Who Should Receive Antimetabolites After Filtering Surgery? tell what think that should do. What would you do if this Don't patient?," and of antimetabolites with the about the me
you
were
questions filtering surgery. go
I your
so
use
In
practice, many difficult and unre-
solved issues remain. Who should receive these medications and for what conditions? Precisely what therapy should we offer, and when should we initiate or repeat it? With what expectation of improved surgical success can we counsel our patients? What price will our patients pay in terms of an increased complication rate and monetary expense, and for what reward? See also pp 1049, 1072, and 1150.
Ever since DeWecker1 first produced a fistula between the anterior chamber and the subconjunctival space, variations on this surgical theme have evolved. The modifications have shared the principle of increasing the rate of aqueous egress through a surgically produced channel that bypasses the malfunctioning drainage of the trabecular meshwork. Until recently, these technical nuances, including the implantation of syn¬ thetic drainage devices, have concentrated largely on the operative intervention itself, rather than on the subsequent wound-healing process. Recent interest has focused on medical therapy designed to maintain the patency of the fistula and to promote filtering bleb formation. Postoperative
topical corticosteroids,2 preoperative subconjunctival corticosteroids,3 postoperative topical ß-aminopropionitrile,4 postoperative -penicillamine,5 implanta¬ tion of bleomycin-impregnated collagen sponges," post¬ operative subconjunctival injections of fluorouracil,7" postoperative topical trifluorothymidine (Viroptic),10·11 and intraoperative subconjunctival mitomycin1214 have been reported to improve success with filtering sur¬ gery in animals
or
Pharmacologie
humans. modulation of
wound-healing
at-
to disrupt the orderly sequence of events that starts with the release of tissue factors in re¬ sponse to incisional injury of the conjunctiva and ends with the formation of a mature scar at the filtering site. The beneficial effect of postoperative topical corticosteroids, the first medical therapy demonstrated to improve the success rate of filter¬ ing surgery in a clinical trial, was described as re¬ cently as 1985.2 The clinical practice of using topical corticosteroids after filtering surgery, however, an¬ tedated this study by at least 10 years. Reduction of postoperative inflammation, a subsequent stimulus for cellular proliferation at the filtering site, is the most likely mechanism of its action. Newer pharmacologie treatments have focused on directly limiting the proliferation of fibroblasts at the filtering site. Historically, research has evolved from an investigation of pharmacologie agents in tissue culture (to limit the proliferation of fibroblasts)15'16 through their application to Altering surgery in an animal model5,7·13 and on to pilot human studies8,12,14 and controlled clinical trials.9,1720 The antimetabolite fluorouracil, best known as an antiproliferative agent in the palliative treatment of colonie and breast can¬ cer, was first described to improve bleb formation after filtering surgery in an owl-monkey model in 1984.7 Subsequent pilot studies have suggested a beneficial effect on the lowering of intraocular pres¬ sure after filtering surgery in human eyes at high risk for filtering surgery failure, such as eyes with aphakia, neovascular glaucoma, and chronic inflam¬ mation and those eyes in which previous filtering surgery has failed.8,21 A multicenter prospective clin¬ ical trial, the Fluorouracil Filtering Surgery Study, was designed to investigate the safety and efficacy of postoperative injections of fluorouracil after filter¬ ing surgery in eyes with uncontrolled glaucoma that had previously undergone either cataract extraction or filtering surgery.9 The 1-year follow-up results
tempts
Downloaded From: http://archopht.jamanetwork.com/ by a University of Arizona Health Sciences Library User on 06/09/2015
statistically significantly improved with filtering surgery with the fluorouracil of compared with trabeculec¬ application tomy alone. Five-milligram subconjunctival injec¬ tions of fluorouracil (0.5 mL of a 10-g/L solution) were given twice daily during the first postoperative week and once daily during the second postoperative week. The necessity of multiple subconjunctival in¬ jections and the high incidence of conjunctival and corneal epithelial toxic effects manifested by con¬ junctival wound leaks and corneal epithelial defects have limited the widespread application of this tech¬ nique. Recently reported complications of unex¬ pected hypotony and associated permanently re¬ duced central visual acuity in young, black, usually myopic, patients undergoing primary filtering sur¬ described chance of
a success
gery have resulted in further caution with the use of fluorouracil in all patients.20 Serious corneal infec¬ tions observed in eyes with préexistent corneal epi¬ thelial edema have argued against the use of fluo¬ rouracil in eyes with this condition.22 The recently reported increased susceptibility to late-onset bleb infections, particularly in eyes with filtering blebs located near the inferior limbus, have suggested fur¬ ther limitations of its use.23 Mitomycin, a rediscovered antimetabolite first de¬ scribed in a single intraoperative application during filtering surgery by Chen12 in 1983, is an increasingly popular alternative to postoperative fluorouracil in eyes with poor prognoses for filtering surgery.14 The primary effect of mitomycin appears to be a cytocidal effect on subconjunctival fibroblasts at the filtering site.16 As such, the focal application limits the toxic ef¬ fects to tissues directly exposed to the drug. The reduced incidence of corneal toxic effects and the sin¬ gle intraoperative application are major attractions of this treatment. Two independent clinical trials at the University of Michigan School of Medicine, Ann Arbor, and Gifii (Japan) University School of Medicine, designed to compare the safety and efficacy of multiple postoper¬ ative subconjunctival injections of fluorouracil with a sin¬ gle intraoperative application of mitomycin, demon¬ strated that corneal and conjunctival toxic effects are less common with mitomycin.18,19 The beneficial effect of both agents on lowering of intraocular pressure appears comparable with that described with postoperative flu¬ orouracil in the Fluorouracil Filtering Surgery Study; however, intraocular pressures remained statistically significantly lower in the mitomycin-treated group.19 Due to the potential for anterior chamber penetration and endothelial damage, mitomycin should not be in¬
jected subconjunctivally after filtering surgery.24 Based on the tissue studies of Khaw et al,25 it seems likely that longer intraoperative subconjunctival appli¬ cations of fluorouracil may have effects similar to mito¬
mycin.
With the plethora of published scientific information and the abundance of clinical hunches, the fact remains that no clear-cut recommendation can be given with respect to the use of any antimetabolite in all patients. The real questions are not if these agents affect wound healing, or even if they improve the chance of filtering
surgery success, but rather what the risk-benefit and cost-benefit ratios are compared with standard filter¬ ing surgery alone. The important ethical issue (how we use incomplete information about a new treatment be¬ fore long-term results are available) remains unan¬ swered. The ongoing controversy regarding the con¬ tinued use of silicone breast implants underscores the im¬ portance of vigilant long-term follow-up with any new
technique.
In the case of fluorouracil and mitomycin, therapeu¬ tic decisions are complicated by the fact that both drugs have already been approved by the Food and Drug Administration for indications of systemic chemother¬ apy. To date, neither agent has been approved as a postoperative or intraoperative adjunct to standard filtering surgery. Unfortunately, we are confronted daily by patients whose glaucoma remains recalcitrant to standard medical and surgical therapy. Our over¬ whelming desire is to effect a speedy and permanent cure; in practice, this means decreasing intraocular pressure to a nondamaging level. In our desire to achieve this goal, we are cautioned to temper our en¬ thusiasm for employing new therapies by the timehonored dictum of medical care, primum non nocete, ie, first do no harm. Unfortunately, this does not help us determine how much new information is necessary be¬ fore a "highly probable beneficial effect" or a "statisti¬ cally significant effect with limited follow-up" qualifies as the standard of care. When does withholding a new medical or surgical therapy become unethical? Where is the dividing line between using a technique or drug that should be investigated only under the aegis of an Insti¬ tutional Review Board acting on behalf of the patient, and a therapy for which the patient alone can give fully informed consent? How much information must we as physicians understand before we can honestly expect patients to give informed consent? The safest advice with respect to the use of antime¬ tabolites with filtering surgery is to base decisionmaking on the results of investigations in which pa¬ tients have been treated as subjects of scientific inquiry. This also implies the continued evaluation and modification of treatment based on the long-term follow-up of these patients. Considering the published findings, it seems reasonable at present to limit the use of fluorouracil and mitomycin to patients with poor prognoses for filtering surgery. With respect to the possible future use of untested antimetabolites, initial patient treatment must be based on more than preliminary tissue culture and an¬ imal surgical results. Originally established to protect patient rights, Institutional Review Boards accelerate legitimate scientific research and assure that the results will be interpretable, irrespective of the out¬ come. Controlled clinical trials have surfaced as the preferred investigative tool for the evaluation of new drugs and surgical techniques on humans. Although clinical trials have historically been multicentered, costly, and administered through the National Insti¬ tutes of Health, Bethesda, Md, scientifically valid con¬ clusions are possible with properly designed singlecenter studies. The sooner such trials are initiated, the
Downloaded From: http://archopht.jamanetwork.com/ by a University of Arizona Health Sciences Library User on 06/09/2015
sooner we
will know
to these
tough
Richard K. Parrish Miami, Fla
II, MD
some answers
questions.
References 1. DeWecker L. La cicatrice a filtration. Ann Oculist. 1882;87:133-143. 2. Starita RJ, Fellman RL, Spaeth GL. Short- and long-term effects of post-
operative corticosteroids on trabeculectomy. Ophthalmology. 1985;92:938-945. 3. Giangiacomo J, Deuker DK, Adelstein E. The effect of preoperative subconjunctival triamcinolone administration on glaucoma filtration, I: trabeculec-
tomy following subconjunctival triamcinolone. Arch Ophthalmol. 1986;104:
838-841. 4. Fourman S. Effects of aminopropionitrile on glaucoma filter bleb in rabbits. Ophthalmic Surg. 1988;19:649-642. 5. McGuigan LJB, Cook DJ, Yablonski ME. Dexamethasone, D-penicillamine, and glaucoma filter surgery in rabbits. Invest Ophthalmol Vis
Sci. 1986;27:1755-1757.
6. Kay JS, Fryczkowski AW, Litin BS, Chvapil M, Jones MA, Herschler J. Delivery of anti-fibroblast agents as adjuncts to filtration surgery, II: delivery of 5-fluorouracil and bleomycin in a collagen implant\p=m-\pilotstudy in the rabbit. Ophthalmic Surg. 1986;17:796-801. 7. Gressel MG, Parrish RK II, Folberg R. 5-fluorouracil and glaucoma filtering surgery, I: an animal model. Ophthalmology. 1984;91:378-383. 8. Heuer DK, Parrish RK II, Gressel MG, Hodapp E, Palmberg PF, Anderson DR. 5-fluorouracil and glaucoma filtering surgery, II: a pilot study. Ophthalmology. 1984;91:384-394. 9. The Fluorouracil Filtering Study Group. Fluorouracil Filtering Surgery Study: one-year follow-up. Am J Ophthalmol. 1989;108:625-635. 10. Katz LJ, Varma R, Spaeth GL, Gross RL, Samuel T. Topical trifluothymidine following trabeculectomy: a case series. Invest Ophthalmol Vis Sci. 1988;29(suppl):367. 11. Katz LJ, Spaeth GL, Steinmann WC, Fahmy IA, Ali MA, Gross RL. Topical trifluridine following filtering surgery: a randomized prospective trial. Invest Ophthalmol Vis Sci. 1991;32(suppl):1121.
12. Chen CW. Enhancement intraocular pressure controlling effectiveness of trabecuectomy by local application of mytomicin-C. Trans Asia Pacific Acad
Ophthamol. 1983;9:172-177. 13. Bergstrom TJ, Wilkinson WS, Skuta GL, Watnick RL, Elner VM. The effects of subconjunctival mitomycin-c on glaucoma filtration surgery in rabbits. Arch Ophthalmol. 1991;109:1725-1730. 14. Palmer SS. Mitomycin as adjunct chemotherapy with trabeculectomy. Ophthalmology. 1991;98:317-321. 15. Blumenkranz MS, Claflin A, Hajek AS. Selection of therapeutic agents for intraocular proliferative disease: cell culture evaluation. Arch Ophthalmol.
1984;102:598-604. 16. Lee DA, Lee TC, Cortes AE, Kitada S. Effects of mitramycin, mitomycin, daunorubicin and bleomycin on human subconjunctival fibroblasts attachment and proliferative. Invest Ophthalmol Vis Sci. 1990;31:
2136-2144. 17. Ruderman JM, Welch DB, Smith MF, Shoch DE. A randomized study of 5-fluorouracil and filtration surgery. Am J Ophthalmol. 1987;104:218-224. 18. Beeson CC, Skuta GS, Higginbotham EJ. Randomized clinical trial of intraoperative subconjunctival mitomycin-c versus postoperative 5-fluorouracil. Invest Ophthalmol Vis Sci. 1991;32(suppl):1122. 19. Kitazawa Y, Kawase K, Matsushita H, Minobe M. Trabeculectomy with mitomycin: a comparative study with fluorouracil. Arch Ophthalmol. 1991; 109:1693-1698. 20. Loftfield K, Ball SF. 5-fluorouracil (5-FU) in primary trabeculectomy: a randomized study. Invest Ophthalmol Vis Sci. 1991;32(suppl):745. 21. Jampel HD, Jabs DA, Quigley HA. Trabeculectomy with 5-fluorouracil for adult inflammatory glaucoma. Am J Ophthalmol. 1990;109:168-173. 22. Knapp A, Heuer DK, Stern GA, Driebe WT. Serious corneal complications of glaucoma filtering surgery with postoperative 5-fluorouracil. Am J
Ophthalmol. 1987;103:183-187. 23. Wolner B, Liebmann JM, Sassani JW, Ritch R, Speaker R, Marmor M. Late bleb-related endophthalmitis after trabeculectomy with adjunctive 5-fluorouracil. Ophthalmology. 1991;98:1053-1060. 24. Derick RJ, Pasquale L, Quigley HA, Jampet H. Potential toxicity of mitomycin c. Arch Ophthalmol. 1991;109:1635. 25. Khaw PT, Sherwood MB, MacKay SLD, Rossi MJ, Schultz G. 5-minute treatments with fluorouracil, floxuridine, and mitomycin have long-term effects on human Tenon's capsule fibroblasts. Arch Ophthalmol. 1992:110:1146-1150.
Downloaded From: http://archopht.jamanetwork.com/ by a University of Arizona Health Sciences Library User on 06/09/2015
you
were
questions filtering surgery. go
I your
so
use
In
practice, many difficult and unre-
solved issues remain. Who should receive these medications and for what conditions? Precisely what therapy should we offer, and when should we initiate or repeat it? With what expectation of improved surgical success can we counsel our patients? What price will our patients pay in terms of an increased complication rate and monetary expense, and for what reward? See also pp 1049, 1072, and 1150.
Ever since DeWecker1 first produced a fistula between the anterior chamber and the subconjunctival space, variations on this surgical theme have evolved. The modifications have shared the principle of increasing the rate of aqueous egress through a surgically produced channel that bypasses the malfunctioning drainage of the trabecular meshwork. Until recently, these technical nuances, including the implantation of syn¬ thetic drainage devices, have concentrated largely on the operative intervention itself, rather than on the subsequent wound-healing process. Recent interest has focused on medical therapy designed to maintain the patency of the fistula and to promote filtering bleb formation. Postoperative
topical corticosteroids,2 preoperative subconjunctival corticosteroids,3 postoperative topical ß-aminopropionitrile,4 postoperative -penicillamine,5 implanta¬ tion of bleomycin-impregnated collagen sponges," post¬ operative subconjunctival injections of fluorouracil,7" postoperative topical trifluorothymidine (Viroptic),10·11 and intraoperative subconjunctival mitomycin1214 have been reported to improve success with filtering sur¬ gery in animals
or
Pharmacologie
humans. modulation of
wound-healing
at-
to disrupt the orderly sequence of events that starts with the release of tissue factors in re¬ sponse to incisional injury of the conjunctiva and ends with the formation of a mature scar at the filtering site. The beneficial effect of postoperative topical corticosteroids, the first medical therapy demonstrated to improve the success rate of filter¬ ing surgery in a clinical trial, was described as re¬ cently as 1985.2 The clinical practice of using topical corticosteroids after filtering surgery, however, an¬ tedated this study by at least 10 years. Reduction of postoperative inflammation, a subsequent stimulus for cellular proliferation at the filtering site, is the most likely mechanism of its action. Newer pharmacologie treatments have focused on directly limiting the proliferation of fibroblasts at the filtering site. Historically, research has evolved from an investigation of pharmacologie agents in tissue culture (to limit the proliferation of fibroblasts)15'16 through their application to Altering surgery in an animal model5,7·13 and on to pilot human studies8,12,14 and controlled clinical trials.9,1720 The antimetabolite fluorouracil, best known as an antiproliferative agent in the palliative treatment of colonie and breast can¬ cer, was first described to improve bleb formation after filtering surgery in an owl-monkey model in 1984.7 Subsequent pilot studies have suggested a beneficial effect on the lowering of intraocular pres¬ sure after filtering surgery in human eyes at high risk for filtering surgery failure, such as eyes with aphakia, neovascular glaucoma, and chronic inflam¬ mation and those eyes in which previous filtering surgery has failed.8,21 A multicenter prospective clin¬ ical trial, the Fluorouracil Filtering Surgery Study, was designed to investigate the safety and efficacy of postoperative injections of fluorouracil after filter¬ ing surgery in eyes with uncontrolled glaucoma that had previously undergone either cataract extraction or filtering surgery.9 The 1-year follow-up results
tempts
Downloaded From: http://archopht.jamanetwork.com/ by a University of Arizona Health Sciences Library User on 06/09/2015
statistically significantly improved with filtering surgery with the fluorouracil of compared with trabeculec¬ application tomy alone. Five-milligram subconjunctival injec¬ tions of fluorouracil (0.5 mL of a 10-g/L solution) were given twice daily during the first postoperative week and once daily during the second postoperative week. The necessity of multiple subconjunctival in¬ jections and the high incidence of conjunctival and corneal epithelial toxic effects manifested by con¬ junctival wound leaks and corneal epithelial defects have limited the widespread application of this tech¬ nique. Recently reported complications of unex¬ pected hypotony and associated permanently re¬ duced central visual acuity in young, black, usually myopic, patients undergoing primary filtering sur¬ described chance of
a success
gery have resulted in further caution with the use of fluorouracil in all patients.20 Serious corneal infec¬ tions observed in eyes with préexistent corneal epi¬ thelial edema have argued against the use of fluo¬ rouracil in eyes with this condition.22 The recently reported increased susceptibility to late-onset bleb infections, particularly in eyes with filtering blebs located near the inferior limbus, have suggested fur¬ ther limitations of its use.23 Mitomycin, a rediscovered antimetabolite first de¬ scribed in a single intraoperative application during filtering surgery by Chen12 in 1983, is an increasingly popular alternative to postoperative fluorouracil in eyes with poor prognoses for filtering surgery.14 The primary effect of mitomycin appears to be a cytocidal effect on subconjunctival fibroblasts at the filtering site.16 As such, the focal application limits the toxic ef¬ fects to tissues directly exposed to the drug. The reduced incidence of corneal toxic effects and the sin¬ gle intraoperative application are major attractions of this treatment. Two independent clinical trials at the University of Michigan School of Medicine, Ann Arbor, and Gifii (Japan) University School of Medicine, designed to compare the safety and efficacy of multiple postoper¬ ative subconjunctival injections of fluorouracil with a sin¬ gle intraoperative application of mitomycin, demon¬ strated that corneal and conjunctival toxic effects are less common with mitomycin.18,19 The beneficial effect of both agents on lowering of intraocular pressure appears comparable with that described with postoperative flu¬ orouracil in the Fluorouracil Filtering Surgery Study; however, intraocular pressures remained statistically significantly lower in the mitomycin-treated group.19 Due to the potential for anterior chamber penetration and endothelial damage, mitomycin should not be in¬
jected subconjunctivally after filtering surgery.24 Based on the tissue studies of Khaw et al,25 it seems likely that longer intraoperative subconjunctival appli¬ cations of fluorouracil may have effects similar to mito¬
mycin.
With the plethora of published scientific information and the abundance of clinical hunches, the fact remains that no clear-cut recommendation can be given with respect to the use of any antimetabolite in all patients. The real questions are not if these agents affect wound healing, or even if they improve the chance of filtering
surgery success, but rather what the risk-benefit and cost-benefit ratios are compared with standard filter¬ ing surgery alone. The important ethical issue (how we use incomplete information about a new treatment be¬ fore long-term results are available) remains unan¬ swered. The ongoing controversy regarding the con¬ tinued use of silicone breast implants underscores the im¬ portance of vigilant long-term follow-up with any new
technique.
In the case of fluorouracil and mitomycin, therapeu¬ tic decisions are complicated by the fact that both drugs have already been approved by the Food and Drug Administration for indications of systemic chemother¬ apy. To date, neither agent has been approved as a postoperative or intraoperative adjunct to standard filtering surgery. Unfortunately, we are confronted daily by patients whose glaucoma remains recalcitrant to standard medical and surgical therapy. Our over¬ whelming desire is to effect a speedy and permanent cure; in practice, this means decreasing intraocular pressure to a nondamaging level. In our desire to achieve this goal, we are cautioned to temper our en¬ thusiasm for employing new therapies by the timehonored dictum of medical care, primum non nocete, ie, first do no harm. Unfortunately, this does not help us determine how much new information is necessary be¬ fore a "highly probable beneficial effect" or a "statisti¬ cally significant effect with limited follow-up" qualifies as the standard of care. When does withholding a new medical or surgical therapy become unethical? Where is the dividing line between using a technique or drug that should be investigated only under the aegis of an Insti¬ tutional Review Board acting on behalf of the patient, and a therapy for which the patient alone can give fully informed consent? How much information must we as physicians understand before we can honestly expect patients to give informed consent? The safest advice with respect to the use of antime¬ tabolites with filtering surgery is to base decisionmaking on the results of investigations in which pa¬ tients have been treated as subjects of scientific inquiry. This also implies the continued evaluation and modification of treatment based on the long-term follow-up of these patients. Considering the published findings, it seems reasonable at present to limit the use of fluorouracil and mitomycin to patients with poor prognoses for filtering surgery. With respect to the possible future use of untested antimetabolites, initial patient treatment must be based on more than preliminary tissue culture and an¬ imal surgical results. Originally established to protect patient rights, Institutional Review Boards accelerate legitimate scientific research and assure that the results will be interpretable, irrespective of the out¬ come. Controlled clinical trials have surfaced as the preferred investigative tool for the evaluation of new drugs and surgical techniques on humans. Although clinical trials have historically been multicentered, costly, and administered through the National Insti¬ tutes of Health, Bethesda, Md, scientifically valid con¬ clusions are possible with properly designed singlecenter studies. The sooner such trials are initiated, the
Downloaded From: http://archopht.jamanetwork.com/ by a University of Arizona Health Sciences Library User on 06/09/2015
sooner we
will know
to these
tough
Richard K. Parrish Miami, Fla
II, MD
some answers
questions.
References 1. DeWecker L. La cicatrice a filtration. Ann Oculist. 1882;87:133-143. 2. Starita RJ, Fellman RL, Spaeth GL. Short- and long-term effects of post-
operative corticosteroids on trabeculectomy. Ophthalmology. 1985;92:938-945. 3. Giangiacomo J, Deuker DK, Adelstein E. The effect of preoperative subconjunctival triamcinolone administration on glaucoma filtration, I: trabeculec-
tomy following subconjunctival triamcinolone. Arch Ophthalmol. 1986;104:
838-841. 4. Fourman S. Effects of aminopropionitrile on glaucoma filter bleb in rabbits. Ophthalmic Surg. 1988;19:649-642. 5. McGuigan LJB, Cook DJ, Yablonski ME. Dexamethasone, D-penicillamine, and glaucoma filter surgery in rabbits. Invest Ophthalmol Vis
Sci. 1986;27:1755-1757.
6. Kay JS, Fryczkowski AW, Litin BS, Chvapil M, Jones MA, Herschler J. Delivery of anti-fibroblast agents as adjuncts to filtration surgery, II: delivery of 5-fluorouracil and bleomycin in a collagen implant\p=m-\pilotstudy in the rabbit. Ophthalmic Surg. 1986;17:796-801. 7. Gressel MG, Parrish RK II, Folberg R. 5-fluorouracil and glaucoma filtering surgery, I: an animal model. Ophthalmology. 1984;91:378-383. 8. Heuer DK, Parrish RK II, Gressel MG, Hodapp E, Palmberg PF, Anderson DR. 5-fluorouracil and glaucoma filtering surgery, II: a pilot study. Ophthalmology. 1984;91:384-394. 9. The Fluorouracil Filtering Study Group. Fluorouracil Filtering Surgery Study: one-year follow-up. Am J Ophthalmol. 1989;108:625-635. 10. Katz LJ, Varma R, Spaeth GL, Gross RL, Samuel T. Topical trifluothymidine following trabeculectomy: a case series. Invest Ophthalmol Vis Sci. 1988;29(suppl):367. 11. Katz LJ, Spaeth GL, Steinmann WC, Fahmy IA, Ali MA, Gross RL. Topical trifluridine following filtering surgery: a randomized prospective trial. Invest Ophthalmol Vis Sci. 1991;32(suppl):1121.
12. Chen CW. Enhancement intraocular pressure controlling effectiveness of trabecuectomy by local application of mytomicin-C. Trans Asia Pacific Acad
Ophthamol. 1983;9:172-177. 13. Bergstrom TJ, Wilkinson WS, Skuta GL, Watnick RL, Elner VM. The effects of subconjunctival mitomycin-c on glaucoma filtration surgery in rabbits. Arch Ophthalmol. 1991;109:1725-1730. 14. Palmer SS. Mitomycin as adjunct chemotherapy with trabeculectomy. Ophthalmology. 1991;98:317-321. 15. Blumenkranz MS, Claflin A, Hajek AS. Selection of therapeutic agents for intraocular proliferative disease: cell culture evaluation. Arch Ophthalmol.
1984;102:598-604. 16. Lee DA, Lee TC, Cortes AE, Kitada S. Effects of mitramycin, mitomycin, daunorubicin and bleomycin on human subconjunctival fibroblasts attachment and proliferative. Invest Ophthalmol Vis Sci. 1990;31:
2136-2144. 17. Ruderman JM, Welch DB, Smith MF, Shoch DE. A randomized study of 5-fluorouracil and filtration surgery. Am J Ophthalmol. 1987;104:218-224. 18. Beeson CC, Skuta GS, Higginbotham EJ. Randomized clinical trial of intraoperative subconjunctival mitomycin-c versus postoperative 5-fluorouracil. Invest Ophthalmol Vis Sci. 1991;32(suppl):1122. 19. Kitazawa Y, Kawase K, Matsushita H, Minobe M. Trabeculectomy with mitomycin: a comparative study with fluorouracil. Arch Ophthalmol. 1991; 109:1693-1698. 20. Loftfield K, Ball SF. 5-fluorouracil (5-FU) in primary trabeculectomy: a randomized study. Invest Ophthalmol Vis Sci. 1991;32(suppl):745. 21. Jampel HD, Jabs DA, Quigley HA. Trabeculectomy with 5-fluorouracil for adult inflammatory glaucoma. Am J Ophthalmol. 1990;109:168-173. 22. Knapp A, Heuer DK, Stern GA, Driebe WT. Serious corneal complications of glaucoma filtering surgery with postoperative 5-fluorouracil. Am J
Ophthalmol. 1987;103:183-187. 23. Wolner B, Liebmann JM, Sassani JW, Ritch R, Speaker R, Marmor M. Late bleb-related endophthalmitis after trabeculectomy with adjunctive 5-fluorouracil. Ophthalmology. 1991;98:1053-1060. 24. Derick RJ, Pasquale L, Quigley HA, Jampet H. Potential toxicity of mitomycin c. Arch Ophthalmol. 1991;109:1635. 25. Khaw PT, Sherwood MB, MacKay SLD, Rossi MJ, Schultz G. 5-minute treatments with fluorouracil, floxuridine, and mitomycin have long-term effects on human Tenon's capsule fibroblasts. Arch Ophthalmol. 1992:110:1146-1150.
Downloaded From: http://archopht.jamanetwork.com/ by a University of Arizona Health Sciences Library User on 06/09/2015
