NIH Health Disparities Strategic Plan Fiscal Years 2009-2013

National Eye Institute

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National Eye Institute
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Mission/Vision Statement

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 blind. Inherent in the NEI’s mission is the investigation of normal visual processes and prevention of blindness through public and professional education programs and through the encouragement of regular eye examinations.

NEI will continue to protect and improve the visual health of the Nation by supporting high-quality laboratory and clinical research aimed at increasing our understanding of the eye and visual system and developing the most appropriate and effective means of prevention, treatment, and rehabilitation, and disseminating research findings and information that will promote visual health.

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Strategy for Addressing Health Disparities

NEI is the principal Federal agency concerned with the support of basic and clinical research aimed at the improved prevention, diagnosis, and treatment of eye diseases and visual disorders that cause visual impairment and blindness. Vision research is supported by the NEI through approximately 1600 research grants and training awards made to scientists at more than 250 medical centers, hospitals, universities, and other institutions across the country and around the world. NEI also conducts laboratory and patient-oriented research at its own facilities located on the National Institutes of Health (NIH) campus in Bethesda, Maryland.

The NEI strategic plan, the National Plan for Eye and Vision Research, was developed with input from vision research experts. In addition, the National Eye Health Education Program (NEHEP) Partnership met to review and evaluate progress, identify new critical areas for applied research, and make recommendations regarding the NEHEP. Both the research priorities and NEHEP recommendations were included in the strategic plan. Several of the priority recommendations made by these groups were related to health disparities. They included research on glaucoma, diabetic retinopathy, health services research, and eye health education. Over 60 professional, scientific, or advocacy organizations that support vision research were asked to review the draft plan to ensure that important areas of vision research had not been overlooked. The final plan reflects the comments and input received during that process and can be found on the NEI website at http://www.nei.nih.gov/strategicplanning.

NEI national plan research priorities related to health disparities have been included in this document. In 2010, NEI will be engaging the vision research community to develop a new strategic plan. In a workshop scheduled for October 2010, panels of biomedical scientists and clinicians will establish research priorities for the core programs supported by the NEI, as well as cross-cutting topics in vision research including health disparities in ocular health. The plan will be available for public comment by patients and patient advocate groups prior to final publication. In addition, NEI’s role as lead agency for vision in the Department’s Healthy People 2020 will be highlighted.

An NIH committee developed strict definitions of minority health and health disparities research so that funding levels can be tracked for clinical or basic research related to diseases, conditions, or biological processes that are either exclusively or almost exclusively found in specific minority or health disparities populations. Specific eye diseases and conditions, however, are not found exclusively or nearly exclusively in minority or health disparities populations. Nonetheless, some eye diseases, such as glaucoma, diabetic retinopathy, and cataract, have a greater prevalence in minority populations resulting in increased visual impairment and blindness compared to other populations. A recent study of causes and prevalence of visual impairment suggested that glaucoma and cataract account for over 60 percent of the blindness in black adults in this country.1 The study also found that despite highly effective surgical treatment, cataract causes approximately 50 percent of the bilateral low vision in Blacks, Hispanics, and Whites. By conducting basic and clinical research into these diseases and ensuring that NEI-supported clinical trials have appropriate inclusion of minority populations, NEI and the vision research community are trying to improve treatment of those afflicted, particularly those who have a disproportionate share of the disease burden.

NEI developed a collaborative research network for diabetic retinopathy. This partnership between NEI, academic research scientists, community-based practices, industry, and private research foundations builds research capacity for testing multiple protocols. Because two thirds of this extensive network is comprised of community clinics, it can conduct comparative effectiveness trials in a wide variety of patient populations to obtain information about the full spectrum of diabetic eye diseases. The network also contributes to the training and knowledge of the ophthalmologic community with regard to rigorous clinical trials and to the state-of-the-science in diabetic eye disease. Other disease specialists (ophthalmic and non-ophthalmic) are considering using the diabetic retinopathy network as a model for community-based research collaboration. Finally, creation of this network is consistent with an Institute of Medicine (IOM) recommendation from its 2006 report to address health disparities in community-based participatory research partnerships (Examining the Health Disparities Research Plan of the National Institutes of Health: Unfinished Business).

NEI, through NEHEP, convenes work groups and conducts focus groups and key informant interviews to ensure the sensitivity of its education programs in addressing the needs and perspectives of minority populations. These activities have resulted in culturally appropriate educational materials for the Glaucoma Education Program, the Low Vision Program and the Diabetic Eye Disease Program, which includes American Indian and Alaska Native outreach. The ¡Ojo Con Su Visión Program! (Watch Out for Your Vision) provides Spanish-language outreach on diabetic eye disease, glaucoma, and low vision.

The goal of strengthening the capacity of minority communities is being addressed through NEHEP with their efforts to expand the number of partnership organizations involved in the planning and conduct of its educational and outreach activities. NEI efforts for Healthy People 2020, the Department of Health and Human Services (HHS) health promotion and disease prevention initiative, are also aimed at strengthening the capacity of minority communities. NEI provides leadership to promote health and prevent disease among Americans through management and coordination of the vision objectives in Healthy People 2020, the Nation’s health agenda.

NEI recognizes the importance of strengthening the capacity of community-based organizations by providing seed money to begin or continue vision-related health education projects. NEI has established a Healthy Vision Community Awards Program that is intended to stimulate collaborative community health education initiatives. These awards provide NEI with opportunities to establish partnerships that extend the reach and effectiveness of its work.

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Areas of Emphasis in Research

Area of Emphasis One: Glaucoma

Glaucoma is not a single disease but 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. Most glaucoma is associated with increased eye pressure, known as intraocular pressure (IOP). Glaucoma often begins with a defect in the front (anterior portion) of the eye where fluid, the aqueous humor, circulates to provide nutrients to various tissues. Aqueous humor enters the anterior chamber via the ciliary body epithelium (inflow), bathing the lens, iris, and cornea, and then leaves the eye via the trabecular meshwork and Schlemm’s canal to flow into the venous system (outflow). Normal IOP is maintained by a balance between fluid inflow and outflow. Almost all high IOP glaucomas are associated with defects that interfere with aqueous humor outflow. The consequence of this elevation in IOP is that optic nerve function is compromised. The result is a distinctive optic nerve atrophy, which is characterized by excavation and cupping of the optic nerve, indicating destruction of optic nerve axons.

Rationale and Priority

Primary open-angle glaucoma (POAG) is usually characterized by high IOP believed to arise from a blockage of the aqueous humor outflow through trabecular meshwork in the front of the eye. POAG is the most common glaucoma subtype in the Western world. Among people 70 years of age or older, the prevalence of open-angle glaucoma is 6 percent in Caucasians, 16 percent among African-derived populations, and 3 percent in Asians.2 Alternatively, another form of POAG, normal-tension glaucoma, is characterized by a severe optic neuropathy with IOP within the normal range, albeit often in the high normal range. Both forms of POAG first appear in midlife or later. However, among African-Americans, the disease may begin earlier in middle age. In contrast, juvenile open-angle glaucoma is a primary glaucoma that affects children and young adults. This rare, earlier onset form of glaucoma also is distinguished from POAG by very high IOP. Although there are a number of other forms of glaucoma, the major focus of NEI-supported research remains on POAG because of the public health impact from the large number of affected people.

POAG is a progressive optic neuropathy that, if left untreated, will lead to blindness. If detected, disease progression can frequently be arrested or slowed with medical and surgical treatment. However, without treatment, the disease can result in irreversible blindness. Even though the initially blocked outflow of fluid occurs in the front of the eye, vision loss is caused by damage to the retinal ganglion cells, whose axons form the optic nerve at the back of the eye.

An estimated 60.5 million people worldwide have glaucoma, and it is estimated that by the year 2020, 5.9 million people will be blind as a result.3 Glaucoma is a major public health problem in the United States. The most recent analysis of population-based data from several studies estimated that 2.2 million Americans had glaucoma in 2000, and by the year 2020 this number is expected to increase to nearly 3.4 million.4 Furthermore, the study found that glaucoma is three times more prevalent in African-Americans than in white individuals3 and is the leading cause of blindness in African-Americans.5 Epidemiological studies conducted in the United States and the West Indies have improved the prevalence and incidence estimates of POAG among white and black populations. These studies are strengthened by using definitions of POAG that focus on visual field loss or optic disc damage but not IOP. The Beaver Dam (Wisconsin) Eye Study of nearly 5,000 individuals between the ages of 43 and 84 reported a prevalence rate of 2.1 percent in a predominantly Caucasian sample.6 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.7 The Barbados Eye Study, which studied over 4,000 black Barbadians ages 40 to 84, reported a prevalence rate of 7 percent.8 Thus, these two studies confirmed substantially higher prevalence of POAG in Caribbean Blacks and African-Americans than in Whites. Recent prevalence estimates of POAG in Hispanics indicate rates slightly lower than African-Americans but higher than Whites.3

Although treatments to slow the progression of the disease are available, at least half of those who have glaucoma are not receiving treatment because they are unaware of their condition.9 In some patients, the beneficial effect of the eye drops lessens with time, and advanced glaucoma develops. 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 trabeculectomy surgery.10

Results from three other clinical trials confirmed the value of reducing IOP in patients with ocular hypertension or glaucoma to prevent the onset of glaucoma in the former case and the progression of disease in the latter. The Ocular Hypertension Treatment Study (OHTS) cosponsored by the NEI and National Center for Minority Health Disparities (NCMHD) noted that a 20 percent decrease of IOP produced a 50 percent protective benefit over baseline among those individuals who had elevated IOP without optic disc or visual field deterioration.11 Analysis of the African-American subgroup in the OHTS revealed that daily pressure-lowering eye drops also reduced the development of POAG in African-Americans by almost 50 percent.12 The Early Manifest Glaucoma Trial determined that patients with newly diagnosed glaucoma progressed less often than untreated patients when IOP was reduced at least 20 percent compared with baseline.13 The Collaborative Initial Glaucoma Treatment Study demonstrated that either pharmacological or surgical therapy are equally effective in delaying progression of disease for at least 5 years.14

Analyses of key baseline factors among ocular hypertensive patients enrolled in the OHTS also described a number of risk factors for the development of glaucomatous damage, including IOP, large cup-to-disc ratio, age, and central corneal thickness.15

Genetic studies have identified a dozen glaucoma loci and the cloning of more than a half dozen glaucoma genes.16 New studies involving genome-wide screening are beginning to identify multiple alleles that may play a role in glaucoma. Identification of trabecular meshwork glucocorticoid response/myocilin, optineurin, cytochrome P450 1B1 (CYP1B1), probably play a less prominent role in causing disease but will provide a better understanding of normal eye development and the molecular pathophysiology of glaucoma. Defining roles for these genes with respect to glaucoma should indicate pathways that are disrupted and increase our understanding of the pathology of all forms of glaucoma.

Elevated IOP is frequently associated with glaucoma, and explanations for how axons become damaged are usually based on the mechanical effects of elevated IOP. However, optic nerve damage abnormally high pressures is observed, and conversely, elevated pressure does not necessarily lead to optic nerve damage. Discovering the basis of optic nerve degeneration is essential for developing the next generation of neuroprotective agents as drugs for treating glaucoma. Recent evidence suggests that nitric oxide is directly involved in mediating the degeneration of axons in the optic nerve head.17 Thus, it is possible that antagonists of nitric oxide could form a new class of neuroprotective agents for treating glaucoma.

It is important to develop methods of diagnosis to detect the disease in the early stages, when treatment is most effective in minimizing irreversible vision loss. This is also critical because of the absence of symptoms in the early stages of glaucoma. Most recently, the diagnosis of glaucoma emphasizes the presence of visual field loss and observable characteristic optic nerve damage rather than simple changes of IOP. 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 IOP-lowering medications that can pose a considerable expense and often have side effects. This dilemma can be avoided with a more thorough understanding of the natural history of the disease and whether early treatment can prevent the onset of glaucoma.

Clinical and laboratory research will continue to provide a greater understanding of the normal functions of the ocular tissues involved in glaucoma. Such studies will continue to lead to the introduction of new drugs to reduce IOP, the development of new diagnostic tools, better estimates of disease prevalence and incidence, and the identification of glaucoma genes.

Objective One: Understanding Glaucoma

Elucidate the prevalence, pathophysiology, natural history, and history of intervention results of optic neuropathies such as glaucoma and optic neuritis over the full time course of these diseases and within ethnic subgroups.

Action Plan

Improve our understanding of the nature and course of glaucoma, incorporating studies of comorbidity, natural history, and genetics. Results from the Baltimore Eye Study, the Beaver Dam Eye Study, and the Barbados Eye Study firmly established race as a significant risk factor for POAG. Although disease prevalence differed in the populations studied, all of these studies confirm a substantially higher prevalence of POAG in African-Americans. Furthermore, the rates for blindness due to POAG in African-Americans are six times higher than for the Caucasian population. A recent report estimated the prevalence of glaucoma in Latinos of Mexican ancestry to be higher than Whites at ages older than 65 years3 which could partly account for the high age-specific rates of visual impairment seen in the Los Angeles Latino Eye Study.18 More research is needed to increase our understanding of the nature and course of the disease and to provide new knowledge upon which to base preventive measures or improved treatments.

Two independent, but complimentary, large-scale genotyping efforts with a harmonized definition for POAG are currently underway. The GENEVA (Gene Environment Association) genome-wide association study represents the largest prospective, population-based study sample where blood samples were collected before the first sign of glaucoma. The NEIGHBOR (NEI Glaucoma Human Genetics Collaboration) consortium consists of clinic-based POAG cases and controls drawn from 15 institutions. In parallel, a new whole genome association technique is utilized for genome-wide association study of POAG in African-Americans. This approach, called admixture mapping, takes advantage of the unique genetic structure of admixed populations such as African-Americans, and has recently been used to map genes for complex diseases.

The availability of these diverse datasets with detailed genotype and phenotype information will accelerate the discovery of gene-gene and gene-environment interactions in POAG that are related to gender and to specific population groups. The discovery of the combination of genetic and environment factors that link normal biologic pathways and pathophysiology to POAG could lead to more rational treatments for the disease, and perhaps to lifestyle modification strategies to prevent or delay POAG.

Questions of comorbidity have not been adequately resolved. Studies that sought to investigate the relationship between glaucoma and myopia have yielded ambiguous results. NEI is supporting the International Collaborative Twin Study of Refractive and Glaucoma Endophenotypes to look at genetic factors that play a common role in these conditions. There is also incomplete and equivocal epidemiologic information available on the relationship between glaucoma and vascular disease. The need to examine comorbidity is highlighted by the fact that the rate of hypertension is often 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 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 IOP, advanced age, optic disc abnormalities, and family history of POAG. However, the contribution of 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 measuring ocular blood flow hampers progress in understanding its impact on the survival of retinal neurons and visual function.

Explore differences in biomechanics that may factor into racial differences in glaucoma susceptibility. NEI is funding research exploring racial variations in optic nerve structure and biomechanics among glaucoma patients of African descent who are at increased risk for glaucoma relative to Caucasians with similar intraocular pressures. The results of several randomized prospective trials have identified multiple risk factors associated with the development or progression of glaucoma.19, 20, 21, 22, 23 Across these studies, IOP, age, central corneal thickness (CCT), increased optic disc cupping, and African ancestry are associated with glaucomatous progression. It is important to note that all of these risk factors have a biologically plausible association with either the level of IOP, the severity of disease (visual field loss), or biomechanical properties of the optic nerve head (ONH).24, 25 In all studies that included individuals of African descent, there has been a significant association of these factors with progression of the disease in this population. Analysis of data from the Ocular Hypertension Treatment Study demonstrated that this racial predilection for progression is largely explained by differences in CCT and in the cup-to-disc ratio, a measure of optic nerve structure. In addition to prospective trials in glaucoma and ocular hypertension, both the Baltimore Eye Survey and Salisbury Eye Evaluation Survey demonstrated a higher prevalence of glaucoma in African-Americans despite minimal differences in IOP. Furthermore, the Barbados Eye Study has also demonstrated rapid progression of glaucoma in an Afro-Caribbean population. Taken together, these findings indicate that the eyes of individuals of African descent are more vulnerable to glaucomatous injury at similar levels of IOP than other racial groups. In the African Descent and Glaucoma Evaluation Study, NEI plans to further explore these differences and develop techniques to quantify the biomechanical behavior of the ONH in individuals of African and European descent to determine how this increase in vulnerability to IOP-related injury is mediated in the causality of glaucomatous injury.

Performance Measures

The NEI will continue to support the highest quality research identified through the peer-review process. The NEI research portfolio is evaluated periodically through the strategic planning process to determine whether the needs and opportunities for glaucoma research are being adequately addressed. When necessary to stimulate research areas not adequately addressed in the portfolio, research solicitations in the form of program announcements, requests for proposals, or requests for applications are issued. Research advances in the form of scientific publications are reviewed yearly and assessed for progress in the following areas: adding to the body of knowledge about normal and abnormal biological functions related to glaucoma; developing new or improved approaches for preventing or delaying the onset of glaucoma and associated visual disability; developing new or improved methods for diagnosing glaucoma and related visual disability; and, developing new or improved approaches for treating glaucoma and its related visual disability.

Outcome Measures

The NEI will support research that will build on the knowledge gained from its investment in the highest quality science and translate the findings of this research program to develop new treatments and diagnosis for glaucoma. The outcome of this support should be significant progress towards improving our understanding of the nature and course of glaucoma, incorporating studies of comorbidity, natural history, and genetics.

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Area of Emphasis Two: Health Services Research

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.

Health services also depend on the health delivery capacity. Telemedicine is a new means of health care diagnosis and delivery that has the potential to reduce access disparities in rural, underserved and geographically isolated communities such as American Indian communities. Research is needed to compare the feasibility, safety, and effectiveness of telemedicine with standard care.

Rationale and Priority

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.26, 27, 28, 29

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, translational research methods, decision and utility analytic methods, health economics, traditional epidemiologic methods, and randomized clinical trials, including comparative effectiveness research. The selection of design methodology should be scientifically justified as appropriate for the research objectives of a given study.

In 2007, NEI engaged the ocular epidemiology research community in a strategic planning effort. Epidemiologic techniques in diverse groups of people has advanced our understanding of infectious, environmental, behavioral, and sociocultural factors that underlie disease incidence, progression, and outcome, and has produced the evidence for effective prevention and treatment strategies. Epidemiological findings inform social science researchers who contribute to developing improved strategies for public health interventions. Recently epidemiological studies are enhanced by applying genetic and molecular biological tools in the context of populations. Combined with behavioral, environmental, and social factors, these tools broaden the potential contribution of epidemiology to our understanding of the major blinding diseases. The epidemiological goals that relate to health disparities are included in this plan.

Quality-of-life assessments have been incorporated into the design of several NEI-funded epidemiologic studies and clinical trials and are considered important 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 information.

The NEI and NCMHD supported 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 have conducted in-depth interviews with study participants on their medical and ophthalmic histories, use of medications, tobacco and alcohol consumption, and utilization of health care services. Because so little is known about the visual health needs of this segment of the population, the data collected from this study have been instrumental in determining the prevalence of cataract, glaucoma, age-related macular degeneration, and diabetic retinopathy among Latinos in this community. The study is also determining the proportion of blindness and visual impairment that is caused by these diseases, and will explore the association of various risk factors, such as smoking or sun exposure with ocular