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Enhancement of filtration surgery with cytosine arabinoside and reversal of toxicity with 2'-deoxycytidine.

Abstract
Antifibrosis agents have improved the success of glaucoma filtration surgery, although undesired side effects are not readily reversible and may present a major limitation in the use of these agents. Our purpose was to study the efficacy of cytosine arabinoside (Ara-C) as an adjunctive antimetabolite in glaucoma surgery in the rabbit, and reversal of toxicity due to this agent with the competitive inhibitor 2'-deoxycytidine. Posterior lip sclerectomy was performed in rabbit eyes treated with 15 mg subconjunctival Ara-C daily for 7 d then every other day for 7 d. Mean intraocular pressure was lower in eyes treated with Ara-C compared with controls at all time points following filtration surgery. On the 10th postoperative day, the mean intraocular pressure of control eyes (25.0 +/- 1.9 mm Hg) had returned to baseline levels, whereas the intraocular pressure of eyes treated with Ara-C was significantly lower (16.0 +/- 1.7 mm Hg) (P < 0.001). Bleb survival was also prolonged in the Ara-C-treated eyes. The major ocular side effect of Ara-C was corneal toxicity, with epithelial defects in 40% of eyes after 8 daily injections of 15 mg Ara-C. Reversal of toxicity was enhanced with 2'-deoxycytidine, with complete resolution of epithelial toxicity after 6.5 +/- 1.7 d following daily topical 10% 2'-deoxycytidine compared with 12.7 +/- 0.58 for control (P < 0.002). These results demonstrate that postoperative subconjunctival injection of Ara-C results in improved bleb function after filtration surgery in the rabbit. Recovery from corneal epithelial toxicity due to Ara-C is markedly enhanced with the competitive inhibitor 2'-deoxycytidine.
AuthorsJ L Chu, S R Shields, P A Netland
JournalCurrent eye research (Curr Eye Res) Vol. 13 Issue 11 Pg. 839-43 (Nov 1994) ISSN: 0271-3683 [Print] England
PMID7851120 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Cytarabine
  • Deoxycytidine
Topics
  • Animals
  • Chemotherapy, Adjuvant
  • Cornea (drug effects)
  • Corneal Diseases (chemically induced, prevention & control)
  • Cytarabine (antagonists & inhibitors, therapeutic use, toxicity)
  • Deoxycytidine (pharmacology)
  • Epithelium (drug effects)
  • Filtering Surgery
  • Glaucoma (drug therapy, surgery)
  • Injections
  • Intraocular Pressure
  • Rabbits
  • Scleroplasty

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