OPHTHALMOLOGY A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES
J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS
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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright 2004 by ICON Group International, Inc. Copyright 2004 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1
Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Ophthalmology: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-597-84137-3 1. Ophthalmology-Popular works. I. Title.
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Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem. It is sold with the understanding that the publisher, editors, and authors are not engaging in the rendering of medical, psychological, financial, legal, or other professional services. References to any entity, product, service, or source of information that may be contained in this publication should not be considered an endorsement, either direct or implied, by the publisher, editors, or authors. ICON Group International, Inc., the editors, and the authors are not responsible for the content of any Web pages or publications referenced in this publication.
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Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on ophthalmology. Books in this series draw from various agencies and institutions associated with the United States Department of Health and Human Services, and in particular, the Office of the Secretary of Health and Human Services (OS), the Administration for Children and Families (ACF), the Administration on Aging (AOA), the Agency for Healthcare Research and Quality (AHRQ), the Agency for Toxic Substances and Disease Registry (ATSDR), the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA), the Healthcare Financing Administration (HCFA), the Health Resources and Services Administration (HRSA), the Indian Health Service (IHS), the institutions of the National Institutes of Health (NIH), the Program Support Center (PSC), and the Substance Abuse and Mental Health Services Administration (SAMHSA). In addition to these sources, information gathered from the National Library of Medicine, the United States Patent Office, the European Union, and their related organizations has been invaluable in the creation of this book. Some of the work represented was financially supported by the Research and Development Committee at INSEAD. This support is gratefully acknowledged. Finally, special thanks are owed to Tiffany Freeman for her excellent editorial support.
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About the Editors James N. Parker, M.D. Dr. James N. Parker received his Bachelor of Science degree in Psychobiology from the University of California, Riverside and his M.D. from the University of California, San Diego. In addition to authoring numerous research publications, he has lectured at various academic institutions. Dr. Parker is the medical editor for health books by ICON Health Publications. Philip M. Parker, Ph.D. Philip M. Parker is the Eli Lilly Chair Professor of Innovation, Business and Society at INSEAD (Fontainebleau, France and Singapore). Dr. Parker has also been Professor at the University of California, San Diego and has taught courses at Harvard University, the Hong Kong University of Science and Technology, the Massachusetts Institute of Technology, Stanford University, and UCLA. Dr. Parker is the associate editor for ICON Health Publications.
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About ICON Health Publications To discover more about ICON Health Publications, simply check with your preferred online booksellers, including Barnes&Noble.com and Amazon.com which currently carry all of our titles. Or, feel free to contact us directly for bulk purchases or institutional discounts: ICON Group International, Inc. 4370 La Jolla Village Drive, Fourth Floor San Diego, CA 92122 USA Fax: 858-546-4341 Web site: www.icongrouponline.com/health
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Table of Contents FORWARD .......................................................................................................................................... 1 CHAPTER 1. STUDIES ON OPHTHALMOLOGY ................................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Ophthalmology.............................................................................. 5 E-Journals: PubMed Central ....................................................................................................... 57 The National Library of Medicine: PubMed ................................................................................ 58 CHAPTER 2. NUTRITION AND OPHTHALMOLOGY ......................................................................... 87 Overview...................................................................................................................................... 87 Finding Nutrition Studies on Ophthalmology ............................................................................ 87 Federal Resources on Nutrition ................................................................................................... 88 Additional Web Resources ........................................................................................................... 89 CHAPTER 3. ALTERNATIVE MEDICINE AND OPHTHALMOLOGY ................................................... 91 Overview...................................................................................................................................... 91 National Center for Complementary and Alternative Medicine.................................................. 91 Additional Web Resources ........................................................................................................... 95 General References ....................................................................................................................... 96 CHAPTER 4. DISSERTATIONS ON OPHTHALMOLOGY ..................................................................... 97 Overview...................................................................................................................................... 97 Dissertations on Ophthalmology ................................................................................................. 97 Keeping Current .......................................................................................................................... 98 CHAPTER 5. PATENTS ON OPHTHALMOLOGY ................................................................................ 99 Overview...................................................................................................................................... 99 Patents on Ophthalmology........................................................................................................... 99 Patent Applications on Ophthalmology..................................................................................... 123 Keeping Current ........................................................................................................................ 131 CHAPTER 6. BOOKS ON OPHTHALMOLOGY .................................................................................. 133 Overview.................................................................................................................................... 133 Book Summaries: Federal Agencies............................................................................................ 133 Book Summaries: Online Booksellers......................................................................................... 134 The National Library of Medicine Book Index ........................................................................... 141 Chapters on Ophthalmology ...................................................................................................... 141 Directories.................................................................................................................................. 145 CHAPTER 7. MULTIMEDIA ON OPHTHALMOLOGY ....................................................................... 147 Overview.................................................................................................................................... 147 Bibliography: Multimedia on Ophthalmology ........................................................................... 147 CHAPTER 8. PERIODICALS AND NEWS ON OPHTHALMOLOGY .................................................... 149 Overview.................................................................................................................................... 149 News Services and Press Releases.............................................................................................. 149 Newsletter Articles .................................................................................................................... 150 Academic Periodicals covering Ophthalmology......................................................................... 151 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 155 Overview.................................................................................................................................... 155 NIH Guidelines.......................................................................................................................... 155 NIH Databases........................................................................................................................... 157 Other Commercial Databases..................................................................................................... 160 APPENDIX B. PATIENT RESOURCES ............................................................................................... 161 Overview.................................................................................................................................... 161 Patient Guideline Sources.......................................................................................................... 161 Finding Associations.................................................................................................................. 169 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 171
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Overview.................................................................................................................................... 171 Preparation................................................................................................................................. 171 Finding a Local Medical Library................................................................................................ 171 Medical Libraries in the U.S. and Canada ................................................................................. 171 ONLINE GLOSSARIES................................................................................................................ 177 Online Dictionary Directories ................................................................................................... 177 OPHTHALMOLOGY DICTIONARY........................................................................................ 179 INDEX .............................................................................................................................................. 245
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FORWARD In March 2001, the National Institutes of Health issued the following warning: "The number of Web sites offering health-related resources grows every day. Many sites provide valuable information, while others may have information that is unreliable or misleading."1 Furthermore, because of the rapid increase in Internet-based information, many hours can be wasted searching, selecting, and printing. Since only the smallest fraction of information dealing with ophthalmology is indexed in search engines, such as www.google.com or others, a non-systematic approach to Internet research can be not only time consuming, but also incomplete. This book was created for medical professionals, students, and members of the general public who want to know as much as possible about ophthalmology, using the most advanced research tools available and spending the least amount of time doing so. In addition to offering a structured and comprehensive bibliography, the pages that follow will tell you where and how to find reliable information covering virtually all topics related to ophthalmology, from the essentials to the most advanced areas of research. Public, academic, government, and peer-reviewed research studies are emphasized. Various abstracts are reproduced to give you some of the latest official information available to date on ophthalmology. Abundant guidance is given on how to obtain free-of-charge primary research results via the Internet. While this book focuses on the field of medicine, when some sources provide access to non-medical information relating to ophthalmology, these are noted in the text. E-book and electronic versions of this book are fully interactive with each of the Internet sites mentioned (clicking on a hyperlink automatically opens your browser to the site indicated). If you are using the hard copy version of this book, you can access a cited Web site by typing the provided Web address directly into your Internet browser. You may find it useful to refer to synonyms or related terms when accessing these Internet databases. NOTE: At the time of publication, the Web addresses were functional. However, some links may fail due to URL address changes, which is a common occurrence on the Internet. For readers unfamiliar with the Internet, detailed instructions are offered on how to access electronic resources. For readers unfamiliar with medical terminology, a comprehensive glossary is provided. For readers without access to Internet resources, a directory of medical libraries, that have or can locate references cited here, is given. We hope these resources will prove useful to the widest possible audience seeking information on ophthalmology. The Editors
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From the NIH, National Cancer Institute (NCI): http://www.cancer.gov/cancerinfo/ten-things-to-know.
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CHAPTER 1. STUDIES ON OPHTHALMOLOGY Overview In this chapter, we will show you how to locate peer-reviewed references and studies on ophthalmology.
The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and ophthalmology, you will need to use the advanced search options. First, go to http://chid.nih.gov/index.html. From there, select the “Detailed Search” option (or go directly to that page with the following hyperlink: http://chid.nih.gov/detail/detail.html). The trick in extracting studies is found in the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Journal Article.” At the top of the search form, select the number of records you would like to see (we recommend 100) and check the box to display “whole records.” We recommend that you type “ophthalmology” (or synonyms) into the “For these words:” box. Consider using the option “anywhere in record” to make your search as broad as possible. If you want to limit the search to only a particular field, such as the title of the journal, then select this option in the “Search in these fields” drop box. The following is what you can expect from this type of search: •
Oral Manifestations of Ehlers-Danlos Syndrome Source: Journal of the Canadian Dental Association. 67(6): 330-334. June 2001. Contact: Available from Canadian Dental Association. 1815 Alta Vista Drive, Ottowa, ON K1G 3Y6. (613) 523-1770. E-mail:
[email protected]. Website: www.cda-adc.ca. Summary: Ehlers Danlos syndrome (EDS) is a rare hereditary disease of the connective tissue which can present oral manifestations. In this article, the authors presents a brief history of the disease, along with the epidemiology and characteristics of the eight main phenotypes of the syndrome. The article also describes the case of the a 12 year old patient presenting with hypermobility of the temporomandibular joint (TMJ) and capillary fragility, and highlights the precautions to take when treating patients with this syndrome. The authors emphasize that oral examination can be instrumental in
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establishing a diagnosis of EDS. The classic signs of EDS are joint hypermobility; hyperelasticity of skin, which is soft, thin, and fragile; the presence of dystophic scars; and a tendency to bleed excessively, manifested by bruises and hematomas. The presence of the classic signs of the syndrome should prompt the clinician to arrange dermatology, genetics, rhematology, cardiology, and ophthalmology consults to confirm and type the diagnosis of EDS. The dentist should perform treatment observing precautions appropriate to this condition. 5 figures. 24 references. •
Spotlight on the Ophthalmic Registered Nurse Source: Diabetes Forecast. 45(7): 76-77. July 1992. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website: www.diabetes.org. Summary: This article describes the work of certified registered nurses in ophthalmology. Topics include the number of nurses in this specialty; the ophthalmic nurses' professional organization, the American Society of Ophthalmic Registered Nurses (ASORN); progress in eye care in the past few years; diabetic retinopathy; eye doctors diagnosing diabetes; the need for people with diabetes to get regular eye examinations; and the role of the eyes as windows to the body's health. 1 figure.
•
Painful Chewing and Blindness: Signs and Symptoms of Temporal Arteritis Source: JADA. Journal of the American Dental Association. 131(12): 1738-1741. December 2000. Contact: Available from American Dental Association. ADA Publishing Co, Inc., 211 East Chicago Avenue, Chicago, IL 60611. (312) 440-2867. Website: www.ada.org. Summary: This article presents a case report that illustrates the need to consider temporal arteritis in the differential diagnosis of jaw or tooth pain. This disease affects the cranial arteries, more frequently in women and usually in those older than age 60 years, causing jaw pain, visual symptoms, headache, scalp pain, and sometimes blindness. In this case, a 71 year old man had jaw pain that increased with chewing and speaking, scalp tenderness, and dimming vision. A temporal artery biopsy confirmed the diagnosis of temporal arteritis. Treatment with decreasing amounts of oral steroids over 23 months was successful in relieving his signs and symptoms and in saving his vision. The authors caution that patients with this disease may seek care from their dentist first, so dentists must maintain a high index of suspicion. Jaw or tooth pain is the most reliable clinical symptom in the diagnosis of temporal arteritis. Diagnosis and timely referral for treatment with oral steroids can prevent blindness. This disease, which has been called the prime medical emergency in ophthalmology, also should be considered a prime medical emergency for dentists. 2 figures. 21 references.
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Preferred Practice Pattern for Diabetic Retinopathy Source: Diabetes Spectrum. 4(2): 64-65. March-April 1991. Summary: This article reviews and summarizes the Preferred Practice Pattern for Diabetic Retinopathy, a guide prepared by the American Academy of Ophthalmology. These standards of care were established as a result of three major nationwide clinical research studies that investigated ways to reduce the threat of visual loss from diabetes. Of significant importance to health-care providers are the suggested examination schedule for patients with diabetes and suggested management recommendations; both are summarized in tables in this article. 4 tables. 1 reference.
Studies
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Federally Funded Research on Ophthalmology The U.S. Government supports a variety of research studies relating to ophthalmology. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.2 CRISP (Computerized Retrieval of Information on Scientific Projects) is a searchable database of federally funded biomedical research projects conducted at universities, hospitals, and other institutions. Search the CRISP Web site at http://crisp.cit.nih.gov/crisp/crisp_query.generate_screen. You will have the option to perform targeted searches by various criteria, including geography, date, and topics related to ophthalmology. For most of the studies, the agencies reporting into CRISP provide summaries or abstracts. As opposed to clinical trial research using patients, many federally funded studies use animals or simulated models to explore ophthalmology. The following is typical of the type of information found when searching the CRISP database for ophthalmology: •
Project Title: ADULT THERAPEUTIC CLINICAL TRIALS PROGRAM FOR AIDS Principal Investigator & Institution: Eron, Joseph J.; Associate Professor; Medicine; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, Nc 27599 Timing: Fiscal Year 2002; Project Start 30-SEP-1987; Project End 31-DEC-2004 Summary: (adapted from the application's abstract): The applicants propose to continue their multidisciplinary multi-year research program, that will integrate institutional expertise in infectious diseases, neurology, ophthalmology, gynecology, pharmacology, immunology, retrovirology, herpes viruses, and numerous clinical resources in North Carolina. The main focus is the evaluation of novel therapies for HIV-infected persons. Clinical investigators at the UNC and two satellite units, Greensboro, and Charlotte will study new compounds active against HIV and associated infections, malignancies, and neurologic disorders in new patients and follow previously enrolled patients. This proposes to continue a high rate of accrual among minorities, women, and intravenous (I.V.) drug users. The trials will be of all Phases (I, II, and III) and types. Patients will be followed for in vivo evidence of study drug effects on HIV, Mycobacterium avium intracellular complex (MAC), cytomegalovirus (CMV), herpes simplex virus (HSV), and other opportunistic infections using the ACTG-certified retrovirology and immunology virus laboratory, as well as UNC hospital laboratories. Pharmacokinetics (PK) will be monitored in the General Clinical Research Center (GCRC) and Microbiology and Pharmacology Laboratories. Concepts for new protocols will originate by participation in the Executive, Neurology, and Complications of HIV, HIV Pharmacology and Immunology ACTG committees. The established scientific advisory board (SAB) also will be involved in concept development. The UNC group application has new proposals for many trials including the eradication of HIV, simplification of regimens, novel therapies, improving adherence and immune restoration. Outreach to the community may be accomplished through the community advisory boards (CAB) at
2 Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).
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each site, the website and through a statewide newsletter. Finally, low protocol costs may be maintained by cost sharing with NIH grants (GCRC, Pediatric ACTU, Center for AIDS Research (CFAR), as well as with UNC Hospitals, and the Departments of Medicine, Neurology, Ophthalmology, Microbiology and School of Pharmacy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: INFECTIONS
AMINOGLYCOSIDE/RNA
INTERACTIONS
AND
CORNEAL
Principal Investigator & Institution: Rando, Robert R.; Gustavus Adolphus Pfeiffer Professor; Biological Chem & Molecular Pharm; Harvard University (Medical School) Medical School Campus Boston, Ma 02115 Timing: Fiscal Year 2001; Project Start 01-DEC-1998; Project End 30-NOV-2003 Summary: RNA molecules are able to form precise three-dimensional structures which can be binding-sites for small organic molecules. An understanding of the rules that govern RNA/small molecule recognition processes rules would allow for an approach to our long-term goal of the de novo design of antagonists directed at particular RNA structures, in much the same way that inhibitors are designed for protein-based enzymes and receptors. Specific inhibitors designed to inhibit RNA molecules could be of enormous interest in ophthalmology and generally in medicine, in the design, for example, of small-molecules that can specifically interfere with the expression of mutant proteins that can lead to retinal degeneration, and in the design of small molecules that can antagonize RNA molecules from infectious disease producing organisms. This proposal describes approaches to gaining an understanding of the rules by which certain classes of naturally occurring RNA antagonists, the aminoglycosides, are recognized by specific RNA molecules. Random RNA molecules are selected by column methods to bind to defined aminoglycoside containing antibiotics with high affinity and specificity. New quantitative fluorescence methods are developed to determine the affinities and stoichiometries of antibiotic binding to the selected RNA aptamers. Novel chemical approaches are developed to reveal the regions of the aptamers which define the binding-sites for the specific antibiotic. High field NMR structural studies on the high affinity binding aptamers are planned. Those motifs in the specific RNA aptamers which recognize particular aminoglycosides will be determined and used as a guide for the future design of specific antagonists directed against naturally occurring RNA molecules. Two biologically occurring RNA molecules of particular interest in this context are the procaryotic 16S rRNA decoding region and the HIV-RRE transcriptional activator region. Quantitative structure-activity studies on aminoglycoside binding to the decoding and RRE regions leads to the design of novel aminoglycosidemimetic diversity libraries containing l,3(2)-hydroxylamine moieties. Specific antagonists directed against the decoding and RRE regions of RNA will be prepared and studies quantitatively. These antagonists are expected to be starting points for the design of drugs useful in the treatment of corneal infections. Overall, the studies described herein will serve as the basis for a general program on the design of specific RNA antagonists. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BECTON DICKINSON FLOW CYTOMETRY SYSTEM Principal Investigator & Institution: Prabhakar, Bellur S.; Professor and Head; Microbiology and Immunology; University of Illinois at Chicago 1737 West Polk Street Chicago, Il 60612 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2004
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Summary: (provided by applicant): The University of Illinois at Chicago College of Medicine and the campus Research Resources Center (RRC), request funds for a stateof-the-art cell sorter from the Shared Instrumentation Grant Program. Within the last three years, the number of basic science and clinical science researchers requiring flow cytometry has tripled. The primary reason for the increased demand for flow cytometry stems from the successful recruitment of a number of new faculty members (Bellur Prabhakar, PhD, Jim Cook, MD, Cristiana Rastellini, MD, Richard Ye, MD, PhD, Bin He, PhD, Oscar Colamonici, MD. Mahmood Ghassemi, PhD, Jianxun Li, PhD, Tom Hope, PhD, Prasad Kanteti, PhD, Zuoming Sun, PhD, etc). The Cancer Center and the Dept. of Pathology with new Heads, are each in the process of recruiting 8-10 new researchers and the Dept. of Ophthalmology is recruiting a new cular immunologist. These recruitments will in crease the demand for research instrumentation like flow cytometry.The secondary reason driving our request for a new flow cytometer is that our NIH funding has doubled in the last 4-5 years due to our university's commitment to expand and strengthen basic and clinical science programs in the areas of genetics, cancer research, organ transplantation, cell biology, immunology and infectious diseases, further increasing the demand for and access to a state-of-the-art flow cytometer. At present, the RRC, a campus core facility, houses a Flow Cytometry Laboratory with an earlier generation Coulter flow cytometer, an Epics Elite ESP, acquired in 1995, that lacks the sorting speed, precision and versatility required of today's advanced technology applications. Even this instrument is no longer manufactured and thus parts and service will not be available beyond 2004. making an upgrade of the instrument not prudent. Increased demand for flow cytometry due to enhanced research activity through new faculty recruitment and the decommissioning of the Epics 753 have created an acute need for a new flow cytometer. Technologically advanced flow cytometers (Coulter Altra, Becton Dickinson FACS Vantage SE and Cytomation MoFlo) are now available with improved sorting speed, sorting precision, biohazard protection, multicolor analysis and other applications required for contemporary research in cell biology, immunology and infectious diseases. Careful evaluation of the three available systems prompted our users group to recommend the BD FACS Vantage SE since it would satisfy the needs of our institution's NIH-funded investigators. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CATARACT MANAGEMENT TRIAL--VISUAL FUNCTION AND COSTS Principal Investigator & Institution: Mangione, Carol M.; Assistant Professor of Medicine; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2001; Project Start 15-MAR-2001; Project End 30-JUN-2001 Summary: Cataract extraction and intraocular lens implantation (CE/IOL) is the most common surgery performed on Medicare beneficiaries accounting for $3.4 billion in the 1991 budget(2). Previous research indicates that approximately 25 percent of patients who undergo CE/IOL have less than a 30 percent chance of reporting improvements in vision function after surgery. These investigators have developed a clinical decision tool that identifies persons who are unlikely to report improvements after CE/IOL (3). However, without a clinical trial, it is impossible to know if patients with low predicted probability for improvement after CE/IOL would have had even greater declines in functioning without surgery. The proposed Intervention Study (IS) will answer this important clinical question. To determine visual outcome for persons with low
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probability for improvements after CE/IOL when managed with non-surgical care, these investigators propose a randomized clinical trial. The goal of this IS is to determine the functional and financial outcomes of surgical versus non-surgical management of age-associated cataracts among patients with low predicted probability of improvement in visual functioning after surgery. The study will also identify the psychophysical mechanisms related to change in visual function that underlie the intervention's effect on functional status. In preparation for the IS, an 18 month IDS is also proposed. The IDS will examine design characteristics that may influence ophthalmologists' and patients' willingness to participate in the IS. The IDS will test the integration of the IS into routine care, and will determine consent rates for randomization. This information will influence the number of ophthalmology practices needed to complete the IS. Most importantly, the IDS will provide a better understanding of the barriers to participation in among non-consenters from diverse cultural backgrounds. This information will be used to refine the IS protocol. Finally the IDS will assess the reliability and validity of two accepted methods of utility assessment to identify the preferred method for use in the IS. In conclusion, the IS addresses a critical step in the evaluation of a clinical, evidence-based approach for identifying patients who are likely to benefit from a common surgical procedure. Findings from the study should improve selections of persons for CE/IOL. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CATARACTOGENESIS IN HYPERFERRITINEMIA CATARACT SYNDROME Principal Investigator & Institution: Brooks, David G.; Medicine; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2001; Project Start 01-SEP-2000; Project End 31-AUG-2004 Summary: Hyperferritinemia cataract syndrome (HCS) is a recently discovered genetic disease defined by elevated serum ferritin and cataracts. Dysregulation of L ferritin gene expression is the basis of this human disorder. Specifically, mutations in a discrete regulatory region of the L ferritin gene, the iron' response element, lead to over production of wild type L ferritin protein. Although ferritin is found at high levels in all tissues and extracellular fluids examined to date, cataracts are the only proven pathologic consequence of this constitutive over expression of ferritin. The mechanism of cataract formation in hyperferritinemia cataract syndrome (HCS) is unknown. Understanding the pathobiology of cataractogenesis in HCS is essential to design a rational approach to cataract prevention and treatment. The objective 9f this proposal is to determine the mechanism of HCS cataractogenesis with a long term goal of developing effective preventive and/or therapeutic strategies for these cataracts. The mechanism of cataract formation in HCS will likely have broader implications for cataract formation in general. The specific aims of this proposal all involve investigation of ferritin in eye. First, the normal expression of ferritin in lens and lens cell lines will be determined. Second, over expression of L ferritin in human cell lines and in mouse will be generated as models of HCS. Third, quantitative expression and distribution of L ferritin in HCS lens material will be determined. An animal model that reproduces cataract promises opportunity to 1investigate cataract formation as a function of the interaction of HCS genotype with environmental factors including iron, antioxidants and UV light. This proposal describes a 4 year training program in which the applicant will acquire the requisite experience to become an independent clinician scientist. The sponsor and collaborator's extensive experience in clinical ophthalmology, eye histopathology, genetic cataract and mouse genetics will complement the applicant's
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prior training in molecular biology, internal medicine and clinical genetics. A strong ophthalmology research program will provide the requisite environment in which to transition the applicant to being an independent physician/researcher in genetics and eye disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CLINICAL TRIALS IN CATARACT PREVENTION Principal Investigator & Institution: Congdon, Nathan G.; Ophthalmology; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2001; Project Start 01-SEP-1999; Project End 31-AUG-2004 Summary: The candidate has a background in clinical ophthalmology and ocular epidemiology, and proposes to extend his work and prevention of eye disease into the field of cataract prevention. This application outlines a three-phase training program in cataract-related clinical trials. In the first phase, class classroom training in the theory of clinical trials will be undertaken at the Center for Clinical Trials of the Johns Hopkins School of Public Health under Dr. Curtis Meinert. Courses in Biostatistics and Epidemiology will provide a theoretical framework for the remainder of the training. The second phase will involve practical training in clinical trials under the auspices of the Age-Related Eye Disease Study. (AREDS). AREDS is a randomized, controlled clinical trial designed to explore in prospective fashion the impact of anti-oxidants and other factors on the progression of age-related cataract. The candidate will be supervised by the Study Chairman, Dr. Frederick Ferris, in a program that will include participation in monthly meetings of the AREDS Study Operations Committee and annual meetings of the Data Monitoring Committee and AREDS Technical Group in Bethesda, participation in Quality Control Site Visits and other activities of the Coordinating Center, and analysis of study data. In the final phase of training, the candidate will design and execute a clinical trial, a follow-up on the Linxian Cataract Trials in China. These were the first randomized, controlled trials to demonstrate that supplementation with anti-oxidants could retard progression of cataract. The proposed study will take advantage of continued examination of this cohort, now aged 55 years and above, by the National Cancer Center Institute for cancer-related events, to obtain unique information on the long-term effects of anti-oxidant treatment on lens opacity over 15 years. This study will exploit the candidate's fluency in written and spoken Chinese. Dr. Sheila West will provide overall direction through the three phases of training. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: CLINICAL VISION RESEARCH UNIT AT UAB Principal Investigator & Institution: Owsley, Cynthia; Professor; Ophthalmology; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2007 Summary: (Applicant's Abstract) Clinical vision research is a high priority at the University of Alabama at Birmingham (UAB). This priority has been tangibly realized through the establishment of the Clinical Research Unit in the Department of Ophthalmology and the appointment of Cynthia Owsley, PhD, MSPH as its Director. The primary goal of this R21 application is to increase the patient-oriented research capability at UAB in the area of eye disease and vision impairment. This area of research has been a largely untapped, but very promising reservoir of opportunity at UAB for public health scientists. The Clinical Research Unit will provide the research resources and infrastructure to facilitate clinical and epidemiological research projects of the
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highest quality among participating faculty. These resources will consist of personnel who will provide collaboration and consultation on: (1) biostatistics and study methodology, (2)database design and data acquisition systems, (3) project management, (4) "grantsmanship", such as identifying grants programs relevant to faculty interests, developing ideas into tangible proposals, and constructing budgets, and (5) facilitating faculty training through encouraging enrollment into existing clinical research training programs on the UAB campus and/or through NIH's clinical scientist training program (K-awards). The UAB community represents a unique venue for clinical vision research. First, the clinical vision research faculty at UAB represents all three types of degree professionals in vision: MDs, ODs, and PhDs, who already work collaboratively. This type of professional interaction is not possible at many institutions where only one or two of the three types of professionals are on the faculty, but not all three. Second, NIH and DHHS have called for scientists to meet the challenge of eliminating health disparities in the U.S. population. The focus of most of our faculty research projects will be on subpopulations that have a higher prevalence of eye disease, vision impairment and decrements in health-related quality of life as compared to the general population (e.g., African Americans, older adults, nursing home residents, persons with low vision). Furthermore, UAB has already established many community relations and research infrastructure contacts with these subpopulations that will immediately facilitate our research efforts. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: COLLABORATIVE IMAGE ANNOTATION IN OPHTHALMOLOGY Principal Investigator & Institution: Jain, Pramod; Innovative Decision Technologies, Inc. 9000 Cypress Green Dr, Ste 108 Jacksonville, Fl 32256 Timing: Fiscal Year 2003; Project Start 15-SEP-2003; Project End 31-AUG-2004 Summary: (provided by applicant): Longer-term objective is to develop a commercial internet-based collaborative image annotation system that will be used by physicians in both clinical and clinical trials settings. This software will accomplish two goals. First, it will significantly enhance the objectivity, ease and accuracy in reading, interpreting and tracking areas of pathology in an image. Second, it will facilitate effective collaboration among physicians and support personnel at multiple clinical centers. This software will embody three technological innovations: rich annotations tied to areas of pathology in an image; web-browser based markings of images and automated computation of physical properties; and collaborative technology to securely retrieve, store and search rich annotations. Phase I and II will focus on research and development of this technology with ophthalmic images. Research approach is to: Collect functional and technical requirements from two sources the Fundus Photography Reading Center (FPRC) in Madison, WI, and Univ. of Florida Ophthalmology (UFO) in Jacksonville, FL; design and develop the collaborative image annotation system with Ophthalmic images; beta test the application at FPRC and UFO. Benefits will be: superior quality data through objective reading, interpretation and tracking (over multiple visits) of areas of pathology in images; faster turn around on image reading and interpretation through paperless, web-based user-friendly system; and easier searching, statistical analysis and documentation of results. Potential commercial applications are: Ophthalmology reading centers; Collaboration system for clinical trials in image related medical areas; Clinical diagnosis, treatment and monitoring of diseases based on sequential imaging, Computer-based instruction, training and testing on image related medical topics. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: COLLABORATIVE INITIAL GLAUCOMA TREATMENT STUDY Principal Investigator & Institution: Simmons, Steven T.; Ophthalmology; Albany Medical College of Union Univ Union University Albany, Ny 12208 Timing: Fiscal Year 2001; Project Start 01-JUL-1993; Project End 30-JUN-2003 Summary: The intent of this application is to document the ability of the Albany Medical College, Department of Ophthalmology to participate as an effective and productive clinical center in the proposed multicenter clinical trial, entitled "Collaborative Initial Glaucoma Treatment Study" (CIGTS). This study's purpose is to evaluate whether initial treatment of open angle glaucoma is more effective by means of a stepped, medial regimen or by means of a surgical approach. The Albany Medical College's Clinical Center will participate in the CIGTS by identifying and recruiting eligible patients, administering the treatment regimen as assigned by the CIGTS's Coordinating Center and defined within the study's Manual of Operations, following and retaining study patients, recording and transferring study data to the Coordinating Center, and contributing to reports that will present the CIGTS results. As a clinical center in the Collaborative Initial Glaucoma Treatment Study, the Glaucoma Service at the Albany Medical College, Department of Ophthalmology, Lions Eye Institute, offers a state of the art clinical research facility for the diagnosis and treatment of glaucoma. The three investigators have extensive experience in glaucoma research and have large consultative practices specializing in glaucoma ( greater than 15, 000 glaucoma patient visits /year). In addition, 26 community board certified ophthalmologists have enrolled to actively participate with this center in the study. As a group, they offer a large clinical base in Northeastern New York ( greater than 150,000 patient visits/year) which maximizes patient recruitment and care. In a 3 month trial recruitment for this study using the criteria outlined in the Manual of Operations, this center identified 18 qualifying patients, representing adequate potential for patient recruitment (Appendix 1). This center expects to recruit 3 patients per month for participation in this study. The study population will include both sexes and patients of a variety of ethnic and racial backgrounds consistent with this geographical region of the country. Details are provided of our plans to identify, recruit, follow, and retain these patients, our intent to obtain consistently high quality data on the visual outcomes of treatment, and the personnel and facilities available within our center to carry out the provisions of the CIGTS's Manual of Operations. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CORE FACILITY FOR THE VISUAL SCIENCES Principal Investigator & Institution: Lass, Jonathan H.; Professor and Chair; Ophthalmology; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2001; Project Start 01-APR-1997; Project End 31-MAR-2002 Summary: Twenty-eight principal investigators, conducting vision research at Case Western Reserve University, University Hospitals of Cleveland, and the Cleveland Veterans Administration Medical Center have constituted a core group from the Departments of Ophthalmology, Genetics, Neurology, Neurosciences, and pathology at CWRU to develop multidisciplinary approach to examine major areas of study in the visual sciences: the CWRU Visual Sciences Research Center. The proposed NEI Core Facility will facilitate collaboration among this group of investigators that includes nine NEI-funded principal investigators and nine with pending or planned submissions. The Core Facility will be composed of three research support modules: 1. The Tissue Culture
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and Cell Analysis Module will assist investigators to establish and maintain a variety of cell lines, provide tissue preparation for histology, electron microscopy, and immunocytochemistry, and offer access to state-of-the-art facilities for flow cytometry, cell sorting, and confocal microscopy. 2. The Molecular Biology Module will provide skilled technical expertise, equipment and techniques for sequencing clone and amplified DNA, PCR amplification and analysis of DNA and RNA, quantitation and digital imaging of DNA gels, bacterial transfection and expression of proteins, and storage of commonly used bacterial strains, vectors, and cDNA constructs. 3. The Specialized Animal Resources Module will provide technical and handling support, isolation racks and cages, and boarding for the production of progeny of specialized mouse and rat strains that are relevant to studies of the eyes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CORE GRANT FOR VISION RESEARCH Principal Investigator & Institution: Edelhauser, Henry F.; Professor; Ophthalmology; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2001; Project Start 01-APR-1986; Project End 31-MAR-2006 Summary: Continued support is requested for the NEI Core Center Grant in the Department of Ophthalmology at Emory University. This Core Center Grant renewal application includes three Modules: (1) Structural Biology, (2) Analytical Biochemistry/Molecular Biology, and (3) Epidemiology and Biostatistics. The past Core Center Grant has successfully utilized supporting collaborative vision research and service involving 33 faculty (including more than 20 NEI funded principal investigators), 20 postdoctoral fellows, six predoctoral fellows and generating over 250 publications over the past five years. Renewal of these basic Core activities will allow us to maintain and expand this high level of productivity in vision research. The scope of research services proposed for each of the Modules reflects expanded scientific capabilities. The Structural Biology Module adds immunohistochemistry, confocal microscopy and fluorescence image analysis to the light and electron microscopy services. With the new 7,000 square feet of research space dedicated to molecular biology and molecular genetics research in the Department of Ophthalmology, we have expanded our Analytical Biochemistry/Molecular Biology Module, including gene array technologies. The Epidemiology and Biostatistics Module proposes to expand its services to basic research projects as well as clinical research projects. The Core Modules have and will continue to enhance our research productivity by providing common centralized services to stimulate and facilitate collaborative studies between faculty and to attract other university disciplines to vision research. This Core faculty also services as a central vision research facility in Atlanta where faculty from Emory University, Yerkes Regional Primate Center, George Institute of Technology, Georgia State University, the Veterans Administration Medical Center and the Centers for Disease Control and Prevention can undertake collaborative studies in vision research. The Core facilities also serves a role in the research projects of our pre- and postdoctoral fellows supported by our departmental NEI Training Grant, recently renewed for the next five years (1995-2004). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CORE GRANT FOR VISION RESEARCH Principal Investigator & Institution: Anderson, Robert E.; Professor; Ophthalmology; University of Oklahoma Hlth Sciences Ctr Health Sciences Center Oklahoma City, Ok 73126
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Timing: Fiscal Year 2001; Project Start 01-JUL-1999; Project End 30-JUN-2004 Summary: Support is requested for an NEI Core Center Grant in the Department of Ophthalmology at the University of Oklahoma Health Sciences Center (OUHSC) in Oklahoma City. Four Modules are proposed: Image Acquisition and Production, Instrumentation, Animal Resources, and Analytical Biochemistry. The first three are housed in the Dean A. McGee Eye Institute (DMEI) building in recently renovated facilities that includes 2,000 square feet for the core modules and 8,900 square feet for research laboratories. Analytical Biochemistry is housed nearby in 291 square feet of newly renovated space in the Biochemistry & Molecular Biology Department. These facilities will be utilized by 16 participating faculty from the ophthalmology and other departments, postdoctoral fellows, graduate students, and other laboratory personnel. These four core modules will increase productivity of the vision research activities t the OUHSC by providing stable, centralized services with core personnel. The modules will promote and enhance funded projects by providing resources that allow multidisciplinary approaches, facilitate the initiation of pilot studies; promote collaborative research projects between investigators, especially clinical and basic vision scientists; aid in the recruitment of other vision researchers to the OUHSC; provide opportunities for researchers on campus to initiate vision research projects, in collaboration with vision Core Center investigations, and provide resources for graduate students and postdoctoral fellows in vision research laboratories. The Provost, Dean of the College of Medicine, Dean of the Graduate College, President and CEO of the Dean McGee Eye Institute, and Chairman of the Board of the Dean McGee Eye Foundation have committed to support the vision Core Center by providing laboratory space; funds for renovation of laboratory space, stipends for graduate students; partial support for core modules, including new instruments and core personnel salaries; and partial support for faculty salaries. This broad-based institutional support will ensure that each Core Module is staffed and supplied to complete sere the needs of basic and clinical vision researchers at the OUHSC. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CORE GRANT FOR VISION RESEARCH Principal Investigator & Institution: Rao, Narsing A.; Professor; Doheny Eye Institute 1450 San Pablo St Los Angeles, Ca 90033 Timing: Fiscal Year 2001; Project Start 30-SEP-1979; Project End 31-MAR-2005 Summary: Funds are requested for continued funding of our Core Grant for Vision Research (EY03040). Since its inception in 1978, this grant has supported the development and growth of a premier program in vision research at the Doheny Eye Institute in association with the Department of Ophthalmology of the University of Southern California at Los Angeles. The Core consists of five service modules: Biostatitistics, Histology and Immunopathology, Tissue Culture, Specialized Microscopy and Vivarium. It supports the salaries of expert supervisor/technicians and a modest amount of supplies for each module. The Director of each module holds at least 1 NEI RO1 grant. The faculty holds 17 NEI RO1 or U10 grants. Productivity of the group has been excellent over the past grant period, with 153 peer review publications, most of which represent collaborative studies. The Core grant has supported the addition of two new faculty, one of whom has been awarded an RO1 grant with the help of preliminary data gathered using the facilities of the Tissue Culture, Specialized Microscopy and Vivarium modules. Each of our NEI grants relies heavily on one or more services provided by the Core modules. The expert staff associated with the modules could not be afforded or justified by the demands of any one grant, but are fully justified by the
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requirements of the combined faculty. The great strength of this program is the level of support it provides a broad range of NEI-supported investigators. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CORE GRANT FOR VISION RESEARCH Principal Investigator & Institution: Kaufman, Herbert E.; Professor and Head; Ophthalmology; Louisiana State Univ Hsc New Orleans New Orleans, La 70112 Timing: Fiscal Year 2001; Project Start 01-APR-1979; Project End 31-MAR-2004 Summary: The purpose of this Core grant is to provide support for the extensive vision research program at the LSU Medical Center, which is centered in the LSU Eye Center Department of Ophthalmology and includes investigators in the LSU Neuroscience Center, the Department of Cell Biology and Anatomy, the Department of Microbiology, Immunology and Parasitology, and the Department of Physiology. To this end, four Modules are proposed: the OCULAR STRUCTURE AND IMAGE ANALYSIS MODULE, which provides light and electron microscopy and image analysis for the documentation of anatomical observations, as well as the services of a system analyst for customizing computer-based image analysis routines for specific applications; the CULTURE MODULE, which provides viruses, bacteria, plasmids, and cells, as well as technical expertise in the management and use of these materials; the INSTRUMENT SHOP MODULE, which provides high quality instrument design and fabrication technical advice for the construction of specialized equipment for research; and the CLINICAL TRIALS AND BIOMETRY MODULE, which provides the services of a biostatistician to aid in the design, preparation, management, and analysis of clinical studies and basic science studies that are preliminary to future clinical studies, as well as a clinical coordinator to assist in implementation of clinical study protocols. The addition of a systems analyst to the Ocular Structure and Image Analysis Module represents a shift in emphasis from the former Computer and Biostatistics Module, with its programming function for mainframe processing, which has been replaced by distributed computing in PCs and workstations. The combination of clinical trials and biometry into a single Module provides experimental design and analysis services in one unit. The vision research program encompasses 22 Module Directors and Participating Investigators wit 27 R01/U10/K08/R37/R43 grants and subcontracts. For these investigators and their collaborators within and outside the LSU Medical Center, the Core grant provides services not available within the confines of any one research grant and, as such, has been an essential factor in the support of this productive group of scientists for the past 19 years. It is hoped that future support will enable the continuation of this high level of quality and productivity in the years to come. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CORE GRANT FOR VISION RESEARCH Principal Investigator & Institution: Johnson, Dianna A.; Professor; Ophthalmology; University of Tennessee Health Sci Ctr Health Science Center Memphis, Tn 38163 Timing: Fiscal Year 2001; Project Start 01-APR-2000; Project End 31-MAR-2005 Summary: Having established the Center for Vision Research and The Ophthalmology Institute within the past two years, The University of Tennessee, Memphis, is providing major resources to support vision research. Part of the expanded support is reflected in the growth of the Department of Ophthalmology which has gained several basic and clinical scientist over the past four years. This expansion complements a strong vision research group within the Departments of Anatomy and Neurobiology, and Physiology,
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as well as investigators at two neighboring institutions-St. Jude Children's Research Hospital and Southern College of Optometry. At present, over 20 active vision scientists with funded research programs participate in the Center for Vision Research. To enhance ongoing NEI-supported programs, four core modules that each serve active facets of our group's research will be supported. The Imaging Module contains a highresolution digital image analysis system for light microscopy, a rapid-response calcium imaging system, an inverted fluorescence photomicroscope, and a state-of the-art motorized cryostat. The Molecular Biology Module provides automated DNA sequencing and genotyping, quantitative real-time PCR, and gene array chip scanning technology. The Cell Biology Module provides a central facility for acquiring, storing, and culturing human donor tissues and human cell lines for morphologica1, biochemical, and genetic analysis. The Bioinformatics Module assists in computer-based database management, biostatistical analyses, Internet publication of large datasets, high level software support for image analysis and genomics, and basic research design and interpretation. Modules are housed within the newly established Ophthalmology Institute and in the Neuroscience Institute, allowing easy access to all research groups. Strong institutional support has been pledged for this effort and includes a total outlaw of $250,000 for equipment, technical support, and instrument service contract. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CORE GRANT FOR VISION RESEARCH Principal Investigator & Institution: Candia, Oscar A.; Professor; Ophthalmology; Mount Sinai School of Medicine of Nyu of New York University New York, Ny 10029 Timing: Fiscal Year 2001; Project Start 01-FEB-1977; Project End 30-JUN-2005 Summary: We request continuing support for a Vision Research Center in the Department of Ophthalmology. The funds will provide investigators in our Center shared resources that are vital for the continuation of current research programs and efficient development of new programs. Our Center is structured into 42 discrete resource/service modules: Machine Shop; Electronics/Computers; Research Photography-Imaging; and Histology/Microscopy. In addition to enhancing the research environment and productivity by providing common centralized services, our Center stimulates and facilitates collaborative studies and strives to attract to vision research scientists in other health-related disciplines. Our group consists of 9 independent investigators who have NEI grants, 5 associate investigators and fellows. Research is conducted in several scientific disciplines such as biochemistry, pharmacology, physiology, cell biology, and neurology. Areas of active research include glaucoma; cataracts; corneal diseases; aqueous humor dynamics; fluid and electrolyte transport in cornea, lens and ciliary epithelium; role of membrane receptors in regulation of intraocular pressure; electroretinogram and visual evoked potentials; visual control of the oculomotor system; mechanisms of glutamate excitotoxicity in glaucoma and methods of neuroprotection; optical imaging, electrophysiological recordings and computer simulations to study the architecture and dynamics of the visual system; and degenerative diseases of the retina. The support of the CORE Center grant is complemented by a strong commitment of the Department and the Mount Sinai Medical Center to excellence in vision research. NEI funds are requested for 4 of the 7 modules. Our Vision Research Center has facilities with an area of more than 15,000 sq. ft. organized as individual laboratories and common space where modules operate. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CORE RESOURCES FOR VISION RESEARCH AT MUSC Principal Investigator & Institution: Crosson, Craig E.; Professor; Ophthalmology; Medical University of South Carolina 171 Ashley Ave Charleston, Sc 29425 Timing: Fiscal Year 2003; Project Start 01-MAY-2003; Project End 30-APR-2008 Summary: (provided by applicant): The goal of this infrastructure development request is to enhance the research environment and accelerate the research objectives of NEIfunded vision scientists at the Medical University of South Carolina (MUSC), facilitate growth, and increase multi-disciplinary collaborative research in the visual system. This request will improve vision research at MUSC by supporting key elements of vision research infrastructure, and by providing new access for vision researchers to cutting edge technology that is not normally supported through the R01 funding mechanism. To accomplish this, two modules are proposed: a Tissue and Organ Culture module, and a Proteomics module. The two modules will be used by at least eight NEI-funded investigators from the Departments of Ophthalmology and Pharmacology who comprise highly interactive and collegial vision research group at MUSC. The infrastructure development grant will be directed by an established vision researcher in the Department of Ophthalmology. Projects benefiting from this infrastructure activity include research on retinoid photochemistry, biology of phototransduction, retinal degeneration, glaucoma, retinal neovascularization, structure-function studies of the retina and retinal pigment epithelium proteins, genetics of photoreceptor development, membrane receptors, lens protein structure in aging and cataractogenesis, and corneal transplantation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CORE--BIOSTATISTICS Principal Investigator & Institution: Cumberland, William Glen.; Professor and Chair; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 31-DEC-2007 Summary: The Biostatistics Core is designed to serve as a centralized resource for biostatistical expertise to support AIDS research at UCLA. The aims of this Core are to enhance HIV/AIDS research and to establish and foster long-term collaborations between clinical, basic and behavioral researchers and biostatisticians at UCLA. This collaboration improves the biostatistical aspects of the AIDS research undertaken at UCLA and ensures that AIDS investigators have access to expert statistical consultation and support, and that the most appropriate and up-to-date methods are used. The kinds of support range from simple consultations to long-term collaborations and grant writing. The Core provides support to AIDS research in the following areas: statistical modeling and expertise to researchers in basic science departments, survey designs and analysis of observational data to social science departments, design of experiments and analysis for interventional studies, and data modeling and analysis for clinical departments. Further it fosters the development of biostatistical methodology for immediate use by researchers in these groups. The Core supports AIDS projects in numerous departments of the Schools of Medicine, Public Health, Nursing and Policy: Medicine, Health Services, Pediatrics, Ophthalmology, Microbiology and Immunology, Nursing, OB Gynecology, Hematology and Oncology, Public Policy, Epidemiology, and Psychiatry. A consequence of the emphasis on long-term collaborative interactions is that this will lead to grant submissions and funding from other sources, thus allowing
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the Biostatistics Core to be available to focus on establishing new collaborations and supporting new research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DATA COORDINATING CENTER FOR EARLY GLAUCOMA TRIAL Principal Investigator & Institution: Leske, M Cristina.; Distinguished Professor; Preventive Medicine; State University New York Stony Brook Stony Brook, Ny 11794 Timing: Fiscal Year 2001; Project Start 02-JUN-1993; Project End 31-MAY-2003 Summary: The Early Manifest Glaucoma Trial (EMGT) is the first large randomized, controlled clinical trial to evaluate the effect of lowering the intraocular pressure (IOP) on the progression of newly detected open-angle glaucoma. As such, it is an extremely important study designed to address a major unresolved issue in ophthalmology. The primary aim of the EMGT is to compare the effect of immediate therapy to lower the IOP (laser trabeculoplasty and betaxolol) versus late or no treatment on the progression of newly detected open-angle glaucoma, as measured by increasing visual field loss or optic disc changes. The primary aim will be achieved by conducting a randomized clinical trial of 300 patients that will compare glaucoma progression in initially treated vs untreated patients with newly detected open-angle glaucoma. This comparison will allow quantification of the effect of immediate IOP-lowering treatment on progression during the followup period. Patients will be followed every three months until the development of glaucoma progression endpoints for a minimum of four years. Secondary aims are to: 1) determine the extent of IOP reduction attained by treatment; 2) explore the factors that may Influence progression; and, 3) describe the natural history of newly detected glaucoma. The proposed EMGT is a collaborative effort that involves a Clinical Center (CC) in Malmo, Sweden, a Disc Photography Reading Center in Lund both at the University of Lund, Sweden, a Data Center (DC) at the State University of New York, Stony Brook, NY and the National Eye Institute. The study originated from a proposal prepared by the CC that was approved and funded by the Swedish Medical Research Council. Funding was limited to a study of 200 patients and involved only the CC. The present collaboration involves several design changes (e.g., increase in study power from 70% to 90% and sample size to 300 patients, incorporation of rigorous clinical trial methodology, inclusion of an independent DC and a Data Safety and Monitoring Committee) to strengthen the original study plan and enhance interpretation of EMGT results. The DC will be involved in all aspects of the study design, implementation and analysis. The specific responsibilities of the DC are to: 1) serve as a collaborating partner in the EMGT and provide epidemiologic and biostatistical input to the organization, design, conduct and analysis of the trial; 2) collaborate in the development and distribution of forms, documents and protocols; 3) develop, implement and maintain quality assurance procedures for all aspects of the study; 4) develop and monitor the randomization process; 5) be responsible for data management, processing and analysis; 6) prepare reports for study committees to monitor recruitment, data collection, adverse effects, endpoints and data quality; 7) coordinate and document study meetings and communications between centers; and 8) collaborate in preparing publications of the results. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DEVELOPMENT NEUROPROTECTION
OF
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ORBITAL
ENDOSCOPE
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Principal Investigator & Institution: Mawn, Louise A.; Ophthalmology and Visual Scis; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917
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Timing: Fiscal Year 2001; Project Start 01-AUG-2001; Project End 30-JUL-2004 Summary: (Applicant's Abstract) Current treatment modalities for optic nerve related blindness focus on topical drug application to lower intra-ocular pressure, systemic antiinflammatory/immune suppression with steroids, or surgical decompression of the nerve sheath. The long-term goal of this research is to create a novel treatment approach for optic nerve axonal disease. The project objectives are to design, construct and test an orbital endoscope for visualization and treatment of optic nerve diseases. Clinical applications of the proposed orbital endoscope include implantation of a slow release drug delivery mechanism for direct and sustained treatment of glaucoma or orbital tumors such as meningiomas, local application of immunosuppressive or neuroprotective agents in diseases such as optic neuritis or traumatic optic neuropathy and laser application to open the nerve sheath in pseudotumor cerebri. Specific project aims include developing an endoscope capable of safely reaching the posterior orbit, developing delivery ports, and demonstrating the safety in an animal model. The design will include an endoscopic image fiber bundle, illuminator bundle, and a delivery channel. This design driven development of an orbital endoscope will have a high impact on many of the blinding diseases which are currently poorly treated. The resultant capability to directly treat optic nerve disease will be a major advance for Ophthalmology. Collaboration on this unprecedented approach includes the expertise of an orbital surgeon/neuroophthalmologist, glaucoma specialist and optical engineer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DIABETIC RETINOPATHY SCREENING IN A PRIMARY CARE SETTING Principal Investigator & Institution: Dean, Juli M.; Surgery; Meharry Medical College 1005-D B Todd Blvd Nashville, Tn 37208 Timing: Fiscal Year 2002; Project Start 15-SEP-2002; Project End 30-JUN-2004 Summary: (provided by applicant):At least 16 million Americans have DM, mostly type 2, with the number expected to rise to 22 million by 2025. Both the American Academy of Ophthalmology (AAO) and American Diabetes Association (ADA) guidelines recommend examination upon diagnosis of type 2 diabetes mellitus (DM) and at least annually thereafter for detection and management of diabetic retinopathy. Yet, only about one quarter of those diagnosed with the disease actually receive the appropriate eye care. The facts that diabetic retinopathy (DR) is the most frequent cause of visual loss in Americans aged 20-74 and that disparities in morbidity and mortality due to diabetes are well documented in African-Americans and other minority populations, bear witness our inadequate detection method. To date, no population-based studies using digital cameras and a simpler (less than seven stereoscopic fields) acquisition protocol have been tested in the United States. The National Eye Institute's Visual Function Questionnaire (NEI-VFQ-25) is a relatively new screening tool, which assesses visual function and vision-specific quality of life. Its use in a high-risk minority population has yet to be studied. 1) Determine whether or not the proposed populationbased screening program for detection of DR in high-risk patients with DM is more effective at meeting AAO and ADA screening guidelines than the standard of care (ophthalmology referral by PCP). This program will use digital fundus imaging (DFI) at the time of the primary care encounter, circumventing the need for ophthalmology referral for screening purposes. 2) To determine whether, in this population, glycosylated hemoglobin (HbA1c) is a predictor of the level of diabetic retinopathy based on DFI while controlling for concomitant eye disease, age, race and gender. 3) a) Correlate composite and domain scores of the National Eye Institute's visual function
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questionnaire-25 (NEI-VFQ-25) with visual acuity (VA) to determine whether an association exists between them in a high-risk, minority population, in which it has not yet been tested.b) To assess visual function and vision-specific quality of life in the DR screening cohort. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EARLY MANIFEST GLAUCOMA TRIAL Principal Investigator & Institution: Heijl, Anders; University of Lund Box 1703 Lund, Timing: Fiscal Year 2001; Project Start 02-JUN-1993; Project End 31-MAY-2003 Summary: The Early Manifest Glaucoma Trial is intended to study whether and to what extent current standard therapy, reduction of the intraocular pressure, influences the course of chronic open angle glaucoma. It is a prospective, randomized study in which two groups of patients, one treated with laser trabeculoplasty and betaxolol and the other untreated, are closely followed with computerized perimetry and fundus photography. The project has been reviewed and approved by the Swedish Medical Research Council (051192) and by the Ethics Committee of the Medical Faculty of the University of Lund (061592). Funding has been obtained for an open study on 200 participants to be carried out at the Department of Ophthalmology at the General Hospital of Malmo, Sweden. Preliminary studies of screening methods begun in 1991. Recruitment for the trial started October 5 1992. The present application is requesting support for a number of modifications intended to strengthen the original study plan. They include: - a major increase in the number of participants (from 200 to over 300). This would improve the power of the study to detect a limited but clinically meaningful effect (from approximately 70 to 90 per cent) at the cost of a greatly expanded community screening effort. - the incorporation of a masking protocol intended to minimize potential sources of bias - the employment of a clinic coordinator - the establishment of an independent disc reading center - the participation of an independent data center with responsibilities described in a separate application. - the participation of an independent data and safety monitoring committee. It is expected, that the large scale community screening effort to recruit study participants with as yet undetected glaucoma, will require screening of 20,000 to 30,000 Malmo citizens in appropriate age groups. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: FAST OCT TECHNOLOGY FOR COMPREHENSIVE DIAGNOSTIC IMAGING Principal Investigator & Institution: De Boer, Johannes F.; Assistant Professor; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2003; Project Start 15-SEP-2003; Project End 30-JUN-2007 Summary: (provided by applicant): Over the past 10 years, optical coherence tomography (OCT) has undergone a rapid development from inception to a versatile method for non-invasive high-resolution optical imaging. A wide range of medical diagnostic applications has been explored in ophthalmology, cardiology and in early cancer diagnosis in general. Preliminary studies have demonstrated that OCT can facilitate the accurate diagnosis of a variety of diseases when used in a point-sampling protocol analogous to random biopsy. The potential diagnostic applications having the highest impact, however, require screening or surveillance of large tissue volumes. The relatively slow image acquisition rate of current OCT technology therefore represents a significant barrier to its utility as a powerful clinical tool. Since the current technology
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commonly operates at its theoretical limit for efficient light collection, dramatic improvements in imaging speed can only be obtained through a technological paradigm shift. We propose to develop a new, parallel detection principle for OCT that is several hundred-fold more efficient than current state of the art technology and that provides vastly improved image acquisition rate and resolution. The system design of the proposed technology is tailored to three high-impact clinical goals: early detection and monitoring of glaucoma, the second-leading cause of blindness in the U.S, detection and characterization of vulnerable coronary plaques responsible for acute myocardial infarction, and comprehensive surveillance for esophageal neoplasia in patients with Barrett's esophagus. Three clinical pilot studies, using technology developed in this work, will be conducted to test system performance relevant to achieving these goals. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENES FOR KERATOCONUS AND OCULAR FEATURES IN TRISOMY 21 Principal Investigator & Institution: Bergwerk, Katherine L.; Cedars-Sinai Medical Center Box 48750, 8700 Beverly Blvd Los Angeles, Ca 90048 Timing: Fiscal Year 2001; Project Start 01-SEP-2000; Project End 31-AUG-2005 Summary: This application for a Mentored Patient-Oriented Clinical Scientist Development Award (K23) seeks support for Katherine Bergwerk, MD, a staff ophthalmologist at Cedars-Sinai Medical Center (CSMC), who recently completed a Clinical fellowship in Ophthalmic Genetics at CSMC and U.C.L.A.'s Jules Stein Eye institute. Under the mentorship of Julie R. Korenberg, MD, PhD, and Yaron S. Rabinowitz, MD, Dr. Bergwerk will pursue investigation of gene loci for keratoconus and other ocular abnormalities in patients with partial trisomies and tetrasomies of chromosome 21. Identifying a gene for keratoconus may allow for early detection of the disease and may enable medical therapy to be developed to retard its progression. This will obviate the need for the current therapy of multiple complex contact lens fittings or corneal transplantation surgery. Keratoconus is a major cause of visual disability and one of the leading causes for penetrating keratoplasty in the United States. In the process of completing comprehensive ocular examinations on these rare patients for keratoconus, attempts will be made to make genotype-phenotype correlations of other eye abnormalities in patients with Down syndrome. Dr. Rabinowitz is a prominent researcher in the field of ophthalmic genetics, who has established a candidate region for a keratoconus gene locus. This region is a 5.4 centimorgan (cM) region which is 11 cM distal to the centromere on the long arm of chromosome 21 (see appendix A). Review of the literature suggests that keratoconus may occur as much as 300 Xs more commonly in Down syndrome patients than in the general population. Dr. Korenberg is a renowned molecular geneticist who has served on the Human Genome Project for defining genes on Chromosome 21. Her unique population of partial trisomy Down syndrome patients are the ideal group to use in refining a gene locus for keratoconus and to make genotype- phenotype correlations of ocular features of Down syndrome. Under Dr. Rabinowitz and Dr. Korenberg's mentorship and with institutional support from the Divisions of Medical Genetics and Ophthalmology at CSMC, Dr. Bergwerk will further her training in clinical genetic research, and enhance her skills in clinical and molecular genetics. Dr. Bergwerk aspires to achieve her goal of becoming an independent investigator who is capable of solving clinical problems in a research laboratory. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GROWTH FACTORS IN MAMMALIAN EYE DEVELOPMENT Principal Investigator & Institution: Bennett, Jeffrey L.; Neurology; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2001; Project Start 01-JUL-1998; Project End 30-JUN-2003 Summary: (Candidate's Abstract) The ultimate aim of this proposal is to formulate a multifaceted program which will guide my development as an independent scientist. This goal is to be accomplished through a mixture of basic research and educational activities. My research will be focused on determining the biologic function of the neurotrophins brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) in the development and maintenance of the mammalian eye. These endeavors will be complemented by extramural workshops, instruction in ocular pathology, and participation at scientific meetings. I have spent the past several years completing my doctoral research and professional training. I am now prepared to embark on a longterm career in academic neuro-ophthalmology, combining clinical practice with basic research. The University of Colorado will provide me with an ideal environment in which to accomplish my immediate and long-term goals. The combined faculties and resources of the Department of Neurology, Ophthalmology, and Molecular, Cellular, and Developmental Biology are particularly well suited for providing me with training in nervous system and eye development, mouse genetics, histochemistry, and transgenic and embryonic stem cell technology. Under the research mentorship of Dr. Kevin Jones, I will investigate the biologic roles of BDNF and NT-3 in the neuroretina and anterior segment of the eye. A multidisciplinary approach will address questions in three main areas. First, the cell specific expression of BDNF and NT-3 and their respective receptors. TrkB and TrkC, will be examined in the neuroretina, lens, ciliary body, and cornea. We will identify the specific cells expressing BDNF, NT-3, TrkB, and TrkC using dual-label immunohistochemistry and confocal microscopy. These results will suggest possible functions for these neurotrophins in the eye. Second, the biologic functions of BDNF and NT-3 in the neuroretina will be investigated using subregion-restricted gene knockout technology. Mice will be generated which lack BDNF and NT-3 in the neuroretina. To achieve this, we will use Cre/loxP-mediated recombination restricted by either the Six3 or Brn-3b promoter. Cre recombinase will be expressed either as a transgene or as a dicistronic message using an intervening ribosome entry sequence (IRES). Third, the biologic role of BDNF and NT-3 in the anterior segment of the eye will be characterized following our recent finding of regulated neurotrophin expression in the ciliary body epithelium, lens epithelium, and cornea. Restricted gene knockouts will be constructed using dicistronic Cre expression driven from the endogenous aquaporin-1 gene. These studies should provide novel insight into the molecular genetics of eye development, potentially broaden our understanding of degenerative eye disorders and open new avenues for their treatment with growth factors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: HIGH RESOLUTION BLOOD FLOW MAPPING IN OCULAR TISSUES Principal Investigator & Institution: Ferrara, Katherine W.; Professor; Biomedical Engineering Div; University of California Davis Sponsored Programs, 118 Everson Hall Davis, Ca 95616 Timing: Fiscal Year 2001; Project Start 01-MAY-1996; Project End 31-AUG-2004 Summary: We have developed a new high-frequency ultrasound scanning system that provides the opportunity to obtain a two-dimensional map of blood flow in the anterior
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segment of the eye in one second, with spatial resolution on the order of 40 microns and velocity resolution on the order of 0.2 mm/s. This represents approximately an order of magnitude improvement in resolution over existing techniques, and provides the first non-invasive opportunity to evaluate blood flow in arterioles and venules in opaque tissues. In addition, a new strategy to estimate capillary volume and flow rate has been developed by combining a theoretical model and a system to interrogate individual contrast microbubbles. This new suite of tools can be applied to improve the understanding of the mechanisms of ophthalmic diseases including glaucoma and agerelated macular degeneration as well as the mechanisms and effectiveness of treatment options. Here, we specifically address glaucoma. The clinical significance of an improvement in the management of ophthalmic diseases is enormous since 3 million people in the US alone suffer from glaucoma, 100,000 per year suffer some form of ocular trauma, and over 6 million people in the US suffer from degenerative retinal diseases. Most experts agree that glaucoma is a series of conditions characterized by a particular form of optic nerve damage that is often associated with elevated intra-ocular pressure, although the mechanisms responsible for damage and successful therapy are not understood. Many drug therapies for glaucoma are assumed to decrease intra-ocular pressure through the constriction of arterioles in the ciliary body, however, it has been impossible to measure these changes in ciliary body blood flow, or to measure optic nerve head perfusion. Our new technique to estimate arteriolar diameter and flow rate will be evaluated in a human study of glaucoma therapies. Contrast-assisted methods for the estimation of capillary volume and flow rate will be developed for the high resolution requirements of ophthalmology. This requires the further development of our experimental system, the evaluation of new contrast agents with higher resonant frequencies, and the validation of our new strategies for the estimation of capillary density. These new techniques will be used to evaluate perfusion in the ciliary body and in the optic nerve head in an animal model study of drug therapies, and compared with the output of a scanning laser Doppler flowmeter. In conjunction with this study, mechanical damage to the vessel wall will be directly assessed through the use of fluorescent markers. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HIGH-RESOLUTION IMAGING OF OCULAR MELANOMA AND RETINA Principal Investigator & Institution: Bartsch, Dirk-Uwe G.; Associate Professor; Ophthalmology; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, Ca 92093 Timing: Fiscal Year 2001; Project Start 01-FEB-2001; Project End 31-JAN-2004 Summary: (Applicant's Description): High-resolution imaging allows improved understanding of retinal disease and pathological conditions, particularly in prognosis of malignant choroidal melanoma, age-related macular degeneration, diabetic retinopathy, ocular complications of AIDS and glaucoma. The eye can only be regarded as a diffraction-limited optical system up to a pupil diameter of 3 mm. Standard retinal imaging technology uses a 3 mm imaging aperture to avoid the higher order aberrations of the outer cornea. However, if these higher order aberrations can be compensated, diffraction-limited imaging at 7 or 8 mm pupil diameter can be achieved. The numerical aperture of the diffraction-limited eye at 7 or 8 mm pupil will allow to visualize retinal detail that was previously not achievable in ophthalmology. To achieve this goal we plan to develop a wavefront sensor that will allow us to measure the existing aberrations of the measured eye. We will test it in an eye model, in animal eyes and in
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human eyes. The wavefront sensor will be attached to a fundus camera and scanning laser ophthalmoscopes. The second aim is to use an adaptive wavefront compensator to correct the aberrations in a feed-back loop setup. We will test the complete system of wavefront sensor and wavefront compensator in an eye model, in animal eyes and in human eyes. The wavefront compensator will be attached to a fundus camera and scanning laser ophthalmoscopes. The third aim is to used digital image processing to correct for the portion of the residual aberrations that could not be compensated with the adaptive wavefront compensator due to mechanical considerations. Our group has previous developed a wavefront sensor and wavefront compensator based on a micromachined membrane deformable mirror. Due to the limited number of electrodes, slow speed of our computer system and the mechanical stiffness of the membrane we were not able to completely correct all measured aberrations. Our preliminary work shows that the system is capable of allowing wavefront correction. In this study we plan to improve the acquisition speed of our wavefront sensor and wavefront compensator to allow rapid wavefront compensation. Our preliminary results have shown that even the best aberration compensation still suffers from residual wave aberrations. Since we can measure and characterize these aberrations, we can develop digital inverse filter based on our experience in image reconstruction to correct the acquired images. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IMMUNE MECHANISMS OF OCULAR INFLAMMATORY DISEASE Principal Investigator & Institution: Gordon, Lynn K.; Jules Stein Eye Institute; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2001; Project Start 01-MAR-1997; Project End 31-AUG-2001 Summary: The immediate goal of the candidate is to develop scientific expertise in molecular immunology and ocular biochemistry as applied to the definition of pathogenic autoantigens. This will lead to the long-term goal of an independent research program on the pathogenesis of ocular inflammatory diseases. The candidate has a strong background in clinical ophthalmology with a demonstrated interest in ocular inflammation. Past graduate school success in basic research is evidence of her scientific abilities. However, the lag time between graduate school and re-entry into basic research demands a period of mentored scientific retraining. UCLA will provide an outstanding scientific environment that will allow the candidate to develop current expertise in molecular biology and immunology. The health-relatedness of the project is that it specifically attempts to define candidate antigens that drive certain endogenous human inflammatory diseases of the eye, which can be used as the basis for novel diagnostic tests and therapeutic interventions. Although many immune-mediated inflammatory diseases are thought to result from activated CD4 T cells, B cell activation and clonal expansion is expected to occur in tandem. These selected B cells have the same antigenic specificity of the pathogenic T cell, and their antibodies offer an important tool to characterize the target antigen driving the immune response. The subject of this proposal is to use new techniques iii antibody phage display cloning to isolate marker antibodies and candidate antigens for a distinctive type of uveitis that commonly occurs with ulcerative colitis (UC). The first aim is to determine whether a unique marker antibody in UC, pANCA, is associated with inflammatory uveitis. This will be tested by ELISA and immunofluorescence screening of human sera for the distinct UC form of pANCA. The correlation between disease activity and level of autoantibody will also be determined. The second aim is to identify uveal antigens that react with 5-3, a human recombinant monoclonal antibody to the pANCA antigen. If
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such antigens are identified, they will be characterized by protein biochemistry, or if necessary, by molecular cloning. Disease association of the antigen will be tested by characterizing the B and T cell responses to the antigen. The third aim is to develop a comprehensive library of uveal antigens reactive with the UC antibody response. Biochemical and immunologic characterization of these antigens will be performed following the experimental model of the preceding aim. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: INTEGRATIVE IMMUNOLOGY TRAINING PROGRAM Principal Investigator & Institution: Scheuermann, Richard H.; Director; Center for Immunology; University of Texas Sw Med Ctr/Dallas Dallas, Tx 753909105 Timing: Fiscal Year 2003; Project Start 01-JUL-1980; Project End 31-AUG-2008 Summary: (provided by applicant): The purpose of the Integrative Immunology Training Program at U.T. Southwestern is to provide comprehensive training of predoctoral and postdoctoral fellows in the conduct of modem immunology research. The goal is to produce sophisticated and highly trained scientists who are capable of developing research programs to investigate normal immune system function and the defects in immune system function that contribute to human disease. This goal is achieved through an integrated combination of training activities that includes formal advanced coursework in Cellular and Molecular Immunology, Genetic Manipulation of the Immune System, Tumor Immunology and Bioinformatics, research fellowship proposal development and oral defense in the form of a Qualifying Exam, regular Works-in-Progress seminars, teaching opportunities, career development programs and interdisciplinary laboratory research. The training program revolves around the Immunology Graduate Program, one of the eight graduate programs in the Division of Cellular and Molecular Biology at U.T. Southwestern. The training program includes thirty-two faculty from several departments/divisions on campus, including Immunology, Microbiology, Pathology, Cancer Immunology, Rheumatology, Neurology, Internal Medicine, Dermatology and Ophthalmology. Research projects pursued in the participating laboratories include investigations of the cellular, molecular and genetic determinants of the autoimmune diseases systemic lupus erythematosis, multiple sclerosis and rheumatoid arthritis; mechanisms of natural killer cell activation and killing; complexities of antigen processing and presentation; mechanisms of tumor cell homing and migration; regulation of tumor cell growth in vitro and in vivo; regulation of normal lymphocyte development and migration; signal transduction in normal and malignant lymphocytes; immune response to HIV and other infectious agents; and development of anti-tumor immunotoxins. The rationale for this training program reflects the need for research scientists with training in immunology given that the immune system plays both positive and negative roles in a variety of human diseases and clinical situations, including cancer prevention and treatment, organ transplantation, autoimmunity, immunodeficiency and infectious disease. With this submission, this training program enters its 27th year of training excellence. Our previous trainees have left the program with strong publications records to excellent research positions in academia and industry. The leadership positions held by many of our faculty and previous trainees reflect the high quality of the training program provided. PARTICIPATING FACULTY: The 32 training faculty include 14 professors, 6 associate professors, and 9 assistant professors. 10 of the training faculty are women. All of the faculty are at the University of Texas Southwestern. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: JEM-123O ELECTRON MICROSCOPE Principal Investigator & Institution: Ryugo, David K.; Professor; Otolaryn & Head & Neck Surgery; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2004 Summary: (provided by applicant): We are requesting funds to purchase an electron microscope to replace our current 17-year-old one that has become increasingly unreliable. The proposed microscope will be used by a group of 11 users primarily from the Departments of Otolaryngology-Head & Neck Surgery and Ophthalmology at the Johns Hopkins University School of Medicine. A total of 13 projects will be supported by 8 RO1, 2 KO8, 1 K23, and several nonfederal grants. The purchase of this microscope is crucial for the continued progress of research supported by NIH programs. The breadth of the projects is broad but unified by a foundation in structural neurobiology. Projects include (a) studies of the synaptic organization and plasticity of the mammalian auditory system; (b) histopathologic studies of the human eye; (c) ultrastructural examinations of sensory receptors and associated structures of the eyes and ears in normal, pathologic, and/or genetically altered animals; (d) localization of molecules (cytoskeletal and synaptic proteins, growth factors, or ion channels) in eyes and ears that pertain to normal function; (e) identification of growth factors that enhance photoreceptor growth; and (f) gene transfer experiments involving factors that influence laryngeal nerve growth, reinnervation, and muscle development. Conceptual and technical approaches utilized by the different research groups emphasize the common themes that link these various projects. Our work is highly dependent upon electron microscopy, and the proposed purchase will provide its users with a reliable instrument that is equipped with a number of advanced features that are currently unavailable anywhere at our institution. Award of this instrument will have an immediate and positive effect on the productivity of these projects. It will serve to catalyze interdisciplinary discussions among users, provide a valuable teaching tool for our trainees, and enhance the progress of biomedical research on hearing, vision, and voice. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: JOHNS HOPKINS ADULT AIDS CLINICAL TRIALS UNIT Principal Investigator & Institution: Flexner, Charles W.; Associate Professor; Medicine; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2001; Project Start 01-JAN-2000; Project End 31-DEC-2004 Summary: (adapted from applicant's abstract): Johns Hopkins University has had an ACTU since its inception in 1986. The Unit is administratively within the Division of Infectious Diseases as a component of the Johns Hopkins HIV Care Program, but it is configured to make maximum use of relevant institutional resources with investigators from multiple departments and divisions including Pharmacology, Neurology, Ophthalmology, Gynecology, Pathology and Internal Medicine. The Hopkins ACTU has provided leadership to the ACTG scientific agenda and has provided HIV clinical trials to Baltimore, a city that ranks ninth among metropolitan areas in AIDS rates. The performance record for the last grant cycle shows average enrollment, data performance and a rank of No. 3 in scientific contributions. Assets of this ACTU include leadership and scientific expertise in virology (B. Jackson), immunology (H. Lederman, T. Quinn, R. Bollinger), quality of life assessment (A. Wu), neurology (J. McArthur), pharmacology (C. Flexner), CMV retinitis (D. Jabs), and mycobacteriology (R. Chaisson). This unit has a subunit in the prison system, has developed an ACTG study of tuberculosis in Haiti and has high enrollment of injection drug users and African-Americans. This application
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proposes to continue a scientific portfolio that has depth and diversity to support the ACTG scientific agenda and a clinical trials program that includes good data performance and the enrollment of high priority participants. All current investigators will continue in their present roles as will the three advanced technology laboratories. Three new investigators, Dr. R. Siliciano (latent reservoirs of HIV), Dr. Richard Moore (HIV outcomes, cost and cost effectiveness), and Dr. David Thomas (hepatitis C coinfection) will be added. Preference will be given to protocols that reflect emphasis areas of the Hopkins ACTU, especially pharmacology, neurology, immunology, mycobacteriology, hepatitis C, long-term outcomes (quality of life and cost analyses) and simplified ART regimens (to better serve the patients). There will be emphasis on enhanced enrollment with a new peer recruiter and a new subunit to increase the catchment area. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: LONGITUDINAL OPHTHALMOLOGY
STATISTICAL
METHODS
FOR
Principal Investigator & Institution: Davidow, Amy L.; Prev Med and Community Health; Univ of Med/Dent Nj Newark Newark, Nj 07103 Timing: Fiscal Year 2001; Project Start 01-FEB-2001; Project End 31-JAN-2003 Summary: (Applicant's Abstract) The proposed project is a two year study to develop inferential and study design aspects of a linear statistical model appropriate to the analysis of longitudinal ophthalmologic data and to apply the improved model in a reanalysis of a data set obtained from the Early Treatment Diabetic Retinopathy Study (ETDRS). The relevant statistical model is the repeated-measures random effects/AR(l) model for continuous data due to Heitjan and Sharma. This model incorporates crosscorrelation between eyes and longitudinal correlation among measurements obtained from a single eye. The re-analysis of the ETDRS data set will consider the effects of aspirin on visual acuity measured continuously. A previously published analysis (ETDRS Report Number 8) analyzed a categorical version of visual acuity, ignoring longitudinal correlation and handling cross-correlation between eyes by analyzing eyes separately. The repeated measures random effects /AR(l) model has already been utilized by Heitjan and Sharma in a published study of intraocular pressure, using the expected information to perform statistical inference. Simulation studies have shown that it performs well in the balanced data case. Our first objective is to develop better inferential methods so as to 1) handle unbalanced (i.e., missing) data such as that arising when only one eye of two has the disease of interest and/or when the number of followup visits varies with subject, 2) control for the use of a possibly mis-specified variance structure, and 3) compensate for the use of estimated variance parameters in the standard error of the fixed effects, a procedure that may result in an underestimation of the standard error. This objective will be accomplished by the following: 1) replacing the expected information with the observed information, the observed information being a more reliable method of performing statistical inference in the presence of missing data, 2) using the robust (sandwich) variance estimator, a method that can control for a possibly mis-specified variance structure, and 3) approximating the degrees of freedom so as to control for the possibility of underestimated standard errors. Methodological advances will be incorporated into a computer package to be made available on the World Wide Web. Our second objective is to carry out power and sample size calculations for several different longitudinal ophthalmologic study designs, under various assumptions about the prevalence of bi-ocular versus uni-ocular disease, differential treatment allocation, loss-to-follow-up, and expected adherence to study
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treatment(s). The implications of treatments applied at the eye-level (e.g., photocoagulation) as well as systemically applied treatments (e.g., aspirin) on sample size, frequency of evaluation, and power will be considered. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MAX-ENTROPY CONTROL FOR HIGH QUALITY DIGITAL IMAGING Principal Investigator & Institution: Truitt, Paul W.; Kestrel Corporation 3815 Osuna Ne Albuquerque, Nm 87109 Timing: Fiscal Year 2001; Project Start 01-AUG-2001; Project End 30-MAY-2002 Summary: A low-cost, high-resolution, high-contrast color digital camera optimized for ophthalmology will be demonstrated. The maximum entropy camera will be tested for its effectiveness in meeting the image quality requirements for telemedicine and for remote screening of pre-proliferative and proliferative diabetic retinopathy. The proposed device exploits recent technological advances in high sensitivity CCD cameras and digital signal processing electronics. Today's low cost 8-bit CCD cameras do not have the dynamic range to image the human retina, which is characterized by regions of high reflectivity (20-40 percent), such as the optic disc, and very low reflectivity (