Enhancement of filtration surgery with cytosine arabinoside and reversal of toxicity with 2'-deoxycytidine.
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.
Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston 02114.
J L
JL
Chu
S R
SR
Shields
P A
PA
Netland
D000818:Animals; D017024:Chemotherapy, Adjuvant; D003315:Cornea / Q000187:drug effects*; D003316:Corneal Diseases / Q000139:chemically induced / Q000517:prevention & control*; D003561:Cytarabine / Q000037:antagonists & inhibitors / Q000627:therapeutic use* / Q000633:toxicity*; D003841:Deoxycytidine / Q000494:pharmacology*; D004848:Epithelium / Q000187:drug effects; D018463:Filtering Surgery; D005901:Glaucoma / Q000188:drug therapy / Q000601:surgery; D007267:Injections; D007429:Intraocular Pressure; D011817:Rabbits; D016639:Scleroplasty
D003561:Cytarabine; D003841:Deoxycytidine