Louis W. Sullivan, Secretary of Health and Human Services, has announced the results of a clinical trial demonstrating a 50 percent improvement in surgical control of glaucoma in patients at high risk for blindness. In the Fluorouracil Filtering Surgery Study (FFSS), glaucoma surgery was followed by injections of the drug, 5-fluorouracil (5-FU), beneath the outer membrane of the eye. 5-FU is used to impede the growth of scar tissue that may reverse the surgery's beneficial effect. The FFSS study was supported by the National EyeInstitute (NEI), a component of the National Institutes of Health.
Open-angle glaucoma, the most common form of glaucoma in America, is one type of disease studied in the FFSS. It is the second leading cause of blindness among all Americans and the leading cause among blacks. The disease is characterized by an abnormal, progressive rise in fluid pressure inside the eye, which gradually damages the optic nerve. Most patients can control their glaucoma with medications that either reduce fluid production or facilitate its outflow, but when drops or pills fail, some patients need filtering surgery to provide a new fluid outlet to lower their pressure. Sometimes, however, scar tissue blocks the outlet channel, necessitating further surgery. This type of surgery is least successful in patients who have had a previous filtering surgery or who have had cataracts removed.
To determine whether postoperative injections of 5-fluorouracil also called 5-FU, could enhance the success of filtering surgery, investigators from seven clinical centers recruited 213 high-risk glaucoma patients for the FFSS. After the investigators performed the surgery and determined that the new outlet was working, the patients were randomized to receive either 5-FU injections or to receive standard post-surgical care without 5-FU.
The study was scheduled to end in 1990, but patient recruitment was stopped in June 1988 when it become evident that the combination of surgery and 5-FU therapy was significantly superior to the surgery alone. When the study’s Safety and Data Monitoring Committee had accumulated 1-year follow-up data, they found nearly a 50 percent improvement in the outcome of operations that were followed by 5-FU injections. Of the 105 operations on eyes treated with 5-FU, 73percent were successful at one year compared to 50 percent of the 108eyes in the standard therapy group.
Filtering surgery followed by postoperative injections of 5-FU provided an additional benefit. Two-thirds of the patients receiving treatment with 5-FU did not need to resume taking medications to control their glaucoma. In the standard therapy group, only about one-third maintained satisfactory pressure control without medication. Moreover, of those requiring medication after surgery, patients in the5-FU group needed fewer types and lower doses of medication than those in the standard treatment group.
The quality of life generally improved for patients receiving 5-FU because they were less likely to require further surgery and needed fewer or no daily medications. However, the 5-FU injections given twice daily for the first week and daily the second week sometimes caused side effects. These side effects were usually short-lived, and the patients tolerated them without substantial problems.
Study chairman Richard K. Parrish, II, M.D., Associate Professor of Ophthalmology at the Bascom Palmer Eye Institute, University of Miami School of Medicine, said, “We will follow these patients for at least five years to determine whether the early results hold true. Now that we know 5-FU improves the short-term outcome for these patients, we can investigate whether lower doses of 5-FU or less rigorous injection schedules may produce the same or even better results.”
NEI Director, Carl Kupfer, M.D., is optimistic about how well the early results will hold up. “If a filtering surgery is providing drainage after one year, it probably will continue to do so for a long time. And if 5-FU improves surgical results for these high-risk patients, it may also improve the outcome for patients who have a lower risk for surgical failure.”
James Mason, M.D., Assistant Secretary for Health, said, “These results are very encouraging since filtering surgery is often the last hope for preventing further visual loss from glaucoma.”
Study results have been published in the December 1989 issue of the American Journal of Ophthalmology.
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- Fluorouracil Filtering Surgery Study One-Year Follow-Up. The Fluorouracil Filtering Surgery Study Group. Am J Ophthalmol. 1989 Dec 15. PubMed