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Prolonged Localized Tissue Effects From 5-Minute Exposures to Fluorouracil and Mitomycin C

Prolonged Localized Tissue Effects From 5-Minute Exposures to Fluorouracil and Mitomycin C Abstract • Rabbits undergoing full-thickness glaucoma filtering surgery were exposed for 5 minutes to one of three intraoperative treatments: (1) distilled water; (2) fluorouracil, 50 mg/mL; or (3) mitomycin C, 0.4 mg/mL. Tissue samples were taken from the subconjunctival and scleral tissues at the treated area and 90° and 180° from the center of the treated area and the adjacent cornea 2 mm from the limbus, 1 hour, 5 days, and 30 days postoperatively. The biopsy specimens were then placed in tissue culture media and the fibroblast outgrowths measured. Five-minute intraoperative treatments with fluorouracil resulted in a reversible delay of fibroblast outgrowths from treated subconjunctival and scleral tissues of just over 1 week in this model, whereas treatment with mitomycin C, 0.4 mg/mL, resulted in prolonged inhibition of at least 30 days. These effects were localized to the area treated. The many clinical implications of these findings are discussed. References 1. Rockwood EJ, Parrish RK II, Heuer DK, et al. Glaucoma filtering surgery with 5-fluorouracil . Ophthalmology . 1987;94:1071-1078.Crossref 2. The Fluorouracil Filtering Surgery Study Group. Fluorouracil Filtering Surgery Study one-year follow-up . Am J Ophthalmol . 1989;108:625-635. 3. Heuer DK, Parrish RK, Gressel MG, et al. 5-fluorouracil and glaucoma filtering surgery, III: intermediate follow-up of a pilot study . Ophthalmology . 1986;93:1537-1546.Crossref 4. Knapp A, Heuer DK, Stern GA, Driebe WT. Serious corneal complications of glaucoma filtering surgery with post operative 5-fluorouracil . Am J Ophthalmol . 1987;103:183-187. 5. Weinreb RN. Adjusting the dose of 5-fluorouracil after filtration surgery to minimize side effects . Ophthalmology . 1987;94:564-570.Crossref 6. Ruderman JM, Rabowsky JH. Low dose 5-fluorouracil and glaucoma filtration surgery . Ophthalmic Surg . 1989;20:347-349. 7. 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.Crossref 8. Pasquale LR,Thibault D, Dorman-Pease ME, Quigley HA, Jampel HD. Effect of topical mitomycin C on glaucoma filtration surgery in monkeys . Ophthalmology . 1992;99:14-18.Crossref 9. Chen CW, Huang HT, Bair JS, Lee CC. Trabeculectomy with simultaneous topical application of mitomycin-C in refractory glaucoma . J Ocul Pharmacol . 1990;6:175-182.Crossref 10. Palmer SS. Mitomycin as an adjunct chemotherapy with trabeculectomy . Ophthalmology . 1991;98:317-321.Crossref 11. Kitazawa Y, Kawase K, Matsushita H, Minobe M. Trabeculectomy with mitomycin: a comparative study with fluorouracil . Arch Ophthalmol . 1991;109:1693-1698.Crossref 12. Skuta GL, Beeson CC, Higginbotham EJ, et al. Intraoperative mitomycin versus postoperative 5-fluorouracil in high-risk glaucoma filtering surgery . Ophthalmology . 1992;99:438-444.Crossref 13. Kawase K, Matsushita H, Yamamoto T, Kitazawa Y. Mitomycin concentration in rabbit and human ocular tissues after topical administration . Ophthalmology . 1992;99:203-207.Crossref 14. Khaw PT, Sherwood MB, MacKay SLD, Rossi MB, Schultz GS. 5-Minute treatments with fluorouracil, floxuridine and mitomycin have long-term effects on human Tenon's capsule fibroblasts . Arch Ophthalmol . 1992;110:1150-1154.Crossref 15. 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. In press. 16. Seetner A, Morin JD. Healing of trabeculectomies in rabbits . Can J Ophthalmol . 1979;14:121-125. 17. Miller MH, Grierson I, Unger WI, Hitchings RA. Wound healing in an animal model of glaucoma fistulizing surgery in the rabbit . Ophthalmic Surg . 1989;20:350-357. 18. Khaw PT, Ward S, Porter A, Grierson I, Hitchings RA, Rice NSC. The long term effects of 5-fluorouracil and sodium butyrate on human Tenon's capsule fibroblasts . Invest Ophthalmol Vis Sci . 1992;33:2043-2052. 19. Yamamoto T, Varani J, Kaz Soong H, Lichter PR. Effect of 5-fluorouracil and mitomycin-c on cultured rabbit subconjunctival fibroblasts . Ophthalmology . 1990;97:1204-1210.Crossref 20. Khaw PT, Ward S, Grierson I, Rice NSC. The effects of beta-radiation on proliferating human Tenon's capsule fibroblasts . Br J Ophthalmol . 1991;75:580-583.Crossref 21. Minckler DS, Shammas A, Wilcox M, Ogden TE. Experimental studies of aqueous filtration using the Molteno implant . Trans Am Ophthalmol Soc . 1987;85:368-392. 22. Heuer DK, Lloyd MA, Abrams DA, et al. Preliminary report of a randomised clinical trial of single plate versus double plate Molteno implantation for glaucomas in aphakia and pseudophakia . In: Kriegelstein GK, ed. Glaucoma Update IV . New York, NY: Springer-Verlag NY Inc; 1991:244-249. 23. Wilson RP, Cantor L, Katz LJ, Schmidt CM, Steinmann WC, Allee S. Aqueous shunts: Molteno vs Schocket . Ophthalmology . 1992;99:672-678.Crossref 24. Nordlund JR, Pasquale LR, Quigley HA, Jampel HD. Effectiveness of intraoperative 5-fluorouracil versus intraoperative mitomycin-c in experimental rabbit glaucoma surgery . Invest Ophthalmol Vis Sci . 1992;33( (suppl) ):1393. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Ophthalmology American Medical Association

Prolonged Localized Tissue Effects From 5-Minute Exposures to Fluorouracil and Mitomycin C

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Publisher
American Medical Association
Copyright
Copyright © 1993 American Medical Association. All Rights Reserved.
ISSN
0003-9950
eISSN
1538-3687
DOI
10.1001/archopht.1993.01090020117035
Publisher site
See Article on Publisher Site

Abstract

Abstract • Rabbits undergoing full-thickness glaucoma filtering surgery were exposed for 5 minutes to one of three intraoperative treatments: (1) distilled water; (2) fluorouracil, 50 mg/mL; or (3) mitomycin C, 0.4 mg/mL. Tissue samples were taken from the subconjunctival and scleral tissues at the treated area and 90° and 180° from the center of the treated area and the adjacent cornea 2 mm from the limbus, 1 hour, 5 days, and 30 days postoperatively. The biopsy specimens were then placed in tissue culture media and the fibroblast outgrowths measured. Five-minute intraoperative treatments with fluorouracil resulted in a reversible delay of fibroblast outgrowths from treated subconjunctival and scleral tissues of just over 1 week in this model, whereas treatment with mitomycin C, 0.4 mg/mL, resulted in prolonged inhibition of at least 30 days. These effects were localized to the area treated. The many clinical implications of these findings are discussed. References 1. Rockwood EJ, Parrish RK II, Heuer DK, et al. Glaucoma filtering surgery with 5-fluorouracil . Ophthalmology . 1987;94:1071-1078.Crossref 2. The Fluorouracil Filtering Surgery Study Group. Fluorouracil Filtering Surgery Study one-year follow-up . Am J Ophthalmol . 1989;108:625-635. 3. Heuer DK, Parrish RK, Gressel MG, et al. 5-fluorouracil and glaucoma filtering surgery, III: intermediate follow-up of a pilot study . Ophthalmology . 1986;93:1537-1546.Crossref 4. Knapp A, Heuer DK, Stern GA, Driebe WT. Serious corneal complications of glaucoma filtering surgery with post operative 5-fluorouracil . Am J Ophthalmol . 1987;103:183-187. 5. Weinreb RN. Adjusting the dose of 5-fluorouracil after filtration surgery to minimize side effects . Ophthalmology . 1987;94:564-570.Crossref 6. Ruderman JM, Rabowsky JH. Low dose 5-fluorouracil and glaucoma filtration surgery . Ophthalmic Surg . 1989;20:347-349. 7. 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.Crossref 8. Pasquale LR,Thibault D, Dorman-Pease ME, Quigley HA, Jampel HD. Effect of topical mitomycin C on glaucoma filtration surgery in monkeys . Ophthalmology . 1992;99:14-18.Crossref 9. Chen CW, Huang HT, Bair JS, Lee CC. Trabeculectomy with simultaneous topical application of mitomycin-C in refractory glaucoma . J Ocul Pharmacol . 1990;6:175-182.Crossref 10. Palmer SS. Mitomycin as an adjunct chemotherapy with trabeculectomy . Ophthalmology . 1991;98:317-321.Crossref 11. Kitazawa Y, Kawase K, Matsushita H, Minobe M. Trabeculectomy with mitomycin: a comparative study with fluorouracil . Arch Ophthalmol . 1991;109:1693-1698.Crossref 12. Skuta GL, Beeson CC, Higginbotham EJ, et al. Intraoperative mitomycin versus postoperative 5-fluorouracil in high-risk glaucoma filtering surgery . Ophthalmology . 1992;99:438-444.Crossref 13. Kawase K, Matsushita H, Yamamoto T, Kitazawa Y. Mitomycin concentration in rabbit and human ocular tissues after topical administration . Ophthalmology . 1992;99:203-207.Crossref 14. Khaw PT, Sherwood MB, MacKay SLD, Rossi MB, Schultz GS. 5-Minute treatments with fluorouracil, floxuridine and mitomycin have long-term effects on human Tenon's capsule fibroblasts . Arch Ophthalmol . 1992;110:1150-1154.Crossref 15. 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. In press. 16. Seetner A, Morin JD. Healing of trabeculectomies in rabbits . Can J Ophthalmol . 1979;14:121-125. 17. Miller MH, Grierson I, Unger WI, Hitchings RA. Wound healing in an animal model of glaucoma fistulizing surgery in the rabbit . Ophthalmic Surg . 1989;20:350-357. 18. Khaw PT, Ward S, Porter A, Grierson I, Hitchings RA, Rice NSC. The long term effects of 5-fluorouracil and sodium butyrate on human Tenon's capsule fibroblasts . Invest Ophthalmol Vis Sci . 1992;33:2043-2052. 19. Yamamoto T, Varani J, Kaz Soong H, Lichter PR. Effect of 5-fluorouracil and mitomycin-c on cultured rabbit subconjunctival fibroblasts . Ophthalmology . 1990;97:1204-1210.Crossref 20. Khaw PT, Ward S, Grierson I, Rice NSC. The effects of beta-radiation on proliferating human Tenon's capsule fibroblasts . Br J Ophthalmol . 1991;75:580-583.Crossref 21. Minckler DS, Shammas A, Wilcox M, Ogden TE. Experimental studies of aqueous filtration using the Molteno implant . Trans Am Ophthalmol Soc . 1987;85:368-392. 22. Heuer DK, Lloyd MA, Abrams DA, et al. Preliminary report of a randomised clinical trial of single plate versus double plate Molteno implantation for glaucomas in aphakia and pseudophakia . In: Kriegelstein GK, ed. Glaucoma Update IV . New York, NY: Springer-Verlag NY Inc; 1991:244-249. 23. Wilson RP, Cantor L, Katz LJ, Schmidt CM, Steinmann WC, Allee S. Aqueous shunts: Molteno vs Schocket . Ophthalmology . 1992;99:672-678.Crossref 24. Nordlund JR, Pasquale LR, Quigley HA, Jampel HD. Effectiveness of intraoperative 5-fluorouracil versus intraoperative mitomycin-c in experimental rabbit glaucoma surgery . Invest Ophthalmol Vis Sci . 1992;33( (suppl) ):1393.

Journal

Archives of OphthalmologyAmerican Medical Association

Published: Feb 1, 1993

References

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