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ORIGINAL ARTICLE
Year : 1997  |  Volume : 45  |  Issue : 3  |  Page : 173-176

Short-term results of initial trabeculectomy with intraoperative or postoperative 5-fluorouracil for primary glaucomas


Maulana Azad Medical College, New Delhi, India

Correspondence Address:
P A Lamba
Maulana Azad Medical College, New Delhi
India
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Source of Support: None, Conflict of Interest: None


PMID: 9475020

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  Abstract 

Thirty-three eyes of 33 patients were prospectively evaluated to study the short term efficacy, safety, and overall surgical outcome of initial trabeculectomy for primary glaucomas with adjunctive intraoperative or postoperative 5-Fluorouracil (5-FU) use. Twelve eyes serving as controls underwent trabeculectomy without adjunctive antimetabolites. Eleven eyes received intraoperative 5-FU, while 10 eyes received subconjunctival 5-FU postoperatively. Intraocular pressure (IOP) was maintained below 22 mmHg at 3 months of follow up in 90.9% and 80% of patients in the intraoperative and postoperative 5-FU groups, respectively, without use of additional antiglaucoma medications, whereas 66.7% of the patients in the control group achieved similar IOP levels. Hypotony (IOP < 6 mmHg) was seen more commonly after intraoperative 5-FU (27.3%). Corneal epithelial defects were seen exclusively in the postoperative 5-FU group (40%). The use of intraoperative 5-FU exclusively as a mode of antimetabolites delivery seems an acceptable alternative to enhance success rates of trabeculectomy for the primary glaucomas.

Keywords: 5-Fluorouracil, intraocular pressure, trabeculectomy


How to cite this article:
Lamba P A, Pandey P K, Raina U K, Krishna V. Short-term results of initial trabeculectomy with intraoperative or postoperative 5-fluorouracil for primary glaucomas. Indian J Ophthalmol 1997;45:173-6

How to cite this URL:
Lamba P A, Pandey P K, Raina U K, Krishna V. Short-term results of initial trabeculectomy with intraoperative or postoperative 5-fluorouracil for primary glaucomas. Indian J Ophthalmol [serial online] 1997 [cited 2020 Feb 18];45:173-6. Available from: http://www.ijo.in/text.asp?1997/45/3/173/15016



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The most common cause of failure after trabeculectomy is excessive scarring at the episcleral-conjunctival interface resulting in a nonfunctional bleb. The use of antimetabolites such as 5 Fluorouracil (5-FU) inhibits this scarring and enhances the success of filtration surgery.[1] Since the initial study of postoperative 5-FU by Heuer et al in 1984,[2] studies have demonstrated the beneficial effect of postoperative 5-FU use on both primary glaucoma filtering surgery[3] and trabeculectomy in eyes with poor surgical prognosis.[4],[5]

However, complications with postoperative subconjunctival injections were noted which included superficial punctate keratopathy. Confluent epithelial defects, subepithelial scarring, striate melanokeratosis apart from hypotony, shallow anterior chamber, cataract and choroidal detachment.[6]

The use of intraoperative 5-FU under the scleral flap and tenon's capsule was first suggested by Doyle et al.[7] They demonstrated an enhanced bleb survival in rabbit eyes with this method.

Clinical studies of introperative use of 5-FU in patients with high risk for filtering surgery failure also demonstrated enhanced success rates.[8][9][10] Associated complications were also minimal, attributable to the smaller dose and less exposure time required in this altered mode of delivery.

The efficacy, dosage and duration of application needs to be evaluated and standardized, with particular reference to patients undergoing uncomplicated filtering surgery where the possibility of a low complication rate might make the antimetabolite more universally acceptable.

The present study was initiated to compare the short term efficacy and ocular toxicity of intraoperative and postoperative delivery of 5-FU, and effect of the antimetabolite on the overall surgical outcome of initial trabeculectomy for the primary glaucomas.


  Materials and Methods Top


The present study was conducted on 33 eyes of 33 patients of primary open angle or chronic angle closure glaucoma who underwent trabeculectomy between September 1993 and March 1994.

All patients were on maximal medical therapy (combination of timolol twice a day, pilocarpine 2% four times a day, acetazolamide three times a day, and use of additional osmotic agents as required) with preoperative intraocular pressure (IOP) exceeding 30 mmHg. The patients were diagnosed to have primary open or chronic angle closure glaucoma based on the gonioscopic demonstration of a open or closed angle. Patients with previously failed trabeculectomy, glaucoma in aphakia, patients with IOP less than 30 mmHg on therapy, and inflammatory and neovascular glaucoma and excluded from the study.

Twelve patients were randomly assigned to the control group (group I), 11 to the intraoperative 5-FU group (group II), and 10 to the postoperative 5-FU group (group III). Randomisation was done by use of the table of random numbers.

Preopeartive baseline information was obtained for each patient and a relevant anterior and posterior segment examination was done.

Trabeculectomy was performed under local anaesthesia, informed consent having been obtained from all patients. All surgeries were performed by a standardized technique by the authors (PAL, PKP, UKR). A limbal based conjunctival flap was raised. A rectangular two-third thickness outer scleral flap, 4x5 mm in size, was raised. In the intraoperative 5-FU group, a cellulose sponge soaked with 50 mg/ml 5-FU was placed under the scleral and conjunctival flap for 5 minutes following which the area was copiously irrigated with balanced salt solution. An inner block of trabecular tissue 1x3 mm in size was excised. A peripheral iridectomy was performed and the scleral flap reapposed with 5 interrupted 10-0 nylon sutures. Releasable sutures were not used in any patient. The conjunctival flap was sutured with 8-0 nylon. Postoperatively, 5 mg subconjunctival injections of 5-FU were given to the patients of group III, 180 degress from the surgical site, everyday in the first week, and on alternate days in the second week, the total number of doses depending on patient response and ensuing complications.

All patients were also kept on oral antibiotics and Ibuprofen for 3 days postoperatively. Topical antibiotic and steroids were given for 4-6 weeks. Antiglaucoma medications were administered as and when IOP control was found to be inadequate (IOP >22 mmHg or demonstrable field loss indicating lack of adequate control).

Visual acuity, visual fields, IOP, bleb characteristics, and the occurrence of anterior and posterior segment complications were monitored at regular intervals for a total duration of 3 months.

An increase or decrease of visual acuity by one or more lines of the Snellen chart was considered significant. Visual fields were performed on the Humphrey field analyser using the 30-2 threshold test preoperatively and at regular intervals of 2 weeks wherever possible. Cataract was graded according to the LOCS II system[11] preoperatively and postoperatively and studied for progression.

Shallow anterior chamber was graded according to the extent of irido-corneal or lenticulo-corneal touch as previously described by Costa et al.[12] Hypotony in the study was defined as IOP <6 mmHg. Hypotony maculopathy was defined as IOP <6 mmHg with retinal striae and decreased visual acuity with no other definable cause of decrease in visual acuity.

Surgical success was defined in the study as IOP <22 mmHg without use of adjunctive antiglaucoma medications and no demonstrable progression of field loss. Qualified success was defined as IOP <22 mmHg with use of additional antiglaucoma medications. Surgical failure was defined as IOP ≥22 mmHg with use of antiglaucoma medications or demonstrable progression of field defects.

Statistical analysis was done by use of the analysis of variance and the Student's t-test.


  Results Top


The 33 patients in the study were 55.9 8.5 (mean SD) years old, and consisted of 18 males and 15 females. There were 12 patients of primary open angle glaucoma and 21 patients of chronic angle closure glaucoma. There was no statistically significant difference in the three groups with regard to age, sex, diagnosis and preoperative IOP levels as determined by analysis of variance.

The pre and postoperative IOP status is shown in [Table - 1]. A statistically significant difference in the IOP levels at 3 months was noted between the control group and groups II (p<0.01) and III (p<0.01). The respective 95% confidence limits of IOP at 3 months were 14.5-17.1 for group II and 13.3-17.1 for group III. The patients of group III received a mean 5-FU dose of 35 14.7 mg. There was no significant correlation found between the dose administered and the final IOP levels (r=0.12, p>0.3).

The success rates for the three groups at three months were 66.7%, 90.9%, and 80%, respectively.

An improvement in the visual acuity (one line or more by Snellen chart) was noted in 3 patients. No case showed worsening of visual acuity. There was no demonstrable progression of field defects postoperatively.

The blebs resulting after trabeculectomy without antimetabolites were low, diffusely elevated with varying degree of residual vascularisation while patients of group II (intraoperative 5-FU) had bleb morphology ranging from low diffuse to frankly cystic, avascular blebs. Cicatrisation developed in 4 cases (33.3%) of group I, and in 1 patient of the postoperative 5-FU group. Three patients (27.3%) of the intraoperative 5-FU group developed cystic changes.

The postoperative complications are listed in [Table - 2]. Corneal epithelial defects (40%) were the commonest complication encountered in group III while hypotony (27.3%) was more commonly seen after intraoperative use of 5-FU.

All cases of shallow anterior chamber resolved with conservative compressive patching except one patient of the intraoperative 5-FU group who required surgical reformation of the anterior chamber.

Patients with corneal epithelial defects responded to patching of the eye. Further administration of subconjunctival 5-FU was withheld in these patients.

None of the patients in this study were noted to have cataract progression.


  Discussion Top


Studies of initial trabeculectomy for the uncomplicated glaucoma have demonstrated a gradual decline in success rates over time.[13] Further, control of IOP is often maintained only with use of additional antiglaucoma medications.[14]

In the present study, additional antiglaucoma medications were required for adequate control of IOP in 4 patients (33.3%) of the control group. Only 1 patient of group II and 2 patients of group III required additional medical therapy for glaucoma control. The average reduction in IOP was found to be similar in the groups where the antimetabolite was used (group II:62.5%; group III:62.4%). However, the success rate was higher in group II (90.9%) than in group III (80%). Both groups however showed a higher success rate and greater reduction in IOP than the control group (success rate: 66.7%; IOP reduction: 56.6%).

While the incidence of hypotony was higher in the intraoperative 5-FU group, corneal epithelial defects were seen exclusively in the postoperative 5-FU group. Further, the postoperative use of the antimetabolite necessitated daily subconjunctival injections enhancing patient discomfort and in most cases prolonging hospital stay. Intraoperative application ensures early delivery of 5-FU thus achieving early commencement of antifibroblastic activity. Higher concentration of the antimetabolite at desired site of action with minimal exposure to other tissues is attained. The use of smaller total antimetabolite dose also accounts for less number of drug induced complications.

Intraoperative application of the drug also provides the advantage of a single intervention with a high success rate necessary in developing countries where cases of glaucoma present in advanced stages, and those affected are seldom aware of the gravity of the disease process or the implications of the lack of a compliant therapy.

Cell culture studies have shown that a signle exposure of 5-FU to fibroblasts results in a prolonged inhibition of growth. However, on recovery the response to growth stimulus is normal. With Mitomycin C marked growth inhibition is followed by extensive histological deformation on subsequent exposure to a growth stimulus.[15]

Therefore a more temporary inhibition of fibroblasts is possible with intraoperative 5-FU instillation which may preserve bleb integrity preventing bleb related complications and long term hypotony.

The present short term clinical assessment of the use of intraoperative 5-FU as an adjunt to uncomplicated trabeculectomy for the primary glaucomas demonstrates this route to be an acceptable mode of antimetabolite therapy to enhance bleb function. Long term success rates, however, have to be determined, keeping in view the temporary and limited nature of fibroblast inhibition noted in cell culture studies with 5-FU. Further investigation is also required to determine the optimum concentration and exposure time of intraoperative 5-FU.

 
  References Top

1.
Skuta GL, Parrish II RK. Wound healing in glaucoma filtering surgery. Surv Ophthalmol 1987;32:149-70.  Back to cited text no. 1
    
2.
Heuer DK, Parrish II RK, Gressel MG, Hodapp E, Palmberg PF, Anderson DR. 5-Fluorouracil and glaucoma filtering surgery: a pilot study. Ophthalmology 1984;91:389-93.  Back to cited text no. 2
    
3.
Leibmann JM, Ritch R, Marmor M, Jose N, Wolner B. Initial 5-Fluorouracil trabeculectomy in uncomplicated glaucoma. Ophthalmology 1991;98:1036-41.  Back to cited text no. 3
    
4.
Weinberg RN. Adjusting the dose of 5-Fluorouracil after filtration surgery to minimise side effects. Ophthalmology 1987;94:564-70.  Back to cited text no. 4
    
5.
The Fluorouracil Filtering Surgery Study Group. Three year followup of the Fluorouracil Filtering Surgery Study. Am J Ophthalmol 1993;115:82-92.  Back to cited text no. 5
    
6.
Knapp A, Heuer DK, Stern GA, Driebe Jr WT. Serious corneal complications of glaucoma filtering surgery with postoperative 5-Fluorouracil. Am J Ophthalmol 1987;103:183-87.  Back to cited text no. 6
    
7.
Doyle JW, Sherwood MB, Khaw PT, Mcgrory S, Smith MF. Intraoperative 5-Flurotiracil for filtration surgery in the rabbit. Invest Ophthalmol Vis Sci. 1993;34:3313-19.  Back to cited text no. 7
[PUBMED]    
8.
Dietze PJ, Fildmann RM, Grass RL. Intraoperative application of 5-Fluorouracil during trabeculectomy. Ophthalmic Surg 1992;23:662-65.  Back to cited text no. 8
    
9.
Egbert PR, Williams AS, Singh K, Dadzie P, Egbert TB. A prospective trial of intraoperative Fluorouracil during trabeculectomy in a black population. Am J Ophthalmol 1993;116:612-16.  Back to cited text no. 9
[PUBMED]    
10.
Whiteside-Michel J, Liebmann JM, Ritch R. Initial 5-Fluorouracil trabeculectomy in young patients. Ophthalmology 1992;99:7-13.  Back to cited text no. 10
[PUBMED]    
11.
Chylack Jr LT, Leske MC, McCarthy D, Khu PM, Kashiwagi T, Sprduto R. Lens opacities classification system II (LOCS II). Arch Ophthalmol 1989;107:991-97.  Back to cited text no. 11
    
12.
Costa VP, Smith M, Spaeth GL, Gandham S, Markovitz B. Loss of visual acuity after trabeculectomy. Ophthalmology 1993;100:599-612.  Back to cited text no. 12
[PUBMED]    
13.
Tornquist G, Drolsum LK. Trabeculectomes: a long term study. Acta Ophthalmol 1991;69:450-54.  Back to cited text no. 13
    
14.
Luntz MH. Trabeculectomy using a fornix-based conjunctival flap and tightly sutured scleral flap. Ophthalmology 1980;87:985-89.  Back to cited text no. 14
[PUBMED]    
15.
Khaw PT, Sherwood MB, Mackay SLD. Five minute treatment with 5-Fluorouracil, 5-Fluorouridine and Mitomydn C have long term effects on human Tenon's fibroblasts. Arch Ophthalmol 1992;110:1150-54.  Back to cited text no. 15
    



 
 
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