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. 2000 Jan;84(1):92–97. doi: 10.1136/bjo.84.1.92

Sponge delivery variables and tissue levels of 5-fluorouracil

M Wilkins 1, N Occleston 1, A Kotecha 1, L Waters 1, P Khaw 1
PMCID: PMC1723231  PMID: 10611106

Abstract

AIM—To study how the delivery of 5-fluorouracil (5-FU) to ocular tissues is affected by altering delivery variables.
METHOD—Sponge(s) soaked in radiolabelled 5-FU were placed between the conjunctiva and sclera of pig eyes. Application time, sponge size, sponge make (Altomed, Weck, Merocel), and 5-FU concentration were varied. Conjunctival and scleral tissue levels were determined in samples taken from the application site.
RESULTS—Dose-response curves for scleral and conjunctival 5-FU levels against application time showed increasing tissue levels that reached a plateau after 2-3 minutes. Application beyond 3 minutes did not increase tissue levels. There was no difference in tissue levels between 7×4 and 3.5×2 mm sponges. Altomed sponges produced 5-FU tissue levels that were twice as high as those obtained with Weck-cell (p<0.01) or Merocel (p<0.02) sponges. Changing the 5-FU concentration from 25 mg/ml to 6.25 mg/ml reduced the conjunctival concentration by a factor of 3.5 (p<0.003).
CONCLUSION—Application time up to 3 minutes, sponge make, and 5-FU concentration can have a large effect on the tissue delivery of 5-FU. Application time beyond 3 minutes, using 3.5×2 mm or 7×4 mm sponges, and replacing sponges every minute did not have a significant effect on tissue levels. This study models the effect that different variables can have on the ocular tissue levels of an antimetabolite applied intraoperatively.



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Figure 1  .

Figure 1  

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Sites of conjunctival and scleral biopsies. Box shows site of sponge application.

Figure 2  .

Figure 2  

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Conjunctival tissue level of 14C 5-FU against duration of single application of Altomed sponge.

Figure 3  .

Figure 3  

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Scleral tissue level of 14C 5-FU against duration of single application of Altomed sponge.

Figure 4  .

Figure 4  

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Regional conjunctival tissue level of 14C 5-FU following single 5 minute application of either 7×4 mm or 3.5×2 mm Altomed sponge. Sites 1, 2, and 3 are shown in Figure 1.

Figure 5  .

Figure 5  

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Regional scleral tissue level of 14C 5-FU following single 5 minute application of either 7×4 mm or 3.5×2 mm Altomed sponge. Sites 1, 2, and 3 are shown in Figure 1.

Figure 6  .

Figure 6  

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Conjunctival tissue level of 14C 5-FU following either a single Altomed sponge applied for 5 minutes or an Altomed sponge replaced every minute for 5 minutes.

Figure 7  .

Figure 7  

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Scleral tissue level of 14C 5-FU following either a single Altomed sponge applied for 5 minutes or an Altomed sponge replaced every minute for 5 minutes

Figure 8  .

Figure 8  

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Conjunctival tissue level of 14C 5-FU following a single application using a Weck, Altomed, or Merocel sponge.

Figure 9  .

Figure 9  

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Conjunctival tissue level of 14C 5-FU following a single 5 minute application of an Altomed sponge soaked in either 25 mg/ml or 6.25 mg/ml 14C 5-FU solution.

Figure 10  .

Figure 10  

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Scleral tissue level of 14C 5-FU following a single 5 minute application of an Altomed sponge soaked in either 25 mg/ml or 6.25 mg/ml 14C 5-FU solution.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Campagna J. A., Munden P. M., Alward W. L. Tenon's cyst formation after trabeculectomy with mitomycin C. Ophthalmic Surg. 1995 Jan-Feb;26(1):57–60. [PubMed] [Google Scholar]
  2. Caronia R. M., Liebmann J. M., Friedman R., Cohen H., Ritch R. Trabeculectomy at the inferior limbus. Arch Ophthalmol. 1996 Apr;114(4):387–391. doi: 10.1001/archopht.1996.01100130383004. [DOI] [PubMed] [Google Scholar]
  3. Chen C. W., Huang H. T., Bair J. S., Lee C. C. Trabeculectomy with simultaneous topical application of mitomycin-C in refractory glaucoma. J Ocul Pharmacol. 1990 Fall;6(3):175–182. doi: 10.1089/jop.1990.6.175. [DOI] [PubMed] [Google Scholar]
  4. Chen P. P., Yamamoto T., Sawada A., Parrish R. K., 2nd, Kitazawa Y. Use of antifibrosis agents and glaucoma drainage devices in the American and Japanese Glaucoma Societies. J Glaucoma. 1997 Jun;6(3):192–196. [PubMed] [Google Scholar]
  5. Cohen J. S., Greff L. J., Novack G. D., Wind B. E. A placebo-controlled, double-masked evaluation of mitomycin C in combined glaucoma and cataract procedures. Ophthalmology. 1996 Nov;103(11):1934–1942. doi: 10.1016/s0161-6420(96)30405-3. [DOI] [PubMed] [Google Scholar]
  6. Cordeiro M. F., Constable P. H., Alexander R. A., Bhattacharya S. S., Khaw P. T. Effect of varying the mitomycin-C treatment area in glaucoma filtration surgery in the rabbit. Invest Ophthalmol Vis Sci. 1997 Jul;38(8):1639–1646. [PubMed] [Google Scholar]
  7. Costa V. P., Comegno P. E., Vasconcelos J. P., Malta R. F., José N. K. Low-dose mitomycin C trabeculectomy in patients with advanced glaucoma. J Glaucoma. 1996 Jun;5(3):193–199. [PubMed] [Google Scholar]
  8. Costa V. P., Moster M. R., Wilson R. P., Schmidt C. M., Gandham S., Smith M. Effects of topical mitomycin C on primary trabeculectomies and combined procedures. Br J Ophthalmol. 1993 Nov;77(11):693–697. doi: 10.1136/bjo.77.11.693. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Costa V. P., Wilson R. P., Moster M. R., Schmidt C. M., Gandham S. Hypotony maculopathy following the use of topical mitomycin C in glaucoma filtration surgery. Ophthalmic Surg. 1993 Jun;24(6):389–394. [PubMed] [Google Scholar]
  10. Dreyer E. B., Chaturvedi N., Zurakowski D. Effect of mitomycin C and fluorouracil-supplemented trabeculectomies on the anterior segment. Arch Ophthalmol. 1995 May;113(5):578–580. doi: 10.1001/archopht.1995.01100050044028. [DOI] [PubMed] [Google Scholar]
  11. Egbert P. R., Williams A. S., Singh K., Dadzie P., Egbert T. B. A prospective trial of intraoperative fluorouracil during trabeculectomy in a black population. Am J Ophthalmol. 1993 Nov 15;116(5):612–616. doi: 10.1016/s0002-9394(14)73204-0. [DOI] [PubMed] [Google Scholar]
  12. Gandolfi S. A., Vecchi M. 5-fluorouracil in combined trabeculectomy and clear-cornea phacoemulsification with posterior chamber intraocular lens implantation. A one-year randomized, controlled clinical trial. Ophthalmology. 1997 Feb;104(2):181–186. doi: 10.1016/s0161-6420(97)30336-4. [DOI] [PubMed] [Google Scholar]
  13. Greenfield D. S., Miller M. P., Suner I. J., Palmberg P. F. Needle elevation of the scleral flap for failing filtration blebs after trabeculectomy with mitomycin C. Am J Ophthalmol. 1996 Aug;122(2):195–204. doi: 10.1016/s0002-9394(14)72010-0. [DOI] [PubMed] [Google Scholar]
  14. Greenfield D. S., Suñer I. J., Miller M. P., Kangas T. A., Palmberg P. F., Flynn H. W., Jr Endophthalmitis after filtering surgery with mitomycin. Arch Ophthalmol. 1996 Aug;114(8):943–949. doi: 10.1001/archopht.1996.01100140151007. [DOI] [PubMed] [Google Scholar]
  15. Higginbotham E. J., Stevens R. K., Musch D. C., Karp K. O., Lichter P. R., Bergstrom T. J., Skuta G. L. Bleb-related endophthalmitis after trabeculectomy with mitomycin C. Ophthalmology. 1996 Apr;103(4):650–656. doi: 10.1016/s0161-6420(96)30639-8. [DOI] [PubMed] [Google Scholar]
  16. Joos K. M., Bueche M. J., Palmberg P. F., Feuer W. J., Grajewski A. L. One-year follow-up results of combined mitomycin C trabeculectomy and extracapsular cataract extraction. Ophthalmology. 1995 Jan;102(1):76–83. doi: 10.1016/s0161-6420(95)31050-0. [DOI] [PubMed] [Google Scholar]
  17. Kawase K., Matsushita H., Yamamoto T., Kitazawa Y. Mitomycin concentration in rabbit and human ocular tissues after topical administration. Ophthalmology. 1992 Feb;99(2):203–207. doi: 10.1016/s0161-6420(92)31992-x. [DOI] [PubMed] [Google Scholar]
  18. Khaw P. T., Doyle J. W., Sherwood M. B., Grierson I., Schultz G., McGorray S. Prolonged localized tissue effects from 5-minute exposures to fluorouracil and mitomycin C. Arch Ophthalmol. 1993 Feb;111(2):263–267. doi: 10.1001/archopht.1993.01090020117035. [DOI] [PubMed] [Google Scholar]
  19. Khaw P. T., Sherwood M. B., Doyle J. W., Smith M. F., Grierson I., McGorray S., Schultz G. S. Intraoperative and post operative treatment with 5-fluorouracil and mitomycin-c: long term effects in vivo on subconjunctival and scleral fibroblasts. Int Ophthalmol. 1992 Sep;16(4-5):381–385. doi: 10.1007/BF00917996. [DOI] [PubMed] [Google Scholar]
  20. Kitazawa Y., Kawase K., Matsushita H., Minobe M. Trabeculectomy with mitomycin. A comparative study with fluorouracil. Arch Ophthalmol. 1991 Dec;109(12):1693–1698. doi: 10.1001/archopht.1991.01080120077030. [DOI] [PubMed] [Google Scholar]
  21. Kitazawa Y., Suemori-Matsushita H., Yamamoto T., Kawase K. Low-dose and high-dose mitomycin trabeculectomy as an initial surgery in primary open-angle glaucoma. Ophthalmology. 1993 Nov;100(11):1624–1628. doi: 10.1016/s0161-6420(93)31426-0. [DOI] [PubMed] [Google Scholar]
  22. Kupin T. H., Juzych M. S., Shin D. H., Khatana A. K., Olivier M. M. Adjunctive mitomycin C in primary trabeculectomy in phakic eyes. Am J Ophthalmol. 1995 Jan;119(1):30–39. doi: 10.1016/s0002-9394(14)73810-3. [DOI] [PubMed] [Google Scholar]
  23. Lachkar Y., Leyland M., Bloom P., Migdal C. Trabeculectomy with intraoperative sponge 5-fluorouracil in Afro-Caribbeans. Br J Ophthalmol. 1997 Jul;81(7):555–558. doi: 10.1136/bjo.81.7.555. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Lamping K. A., Belkin J. K. 5-Fluorouracil and mitomycin C in pseudophakic patients. Ophthalmology. 1995 Jan;102(1):70–75. doi: 10.1016/s0161-6420(95)31051-2. [DOI] [PubMed] [Google Scholar]
  25. Lederer C. M., Jr Combined cataract extraction with intraocular lens implant and mitomycin-augmented trabeculectomy. Ophthalmology. 1996 Jul;103(7):1025–1034. doi: 10.1016/s0161-6420(96)30571-x. [DOI] [PubMed] [Google Scholar]
  26. Madhavan H. N., Rao S. B., Vijaya L., Neelakantan A. In vitro sensitivity of human Tenon's capsule fibroblasts to mitomycin C and its correlation with outcome of glaucoma filtration surgery. Ophthalmic Surg. 1995 Jan-Feb;26(1):61–67. [PubMed] [Google Scholar]
  27. Mietz H., Krieglstein G. K. Short-term clinical results and complications of trabeculectomies performed with mitomycin C using different concentrations. Int Ophthalmol. 1995;19(1):51–56. doi: 10.1007/BF00156420. [DOI] [PubMed] [Google Scholar]
  28. Mora J. S., Nguyen N., Iwach A. G., Gaffney M. M., Hetherington J., Jr, Hoskins H. D., Jr, Wong P. C., Tran H., Dickens C. J. Trabeculectomy with intraoperative sponge 5-fluorouracil. Ophthalmology. 1996 Jun;103(6):963–970. doi: 10.1016/s0161-6420(96)30578-2. [DOI] [PubMed] [Google Scholar]
  29. Munden P. M., Alward W. L. Combined phacoemulsification, posterior chamber intraocular lens implantation, and trabeculectomy with mitomycin C. Am J Ophthalmol. 1995 Jan;119(1):20–29. doi: 10.1016/s0002-9394(14)73809-7. [DOI] [PubMed] [Google Scholar]
  30. Mégevand G. S., Salmon J. F., Scholtz R. P., Murray A. D. The effect of reducing the exposure time of mitomycin C in glaucoma filtering surgery. Ophthalmology. 1995 Jan;102(1):84–90. doi: 10.1016/s0161-6420(95)31049-4. [DOI] [PubMed] [Google Scholar]
  31. Robin A. L., Ramakrishnan R., Krishnadas R., Smith S. D., Katz J. D., Selvaraj S., Skuta G. L., Bhatnagar R. A long-term dose-response study of mitomycin in glaucoma filtration surgery. Arch Ophthalmol. 1997 Aug;115(8):969–974. doi: 10.1001/archopht.1997.01100160139001. [DOI] [PubMed] [Google Scholar]
  32. Shields M. B., Scroggs M. W., Sloop C. M., Simmons R. B. Clinical and histopathologic observations concerning hypotony after trabeculectomy with adjunctive mitomycin C. Am J Ophthalmol. 1993 Dec 15;116(6):673–683. doi: 10.1016/s0002-9394(14)73465-8. [DOI] [PubMed] [Google Scholar]
  33. Shin D. H., Hughes B. A., Song M. S., Kim C., Yang K. J., Shah M. I., Juzych M. S., Obertynski T. Primary glaucoma triple procedure with or without adjunctive mitomycin. Prognostic factors for filtration failure. Ophthalmology. 1996 Nov;103(11):1925–1933. doi: 10.1016/s0161-6420(96)30406-5. [DOI] [PubMed] [Google Scholar]
  34. Shin D. H., Reed S. Y., Swords R. C., Reed A. H., Simone P. A., Birt C. M. Cellulose sponge punch for controlled mitomycin application. Arch Ophthalmol. 1994 Dec;112(12):1624–1625. doi: 10.1001/archopht.1994.01090240130041. [DOI] [PubMed] [Google Scholar]
  35. Shin D. H., Simone P. A., Song M. S., Reed S. Y., Juzych M. S., Kim C., Hughes B. A. Adjunctive subconjunctival mitomycin C in glaucoma triple procedure. Ophthalmology. 1995 Oct;102(10):1550–1558. doi: 10.1016/s0161-6420(95)30832-9. [DOI] [PubMed] [Google Scholar]
  36. Smith M. F., Sherwood M. B., Doyle J. W., Khaw P. T. Results of intraoperative 5-fluorouracil supplementation on trabeculectomy for open-angle glaucoma. Am J Ophthalmol. 1992 Dec 15;114(6):737–741. doi: 10.1016/s0002-9394(14)74053-x. [DOI] [PubMed] [Google Scholar]
  37. Wolner B., Liebmann J. M., Sassani J. W., Ritch R., Speaker M., Marmor M. Late bleb-related endophthalmitis after trabeculectomy with adjunctive 5-fluorouracil. Ophthalmology. 1991 Jul;98(7):1053–1060. doi: 10.1016/s0161-6420(91)32177-8. [DOI] [PubMed] [Google Scholar]
  38. Zacharia P. T., Deppermann S. R., Schuman J. S. Ocular hypotony after trabeculectomy with mitomycin C. Am J Ophthalmol. 1993 Sep 15;116(3):314–326. doi: 10.1016/s0002-9394(14)71349-2. [DOI] [PubMed] [Google Scholar]

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