- Areas of Focus
The National Eye Institute’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.
For this Strategic Plan on Reducing Health Disparities the background, recent progress, and current research were updated. The areas of research priority and research needs and opportunities related to health disparities that identified in full strategic plan were extracted. 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 and its activities as a co-lead agency for the new focus area on Vision and Hearing in the Department’s Healthy People 2010 are highlighted.
Future strategic plans for reducing health disparities will be integrated into the formal planning process the NEI has used over the past 25 years. However, additional emphasis will be given by highlighting health disparities as a specific focus area within the overall institute strategic plan. By creating a focus area for reducing health disparities, all research and policy issues can be considered together rather than within each programmatic area, thereby facilitating the development of recommendations that cut across the formal NEI programs.
Congress established the National Eye Institute (NEI) in 1968 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 individuals who are visually impaired. Inherent in the NEI’s mission is the investigation of normal visual processes and health information dissemination activities to conduct activities related to the prevention of blindness through public and professional education programs and through the encouragement of regular eye examinations.
Areas of Focus
Advance understanding of the development and progression of disease that contributes to health disparities.
Introduction. Glaucoma is not a single disease but rather a heterogeneous group of disorders that share a distinct type of optic nerve damage that can lead to blindness caused by the death of retinal ganglion cells. These diseases involve several tissues in the front and back of the eye. Commonly, but not always, glaucoma begins with a defect in the front of the eye. Fluid in the anterior portion of the eye, the aqueous humor, forms a circulatory system that brings nutrients and supplies to various tissues. Aqueous humor enters the anterior chamber via the ciliary body epithelium (inflow), flows through the anterior segment bathing the lens, iris, and cornea, and then leaves the eye via specialized tissues known as the trabecular meshwork and Schlemm’s canal to flow into the venous system. Intraocular pressure is maintained by a balance between fluid secretion and fluid outflow. Almost all glaucomas are associated with defects that interfere with aqueous humor outflow and, hence, lead to a rise in intraocular pressure. The consequence of this impairment in outflow and elevation in intraocular pressure is that optic nerve function is compromised. The result is a distinctive optic nerve atrophy, which clinically is characterized by excavation and cupping of the optic nerve, indicative of loss of optic nerve axons.
Primary open-angle glaucoma, the most common form of the disease, is characterized by relatively high intraocular pressures believed to arise from a blockage of the outflow drainage channel or trabecular meshwork in the front of the eye. However, another form of primary open-angle glaucoma, normal-tension glaucoma, is characterized by a severe optic neuropathy in the absence of abnormally high intraocular pressure. Patients with normal-tension glaucoma have pressures within the normal range, albeit often in the high normal range. Both these forms of primary open-angle glaucoma are considered to be late-onset diseases in that, clinically, the disease first presents itself around midlife or later. However, among African-Americans, the disease may begin earlier than middle age. In contrast, juvenile open-angle glaucoma is a primary glaucoma that affects children and young adults. Clinically, this rare form of glaucoma is distinguished from primary open-angle glaucoma not only by its earlier onset but also by the very high intraocular pressure associated with this disease. Although there are a number of other forms of glaucoma, the major focus of NEI supported research remains on primary open-angle glaucoma, because of the large number of people affected and its public health impact.
Background. Primary open-angle glaucoma can be insidious. The disease is manifest as a progressive optic neuropathy that, if left untreated, leads to blindness. It usually begins in midlife and progresses slowly but relentlessly. If detected, disease progression can frequently be arrested or slowed with medical and surgical treatment. However, without treatment, the disease can result in absolute irreversible blindness. Even though the initial site is believed to occur in the outflow drainage channels at the front of the eye, vision loss from primary open-angle glaucoma is the result of damage to the retinal ganglion cells, whose axons form the optic nerve at the back of the eye.
An estimated 66.8 million people worldwide will have glaucoma in 2000 and nearly 6.7 million will be bilaterally blind as a result.1 Glaucoma is a major public health problem in this country, as well. It is estimated that as many as 3 million Americans2 have the disease and as many as 120,0003 are blind. Furthermore, it is the number one cause of blindness in African-Americans.4 Epidemiological studies conducted in the United States and the West Indies have improved the prevalence and incidence estimates of primary open-angle glaucoma among white and black populations. One strength of these studies is the adoption of more inclusive definitions of primary open-angle glaucoma that require the presence of visual field loss or optic disc damage, but do not necessarily require the presence of elevated intraocular pressure. The Beaver Dam (Wisconsin) Eye Study, which studied nearly 5,000 individuals between the ages of 43 and 84, reported a prevalence rate of 2.1 percent in a predominantly Caucasian sample.5 The Baltimore Eye Study, with over 5,000 participants age 40 and older, reported a prevalence rate of 1.7 percent among Caucasian Americans and 5.6 percent among African-Americans.6 The Barbados Eye Study, which studied over 4,000 black Barbadians ages 40 to 84, reported a prevalence rate of 7 percent.7 The Barbados Eye Study and the Baltimore Eye Study confirm a substantially higher prevalence of primary open-angle glaucoma in Caribbean blacks and African-Americans than in whites.
Recent Progress. Treatments to slow the progression of the disease are available; however, at least half of those who have glaucoma are not receiving treatment because they are unaware of their condition.8 Glaucoma is three to four times as common in blacks as in whites, and blindness from glaucoma is six times as common in blacks than in whites. In its early stages, glaucoma is usually treated with drugs in daily eye drops. In some patients, the beneficial effect of the eye drops lessens with time, and “advanced glaucoma” develops. Recent findings from the NEI-supported Advanced Glaucoma Intervention Study suggest that black and white patients with advanced glaucoma respond differently to two surgical treatments for the disease. Although both groups benefit from treatment, scientists found that blacks with advanced glaucoma benefit more from a regimen that begins with laser surgery, while whites benefit more from one that begins with an operation called a trabeculectomy.9
In an effort to understand the genetics of susceptibility to open-angle glaucoma, scientists have been actively pursuing genes responsible for minor forms of the disease that have clear patterns of inheritance. Presently, ten glaucoma loci have been identified and five of the genes are cloned. A major advance came with the cloning of the gene linked to juvenile glaucoma on chromosome 1. This gene, GLC1A, encodes a protein, which is expressed in a tissue involved in the maintenance of intraocular pressure. Two genes for congenital glaucoma syndromes have been isolated and a third has been mapped to chromosome 1. Three distinct loci associated with Reiger’s syndrome, a congenital syndrome that includes glaucoma, have been mapped, and one of these has been cloned. Also, the gene for Nail-Patella syndrome, another congenital disorder associated with glaucoma, has been cloned. Other loci mapped include one linked to pigment dispersion glaucoma and two for rare forms of adult onset POAG. Defining roles for these genes with respect to glaucoma should indicate pathways that are disrupted and thereby, help increase our understanding of the pathology of all forms of glaucoma.
Progress has also been made in the development of new pharmacological agents that might protect axons from damage due to glaucoma. Elevated intraocular pressure is frequently associated with glaucoma and explanations for how axons become damaged are usually based on the mechanical effects of elevated intraocular pressure. However, optic nerve damage can occur without abnormally high pressures and conversely, elevated pressure does not necessarily lead to optic nerve damage. Discovering the basis of optic nerve degeneration is essential for the development of the next generation of glaucoma drugs, neuroprotective agents. Scientists now have evidence that the molecule nitric oxide (NO) is directly involved in mediating the degeneration of axons in the optic nerve head.10 Research is now being aimed at identifying and developing neuroprotective agents as a new class of glaucoma drugs.
Current Research. An important aim of current research is to develop methods of early diagnosis to detect the disease in the early stages, when treatment is most effective in minimizing irreversible vision loss. This is made more critical by the apparent absence of symptoms in the early stages of glaucoma. Because elevated intraocular pressure is not always accompanied by pathology, nor does elevated intraocular pressure always lead to optic neuropathy, the diagnosis of glaucoma now emphasizes the presence of visual field loss and observable characteristic optic nerve damage. Individuals with ocular hypertension present a unique dilemma for clinicians. In the absence of any overt pathology, clinicians must decide whether or not to treat these individuals with intraocular pressure-lowering medications that can pose a considerable expense and often have side effects. This dilemma can be avoided with more through gaining an understanding of the natural history of the disease and whether early treatment can prevent the onset of glaucoma.
In its early stages, glaucoma is usually treated with drugs in daily eye drops. In some patients, the beneficial effect of the eye drops lessens with time, and “advanced glaucoma” develops. However, the role of topical medications in preventing or delaying sight-threatening damage to the eye from glaucoma remains unclear. In order to evaluate the safety and efficacy of topical ocular hypotensive medications in preventing or delaying damage to the optic nerve and loss of vision from primary open angle glaucoma, the NEI has funded the Ocular Hypertension Treatment Study (OHTS). The OHTS is designed to determine the potential benefit of treatment with ocular hypotensive medications in preventing or delaying damage to the eye from glaucoma. Additionally, the high percentage of African Americans participating will also ensure adequate evaluation of the effectiveness of topical medication in treating African Americans with glaucoma as the study progresses toward conclusion in the coming years.11
Because characteristic visual field changes in glaucoma patients are due to degeneration of retinal ganglion cells, clinical progress goes hand-in-hand with progress in understanding how retinal ganglion cell loss occurs and the role played by elevated intraocular pressure in this process. Clinical and laboratory research will continue to provide a greater understanding of the normal functions of the ocular tissues involved in the disease. Such studies have already led and will continue lead to the introduction of a variety of new drugs to reduce intraocular pressure, the development of new diagnostic tools, better estimates of disease prevalence and incidence, and the identification of glaucoma genes.
Research Goal. Develop improved measures to aid clinical diagnosis of glaucoma; monitor progression of disease and treatment effectiveness; and elucidate the pathophysiology and natural history of the disease.
Glaucoma Initiative: Improve our understanding of the nature and course of glaucoma, incorporating studies of comorbidity, natural history, and genetics, with special emphasis on Hispanic, Native American, and African-American populations.
Results from the Baltimore Eye Study, the Beaver Dam Eye Study, and the Barbados Eye Study have firmly established race as a significant risk factor for primary open-angle glaucoma. Though there is variation in estimates that reflects the different populations studied, all of these studies confirm a substantially higher prevalence of primary open-angle glaucoma in blacks. Furthermore, the rates for blindness due to primary open-angle glaucoma in African-Americans are six times higher than the rates for the Caucasian population, reflecting not only an increased rate of the disease but also more severe disease. Other ethnic and racial groups have been studied less rigorously. There is a dearth of information about the prevalence and incidence of glaucoma in Hispanic and Native American populations; therefore, studies need to be initiated in these populations to obtain this critical information.
Questions of comorbidity have not been adequately resolved. Studies that sought to investigate the relationship between glaucoma and myopia have yielded ambiguous results. There is also incomplete and equivocal epidemiologic information available on the relationship between glaucoma and vascular disease. The need to resolve the question of comorbidity is highlighted by the fact that the rate of hypertension is high in minority populations.
Risk factors for glaucoma need to be identified and verified. The question of whether there are susceptibility genes that can affect the course of the disease, especially in regard to ethnic and racial differences, is being actively pursued. With advances in genetics, environmental effects also need to be understood so that researchers can better determine the interaction of genetics and environment in the natural history of this disease. Currently, important known risk factors for glaucoma include elevated intraocular pressure, advanced age, optic disc abnormalities, and family history of primary open-angle glaucoma. However, the contribution each of these known risk factors to the progression of glaucoma is unknown. Questions remain concerning whether or not a compromised vascular system contributes to glaucomatous pathology. The difficulty of adequately measuring ocular blood flow hampers progress in understanding its impact on the survival of retinal neurons and visual function.
The large number of gaps in knowledge about the nature and course of glaucoma point to the need for rigorous epidemiologic studies. Well-designed studies that use systematically selected sample sizes (from census tract data, for example) have high rates of participation by the study sample, and use standard procedures for assessing disease and measuring risk factors needed to address these issues. There is also a critical need for better population-based screening procedures that are simple, inexpensive, portable, and effective. Developing such methods will be useful for testing populations that historically have limited access to formal healthcare systems, for determining more accurately the incidence and prevalence of glaucoma in epidemiologic studies, and for screening large populations in remote regions of the world.
Introduction. Myopia, or nearsightedness, is a common condition in which images of distant objects are focused in front of, instead of on, the retina, usually because the eye is too long. More than 30 years ago, scientists found that raising a variety of animals with a closed eyelid led to the development of myopia, because the eye became elongated. Similar observations were made in human infants in which trauma or some other disorder resulted in neonatal eyelid closure. Over the next three decades a clearer picture of some of the processes involved in the control of refractive error in growing eyes has emerged.
Background. Myopia occurs in approximately 25 percent of the population of the United States.12 Myopia is an important public health problem, which entails substantial societal and personal costs. It is highly prevalent in our society and even more frequent in Asian countries; furthermore, its prevalence may be increasing over time. The most common form of myopia is childhood myopia, which begins after age 6 and progresses rapidly until age 16. Myopia progression results from excessive growth of the eye, primarily by enlargement of the vitreous chamber. Excessive elongation of the eye is a major risk factor for retinal detachment. A clinical study of myopia in first and second generation Hispanic, white, Asian, and black immigrant students in this country demonstrated that Asian immigrants have a significantly higher prevalence of myopia.12 Increased prevalence of myopia among Alaskan Eskimos and some American Indian Tribes has also been reported.13,14
High myopia contributes to significant loss of vision and blindness. At present, the mechanisms involved in the etiology of myopia are unclear, and there is no way to prevent the condition. Current methods of correction require lifelong use of lenses or surgical treatment, which is expensive and may lead to complications.
Recent Progress. After extensive argument about whether to attribute myopia to visual factors or genetic factors, experimentation on animals in the past two decades has provided a clearer, but as yet incomplete, picture of some of the processes involved in the control of refractive error in growing eyes. Two insights are especially important. First, images not focused on the retina guide the developing eye to correct for this defocus. Thus, animals with either hyperopia (farsightedness) or myopia imposed by spectacle lenses alter the shape of their eyes to bring the images back into focus. Second, changes in focus of images on the retina can cause changes in eye growth directly by a cascade of chemical signals from the retina to the sclera. Thus, in animals, normal refractive development and myopia of moderate severity may involve a visual feedback mechanism that controls eye growth. Recent evidence that this feedback occurs in primates suggests that these discoveries have substantial practical implications for the clinical treatment of myopia and other refractive disorders in humans, affording opportunities for testing this hypothesis in clinical trials.
Current Research: The NEI is currently conducting a number of studies designed to provide more information on the development and prevention or treatment of myopia. One such study is the Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error (CLEERE) Study. It is a multi-center, observational investigation of ocular development and refractive error development in schoolchildren. It adds three clinical centers to the Orinda Longitudinal Study of Myopia (OLSM), begun in 1989, specifically to describe normal ocular growth in children ages 6 to 14 years, and to develop the ability to predict juvenile onset myopia before it is clinically evident. In addition to the more than 1,300 predominantly Caucasian children enrolled in the OLSM, three additional clinical sites enroll African-American, Hispanic, and Asian children. The children are examined annually for at least four years.
Another ongoing study is the Correction of Myopia Evaluation Trial (COMET), a multicenter, randomized, double-masked clinical trial designed to evaluate whether progressive addition lenses slow the progression of juvenile-onset myopia as compared with single vision lenses. The primary outcome of the study is progression of myopia, defined as the magnitude of the change relative to baseline in. The secondary outcome of the study is axial length measured by A-scan ultrasonography.
In a similar study being conducted in Oklahoma, the hypothesis that correction with bifocal spectacle lenses rather than single-vision lenses will slow the progression of myopia in children with near-point esophoria will be tested. The primary outcome variable is refraction as measured with an automated refractor. Axial length is measured with ultrasound in order to test the corollary hypothesis that use of bifocals will slow ocular growth in these myopic children. We will also examine the amount of close work performed by subjects and the degree of parental myopia as factors that may influence myopia progression.
Research Goal. Determine the etiology of human myopia and identify the risk factors associated with this and other refractive errors so as to prevent their occurrence or progression.
Myopia Initiative 1: Identify the visual error signals that govern eye growth during correction for refractive error.
In animal models, it is now accepted that visual circumstances can influence refractive error, and that this influence involves modification of the growth of the eye. Thus, a feedback mechanism is at work in ocular growth–visual input influences growth, which in turn modifies the visual input. Importantly, the influence of vision on growth can be communicated directly from the retina to the sclera without involvement of the brain. This view of the mechanisms of refractive adjustments has provoked a search for the visual cues the retina uses to discern whether to accelerate or retard the axial growth of the eye and for the signals, presumably chemical, by which the retina communicates to the sclera the appropriate direction of growth. The most provocative candidates are dopamine and acetylcholine because agonists and antagonists, respectively, reduce form-deprivation myopia in both birds and primates.
Myopia Initiative 2: Identify human risk factors for myopia and abnormal eye growth and evaluate promising treatments for preventing the onset of or slowing the progression of myopia, such as special spectacles or contact lenses or pharmacological treatments.
As knowledge of the underlying mechanisms that control eye growth and refractive compensation increases, the ability to assess the risk factors that predict the development of myopia in children or adults has increased as well. Reading is the most established risk factor for myopia. More recent observations have strengthened the association of the amount of near work with the rate of myopic progression.
Because the sharpness of the image during reading depends on the precision of accommodation, it is significant that myopic children have poorer accommodation than others. Additional research is needed into how accommodation and convergence are related to myopia. Researchers have also long suspected that genetic factors play a role in the cause of myopia. The evidence is especially strong in the case of pathological myopia (myopia of high degree). Refractive errors of monozygotic twins are more closely aligned than they are for dizygotic twins. A greater prevalence of myopia exists among the children of myopic parents than among the children of nonmyopic parents. Recent studies of the eye in infancy have also shown that the seeds of myopia may appear early in development. Longitudinal studies of refractive error have suggested that some myopic children may have previously been myopic as infants.
To make the transition from animal studies to clinical studies, there is a pressing need to determine how similar the biological mechanisms of eye growth are in different species, and how similar experimental models of myopia (by visual deprivation or the imposition of hyperopia by spectacle lenses) are to the myopia that develops in schoolchildren. Enough is presently known to begin to evaluate promising treatments for preventing the onset or slowing the progression of myopia and systematically investigate the risk factors associated with the development of myopia.
Introduction. To understand the impact of eye disease and visual impairment on the Nation’s health, data are needed on the number and characteristics of people with various eye conditions, the effects of these conditions on quality of life, and the economic burden of these conditions. This information will serve to increase public awareness of the personal and societal costs of visual impairment and be useful to those who are interested in allocating adequate resources to Americans most in need of vision care services.
Background. To advance understanding of these issues, the National Eye Institute (NEI) devoted a section to health services research in its strategic plan, Vision Research-A National Plan: 1999-2003. The NEI defines the field of health services research broadly to include such diverse topics as: increasing patient access to and utilization of vision care services, improving the delivery of vision services by eye care professionals, and measuring the visual health of patients receiving eye care services. Various studies have demonstrated the need to ensure patient access and utilization of vision care services particularly where treatments are available to improve or preserve vision. In blacks under treatment has been reported for cataract, diabetic retinopathy, and glaucoma.15,16,17,18
A number of different scientific methodologies are used in conducting health services research projects. These include but are not limited to: clinical outcomes research of new or existing data survey research techniques, transnational research methods, decision and utility analytic methods, health economics, traditional epidemiologic methods, and randomized clinical trials. The selection of design methodology should be scientifically justified as appropriate for the research objectives of a given study.
Recent Progress. Quality-of-life assessments have been incorporated into the design of several NEI-funded epidemiologic studies and clinical trials, therein recognizing that a patient’s quality of life is an important facet to consider in assessing visual health. In response to the need to more completely understand the impact of clinical interventions specifically on vision-related quality of life from a patient perspective, the NEI fostered the development and testing of a questionnaire, the NEI-Visual Functioning Questionnaire (NEI-VFQ), to collect this important information.
Findings from recent studies have shown that the majority of people having cataract extraction surgery subsequently report substantial improvement in their ability to see and to perform common, necessary, daily activities.
Numerous studies have reported that a large number of people who have diabetes do not obtain an annual dilated eye examination. Currently funded projects are attempting to identify specific reasons why the medical system is failing to reach this population at increased risk of visual impairment. Other studies are testing specific interventions geared toward the patient or the eye care provider to increase the rates of ophthalmic screening among people with diabetes.
Current Research. The NEI is currently supporting the Ophthalmic Complications Prevention Trial designed to evaluate the efficacy of an inexpensive educational intervention to promote annual ophthalmic screening among low-income Black women with diabetes.
Another study entitled Why Preventable Blindness Occurs in Diabetes is attempting to learn why the current health care system is unsuccessful in preventing blindness from diabetic retinopathy, a disease for which effective treatment is available.
The NEI is also supporting a study to develop, implement, and evaluate a comprehensive culture-specific and community-based education program for the prevention of eye disease in diabetic Oklahoma Indians.
The Diabetic Retinopathy Awareness program is seeking to control visual loss from diabetic retinopathy in the community by evaluating various methods of increasing the use of ophthalmology services among people with diabetes.
The NEI is supporting a major research project in Los Angeles County, California, the Los Angeles Latino Eye Study, to gain a greater understanding of the prevalence and incidence of eye disease among Latinos. Researchers a