Invited Lecturer: Dunphy Lecture, 1977; Lorand V. Johnson Lecture, 1980; C. Other Scientific Activities: Editorial Bd, Investigative Ophthalmology, International Appointments: Mbr, Brd. of Trustees, Helen Keller Internat'l Inc., 1975-pres't; Coord. U.S.-Japan Collaborat. Agree'nt in Vision Research, 1976-pres't; Mbr, Internat'l Vitamin A Consultative Group, WHO, 1973-pres't; Mbr of U.S. Delegation to World Health Assembly, 1978; Mbr, WHO Advisory Group for Prevent. of Blindness Prog., 1978-84; Consultant, Pan Amer. Hlth Org., 1978-pres't; Coord. for USA, Priority Area "Eye Diseases," U.S. -U.S.S.R. Prog. for Health Cooperation, 1978-pres't; Mbr, WHO Expert Advis. Panel on Trachoma and Prevent. of Blindness, 1979-pres't; Dir., WHO Collabor. Ctr. for the Prevent. of Blindness, Nat'l Eye Inst., Bethesda, MD, 1979 -pres't; Pres.. Internat'l Agency for the Prevent. of Blindness, Oct. 1982 -Nov. 1990. DETERIORATING VISION Senator HARKIN. I just learned something new that I will have to remember. The back part of the eye is part of the brain. Dr. KUPFER. Yes, sir; it is. Senator HARKIN. I'll have to think more about that. Tell me this. Why is this? When I was 30 years old and a fighter pilot in the Navy, I had 20/15 vision. I had great eyesight. And about age 43, 44, somewhere in there, all of a sudden there were things I couldn't read too well any longer. So, I had to get a pair of glasses, and they gave me these reading glasses. Then it got worse and worse. I am now 51. It seems like I went along and it took one drop and it sort of leveled off. Then it took another drop. Now it has leveled off, and I have to wear these now. Why is that? I can understand if you are born with an unhealthy eye or something, but when you have really healthy eyes and you have good eyesight, what happens? Why does it always happen around ageas I am told, around 45 to 50 years of age? Dr. KUPFER. That is correct. Your information is quite correct. The ability for us to look from a distance to near depends on changing the shape of the lens inside our eye. This ability to change the shape begins to decrease about the age of 40. So, that is why we need help from reading glasses or bifocal contact lenses, such as I and others wear to enable us to see what is close. Now research is being done on this condition, as you might imagine. It is very distressing, especially for those of us who have never worn glasses. Perhaps in the next 5 or 10 years we will have ways to correct this problem. Senator HARKIN. I can't wait. [Laughter.] How much more money do you need in your budget? [Laughter.] Dr. KUPFER. I think this will happen within our budget at the moment. GLAUCOMA TREATMENT Senator HARKIN. I wanted to ask one other question about glaucoma. Two typical treatments for glaucoma are medications, which reduce the pressure, and surgery to accomplish the same purpose. What can you tell us about the relative effect of these two approaches and quality of life considerations? Which is the better approach? Or is there one that is better than the other, or does it depend upon the situation? Dr. KUPFER. That is an excellent question. The situation with glaucoma is that it is completely asymptomatic. This is the openangle glaucoma which is the most common. Therefore, the individual can lose visual function without really being aware of any signs or symptoms until very late. When the diagnosis is made, we ask the patient to take drops. These drops themselves sometimes have adverse effects, plus the fact that it is very difficult to remember to take drops once, twice, or three times a day. On the other hand, to lower pressure, another possibility would be to perform a surgical intervention which creates a new path for the fluid to leave the eye. We do not know which is the better intervention. As a matter of fact, we are considering supporting a clinical trial which will randomly assign individuals who are newly diagnosed as having glaucoma to either medical treatment or surgical treatment with one of the major outcomes being which offers a better quality of life. So, in a number of years-hopefully not more than 3 or 4-we will begin to have information on this very question. I might say that in the United Kingdom, surgery is now used as the primary intervention, whereas in the United States, we still prefer medical treatment as the primary intervention. This clinical trial will give us a very definitive answer. QUESTIONS SUBMITTED BY THE SUBCOMMITTEE Senator HARKIN. Good. I look forward to that. Dr. Kupfer, thank you. I have some additional questions which we will submit to you in writing. [The following questions were not asked at the hearing, but were submitted to the Department for response subsequent to the hearing:] QUESTIONS SUBMITTED BY THE SUBCOMMITTEE GLAUCOMA TREATMENT Question. Dr. Kupfer, two typical treatments for glaucoma are medications which reduce the pressure within the eye and surgery to accomplish the same purpose. What can you tell us about the relative effect of these two approaches and the quality of life considerations associated with these two strategies? Answer. In the United States, the standard approach to the treatment of glaucoma has been to prescribe medications that reduce the intraocular pressure. When medications fail, attempts are made to reduce the intraocular pressure using argon laser trabeculoplasty, followed, if necessary, by filtration surgery. Results from the NEI-supported Glaucoma Laser Trial suggest that argon laser therapy may be a safe and effective alternative to eye drops, as a first treatment for patients with newly diagnosed openangle glaucoma, Another NEI-supported clinical trial of patients with uncontrolled glaucoma has shown that the use of 5-fluorouracil with surgery is more effective in controlling intraocular pressure than filtration surgery alone. Patients using glaucoma medicines often report serious side effects, including eye irritations, poor vision, fatigue, confusion, loss of appetite, and weight loss. The ophthalmologist attempts to maintain the patient's visual function without causing side effects that might offset the benefits of treatment. No major glaucoma studies have been conducted that specifically measure quality of life as an outcome of treatment decisions. Investigators are currently planning a randomized, clinical trial to evaluate the relative effects of medications versus surgery in managing newly diagnosed glaucoma patients. Quality of life will be assessed in this planned clinical trial. GLAUCOMA DISPARITY Question. Dr. Kupfer, it has been known for a long time that the prevalence of glaucoma in the black population is 4 to 5 time more than in the white population in the U.S. What factors lead to this great disparity? We Answer. Although we now have some new data on the magnitude of black/white population differences in the prevalence of glaucoma, we need better information on why these differences exist. Differences in glaucoma prevalence rates reported for whites and for different groups of blacks may be due to genetic influences, variable access to health care, or unknown factors. know that the prevalence of glaucoma reported from studies of blacks living in the United States is less than that of blacks residing in St. Lucia and Barbados. Well-designed epidemiologic studies examining risk factors for the development of glaucoma are needed since few risk factors, other than family history and diabetes, have been identified. AGE RELATED CATARACT AND MACULAR DEGENERATION Question. Age related cataract and age related macular degeneration are the major causes of visual impairment and blindness in the aging U.S. population. I understand that some physicians have already begun to recommend preventative treatments and to treat patients with vitamins and other nutritional supplements to slow or prevent macular degeneration and the development of cataracts. Is this a case of non-traditional medicine leap frogging ahead of conventional practice? Answer. At present, standard medical practice does not prescribe the use of vitamins or minerals for the prevention of cataract or macular degeneration. There is no convincing evidence that nutritional supplements can affect either the development or progression of these age-related eye conditions. There is a public perception that the use of over-the-counter nutritional supplements may be beneficial in the treatment of a wide range of diseases. This practice carries some risk since many micro-nutrients are toxic at high doses and may give undesirable interactions with drugs of other nutrients. IMPACT OF NUTRITION ON VISION Question. What does NEI plan, in terms of clinical trials, to demonstrate the usefulness of vitamins and mineral supplements for prevention and treatment of eye disease? Answer. The NEI is currently conducting the Age Related Eye Diseases Study (AREDS), which aims to determine how age-related macular degeneration and lens opacities develop and progress. The role of nutrition will be assessed in two ways. First, a natural history study will delineate the role of nutrition as a risk factor for the development of these diseases. Secondly, the feasibility of conducting a randomized, placebo-controlled clinical trial of vitamin and mineral supplements will be evaluated. If such a trial were feasible it would assess the effect of vitamin therapy on the development and progression of lens opacities and age-related macular degeneration. CLINICAL TRIALS Question. Dr. Kupfer, I understand that there are at least 10 major/new clinical trials ready to begin in FY 1992 if funds are available. These trials have an estimated total first year cost of $25.1 million and a total cost of $178.6 million. If the Congress provides additional funding to NEI over and above the Administration request, would funding these new clinical trials be your highest priority? Answer. The highest priorities of the National Eye Institute include expansion and strengthening of research and related activities for age-related macular degeneration, vision research related to the Decade of the Brain, and glaucoma. These initiatives require both a clinical and basic research focus. Therefore, within each of these initiatives are opportunities for major clinical trials. Question. Which of these several new clinical trials that are ready to go are your highest priority? Answer. In priority category order, those clinical trials that are ready to initiate are: Age-Related Macular Degeneration Low Birthweight Effect of Light Reduction in Retinopathy of Prematurity AIDS Oral vs. IV Intravenous Ganciclovir Retinitis Trial Glaucoma Assessment of Glaucoma Treatments Efficacy of Intraocular Pressure Lowering In Ocular Barbados Glaucoma Treatment Trial Grave's Disease Graves' Ophthalmopathy Strabismus Treatment of Congenital Esotropia Corneal Dystrophies Contact Lens Evaluation in Keratoconus Low Birthweight & Optic Neuritis Advanced Retinopathy of Prematurity Study A NATIONAL VISION RESEARCH PLAN Question. Dr. Kupfer, I understand that your National Vision Research Plan for 1992 to 1996 is soon to be completed. Could you tell us, in broad terms, the focus this research agenda will have? Answer. In the National Eye Institute's fourth long-range plan, Vision Research--A National Plan: 1992-1996, the broad focus of the research will be on each of the NEI's major programs-Retinal Diseases, Corneal Diseases, Lens and Cataract, Glaucoma, and Strabismus, Amblyopia, and Visual Processing. In addition, a section of the report will be devoted to Low Vision and Its Rehabilitation and another to Clinical and Epidemiologic Research. NEW AREAS OF RESEARCH Question. Are there new areas of research recommended in the National Plan? Answer. In an effort to identify new areas of research opportunity, panels of experts were established for each of these programs and were charged to: define the scope and impact of important research areas; update program goals and objectives; review current research support and recent scientific advances; and determine the key research questions to be addressed in vision research in FY 1992-1996. These research questions pertain to some of the key new areas of research such as the transplantation of retinal tissues as a potential means of halting or preventing the progressive loss of vision in retinal degenerative diseases. They |