD was more likely to be repaired successfully than total RRD (OR, 3.6; 95% CI, 1.5–8.4; P = 0.0100), and eyes with previous vitreoretinal surgery were less likely to undergo successful repair (OR, 0.30; 95% CI, 0.12–0.78; P = 0.0258). There was no significant difference between age groups in the rate of surgical success (P = 0.55). There was a significantly higher success rate with primary scleral buckle (SB; 63%; OR, 2.2; 95% CI, 1.1–4.5) and combined SB plus pars plana vitrectomy (PPV; 68%; OR, 2.3; 95% CI, 1.1–5.1) compared with PPV alone (51%). Conclusions Most pediatric patients with RRD achieved complete reattachment with surgery. Success was more common in patients with a subtotal RRD at presentation. Previous vitreoretinal surgery was a risk factor for failure. Younger patients were more likely to demonstrate RRD involving the macula, but there was no difference between age groups in successful reattachment at final follow-up. Primary PPV showed a lower rate of success than SB or combined SB plus PPV.

Published
2019

28. 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

29. 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

30. Application of the Postnatal Growth and Retinopathy of Prematurity (G-ROP) criteria at a tertiary referral hospital

Author

Ijeoma, Chinwuba, G Baker, Hubbard, Prethy, Rao, Natalie, Weil, and Amy K, Hutchinson

Subjects
Infant, Newborn, Infant, Gestational Age, Weight Gain, Tertiary Care Centers, Ophthalmology, Neonatal Screening, Risk Factors, Pediatrics, Perinatology and Child Health, Birth Weight, Humans, Retinopathy of Prematurity, Child, Retrospective Studies
Abstract

Application of current retinopathy of prematurity (ROP) screening criteria results in many unnecessary examinations, because only 5%-10% of infants screened require treatment. Application of screening criteria established by the Postnatal Growth and Retinopathy of Prematurity Study could significantly reduce unnecessary examinations without sacrificing sensitivity to detect treatment-requiring ROP. We evaluated the performance of the G-ROP criteria in a population of high-risk, outborn infants.The medical records of consecutive infants screened and/or treated for ROP at Children's Health Care of Atlanta Hospitals from May 1, 2013, to September 6, 2019, were reviewed retrospectively. The sensitivity of the G-ROP birthweight and gestational age screening criteria to detect treatment-requiring ROP was calculated.During the study period, 901 children underwent examinations for ROP; of these, 5 were excluded from the analysis because birth weight (BW) data was lacking. Of the 896 remaining patients, 120 patients were treated for ROP. Application of G-ROP birth weight and gestational age (GA) criteria alone resulted in a sensitivity of 99.2% to detect infants requiring treatment. Application of weight gain criteria was problematic, because many patients were transferred into our institutions after the specified intervals of 10-19, 20-29, and 30-39 days.G-ROP BW and GA screening criteria were highly sensitive in detecting treatment-requiring ROP. Applying weight gain criteria in referral centers can be problematic. Intake procedures at referral centers should include documentation of weight gain during 10-19, 20-29, and 30-39 days of life.

Published
2022

31. 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

32. A Dosing Study of Bevacizumab for Retinopathy of Prematurity

Author

G. Baker Hubbard, Mary Lou McGregor, Lingkun Kong, Catherine O. Jordan, Iason S. Mantagos, Lois E.H. Smith, Raymond T. Kraker, Trevano W. Dean, Edward F. Bell, Mary Elizabeth Hartnett, and David K. Wallace

Subjects
medicine.medical_specialty, genetic structures, Bevacizumab, medicine.medical_treatment, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, medicine, 030212 general & internal medicine, Dosing, business.industry, Gestational age, Retinal detachment, Retinopathy of prematurity, medicine.disease, eye diseases, Confidence interval, Surgery, Ophthalmology, 030221 ophthalmology & optometry, sense organs, business, Laser coagulation, medicine.drug
Abstract

Purpose Intravitreal bevacizumab is increasingly used to treat severe retinopathy of prematurity (ROP), but it enters the bloodstream, and there is concern that it may alter development of other organs. Previously we reported short-term outcomes of 61 infants enrolled in a dose de-escalation study, and we report the late recurrences and additional treatments. Design Masked, multicenter, dose de-escalation study. Participants A total of 61 premature infants with type 1 ROP. Methods If type 1 ROP was bilateral at enrollment, then the study eye was randomly selected. In the study eye, bevacizumab intravitreal injections were given at de-escalating doses of 0.25 mg, 0.125 mg, 0.063 mg, or 0.031 mg; if needed, fellow eyes received 1 dose level higher: 0.625 mg, 0.25 mg, 0.125 mg, or 0.063 mg, respectively. After 4 weeks, additional treatment was at the discretion of the investigator. Main Outcome Measures Early and late ROP recurrences, additional treatments, and structural outcomes after 6 months. Results Of 61 study eyes, 25 (41%; 95% confidence interval [CI], 29%–54%) received additional treatment: 3 (5%; 95% CI, 1%–14%) for early failure (within 4 weeks), 11 (18%; 95% CI, 9%–30%) for late recurrence of ROP (after 4 weeks), and 11 (18%; 95% CI, 9%–30%) for persistent avascular retina. Re-treatment for early failure or late recurrence occurred in 2 of 11 eyes (18%; 95% CI, 2%–52%) treated with 0.25 mg, 4 of 16 eyes (25%; 95% CI, 7%–52%) treated with 0.125 mg, 8 of 24 eyes (33%; 95% CI, 16%–55%) treated with 0.063 mg, and 0 (0%; 95% CI, 0%–31%) of 10 eyes treated with 0.031 mg. By 6 months corrected age, 56 of 61 study eyes had regression of ROP with normal posterior poles, 1 study eye had developed a Stage 5 retinal detachment, and 4 infants had died of preexisting medical conditions. Conclusions Retinal structural outcomes are very good after low-dose bevacizumab treatment for ROP, although many eyes received additional treatment.

Published
2018

33. 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

35. Dopamine metabolite levels in the vitreous of diabetic and non-diabetic humans

Author

Steve Yeh, Blaine Cribbs, Andrew Hendrick, Li He, Susov Dhakal, Jiong Yan, Scott Barb, G. Baker Hubbard, Nieraj Jain, Jesse M. Smith, Chris Stelton, and P. Michael Iuvone

Subjects
0301 basic medicine, Pars plana, medicine.medical_specialty, genetic structures, medicine.medical_treatment, Metabolite, Dopamine, Vitrectomy, Article, 03 medical and health sciences, Cellular and Molecular Neuroscience, chemistry.chemical_compound, 0302 clinical medicine, Diabetes mellitus, Ophthalmology, medicine, Diabetes Mellitus, Humans, Diabetic Retinopathy, business.industry, Retinal, Diabetic retinopathy, medicine.disease, Sensory Systems, eye diseases, Vitreous Body, 030104 developmental biology, medicine.anatomical_structure, chemistry, 030221 ophthalmology & optometry, sense organs, business, Biomarkers, Retinopathy, medicine.drug
Abstract

Animal studies suggest that the retinal dysfunction in diabetic subjects that precedes overt clinical vasculopathy may be due to a retinal dopamine deficit. We analyzed levels of dopamine (DA) and its primary metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC), in the vitreous of diabetic and non-diabetic human subjects. Adult patients undergoing pars plana vitrectomy for non-hemorrhagic indications were prospectively recruited from the Emory Eye Center in Atlanta, GA. Vitreous samples were analyzed using high performance liquid chromatography (HPLC) to measure levels of DOPAC and DA in the vitreous specimens. Vitreous samples from 9 diabetic patients and 20 from non-diabetic patients were analyzed. No eyes had apparent diabetic retinopathy. Mean normalized DA concentration in vitreous of diabetic subjects was 0.76 ± 0.12 pg/μL vs. 0.73 ± 0.08 pg/μL in non-diabetic vitreous (p = 0.849). DOPAC concentration was 8.84 ± 0.74 pg/μL in vitreous of diabetic subjects vs. 9.22 ± 0.56 pg/μL in vitreous of non-diabetic subjects (p = 0.691). No difference was observed in the concentrations of DA and DOPAC in the vitreous of people without diabetes compared to those with diabetes without retinopathy.

Published
2020

36. Local Anatomic Precursors to New-Onset Geographic Atrophy in Age-Related Macular Degeneration as Defined on OCT

Author

Malini Veerappan Pasricha, Vincent Tai, Karim Sleiman, Katrina Winter, Stephanie J. Chiu, Sina Farsiu, Sandra S. Stinnett, Eleonora M. Lad, Wai T. Wong, Emily Y. Chew, Cynthia A. Toth, Michelle McCall, Sunil Srivastava, Neeru Sarin, Stefanie Schuman, Monica Sevilla, Christopher Harrington, Randall Gunther, Du Tran-Viet, Francisco Folgar, Eric Yuan, Wai Wong, Katherine Hall, Emily Chew, Thomas Hwang, Patti McCollum, G. Baker Hubbard, Linda Curtis, Traci Clemons, and Molly Harrington

Subjects
Male, medicine.medical_specialty, Time Factors, genetic structures, Eye disease, Retinal Pigment Epithelium, Drusen, New onset, 03 medical and health sciences, Macular Degeneration, 0302 clinical medicine, Optical coherence tomography, Ophthalmology, Age related, Geographic Atrophy, Medicine, Humans, Macula Lutea, Prospective Studies, 030304 developmental biology, Aged, Aged, 80 and over, 0303 health sciences, medicine.diagnostic_test, business.industry, Macular degeneration, Middle Aged, medicine.disease, eye diseases, Hyperreflective foci, Geographic atrophy, 030221 ophthalmology & optometry, Female, sense organs, business, Tomography, Optical Coherence, Follow-Up Studies
Abstract

In macula-wide analyses, spectral-domain (SD) optical coherence tomography (OCT) features including drusen volume, hyperreflective foci, and OCT-reflective drusen substructures independently predict geographic atrophy (GA) onset secondary to age-related macular degeneration (AMD). We sought to identify SD OCT features in the location of new GA before its onset.Retrospective study.Age-Related Eye Disease Study 2 Ancillary SD OCT Study participants.We analyzed longitudinally captured SD OCT images and color photographs from 488 eyes of 488 participants with intermediate AMD at baseline. Sixty-two eyes with sufficient image quality demonstrated new-onset GA on color photographs during study years 2 through 7. The area of new-onset GA and one size-matched control region in the same eye were segmented separately, and corresponding spatial volumes on registered SD OCT images at the GA incident year and at 2, 3, and 4 years previously were defined. Differences in SD OCT features between paired precursor regions were evaluated through matched-pairs analyses.Localized SD OCT features 2 years before GA onset.Compared with paired control regions, GA precursor regions at 2, 3, and 4 years before (n = 54, 33, and 25, respectively) showed greater drusen volume (P = 0.01, P = 0.003, and P = 0.003, respectively). At 2 and 3 years before GA onset, they were associated with the presence of hypertransmission (P0.001 and P = 0.03, respectively), hyperreflective foci (P0.001 and P = 0.045, respectively), OCT-reflective drusen substructures (P = 0.004 and P = 0.03, respectively), and loss or disruption of the photoreceptor zone, ellipsoid zone, and retinal pigment epithelium (RPE, P0.001 and P = 0.005-0.045, respectively). At 4 years before GA onset, precursor regions were associated with photoreceptor zone thinning (P = 0.007) and interdigitation zone loss (P = 0.045).Evolution to GA is heralded by early local photoreceptor changes and drusen accumulation, detectable 4 years before GA onset. These precede other anatomic heralds such as RPE changes and drusen substructure emergence detectable 1 to 2 years before GA. This study thus identified earlier end points for GA as potential therapeutic targets in clinical trials.

Published
2020

37. Analysis of Predisposing Clinical Features for Worsening Traction After Treatment of Familial Exudative Vitreoretinopathy in Children

Author

G. Baker Hubbard and Alexa L. Li

Subjects
Male, medicine.medical_specialty, Visual acuity, genetic structures, Fundus Oculi, medicine.medical_treatment, Familial Exudative Vitreoretinopathies, Visual Acuity, Retina, Article, 03 medical and health sciences, 0302 clinical medicine, Postoperative Complications, Ophthalmology, medicine, Humans, Fluorescein Angiography, 030304 developmental biology, Retrospective Studies, 0303 health sciences, business.industry, Laser treatment, Retrospective cohort study, Traction (orthopedics), medicine.disease, eye diseases, Child, Preschool, 030221 ophthalmology & optometry, Familial exudative vitreoretinopathy, Comparison study, Vitreoretinal traction, Female, Laser Therapy, medicine.symptom, business, After treatment, Follow-Up Studies
Abstract

Purpose To determine the incidence of worsening vitreoretinal traction after laser treatment for familial exudative vitreoretinopathy (FEVR) and to determine whether any baseline clinical features are associated with worsening. Design Retrospective cohort comparison study in a university tertiary referral center. Methods: All patients 0-21 years of age treated with laser from January 1, 2001, to June 1, 2018, were studied. Worsening traction after treatment was defined as the occurrence within 6 months of worsening or development of tractional retinal detachment, folds, dragging, breaks, rhegmatogenous detachment, or worsening tractional membranes. Comparisons of baseline features between groups with and without worsening were performed to determine features associated with higher risk. Results A total of 46 eyes from 28 patients met inclusion criteria. Of the 46 eyes, 6 (13%) had worsening after treatment. There were no significant differences in age or other baseline demographics between the cohorts with and those without worsening traction. The presence of proliferative tissue in contact with the lens was found in 2 of 6 patients with worsening compared to 1 of 40 (3%) without worsening (P = .04). Mean follow-up was 57.8 months (range, 6.6-134 months). At the 6-month follow-up, median logMAR visual acuity in the cohorts with and without worsening was 1.7 (Snellen 20/1002; n = 5) and 0.24 (Snellen 20/35; n = 16), respectively. Conclusions Laser treatment resulted in worsening traction in a substantial proportion of eyes with FEVR. Children with proliferative tissue in contact with the lens may be at higher risk of worsening after laser. Potential measures to reduce risk will require further study to establish efficacy.

Published
2020

38. Neurodevelopmental Outcomes of Preterm Infants With Retinopathy of Prematurity by Treatment

Author

Michael P. Blair, G. Baker Hubbard, Michael J. Shapiro, Timothy G. Murray, Sarah Hilkert Rodriguez, Audina M. Berrocal, and Maria Ann Martinez-Castellanos

Subjects
Pediatrics, medicine.medical_specialty, Bevacizumab, biology, business.industry, Birth weight, VEGF receptors, Gestational age, Retinopathy of prematurity, medicine.disease, 03 medical and health sciences, 0302 clinical medicine, Primary outcome, 030225 pediatrics, Baseline characteristics, Pediatrics, Perinatology and Child Health, medicine, biology.protein, business, medicine.drug
Abstract

Because most studies regarding neurodevelopment in retinopathy of prematurity (ROP) are small and single-center studies, we commend the authors for this retrospective multicenter analysis of prospectively collected data comparing anti–vascular endothelial growth factor (VEGF) with laser treatment.1 Although they found no difference in their primary outcome of severe neurodevelopmental impairment (NDI) or death, when examined separately, they found a higher rate of death but not of NDI. Unfortunately, as a nonrandomized study, it suffers from imbalance in baseline characteristics, which limits robustness. First, as the authors acknowledge, infants who received bevacizumab were smaller and sicker. At baseline, infants treated with bevacizumab had lower median birth weight ( P = .02), gestational age ( P = .05), and … E-mail: gnatara{at}med.wayne.edu

Published
2020

39. Reactivation of Retinopathy of Prematurity in Adults and Adolescents

Author

Prethy Rao, Ogul E. Uner, and G. Baker Hubbard

Subjects
Adult, Male, medicine.medical_specialty, Pediatrics, Visual acuity, Time Factors, genetic structures, Adolescent, Fundus Oculi, medicine.medical_treatment, Population, Visual Acuity, Vitrectomy, Cryotherapy, Single Center, Scleral buckle, Retina, Article, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Ophthalmology, medicine, Humans, Retinopathy of Prematurity, Fluorescein Angiography, education, Child, 030304 developmental biology, Retrospective Studies, 0303 health sciences, education.field_of_study, business.industry, Disease Management, Retinopathy of prematurity, medicine.disease, eye diseases, 030221 ophthalmology & optometry, Disease Progression, Female, sense organs, Phthisis bulbi, medicine.symptom, business, Follow-Up Studies
Abstract

Purpose To review the clinical features, treatment outcomes, and prevalence within our clinic population of adolescents and adults with previously regressed retinopathy of prematurity (ROP) who demonstrate late-onset exudation and vasoproliferative changes. Design Retrospective review of consecutive patients at a single center. Participants Five patients (5 eyes) with a history of ROP who showed new exudates or worsening fibrovascular proliferation diagnosed after 10 years of age. Methods Patients were identified by a computerized search of the Emory Eye Center billing records. Data extracted from charts included baseline ROP information, visual acuity and other examination findings, imaging, and treatments. Main Outcome Measures Status of exudation and vasoproliferation. Results Among 138 patients older than 10 years with ROP seen at our tertiary referral center from 2000 through 2018, 5 (3.6%) demonstrated late-onset exudation or vasoproliferation. Three patients were female and 3 underwent ROP treatment as neonates. Mean age at onset of late reactivation was 25.6 years (range, 13–43 years). Previous treatments for neonatal ROP included peripheral laser ablation (n = 3), scleral buckle (n = 2), pars plicata vitrectomy (n = 2), and no treatment (n = 2). Management strategies for late reactivation included observation (n = 1), intravitreal anti–vascular endothelial growth factor agents (n = 4), vitrectomy (n = 2), and cryotherapy (n = 1). With mean follow-up of 4.8 years (range, 1–7 years), outcomes were resolution of exudation or proliferation with return to baseline vision (n = 2), stable mild exudation (n = 1), and progressive vasoproliferation with traction leading to phthisis (n = 2). Conclusions Late-onset exudation and fibrovascular proliferation in adolescents and adults with ROP can occur rarely with previously regressed ROP. Two of 5 patients were refractory to all treatments and demonstrated phthisis bulbi. One patient showed reactivation in the form of a reactive retinal astrocytic tumor. Our findings highlight the importance continued monitoring with regular fundus examination in adolescents and adults with regressed ROP.

Published
2019

40. Plasma Vascular Endothelial Growth Factor Concentrations after Intravitreous Anti–Vascular Endothelial Growth Factor Therapy for Diabetic Macular Edema

Author

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

Subjects
Male, Vascular Endothelial Growth Factor A, medicine.medical_specialty, Visual acuity, genetic structures, Bevacizumab, Recombinant Fusion Proteins, Visual Acuity, 030232 urology & nephrology, Angiogenesis Inhibitors, Enzyme-Linked Immunosorbent Assay, Gastroenterology, Macular Edema, Article, law.invention, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Randomized controlled trial, law, Ranibizumab, Internal medicine, medicine, Humans, Stroke, Aflibercept, Diabetic Retinopathy, business.industry, Middle Aged, medicine.disease, Confidence interval, Vascular endothelial growth factor, Ophthalmology, Receptors, Vascular Endothelial Growth Factor, Treatment Outcome, chemistry, Intravitreal Injections, Retreatment, 030221 ophthalmology & optometry, Female, medicine.symptom, business, Tomography, Optical Coherence, Follow-Up Studies, medicine.drug
Abstract

PURPOSE: Assess systemic vascular endothelial growth factor-A (VEGF) levels after treatment with intravitreous aflibercept, bevacizumab or ranibizumab. DESIGN: Comparative-effectiveness trial with participants randomly assigned to 2-mg aflibercept, 1.25-mg bevacizumab, or 0.3-mg ranibizumab following a retreatment algorithm. PARTICIPANTS: Participants with available plasma samples (N=436) METHODS: Plasma samples were collected before injections at baseline, 4-week, 52-week and 104-week visits. In a pre-planned secondary analysis, systemic free-VEGF levels from an ELISA immunoassay were compared across anti-VEGF agents and correlated with systemic side effects. MAIN OUTCOME MEASURES: Changes in the natural log (ln) of plasma VEGF levels. RESULTS: Baseline free-VEGF levels were similar across all 3 groups. At 4 weeks, mean ln(VEGF) changes were −0.30±0.61, −0.31±0.54, −0.02±0.44 pg/ml for the aflibercept, bevacizumab, and ranibizumab groups, respectively. The adjusted differences between treatment groups (adjusted CI; P-value) were −0.01 (−0.12, +0.10; P=0.89), −0.31 (−0.44, −0.18; P

Published
2018

41. Treatment of Geographic Atrophy with Intravitreal Sirolimus

Author

G. Baker Hubbard, Ronald P. Danis, Gary Gensler, Michael J. Elman, Amitha Domalpally, Michael E. Rauser, Jack Wells, Alexander J. Brucker, Barbara A Blodi, Traci E Clemons, Emily Y. Chew, Gary E. Fish, John Hoskins, and Alan R. Margherio

Subjects
0301 basic medicine, medicine.medical_specialty, Visual acuity, genetic structures, business.industry, Eye disease, Phases of clinical research, Age-Related Eye Disease Study, Macular degeneration, Fundus (eye), medicine.disease, eye diseases, Clinical trial, 03 medical and health sciences, Ophthalmology, 030104 developmental biology, 0302 clinical medicine, Sirolimus, 030221 ophthalmology & optometry, medicine, sense organs, medicine.symptom, business, medicine.drug
Abstract

Purpose To evaluate the efficacy and safety of sirolimus, an immunosuppressive drug, for the treatment of age-related macular degeneration (AMD)–associated geographic atrophy (GA). Design Randomized, controlled, single-masked multicenter phase II clinical trial of intravitreal sirolimus versus sham therapy in Age-Related Eye Disease Study 2 (AREDS2) clinical centers. Participants Patients with GA. Methods Participants were assigned randomly to a monthly intravitreal injection of sirolimus (20 μL [440 μg]) or sham treatment. Best-corrected visual acuity (BVCA), spectral-domain OCT, fundus color photography, and fundus autofluorescence (FAF) images were obtained at baseline and every 6 months until visit month 24. Main Outcome Measures Rate of progression of GA (square millimeters per year) measured on color fundus photographs from baseline to 24 months. Secondary outcome measures include change in BVCA, worsening of vision by 3 lines or more, and changes in area of GA measured on FAF and OCT. Results Fifty-two participants (mean age, 79 years) were enrolled, with 27 study eyes assigned to sirolimus from May 2012 through March 2014. The baseline median area of GA was 4.73 disc areas (DA; 12.01 mm 2 ). The mean growth rates of GA detected on color fundus photographs were 2.27 mm 2 (standard deviation [SD], 2.17 mm 2 ) and 1.91 mm 2 (SD, 2.27 mm 2 ) at month 12 and 4.94 mm 2 (SD, 2.96 mm 2 ) and 5.72 mm 2 (SD, 3.97 mm 2 ) at month 24 for the sirolimus and sham groups, respectively. There was no statistically significant difference in the GA growth rates between the 2 treatment groups ( P = 0.33). Median visual acuity changes and incidence of 15-letter loss from baseline were not different between the 2 treatment groups ( P = 0.19). The intervention was stopped early because of sterile endophthalmitis that occurred in 3 participants in the sirolimus group. Participants were followed up for safety until the study was closed in May 2015 because of lack of efficacy. Conclusions Sirolimus did not result in different rates of GA growth in this phase II study. Immunosuppression may be important for some stages of the AMD process, but may not necessarily be the main pathway for the development of GA.

Published
2018

42. Formulation of a Peribulbar Block for Prolonged Postoperative Pain Management in Vitreoretinal Surgery

Author

Chris S. Bergstrom, Timothy W. Olsen, Andrew Hendrick, Rui Zhang, G. Baker Hubbard, Philip W. Laird, Matthew R. Debiec, Cindy S. Hwang, Steven Yeh, Alcides Fernandes, Sonia Mehta, and Jiong Yan

Subjects
Bupivacaine, medicine.medical_specialty, Intraocular pressure, Triamcinolone acetonide, business.industry, medicine.medical_treatment, Analgesic, Chronic pain, Vitrectomy, medicine.disease, Scleral buckle, Surgery, law.invention, 03 medical and health sciences, Ophthalmology, 0302 clinical medicine, Randomized controlled trial, 030202 anesthesiology, law, Anesthesia, 030221 ophthalmology & optometry, medicine, business, medicine.drug
Abstract

Purpose To evaluate postoperative pain level using a supplemental peribulbar injection at the conclusion of retinal surgery. Design Prospective, parallel-assigned, single-masked, randomized clinical trial. Participants Fifty-eight patients undergoing scleral buckle, vitrectomy, or combined surgery. Methods In a single academic institutional practice, 58 patients undergoing scleral buckle, vitrectomy, or combined surgery were enrolled. Exclusion criteria included those with a risk for glaucoma, a pre-existing chronic pain disorder, among others. Patients were assigned randomly to receive a postoperative peribulbar formulation of either bupivacaine, triamcinolone acetonide, and cefazolin (group A) or bupivacaine, balanced salt solution, and cefazolin (group B). The postoperative pain score and ocular motility were assessed by a masked observer on the first postoperative day. Main Outcome Measures The primary outcome measure was the postoperative pain score. Secondary outcome measures included oral analgesic use, ocular motility, and intraocular pressure (IOP). Results The mean pain scores were 2.8±2.9 for group A and 3.8±2.6 for group B (P = 0.095). Pain was absent in 28% of group A patients versus 14% of group B patients (P = 0.11). Group A required less narcotic pain medication (hydroxycodone: group A, 0.7±3 mg vs. group B, 3±6 mg; P = 0.05; oxycodone: group A, 7±7 mg vs. 9±13 mg; P = 0.2) than group B. Motility was full in group B and limited in group A (P ≤ 0.001), with no differences in mean IOP measurements at any point after surgery. Conclusions We did not demonstrate a statistically significant reduction in mean postoperative pain scores. However, patients in group A required less hydroxycodone use and had greater akinesia, suggesting prolonged neural blockade.

Published
2018

43. Single grading vs double grading with adjudication in the telemedicine approaches to evaluating acute-phase retinopathy of prematurity (e-ROP) study

Author

Ebenezer Daniel, Wei Pan, Graham E. Quinn, Eli Smith, Agnieshka Baumritter, Gui-Shuang Ying, Kelly Wade, Trang B. Duros, Lisa Erbring, Michael X. Repka, Jennifer A. Shepard, David Emmert, C. Mark Herring, Deborah VanderVeen, Suzanne Johnston, Carolyn Wu, Jason Mantagos, Danielle Ledoux, Tamar Winter, Frank Weng, Theresa Mansfield, Don L. Bremer, Mary Lou McGregor, Catherine Olson Jordan, David L. Rogers, Rae R. Fellows, Suzanne Brandt, Brenda Mann, David Wallace, Sharon Freedman, Sarah K. Jones, Du Tran-Viet, Rhonda 'Michelle' Young, Charles C. Barr, Rahul Bhola, Craig Douglas, Peggy Fishman, Michelle Bottorff, Brandi Hubbuch, Rachel Keith, Erick D. Bothun, Inge DeBecker, Jill Anderson, Ann Marie Holleschau, Nichole E. Miller, Darla N. Nyquist, R. Michael Siatkowski, Lucas Trigler, Marilyn Escobedo, Karen Corff, Michelle Huynh, Kelli Satnes, Monte D. Mills, Will Anninger, Gil Binenbaum, Graham Quinn, Karen A. Karp, Denise Pearson, Alice Gong, John Stokes, Clio Armitage Harper, Laurie Weaver, Carmen McHenry, Kathryn Conner, Rosalind Heemer, Elnora Cokley, Robert Hoffman, David Dries, Katie Jo Farnsworth, Deborah Harrison, Bonnie Carlstrom, Cyrie Ann Frye, David Morrison, Sean Donahue, Nancy Benegas, Sandy Owings, Sandra Phillips, Scott Ruark, Anna Ells, Patrick Mitchell, April Ingram, Rosie Sorbie, Maureen Maguire, Mary Brightwell-Arnold, Max Pistilli, Kathleen McWilliams, Sandra Harris, Claressa Whearry, E. Revell Martin, Candace R. Parker Ostroff, Krista Sepielli, Antonio Capone, G. Baker Hubbard, Peter Lloyd, Kerry Davis, G. Carl Gibson, Regina Hansen, Alex R. Kemper, Lisa Prosser, David C. Musch, Stephen P. Christiansen, Ditte J. Hess, Steven M. Kymes, SriniVas R. Sadda, Ryan Spaulding, and Eleanor B. Schron

Subjects
medicine.medical_specialty, Telemedicine, business.industry, Infant, Newborn, Infant, Retinopathy of prematurity, medicine.disease, Sensitivity and Specificity, Article, Ophthalmoscopy, 03 medical and health sciences, Ophthalmology, 0302 clinical medicine, 030225 pediatrics, Pediatrics, Perinatology and Child Health, Image Processing, Computer-Assisted, 030221 ophthalmology & optometry, medicine, Humans, Infant, Very Low Birth Weight, Retinopathy of Prematurity, Grading (education), business
Abstract

To evaluate the sensitivity and specificity of single, independent, nonphysician trained reader (TR) gradings in the Telemedicine Approaches to Evaluating Acute-phase Retinopathy of Prematurity (e-ROP) study.Secondary analyses of image grading results from 1,235 infants of birth weights1251 g. Two of three TRs independently graded image sets; discrepancies were adjudicated by the reading center director (an ophthalmologist) to reach final grading. Sensitivity and specificity of each TR grading and final grading was calculated by comparing gradings to clinical examination results.Of 7,808 double graded image sets, TR1 graded 5,165; TR2, 3,787; and TR3, 6,664. Compared to final grading for referral warranted retinopathy of prematurity (RW-ROP), two TRs had relatively lower sensitivity (TR1, 75% vs 79% [P = 0.03]; TR2, 73% vs 77% [P = 0.02]) and specificity (TR1, 80% vs 83% [P 0.001]; TR2, 82% vs 83% [P = 0.09]). TR3 had similar sensitivity (83% vs 83% [P = 0.78]) and specificity (83% vs 84% [P = 0.02]). Compared to final grading, TR1 had lower sensitivity for zone I ROP (47% vs 56% [P = 0.04]) and stage ≥3 ROP (71% vs 77% [P = 0.002]); TR2 had lower sensitivity for stage ≥3 ROP (69% vs 77% [P 0.001]) and lower specificity for all three components (P 0.001); TR3 had lower sensitivity for detecting plus disease (23% vs 35% [P 0.001]) and similar sensitivity for zone I ROP and stage ≥3 ROP.There is a small but significant decrease in the sensitivity and specificity for RW-ROP when single-reader grading is compared to double adjudicated grading.

Published
2018

44. Intravitreous Cutaneous Metastatic Melanoma in the Era of Checkpoint Inhibition: Unmasking and Masquerading

Author

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

Subjects
Adult, Aged, 80 and over, Male, Skin Neoplasms, genetic structures, Eye Neoplasms, Middle Aged, eye diseases, Article, Vitreous Body, Young Adult, Humans, Female, sense organs, Immunotherapy, Antineoplastic Agents, Alkylating, Melanoma, Melphalan, Aged, Retrospective Studies
Abstract

PURPOSE: Cutaneous melanoma metastatic to the vitreous is very rare. This study investigates the clinical findings, treatment and outcome of patients with metastatic cutaneous melanoma to the vitreous. The majority of patients received checkpoint inhibition for the treatment of their systemic disease and the significance of this is explored. PARTICIPANTS: 14 eyes of 11 patients with metastatic cutaneous melanoma to the vitreous. DESIGN: Multicenter, retrospective cohort study METHODS: Clinical records, including fundus photography and ultrasound, were retrospectively reviewed and relevant data was recorded for each patient eye. MAIN OUTCOME MEASURES: Clinical features at presentation, ophthalmic and systemic treatments and outcome 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 eleven patients were treated with immune checkpoint inhibition, at some point in their treatment course. The median time from starting immunotherapy to ocular symptoms was 17 months (range 4.5 to 38 mos). Half the eyes had amelanotic vitreous debris. Five eyes developed elevated intraocular pressure and four eyes developed a retinal detachment. Six patients had metastatic disease in their central nervous system. Ophthalmic treatment included: external beam radiation (30–40Gy) in six eyes, intravitreous melphalan (10–20μg) in four eyes, enucleation in one eye, local observation while on systemic treatment in two eyes. Three eyes received intravitreous bevacizumab for neovascularization. The final Snellen visual acuity ranged from 20/20 to no light perception (NLP). CONCLUSION: The differential diagnosis of vitreous debris in the context of metastatic cutaneous melanoma includes intravitreal metastasis, and this appears 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 the majority of eyes have poor visual potential. Approximately one quarter of the patients had 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
2019

45. Strength of Association between Pentosan Polysulfate and a Novel Maculopathy

Author

Andrew Hendrick, Purnima Patel, Ghazala O'Keefe, Jessica G. Shantha, Shivani A. Patel, Steven Yeh, Blaine Cribbs, Jithin Sam Varghese, Adam M. Hanif, Nieraj Jain, Rachel Shah, Prethy Rao, Jiong Yan, and G. Baker Hubbard

Subjects
Male, Pentosan Sulfuric Polyester, medicine.medical_specialty, Extramural, business.industry, Cystitis, Interstitial, Retinal Pigment Epithelium, Pentosan polysulfate, Middle Aged, medicine.disease, Ophthalmology, Macular Degeneration, Internal medicine, medicine, Maculopathy, Humans, Female, business, medicine.drug, Aged
Published
2019

46. Fluorescein Angiography in Retinopathy of Prematurity-Comparison of Infants Treated with Bevacizumab to Those with Spontaneous Regression

Author

Amy K. Hutchinson, G. Baker Hubbard, John C. Allen, Sasha A. Mansukhani, Joseph Schertzer, and Rebecca F. Neustein

Subjects
medicine.medical_specialty, Bevacizumab, genetic structures, Birth weight, Posterior pole, Article, 03 medical and health sciences, 0302 clinical medicine, Ophthalmology, Medicine, 030304 developmental biology, 0303 health sciences, medicine.diagnostic_test, business.industry, Gestational age, Retrospective cohort study, Retinopathy of prematurity, medicine.disease, Fluorescein angiography, eye diseases, Cohort, 030221 ophthalmology & optometry, sense organs, business, medicine.drug
Abstract

Objective Medium- and long-term sequelae of intravitreal bevacizumab (IVB) for type 1 retinopathy of prematurity (ROP) are uncertain. Our aim was to describe the fluorescein angiography (FA) findings in patients who received IVB as primary treatment for type 1 ROP and compare them to findings in patients with ROP that spontaneously regressed. Design Retrospective cohort. Participants Twenty-eight patients with a history of ROP who underwent fluorescein angiography between December 1, 2013, and July 31, 2018. Patients were divided into 2 groups based on whether they had received IVB or had ROP that spontaneously regressed. Methods We reviewed the angiograms in the 2 groups for neovascularization (NV) and other abnormal vascular patterns in both the periphery and the posterior pole. Main Outcome Measures Fluorescein angiography findings, including NV, peripheral, and macular vascular abnormalities. Results Forty eyes of 20 infants were included in the IVB group and 16 eyes of 8 infants in the untreated group. Median gestational age at birth was similar in the 2 groups (24.5 and 24.7 weeks, respectively; P = 0.44), as was the median birth weight (648.5 and 560.0 g, respectively; P = 0.26). Median postmenstrual age at the time of FA was 65.1 and 83.9 weeks, respectively (P = 0.0002). Review of angiograms demonstrated NV in 30.0% and 37.5% in the IVB and untreated cohorts, respectively (P = 0.75). Abnormal vascular patterns in the periphery were similar in both groups (100.0%), whereas posterior pole findings of vessels encroaching onto the fovea were more prevalent in the IVB cohort (65.0% vs. 25.0%; P = 0.009). Conclusions Fluorescein angiography after bevacizumab for ROP reveals abnormal vascular patterns in all eyes and NV in approximately one-third. Similar abnormal vascular patterns on FA are seen at a similar prevalence after spontaneous regression of ROP. These findings suggest that the abnormal vascular patterns identified by FA in patients with ROP result from the disease process itself rather than as a result of exposure to anti–vascular endothelial growth factor medications.

Published
2019

47. Distinct Gene Expression Profiles Define Anaplastic Grade in Retinoblastoma

Author

Jill R. Wells, Charles S. Specht, Eldon E. Geisert, Lauren E. Hudson, Alison Ziesel, William H. Hudson, Jeanne Kowalski, Hans E. Grossniklaus, Sandra Seby, Bhakti Dwivedi, Pia R. Mendoza, Viren Patel, and G. Baker Hubbard

Subjects
0301 basic medicine, Genetic Markers, Male, Retinal Neoplasms, Gene Expression, Disease, Biology, Article, Pathology and Forensic Medicine, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Gene expression, medicine, Humans, Genes, Retinoblastoma, Gene, Anaplasia, Neoplasm Grading, Microarray analysis techniques, Retinoblastoma, Gene Expression Profiling, Infant, medicine.disease, Gene expression profiling, 030104 developmental biology, Child, Preschool, 030221 ophthalmology & optometry, Cancer research, Female, medicine.symptom
Abstract

Morbidity and mortality associated with retinoblastoma have decreased drastically in recent decades, in large part owing to better prediction of high-risk disease and appropriate treatment stratification. High-risk histopathologic features and severe anaplasia both predict the need for more aggressive treatment; however, not all centers are able to assess tumor samples easily for the degree of anaplasia. Instead, identification of genetic signatures that are able to distinguish among anaplastic grades and thus predict high- versus low-risk retinoblastoma would facilitate appropriate risk stratification in a wider patient population. A better understanding of genes dysregulated in anaplasia also would yield valuable insights into pathways underlying the development of more severe retinoblastoma. Here, we present the histopathologic and gene expression analysis of 28 retinoblastoma cases using microarray analysis. Tumors of differing anaplastic grade show clear differential gene expression, with significant dysregulation of unique genes and pathways in severe anaplasia. Photoreceptor and nucleoporin expression in particular are identified as highly dysregulated in severe anaplasia and suggest particular cellular processes contributing to the development of increased retinoblastoma severity. A limited set of highly differentially expressed genes also are able to predict severe anaplasia accurately in our data set. Together, these data contribute to the understanding of the development of anaplasia and facilitate the identification of genetic markers of high-risk retinoblastoma.

Published
2018

48. The Economic Model of Retinopathy of Prematurity (EcROP) Screening and Treatment: Mexico and the United States

Author

David Berrones, Alcides Fernandes, Timothy W. Olsen, Zhou Yang, Christopher J. Williams, Maria Ana Martinez-Castellanos, Bhavesh Patel, R.V. Paul Chan, Kathryn A. Brennan, Rebecca Russ, Michael Rothschild, and G. Baker Hubbard

Subjects
Male, Pediatrics, medicine.medical_specialty, Cost-Benefit Analysis, MEDLINE, 03 medical and health sciences, Indirect costs, Neonatal Screening, 0302 clinical medicine, Quality of life (healthcare), Environmental health, Health care, Humans, Medicine, Retinopathy of Prematurity, 030212 general & internal medicine, Child, Mexico, health care economics and organizations, Cost–benefit analysis, business.industry, Infant, Newborn, Retinopathy of prematurity, Health Care Costs, medicine.disease, United States, Quality-adjusted life year, Ophthalmology, Models, Economic, Economic data, 030221 ophthalmology & optometry, Female, Quality-Adjusted Life Years, business
Abstract

Purpose To describe an economic (Ec) model for estimating the impact of screening and treatment for retinopathy of prematurity (ROP). Design EcROP is a cost-effectiveness, cost-utility, and cost-benefit analysis. Methods We surveyed caregivers of 52 children at schools for the blind or pediatric eye clinics in Atlanta, Georgia and 43 in Mexico City. A decision analytic model with sensitivity analysis determined the incremental cost-effectiveness (primary outcome) and incremental monetary benefit (secondary outcome) of an ideal (100% screening) national ROP program as compared to estimates of current practice. Direct costs included screening and treatment expenditures. Indirect costs estimated lost productivity of caretaker(s) and blind individuals as determined by face-to-face surveys. Utility and effectiveness were measured in quality-adjusted life years and benefit in US dollars. EcROP includes a sensitivity analysis to assesses the incremental cost-effectiveness and societal impact of ROP screening and treatment within a country or economic region. Estimates are based on evidence-based clinical data and region-specific economic data acquired from direct field survey. Results In both Mexico and the United States, an ideal national ROP screening and treatment program was highly cost-saving. The incremental net benefit of an ideal ROP program over current practice is $5556 per child ($206 574 333 annually) and $3628 per child ($205 906 959 annually) in Mexico and the United States, respectively. Conclusion EcROP demonstrates that ROP screening and treatment is highly beneficial for quality of life, cost saving, and cost-effectiveness in the United States and Mexico. EcROP can be applied to any country or region to provide data for informed allocation of limited health care resources.

Published
2016

50. Phenotypic Spectrum of Pentosan Polysulfate Sodium–Associated Maculopathy

Author

G. Baker Hubbard, Rahul N. Khurana, Nieraj Jain, K. Thiran Jayasundera, Christina J. Flaxel, Paul Yang, Adam M. Hanif, Jenelle E. Foote, Austin D. Igelman, Mark E. Pennesi, Jiong Yan, Stephen T. Armenti, Rachel Shah, Ghazala O'Keefe, Joshua D. Stein, Stanford Taylor, and Thomas S. Hwang

Subjects
medicine.medical_specialty, Visual acuity, Retinal pigment epithelium, genetic structures, business.industry, Retinal, Fundus (eye), medicine.disease, eye diseases, Ophthalmology, chemistry.chemical_compound, medicine.anatomical_structure, chemistry, Blurred vision, medicine, Maculopathy, Retinal pigment epithelial atrophy, Metamorphopsia, sense organs, medicine.symptom, business, Original Investigation
Abstract

IMPORTANCE: A unique pigmentary maculopathy was recently described in 6 patients with long-term exposure to pentosan polysulfate sodium (PPS), a long-standing oral therapy for interstitial cystitis. OBJECTIVE: To characterize the exposure characteristics and clinical manifestations of PPS–associated maculopathy. DESIGN, SETTING, AND PARTICIPANTS: In this multi-institutional case series, medical records of patients who exhibited the characteristic maculopathy in the setting of prior PPS exposure were retrospectively reviewed. Data were collected from August 1, 2012, to October 1, 2018, and data were analyzed from October 2018 to January 2019. MAIN OUTCOMES AND MEASURES: Drug exposure, visual acuity, and retinal imaging characteristics. RESULTS: Of the 35 included patients (70 eyes), 34 (97%) were female, and the median (range) age was 60 (37-79) years. The median (range) duration of PPS intake was 15 (3-22) years, and the median (range) cumulative exposure was 1.61 (0.44-4.31) kg. The leading visual symptoms were metamorphopsia, blurred vision, and prolonged dark adaptation. Median (range) logMAR visual acuity of all eyes was 0.10 (−0.12 to 1.18). Fundus examination often revealed hyperpigmented macular spots (34 of 64 eyes [53%]) with interspersed pale-yellow deposits, although less commonly in eyes that exhibited retinal pigment epithelial atrophy (6 of 26 eyes [23%]; P

Published
2019

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