Paul A. Sieving, MD, PhD, takes the NEI in new directions

Dr. Sieving, appointed as director of the National Eye Institute last year, speaks about current projects and the vital research he hopes the NEI will continue to support.

Issue: December 1, 2002

ByJeanne Gonzalez

BETHESDA, Md. – With a year already behind him as head of the National Eye Institute, Paul A. Sieving, MD, PhD, has established his vision for the future role of the institute. He wants to maintain its current flow of studies in the prevention and treatment of eye diseases while expanding certain areas of research for generations to come.

In addition to this metaphorical vision, Dr. Sieving is also captivated by real vision, a human sense by which he is continually amazed.

“I think vision is fascinating. It’s a very precious sense. In addition to people at the eye institute being eye doctors and vision researchers, I hope all of us, as people and as scientists, really enjoy the pleasures of the science of vision,” Dr. Sieving said.

Dr. Sieving spoke to Ocular Surgery News about his work as director of the NEI since he started in the position in July 2001. He said the NEI is not lacking in areas of research, but there is room for expansion — including more exploration of genetics, a field from which much of medicine is seeking answers.

One priority in the past year has been to acquaint himself with the task at hand, the current body of work of the NEI. Dr. Sieving was previously a professor of ophthalmic genetics and of ophthalmology and visual sciences at the University of Michigan, where he led research on the basic biology of retinal cells directly related to vision loss.

“The programs here are robust, but what I’m seeing is that they need to be expanded to cover some diseases that all of us are interested in, particularly in diseases that the American people are concerned about,” Dr. Sieving said.

In response to congressional requests, Dr. Sieving wants to expand the NEI’s research in glaucoma, age-related macular degeneration (AMD), retinal dystrophies such as retinitis pigmentosa, and diabetic retinopathy (DR). These diseases are becoming more prevalent as the population grows older. There has also been an increase in the population at risk for diabetes mellitus.

“Those are areas taxpayers question us about. Unfortunately, science has not yet come to the point of definitive treatments, so we need to focus on those in the intramural program, which has not had as strong or as broad a program in these areas thus far. One of the research agendas here is to respond to the national need for work in glaucoma, AMD and DR,” he said.

The NEI, a division of the National Institutes of Health, has two main methods for achieving research goals. One is external, the funding of research at universities and hospitals outside the NEI. The other is the intramural basic science research program, a clinical program researching the underlying intricacies of the eye that could explain the causes of disease.

“It’s really a privilege to be the director of an institute with such a good, strong community of scientists and clinicians,” he said of the intramural program.

New areas for the NEI

In addition to expansion of the NEI’s disease research, Dr. Sieving said the intramural basic science program will expand its research into the structures of the eye.

“The lens, the cornea, the retina and the optic nerve account for a major portion of eye disease,” Dr. Sieving said.

Pediatric conditions such as amblyopia and strabismus are areas in which research may be expanded, he said.

Studying pediatric conditions can be complex because it involves understanding how the brain processes visual information. As part of its strabismus research, one of the NEI intramural laboratories is currently investigating oculomotor control in primates, Dr. Sieving said.

Genetics will also be an important area of future research, he said.

“Eye diseases, vision diseases are heavily represented as having genetic components. Genes have already been identified that cause or contribute to glaucoma, to corneal diseases, cataract and macular degeneration, particularly juvenile macular degeneration,” Dr. Sieving said.

Genetic research has shown that a family history of a disease can mark other members as being at risk for developing the disease. Future research will concentrate on what makes some members of a family more vulnerable to a disease than others.

In addition, Dr. Sieving expects that genetic research in other areas of medicine will have lessons that carry over into ophthalmology. Research on diabetes mellitus could identify genes that cause diabetic retinopathy.

Conversely, he said, ophthalmic genetic research may benefit other specialties. Genes linked to macular degeneration and glaucoma could answer questions regarding other conditions related to aging, he said.

“It’s going to be very difficult because we don’t know quite what we’re looking for yet. It could be three or five genes working in synergy, each of which contribute their own little bit to the tissue developing glaucoma, cataract or macular degeneration,” he said.

Setting a foundation

The intramural program at the NEI focuses on basic science research. By investigating the factors that cause diseases, the research complements external and private industry research and helps them advance.

“The basic study of how the eye tissue works and how the cells work are the bedrock for work in future years that will contribute to solutions,” Dr. Sieving said.

He cited as an example the NEI’s work in macular degeneration. Traditionally there have not been many treatment options for exudative AMD, but several trials are underway that may help address questions about the condition, Dr. Sieving said.

“Some of the antivascular endothelial growth factor compounds being tested for the wet form of macular degeneration have come out of basic science. The NEI supports studies on the basic biology of blood vessels and corneal, lens and retinal cells,” he said.

Research from such NEI basic science studies inevitably aids industry; the two work in parallel and their goals are complementary, Dr. Sieving said. The goal of industry is to create a product useful for a particular condition. For the NEI, the goal is to understand how cells work, how disease works, how the eye works, Dr. Sieving said. These goals are mutually supportive, he said.

“There are components that the Eye Institute can contribute to industry. In respect to keratorefractive surgery, we fund efforts on the basic science of corneal wound healing. That’s an area where the Eye Institute has contributed to the health and safety of eye surgery and the commercial development of it,” he said.

The NEI works to benefit the public’s eye and vision health. According to Dr. Sieving, if industry benefits from NEI research and reaches a similar goal, then part of the NEI’s goal has been met as well.

Yet the basic mission is to find the root of eye disease, he said.

“You provide for eye and vision health by addressing prevention and treatment,” he said.

Recent NEI study

In mid-October, the NEI released results of the Early Manifest Glaucoma Trial. Results of the study add to the evidence for the effectiveness of lowering intraocular pressure in glaucoma, even in normal tension glaucoma, Dr. Sieving said.

“There’s been a real wealth of studies asking questions about the ways to treat and the ways to study glaucoma. They always converge on this finding somehow,” he said. “IOP is critical toward developing glaucoma and toward losing vision as the nerve cells in the retina die, so it’s clear that glaucoma involves some aspect of pressure.”

What is new about the EMGT is its demonstration of how much pressure can affect the eye. Previous studies have shown the effectiveness of lowering IOP in patients with normal tension glaucoma, he said. Lowering pressure preserves vision and slows the progression of the disease.

In this study, researchers monitored 255 patients, split into two groups, for 6 years. One group received medication to lower IOP and the other did not. The progression of visual field damage was delayed more in patients whose IOP was lowered.

Future NEI-sponsored studies will focus on the mechanism of nerve cell damage and how to preserve them against the effects of increased IOP, Dr. Sieving said.

“Some of the next set of studies will address how to protect the nerve cells in the face of pressure, or what the mechanism is for pressure to affect the death of nerve cells that cause glaucoma,” he said.

Results of the EMGT were published in the October issue of Archives of Ophthalmology.

For Your Information:

Paul Sieving, MD, PhD, can be reached at the National Eye Institute, 2020 Vision Place, Bethesda, MD 20892-3655; (301) 496-2234; fax: (301) 496-9970; Web site: www.nei.nih.gov.

The National Institutes of Health can be contacted at 9000 Rockville Pike, Bethesda, MD 20892; www.nih.gov.