Findings from the present meta-analysis indicate that adjunctive intraoperative MMC application with EN-DCR surgery had a significantly higher success rate than EN-DCR surgery without MMC. Sensitivity and subgroup analysis also suggested that the results were comparatively reliable. Moreover, in three studies included in this meta-analysis, mean ostium size was significantly bigger in MMC group than that in control group at 3, 6 months postoperatively. However, the difference of mean ostium size was not significant between two groups at 12 months postoperatively.
The most common reason for the failure of this operation is the formation of scar or granulation tissue over the rhinostomy site 
It is postulated that adjunctive use of MMC over the osteotomy site in EN-DCR surgery could inhibit scarring and granulation tissue formation around the osteotomy site or common canaliculus and enhance the success of EN-DCR surgery. Based on our meta-analyses, it appears that it will be helpful to apply MMC over the osteotomy site to increase the success rate of primary EN-DCR (P
0.045). For revision DCR, the endoscopic approach is especially superior to the external approach. The normal scarring produced after the external incision makes a revision procedure very uncomfortable, and the final aesthetic and functional results are usually poor. In contrast, endoscopic revision DCR is an easy procedure with mainly good results 
. Moreover, Korkut and associates 
evaluated the results of primary and revision EN-DCR. They stated that EN-DCR is a safe and effective procedure in revision cases, as well as in primary cases. In the present meta-analysis, only four studies of revision EN-DCR were included. Although the results showed that the success rate was higher in the MMC group than control group (P
0.029), future larger sample size comparative clinical trials are needed to prove it.
Only three trials compared the ostium size between MMC groups and control group after surgery 
. All these studies clearly showed the mean size of the ostium 3, 6 and 12 months postoperatively was bigger in the MMC group than in the control group, though the difference was not significant at 12 months [WMD
11.63, 95% CI (−1.04, 24.29), P
0.072]. This manifestation strongly supports the antifibrotic property of the MMC in maintaining the ostium size in the postoperative period. In addition, Mudhol and associates 
shown that there is a small reduction in the size of the lacrimal ostium in the first 4 weeks which corresponds to the initial stages of healing. However, after 4 weeks there was no significant change in ostium size. Their findings correlate with the results of Mann and associates 
. Furthermore, the large reduction in sizes might reflect variations in surgical techniques and the strong healing process and remodeling that could be different in ethnicity 
There is a difference of opinion as to whether a silicone tube should be inserted. To prevent obliteration of the intranasal lacrimal sac ostium, many surgeons prefer to insert either bi- or monocanalicular silicone tubes to stent the internal ostium. However, it has been postulated that silicone tubing itself may cause tissue granulation, predisposing the site to postoperative infection and adhesions, and canalicular lacerations, resulting in surgical failure 
. Thus, some surgeons suggested the use of MMC to suppress fibrous proliferation and scar formation during EX-DCR surgery with silicone intubation. The results of the subgroup analysis demonstrated that there was no significant difference between patients undergoing silicone intubation accompanied by MMC application and silicone intubation alone during EX-DCR (P
Some complications such as corneal ulcus, corneal perforations, scleral calcification, secondary cataract, endophthalmitis, hypotony and maculopathy have been reported from the use of MMC in pterygium and glaucoma surgery 
. Nevertheless, the application of MMC in EN-DCR appears to be safe, and the occurrence of complications was at a relatively low level. No articles included in this study reported MMC-related complications such as abnormal nasal bleeding, mucosal necrosis, or infection.
After surgery, there is a natural tendency for the stoma to contract during the healing process, hence, the follow-up period must be adequate to accommodate completion of this healing process. An analysis by Boush and associates 
showed that most surgical failures occurred within the first 4 months after surgery. Similar findings were reported by Kong and associates 
who observed that the average onset of stomal closure after primary operation was 12.7 weeks. Woog and associates 
reported that the average onset of failure was 7.5 weeks postoperatively. Therefore, only studies with a minimum follow-up period of 6 months were selected in this systematic review. However, most patients included in this meta-analysis were relatively young. A recently retrospective study 
reported that in EN-DCR for primary acquired nasolacrimal duct obstruction, younger patient age at time of surgery was associated with a higher rate of failure. However, we did not perform an analysis of this subgroup of patients with different ages due to lack of data.
This meta-analysis may have some limitations. First, two comparative studies included in the analysis were not randomized, which may leave them vulnerable to bias. Although the Begg and the Egger test demonstrated no evidence of publication bias, the results should be interpreted with caution publication bias. Second, a potential source of heterogeneity in the results was the different concentrations and exposure time of MMC application. In the current systematic review of eleven studies, the dose of MMC used ranged between 0.2 and 0.5 mg/mL and the exposure time from 2–15 minutes. Thus, a further controlled study with a large sample size is needed to evaluate the optimum concentration, as well as applied duration of MMC for EN-DCR. This may provide more conclusive information for determining whether intraoperative MMC in EN-DCR is a safe and effective adjuvant.
In summary, this meta-analysis suggests that intraoperative MMC application seems to be a safe adjuvant that could help achieve favorable success rates and reduce the closure rate of the osteotomy site after EN-DCR.