|Year : 2016 | Volume
| Issue : 3 | Page : 135-139
The safety and efficacy of minimal dose of mitomycin C in trabeculectomy
Rekha Bellulli Kotrappa, Arvind Y Yakkundi, Bhagyajyothi Balappa Khangavi, Anju Meena, Dhara Shah
Department of Ophthalmology, Jawaharlal Nehru Medical College, Belagavi, Karnataka, India
|Date of Web Publication||14-Sep-2016|
Rekha Bellulli Kotrappa
Department of Ophthalmology, Jawaharlal Nehru Medical College, JNMC Campus, Nehru Nagar, Belagavi - 590 010, Karnataka
Source of Support: None, Conflict of Interest: None
Aim: To evaluate the safety and efficacy of minimal concentration and exposure time of mitomycin C (MMC) (0.1 mg/mL for 2 min) as an adjunct to trabeculectomy and to evaluate the complications of minimal dose of MMC in trabeculectomy. Background: Glaucoma ranks second as the most common cause of blindness worldwide. The introduction of MMC as an adjunct to trabeculectomy was a major advancement in the ability to improve the intraocular pressure (IOP)-lowering efficacy of the procedure. Materials and Methods: In this study, 40 patients, who had primary open-angle glaucoma, were included. Both with MMC in a dose of 0.1 mg/mL for 2 min, 20 underwent trabeculectomy alone, and 20 underwent combined surgery. Postoperative IOP at each follow-up, bleb appearance, the need for postoperative medical glaucoma treatment, and improvement of vision were recorded. We evaluated the IOP, bleb appearance, and complications on day 1, 1 week, 1 month, and 3 months postoperatively. Results: A total number of 40 patients were studied. There were 25 males and 15 females with mean age 65 ± 10 years. The IOP at 3 months follow-up was 12.0 ± 1.5 mmHg, 1 day was 17 + 1.5 mmHg, 1 week was 14.6 ± 5 mmHg, and 1 month was 12.2 ± 5 mmHg. No bleb related complications or any other complications were noted in any of the patients. In all the patients, bleb appearance was grade II-III according to Moorfields classification. Visual acuity in all the 20 patients was between 6/24 and 6/9, who underwent combined procedure. Conclusion: Trabeculectomy with intraoperative MMC in a dose of 0.1 mg/mL and exposure time of 2 min tested to be a safe and effective modality in the management of glaucoma.
Keywords: Bleb, intraocular pressure (IOP), mitomycin C (MMC), trabeculectomy
|How to cite this article:|
Kotrappa RB, Yakkundi AY, Khangavi BB, Meena A, Shah D. The safety and efficacy of minimal dose of mitomycin C in trabeculectomy. J Sci Soc 2016;43:135-9
| Introduction|| |
Glaucoma ranks second as the most common cause of blindness worldwide.  Glaucoma surgery has many sight-threatening complications and a high risk of failure. This risk of failure is multiplied many times in high risk populations such as the young people and the black people. The cause of failure in these cases is scarring due to proliferation of fibroblasts at the surgical site.  So, to increase the success rates in the glaucoma filtration surgeries, antifibrotic agents are being used to modulate wound healing. 
The introduction of mitomycin C (MMC) as an adjunct to trabeculectomy was a major advance in the ability to improve the intraocular pressure (IOP)-lowering efficacy of the procedure.  MMC is an antineoplastic antibiotic agent isolated from the fermentation filtrate of Streptomyces caespitosus, has been shown to suppress fibroblastic activity. The advantages of its use as an adjunctive to glaucoma filtering surgery are a reduction of corneal complications, a more profound reduction in IOP, and elimination of the need for postoperative administration of drugs. 
However, there is an increased risk of serious complications including hypotony and maculopathy in the early postoperative course. Many investigators have attempted to find protocols for the adjunctive therapy that will provide an acceptable balance between the benefits and risks. 
The purpose is to evaluate the safety and efficacy of low-dose MMC in trabeculectomy. The introduction of MMC as an adjunct to trabeculectomy was a major advance in the ability to improve the IOP-lowering efficacy of the procedure. It is known that this antiproliferative agent acts in a dose- and time-dependent way. 
Treatment of glaucoma is usually by medical therapy but in situations such as poor compliance, lack of awareness, poor follow-up facilities, and nonaffordability, surgical intervention becomes the method of choice.  To increase the success rates in the glaucoma filtration surgeries, MMC helps to modulate wound healing. 
So, the study is aimed to evaluate the safety and efficacy of minimal concentration and exposure time of MMC (0.1 mg/mL for 2 min) as an adjunct to trabeculectomy.
| Materials and methods|| |
All patients diagnosed with glaucoma and IOP >21 mmHg and follow-up patients who have IOP, did not come under control with medical management, and patients diagnosed with both cataract and glaucoma were included in the study. Written and informed consent of the participating patients were taken. Visual acuity, slit-lamp examination, visual fields, gonioscopy, and IOP were checked and fundus photographs were taken. The postoperative IOP at each follow-up, the bleb appearance, the need for postoperative medical glaucoma treatment, and the change in vision were noted.
In all cases, the surgery was performed after giving peribulbar anesthesia. A superior rectus bridle suture was taken and a limbus-based conjunctival flap was raised. After hemostasis was obtained, MMC was applied beneath the scleral flap for 2 min with a surgical sponge measuring 4.5 mm × 4.5 mm, which was soaked in a 0.1 mg/mL solution. After 2 min, the sponge was removed and the entire surgical field was irrigated thoroughly with a balanced saline solution.
A 4 mm × 4 mm scleral flap was fashioned 1 mm into clear cornea; a 1 mm × 2 mm scleral block was excised. The scleral flap was closed with four interrupted 8-0 vicryl sutures and the conjunctiva was closed tightly with interrupted 8-0 vicryl sutures. A subconjunctival injection of 2.0 mg gentamicin and 2.0 mg dexamethasone was administered. Ciprofloxacin eye ointment was applied.
Postoperatively, all patients received systemic antibiotics and analgesics for 5 days, topical antibiotics and steroid eye drops for six times per day for 2 weeks and tapered over 6-8 weeks, topical cycloplegic two times per day for 4 weeks.
Follow-up was done on the first postoperative day, at 1 week, at 1 month, and 3 months postoperatively. A "complete success" was when the IOP was less than 21 mmHg without glaucoma medication, a "qualified success" when the IOP was less than 21 mmHg with glaucoma medication, and a "failure" when the IOP was greater than or equal to 21 mmHg with medical treatment or when repeat surgery was required.  Hypotony was defined as an IOP less than 5 mmHg, documented at two postoperative visits separated by at least 1 week.
| Results|| |
Out of 40 patients, 25 patients were males and 15 patients were females with a mean age of 65 ± 10 years. A total number of 20 patients underwent trabeculectomy alone and 20 patients underwent combined surgeries. We evaluated the IOP and bleb appearance on day 1, 1 week, 1 month, and 3 months postoperatively.
Mean postoperative IOP
On day 1-17.1 ± 1.5 mmHg
On 1 week-14.6 ± 1.5 mmHg
On 1 month-12.2 ± 5 mmHg
On 3 months-12 ± 5 mmHg
All patients had mildly elevated, diffuse, normally vascularized bleb (grade 2-3) associated with good filtration according to Moorefields bleb morphological classification [Figure 1].
Moorfields bleb grading system
The bleb is assessed either photographically or at the slit-lamp, and characterized with respect to height and to vascularity in three zones: Central bleb, peripheral bleb, and nonbleb. An elaborate photographic set of standards is available, as well as a standardized form for reporting.
- Central bleb area: An estimation into five categories of percentages (0%, 25%, 50%, 75%, and 100%) is made of the relative size of the central demarcated area of the bleb relative to the visible conjunctival field superiorly. Often, this is confined to the area over the scleral flap; in a uniform bleb, central and peripheral estimations are congruent.
- Peripheral bleb area: The maximal extent of the bleb is assessed using a similar scale of 5% estimations.
This parameter assesses the maximal diffusion area of the bleb, as evidenced by slight bogginess or guttering at the edges.
- Bleb height: In reference to the standardized photographs, the maximal central bleb height is scaled as flat, low, moderately elevated, or maximally elevated.
- Vascularity: Considered the most important prognostic parameter for bleb failure, this scale is applied to three areas: The central demarcated bleb, the bleb's peripheral extent of diffusion, and the surrounding nonbleb conjunctiva.
Five grades of vascularity are used: Avascular, normal, mild vascularity, moderate vascularity, and severe vascularity. Subconjunctival blood is notated as well.
All patients with IOP were well controlled with posttrabeculectomy without medication. There were no postoperative complications related to MMC. Only one patient required resuturing due to bleb leakage.
Twenty patients underwent combined procedure, whose uncorrected visual acuity (UCVA) on 6 weeks postoperatively was ranging 6/24-6/12. The best corrected visual acuity (BCVA) on 6 weeks was up to 6/9.
There was a complete success rate in controlling postoperative IOP without medication.
| Discussion|| |
The use of MMC during glaucoma filtration surgery has improved the outlook for cases known to have a high risk of surgical failure. Several doses and application time regimes have been evaluated for MMC. Higher doses and duration of MMC increases the surgical success rate, but unfortunately, complication rates increase as well. Therefore, there is a need to optimize the dose of MMC. In our study, we evaluated the safety and efficacy of minimal concentration and exposure time of MMC. Combining the cataract operation with trabeculectomy offers the main advantage of requiring only one operation to achieve a lower IOP after cataract surgery. With MMC, the overall incidence of bleb leaks and infections appears to be constant over time. Postoperatively, we saw no persistent complications or infections.
In our study, the mean postoperative IOP at a 3-month follow-up was 12.5 ± 1.5 mmHg. In a study conducted, in which combined trabeculectomy was done in 16 eyes and trabeculectomy with MMC was done in 16 eyes. Mean preoperative IOP in group 1 was approximately 24 and for group 2 was 27 that was reduced to around 12.5 and 13.2 mmHg, respectively. No complications were noted.  The results of this study were similar to our study in relation to postoperative IOP.
There is a study to evaluate the effect of low and high dose adjunctive MMC in trabeculectomy. The time of application was 5 min with concentrations of 0.1 mg/mL, 0.2 mg/mL, and 0.4 mg/mL, respectively. The postoperative IOP at 3 months was 13.5 + 3 mmHg. The patients who underwent combined procedure had good visual acuity. There was no statistical difference among the three groups in the success rate, regardless of medication.  These study results were similar to our study in relation to postoperative IOP as well.
In a study conducted, based on low-dose and high-dose MMC in trabeculectomy was applied for 5 min. They found that low-dose drug inhibited fibroblast proliferation for a prolonged period and the effect was localized to the treated area.  In our study, we used a low dose of MMC that proved to be safe and effective.
In a study that compared protocols of 0.2 mg/mL for 2 min, 0.2 mg/mL for 4 min, and 0.4 mg/mL of MMC for 2 min. They found a possible dose-response relationship, with exposure time appearing to be more important than concentration. They concluded that a low dose with minimum exposure time proves beneficial, i.e., 0.2 mg/mL for 2 min. 
The study was done in Korea, in which 26 patients underwent trabeculectomy with the different concentrations of MMC, i.e., 0.4 mg/mL, 0.2 mg/mL, 0.1 mg/mL for 5 min. All the patients were followed up for 3 months. At postoperative 3 months, the mean IOP with 0.4 mg/dL MMC was 10.1 mmHg, mean IOP with 0.2 mg/dL MMC was 16.1 mmHg, mean IOP with 0.1 mg/dL MMC was 16.5 mmHg. Bleb score was 7.0, 6.0, 6.1, respectively.  This study concluded that MMC in dosage of 0.2 mg/mL gave good results in terms of postoperative IOP and bleb formation.
The study was done in the US, in which consecutive glaucoma patients were evaluated, who underwent trabeculectomy with adjunctive MMC that was titrated for concentration and exposure time (0.2, 0.3, 0.4 mg/dL for 1-5 min). Out of the 119 patients who were defined as having a successful outcome, the mean preoperative IOP was 23.2 ± 9.2 mmHg and the mean final IOP in this outcome group was 11.7 ± 2.9 mmHg with 0.2 mg/mL for 2 min. This study showed results similar to our study in relation to the dosage and complications. 
In a study conducted by Ibrahim et al., who used 0.2 mg/mL of MMC for 1 min.  They had 73% patients with IOP between 11 mmHg and 20 mmHg. In another study, who had 89% patients with IOP at 3 months <15 mmHg  that was similar to our study.
In our study, we showed that 0.1 mg/mL of MMC for 2 min caused very few complications. So, we demonstrated the long-term efficacy and safety of low-dose MMC.
In our study, all patients had mildly elevated, diffuse, normally vascularized bleb (grade 2-3) associated with good filtration according to Moorefields bleb morphological classification.
In our study, 20 patients underwent combined procedure, they had good visual outcome in the range of 6/24-6/9 with postoperative IOP, approximately 12.2 mmHg without medication. So, there was complete success.
In summary, our series of trabeculectomy alone and combined small incision cataract surgeries/trabeculectomies resulted in excellent IOP control, substantial visual recovery, and a decrease in the number of glaucoma medication without complications. This combined technique adds to our armamentarium-a surgery that is reasonably safe, effective, predictable, and stable with the use of antimetabolites.
| Conclusion|| |
The best approach to glaucoma therapy in developing countries is currently intermediate. The chronic use of topical medications that have high cost imposes a significant economic burden on patients, many of whom live at a subsistence level.
Trabeculectomy with intraoperative MMC in a dose of 0.1 mg/mL and exposure time of 2 min tested to be a safe and effective modality in the management of glaucoma.
The results illustrate that MMC applied beneath the scleral flap during trabeculectomy is associated with a success rate comparable to other modes of application. The incidence of potentially serious complications such as conjunctival wound leak and prolonged hypotony was lower.
Financial support and sponsorship
The authors do not have any financial interests in any product/procedure mentioned.
Conflicts of interest
The authors do not have any competing interests in any product/procedure mentioned in this study.
| References|| |
Baig MS, Ahmed J, Ali MA. Trabeculectomy with Mitomycin-C. Pak J Surg 2008;24;49-52.
Agarwal HC, Sharma TK, Sihota R, Gulati V. Cumulative effect of risk factors on short-term surgical success of mitomycin augmented trabeculectomy. J Postgrad Med 2002;48:92-6.
Lee JJ, Park KH, Youn DH. The effect of low-and high-dose adjunctive mitomycin C in trabeculectomy. Korean J Ophthalmol 1996; 10:42-7.
Skuta GL, Parrish RK 2 nd
. Wound healing in glaucoma filtering surgery. Surv Ophthalmol 1987;32:149-70.
Casson R, Rahman R, Salmon JF. Long term results and complications of trabeculectomy augmented with low dose mitomycin C in patients at risk for filtration failure. Br J Ophthalmol 2001;85:686-8.
Hyung SM, Kim SK. Mid-term effects of trabeculectomy with mitomycin C in neovascular glaucoma patients. Korean J Ophthalmol 2001; 15:98-106.
Lee SJ, Paranhos A, Shields MB. Does titration of mitomycin C as an adjunct to trabeculectomy significantly influence the intraocular pressure outcome? Clin Ophthalmol 2009;3:81-7.
Reddy B, Dada T, Sihota R, Pandya A, Khokkar S, Gupta V. Comparison of trabeculutomy- trabeculectomy with Mitomycin-C vs trabeculectomy with Mitomycin-C in primary congenital glaucoma. JOCGP 2011;5:15-9.
Robin AL, Ramkrishnan R, Krishnadas R, Smith SD, Katz JD, Selvaraj S, et al
. A long-term dose-response study of mitomycin in glaucoma filtration surgery. Arch Ophthalmol 1997;115:969-74.
Ibrahim FN, Huseyin B, Shaffer N. Surgical management of inflammatory glaucoma. Perspect Ophthalmol 1977;1:173.
Costa VP, Moster MR, Wilson RP, Schmidt CM, Gandham S, Smith M. Effects of topical mitomycin C on primary trabeculectomies and combined procedures. Br J Ophthalmol 1993;77:693-7.