|Year : 2008 | Volume
| Issue : 1 | Page : 7-12
Trabeculectomy with Mitomycin-C versus trabeculectomy with 5-Fluorouracil for the treatment of childhood glaucoma
Osama M Badeeb
Department of Ophthalmology, Glaucoma Service, King Abdulaziz University and Hospital, PO 512, Jeddah 21422, Saudi Arabia
Osama M Badeeb
Department of Ophthalmology, King Abdulaziz University and Hospital, PO 512, Jeddah 21422
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Background: Childhood Glaucoma (CG) is common in Saudi Arabia and challenging.
Purpose: To compare efficacy and safety of trabeculectomy with Mitomycin-c (TMMC) and trabeculectomy with 5-Fluorouracil (T5FU) in children with CG.
Materials and Methods: The charts of 35 children with CG who underwent T5FU or TMMC between January 1994 and December 2004, were retrospective reviewed. The efficacy and safety of the two procedures were compared.
Results: 33 eyes of 20 children underwent T5FU and 24 eyes of 15 children underwent TMMC. There was no significant difference between the groups preoperatively, except for mean pre-operative age at the time of operation and medications. 25 (75.8%) eyes in T5FU and 18(75%) eyes in TMMC group were considered successful at mean follow up of 58.6 and 42.2 months respectively. 14 (56%) eyes in T5FU and 12 (66.7%) eyes in TMMC were on no antiglaucoma medications. 10 eyes in T5FU and 6 eyes in TMMC had previous failed procedures. No significant difference between the groups was present on last follow up, with respect to success rate ( P =1.00), follow up ( P =0.4012), medications ( P =0.3467), complications ( P =0.303)] and visual outcome ( P =0.593). Serious complications including, hypotony, retinal detachment, and flat anterior chamber occurred after T5FU and one eye in TMMC group developed bleb-related endophthalmitis. Intraoperative (topical and injection) use of 5FU was as effective as MMC.
Conclusions: 5-Fluorouracil and Mitomycin-C are equally effective as adjuncts to trabeculectomy in CG. Their use can be associated with serious complications. Further study is needed to evaluate intraoperative 5-Fluorouracil augmented trabeculectomy in CG.
Keywords: Trabeculectomy, childhood glaucoma, Mitomycin-C, 5Fluorouracil
|How to cite this article:|
Badeeb OM. Trabeculectomy with Mitomycin-C versus trabeculectomy with 5-Fluorouracil for the treatment of childhood glaucoma. Oman J Ophthalmol 2008;1:7-12
|How to cite this URL:|
Badeeb OM. Trabeculectomy with Mitomycin-C versus trabeculectomy with 5-Fluorouracil for the treatment of childhood glaucoma. Oman J Ophthalmol [serial online] 2008 [cited 2022 Jan 21];1:7-12. Available from: https://www.ojoonline.org/text.asp?2008/1/1/7/43314
| Introduction|| |
Management of childhood glaucoma (CG) is challenging. It is more common, aggressive and difficult to control in Saudi Arabia than in Western countries. ,, In the Saudi Arabian pediatric population, goniotomy and trabeculotomy are rarely successful.  Trabeculectomy has been reported to have a lower success rate in children compared with adults. , This was attributed to the inherent tendency toward excessive scarring in young children, in addition to other risk factors for surgical failure such as prior conjunctival or intraocular surgery, aphakia, or uveitis.  The success rate of trabeculectomy in children has improved with the use of 5-Fluorouracil (5FU) , and Mitomycin-C (MMC). 
This retrospective study is aimed to evaluate and compare the efficacy and safety of MMC and 5FU when used as adjuncts with trabeculectomy in CG.
| Materials and Methods|| |
The charts of 35 consecutive children with CG who underwent Trabeculectomy with MMC (TMMC) or 5FU (T5FU) between January 1994 and December 2004 at King Abdul-Aziz University Hospital, Jeddah, Saudi Arabia were reviewed.
A standard data collection form was used to record demographic data, pre and post-operative (P-OP) ocular status, intraocular pressure (IOP), visual acuity, age of child at diagnosis of disease and operation, and complications. Prior medical and surgical treatment, family history of CG and consanguinity, and final IOP and visual acuity were recorded. The diagnosis of CG was established by measurements of IOP and the presence of accompanying signs and symptoms of CG. All patients were examined awake or under chloral hydrate (50-100mg/kg) sedation in the clinic preoperatively.
Superior rectus bridle suture was placed to depress and expose the superior limbal region. A fornix-based flap of conjunctiva and tenon's capsule was created. Hemostasis was maintained. A 4 × 6 mm piece of Weck-cel sponge soaked in MMC (0.2-0.5 mg/ml) or 5FU (50mg/ml) was placed on the scleral surface before or after scleral flap dissection. The concentration of MMC and the time of its application varied according to the risk factors. Care was taken to minimize contact of antimetabolites with the edges of the conjunctival-tenon flap. After an exposure time of 3 to 5 minutes to MMC or 5 minutes to 5FU, the sponge was removed and the area was irrigated with 60-80 ml of balanced salt solution. A triangular, partial-thickness, approximately 3.0 × 3.0 mm scleral flap was dissected into clear cornea. The internal trabeculectomy ostium was created by corneoscleral punch beneath the scleral flap. A peripheral iridectomy was performed. The scleral flap was closed with three interrupted 10-0 monofilament nylon sutures, the knots of which were buried within the sclera. The conjunctival and tenon capsule were resutured to limbal area by, interrupted 10-0 nylon or 8-0 vicryl sutures. Some eyes of 5FU group were given subconjunctival injection of 5FU (5mg/0.1ml) at the conclusion of the procedure with and without topical (sponge) application of 5FU. Gentamycin and Dexamethasone injections were given subconjunctivally or into the anterior retrobulbar space in doses depending on age. Maxitrol (Dexamethasone 0.1%, Polymyxin B, and Neomycin) ointment was instilled and the eye was patched overnight.
Post-opertively, 1-10 (5mg/0.1ml) subconjunctival or anterior retrobulbar injections of 5FU were given to patients in the 5FU group with high risk or showing sign of failure, while awake or under chloral hydrate sedation.
Routine postoperative drug therapy included topical Maxitrol drops q3hours and ointment at bed time. If IOP increased to unacceptable levels, topical antiglaucoma medications were used. Further surgery was performed if IOP could not be controlled medically after three to four months post-operatively.
All patients were examined 1, 2, and 3 days after surgery, followed by examination in the clinic at the end of 1, 4, and 8 weeks and every 3 months thereafter. At each visit, patients were examined fully, and the anterior chamber depth, corneal appearance, bleb appearance, IOP, fundus, and any complications were recorded.
The surgical procedure was considered successful if IOP ≤ 21 mmHg was present without or with antiglaucoma medication.
The best-corrected visual acuities measured during the final postoperative examination were used to determine outcome. Monocular visual acuity was measured in an age-appropriate fashion using Snellen letters, the illiterate E game, or Allen pictures. Vision in preverbal children was evaluated by observing the fixation pattern (central, steady, maintain). In children with severely impaired vision, the ability to count fingers and to perceive light, colors, and movement was assessed. Refractive errors were corrected with spectacles, when possible to do refractions. Amblyopia was treated with patching. Visual fields could not be done due to the young age of the patients or poor vision.
Graph Pad Prism5 software was used to analyze the data.
| Results|| |
57 eyes of 35 children were treated by the author. 24 eyes of 15 patients had TMMC and 33 eyes of 20 patients had T5FU.
[Table 1] summarizes baseline characteristics of the two groups. There was no significant difference between the two groups, except for the mean age at time of surgery and mean number of pre-operative medications. Most patients were male, and had primary infantile glaucoma. Developmental glaucoma was diagnosed in two patients (two eyes aniridia, one eye irido-corneal dysgenisis) in 5FU group and three patients (two eyes aniridia, one eye Reiger's syndrome, two eyes irido-corneal dysgenisis) in MMC group. Secondary glaucoma was diagnosed in three patients (three eyes aphakia, one eye uveitis) in 5FU group and two patients (three eyes aphakia) in MMC group.
[Table 2] compares the results of the two groups on final P-OP follow up. 33 eyes had 33 T5FU; seven eyes of seven patients had unilateral operation, and 13 patients had bilateral procedures. 25 (75.8 %) eyes considered successful, of which ten (40%) eyes had previous failed procedures. 24 eyes had 24 TMMC, nine patients had bilateral procedure. 18 (75%) eyes considered successful, of which 6 (33.3%) eyes had previous failed procedures. No statistically significant difference was present between the groups.
The success rates according to type of glaucoma showed no significant difference between the two groups [Table 3].
Pre-operatively all eyes in both groups were on antiglaucoma medications. On final follow up, six (33.3%) eyes of the MMC group and 11(44%) eyes of the 5FU group were on antiglaucoma medications, with no significant difference ( P =0.773) between the grpups. Both groups had significant drop in the number of antiglaucoma medications at final follow up as compared to preoperative status ( P = 0.044 MMC, P = 0.000 5FU).
The final visual acuity in the two groups is presented in [Table 4]. Seven (38.9%) eyes of MMC group and 15(60%) eyes of 5FU group were legally blind (≤ 6/60). Good vision (≥ 6/36) was present in 11(61.1%) eyes of MMC group and ten (40%) of 5FU group. Even though there was a better visual outcome of MMC group, there was no statistically significant difference between the groups ( P =0.593).
Six (25%) eyes in MMC group and 16 (48.5%) eyes in the 5FU group developed complications [Table 5]. Most occurred intraoperatively or immediately P-OP and were successfully managed. A late (two year P-OP) bleb-related infectious endophthalmitis occurred in one eye in the MMC group following blunt trauma, which led to bleb leak. This was successfully treated, with preservation of sight, bleb and control of IOP. Hypotony occurred in one eye in the 5FU group due to over filtration, but it was not associated with maculopathy. It resolved with conservative treatment.
The optimal dosing and administration of 5FU and MMC was not known in children in 1994, so different concentrations and root of administration were tried. Methods of application of 5FU and success rate are shown in [Table 6]. The mean number of injections of 5FU given P-OP was 6.9 3.4 (range 1-10). Anterior retrobulbar injection of 5FU was as effective as subconjunctival injection, more safe, and easy to be given to a young awake child.
Patients in MMC group received a mean concentration 0.31 + 0.14 (range 0.2 - 0.5) mg/ml, and had a mean application time 4.3 + 0.9 (range 3 - 5) minutes.
| Discussion|| |
The optimal surgical procedure for CG in Saudi Arabia remains controversial. Al-Hazmi etal reported low success rate of goniotomy (42%) and trabeculotomy (29%) in CG.  In recent times the success rate achieved by trabeculectomy, combined trabeculotomy -trabeculectomy, trabeculotomy, and goniotomy was (42.9%), (35.7%), (33.3%), and (0%) respectively in Saudi Arabia Manuscript accepted by Journal of Taibah university Medical Sciences, in press now(Badeeb O.: Long-term outcome of surgical management of congenital glaucoma, JTUMS, 2008, in press). Trabeculectomy is the treatment preferred by most ophthalmologists in Saudi Arabia for CG, due to their familiarity with the technique, its high success rate, and low success rate of goniotomy and trabeculotomy. Khatib et al . and Debnath et al reported 63% and 54% success rate of primary trabeculectomy respectively in Saudi Arabian children. , The success rate of trabeculectomy increases with age, and has been reported to be 32% for patients younger than 6 months and 85% for patients older than 4 years of age.  The success rate of trabeculectomy decreases on long-term follow up, and it is lower for secondary types of CG. ,,
The adjunctive use of antimetabolites (5FU and MMC) has been reported to increase the success rate of trabeculectomy in CG. Surgical results improved with postoperative application of 5-FU, but the need for multiple subconjunctival injections is a significant drawback for pediatric use. , This problem does not occur with the intraoperative application of MMC, which is as effective as 5FU injections in achieving IOP control. ,, The success rate of TMMC in CG has been reported to range from 48% to 95%, depending on the patient's age, definition of success, length of follow up, and concentration and exposure time to MMC.  The success rate of trabeculectomy in CG improved from 42.9% to 75% after using either 5FU or MMC (author's unpublished data). There are no published reports of intraoperative sponge application of topical 5FU in CG. In this study, intra-operative sponge application of 5FU, with and without subconjunctival injections, was associated with a 63.6% mean success rate.
Comparison studies of 5FU and MMC adjuncts to trabeculectomy were found to be equally safe and effective in adult glaucoma, , but no published reports in CG. The present study could be the first comparison study in literature of 5FU and MMC augmented trabeculectomy in CG with long-term follow up. It shows equal effectiveness of the two drugs in CG. Previous studies have shown that single intraoperative dose of MMC has a distinctive advantage over 5FU injections, particularly in children. , The present study suggests that 5FU can be as effective as MMC when applied by sponge or single subconjunctival injection intraoperatively, but further study is needed to confirm this finding.
Even though antimetabolites improve the success rate of trabeculectomy in this study, their use may be associated with serious complications. Hypotony, retinal detachment, and bleb related infection (BRI) occurred in some patients in this study, as previously reported by Susanna et al , and Mandal et al . , Only one eye in the MMC group developed late BRI, even though a higher incidence is reported in literature.  Hypotony maculopathy is well described after antimetabolite use in trabeculectomy, with rates varying from 3.0% to 13.5%.  In this study, the incidence of hypotony was low; no patient developed hypotony maculopathy in the MMC group. These findings could be consequent to tight closure of the scleral flap.
This study should be viewed in light of certain limitations. First, because it is a retrospective review, it lacks randomization of selecting eyes for procedure and control group. Second, there is disparity in sample size of the two groups, which may skew results in favor of the T5FU group. Therefore, a direct comparison of success rates of the two groups must be interpreted with caution. Third, different concentrations and methods of applying the drugs, may underestimate the efficacy of topical MMC in achieving ahigher success rate. Sidoti etal reported a higher success rate of trabeculectomy (82-95%) when MMC concentration was 0.5 mg/ml and applied for 1.5-5 minutes.  In spite of these limitations, this study shows a considerable improvement of success rate of trabeculectomy on long term follow up, when adjunctive 5FU or MMC is used. A larger, prospective study is needed to confirm the results of this study.
| References|| |
|1.||Al-Faran M, Gammon A, Al-Mutlaq F. Congenital glaucoma in Saudi Arabia. Saudi J Ophthalmol 1991;5:76-9. |
|2.||Khatib H, Al-Faran M, Rasheed K, Zakir M. Standard trabeculectomy with adjunctive 5-FU for the treatment of Congenital glaucoma. Saudi J Ophthalmol 2001;15:123-9. |
|3.||Mullaney P, Selleck C, Al-awad A, Al-Mesfer S, Zawaan J. Combined trabeculotomy and trabeculectomy as an initial procedure in uncomplicated Congenital glaucoma. Arch Ophthalmol 1999;117:457-60. |
|4.||Beauchamp GR, Parks MM. Filtering surgery in children: Barriers to success. Ophthalmology 1979;86:170-80. [PUBMED] |
|5.||Cadera W, Pachtman M, Cantor L, Ellis F, Helveston E. Filtering surgery in childhood glaucoma. Ophthalmic Surg 1984;15:319-22. |
|6.||Skuta GL, Parrish RK 2nd. Wound healing in glaucoma filtering surgery. Surv Ophthalmol 1987;32:149-70. [PUBMED] |
|7.||Zalish M, Leiba H, Oliver M. Subconjunctival injection of 5-fluorouracil following trabeculectomy for congenital and infantile glaucoma. Ophthalmic Surg 1992;23:203-5. [PUBMED] |
|8.||Al-Hazmi A, Zwaan J, Awad A, Al-Mesfer S, Mullaney P, Wheeler D. Effectiveness and complications of Mitomycin C use during pediatric glaucoma surgery. Ophthalmology 1998;105:1915-20. |
|9.||Al-Hazmi A, Awad A, Zwaan J, Al-Mesfer S, Al-Jadaan I, Al-Mohammed A. Correlation between surgical success rate and severity of congenital glaucoma. Br J Ophthalmol 2005;89:449-53. |
|10.||Debnath S, Teichmann K, Salamah K. Trabeculectomy versus trabeculotomy in congenital glaucoma. Br J Ophthalmol 1989;73:608-11. |
|11.||Chen T, Wilensky J, Viana M. Long-term follow-up of initially successful trabeculectomy. Ophthalmology 1997;104:1120-5. |
|12.||Mandal A, Walton D, John T, Jayagandan A. Mitomycin C-augmented trabeculectomy in refractory congenital glaucoma. Ophthalmology 1997;104:996-1001. |
|13.||Sidoti P, Belmonte SJ, Liebmann J, Ritch R. Trabeculectomy with Mitomycin-C in the treatment of pediatric glaucoma. Ophthalmology 2000;107:422-9. |
|14.||Kitazawa Y, Kawase K, Matsushita H, Minobe M. Trabeculectomy with mitomycin. A comparative study with fluorouracil. Arch Ophthalmol 1991;109:1693-8. |
|15.||Skuta G, Beeson C, Higginbotham E, Lichter PR, Musch D, Bergstrom T, et al. Intraoperative mitomycin versus postoperative 5-fluorouracil in high-risk glaucoma filtering surgery. Ophthalmology 1992;99:438-44. |
|16.||Katz GJ, Higginbotham E, Lichter PR, Skuta GL, Musch DC, Bergstrom TJ, et al. Mitomycin C versus 5-fluorouracil in high-risk glaucoma filtering surgery: Extended follow-up. Ophthalmology 1995;102:1263-9. |
|17.||Mandal A, Netland P. The Pediatric Glaucomas. Philadelphia: Butterworth Heinemann, Elsevier Inc; 2006. |
|18.||Singh K, Mehta K, Shaikh NM, Tsai JC, Moster MR, Budenz DL, et al. Trabeculectomy with intraoperative mitomycin C versus 5-fluorouracil: Prospective Randomized clinical trial. Ophthalmology 2000;107:2305-9. [PUBMED] [FULLTEXT]|
|19.||WuDunn D, Cantor LB, Palanca-Capistrano AM, Hoop J, Alvi NP, Finley C, et al. A prospective randomized trial comparing intraoperative 5-fluorouracil Vs mitomycin C in primary trabeculectomy. Am J Ophthalmol 2002;134:521-8. [PUBMED] [FULLTEXT]|
|20.||Susanna Jr, Oltrogge E, Carani J, Nicolela M. Mitomycin as adjunct chemotherapy with trabeculectomy in congenital and developmental glaucoma. J Glaucoma 1995;4:151-7. |
|21.||Mandal AK, Walton DS, John T, Jayagandan A. Mitomycin C-augmented trabeculectomy in refractory congenital glaucoma. Ophthalmology 1997;104:996-1001. [PUBMED] |
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]