A Prospective Randomized Trial Comparing Intraoperative 5-Fluorouracil Vs Mitomycin C in Primary Trabeculectomy DARRELL WUDUNN, MD, PHD, LOUIS B. CANTOR, MD, ANGELITA M. PALANCA-CAPISTRANO, MD, JONI HOOP, COT, NISHAT P. ALVI, MD, CHARLES FINLEY, MD, VIPUL LAKHANI, MD, ALAN BURNSTEIN, MD, AND STEPHENIE L. KNOTTS
● PURPOSE:
To compare the safety and efficacy of intraoperative 5-fluorouracil (5-FU) or Intraoperative mitomycin C (MMC) in eyes undergoing primary trabeculectomy. ● DESIGN: Prospective double-masked randomized clinical trial. ● METHODS: One hundred fifteen eyes of 103 patients with uncontrolled intraocular pressure (IOP) despite maximally tolerated medical therapy or laser were prospectively randomized in a double-masked fashion to one of two treatment groups in a single institution setting. Subject’s eyes underwent primary trabeculectomy with either topical 5-FU (50 mg/ml for 5 minutes) or topical MMC (0.2 mg/ml for 2 minutes). Primary outcome measures included the number of eyes achieving target pressures of 21, 18, 15, and 12 mm Hg at 6 and 12 months postoperatively. Secondary outcome measures included IOP, best-corrected visual acuity, complications, and interventions. ● RESULTS: Of the 115 eyes, 57 received 5-FU while 58 received MMC. A target IOP of 21 mm Hg at 6 months was achieved in 53 of 56 (95%) eyes in the 5-FU group and 54 of 57 (95%) eyes in the MMC group (P ⴝ 1.00). At 12 months, 45 of 48 (94%) eyes in the 5-FU group met a target IOP of 21 mm Hg while 48 of 54 (89%) eyes in the MMC group did (P ⴝ .49). The most common complications in each group were persistent choroidal effusions and bleb leak. ● CONCLUSION: Our study suggests that intraoperative topical 5-FU is at least as effective as intraoperative Accepted for publication May 10, 2002. From the Department of Ophthalmology, Indiana University, Indianapolis, Indiana. This study was supported by an unrestricted grant from Research to Prevent Blindness, Inc., New York, New York. Inquiries to Darrell WuDunn, MD, PhD, Indiana University, Department of Ophthalmology, 702 Rotary Circle, Indianapolis, IN 46202; fax: (317) 278-1007; e-mail:
[email protected] 0002-9394/02/$22.00 PII S0002-9394(02)01627-6
©
2002 BY
topical MMC in reducing IOP of eyes undergoing primary trabeculectomy. (Am J Ophthalmol 2002;134: 521–528. © 2002 by Elsevier Science Inc. All rights reserved.)
U
NLIKE MOST SURGICAL PROCEDURES, SUCCESS OF
glaucoma filtering surgery is achieved through the inhibition of wound healing.1 Antimetabolites such as mitomycin C (MMC) and 5-flurouracil (5-FU) have been used in trabeculectomy to delay wound healing and hence to improve the success of surgery. Since the 1980s, these agents have been used as adjuncts to obtain lower intraocular pressures (IOP) because of their inhibition of fibroblast migration and proliferation that would otherwise lead to scarring over the filter site.2–14 Experimental studies in the rabbit showed that application of a sponge soaked in either 5-FU or MMC delayed the fibroblast outgrowth in a more localized area and prolonged the survival of filtration surgery for different lengths of time.15,16 Subsequent studies in patients with eyes at high risk for failure reported similar results when either antimetabolite was applied intraoperatively.5–7,17–20 Recently, these antimetabolites were reported to be equally safe and effective in primary trabeculectomy.21–23 Today, three out of four glaucoma specialists in the United States use either one of these antimetabolites in primary trabeculectomy, although the dose and antimetabolite still varies according to clinical situation and from surgeon to surgeon.24
DESIGN WE CONDUCTED A SINGLE CENTER, PROSPECTIVE, DOUBLE-
masked, randomized clinical trial to compare the safety and efficacy of intraoperative 5-FU versus MMC in pri-
ELSEVIER SCIENCE INC. ALL
RIGHTS RESERVED.
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mary trabeculectomy in achieving target intraocular pressures.
was also enrolled, it was assigned to the opposite group of the first eye. Hence, if both eyes of a patient were enrolled, one eye would receive 5-FU while the fellow eye would receive MMC. Group assignment was made on the morning of surgery by the study coordinator and relayed directly to the operating room circulating nurse. Only the clinical coordinator and the operating room circulating nurse, who prepared the antimetabolite solutions, knew to which group the eye was randomized. The assignment code was kept in a locked drawer in the office of the study coordinator during the trial and the code was broken to allow for data analysis at least 6 months after all trabeculectomies were performed.
METHODS ● PROTOCOL:
Eligible subjects included persons with inadequate intraocular pressure (IOP) control despite maximally tolerated medical therapy, but without previous intraocular surgery except laser trabeculoplasty. Subjects were recruited from the patient population of the Glaucoma Service of Indiana University Department of Ophthalmology from 1997 to 2001. Institutional Review Board approval was obtained for this study and informed consent was obtained from all study subjects before enrollment. Enrolled eyes were randomized to receive either topical 5-FU (50 mg/ml for 5 minutes) or MMC (0.2 mg/ml for 2 minutes) during trabeculectomy. The percentage of eyes achieving target pressures of 21, 18, 15, and 12 mm Hg was the primary outcome measure. Secondary outcome measures included IOP, best-corrected visual acuity, number of glaucoma medications, postoperative interventions, and complications. Assuming a two-tailed ␣ ⫽ 0.05, a power of 0.80, and a 90% success rate at 1 year for the MMC group, approximately 58 eyes/group were required to detect a statistically significant 20% lower success rate for the 5-FU group. All statistical methods were performed with SPSS for Windows, version 10.0 (SPSS, Inc, Chicago, Illinois, USA), Microsoft Excel 2000 (Microsoft, Redmond, Washington, USA), or InStat (Graphpad, San Diego, California, USA). Final analysis included all randomized subjects as originally assigned. Best-corrected visual acuities were converted into logarithm of the minimum angle of resolution (logMAR) units and the difference between pre- and post-trabeculectomy logMAR units was calculated. For comparisons between groups, the Student t test was used for parametric data (age, IOP), the Mann–Whitney U test for nonparametric data (logMAR, number of preoperative medications), and the Fisher exact test for proportions (gender, race, success rate). Successful IOP control was defined as an IOP equal to or lower than target IOP (21, 18, 15, or 12 mm Hg), with or without glaucoma medications. Patients with preoperative IOP ⬍ 21 mm Hg were considered as failures if the IOP reduction was less than 20%. Surgical failure was defined as a postoperative IOP ⬎ target IOP after resumption of medical therapy. Eyes that required further surgery to lower the IOP were considered failures.
● MASKING:
All subjects underwent a standard primary trabeculectomy with the patient and surgeon masked to antimetabolite. Each subject received a retrobulbar or peribulbar anesthetic block and facial block using a 50/50 mixture of 2% lidocaine and 0.5% bupivicaine. Either a 4-0 silk superior rectus bridle suture or 7-0 vicryl superior corneal traction suture was placed. A limbus based conjunctival incision was made approximately 8 mm posterior to the limbus. The conjunctiva and the Tenon fascia were dissected forward until the limbus was identified. Hemostasis was achieved with wet field cautery. Two cellulose sponges (Weck-Cel, Solan, Jacksonville, Florida, USA), presoaked in a Gentian violet-tinted solution, were applied in succession on the anterior surgical limbus. Since MMC solutions normally have a slight violet color, the Gentian violet coloring prevented the surgeon from knowing which antimetabolite was in the solution. The first sponge, applied for 3 minutes, contained either balanced salt solution (MMC group) or 5-FU (50 mg/ml; 5-FU group). The area was then dried before application of the second sponge. The second sponge contained either MMC (2 mg/ml) or 5-FU (50 mg/ml) and was applied for 2 minutes. After the sponges were removed, the area was irrigated with 30 ml of balanced salt solution. A partial thickness scleral flap was constructed and dissected anteriorly to the limbus and undermined into clear cornea. At this point, a paracentesis was made with a 25-gauge tuberculin syringe or a 15 degree knife. The eye was entered with a blade and a sclerotomy performed by excision with scissors or by a punch followed by a peripheral iridectomy. The trabeculectomy flap was closed with 10-0 nylon sutures. The Tenon capsule and conjunctiva were closed with an 8-0 vicryl suture on a tapered needle either together or separately. The anterior chamber was reformed with viscoelastic or balanced salt solution and the wound checked for leaks. A corticosteroid/antibiotic ointment and atropine ointment were instilled, followed by a sterile eye patch and shield. Postoperatively, all eyes received prednisolone acetate 1%, 4 times/day, atropine 1%, and an antibiotic. Subjects were evaluated on day 1, week 1, months 1, 3, 6, and 12, and as necessary. Glaucoma medications for the nonoper-
● ASSIGNMENT:
Enrolled eyes were randomized in a double masked fashion just before surgery. To ensure approximately equal numbers in each group, the assignment schedule was generated in blocks of 50 (25 per group) by a study coordinator who was not involved in the surgical procedure or clinical care. If the second eye of a patient
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TABLE 1. Preoperative Characteristics of Study Eyes
Total (n) Age in years (mean ⫾ SD [range]) Male:Female Race White African American Hispanic/Asian Eye operated (right:left) Type of glaucoma Primary open-angle glaucoma Pigmentary glaucoma Chronic angle closure glaucoma Other
5-FU Group
MMC Group
P Value
57 65.5 ⫾ 12.8 (29–83) 28:29
58 65.4 ⫾ 12.1 (32–82) 36:22
42 15 0/0 30:27
42 14 1/1 27:31
1.00† .83†
48 2 3 3 secondary openangle glaucoma, 1 pseudoexfoliation
49 4 3 1 aniridia, 1 Fuchs iridocyclitis
1.00†
.99* .19†
.58†
5-FU ⫽ 5-fluorouracil; MMC ⫽ mitomycin C; SD ⫽ standard deviation. *Student t test. † Fisher exact test.
ated eye were continued with the exception of any oral carbonic anhydrase inhibitors.
RESULTS A TOTAL OF 115 EYES OF 103 SUBJECTS WERE ENROLLED IN
this study, of which 57 received 5-FU while 58 received MMC. Table 1 summarizes baseline characteristics including gender, age, race, glaucoma diagnosis, and operated eye for each group. There were no significant differences between the groups with regard to these baseline characteristics. The majority of the patients in both groups had primary open-angle glaucoma. All enrolled eyes had at least 6 months of follow up except for one subject in the 5-FU group who died and one subject in the MMC group who was lost to follow up. By 12 months, eight additional eyes in the 5-FU group and three additional eyes in the MMC group were lost to follow up. The preoperative and postoperative mean best-corrected logMAR vision, IOP, and number of glaucoma medications are shown in Table 2. Mean preoperative IOP in the 5-FU group was 2.4 mm Hg higher than the mean preoperative IOP in the MMC group, although this difference was not statistically significant (P ⫽ .09). The decrease in IOP from preoperative visit to 12 months postoperative was statistically significant for both the 5-FU and MMC groups (P ⬍ .0001 for each group, paired t test). The decrease in best-corrected logMAR vision from preoperative visit to 12 months postoperative was also statistically significant for each group (5-FU group: P ⫽ .0004; MMC group: P ⫽ .003, Wilcoxon matched-pairs signedVOL. 134, NO. 4
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rank test). Both groups showed a significant drop in the number of glaucoma medications used at 12 months compared with preoperatively (P ⬍ .0001 for each group, Wilcoxon matched-pairs signed-rank test). Table 3 shows the failures and complications by 12 months in both groups. The IOP criterion for failure for this table was IOP ⬎ 21 mm Hg. While there were more complications in the MMC group, the differences were not statistically significant for any of the categories or as a whole. All three failures in the 5-FU group were due to bleb failures that required revision or further glaucoma surgery. There were two bleb failures in the MMC group. In one of these eyes, the sclera was punctured inadvertently during placement of the superior rectus bridle suture and a vitreous hemorrhage developed during the trabeculectomy surgery. It is unclear if these intraoperative complications caused the bleb to fail. Complications that resulted in permanent vision loss occurred in four eyes in the MMC group, including two cases of endophthalmitis associated with a bleb leak, one case of a delayed suprachoroidal hemorrhage, and one case of severe hypotony maculopathy that decreased vision from 20/30 to counting fingers. Success rates for various target IOPs were similar between the antimetabolite groups. Figures 1 and 2 show the proportion of eyes with successful outcomes at 6 and 12 months for target pressures of 21, 18, 15, and 12 mm Hg. Successful eyes had IOPs that were at or lower than target IOP and had no serious complication that resulted in permanent vision loss. When a postoperative IOP of less than 21, with or without medications, was considered a success, 53 of 56 eyes (95%) in the 5-FU group and 54 of MMC
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TABLE 2. Best-corrected logMAR Visual Acuity, Intraocular Pressure, and Number of Glaucoma Medications Pre- and Postoperatively
Best-corrected logMAR (mean ⫾ SD) Preoperative 6 months postoperative 12 months postoperative IOP in mm Hg (mean ⫾ SD) Preoperative 6 months postoperative 12 months postoperative Medications (mean ⫾ SD) Preoperative 6 months postoperative 12 months postoperative
5-FU Group
MMC Group
P Value
0.19 ⫾ 0.35 0.32 ⫾ 0.47 0.42 ⫾ 0.63
0.26 ⫾ 0.51 0.37 ⫾ 0.48 0.36 ⫾ 0.56
.40* .33* .49*
24.3 ⫾ 8.1 10.1 ⫾ 6.4 10.9 ⫾ 6.4
21.9 ⫾ 6.6 9.4 ⫾ 4.6 9.9 ⫾ 5.0
.09† .52† .36†
2.7 ⫾ 1.2 0.1 ⫾ 0.6 0.2 ⫾ 0.6
2.4 ⫾ 1.2 0.1 ⫾ 0.5 0.1 ⫾ 0.5
.17* .86* .90*
IOP ⫽ intraocular pressure; logMAR ⫽ logarithm of the minimum angle of resolution; SD ⫽ standard deviation. *Mann–Whitney U test. † Student t test.
TABLE 3. Bleb Failures and Complications by 12 Months Post Trabeculectomy
Bleb failures (IOP ⬎ 21 mm Hg or bleb revision) Complications Bleb leak Persistent hypotony maculopathy Drainage of choroidal effusions Suprachoroidal hemorrhage Endophthalmitis Total complications Total eyes with complications
5-FU Group
MMC Group
P Value*
3
2
.68
2 0 2 0 0 4 4
4† 1 3 1 2 11 9†
.68 1.00 1.00 1.00 .50 .09 .24
IOP ⫽ intraocular pressure; MMC ⫽ mitomycin C; 5-FU ⫽ 5-fluorouracil. *Fisher exact test. † Two cases of bleb leak were associated with endophthalmitis.
57 (95%) in the MMC group had successful outcomes at 6 months (P ⫽ 1.00). At 6 months, the 5-FU and MMC groups had essentially identical success rates (IOP ⱕ 18 mm Hg, P ⫽ 1.00; IOP ⱕ 15, P ⫽ .79; IOP ⱕ 12, P ⫽ 1.00). At 12 months, 45 of 48 eyes (94%) in the 5-FU group and 48 of 54 eyes (89%) in the MMC group met a target IOP of 21 mm Hg (P ⫽ .49). Although the proportion of eyes considered successful was slightly higher in the 5-FU group for each target IOP at 12 months, there was no statistically significant difference between the two groups for any of the IOP criteria (IOP ⱕ 21, P ⫽ .49; IOP ⱕ 18, P ⫽ .33; IOP ⱕ 15, P ⫽ .81; IOP ⱕ 12, P ⫽ 1.00). Several eyes in each group were put on glaucoma medications after surgery to help control the IOP. At 12 months postoperative, five of the 45 successful (IOP ⱕ 21 524
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mm Hg) eyes in the 5-FU group and six of the 48 successful eyes in the MMC group were on glaucoma medications to control their IOP. All were on just one medication except for one eye in the MMC group that was on three medications. Postoperative procedures were performed on several eyes in each group. Table 4 shows the immediate postoperative interventions performed. In the 5-FU group, four eyes underwent argon laser suture lysis, seven received subconjunctival 5-FU injections, two had both argon laser suture lysis and 5-FU injections, one received an autologous blood injection into the bleb to correct hypotony due to overfiltration, and one underwent Nd:YAG laser to the sclerostomy site within the first month to control the IOP. In the MMC group, six eyes underwent argon laser suture lysis, four received subconjunctival 5-FU injections, two OF
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FIGURE 1. Proportion of eyes achieving various target intraocular pressures (IOP) at 6 months post-trabeculectomy. An eye was considered a success if the IOP was less than or equal to the target IOP and there was no serious complication that resulted in permanent vision loss. At each target IOP, the success rates for the two groups were compared by the Fisher exact test for proportions. 5FU ⴝ 5-fluorouracil; MMC ⴝ mitomycin C.
had both argon laser suture lysis and 5-FU injections, four received an autologous blood injection into the bleb to correct hypotony resulting from overfiltration or bleb leak, and three underwent Nd:YAG laser to the internal sclerostomy. During the initial 12-month postoperative period, four eyes in the 5-FU group and 14 eyes in the MMC underwent phacoemulsification with intraocular lens implantation (P ⫽ .02, Fisher exact test). There did not appear to be any correlation between the cataract surgery rate and incidence of hypotony. One of the four eyes in the 5-FU group and three of the 14 eyes in the MMC group that underwent cataract extraction had already experienced bleb failure or serious complication before their cataract surgery. Of the remaining three eyes in the 5-FU group and 11 eyes in the MMC group that were still considered successful at the time of their cataract surgery, all remained successful at 12 months.
DISCUSSION IN THIS PROSPECTIVE, RANDOMIZED, DOUBLE-MASKED,
clinical trial comparing intraoperative use of topical 5-FU and MMC, the surgeons remained masked to the antimeVOL. 134, NO. 4
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tabolite used during the procedure and the postoperative management. Unlike previous similar studies, our surgeons were unable to vary the postoperative management of each patient based on knowledge of the antimetabolite used intraoperatively.22,23 This surgeon masking ensured uniformity of postoperative management. In a prospective randomized multicenter trial, Singh and associates also detected no difference in efficacy and safety of 5-FU and MMC, although they used a higher dose of MMC than we did (0.4 mg/ml vs 0.2 mg/ml).23 The surgeons in the study were not masked to the antimetabolite used, which allows for some differences in surgical technique and postoperative management based on the surgeon’s knowledge of the antimetabolite used. In essence, the study by Singh and associates23 compares 5-FU trabeculectomy versus MMC trabeculectomy, whereas our study compares intraoperative 5-FU versus intraoperative MMC during trabeculectomy. If a surgeon believes a priori that 5-FU is less effective than MMC, then with a 5-FU trabeculectomy he or she may suture the trabeculectomy flap looser, cut flap sutures sooner, or be more apt to give 5-FU injections postoperatively. By masking our surgeons both intraoperatively and postoperatively, we minimized any surgeon bias in how the trabeculectomy was performed and how the eyes were managed postoperatively. MMC
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FIGURE 2. Proportion of eyes achieving various target intraocular pressures (IOP) at 12 months post-trabeculectomy. An eye was considered a success if the IOP was less than or equal to the target IOP and there was no serious complication that resulted in permanent vision loss. At each target IOP, the success rates for the two groups were compared by the Fisher exact test for proportions. 5FU ⴝ 5- fluorouracil; MMC ⴝ mitomycin C.
TABLE 4. Postoperative Interventions by 12 Months Postoperative Interventions
5-FU Group
MMC Group
P Value*
Autologous blood injection into bleb Argon laser suture lysis Subconjunctival 5-FU injections Both argon laser suture lysis and 5-FU injections Nd:YAG laser to sclerotomy
1† 4 7 2 1
4‡ 6 4 2 3
.36 .74 .36 1.00 .62
5-FU ⫽ 5-fluorouracil; MMC ⫽ mitomycin C; Nd:YAG ⫽ neodymium:yttrium-aluminum-garnet. *Fisher exact test. † For hypotony. ‡ For hypotony (3) and bleb leak.
The results of an in vitro study led Khaw and associates2 to propose that a single intraoperative application of these antimetabolites may achieve similar results to those protocols that involve repeated application. Another study evaluated the effect of intraoperative application of both antimetabolites on glaucoma filtering surgery on rabbits using a cellulose sponge similar to what we used in our study. The report found no significant difference in IOP control between 50 mg/ml of 5-FU and 0.2 mg/ml of MMC when applied in this manner.16 Unlike our study, however, each sponge was applied for 1 minute and repeated five times to total 5 minutes. 526
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In our study, the cellulose sponge was applied with positive pressure on the sclera and the conjunctiva was draped over it. In essence, the soaked cellulose sponge was wedged into a pocket formed between the conjunctiva and sclera. This allowed the tissues being treated to be soaked in the antimetabolite while the cellulose sponge was applied, not relying on passive diffusion of the antimetabolite from the sponge into the tissues. The question of whether we achieved steady and adequate drug delivery using one Weck-Cel sponge may be raised. However, in an in vitro study comparing a 1-minute exposure and a 5-minute exposure of the Tenon capsule to 5-FU, MerriOF
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man and associates25 reported similar antiproliferative effects on fibroblasts. In patient eyes, even a single short duration exposure to topical antimetabolite results in adequate IOP control in most cases. In a nonrandomized clinical study comparing antimetabolites during primary trabeculectomy, a single 1-minute application of MMC or 5-FU resulted in high rates of IOP control that were similar to our results.26 Our results show excellent IOP control in the 5-FU group along with a lower rate of complications. Although previous studies have reported similar results upon comparing these two antimetabolites,2,4 – 6,16,22,23 our study is the only masked clinical study comparing the topical intraoperative application of 5-FU with topical intraoperative MMC in low-risk eyes. Although the percentage of subjects achieving target IOP in 5-FU and MMC groups were similar, the MMC group tended to have more complications including hypotony, maculopathy, and infection. Although hypotony and maculopathy have been reported with the intraoperative use of these antimetabolites, a high rate of occurrence has been linked with MMC especially at high doses.3,5– 8,27–33 Our study has several significant limitations. Our sample size allowed us to detect only fairly large differences in success rates between the 5-FU and MMC groups. In retrospect, we underestimated the efficacy of topical 5-FU in achieving good outcomes. Furthermore, a sizable number of eyes were lost to follow up, particularly in the 5-FU group, which further reduced the power of the study. In addition, because the complication rates were fairly low in both groups, to show a statistically significant difference in the complication rates would require considerably greater sample sizes. Our study suggests that intraoperative topical 5-FU is at least as effective as intraoperative topical MMC in reducing IOP of eyes undergoing primary trabeculectomy according to our protocol. In addition, intraoperative topical 5-FU may have a lower rate of hypotony and its associated sequelae compared with intraoperative topical MMC. However, long-term results are still needed before definite conclusions can be made.
1. Skuta GL, Parrish RK 2nd. Wound healing in glaucoma filtering surgery. Surv Ophthalmol 1987;32:149 –170. 2. Khaw PT, Sherwood MB, MacKay SL, Rossi MJ, Schultz G. Five-minute treatments with fluorouracil, floxuridine, and mitomycin have long-term effects on human Tenon’s capsule fibroblasts. Arch Ophthalmol 1992;110:1150 –1154. 3. Knapp A, Heuer DK, Stern GA, Driebe WT, Jr. Serious corneal complications of glaucoma filtering surgery with postoperative 5-fluorouracil. Am J Ophthalmol 1987;103: 183–187. 4. Yamamoto T, Varani J, Soong HK, Lichter PR. Effects of
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6. 7. 8.
9. 10. 11. 12. 13.
14. 15.
16.
17. 18.
19.
20.
REFERENCES
VOL. 134, NO. 4
5.
VS
21. 22. 23.
24.
MMC
5-fluorouracil and mitomycin C on cultured rabbit subconjunctival fibroblasts. Ophthalmology 1990;97:1204 –1210. Skuta GL, Beeson CC, Higginbotham EJ, et al. Intraoperative mitomycin versus postoperative 5-fluorouracil in highrisk glaucoma filtering surgery. Ophthalmology 1992;99: 438 – 444. Kitazawa Y, Kawase K, Matsushita H, Minobe M. Trabeculectomy with mitomycin. A comparative study with fluorouracil. Arch Ophthalmol 1991;109:1693–1698. Palmer SS. Mitomycin as adjunct chemotherapy with trabeculectomy. Ophthalmology 1991;98:317–321. Dunn JP, Seamone CD, Ostler HB, Nickel BL, Beallo A. Development of scleral ulceration and calcification after pterygium excision and mitomycin therapy. Am J Ophthalmol 1991;112:343–344. The Fluorouracil Filtering Surgery Study Group. Fluorouracil Filtering Surgery Study one-year follow-up. Am J Ophthalmol 1989;108:625– 635. Liebmann JM, Ritch R, Marmor M, Nunez J, Wolner B. Initial 5-fluorouracil trabeculectomy in uncomplicated glaucoma. Ophthalmology 1991;98:1036 –1041. Jampel HD. Effect of brief exposure to mitomycin C on viability and proliferation of cultured human Tenon’s capsule fibroblasts. Ophthalmology 1992;99:1471–1476. Mora JS, Nguyen N, Iwach AG, et al. Trabeculectomy with intraoperative sponge 5-fluorouracil. Ophthalmology 1996; 103:963–970. Smith MF, Doyle JW, Nguyen QH, Sherwood MB. Results of intraoperative 5-fluorouracil or lower dose mitomycin-C administration on initial trabeculectomy surgery. J Glaucoma 1997;6:104 –110. The Fluorouracil Filtering Surgery Study Group. Five-year follow-up of the Fluorouracil Filtering Surgery Study. Am J Ophthalmol 1996;121:349 –366. Khaw PT, Doyle JW, Sherwood MB, Grierson I, Schultz G, McGorray S. Prolonged localized tissue effects from 5-minute exposures to fluorouracil and mitomycin C. Arch Ophthalmol 1993;111:263–267. Khaw PT, Doyle JW, Sherwood MB, Smith MF, McGorray S. Effects of intraoperative 5-fluorouracil or mitomycin C on glaucoma filtration surgery in the rabbit. Ophthalmology 1993;100:367–372. Dietze PJ, Feldman RM, Gross RL. Intraoperative application of 5-fluorouracil during trabeculectomy. Ophthalmic Surg 1992;23:662– 665. Egbert PR, Williams AS, Singh K, Dadzie P, Egbert TB. A prospective trial of intraoperative fluorouracil during trabeculectomy in a black population. Am J Ophthalmol 1993;116:612– 616. Lanigan L, Sturmer J, Baez KA, Hitchings RA, Khaw PT. Single intraoperative applications of 5-fluorouracil during filtration surgery: early results. Br J Ophthalmol 1994;78:33– 37. Megevand GS, Salmon JF, Scholtz RP, Murray AD. The effect of reducing the exposure time of mitomycin C in glaucoma filtering surgery. Ophthalmology 1995;102:84 –90. Kupin TH, Juzych MS, Shin DH, Khatana AK, Olivier MM. Adjunctive mitomycin C in primary trabeculectomy in phakic eyes. Am J Ophthalmol 1995;119:30 –39. Singh K, Egbert PR, Byrd S, et al. Trabeculectomy with intraoperative 5-fluorouracil versus mitomycin C. Am J Ophthalmol 1997;123:48 –53. Singh K, Mehta K, Shaikh NM, et al. Trabeculectomy with intraoperative mitomycin C versus 5-fluorouracil. Prospective randomized clinical trial. Ophthalmology 2000;107: 2305–2309. Chen PP, Yamamoto T, Sawada A, Parrish RK, 2nd, IN
TRABECULECTOMY
527
25.
26.
27. 28.
29. Lee DA, Hersh P, Kersten D, Melamed S. Complications of subconjunctival 5-fluorouracil following glaucoma filtering surgery. Ophthalmic Surg 1987;18:187–190. 30. Costa VP, Wilson RP, Moster MR, Schmidt CM, Gandham S. Hypotony maculopathy following the use of topical mitomycin C in glaucoma filtration surgery. Ophthalmic Surg 1993;24:389 –394. 31. Zacharia PT, Deppermann SR, Schuman JS. Ocular hypotony after trabeculectomy with mitomycin C. Am J Ophthalmol 1993;116:314 –326. 32. Shields MB, Scroggs MW, Sloop CM, Simmons RB. Clinical and histopathologic observations concerning hypotony after trabeculectomy with adjunctive mitomycin C. Am J Ophthalmol 1993;116:673– 683. 33. Stamper RL, McMenemy MG, Lieberman MF. Hypotonous maculopathy after trabeculectomy with subconjunctival 5-fluorouracil. Am J Ophthalmol 1992;114:544 –553.
Kitazawa Y. Use of antifibrosis agents and glaucoma drainage devices in the American and Japanese Glaucoma Societies. J Glaucoma 1997;6:192–196. Merriman MB, Mora JS, Beaumont BW, Merrilees MJ. Effects of varying 5-fluorouracil exposure duration on Tenon’s capsule fibroblasts. Clin Experiment Ophthalmol 2001; 29:248 –252. Vijaya L, Mukhesh BN, Shantha B, Ramalingam S, Sathi Devi AV. Comparison of low-dose intraoperative mitomycin-C versus 5-fluorouracil in primary glaucoma surgery: a pilot study. Ophthalmic Surg Lasers 2000;31:24 –30. Katz GJ, Higginbotham EJ, Lichter PR, et al. Mitomycin C versus 5-fluorouracil in high-risk glaucoma filtering surgery. Extended follow-up. Ophthalmology 1995;102:1263–1269. Mermoud A, Salmon JF, Murray AD. Trabeculectomy with mitomycin C for refractory glaucoma in blacks. Am J Ophthalmol 1993;116:72–78.
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