Mr. Chairman and Members of the Committee:
I am pleased to present the President’s Budget request for the National Eye Institute (NEI) of the National Institutes of Health (NIH). The fiscal year (FY) 2014 budget of $699,216,000 includes a decrease of $2,191,000 below the comparable FY 2012 level of $701,407,000. As the director of the NEI, it is my privilege to report on the many research opportunities that exist to reduce the burden of eye disease.
The NEI Challenge to Identify Audacious Goals in Vision Research and Blindness Rehabilitation was a novel strategic planning iitiative designed to identify innovative, groundbreaking long-term research goals. The challenge was open to anyone with an idea for a 10-year audacious research goal including scientists, engineers, clinicians, and the public. NEI used a new prize competition authority, from the America COMPETES Reauthorization Act of 2010, to attract attention and received more than 500 ideas for audacious goals. A federal review panel selected 10 winning entries for further consideration. Then, more than 200 leading scientists and clinicians met to further develop these ideas at the NEI Audacious Goals Development Meeting held in February 2013. Afterwards, NEI announced an audacious goal (Regenerate Neurons and Neural Connections in the Eye and Visual System) and two high-priority areas (Molecular Therapy for Eye Disease and the Intersection of Aging and Biological Mechanisms of Eye Disease) at the Association for Research in Vision and Ophthalmology meeting on May 5. NEI is now identifying the necessary steps to boldly attack these research endeavors over the coming decade.
This month, NEI-supported investigators published results of the Age-Related Eye Disease Study 2 (AREDS2), a large, multi-center clinical trial designed to refine the antioxidant and mineral supplement formulation that was evaluated in the original AREDS clinical trial. The original Age-related Eye Disease Study (AREDS) established that daily doses of vitamins C and E, beta-carotene, zinc, and copper slows the progression to advanced age-related macular degeneration (AMD), the leading cause of visual impairment and legal blindness in older Americans. AREDS2 was undertaken for three reasons. First, preliminary evidence indicated that Omega-3 fatty acids might be beneficial. Second, beta-carotene, used in AREDS, was found to increase lung cancer risk in cigarette smokers. Third, it was suggested that the rather high zinc level in AREDS might cause minor side effects, such as stomach upset. AREDS2 investigators found that adding Omega-3 fatty acids, replacing beta-carotene with two other carotenoids, lutein and zeaxanthin, and lowering zinc levels maintained, but did not improve the effectiveness of the original formulation. Thus, changing the carotenoid and lowering the zinc in original AREDS formulations offers an equally effective alternative with fewer side effects. The AREDS2 study results provide physicians and patients with new information about delaying or preventing vision loss from AMD.
In February 2013, The FDA approved the Argus II Retinal Prosthesis System, a medical device capable of restoring ambulatory vision to those blind from retinitis pigmentosa. Argus II consists of a miniature video camera that is mounted on a pair of glasses. A processing unit worn on a belt converts images captured by the camera into electrical impulses that are wirelessly transmitted to a 60-electrode grid implanted in the eye. Users perceive the electrical impulses as patterns of light that produce visual information. The Argus II, developed by Second Sight, Inc., was made possible through more than a decade of clinical trial support from NEI.
Retinitis pigmentosa (RP) is a group of rare, degenerative diseases that result from mutations in any one of 40 genes that function in rod photoreceptor cells in the retina. These cells form our peripheral vision and allow us to see in dim and dark environments. As RP progresses, patients experience night blindness and severely restricted visual fields. For reasons that are not understood, the loss of rods eventually leads to the degeneration and death of cones, the photoreceptor cells in the central portion of the retina that allow us to perceive fine visual detail and color. Without central vision, it is impossible to perform essential tasks of daily life such as reading, driving, walking without assistance, or recognizing faces and objects.
Vision researchers have long sought a therapeutic approach that can address multiple RP genotypes. However, current efforts with gene therapy address only one specific gene defect at a time. In a highly novel approach that could be applied to most, if not all, forms of RP, NEI-supported investigators genetically reprogrammed rods to become cone-like cells in a rodent model of RP. This approach reduced rod cell function but preserved cone cells. Although such a treatment would leave patients with limited peripheral vision and night blindness, this would be preferable to the added debilitating loss of central vision for the estimated 200,000 Americans who live with RP.
NEI-supported investigators have developed a potential new treatment to prevent proliferative vitreoretinopathy (PVR) a sight-threatening complication of retinal detachment that requires prompt surgical treatment. PVR occurs in about 10 percent of retinal detachments, resulting in permanent scarring of the retina. In this condition, retinal pigment epithelial (RPE) cells, which line the neural retina, migrate through the retinal detachment into the vitreous fluid where they rapidly multiply, dedifferentiate and contribute to the formation of an abnormal membrane on the surface of the retina. This membrane eventually contracts, pulling at the retina and forming a larger detachment. PVR causes heavy scarring of the retina and severe visual impairment. NEI investigators identified seven classes of biological growth factors and regulatory proteins that promote the proliferation and contraction of the RPE-derived membrane in an animal model of PVR. By inhibiting the expression of these biological factors, the investigators prevented PVR. This study provides insight into the causes of PVR and proof-of-concept for treating the condition.
The cornea, the outer protective layer of the eye, is amazingly resilient to infection. By exposing cultured human corneal cells to bacteria, NEI researchers identified a class of peptides important in the cornea’s defense against bacterial infection. Blocking these peptides in a rodent model led to a marked increase in corneal infections. Synthetic variations of these peptides effectively killed bacteria that lead to flesh-eating disease and strep throat, staph infections, diarrhea, and cystic fibrosis associated lung infections. The findings could lead to a powerful new class of low-cost antibiotics at a time when antibiotic resistance to existing agents is of growing concern.
Dr. Sieving became director of the National Eye Institute, NIH, in 2001. He came from the University of Michigan Medical School, where he was the Paul R. Lichter Professor of Ophthalmic Genetics and the founding Director of the Center for Retinal and Macular Degeneration in the Department of Ophthalmology and Visual Sciences.
After undergraduate work in history and physics at Valparaiso University, Dr. Sieving studied nuclear physics at Yale Graduate School in 1970-73 under D. Allan Bromley and attended Yale Law School from 1973-74. He received his M.D. from the University of Illinois College of Medicine in 1978 and a Ph.D. in bioengineering from the University of Illinois Graduate College in 1981. Dr. Sieving completed an ophthalmology residency at the University of Illinois Eye and Ear Infirmary in Chicago. After post-doctoral study of retinal physiology with Roy H. Steinberg in 1982-83 at the University of California, San Francisco, he did a clinical fellowship in genetic retinal degenerations with Eliot Berson in 1984-85 at Harvard Medical School, Massachusetts Eye and Ear Infirmary.
Dr. Sieving is known internationally for studies of human progressive blinding genetic retinal neurodegenerations, including retinitis pigmentosa, and rodent models of these conditions. His laboratory study of pharmacological approaches to slowing degeneration in transgenic animal models led to the first human clinical trial of ciliary neurotrophic factor (CNTF) for retinitis pigmentosa, published in Proceedings of the National Academy of Sciences, 2006. He also developed a mouse model of X-linked retinoschisis and successfully treated this using gene therapy which restored retinal function. He maintains a clinical practice at NEI for patients with these and other genetic retinal diseases, including Stargardt juvenile macular degeneration.
Dr. Sieving served as Vice Chair for Clinical Research for the Foundation Fighting Blindness from 1996-2001. He is on the Bressler Vision Award committee and is a jury member for the €1 million annual ‘Vision Award’ of the Champalimaud Foundation, Portugal. He was elected to membership in the American Ophthalmological Society in 1993 and the Academia Ophthalmologica Internationalis in 2005. He received an honorary Doctor of Science from Valparaiso University in 2003 and has been named among the ‘Best Doctors in America’ multiple years. He has received numerous awards, including the Research to Prevent Blindness Senior Scientific Investigator Award, 1998; the Alcon Research Institute Award, 2000; and the Pisart Vision Award from the New York Lighthouse International for the Blind in 2005. Dr. Sieving was elected to the Institute of Medicine of the National Academy of Sciences in 2006.