DEPARTMENT OF HEALTH AND HUMAN SERVICES

NATIONAL INSTITUTES OF HEALTH

Fiscal Year 2006 Budget Request

Witness appearing before the

House Subcommittee on Labor-HHS-Education Appropriations

Dr. Paul Sieving, Director

National Eye Institute

March 9, 2005

Number range CHAPTERWilliam Beldon, Deputy Assistant Secretary, Budget

Mr. Chairman and Members of the Committee:

I am pleased to present the Fiscal Year (FY) 2006 President's budget
request for the National Eye Institute (NEI). This budget includes
\$673,491,000, an increase of \$4,421,000 over the FY 2005 enacted level
of \$669,070,000 million comparable for transfers proposed in the
President's request. Number range CHAPTERAs the Director of the NEI it
is my privilege to report on the progress laboratory and clinical
scientists are making in combating blindness and visual impairment and
about the unique opportunities that exist in the field of vision
research.

Number range CHAPTERGLAUCOMA AND OPTIC NEUROPATHIES

Glaucoma is a group of eye disorders that causes optic nerve damage that
can lead to severe visual impairment or blindness. Elevated intraocular
pressure (IOP) is frequently, but not always, associated with glaucoma.
Glaucoma is a major public health problem and published studies find it
is the most common cause of visual impairment and blindness in African
Americans.

The prevalence of glaucoma is three times higher in African Americans
than in non-Hispanic whites[^1]. Additionally, the risk of visual
impairment is much higher and the age of onset is earlier than in
Whites. An NEI-supported follow-up study to the *Ocular Hypertension
Treatment Study* (OHTS) found that early treatment of elevated IOP
reduces the risk of developing glaucoma in African Americans. Of the
participants in the treatment arm of the study, 8.4 percent developed
glaucoma whereas 16.1 percent in the observation group developed the
disease. Additionally, the OHTS follow-up study found that certain
biological characteristics of the eye including corneal thickness are
helpful in predicting who will likely develop glaucoma and who will
benefit from therapy. This study provides important treatment and
prognostic information for clinicians in caring for this at risk
population.

RETINAL DISEASES

Retinal diseases are a diverse set of sight-threatening conditions that
include age-related macular degeneration, diabetic retinopathy,
retinopathy of prematurity, retinitis pigmentosa, Usher's syndrome,
ocular albinism, retinal detachment, uveitis (inflammation) and cancer
(choroidal melanoma and retinoblastoma). This year, NEI supported
laboratory researchers made great strides in developing therapies for
these diseases. For example, a recent NEI study found that eye
injections of bone marrow stem cells from adult animals prevented vision
loss in two rodent models of retinitis pigmentosa (RP). These findings
raise the possibility of a therapy in which patients could receive an
injection of their own bone marrow stem cells to preserve vitally
important central vision.

Age-related macular degeneration (AMD) is a leading cause of blindness
and visual disability in older age Americans. The inability to prevent
the development of AMD and its complications is largely due to an
imprecise understanding of the pathologic mechanisms of the disease.
Genetic and environmental factors have previously been implicated in the
disease. A recent NEI supported study in animal models has found
evidence that inflammation may also play a role. These animal models
suggest that the immune system contributes to the disease and offer new
insights into possible mechanisms of the disease. The availability of
animal models of the disease will also allow for the testing of new
intervention strategies.

CORNEAL DISEASES

Number range CHAPTERThe cornea is the transparent tissue at the front of
the eye. Corneal disease and injuries are the leading cause of visits to
eye care professionals, and are some of the most painful ocular
disorders.

The epithelial cells of the cornea form a surface barrier that protects
the underlying tissues from the external environment. When this layer is
damaged, the epithelial cells normally respond quickly to close the
wound and reform the barrier. In some cases, however, this response is
defective, leading to the formation of persistent and painful corneal
ulcers. Development of more effective treatments for this condition has
been hampered by the limited information about the cellular and
biochemical events that regulate corneal wound closure. This year,
scientists at the NEI discovered that an enzyme called Cdk5 plays a
central role in regulating the migration of epithelial cells to close
corneal wounds. More importantly they discovered that drugs which
inhibit Cdk5 promote cell migration and wound closure. These findings
suggest a new therapeutic approach for treating persistent corneal
ulcers and other conditions that impair wound healing. Animal studies
are in progress to determine whether inhibitors of Cdk5 can safely be
used in the eye to enhance wound healing.

Number range CHAPTERCATARACT

Cataract, an opacity of the lens of the eye, interferes with vision and
is the leading cause of blindness in developing countries. It is also a
major public health problem in this country. Throughout life, the lens
carries out a process of continued growth with epithelial cells dividing
and differentiating into fiber cells. As epithelial cells differentiate
into fiber cells they become denuded of certain cell components so they
will not interfere with vision or cause cataracts. NEI supported
scientists have recently discovered that the epithelial cells "borrow"
enzymes involved in programmed cell death, or apoptosis, to mediate the
destruction of these cell parts. Apoptosis is a normal biologic process
that guides an orderly destruction of cells that are no longer
functional or needed. This study defines a critical step in how fiber
cells are formed and will spark further investigation into whether
alterations in apoptotic enzymes play a role in cataract formation.

Number range CHAPTERSTRABISMUS, AMBLYOPIA AND VISUAL PROCESSING

Developmental disorders such as strabismus (misalignment of the eyes)
and amblyopia (commonly known as \"lazy eye\") are among the most common
eye conditions that affect the vision of children. In addition,
published data estimates that more than three million Americans suffer
from visual processing disorders not correctable by glasses or contact
lenses.

It is estimated that 20 percent of preschool children ages 3-4 have a
treatable eye condition[^2]. While many states are developing guidelines
for preschool screening programs, none of the commonly used vision tests
have been evaluated in a research-based environment to establish their
effectiveness. Initial results from the NEI-sponsored Vision in
Preschoolers (VIP) Study found that 11 commonly used screening tests
vary widely in identifying children with symptoms of common childhood
eye conditions such as amblyopia, strabismus, and significant refractive
error. When the best tests are used by highly skilled personnel in a
controlled setting, approximately two-thirds of children with one or
more of the targeted disorders were identified. These better tests were
able to detect 90 percent of children with the most severe visual
impairments. The ongoing VIP study will continue to provide state and
local agencies with data to select the most effective vision screening
exams that are currently available. The VIP study will also help ensure
that more children are detected and treated at an early stage when
therapy is most effective.

A fundamental issue in neuroscience has been the inability of nerve
cells to regenerate. If researchers could develop therapies that
overcome this limitation, the deleterious effects of many neurologic
diseases and central nervous system (CNS) injuries might be reversed or
greatly improved. NEI-supported researchers provoked nerve cell
regeneration in rodents by activating a nerve cell's natural growth
capacity and using gene therapy to suppress the effects of
growth-inhibiting factors. Although vision was not restored, this
combined approach stimulated nerve cell regeneration three times greater
than prior attempts. Regeneration of the mature CNS would provide an
opportunity to treat blindness and other neurologic diseases.

HEALTH DISPARITIES

Census 2000 data indicate that 12.5 percent of residents in the United
States, or 35 million people, are Latino. Based on these data, it is
estimated that by the year 2025, 61.4 million Latinos will live in this
country, making this the fastest growing minority population. However,
there is little available data to ascertain the prevalence and severity
of major eye diseases in this population. Results from the NEI-sponsored
*Los Angeles Latino Eye Study* (LALES) suggest that Latinos have some of
the highest rates of visual impairment and blindness in the United
States. The prevalence of visual impairment and blindness in Hispanics
increased with age and women were more frequently affected than men.
From a socio-economic perspective, Latinos who were unemployed, divorced
or widowed, or less educated had increased rates of visual impairment
and blindness. The prevalence statistics, coupled with the
socio-economic data from LALES concerning the factors that negatively
influence access to health care, will aid the NEI, through its public
education programs, to devise strategies that better target these
at-risk populations.

NIH ROADMAP

A major theme of the NIH Roadmap, *Re-engineering the Clinical Research
Enterprise*, is aimed at accelerating and strengthening the clinical
research process. This Roadmap theme is consonant with the NEI's own
goal of supporting the highest quality clinical research. The NEI and
vision research community have anticipated these opportunities by
creating networks such as the Pediatric Eye Disease Investigator Group
(PEDIG) and the newly launched Diabetic Retinopathy Clinical Research
Network. Continuation and expansion of these initiatives should
facilitate and hasten the translation of research discoveries from the
laboratory to the clinic for the benefit of those afflicted with a range
of eye disorders and diseases.

NIH NEUROSCIENCE BLUEPRINT

The NIH Neuroscience Blueprint was launched in 2004 to further enhance
cooperation among fifteen NIH Institutes and Centers that support
research on the nervous system.  Blueprint participants are developing
an initial set of initiatives focused on tools, resources, and training
that can have a quick and substantial impact because each builds on
existing programs.  Among the Blueprint initiatives for FY 2006, NEI
will participate in the systematic development of genetically engineered
mouse strains for research on the nervous system and training in
neuroimaging and computational biology. NEI will also participate with
other Institutes in an initiative to provide specialized neuroscience
resources such as animal model, imaging, gene sequencing and screening
facilities.

Number range CHAPTERMr. Chairman, this concludes my prepared statement.
I would be pleased to respond to any questions you or other members of
the committee may have.

Number range CHAPTER

DEPARTMENT OF HEALTH AND HUMAN SERVICES

NATIONAL INSTITUTES OF HEALTH

NATIONAL EYE INSTITUTE

BIOGRAPHICAL SKETCH

PAUL A. SIEVING, M.D., Ph.D.

Position: Director, National Eye Institute, NIH, 2001-Present

Education:

B.A., Valparaiso University (Physics with honors), 1970

M.S., Yale University Graduate School (Physics), 1973

Yale Law School, 1973-1974, leave of absence

M.D., University of Illinois Medical School, 1978

Ph.D., University of Illinois (Biomedical Engineering), 1981

Licensure:

National Board of Medical Examiners, 1978

American Board of Ophthalmology, 1983

Medical License: IL, 1978; CA, 1982; MA, 1984; MI, 1985

Professional Experience:

> Medical Internship and Ophthalmology residency, University of Illinois
> Hospital, 1978-1982. Postdoctoral Fellowship (Retinal Physiology),
> University of California, San Francisco, 1982-1984. Medical Fellowship
> (Inherited Retinal Degenerations), Harvard Medical School /
> Massachusetts Eye and Ear Infirmary, 1984-1985.

Academic Appointments:

> At the University of Michigan: Assistant Professor of Ophthalmology,
> 1985-1989. Faculty, Rackham Graduate School Programs in Neuroscience,
> 1985-2001; Bioengineering, 1985-2001. Associate Professor of
> Ophthalmology, 1989-1994. Founding Director, Center for Retinal and
> Macular Degenerations, 1990-2001. Founding Director, Ocular Molecular
> Diagnostics CLIA Laboratory, University of Michigan, 1999-2001.
> Professor of Ophthalmology and Visual Sciences, 1994-2001. The Paul R.
> Lichter Professor of Ophthalmic Genetics, 1990-2001.

Honors and Awards:

> James Scholar Award and Leon F. Moldavsky Physiology Award, University
> of Illinois Medical School. Fight-for-Sight Award. Career Development
> Award, National Retinitis Pigmentosa Foundation. Olga Keith Wiess
> Scholar, Research To Prevent Blindness. Distinguished Alumnus Award,
> Valparaiso University. American Ophthalmological Society. The
> Foundation Fighting Blindness, Scientific Advisory Board. Senior
> Scientific Investigator Award, Research to Prevent Blindness. Alcon
> Award. Doctor of Science (honorary), Valparaiso University. The Best
> Doctors in America.

Number range CHAPTERProfessional Organizations:

> Association for Research in Vision and Ophthalmology. International
> Society for Clinical Electrophysiology of Vision. American Academy of
> Ophthalmology. American Ophthalmological Society. Society for
> Neuroscience. American Society of Human Genetics. National Board of
> Visitors, Christ College, Valparaiso University.

Department of Health and Human Services

Office of Budget

William R. Beldon

Mr. Beldon is currently serving as Deputy Assistant Secretary, Budget in
the Department of Health and Human Services. He has been a Division
Director in the Budget Office for sixteen years, most recently as
Director of the Division of Discretionary Programs. Mr. Beldon started
in federal service as an auditor in the Health, Education and Welfare
Financial Management Intern program. Over the course of more than 30
years in the Budget Office, Mr. Beldon has held Program Analyst, Branch
Chief and Division Director positions. Mr. Beldon received a Bachelor's
Degree in History and Political Science from Marshall University and
attended the University of Pittsburgh where he studied Public
Administration. He resides in Fort Washington, Maryland.

[^1]: ^1^ The Eye Diseases Prevalence Research Group: Prevalence of
    open-angle glaucoma among adults in the United States. Arch
    Ophthalmol 122:532-538, 2004.

[^2]: Comparison of preschool vision screening tests as administered by
    licensed eye care professionals in the Vision in Preschoolers Study.
    Ophthalmology 111(4): 637-50, 2004.