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Leo T. Chylack, Jr., M.D.
Director of Research, Center for Ophthalmic Research
Professor and Vice Chairman of Research
Dept. of Ophthalmology, Harvard Medical School
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How does one assess the type
and severity of
these lens opacities?
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Introduction
Dr. Leo T. Chylack directs the Center for Ophthalmic Research (COR), a group of laboratories dedicated to the study of mechanisms of normal vision and blinding diseases. Its primary disease-related focus is the study age-related and other forms of lens opacification and cataract.
Areas of research within COR include:
- Ophthalmic Clinical Research
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Director: Leo T. Chylack, Jr., M.D. |
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Director: Jack Liang, Ph.D. |
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Director: Jeremy Wolfe, Ph.D. |
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Projects
1. The NASA Study of Cataract in Astronauts (NASCA)
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In Dr. Chylack’s research group the present primary focus is the study of lens opacification in astronauts, particularly the relationship between radiation in deep space and the prevalence, incidence, and progression rates of cataracts in the entire population of American astronauts and control groups of military pilots and ground-based controls in the Longitudinal Study of Astronaut Health (LSAH). He is the Principal Investigator of this five-year 3.2 million dollar project involving the BWH, Baylor College of Medicine (BCM), National Aeronautics and Space Administration (NASA), Johnson Space Center (JSC), Wyle Laboratories (WL), and Space Center Eye Associates (SCEA).
The NASCA Study is a cross-sectional and longitudinal five-year epidemiological study of the risk factors associated with cataract incidence and progression in the whole population of American astronauts and two control populations – pilots with military aviation experience and participants in the Longitudinal Study of Astronaut Health (LSAH). The study of risk factors focuses on the types and doses of radiation exposure in space flight, measures of nutrition, and general health. The assessment of cataract will use digital images of the lens and validated measures of severity. The study will measure the prevalence, incidence, and progression rates of cortical, nuclear, posterior subcapsular, and mixed cataracts, and it will relate these measures to measures of radiation, nutrition, and general health. A secondary goal of this project will be to improve the routine annual clinical assessment of the ocular lens by including Nidek EAS 1000 digital imaging of the lens in the annual ocular examination.
The objectives the NASCA project are:
1. NASCA contains an initial cross-sectional assessment of prevalence, and a follow-on assessment of progression rates of lens opacification in the populations of astronauts, military pilots, and ground based comparison participants in the Longitudinal Study of Astronaut Health (LSAH).
2. Main goal of cross-sectional study: To determine the prevalence of the three main classes of age-related lens opacification in the complete sample of astronauts and in two control populations: military pilots and ground-based subjects in the LSAH. We will determine the risk of each class of cataract associated with exposure to various components and dosages of radiation during space flight.
3. A secondary goal of the cross-sectional study is to estimate the prevalence of the three main classes of age-related lens opacification and determine the risk of each class of cataract associated with various factors (nutrition, general health, UV radiation, and others) encountered non-space flight.
4. A tertiary goal of the cross-sectional study is to modify the ocular assessment protocol in the astronauts’ regular annual medical examination to improve the assessment of the status of the crystalline lens.
5. The main goal of the five-year longitudinal study is to determine the progression rates of the three main types of lens opacification in the complete sample of astronauts, the control populations of pilots and ground-based subjects in the LSAH, and then determine the risk factors associated with cataract progression with a specific focus on the components and doses of radiation exposure during space flight. Specifically, total radiation lens dose, space radiation lens dose, and individual contributions from space galactic cosmic ray and trapped proton lens dose will be assessed.
Dr. Chylack’s collaborators at the BWH on this project are Mr. William Tung, B.S. (Image Analyst) and Ms. Sherlaine Holliday, M.P.H. (Project Coordinator).
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2. Developing Methods of Teaching the "LOCS" Methods of Classifying Age-Related Opacification of the Ocular Lens
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Dr. Chylack was the first author of a publication describing novel methods of classifying they type and severity of opacification in the crystalline lens. The two systems developed here at the BWH, Lens Opacities Classification System II (so-called “LOCS II”) and Lens Opacities Classification System III (so-called “LOCS III”) are widely used worldwide by clinical researchers and pharmaceutical companies needing to accurately classify age-related or drug-related opacification of the crystalline lens.
Dr. Chylack has developed face-to-face, interactive web-based, and self-administered web-based courses for training and certifying physicians and scientists in these classification systems.
He works closely with Dr. Wendi Yajnik in the Office of Corporate Sponsored Research and Licensing (OSCRL) in this effort.
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3. Massachusetts Lions Eye Research Fund-Sponsored Projects
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For many years the Massachusetts Lions Eye Research Fund (MLERF) has awarded Dr. Chylack a substantial grant for the support of research at the BWH on blinding eye disease. These projects have included studies of the mechanisms of protein aggregation in the lens (Dr. Liang), means by which Alzheimer’s disease (AD) protein A-beta causes increased aggregation of proteins in the lens of patients with AD (Dr. Goldstein), studies of the transcription factor LEDGF in the lens and central nervous system (Drs. Fu and Goldstein). Dr. Chylack collaborates with the investigators in these laboratories.
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4. Alcon-Sponsored European Clinical Study of the Acrysof Angle-Supported Phakic Intraocular Lens
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Alcon is studying a new treatment for myopia – the implantations into the eye of a synthetic intraocular lens. Since the natural lens of the eye is clear and present in the eye with the implant the implant is called a “phakic” intraocular lens. Dr. Chylack is assessing the effect of a synthetic phakic intraocular lens on the transparency of the natural lens of the eye. He and his colleagues are using digital images from the Nidek EAS 1000 Lens Imaging System to image the lens and any changes in its clarity. Dr. Chylack and Mr. William Tung then subject these digital images to image analysis to derive continuous measures of lens clarity or lens opacity. Since this is a longitudinal study these measures can be used to assess the incidence and progression rates of any opacities that appear during the course of this trial.
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Techniques Used in Ophthalmic Clinical Research
Ocular photography: Digital color imaging of the anterior segment of the eye is possible with the new Haag-Streit EyeCap Imaging system. This state-of-the-art device is excellent for imaging the eyelids, conjunctiva, cornea, anterior chamber, iris, pupil, and ocular lens. With appropriate lenses one can also image the optic nerve, and retina. With the imaging part of the EyeCap system there is associated image analysis and measurement software.
Nidek EAS 1000 Lens Imaging System: This state-of-the-art system for digital imaging the ocular lens of the eye captures nearly completely artifact-free Scheimpflug slit images of the anterior segment and lens, and bright retroillumination images of cortical, supranuclear, and posterior subcapsular cataracts. These images are amenable to analysis by Nidek software or by routines developed by Dr. Chylack and Mr. Tung. The continuous measures of opacification that are derived can enable on to measure incidence and progression rates in vivo.
Quasielastic light scattering techniques: In collaboration with Dr. Lee E. Goldstein, and Dr. Norman Ford (Neuroptix Corporation, Amherst, MA) Dr. Chylack has developed instrumentation to measure light scattering in the animal or human eye in vivo. These measures are extremely sensitive and enable the user to assess protein aggregation in the ocular lens prior to the onset of visible lens opacification. The ability to do this has many applications in diagnosing and monitoring diseases that effect changes in the lens.
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Funding
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NASA (NAG9 1491)
"The Precise Assessment of Prevalence and Progression of Lens Opacities in Astronauts as a Function of Radiation Exposure During Space Flight and Development of Improved Clinical Assessment of Ocular Lens."
PI: Leo T. Chylack, Jr., M.D.
Date: 2004-2008
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Alcon Research Ltd.
"Alcon-Sponsored European Clinical Study of the Acrysof Angle-Supported Phakic Intraocular Lens."
PI: Leo T. Chylack, Jr., M.D., Principal Investigator
Date: 2002-2005
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Massachusetts Lions Eye Research Fund
"Study of Age-related Cataract."
Date: 2004-2005
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Selected Publications
For other articles by Dr. Leo Chylack, please visit 
and enter Chylack LT or Chylack LT Jr in the query field.
1. Singh DP, Fatma N, Kimura A, Usukura J, Chylack LT Jr, Shinohara T. LEDGF binds to heat shock and stress-related element to activate the expression of stress-related genes.Biochem Biophys Res Commun 2001;283:943-55.
2. Weintraub JM, Taylor A, Jacques P, Willett WC, Rosner B, Colditz GA, Chylack LT Jr, Hankinson SE. Postmenopausal hormone use and lens opacities. Ophthalmic Epidemiology, 2002;9:179-90
3. Kubo E, Fatma N, Shinohara T, Chylack LT Jr, Akagi Y, Singh DP. Transactivation of involucrin, a marker of differentiation in keratinocytes, by lens epithelium-derived growth factor (LEDGF). J Mol. Biol. 2002;320:1053-63.
4. Sharma P, Fatma N, Kubo E, Shinohara T, Chylack LT Jr, Singh DP. Lens epithelium-derived growth factor (LEDGF) relieves TGF b1 induced transcription repression of heat shock proteins in human lens epithelial cells. JBC. 2003;278:20037.
5. Kubo E, Singh DP, Fatma N, Shinohara T, Zelenka P, Reddy VN, Chylack LT Jr. Cellular distribution of lens epithelium-derived growth factor (LEDGF) in the rat eye: loss of LEDGF from nuclei of differentiating cells. Histochemistry and Cell Biology, April 12, 2003;119:289-99.
6. Davison JA and Chylack LT Jr. Clinical application of the Lens Opacities Classification System III in the performance of phacoemulsification. JCRS. 2003;29:138-45.
7. Jacques PF, Moeller SM, Hankinson SE, Chylack LT Jr, Rogers G, Tung WH, Wolfe JK, Willett WC, Taylor A. Weight status, abdominal adiposity, diabetes, and early age-related lens opacities. AJCN, 2003;78:400-5.
8. Goldstein LE, Muffat JA, Cherny RA, Moir RD, Ericsson MH, Huang X, Mavros c, Coccia JA, Faget KY, Fitch KA, Masters CL, Tanzi RE, Chylack LT Jr, Bush AI. Cytosolic beta-amyloid deposition and supranuclear cataracts from people with Alzherimer’s disease. Lancet 2003;361:1258-65.
9. Morris MS, Jacques PF, Hankinson SE, Chylack LT Jr, Willett WC, and Taylor A. Moderate alcoholic beverage intake and early nuclear and cortical lens opacities. AJCN. 2004;11:53-65.
10. Fatma N, Kubo E, Chylack LT Jr, Shinohara T, Singh DP. LEDGF regulation of alcohol/aldehyde dehydrogenases in lens epithelial cells: stimulation of retinoic acid production and protection from ethanol toxicity. Am J Physiol Cell Physiol2004;287:C508-16.
11. Moeller SM, Taylor A, Tucker KL, McCullough ML, Chylack LT Jr, Hankinson SE, Willett WC, Jacques PF. Overall adherence to the Dietary Guidelines for Americans is associated with reduced prevalence of early age-related nuclear lens opacities. J Nutr. 2004;134:1812-1819.
12. Chylack LT Jr, Fu L, Mancini R, Konopka G, Folkerth DR, Hedley-White ET, Bush AI, Faget KY, Martin-Rehrmann MD, Saunders AJ, Kubo E, Singh DP, Goldstein LE. Lens epithelium-derived growth factor (LEDGF.p75) expression in fetal and adult human brain. Experimental Eye Res 2004;79:941-8.
13. Lu M, Taylor A, Chylack LT Jr, Rogers G, Hankinson SE, Willett WC, Jacques PF. Dietary fat intake and early age-related lens opacities. Am J Clin Nutr. 2005 Apr;81(4):773-9.
14. Chiu CJ, Morris MS, Rogers G, Jacques PF, Chylack LT Jr, Tung W, Hankinson SE, Willett WC, Taylor A. Carbohydrate intake and glycemic index in relation to the odds of early cortical and nuclear lens opacities. Am J Clin Nutr. 2005 Jun;81(6):1411-6.
15. Jacques PF, Taylor A, Moeller S, Hankinson SE, Rogers G, Tung W, Ludovico J, Willett WC, Chylack LT Jr. Long-term nutrient intake and 5-year change in nuclear lens opacities. Arch Ophthalmol. 2005 Apr;123(4):517-26.
16. Chang PY, Bjornstad KA, Rosen CJ, McNamara MP, Mancini R, Goldstein LE, Chylack LT, Blakely EA. Effects of iron ions, protons and X rays on human lens cell differentiation. Radiat Res. 2005 Oct;164(4 Pt 2):531-9.
17. Singh DP, Kubo E, Takamura Y, Shinohara T, Kumar A, Chylack LT Jr, Fatma N. DNA Binding Domains and Nuclear Localization Signal of LEDGF: Contribution of two Helix-Turn-Helix (HTH)-like Domains and a Stretch of 58 Amino Acids of the N-terminal to the Trans-activation Potential of LEDGF. J Mol Biol. 2006 Jan; 355(3):379-94.
18. Chiu CJ, Hubbard LD, Armstrong J, Rogers G, Jacques PF, Chylack LT Jr, Hankinson SE, Willett WC, Taylor A. Dietary glycemic index and carbohydrate in relation to early age-related macular degeneration. Am J Clin Nutr. 2006 Apr;83(4):880-6.
19. Herman DC, Gordon MO, Beiser JA, Chylack LT Jr, Lamping KA, Schein OD, Soltau JB, Kass MA; Ocular Hypertension Treatment Study (OHTS) Group. Topical ocular hypotensive medication and lens opacification: evidence from the ocular hypertension treatment study. Am J Ophthalmol. 2006 Nov;142(5):800-10.
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Colleagues
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Mr. William H. Tung
Ms. Evelyn Hernandez, B.S.
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Contact
Leo T. Chylack, Jr., M.D.
Director of Research
Center for Ophthalmic Research
221 Longwood Ave., EBRC Rm. 323
Boston, MA 02115
Ph: 617-732-7355 (O)
Fax: 617-732-7812 (O)
Email: LTCHYLACK@RICS.BWH.HARVARD.EDU
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