Congressional Justification for FY 2009
National Eye Institute
Department of Health and Human Services
National Institutes of Health
FY 2009 Budget:
- Justification of Budget Request
- Appropriation language
- Major changes in budget request
- Budget graphs
- Justification narrative
Justification of Budget Request
Authorizing Legislation: Section 301 and Title IV of the Public Health Service Act, as amended.
|FY2007 Actual||FY2008 Enacted||FY2009 Estimate||Increase or Decrease|
This document provides justification for the Fiscal Year (FY) 2009 activities of the National Eye Institute including HIV/AIDS activities. Details of the FY 2009 HIV/AIDS activities are in the "Office of AIDS Research (OAR)" section of the Overview. Details on the NIH Common Fund are located in the Overview, Volume I. Program funds are allocated as follows: Competitive Grants/Cooperative Agreements; Contracts; Direct Federal/Intramural and Other.
For carrying out section 301 and title IV of the Public Health Services Act with respect to eye diseases and visual disorders $667,764,000 (Department of Health and Human Services Appropriation Act, 2008)
Major changes in budget request
Major changes by budget mechanism and/or budget activity detail are briefly described below. Note that there may be overlap between budget mechanism and activity detail and these highlights will not sum to the total change for the FY 2009 budget request for NEI, which is $.6 million more than the FY 2008 Estimate, for a total of $667.8 million.
Research Project Grants (-$.8 million; total $417.7 million): The NIH Budget policy for RPGs in FY 2009 is to provide no inflationary increases in noncompeting awards and no increase in average cost for competing RPGs. NEI will continue to support new investigators and to maintain an adequate number of competing RPGs. NEI will support 1,039 Research Project Grant (RPG) awards in FY 2009. Noncompeting RPGs will increase by 29 awards and increase by $15.3 million. Competing RPGs will decrease by 44 awards and decrease by $16.0 million. Intramural Research and Research Management and Support receive modest increases to help offset the cost of pay and other increases.
Intramural Research (+$1.0 million; total $69.6 million): NEI will support a new laboratory to integrate basic, pre-clinical, and translational research to develop and test therapeutic interventions in neurodegenerative eye diseases.
History of Budget Authority and FTEs:
Distribution by Mechanism:
Change by Selected Mechanisms:
The National Eye Institute's (NEI) mission is to conduct and support research, training, health information dissemination, and other programs with respect to blinding eye diseases, visual disorders, mechanisms of visual function, preservation of sight, and the special health problems and requirements of individuals who are visually impaired. Inherent in this mission is clinical research across the spectrum of eye diseases and vision disorders, as well as the investigation of the normal tissue and normal visual processes that will help gain a more complete understanding of abnormal circumstances that lead to these conditions. These investigations are conducted in hundreds of laboratories and clinics throughout the U.S. and in NEI's own intramural research facilities in Bethesda, Maryland.
NEI has continued to reinvigorate its intramural research program (IRP) to better leverage new scientific opportunities. The newly established Laboratory of Neurobiology, Neurodegeneration and Repair will be expanded further in FY 2009. This laboratory integrates basic, pre-clinical, and translational research to develop and test therapeutic interventions in neurodegenerative eye diseases such as macular degeneration, glaucoma and retinitis pigmentosa. Interventions including gene therapy, small molecules, neurotrophic factors, and cell-based systems, will be explored and assessed in combination with a variety of treatment delivery technologies. A senior scientist was recruited in FY 2008 to head the laboratory and additional laboratory sections will be added in FY 2009 following national recruitment searches.
FY 2009 will also bring enhancements to the Ophthalmic Genetics and Visual Function Branch within the IRP. NEI established eyeGENE, a partnership involving the IRP and laboratories across the vision research community, to enhance diagnostic genetic testing for eye diseases. eyeGENE provides genotyping information to participating patients and their doctors that will help to predict an individual's risk of developing eye disease while also creating a centralized repository of genetic material and diagnostic information for research purposes. The eyeGENE network will add several additional genotyping tests and testing sites in FY 2009.
The first patients have been entered into a phase I clinical trial to evaluate gene transfer therapy for a rare but severe retinal degenerative disease, Leber's congenital amaurosis (LCA), that causes blindness in children. The clinical trial includes a dose escalation study, a re-dosing study and evaluation of the treatment in adults and adolescents with the disease. Data generated from the proposed studies will test the hypothesis that this vector is safe and warrants consideration for use in larger clinical trials assessing efficacy. Gene transfer is particularly well-suited to the treatment of retinal degenerative diseases. Nearly 200 single gene defects have been implicated in these diseases. This clinical trial is an important step in treating LCA and in establishing proof-of-concept for gene transfer as a viable therapy for an entire family of eye diseases.
NIH developed the database of Genotype and Phenotype (dbGaP) program to archive and distribute genetic sequences and disease information from large clinical trials and epidemiology studies. The intent of this program is to disseminate genetic data and clinical information to qualified investigators to accelerate the pace of discovery. These data sets are pivotal to understanding genetic and environmental interactions in disease. The dbGAP program was launched with data from NEI's Age-Related Eye Diseases Study (AREDS), a landmark study of the clinical course of age-related macular degeneration (AMD) and cataracts. NEI anticipates that additional datasets will be added to the dbGAP during FY 2009.
AMD, the leading cause of blindness in the elderly in the United States, will impose an increasing burden in future years based on demographics. The original AREDS clinical trial, completed in 2005, demonstrated that antioxidant vitamin and mineral supplements reduced the progression to advanced AMD by 25 percent on average. Building on these landmark findings, AREDS2 is assessing additional supplements (lutein, zeaxanthin, and long-chain omega-3 fatty acids) as a treatment for AMD and cataracts. AREDS2 is also evaluating effects of eliminating beta-carotene and/or reducing zinc in the original AREDS formulation on AMD progression. Additionally, AREDS2 investigators will be exploring gene-environment interactions in the development of these conditions, as well as investigating how these interactions influence cognitive function, and cardiovascular health. NEI anticipates completion of enrollment of the 4000 participants in this large, multi-center trial by FY 2009.
The NEI extramural research program recently implemented a new initiative to investigate the role of inflammation in degenerative eye diseases such as AMD, uveitis, and other chronic disorders of the eye. This initiative will expand in FY 2009 to leverage the latest knowledge of the molecular and cellular aspects of inflammation and to study the development and progression of degenerative eye diseases. A second emphasis is to expand our knowledge of how the inflammatory process is kept under tight control using the eye as a model system. This knowledge will be pivotal to the development of new diagnostic and intervention strategies to halt and reverse the progression of degenerative eye diseases.
Justification of the FY 2009 Budget by Activity Detail
Program Descriptions and Accomplishments
Retinal Diseases Research:
The light-sensitive retina of the eye is susceptible to many sight-threatening conditions including age-related macular degeneration, diabetic retinopathy, retinopathy of prematurity, retinitis pigmentosa, Usher's syndrome, ocular albinism, retinal detachment, uveitis (inflammation), and eye cancer. The goals of this program area are to understand the disease mechanisms that cause vision loss and to develop improved methods of prevention, diagnosis, and treatment. To meet these goals, NEI supports research on the cell biology, physiology, and immunology of the retina and on the role of gene expression, gene regulation, and the environment in retinal health and disease.
Recent accomplishments include the successful launch of a phase I clinical trial to assess the safety of gene transfer in treating people with a form of Leber congenital amaurosis (LCA). People with LCA are born with severe visual impairment or develop vision loss early in childhood.
The FY 2009 budget estimate for Retinal Diseases Research activities is $262.6 million, a change of -$.3 million or -.1% from the FY 2008 estimate. The program plans for FY 2009 and accomplishments expected include an acceleration of research on the genetic and environmental basis for AMD, including the role of possible immunological factors. This will include an expansion of genome wide association studies and related efforts in bioinformatics. NEI will support projects that address the possible restoration of vision in retinal degenerative diseases by building on recent advances in cell transplantation and precursor cell biology, including the use of bone marrow stem cell transplantation, and on "re-engineering" the production of light-sensitive proteins in retinal neurons. Research will continue in efforts to control abnormal new blood vessel growth (angiogenesis) in a number of eye diseases, and will include the conduct of clinical trials in this area. These areas were among those designated as research priorities in NEI's latest strategic plan. The program plans for FY 2009 also include the conclusion of the remarkably productive Age-Related Eye Disease Study (AREDS), a multicenter study of cataract and AMD. AREDS demonstrated that high-dose antioxidant supplements (beta-carotene, vitamins C and E, and zinc) can slow the progression of AMD, and added to our understanding of the epidemiology of cataract and AMD, including the demonstration of new genetic associations. NEI will expand the activities of AREDS 2 to evaluate the use of additional oral supplements for the treatment of AMD and cataract. NEI also plans to continue collaborating with the National Heart Lung and Blood Institute on the follow-up ocular component of the Multi-Ethnic Study of Atherosclerosis (MESA) study. The study is attempting to identify factors that predict the development of symptoms and progression to overt cardiovascular disease in different ethnic groups in diverse geographical locations.
Corneal Diseases, Cataract, and Glaucoma Research:
Portrait of a Program: Gene Transfer Therapy for Childhood-Onset Blindness
FY 2008 Level: $1.5 million
FY 2009 Level: $2.0 million
Change $0.5 million
NEI has launched a clinical trial to assess the safety and efficacy of gene transfer in treating people with a form of childhood blindness called Leber congenital amaurosis (LCA). NEI scientists discovered RPE65, a protein within the retina that is critical for regeneration of photoreceptor cell visual pigment following exposure to light. One form of LCA is caused by mutations in the RPE65 gene. Proof-of-concept for gene transfer as a treatment for LCA was demonstrated by NEI-supported investigators both in extensive studies using a dog breed that has LCA and in studies using other animal models. Restoration of visual function in these affected dogs following a single treatment has been remarkable, and has persisted for more than five years.
NEI-supported scientists conducted rigorous pre-clinical safety studies in animals and received approval by the NIH Recombinant DNA Advisory Committee and the FDA to begin human safety studies. The first volunteers with LCA were treated in late 2007. If successful, the clinical trial will continue and expand through FY 2009 to assess the efficacy of this approach. The expectation and hope is that transferring the RPE65 gene will restore useful visual function in people with LCA. An independent data and safety monitoring board is providing careful oversight for all aspects of this trial.
Portrait of a Program: Role of Inflammation in Age Related Macular Degeneration
FY 2008 Level: $2.0 million
FY 2009 Level: $2.5 million
Change $0.5 million
Recognition that inflammation may play an important role in the pathogenesis of age-related macular degeneration (AMD) has led to a major paradigm shift in our understanding of this disease. Investigators now hypothesize that the underlying mechanism that leads to AMD is immune driven, perhaps sharing some of the characteristics of atherosclerosis and other degenerative disorders. NEI funding has provided crucial support for these discoveries. A phase II clinical trial, with supporting laboratory investigations, has been initiated within the NEI clinic. Participants with AMD are randomized to receive one of three immunomodulatory agents or to be observed in conjunction with their standard anti-angiogenic therapy. A second clinical trial based on promising preliminary results will begin in FY 2008 and be expanded during FY 2009.
Corneal diseases, cataract, and glaucoma are among the most prevalent disorders of the eye. Corneal injuries, infections, and diseases can be extremely painful, requiring immediate medical attention. NEI grantees are exploring how infectious, inflammatory, and immunological processes affect the cornea, and how the cornea heals following a wound. The cornea, tear film, eyelids, and conjunctiva form a highly-integrated biological system.
By 2020 researchers estimate that about 40 million Americans will be affected by cataracts1. The economic burden of cataract will only worsen as the American population ages. NEI cataract research seeks to understand the physiological basis of lens transparency at the cellular and molecular levels and seeks strategies to prevent cataract formation and progression.
Approximately 2.2 million Americans have glaucoma and the prevalence of the disease will rise to a projected 3 million by 20203. Glaucoma is the leading cause of blindness in African Americans. Glaucoma research aims to understand the complex genetic and biological factors that cause the disease and to develop treatments that protect optic nerves from the damage that leads to vision loss.
Recent accomplishments include new findings that may explain how glaucoma causes blindness and may provide new drug targets for protecting the optic nerve. In animal models of glaucoma, increased levels of an inflammatory molecule (TNF-alpha) was found to activate microglia, cells that are part of the eye's immune system. These activated microglia in turn killed many of the cells (oligodendrocytes) that ordinarily support the optic nerve fibers. The unsupported optic nerves then began to die, and vision was lost, reproducing the hallmark clinical features of clinical glaucoma.
The FY 2009 budget estimate for Corneal Diseases, Cataract, and Glaucoma Research activities is $167.9 million, a change of -$.2 million or -.1% from the FY 2008 estimate. The program plans for FY 2009 and accomplishments expected include following up on a recent finding that certain receptors that bind to vascular endothelial growth factor may play an important role in maintaining the normal transparency of the cornea by blocking the formation of new blood vessel growth. Research will continue to explore the role of precursor cells in accelerating corneal wound healing. The cornea is the most densely innervated tissue in the body and is extremely painful when subjected to trauma; however, relatively little is known of interventions, which could limit and/or reduce corneal pain. NEI expects to fund new projects to identify therapeutic approaches. A growing body of evidence suggests that movement of nutrients through small channels between cells in the lens, known as gap junctions, plays a significant role in maintaining the function of lens epithelial cells. Projects will be funded to examine the possible contribution of defects in the gap junctions in the development of cataracts. Genome wide association studies and related bioinformatics efforts will be launched to explore further the role of genetics and the environment on the development of glaucoma and to understand better the differential response of individuals to glaucoma medications. Research will also be conducted to follow up on the surprising finding in an animal model of glaucoma that death of retinal ganglion cells, a hallmark of the disease, may be initiated by the immunologic destruction of certain cells that normally surround and support the optic nerve. NEI will expand its collaborative participation in the Age Gene/Environment Susceptibility Study with the National Institute on Aging and several other participating institutes. NEI will fund the follow-up ocular component of this study, which is investigating the contribution of candidate genes and the environment in diseases that are common in old age.
Sensorimotor Disorders and Rehabilitation Research:
Strabismus (misalignment of the eyes) and amblyopia (commonly known as "lazy eye") occur during development and affect 2-4 percent of the U.S. population3 4. Program goals center on gaining a better understanding of the development of the visual system in children at high risk for these conditions, and of the neuromuscular control of gaze.
Refractive errors, such as nearsightedness (myopia), farsightedness (hyperopia) and astigmatism are the most common, correctable visual disorders. A major goal of this program is to prevent refractive error by discovering the biochemical pathways that govern eye growth and uncovering the risk factors associated with refractive errors.
Much of the cerebral cortex is devoted to processing the visual information that floods our eyes. Vision scientists seek to understand how the brain processes visual information, how neural activity is related to visual perception, and how the visual system interacts with cognitive and motor systems.
Three million Americans now have low vision, a term used to describe chronic visual conditions that are not correctable by eye glasses or contact lenses5. The NEI supports rehabilitation research on improving the quality of life of persons with visual impairments by helping them maximize the use of remaining vision and by devising improved aids and strategies to assist those without useful vision.
Recent accomplishments include the discovery of a protein, expressed as a gradient during development, which controls the proper guidance of nerves from the two eyes to the brain, a process that is critical for normal visual function.
The FY 2009 budget estimate for Sensorimotor Disorders and Rehabilitation Research activities is $144.4 million, a change of -$.1 million or -.1% from the FY 2008 estimate. The program plans for FY 2009 and accomplishments expected include pursuing the research finding of several genes involved in Leber's Hereditary Optic Neuropathy, a genetic disease that frequently results in a substantial loss of central vision. The development of animal models carrying these mutations could lead to successful gene-based therapy for this disease. Research will also pursue remarkable new findings about how the activity of certain brain cells allows us to perceive a stable view of our surroundings despite constant head and eye movements, as highlighted in NEI's strategic plan. This research will help us to understand better the neural control of eye movements and associated disorders, and may have applicability in other sensory systems.
The program conducts vision research in its laboratories and clinic located on the NIH campus in Bethesda and other facilities in Rockville, Maryland. Program activities include: clinical studies concerned with the cause, prevention, and treatment of major eye diseases and vision disorders; basic research on cellular and molecular mechanisms of eye development, including the expression and function of genes within the eye; research in immunology and infectious diseases of the eye; and, developing a better understanding of our critical ability to guide movements under sensory control.
Recent accomplishments include the release of initial Age-Related Eye Disease Study (AREDS) genotype and clinical phenotype data into dbGaP, the new NIH database designed to archive and facilitate data sharing from NIH genome wide association studies.
The FY 2009 budget estimate for Intramural Research activities is $69.6 million, a change of $1.0 million or +1.5% from the FY 2008 estimate. The program plans for FY 2009 and accomplishments expected include the expansion of the recently established Laboratory of Neurobiology, Neurodegeneration and Repair to integrate basic, pre-clinical, and translation research in developing and testing therapeutic interventions in neurodegenerative eye diseases. These therapeutic approaches will include gene therapy, small molecules, neurotrophic factors, and cell based systems, in combination with a variety of treatment delivery technologies. NEI will also enhance the Ophthalmic Genetics and Visual Function Branch and expand the eyeGENE network to facilitate research on the discovery of the genetic causes of ocular diseases.
Research Management and Support:
Provides support to sustain, guide, and monitor the extramural and intramural research programs. Included in these funds are the support necessary for personnel to carry out leadership and management functions, human resource support, training, travel, purchasing, facilities, budget, planning, information technology, and extramural grant award and management. NEI currently oversees more than 1,400 grants and contracts, including research project grants, core center grants, research career development awards, cooperative clinical research agreements, and research and development contracts.
The FY 2009 budget estimate for Research Management and Support activities is $23.3 million, a change of $.3 million or 1.5% from the FY 2008 estimate. The management plans for FY 2009 and accomplishments expected include the continued prudent use of RMS funds while implementing strategic change through continuous improvement, business process reengineering, and other change strategies to meet NEI goals. For example, as part of its strategic planning process, NEI scientific programs undergo regular portfolio review at its National Advisory Eye Council meetings. NEI is participating in a variety of trans-NIH objectives such as using Knowledge Management to implement a transparent coding and disease reporting system and embracing the electronic submission of grant applications to replace previous paper applications. NEI will develop a Risk Management Program that will align with that of the NIH to standardize the risk management process and implement this risk management methodology, approach, tools, and procedures across NEI organizations.
The NEI is the lead institute for the Nanomedicine Initiative supported through the NIH Common Fund.
- Prevalence of cataract and pseudophakia/aphakia among adults in the United States. Arch Ophthalmol 122: 487-494, 2004.
- Prevalence of open-angle glaucoma among adults in the United States. Arch Ophthalmol 122: 532-538, 2004.
- The evolving concept of amblyopia: a challenge to epidemiologists. Am J Epidemiol 118(2): 192-205, 1983.
- Baltimore Vision Screening Project. Ophthalmology 103(1): 105-109, 1996.
- Blindness and Visual Impairment in an American Urban Population. Arch Ophthalmol 108: 286-290, 1990.