|Year : 1993 | Volume
| Issue : 4 | Page : 185-186
Incidence of complications following 5-fluorouracil with trabeculectomies
Ravi Thomas, Aby Jacob, Renu Raju, Stephen C Gieser, Subir Sen
Department of Ophthalmology, Christian Medical College, Vellore, India
Schell Eye Hospital, Vellore, Tamil Nadu 632 001
Source of Support: None, Conflict of Interest: None
To investigate the incidence of complications reportedly caused by the use of 5-fluorouracil (5-FU) in glaucoma filtering surgery, we performed trabeculectomy with 5-FU on 57 eyes of 56 patients with advanced glaucoma. The mean preoperative intraocular pressure was 34.8 mm Hg. The most frequent complication encountered was superficial punctate keratopathy (26%), followed by shallowing of the anterior chamber (12%), choroidal detachment (9%), and flap retraction (7%). We, however, did not encounter any cases of confluent corneal epithelial defect, subepithelial scarring, or striate melanokeratosis which are usually described with the use of 5-FU. With a mean follow-up of 7.1 months, an intraocular pressure less than 16 mm Hg without hypotensive therapy were achieved in 73.7% of cases, and less than 21 mm Hg without hypotensive therapy in 86%. Considering the low incidence of complications and the high success rate, we recommend the use of 5-FU in routine glaucoma filtering surgery
Keywords: Trabeculectomy - 5-FU - Complications
|How to cite this article:|
Thomas R, Jacob A, Raju R, Gieser SC, Sen S. Incidence of complications following 5-fluorouracil with trabeculectomies. Indian J Ophthalmol 1993;41:185-6
|How to cite this URL:|
Thomas R, Jacob A, Raju R, Gieser SC, Sen S. Incidence of complications following 5-fluorouracil with trabeculectomies. Indian J Ophthalmol [serial online] 1993 [cited 2020 May 28];41:185-6. Available from: http://www.ijo.in/text.asp?1993/41/4/185/25596
Conjunctival scarring due to fibroblast proliferation is the major cause of failure of filtration surgery. , 5-fluorouracil (5-FU) is an antimetabolite that has been used extensively to enhance the formation of filtering blebs. , However, since it affects cellular replication, it has adverse effects on tissues with a rapid turnover rate such as the corneal epithelium.
A survey of the literature indicates a high incidence of corneal complications, conjunctival wound and suture tract leaks, and several other disorders caused by the use of 5-FU.  We undertook this study to investigate the incidence of complications caused by the use of 5-FU.
| Materials and methods|| |
All patients who underwent trabeculectomy with 5-FU between November 1988 and May 1991 in the glaucoma service of Schell Eye Hospital were assigned to this study. Fifty-seven eyes of 56 patients underwent surgery. All patients had a fornix-based conjunctival flap and a Cairns-type of trabeculectomy.  5-FU was not injected on the operating table.
Postoperatively, all patients were placed on homatropine 2% and betamethasone drops, as well as oral indomethacin 25 mg three times a day. Topical therapy was modified as required. Five milligram of 5-FU in a volume of 0.1 ml was injected subconjunctivally, 180° away from the bleb, from the first postoperative day onwards. The target dose was a minimum of seven injections per patient, but the actual number given was titrated according to the response of the individual patient.  The mean number of injections per patient was 7.3.
All patients were examined twice daily while in the hospital and then were usually seen at one, three, and six weeks after discharge. At each visit, in addition to slit-lamp examination with special reference to the bleb and intraocular pressure measurement, the cornea was stained with fluorescein and examined for epithelial defects and conjunctival leaks. Injections were deferred if complications such as significant superficial punctate keratopathy or grade 2 shallow anterior chamber were detected, and restarted once they resolved.
Intraocular pressures were measured using Goldmann applanation tonometer, anterior chamber depth was assessed, and the structure of the bleb was noted. Careful attention was paid to any persistent leakage from under the conjunctival flap or site of injection.
| Results|| |
The mean preoperative intraocular pressure was 34.8 mm Hg. The mean intraocular pressure at the last follow-up (mean follow-up, 7.1 months) was 13.9 mm Hg. Final intraocular pressures of less than 16 mm Hg without hypotensive therapy was achieved in 73.7% of cases, and less than 21 mm Hg without hypotensive therapy in 86%.
The complications encountered are shown in the [Table - 1]. The most frequent complication was superficial punctate keratopathy (SPK) in 26% of cases. We, however, did not find any typical confluent corneal epithelial lesions which are described as the most common complication in the literature.  Since we used fornix-based conjunctival flaps, we disregarded minor conjunctival leaks persisting less than five days, which are expected with such flaps. Nonetheless, we did not encounter any case of clinically significant leaks.
Shallowing of the anterior chamber was seen in 12% of cases, and choroidal detachment in 9%. Ophthalmic complications repotted with systemic 5-FU therapy such as subepithelial scarring, cicatricial ectropion, and lacrimal system obstruction were, however, not encountered.  While minimal scarring was noticed at the conjunctival injection site, corneal scarring was not seen.
| Discussion|| |
5-Fluorouracil is a fluorinated pyrimidine analogue that competitively inhibits thymidylate synthetase and cell division, thereby decreasing fibroblast proliferation. The use of 5-FU has shown to increase the success rate of trabeculectomies in aphakia or pseudophakia, neovascular glaucoma, uveitis, and in failed filtration surgery. 
In our patients, the most common complication encountered was superficial punctate keratopathy which was mild and did not cause permanent visual loss in any patient. Due to the potential risk of a wound leak, many authors recommend a limbus-based flap when using 5-FU. Although we used a fornix-based conjunctival flap, microscopic wound leaks encountered were considered clinically insignificant and healed without intervention. We attribute this to the technique of closure of such a flap wherein the needle is tunnelled under the conjunctival edge thereby putting the flap on stretch and preventing a gross leak. Leakage is also looked for when the chamber is reformed through paracentesis, and an additional similar suture placed in the opposite edge of the conjunctival flap if necessary.
Shallow anterior chambers (12%) were of grade 1 or 2, and did not require surgical intervention. Choroidal detachments (9%) were managed conservatively and injections were not postponed unless associated with a grade 2 shallow anterior chamber. The incidence of superficial punctate keratopathy, shallow anterior chambers, and choroidal detachments are similar to other reports  One patient developed a retinal detachment with a giant retinal tear three weeks after surgery. Others have also described the occurrence of retinal detachment following the use of 5-FU but the association is likely to be incidentals
We did not encounter any case of confluent corneal epithelial defect or striate melanokeratosis. This could be related to our protocol which avoids 5-FU injection on the table when the corneal epithelium is desiccated and presumably more susceptible due to a combination of prolonged exposure, bright light, and local anaesthetic. The lower incidence of corneal complications could also be attributed to the lower dose of 5-FU used, titration of dosage against response as opposed to a fixed dose, and the strategy of postponing injections if a complication was encountered.
While this study emphasizes the complications encountered due to the use of 5-FU, a comment on the success rate is in order. An intraocular pressure of less than 16 mm Hg without hypotensive medications, a target pressure suitable for most glaucomatous eyes, was achieved in 73.7% of cases, and less than 16 mm Hg with medications in 75.45%.
In view of the absence of major complications, such as confluent corneal epithelial defects, subepithelial scarring and striate melanokeratosis, and considering the high success rates, we recommend the use of 5-FU in routine glaucoma filtering surgery.
| References|| |
Addicks EM, Quigley HA, Green WR, et al. Histologic characteristics of filtering blebs in glaucomatous eyes. Arch Ophthalmol. 101:795-798, 1983.
Skuta GL and Parrish RK II. Wound healing in glaucoma filtration surgery. Surv Ophthalmol. 32:149-170, 1987.
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Heur DK, Parrish RK, Gressel MG, et al. 5-Fluorouracil and glaucoma filtering surgery: intermediate follow-up of a pilot study. Ophthalmology. 93:1537-1546, 1986.
Weinreb RN. Adjusting the dose of 5-Fluorouracil after filtration surgery to minimize side effects. Ophthalmology. 94:564-570, 1987.
Cairns JE. Trabeculectomy: preliminary report of a new procedure. Am J Ophthalmol. 66:673-679, 1968.
Liebmann JM, Ritch R, Marmor M, et al. Initial 5Fluorouracil trabeculectomy in uncomplicated glaucoma: Ophthalmology. 98:1036-1041, 1991.
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Caravella LP, Burns JA, and Zangmeister M. Punctal canalicular stenosis related to systemic Fluorouracil therapy. Arch Ophthalmol. 99:284-286, 1981.
[Table - 1]