The first goal of this two-part application is the determination of the long-term, five year, safety and efficacy of subconjunctivally injected 5- FU through the continued follow-up of 213 patients in the Fluorouracil Filtering Surgery Study (FFSS)-Clinical Trial. The FFSS-Clinical Trial, a multicenter randomized clinical trial, began in September 1985, to determine if postoperative subconjunctival injections of 5-fluorouracil (5- FU) would increase the success rate of glaucoma filtering surgery in patients with poor prognoses. Patients with medically uncontrolled glaucoma after previous cataract extraction or unsuccessful filtering surgery, or both, were randomized to a trabeculectomy alone (standard treatment), or to trabeculectomy with adjunctive 5-FU injections. Postoperative success and failure rates were determined by reoperation rates and by defined intraocular pressure (IOP) levels. Possible risks of 5-FU, such as corneal, lenticular, retinal, and hematologic toxicities were monitored. The Safety and Data Monitoring Committee recommended stopping recruitment in June, 1988 when the success rate after one year follow-up was determined to be approximately 80% in the 5-FU group versus 60% in the standard treatment group (p=0.0004). The continued five year follow-up of these 213 patients will be sufficient to determine the long-term status of visual function, as measured by the stability of visual field and of visual acuity, and to assess the attendant risks of treatment with 5-FU. Important information regarding the long-term effect of IOP control in eyes with advanced glaucoma will also be generated through the continued follow- up. The second goal is the establishment of a FFSS-Patient Registry to determine the efficacy and safety of a standardized low-dose 5-FU dosage regimen, 5 mg once daily on postoperative days 1 - 7, and 5 mg three times during postoperative days 8 - 14 in patients comparable to those in the FFSS-Clinical Trial. This does has been chosen to minimize corneal and conjunctival epithelial toxicity. Currently most non-FFSS ophthalmologists are using a variably reduced 5-FU dose that has not been tested in a controlled fashion. The FFSS-Patient Registry will establish a baseline of efficacy and side effects for future comparison of low-dose 5-FU with newer alternative surgical therapies. The clinical course will be determined by standardized measurements of visual acuity,k perimetry,k and IOP, and by standardized assessment of side-effects with the same personnel and equipment as in the FFSS-Clinical Trial. A sample size of 100 patients in the FFSS-Patient Registry will be compared to the 105 patients in the FFSS- Clinical Trial who received high-dose 5-FU to generate sufficient data regarding efficacy, as well as corneal and conjunctival toxicity.
