The first goal of this two-part application is to determine 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 Clinical Trial (FFSS). The FFSS 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 eyes with poor prognoses. Patients with medically uncontrolled glaucoma after previous cataract extraction or unsuccessful filtering surgery, or both, were randomized to undergo trabeculectomy alone (standard treatment) or 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 in the 5-FU group was approximately 80% vs 60% in the standard treatment group (p=.0004). The 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 acuity, and 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 of this two-part application is to establish a FFSS-Patient Registry to determine the efficacy and safety of a standardized low-dose 5- FU dosage regimen: 5mg once daily on postoperative days 1-7, and 5mg three times during days 8-14 in patients comparable to those in the FFSS-Clinical Trial. This dose 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 the baseline efficacy and side effects of low dose 5-FU for future comparison with newer alternative surgical therapies. The clinical course will be determined by standardized measurements of visual acuity, perimetry and IOP, and assessment of the side effects using the same personnel and equipment as in the FFSS Clinical Trial. A sample size of 100 patients in the FFSS Patient Registry will provide results to be compared with the 105 patients who received high dose 5-FU in the FFSS Clinical Trial generate sufficient data regarding efficacy and toxicity.
