|Year : 1993 | Volume
| Issue : 2 | Page : 74-77
The role of 5-fluorouracil in complicated glaucomas
AM Khan, FA Jilani, S Das
Institute of Ophthalmology, Aligarh Muslim University, Aligarh, India
A M Khan
Institute of Ophthalmology, Aligarh Muslim University, Aligarh, U.P. 202002
Source of Support: None, Conflict of Interest: None
The long-term efficacy of trabeculectomy in controlling intraocular pressure (IOP) has been found unsatisfactory in various complicated and refractory glaucomas. The most common cause for failure is excessive scarring at the filtering site. Several wound modulating agents which reduce scarring have been tested. In this study, 5-Fluorouracil (5-FU), a halogenated pyrimidine analogue and a potent anti-mitotic agent, was applied for seven days after trabeculectomy in eighteen complicated and unsuccessful filtering glaucomas, at a daily dosage of 5 mg in the form of 0.5 ml subconjunctival injections. The common postoperative complications encountered were corneal epithelial erosion (38%), wound leakage (16%), subconjunctival haemorrhage (32%) and hyphaema (10%), all during the first 7 to 10 days. Monitoring at regular intervals up to six months showed adequate control of IOP (less than 22mm Hg.) in 88% of the cases. Cases of aphakic glaucoma and neovascular glaucoma showed poor response. Use of 5-FU as an adjuvant to filtering surgery in various complicated glaucomas improves the long-term results
Keywords: 5 Fluorouracil, trabeculectomy, intraocular pressure, complicated glaucomas
|How to cite this article:|
Khan A M, Jilani F A, Das S. The role of 5-fluorouracil in complicated glaucomas. Indian J Ophthalmol 1993;41:74-7
|How to cite this URL:|
Khan A M, Jilani F A, Das S. The role of 5-fluorouracil in complicated glaucomas. Indian J Ophthalmol [serial online] 1993 [cited 2020 Nov 24];41:74-7. Available from: https://www.ijo.in/text.asp?1993/41/2/74/25619
Many reports of long-term success provide proof of the efficacy of trabeculectomy in dealing with primary glaucomas. However, it has not been as successful in controlling intraocular pressure (IOP) in various types of complicated and refractory glaucomas, viz. aphakic, inflammatory, neovascular, congenital and juvenile glaucomas, and in failed filtration cases. The most common cause of trabeculectomy failure is excessive scarring at the filtering site. This study examines the adjunctive use of a pharmacological wound modulating agent to reduce such scarring.
Of the various pharmacological wound modulators in use, 5 fluorouracil (5-FU), a halogenated pyrimidine analogue which acts as a potent antimitotic agent has gained popularity since its introduction in 1984. Several researchers have reported the beneficial effects of 5-FU in treating difficult glaucoma cases. In the present study, post-trabeculectomy application of 5-FU was tried in various complicated glaucomas and its effect on long-term control of IOP and side effects on various ocular structures were studied.
| Materials and methods|| |
This study was carried out on eighteen complicated, refractory and high-risk glaucoma cases that were not controlled by medical treatment. The distribution of these cases is shown in [Table - 1]. After thorough examination and assessment of anterior and posterior segments, all cases were subjected to the standard trabeculectomy procedure. The wound at the conjunctival flap was meticulously closed after suturing the scleral flap at both ends. Following this, each patient received subconjunctival injection of 20 mg of gentamicin and 2 mg of dexamethasone.
From the first to the seventh postoperative day, a 5 mg subconjuctival injection of 5-FU was given everyday in the lower fornix 180° away from the site of the bleb. This injection was discontinued if it produced any serious complication and was restarted when this subsided. During this period all cases were thoroughly checked under a slit lamp for bleb configuration and leakage if any (with Seidel's test), corneal erosion, anterior chamber reaction and lenticular changes. Applanation tonometry and direct ophthalmoscopy were done to check any fundus changes.
The same parameters were checked in the followup examinations at 2 to 4 weeks, I to 3 months and 3 to 6 months.
| Results|| |
None of these eighteen cases had a visual acuity better than 6/9 [Table - 2]. Five cases were within the 6/9 to 6/12 range (27.7%). Three cases fell within 6/ 18 to 6/36 range (16.6%) and the remaining 10 cases had acuity of 6/60 or worse (55.5%). The preoperative refractive status of these cases is shown in [Table - 3]. This shows that 6 cases (33.3%) were hypermetropes, 4 were emmetropes (22.2%) and 8 cases (44.4%) were myopes.
At the 6-month postoperative follow up, 6 cases (33%) gained better visual acuity, eight cases (44%) remained the same and four cases (22%) worsened. There was a postoperative trend towards a myopic error (-.25D Sph.) irrespective of the type of glaucoma [Table - 3].
As far as IOP is concerned, the mean preoperative IOP of 40 ± 11.79 mm of Hg fell precipitously to a level of 15.3 ± 7.42 mm of Hg on the 7th day, as shown in [Table - 4] and [Figure 1]. At three months, IOP stabilized at a mean value of 18 ± 6.88 mm Hg, following which the change was negligible up to six months (mean 1OP at six months: 18.3 ± 7.07 mm of Hg). However, the mean fall of IOP at the 6th month was 22.7 + 8.43 mm Hg. Considering 22mm Hg. as the criterion for success, it was found that three cases fell short of the mark. The overall success rate was 83.3%. Of the failed cases 2 were aphakic glaucomas and one, neovascular glaucoma.
The complications encountered in the present study are shown in [Table - 5]. Corneal epithelial erosion was the most frequent problem (38%), followed closely by subconjunctival haemorrhage (32%), wound leakage (16%) and hyphaema (16%). On appearance of corneal erosion the 5-FU injection was stopped and restored when it subsided. All these complications subsided with conservative treatment within two weeks.
| Discussion|| |
5-Fluorouracil is a potent antimitotic agent which acts as a pharmacological wound modulator by its anti-proliferative action against fibroblasts at the wound margin. Since the most common cause of trabeculectomy failure is excessive scarring of the wound margins leading to a flat non-functioning bleb, the role of 5-FU in such cases was established by Heuer et al' in 1984. Since then a number of studies were published but all reported a significant incidence of complications. Weinreb 2 adjusted the administration of 5-FU according to the appearance of complications with positive results. Similarly, in the present study the dosage of 5-FU was adjusted depending upon complications.
As is evident from this study six cases (33%) obtained better visual acuity following surgery due to the reduction of corneal edema. However, four cases (22%) worsened. Of these, one was because of vitreous haemorrhage, another, due to cystoid macular edema, and the remaining two due to progressive lenticular changes secondary to prolonged postoperative hypotony. This was in accordance with similar observations by Rockwood et al.  Considering a postoperative IOP of less than 22 mm of Hg as the criterion for success, three cases "failed" in this series. Amongst these, two were of aphakic glaucoma (success rate 33%). Both cases failed due to excessive scarring which resulted in flat blebs. An increased tendency towards flat bleb formation in these cases was probably due to a previously scarred conjunctiva from earlier surgery, as also reported by Rockwood et al. sub The case of neovascular glaucoma included in this study failed even after use of 5-FU in the second postoperative week, probably due to a nonregression of neovascularization of the iris, which is a strong stimulus for fibroblastic proliferation even after 5-FU therapy, as pointed out by Ruderman et al.  However, all the other types of glaucomas included in this study showed a 100% success rate.
Even with an adjustable dose of 5-FU, several complications were encountered. The highest incidence was of corneal epithelial erosion (38%). This was found to be mostly dose related, appearing at the sixth postoperative day, after 30 mg of subconjunctival 5-FU. Krug et al' reported similar findings. Wound leakage (16%) and excessive drainage of bleb (5%) occured mainly in the earlier part of the first postoperative week when maximum fibroblastic activity occurs. For the same reason Krug et al  advocated a delayed 5-FU application in their series and achieved no wound leak in their cases.
The complications and success rates reported in earlier studies are compared with those in present study.
In this study, a relatively lower incidence of different complications was encountered along with adequate IOP control up to the sixth month follow up. Therefore, it can be said that use of 5-FU administered as a 5mg subconjunctival injection daily for seven days is well tolerated and is recommended for better longterm IOP control in complicated and refractory glaucomas.
| References|| |
Heuer DK, Parrish RK, Gressel MG, Hodapp E, Palmberg PF and Anderson DR. 5-FU and glaucoma filtering surgery II - A pilot study. Ophthalmology 91: 384-394, 1984.
Weinreb RN. Adjusting the dose of 5-FU after filtering surgery to minimise side effects. Ophthalmology 94: 564590, 1987.
Ruderman IM, Weich DB, Smith MF and Shoch DE. A randomized study of 5-FU and filtering surgery. Am J Ophthalmol. 104: 218-224, 1987.
Rockwood EJ, Parrish RK, Heuer DK, Skuta GL, Hodapp E, Palmberg PF, Gressel MG and Fener W. Ophthalmology 94: 1071-1078, 1987.
Krug JH and Melamed S. Adjunctive use of delayed and adjustable low dose of 5-FU in refractory glaucoma. Am J Ophthalmol. 109: 412-418, 1990.
Gupta A, Bansal RK, Grewal SPS and Jain IS. 5-FU as an adjuvant in glaucoma filtering surgery. Proc AIOS Con. 234 -236, 1990.
Sood NN, Kumar H, Agarwal HC and Sihota R. Sub conj 5-FU for maintaining the patency of filtering blebs in failed glaucoma surgery. Proc AIDS Con. 237-240, 1990.
[Table - 1], [Table - 2], [Table - 3], [Table - 4], [Table - 5], [Table - 6]