Corneal Complications

The desired effects of antifibrotic agents 5-fluorouracil (5-FU) and mitomycin-C (MMC) in glaucoma filtration surgery result from their ability to limit postoperative scarring by inhibiting vascular proliferation and fibroblastic transformation. However, these same mechanisms of action can have deleterious effects on surrounding normal tissues such as the cornea. Knowing how to use these agents is important in preventing antifibrotic-related complications. 5-FU is an inhibitor of DNA synthesis, specifically thymidylate synthetase, and blocks thymidine from being incorporated into DNA. In addition to affecting DNA synthesis, 5-FU also may be incorporated into RNA, interfering with RNA synthesis and therefore protein synthesis. Thus, it is more toxic to actively proliferating cells. In glaucoma filtration surgery, 5-FU is generally administered intraoperatively (50 mg/mL for 5 minutes). 5-FU can also be administered as a subconjunctival injection postoperatively with a dosage of 5.0–7.5 mg in 0.1–0.15 mL solution directly from the 50 mg/mL bottle. A series of injections may be given over several weeks and titrated based on clinical response. In addition to glaucoma filtration surgery, 5-FU has also been used for other ophthalmic applications such as pterygium surgery, lacrimal surgery, and during vitrectomy to prevent proliferative vitreoretinopathy. MMC is an alkylating agent that crosslinks DNA. It requires enzymatic activation via cytochrome p450 prior to exerting its inhibitory effects on DNA synthesis. MMC activity is independent of cell cycle and affects both actively replicating and nonreplicating cells. However, variations in enzymatic activity among individuals may contribute to the differences in efficacy, as well as toxicity of MMC. In glaucoma filtration surgery, MMC is typically administered as a single intraoperative application. It is applied after dissection of the conjunctival flap and prior to the formation of the scleral flap. Most surgeons use a dose of 0.1–0.5 mg/mL with an exposure time of 1–5 minutes depending upon the clinical indication. MMC use has also been well established for refractive surgery to prevent corneal haze after photorefractive keratectomy in patients at high risk of developing corneal haze, pterygium surgery, and corneal intraepithelial neoplasia. For more information on 5-FU and MMC in glaucoma surgery, see Chapter 3.