also address new opportunities that have been created by recent technological advances in molecular biology and immunology for progress against some of the more perplexing eye diseases.

NUMBER OF RESEARCHERS SUPPORTED

Question. We often get caught up in looking at the number of grants funded, the number of centers funded and the other mechanisms. A more useful measure might be the number of scientists that we support. Has your Institute made an effort to calculate and track the number of scientists that are supported by your funding?

Answer. The Vision Research Program Planning Subcommittee of the National Advisory Eye Council hosted a Policy Planning Forum in August 1989. One of the action items arising from that meeting was a recommendation that a study be conducted to determine trends in NEI research project grants costs and in other grant-related data. Such a study was undertaken and designed to provide baseline information upon which Council funding recommendations and policies could be based. One of the areas selected for study was the size and composition of the research teams funded on NEI research project grants. The results of the study will be published later this year as part of Vision Research A National Plan: 1992-1996. The report will indicate that between 1985 and 1989 there was little change in the total level of staff effort per grant. However, there were definite changes over that time in the staffing patterns of the research team. For example, while there was little, if any, change in the level of efforts of principal investigators, there was an increase in the total level of doctoral-level staff effort per grant, and a decrease in the efforts of research technicians.

Question. Do you think this measure should be implemented NIH-wide so that the Congress and the public would know the number of scientists which are being supported by our research dollars?

Answer. The National Advisory Eye Council has recommended that it is important to examine all mechanisms of research support, not just research project grants, in assessing the overall health of the NIH-supported biomedical enterprise. The Council has stated that other, more broad, indicators of program performance are needed, including the total number and efforts of scientists supported by these diverse mechanisms. In this regard, the NIH has begun, in response to a request in the FY 1992 OMB Passback, an evaluation of the staffing patterns on research project grants. The NEI is participating fully in this data collection effort.

CONTROLLING COSTS

Question. Dr. Kupfer, the average cost of research project grants funded by your Institute has remained well below the NIHwide average for the last 10 years. One of the ways NEI has done this is to not award large program project grants. Your Institute has also been very successful in funding a large percentage of grant applications by holding down costs. As you know, the Congress is considering NIH's Cost Control Plan. Would you care to make any comments on the Plan?

Answer. The NEI has contributed to the development of this plan, and fully supports its objectives. The National Advisory Eye Council and vision research scientists had an opportunity to comment on earlier drafts of the plan and to make recommendations for its improvement. The Council views the Congressional call to action in a very positive way. It finds this approach, when combined with a strategic research planning initiative to address the burgeoning opportunities in biomedical research, fully consistent with its own extensive program planning efforts for vision research.

Question. The entire scientific community very closely watches the number of new grants that are funded each year as a measure of progress being made. Is this the correct measure to follow or should we instead follow the number of scientists who are funded each year as a better indicator of Congressional support of biomedical research?

Answer. The number of new grants funded each year is

certainly important. However, there are other performance measures that seem to me to be even more important. The total number of grants funded (competing and noncompeting) is one such measure. The total number of doctoral-level scientists supported through all mechanisms of grant and contract support, not just research project grants, would seem to be another very important measure. Another useful measure of the overall strength of federally funded biomedical research might be the resources (in constant dollars) available for research per principal investigator or full-time doctoral level scientist. I am sure that there are other measures that need to be explored, and I think that the NIH plan has indicated that this will be done.

THE OLDEST OLD

Question. Americans age 85 and older (the oldest old) is the fastest growing age segment of the population, and it is felt by some that this group may grow more rapidly than official estimates. Along with this increased longevity comes a decline in vision. What accounts for this correlation?

Answer. Glaucoma, cataract, and age-related macular degeneration are all eye diseases that become more prevalent with advancing age. We remain uncertain, however, as to what specific factors are responsible for the association of age with the development of these chronic eye diseases. We also know that the development of these eye disorders is not solely explained by the aging process. Cigarette smoking, diet, sunlight exposure, diabetes, hypertension, and family history have been shown to be important etiologic factors in the development and progression of these blinding eye diseases in certain populations.

Question. What special initiatives are underway or planned at your Institute to address this concern?

Answer. The NEI has supported a study, conducted in more than thirty nursing homes in the Baltimore area, of the prevalence of ocular diseases in a nursing home population. Information on this population is extremely important in determining its need for eye care and to determine the extent and severity of ocular disorders

in this oldest of the old age group. A clinical trial to evaluate the effect of vitamins and mineral supplements on the development and progression of cataracts and age-related macular degeneration in an older population is being planned. The NEI has placed a high priority on epidemiologic studies to identify specific risk factors for the development of glaucoma and cataract with the hope that the information obtained will hasten the development of trials of the early treatment of these diseases, before they cause severe visual impairment.

PREVENTION

Question. What is your Institute doing in the area of prevention regarding eye diseases?

Answer. The National Eye Institute currently supports a variety of prevention and prevention-related studies. These studies include those directed at the prevention of: hereditary and developmental degenerations of the retina, diabetic retinopathy, retinopathy of prematurity, uveitis and other ocular inflammations, corneal infection from herpes simplex virus, cataract, trachoma, amblyopia and strabismus, eye diseases related to nutritional deficiencies, macular diseases, visual impairment from corneal burns and ulcers, nearsightedness and other refractive errors, and glaucoma.

During the past year the results from two years of patient followup have been released from one of these studies, the Glaucoma Laser Trial (GLT). In primary open-angle glaucoma, minute changes within the eye gradually interfere with the flow of fluids that nourish the tissues in the front of the eye. If these fluids fail to drain properly, the resulting increased pressure inside the eye can eventually damage the optic nerve and cause vision loss or blindness. Treatment for primary open-angle may involve the use of eyedrops or pills that improve fluid drainage or slow fluid formation. Unfortunately, these medications can produce annoying and sometimes serious side effects. If medications fail, argon laser surgery may be required to create a tiny hole in the coat of the eye or to treat the drainage tissue directly.

The GLT is a randomized clinical trial designed to evaluate the relative efficacy of drug and laser treatment either alone or in combination, and to determine whether laser treatment is a safe and effective alternative to eyedrops as a first treatment for patients with newly diagnosed open-angle glaucoma. After two years of followup, laser treatment alone was sufficient to control pressure in 44 percent of the eyes, compared to 30 percent of the eyes treated with the anti-glaucoma medication alone. In eyes receiving laser alone or laser followed by medication, the intraocular pressure could be controlled in 70 percent of the eyes treated. In addition, eyes first treated with laser generally required less medication to control pressure than those receiving medication alone.

These results suggest that argon laser therapy may be a safe and effective alternative to eyedrops as a first treatment for patients with newly diagnosed open-angle glaucoma. Although these early results for laser treatment look promising for preventing the progression of open-angle glaucoma and its ensuing loss of vision,

eye care specialists need to await longer-term results of the GLT Follow-up study in their overall evaluation of these forms of treatment for their glaucoma patients.

HEREDITY FACTORS IN EYE DISEASES

Question. Would you please elaborate on heredity factors in eye diseases?

Answer. Of the approximately 2,000 known human genetic disorders, an estimated 30 percent affect the eye. Hereditary and congenital diseases are the cause of blindness in one of every five blind people in this country and an additional 300,000 suffer from visual impairment from these causes. Because such visual

impairment often begins early in life, the economic, social and personal costs are substantial.

Retinitis pigmentosa, a degenerative disease of the retina, is the most common cause of inherited blindness and affects approximately 100,000 people in the United States and countless others around the world. The incidence has been estimated to be approximately 1 in 3,500 births, and all social, ethnic, and racial groups are affected. Recent progress has been made in locating the gene responsible for one form of this disease, autosomal dominant retinitis pigmentosa (ADRP).

Patients with ADRP have been shown to have a mutation in the gene that produces rhodopsin, a light-sensitive protein that initiates the conversion of light energy into visual signals in the retina. The finding of this defective gene provides a focus for studies of the mechanisms that lead to blindness in ADRP and may ultimately provide a means of preventing this devastating disease.

OLDER PEOPLE AND VITAMINS

Question. A recent article in the New York Times indicated that older people who consume large amounts of vitamins by eating lots of fruits and vegetables or by taking daily supplements appear to have a lower risk of developing cataracts. Could you comment on this research?

Answer. Yes, that study was conducted by an NEI-supported scientist. This article described an observational, case-control study in which cataract patients were compared to cataract-free individuals with regard to nutritional and other factors, such as medical history, sociodemographic characteristics, and lifestyle. This study provided evidence of an association between the regular use of multi-vitamin supplements and a decreased risk for the development of cataract. Given the prevalence of cataract, even a modest decrease in cataract risk has major public health implications. From this viewpoint, the delineation of risk factors amenable to modification or intervention is most interesting. However, in studies of this type, cause and effect cannot be determined. Associations reported from such case-control studies need to be confirmed and evaluated in other types of research designs. Because reducing cataract risk would have major implications, future studies, such as longitudinal studies, are needed to confirm and evaluate the potentially modifiable factors suggested by the case-control study reported in the New York Times.

RESEARCH INITIATIVE IN REFRACTIVE ERROR

Question. It is estimated that approximately 100 million Americans are affected by vision problems related to refractive error (nearsightedness, farsightedness, and astigmatism). What research efforts is NEI currently engaged in toward making advances in this area?

Answer. Research on the mechanisms of nearsightedness has begun to move rapidly, both with animal models that can be manipulated experimentally and with longitudinal studies in humans. Restriction of patterned light during critical periods of development results in excessive growth of the eyeball, so that light is focussed in front of the retina instead of on it (axial myopia). This phenomenon has been confirmed in animal species ranging from chickens to primates as well as in human children. Current research supported by the NEI is investigating factors in the retina that appear to provide feedback information the eye uses to regulate its growth. The potential for recovery from experimentally-induced myopia has recently been demonstrated. eye, during the critical developmental period, can apparently compensate for refractive errors through an active regulatory mechanism that coordinates axial length with the optics of the eye so as to produce emmetropia (light focussed clearly on the retina).

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In another important area of research on refractive errors, the NEI is supporting investigations of the cell biological response of the cornea to excimer laser sculpting and other forms of refractive keratoplasty. Such information will be necessary to establish the long-term safety of these emerging techniques.

INTRAMURAL RESEARCH

Question. Could you update the Committee on the status of NEI's intramural research initiatives involving retinal transplantation, retinitis pigmentosa, and cataracts?

Answer. NEI intramural scientists are intensely involved in conducting research in each of those areas. Studies on retinal cell transplant techniques and the effects of tropic Growth Factors on retinal development and degeneration, although yet in their infancy, show promise for treating retinitis pigmentosa (RP) and possibly a number of other retinal diseases as well. In one RP animal model, transplantation of normal retinal pigment epithelial cells (known for 15 years to harbor the defect) greatly delays retinal degeneration. This line of investigation has also recently shown us that injection of a specific growth factor, bFGF, into the eye can result in extensive rescue photoreceptors and a marked delay in the general degenerative process. For the first time, therefore, we have knowledge that at least one specific factor can control degeneration in an animal model of RP. Similar studies now can be formulated to see if the same mechanisms operate in the humans and if bFGF or other such neurotropic factors will delay in the disease process in man.

Retinitis pigmentosa and gyrate atrophy are among the many forms of retinal degeneration under investigation by NEI intramural researchers. Retinitis pigmentosa is a name applied to a number of hereditary degenerative conditions of the neural retina. RP and