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Congressional Justification for FY 2002

National Eye Institute


Authorizing Legislation: Section 301 of the Public Health Service Act, as amended. Reauthorizing legislation will be submitted.

Budget Authority:

FY2000 Actual FY 2001 Estimate FY 2002 Estimate Increase or Decrease
FTEs BA FTEs BA FTEs BA FTEs BA
221 $449,889,000 250 $510,622,000 257 $571,126,000 7 $60,504,000

This document provides justification for the Fiscal Year 2002 activities of the National Eye Institute (NEI) including HIV/AIDS activities. A more detailed description of NIH-wide Fiscal Year 2002 HIV/AIDS activities can be found in the NIH section entitled "Office of AIDS Research (OAR)."

INTRODUCTION

Congress created the National Eye Institute (NEI) with the mission 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 the blind. Inherent in this mission is clinical research across the spectrum of diseases of the eye and disorders of vision, as well as the investigation of the normal tissue and normal visual processes that will help gain a more complete understanding of the abnormal processes that lead to these conditions. These investigations are conducted in hundreds of extramural laboratories and clinics throughout the United States and in the NEI's own intramural facilities in Bethesda, Maryland. The highlights that follow are examples of the research progress that has been made with the investment of federal funds in NEI-supported research and the direction that research will take over the next year.



Story of Discovery

New Therapy for Sight-threatening Uveitic Disease. Intraocular inflammatory disease, or uveitis, is a commonly seen ocular disorder that mainly affects children and young adults. It is a significant cause of the severe visual handicap in the United States and, if untreated, can rapidly lead to blindness. Some inflammations may be due to an infectious agent. However, a large number of intraocular inflammatory conditions appear not to be caused by an infectious agent but rather by an altered immune response of the body to itself, known as autoimmunity.

The present therapy for these non-infectious uveitic disorders are drugs that suppress the immune response. Unfortunately, there are significant side effects in terms of toxicity as well as suppression of beneficial immune responses to microorganisms. The goal of vision scientists has been to better understand the underlying mechanisms that lead to autoimmunity and ocular inflammation, so as to more specifically turn off only the harmful response, and try to do so with minimal or no side effects. One central mechanism in uveitis appears to involve a particular population of white blood cells or lymphocytes known as T cells. These cells carry the "immune memory" and are able to "orchestrate" inflammatory responses in the body. One of the major ways they orchestrate these inflammatory responses is to produce mediators of inflammation called interleukins and growth factors. Interleukin-2 (IL-2), for example, plays a central role in recruiting and perpetuating the immune response and serves as a growth factor to the T cells themselves. On the surface of activated T cells are receptors that interact with IL-2 and are crucial for cell survival. These receptors are a good target for therapy.

The approach of therapeutically targeting the IL-2 receptor of activated T-cells was initially evaluated in 1989 in a rodent model of endogenous uveitis, however due to its toxicity, it was not considered a safe therapy for humans. The next approach was to prepare a monoclonal mouse antibody to the human IL-2 receptor. A "humanized" version of this antibody dubbed HAT (for Humanized Anti-T-activated) and given the trade name Zenopax, was initially evaluated in a non-human primate model of uveitis that shares even more similarity with the human disease than do rodent models. The therapy was very effective in both preventing the development of the experimental uveitis and in treating the disorder once it appeared. Zenopax was then used in a small clinical trial conducted at the NIH Clinical Center to treat ten patients with severe sight threatening uveitis who had to be treated with potent immunosuppressive medications to keep their disease in check. Nine of the ten patients were able to be gradually taken off their immunosuppressive medication(s) and continued to be treated with Zenopax alone. The disease appears to remain under control with infusions of Zenopax given once a month with fewer complications and an improved quality of life. Planning has begun for a multicenter study to define better the potential indications for this new approach to treat sight-threatening diseases.

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Science Advances and Future Research Directions

Retinal Diseases

The retina is the complex, light-sensitive, neural tissue in the back of the eye that contains highly-specialized and metabolically active photoreceptor cells (rods and cones). These cells respond to light by emitting chemical and electrical signals. These signals are received by other retinal cells that process and transmit visual information via the optic nerve to the brain for further processing. The choroid is the underlying layer of blood vessels that nourish the retina. The retina and choroid are susceptible to a variety of diseases that can lead to visual loss or complete blindness. These sight-threatening conditions include age-related macular degeneration, diabetic retinopathy, retinopathy of prematurity, retinitis pigmentosa, retinal detachment, uveitis (inflammation), and cancer (choroidal melanoma and retinoblastoma).

Risk Factors for Age-Related Macular Degeneration. Age-related macular degeneration (AMD) is the leading cause of irreversible vision loss in the United States among persons over 65 years of age, the fastest growing segment of the US population. In spite of the public health significance of AMD, there is no treatment for most affected persons and information about its clinical course and the factors that predispose to it is limited. The identification of risk factors for AMD can help provide clues about the etiology of the condition and help to develop possible strategies for intervention. The Age-Related Eye Disease Study (AREDS), sponsored by the National Eye Institute, is an ongoing multi-center study of the clinical course of AMD and cataract. One part of the study attempts to identify possible risk factors for the presence of moderate to large-sized drusen (deposits that accumulate in the retina) and pigment abnormalities, both of which are prominent features of patients with AMD. Both large drusen and pigment abnormalities are considered to be high risk characteristics for the development of geographic atrophy or neovascular AMD--the form of AMD most associated with severe vision loss--and are often viewed as manifestations of "early" AMD. Two potentially modifiable risk factors, smoking and systemic hypertension are associated with the presence of large drusen and neovascular AMD. Additionally, the avoidance of smoking and the control of hypertension have wide-ranging health benefits beyond potentially reducing the risk of AMD. For some patients, prevention of vision impairment may be an additional motivating factor to help them modify these risk factors. This study will continue during the coming year.

Neovascularization Associated with Age-Related Macular Degeneration. Age-related macular degeneration is the leading cause of blindness in patients over the age of 65. While the disease has been recognized for many years, our understanding of the causes and reasons for progression of this disease are still limited. In the later stages of the disease, abnormal blood vessels grow beneath the retina and cause severe vision loss resulting in an inability to drive, read, recognize faces, and perform other visual tasks of day to day living. One of the primary reasons for this dearth of knowledge has been the lack of an appropriate animal model that mirrors the clinical presentations of the disease. Research has indicated that certain proteins involved in growth of blood vessels are elevated in patients and that one growth factor, vascular endothelial growth factor (VEGF), is consistently elevated in patients with abnormal blood vessels.

For the first time, scientists at the National Eye Institute, using a system to manipulate the genetic expression of VEGF have been able to cause rats to develop abnormal blood vessels that are identical in location and appearance to those seen in humans afflicted with the disease. Modeling this condition in animals will provide an invaluable research tool to study the causes and to test treatments for this condition. Because the model takes advantage of a stimulus known to occur in the human condition, a more precise understanding of the trigger factors for the growth of the blood vessels will be gained. Subsequently, these trigger factors can then be manipulated through various therapeutic mechanisms that should be directly applicable to patient care for other diseases in addition to AMD. These studies will continue to be pursued during the next year.

The Genetic Basis of Stargardt Macular Dystrophy. Stargardt macular dystrophy is associated with an inherited progressive loss in central vision. Affected individuals have progressive degeneration of the fovea (a specialized region of the central retina or macula that is rich in a type of cone photoreceptor cells). This disease is associated with mutations in a gene encoding a protein that removes by-products that are produced by the normal response of cone cells to light. Recent studies have demonstrated that this protein is located in cone cells. Mutations in the gene lead to an accumulation of these by-products, leading to degeneration of the cones. These studies may have even greater significance in that the affected gene now appears to play an important role in a number of retinal degenerative diseases. Further studies may suggest ways to prevent or treat this disease more effectively.

Retinal Damage Triggered by Infection. Ocular tissue damage is caused, in part, by the manner in which the host responds to an insult, such as an infection. The protozoan parasite, Toxoplasma gondii, infects millions of humans worldwide. This organism is also the most frequently identified cause of ocular inflammation, and the retinal damage is an important initiator of blindness in young adults. Scientists at the NEI demonstrated in the laboratory that T. gondii infection of specific cells in the retina can cause secretion of molecules that contribute to the damage of ocular tissues. These findings identify key molecules produced by retinal cells in response to infection and suggest therapeutic strategies to prevent retinal tissue damage that can be explored in future studies.

Leber's Congenital Amaurosis. Leber's congenital amaurosis (LCA) is a genetic, early-onset, retinal degeneration that causes blindness in children. No treatment is currently available for LCA. Disease-causing mutations in a gene known as RPE-65 have been linked to an estimated 10% of LCA cases and to some cases of retinitis pigmentosa. Recently, NEI scientists have produced mice lacking the RPE-65 gene. This lack of the RPE-65 gene produces a defect in the visual cycle, a series of biochemical events in the light-sensing retina that initiate vision, resulting in impairment of photoreceptor cell function and retinal degeneration. Using this animal model, other researchers found a way to bypass the defect in the visual cycle by feeding the RPE-65 deficient mice a form of vitamin A called 9-cis-retinal. The effect was dramatic and resulted in improved photoreceptor physiology and function. These studies have opened the door to studies in humans that may contribute to the development of improved treatments. Additionally, this animal model may have broader implications for the study of other retinal degenerative diseases and the search for new treatments.

Visual Proteins. Vision begins when light causes a change in the three-dimensional structure of rhodopsin, which initiates a cascade of events that result in vision. Understanding how the dynamic structure of rhodopsin acts as a trigger in the cascade of events leading to vision has been an important and difficult goal of scientists studying vision and vision loss. NEI-supported researchers have now succeeded in identifying, for the first time and at very high resolution, the three-dimensional structure of rhodopsin. Mutations in the rhodopsin gene are related to many of the cases of retinitis pigmentosa, a group of inherited, blinding, retinal degenerations. This finding is significant because it will help scientists understand how structural changes in rhodopsin initiate the next step in the vision cascade, the activation of a protein known as G-protein. Elucidating the coupling of the rhodopsin receptor with the G-protein may provide a significant new avenue for the development of therapeutics to combat vision loss.

High resolution identification of the three-dimensional structure of rhodopsin also has broader implications for other biological systems besides vision. Rhodopsin is a member of the large class of G-protein-coupled receptors. Instead of responding to light, other receptors respond to stimuli such as hormones, calcium ion levels, or odorants to initiate a biological response. Continuation of this line of research will help explain how these receptors transmit signals and will have important implications for research in many biological systems.

Oxygen Restrictions and Retinopathy of Prematurity. Many premature infants need supplemental oxygen soon after birth because their lungs are not sufficiently mature to efficiently transfer oxygen into their bodies. Researchers have long known that high levels of supplemental oxygen, while helping infants survive, might increase cases of retinopathy of prematurity (ROP). ROP develops in very premature infants when abnormal blood vessels grow and spread throughout the retina, the nerve tissue that lines the back of the eye. The scarring and bleeding caused by the excess growth of these blood vessels can lead to retinal detachment, resulting in vision loss. Recent research had suggested that controlled amounts of supplemental oxygen might actually keep ROP from progressing from moderate to severe stages. In order to test the safety and efficacy of providing infants carefully-regulated supplemental oxygen, the National Eye Institute supported the Supplemental Therapeutic Oxygen for Pre-threshold ROP (STOP-ROP) study. Researchers found that supplemental oxygen given to premature infants with moderate cases of retinopathy of prematurity (ROP) did not improve ROP, but also did not make it worse. The results mean that clinicians do not have to be as restrictive as they have been when giving supplemental oxygen to infants who have already developed moderate ROP.

Corneal Diseases

The cornea is the transparent tissue at the front of the eye that serves two specialized functions. The cornea forms a protective physical barrier that shields the eye from the external environment. It also serves as the main refractive element of the eye, directing incoming light onto the lens. Refraction depends on the cornea acquiring transparency during development and maintaining this transparency throughout adult life. Corneal disease and injuries are the leading cause of visits to eyecare clinicians, and are some of the most painful ocular disorders. In addition, approximately 25 percent of the American population have a refractive error known as myopia or nearsightedness that requires correction to achieve sharp vision (1); many others are far-sighted or have astigmatism.

Cornea.The transparent vertebrate cornea is composed of an external five to six cell thick layer called the epithelium, a thicker stroma containing keratocytes, and a single-layered endothelium. While the physical basis for transparency of the corneal stroma is well studied, much less is known about the optical properties of the corneal epithelium. Interestingly, the corneal epithelium accumulates surprisingly high proportions of just a few proteins, often enzymes. These abundant proteins of the corneal epithelium often differ in different species. For example, NEI intramural investigators recently examined the protein composition of the zebrafish corneal epithelium. A protein called gelsolin was found to comprise approximately 40-50% of the water soluble proteins. Gelsolin is a large protein that regulates the cellular cytoskeleton and has important roles in cellular motility among other processes. The finding that gelsolin is the major soluble protein of the zebrafish corneal epithelial cells suggests a novel role for this protein in vision.

Interestingly, a single-base mutation of the human gelsolin gene has been shown to cause a form of corneal dystrophy, making the high concentration of gelsolin in the zebrafish of great medical interest.

Herpes Simplex Virus Latency and Movement in Nerves. Herpes simplex virus (HSV) is a leading cause of blindness in the US. After initial infection, some nerve cell populations allow the virus to enter a dormant (latent) state that persists for the life of the infected individual. Reactivation of the latent virus occurs periodically and can lead to reappearance and potential spread of virus on the surface of the eye, skin, or other tissues. Repeated cycles of latency-reactivation cause progressive scarring and clouding of the cornea that, in turn, leads to blindness. While survival of HSV in this dormant or latent state obviously requires survival of the host cells, infected cells normally undergo a process called programmed cell death, or apoptosis. Researchers recently discovered that a viral gene expressed during latency, the LAT gene, inhibits programmed cell death in infected nerve cells, thereby providing a host for the latent state.

Other NEI-supported scientists have developed a model of HSV movement in nerves by injecting a known quantity of virus directly into a cluster of nerve cell bodies that allowed researchers to follow the movements of virus during reactivation and spread of the virus. Movement of virus from the nerves to the corneal epithelial cell layers has a distinct pattern: the virus leaves the nerve endings, enters the middle layers of epithelial cells, and then preferentially spreads outward into the tears. Similarly, movement of virus toward the cell body was directly observed and indicated that certain viral components are essential for transport to the nerve cell body and therefore establishment of latency.

Understanding the mechanism of viral latency and reactivation and learning how virus is transported from the corneal epithelium to the nerve cell body or vice versa may lead to treatments that inhibit these processes and prevent recurrent disease and scarring. In future studies researchers will be able to examine the gene products that are essential to viral release from nerves, the genes involved in the spread of virus between the cells of the epithelium, and the transport machinery that mediates these movements. Any or all of these may be investigated as targets for new therapies that would prevent latency-reactivation, spread of the virus, and scarring of the cornea.

Tear Components. The external surface of the eye is covered by a thin tear film that lubricates and protects it from the external environment. Human tears that form this film consist of several proteins that are essential for its maintenance and proper function. Three major proteins are packaged and secreted together by the lacrimal gland that produces tears. One of these proteins, lipocalin, strongly interacts with the other two proteins, as well as with lipids. Scientists are uncovering those structural features of this molecule that confer its capacity to interact with other tear components. Knowledge of the structural basis for tear formation will lead to better strategies to treat dry eye. This debilitating condition often occurs in women as a result of the aging process or as a result of an autoimmune disease known as Sjšgrens syndrome. Because dry eye condition affects millions of people in the United States, future studies to develop better treatments may be important in improving the quality of life for those afflicted.

Lens and Cataract

Cataract, an opacity of the lens of the eye, interferes with vision and is the leading cause of blindness in developing countries. In the U.S., cataract is also a major public health problem. Approximately 1.35 million cataract surgical procedures were performed on Medicare beneficiaries alone in 1991 costing approximately $3.4 billion. (2) Cataract surgery accounts for approximately 12 percent of the entire Medicare Part B budget and is the most commonly performed surgical procedure. (3) The enormous economic burden of cataract will worsen significantly in coming decades as the American population ages. The major goals of this program, therefore, are to determine the causes and mechanisms of cataract formation, to search for ways to slow or prevent the progression of cataract, and to develop and evaluate new diagnostic and therapeutic techniques in cataract management.

Smoking Cessation Reduces Risk of Cataract. Smokers are known to be at increased risk of developing cataracts. A large prospective epidemiologic study following a group of almost 21,000 male physicians for 14 years has determined that those who stop smoking reduce their risk of cataract. At least part of this decreased risk is due to less lifetime cigarette usage, although the investigators provide evidence to suggest that some smoking-related damage to the lens of the eye is reversible. These findings provide additional evidence of the benefits derived from smoking cessation.

Risk Factors for Age-Related Cataract. Visual impairment and blindness from cataract is an important public health problem throughout the world. Most people with severe impairment from cataract are in the developing countries of Asia and Africa where barriers to cataract surgery are greatest. In developed countries, where cataract surgery is widely available, cataracts are a less frequent cause of blindness, but a common cause of visual impairment. In the population-based Baltimore Eye Study and the Salisbury Eye Evaluation Project, cataracts were found to be the leading cause of visual impairment among older adults. The identification of modifiable risk factors or interventions that affect the development of cataract could have a large economic impact and reduce rates of blindness and visual impairment throughout the world.

The Age-Related Eye Disease Study (AREDS), sponsored by the National Eye Institute, is an ongoing multi-center study of the natural history of cataract and AMD. AREDS has been designed in part to search for clues about the etiology of cataract and possible strategies for intervention. Data were collected at entry on a wide range of possible risk factors for cortical and nuclear cataracts, two of the most common types of cataract. Results from the study reinforce a growing consensus that smoking increases the risk of development of nuclear cataract and that higher levels of sunlight exposure increase the risk of cortical cataract. The identification of these potentially modifiable risk factors for cataract reinforces public health recommendations to avoid smoking and decrease exposure to sunlight. This study will continue during the next year.

Glaucoma

Glaucoma is a group of eye disorders which share a distinct type of optic nerve damage that can lead to blindness. Elevated intraocular pressure is frequently, but not always, associated with glaucoma. Glaucoma is a major public health problem and the number one cause of blindness in African Americans. Approximately three million Americans have glaucoma (4), with about half of these unaware that they have the disease. As many as 120,000 are blind from this disease (5). Most of these cases can be attributed to primary open angle glaucoma, an age-related form of the disease. NEI activities in glaucoma research are directed toward understanding the mechanisms of the disease through basic research, identifying risk factors, and preventing blindness.

Vision Loss in Glaucoma. Elevated intraocular pressure (IOP) has been associated with vision loss in glaucoma, but experimental studies have not yet shown definitively that IOP causes glaucoma. Since all current treatments attempt to slow the progressive loss of neurons by reducing intraocular pressure, establishing this relationship would justify the continued use of these therapeutic strategies. Scientists now have evidence that increases in intraocular pressure have a profound effect on ganglion cell survival. Optic nerve fibers from retinal ganglion cells connect to neurons in a part of the brain called the lateral geniculate nucleus (LGN). Neurons from the LGN then relay this information to the visual cortex for processing. Using a primate model of glaucoma, scientists showed that even relatively moderate elevations of intraocular pressure cause loss of LGN neurons over an extended period of time. These data demonstrate that chronic elevation of intraocular pressure has a neurodegenerative effect on neurons critical for the integration and transmission of visual information and point to areas for future research to prevent or treat this damage.

Advanced Imaging Instrumentation for Diagnosis of Eye Diseases. Optical coherence tomography (OCT) is a non-invasive imaging technique, similar to ultrasound, that has a broad range of applications to the diagnosis and management of ocular disease. One of the most advanced application is for optic nerve measurements in glaucoma patients. Ultra-high resolution OCT has been demonstrated to achieve resolution of less than one micrometer, allowing for subcellular imaging of tissues. Imaging of living human cells with a resolution of about 10 micrometers should be possible. Increased imaging precision may allow earlier diagnosis as well as more certain identification of progressive changes that impact sight. Reliable assessment of optic nerve damage has been a long sought goal in glaucoma diagnosis and clinical management. And advanced OCT should become an indispensable tool for glaucoma clinicians.

Strabismus, Amblyopia, and Visual Processing

Developmental disorders such as strabismus (misalignment of the eyes) and amblyopia (commonly known as "lazy eye") affect 2-4 percent of the United States population (6), (7). The correction of strabismus is one of the most frequently-performed surgical procedure. In addition to research relevant to strabismus and amblyopia, the NEI supports investigations of the age-related inability of the lens to focus on nearby objects, irregular eye movements, and refractive errors. Three million Americans now have chronic visual conditions that are not correctable by eye glasses or contact lenses (8). Therefore, the NEI also supports research on improving the quality of life of persons with visual impairments by helping them maximize the use of remaining vision and by devising aids to assist those without useful vision.

Coordinated Eye Movement. Ocular saccades are coordinated movements of the eyes. Saccades occur, for example, when we are reading, watching TV, or scanning the environment. This coordinated movement is accomplished primarily by two pairs of extraocular muscles that are attached to the globe. In visual disorders such as strabismus, the two eyes do not function as a unit and the result is a loss of binocular vision. Surgical and chemical approaches to correcting strabismus act by affecting the extraocular muscles. These treatments are often effective but may have unintended effects. Therefore, a better understanding of the function of the extraocular muscles could lead to improvements in therapy.

An NEI grantee recently developed the "active pulley hypothesis" to explain extraocular eye movement, using Magnetic Resonance Imaging (MRI). Data from normal subjects has permitted a high-resolution picture of the globe and associated extraocular muscle and connective tissue. The data clearly show these muscles have different insertion points, either on the sclera (outer white covering) of the eye or on connective tissue in the orbit or socket of the eye. The identification of this organization of the muscle fibers has important implications for mathematical models of rotation properties in the eye and with further research has the potential to improve surgical approaches to the treatment of strabismus.

Seeing with Rewired Brains. NEI-supported researchers have approached the question of how our brains organize information from our senses during development using an animal model. The approach involves surgically manipulating the sensory nerves that go to sensory centers of the brain. Nerves from the eye are misrouted from their usual target, the primary visual center or visual cortex, to the hearing center or auditory cortex, which has been deprived of its normal auditory input. Work with this model demonstrated that the "rewiring" procedure resulted in the development of a functional visual cortex in a part of the brain that was otherwise destined to become the auditory cortex. In these animals, the rewired visual cortex had the organization that is found in a normally wired visual cortex, and the nerve cells were taken over by the visual input. These experiments suggested that the organization and response characteristics of different regions of the brain can be shaped by the activity of nerve cells arising from the sensory input; in this case visual vs. auditory inputs.

Behavioral studies on rewired animals show that they respond appropriately to visual stimuli arising from the activity of neural circuits in the rewired centers of their brains. These animals "see" with their auditory cortex. These observations suggest that the development of brain organization is dependent on the input activity and that the sources of inputs to the brain play a significant role in determining perception and brain function. Studies of this type give us a better understanding of the development of the brain and its visual center. This information will serve as a foundation for future research on normal development, as well as abnormal development and trauma that can cause visual disorders.

Development of Myopia. About 25% of the adult population of the United States is nearsighted (myopic) (9). In the most serious cases, myopia can lead to retinal detachment, glaucoma, amblyopia, and vision loss. At present there is no definitive treatment or cure for myopia. Corrective lenses and corneal surgeries merely compensate for the condition, and these treatments do not affect the underlying predisposition to myopia. The cost each year to our society for eye examinations and corrective lenses for refractive error is enormous. Animal models have recently contributed two important insights to our understanding of the biological basis of myopia. First, images which are not focused on the retina guide the developing eye to correct for this defocus. Second, changes in the focus of images on the retina cause changes in eye growth directly. Through a cascade of signals from the retina to the sclera, the outer tunic of the eye, the axial length of the eye is changed. One class of retinal interneurons, amacrine cells, appear to mediate the regulatory mechanisms and intercellular signals that control eye growth in response to optical defocus. Additional research identifying the specific factors which control eye growth will have significant implications for preventing or treating myopia.

Low Vision

Assistive Technology for the Visually Impaired. Researchers supported by the NEI have recently created a dual-use assistive network using ordinary fluorescent lights already installed in a building. Through a minor modification to the light ballast, each light continues to perform its primary illumination function while also carrying an encoded signal. There is no additional energy use and no visible flickering or change in the light. The system uses commercial fixtures, so the costs of installation and use are low. The encoded signal can be audio, textual, graphic, or computer-control information. The Talking Lights System provides guidance and way finding information to blind users. Each individual light fixture transmits a unique signal which the user accesses through a hand-held receiver. The receiver decodes the signal and provides audio assistive information about room location and direction of travel. Preliminary trials with individuals who are blind in an office/industrial environment showed that the Talking Lights System was more effective than verbal directions given by a skilled mobility specialist. Research into other assistive technologies will continue during the next year.

Traveling Exhibit on Low Vision.In October 1999 the NEI's National Eye Health Education Program launched the Low Vision Education Program to increase awareness of low vision and its impact on quality of life. This program is directed toward people with low vision, their families and friends, and the health care and service professionals who care for them. As part of this effort, the NEI has developed a mobile exhibit on low vision that is currently traveling to shopping malls and centers throughout the United States. The exhibit consists of five colorful kiosks designed to attract a cross section of the population. It contains an interactive multimedia touchscreen program; provides information on low vision services and resources; and displays aids and devices that help people with low vision. The exhibit and touchscreen program explain the causes of low vision; offer personal accounts of people living with low vision; and provide a self-assessment to help people determine if they or someone they know may have low vision.

Health Disparities

Strategic Plan on Reducing Health Disparities. The NEI's latest strategic plan, Vision Research-A National Plan: 1999-2003, was developed under the auspices of the National Advisory Eye Council. Over 100 experts from all fields of vision research were assembled to make recommendations on research priorities over the period covered by the plan. Among the priorities identified by these experts were several related to health disparities. These priorities included research on glaucoma, diabetic retinopathy, myopia, and health services delivery and use. Recommendations were also made regarding training and attracting minority scientists into vision research. During the review of the strategic plan, the draft was sent to over 50 professional, scientific, or advocacy organizations that support vision research. They were asked to consider whether any important areas of research or specific issues of importance to vision research had been overlooked. The final document reflects the comments and input received during that process.

As part of the NIH effort to produce a strategic plan on reducing health disparities, the NEI developed an extract of the last strategic plan devoted to minority health issues. In this Strategic Plan on Reducing Health Disparities,the background, recent progress, and current research were updated and the areas of research priority and research needs and opportunities related to health disparities that were identified in full strategic plan were highlighted. These areas form the core elements for the NEI Strategic Plan on Reducing Health Disparities. In addition, the NEI's National Eye Health Education Program with its considerable emphasis on minority health issues was emphasized.

Reducing the Risk of Vision Loss from Diabetic Retinopathy. It is important that people with diabetes receive dilated eye exams because early detection and treatment of diabetic eye disease can prevent vision loss. The early detection of diabetic eye disease, as well as laser surgery when needed, has helped preserve vision in about 90 percent of those who might otherwise lose their vision. Researchers have determined that health education programs can substantially increase the rates of dilated eye exams for African Americans with diabetes, the first step in reducing the risk of vision loss. The findings clearly showed that African Americans with diabetes who receive educational messages about the importance of dilated eye exams were more likely to seek an eye exam than those who do not receive those messages.

AIDs-Related Research

Ocular Complications of AIDS. Cytomegalovirus (CMV) retinitis is the most common serious eye complication in patients with AIDS. If untreated, CMV retinitis causes visual impairment, blindness, and diminished quality of life. The NEI continues to support resource centers and participating clinical centers established to assist in developing and evaluating new treatments for the ocular complications of AIDS through its Studies of the Ocular Complications of AIDS and Longitudinal Study of the Complications of AIDS. These studies have already resulted in therapies that can slow or stop the progression of CMV retinitis but unfortunately do not cure it. Additional research is focused on the development of new delivery systems to administer the drugs directly to ocular tissues where they are needed, as well as the testing of new drugs that can be used in these systems.

Research will be expanded on developing a better understanding of the pathogenesis of CMV retinitis not only for identifying effective treatments that arrest the progression of the disease, but also for identifying preventive strategies. Another avenue of this research will investigate the possible mechanisms of retinal and optic nerve impairment due to the accumulation of toxic substances released by the invading virus or the body's own immune system cells that respond to the disease. Because the retina is neural tissue and does not regenerate when damaged by disease or trauma, it is essential that efforts also be directed to developing reliable diagnostic tools to detect the presence of ocular opportunistic infections before they damage the retina and optic nerve.

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New Activities

Small Grants for Pilot Projects. The NEI is developing an initiative to provide support for short-term studies that would generate pilot data for more extensive research. These brief applications would cover all programmatic areas of the NEI, would include both design-driven and hypothesis-driven research, and could include feasibility studies that lack extensive preliminary data. The grants would be for three years, with annual direct costs up to $100,000. They will be reviewed in the NEI Scientific Review Branch using special review guidelines developed for this program.

Collaborative Research Program.The NEI will provide funds to support collaborations of scientists that could merge different scientific disciplines and technologies, share access to services and facilities, and provide a comprehensive approach for applied research on ocular diseases and disorders. Several scientific areas such as gene therapy for retinal degenerations, rehabilitation of low vision, gene therapy for pseudoxanthoma elasticum, and the treatment of diabetic retinopathy have generated approaches that the NEI would like to see move more quickly into clinical trials or applications.

Identification of Genes Expressed in the Visual System. As part of its research activity to identify the genes in the visual system, the NEI convened a group of scientists to establish recommendations for the development of genomic resources needed to facilitate understanding of the normal visual system and its related disorders and diseases. This included vision scientists who have a working knowledge of genome technology and scientists outside the field of vision who have expertise in genome technology and developing genomic resources in non-vision scientific disciplines. The goals of the workshop were to: determine the current status of genomic resources for the visual system in areas such as ESTs, cDNAs, cDNA libraries, microarrays, proteinomics, databases, and informatics; identify genomic resources that are needed for studying the normal and dysfunctional visual system; and develop a set of recommendations based on the identification of genomic resources needed. Many of the recommendations are well underway, including the establishment of a prototype website to house the information collected, so as to be available to all researchers in the vision community.

Healthy People 2010. The Department of Health and Human Service's Healthy People 2010 initiative brings together national, state, and local government agencies; nonprofit, voluntary and professional organizations; businesses; communities; and individuals for the purpose of improving the health of all Americans, eliminating disparities in health, and improving the quality of healthy life. The Healthy People initiative contains 467 objectives within 28 focus areas or chapters. The NEI shares co-lead responsibilities for a combined Vision and Hearing chapter with the National Institute on Deafness and Other Communication Disorders. The Healthy Vision initiative is a direct result of the combined efforts of many of the voluntary and professional organizations concerned about visual health. The initial emphasis for the coming year is focused on the baseline population data needs for the objectives and preliminary planning to ensure achievement of the objectives.

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Innovations in Management and Administration

The rapid translation of advances in the laboratory to applications in the clinic is a very high

priority for the NEI. As a means to this end, the leadership of the institute undertook a reconfiguration of key Institute clinical components. First, the Clinical Director has assumed greater authority and responsibility for supporting NEI clinical research. These activities include: (1) providing for biostatistics support, protocol review and tracking, clinical informatics, data management, quality assurance, and quality control; (2) providing necessary infrastructure, including space, personnel, equipment for ophthalmic examination and evaluation, and ophthalmic photography; (3) overseeing all clinic activities, assuring the highest standards of medical care; and, (4) working with the Scientific Director to provide a rich, nurturing environment for clinical research training and career development. Secondly, the Division of Epidemiology and Biometry was expanded and renamed the Division of Epidemiology and Clinical Research. The Office of the Clinical Director was moved organizationally into this renamed Division. This action should consolidate and focus Institute expertise and resources to foster clinical research activities within the NEI intramural program and encourage collaborative research.

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NEI Budget Policy

The Fiscal Year 2002 budget request for the NEI is $571,126,000, including AIDS, an increase of $60,504,000 and 11.8 percent over the FY 2001 level, and $121,237,000 and 26.9 percent over FY 2000.

A five year history of FTEs and Funding Levels for NEI are shown in the graphs below.

FTEs by Fiscal Year.
d.

Funding Levels by Fiscal Year.
d.

One of NIH's highest priorities is the funding of medical research through research project grants (RPGs). Support for RPGs allows NIH to sustain the scientific momentum of investigator-initiated research while providing new research opportunities. The Fiscal Year 2002 request provides average cost increases for competing RPGs equal to the Biomedical Research and Development Price Index (BRDPI), estimated at 4.3 percent. Noncompeting RPGs will receive increases of 3 percent on average for recurring direct costs. In FY 2002, total RPGs funded will be 1,219 awards, an increase of 65 awards over the FY 2001 Estimate, the highest annual total ever awarded.

Promises for advancement in medical research are dependent on a continuing supply of new investigators with new ideas. In the Fiscal Year 2002 request, NEI will support 257 pre- and postdoctoral trainees in full-time training positions. An increase of 10 percent over Fiscal Year 2001 levels is provided for stipends and training-related expenses (e.g., health insurance, research supplies and equipment, and travel to scientific meetings).

The Fiscal Year 2002 request includes funding for 39 research centers, 201 other research grants, including 3 new clinical career awards, and 31 R&D contracts. The R&D contracts mechanism also includes support for 2 contracts for the Extramural Clinical and Pediatric Loan Repayment Programs.

The FY 2002 budget request includes increased funding within Research Management and Support (RMS) to support essential activities. One such activity is the NEI's traveling exhibit on low vision, part of the National Eye Health Education Program, discussed above. The NEI plans to construct a second exhibit and to incorporate oral and written Spanish language messages within the exhibits. The NEI will produce audio CD ROMs that may be used independent of the exhibit, for example, in doctors' offices and senior citizen centers. Another major area relates to the increase in extramural research activity. The NEI will need funding to manage the rapidly expanding extramural research program, particularly the increasingly complex clinical research grant portfolio. The NEI staff will participate more fully in basic and clinical research projects within NIH, and also with industry and private sector institutions. The NEI must also increase information technology security. In addition, the NEI will use RMS funds to develop baseline population data needs, necessary for addressing the visual health objectives in Healthy People 2010, described earlier. The NEI also plans to publish its very popular minority health brochure in Spanish and to put this information on the NEI internet site. This brochure describes NEI's health disparity activities--highlighting opportunities for minority extramural scientists in the vision research community and also clinical trials that focus on vision disorders that disproportionately affect minority populations.

The mechanism distribution by dollars and percent change are displayed below:

FY 2002 Budget Mechanism
d.

FY 2002 Percentage From Mechanism.
d.

1. Sperduto R, Seigel D, Roberts J, Rowland M: Prevalence of myopia in the United States. Arch Ophthalmol 101(3):405-407, 1983.

2. Steinberg EP, Javitt JC, Sharkey PD, et al: The content and cost of cataract surgery. Arch Ophthalmol 111:1041-1049, 1993.

3. Ellwein LB, Friedlin V, McBean AM, Lee PP: Use of eye care services among the 1991 Medicare population. Ophthalmology 103(11):1732-12743, 1996.

4. Rahmani B, Tielsch J, Katz J, et al: The cause-specific prevalence of visual impairment in an urban population, the Baltimore Eye Survey. Ophthalmology 103(11): 1721-1726, 1996.

5. Kahn HA and Moorhead HB: Statistics on blindness in the model reporting area, 1969-1970. U.S. Department of Health, Education, and Welfare. Public Health Service. Publication No. (NIH)73-427. pp. 120-143.

6. Hillis A, et al: The evolving concept of amblyopia: a challenge to epidemiologists. Am J Epidemiol 118(2):192-205, 1983.

7. Preslan M, Novak A: Baltimore Vision Screening Project. Ophthalmology 103(1):105-109, 1996.

8. Tielsch J, Sommer A, Will K, Katz J, Royall R: Blindness and visual impairment in an American Urban population, the Baltimore Eye Survey. Archives of Ophthalmology 108:286-290, 1990.

9. Sperduto R, Seigel D, Roberts J, Rowland M: Prevalence of myopia in the United States. Arch Ophthalmol 101(3):405-407, 1983.

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April 2001



Department of Health and Human Services NIH, the National Institutes of Health USA.gov