while the use of mmc has been increasingly popular in dcr , there is a lack of consensus regarding multiple variables ; namely the dosage , the route of delivery / application , the time of exposure and subsequently what role each of these variables plays in the final outcome of the surgery . ever since the intraoperative use of mmc has been a part of dcr , various studies have put forth their data with varying concentrations of mmc . the efficacy of different dosages of intraoperative mmc in external dcr in 50 eyes was studied by you and fang . in one group , 0.2 mg / ml of mmc was used for 5 min intraoperatively , and in the other group , 0.5 mg / ml of mmc was used for 5 min . these two groups were compared with a control group with no mmc . the patency rate and osteotomy size differences between the patients treated with mmc and the control group were statistically significant . however , there was no significant difference between the two groups in which mmc was used . studied the effects of intraoperative mmc on the clinical evolution and osteotomy size following an external dcr with helical computed tomography . they concluded that intraoperative mmc may increase the success rates over the traditional dcr procedure and is effective in reducing the closure rate of the osteotomy after dcr . , in their study to find the role of topical mmc as a postoperative adjunct to endonasal dcr ; placed a nasal pack soaked in 1 ml of 0.05% ( 2 mg in 5 ml of distilled water ) mmc after dcr . this was in place for 48 h. in their study , they observed that postoperative retention of nasal packs for 48 h after endonasal dcr did not cause any major side effect . improvement in clinical symptoms was noted in all patients who had nasal packing with mmc . postoperatively , the nasal cavity which had been packed with mmc had healthy nasal mucosa during the entire follow - up , as compared to the control group where the saline nasal pack was used , where synechiae were seen in 65.2% of the patients . used 3 groups : control group 1 , operated without mmc ; experimental group 2 , with mmc at a concentration of 0.05 mg / ml for 2 min ; and experimental group 3 , with mmc applied at a concentration of 0.4 mg / ml for 2 min . furthermore , half of the cases in each group underwent single - flap dcr , and half underwent double - flap dcr surgery . they concluded that the ostium size in group 3 was found to be significantly bigger in comparison with group 1 and with group 2 . nemet et al . , reported their experience in treating distal and common canalicular obstruction by trephination followed by topical low - dose ( 0.03% ) mmc and silicone intubation during endoscopic dcr 4 patients out of 5 remained asymptomatic with endoscopically seen open ostia for an average follow - up period of 15.4 months . while these reports have given a favorable verdict on the use of mmc in dcrs ; there are few on the other end of the spectrum who have published evidence that is , equivocal . zilelioglu et al . in one of the earlier studies to comment on the adjunctive use of mmc in endoscopic dcr ; used topical 0.5 mg / ml solution of mitomycin intraoperatively and applied the drug for 2.5 min . they demonstrated histopathological evidence that 0.5 mg / ml of mmc for 2.5 min favorably affected wound healing in the osteotomy site . however , this limited series showed no benefit of using mmc intraoperatively as their surgical success rates with and without mmc had success rates of 77.8 and 77.3% , respectively , at a mean follow - up period of 18.2 months . the adjunctive use of mmc in external dcrs noted that while the success rates of the mmc group were higher than those of the control group , the differences did not reach statistical significance . prasannaraj et al . in their results of endoscopic dcr where 38 patients were randomized into either an mmc group ( 0.2 mg / dl ) or a control group , reported a success rate of 82.3% with mmc 85.7% without mmc . granulations , adhesions , and obliterative sclerosis occurred in a similar number of patients in both groups , and the authors were of the opinion that granulations and adhesions did not have a bearing on the success rate in either group . while there are many reports which have shown the beneficial effect of mmc , it is equally important to note that there remains no study till date , which has reported a worse success rate for dcr with mmc when compared with dcrs without the use of mmc [ table 1 ] . select studies ( not exhaustive ) which have used different concentrations of mmc intraoperatively during dcr and for varying durations most studies have found that intraoperative mmc application seems to be safe ; furthermore no deleterious effects were noted with mmc application . mere eyeballing the data suggests that mmc plays a role in reducing the closure rate of the osteotomy site after a dcr . feng et al . in their meta - analysis of primary external dcr with and without mmc included nine randomized controlled trials reporting on a total of 562 dcrs including patients in the age range 3057 years . they mentioned that there was a significantly higher success rate in the mmc group in comparison with the control group ( odds ratio , 2.11 ; 95% confidence interval , 1.193.74 , p = 0 . the meta - analysis also found that intraoperative mmc application seems to be a safe adjuvant and helps in maintaining the patency of the ostium . cheng et al . in their recently published meta - analysis of endoscopic dcrs to compare the clinical results with and without mmc concluded that in addition to being safe , mmc helps reduce the closure rate of the osteotomy and enhance the success rate after both primary and revision endonasal dcr . ali et al . evaluated the ultrastructural effects of topical and circumostial injection of mitomycin - c ( cos - mmc ) on nasal mucosa and compared them with the controls ( untreated nave nasal mucosa ) . this was the first study to document detailed subcellular effects and classify the transmission electron microscopy findings as those of epithelial , glandular , vascular , and fibro collagenous . they reported that both , topical and cos - mmc showed profound changes in nasal mucosa , but more marked changes were observed in the cos - mmc group . the nasal fibroblasts showed a dramatic structural response to mmc : intracellular edema , pleomorphic and vesicular mitochondria , dilated smooth and rough endoplasmic reticulum , and chromatin condensation . it is evident from the varying concentrations of mmc that different studies have used that there is no agreement on the issue . it is further unclear as to how researchers arrived at each of these arbitrary concentrations before applying it to practice . ali et al . studied the effect of varying concentrations of mmc and treatment durations on cellular proliferation and viability of the fibroblasts . nasal mucosa harvested from patients undergoing a dcr was used to establish primary cultures by explant culture method . the cells were then treated with different concentrations of mmc ( 0.10.5 mg / ml ) for different time periods ( 3 , 5 , and 10 min ) . the significant findings of this study were that the doubling time of cultured nasal mucosal fibroblasts was found to be approximately 24 h. mmc at 0.4 mg / ml beyond 5 min and 0.5 mg / ml concentration at all time points were lethal and caused extensive cell death when compared with controls . the minimum effective concentration appeared to be 0.2 mg / ml for 3 min as it prevented cell proliferation of the fibroblasts by inducing cell cycle arrest , without causing extensive apoptosis . as mentioned in the discussion above , there have been different routes of application of mmc to the nasal and lacrimal sac mucosal surfaces . most studies have used a cotton - tip applicator soaked in mmc applied under the nasal and lacrimal flaps for the desired duration followed by copious irrigation with normal saline . used 0.03% solution of mmc in a 2 ml syringe with a 26 gauge lacrimal cannula to irrigate the newly trephined canaliculus via the punctum into the nose , with the stents in place . a neurosurgical patty was preplaced in the nose to soak up any excess mmc and finally , the conjunctival sac was immediately irrigated with normal saline . rathore et al . in their series of endonasal dcrs , packed the nasal cavity with 0.05% mmc nasal pack for 48 h. another promising variation in the delivery technique of mmc is cos - mmc introduced by kamal et al . , where after fashioning the mucosal flaps , intramucosal injection of 0.02% mmc was injected at four points ( 0.1 ml at each point ) along the edges of the freshly created ostium [ figs . 1 and 2 ] . their high clinical success rates along with basic science evidence indicate that cos - mmc may be an effective adjunctive modality in high - risk cases like revision and posttraumatic dcr 's . ( a - c ) the sites of injection of intramucosal ( nasal mucosa ) circumostial mitomycin - c seen endoscopically ( sites marked with yellow asterisks ) . a lacrimal probe has been introduced transcanalicular route and is seen at the ostium endoscopic view , the ostium of a 2-year - old child who underwent dacryocystorhinostomy with circumostial mitomycin - c . note the large ostium , which is unusual given the exuberant healing response commonly seen in the pediatric population postoperative mmc application has also been studied by henson et al . an 8 mm cotton ball was soaked with 0.5 ml of mmc ( 0.4 mg / dl ) and placed on the tip of a curved mosquito forceps . this 5 min application of mmc ( 0.4 mg / ml ) , without irrigation , was done on the 1 , 2 , and 3 week . all failures were due to cicatricial closure of the ostium . more importantly , no significant intra - operative and postoperative nasal complications from the mmc were recorded . the major disadvantage of all the clinical studies is the heterogeneity with regards to multiple factors , and this prevents head to head comparisons and subsequent drawing of useful conclusions . some studies have included revision cases and others have not ; some surgeons prefer to wash off the mmc after application while others do not ; variable techniques , dosages , and follow - ups are some of the many confounders while comparing the outcomes dcrs with and without mmc . the expertise of the surgeon often plays a role in the outcome of a surgery : in a dcr , a beginner is more likely to traumatize the nasal mucosa and , in particular , the nasal septum which can promote the formation of septal adhesions . other factors such as racial variations , age and sex of the patient can also affect the eventual outcome of the surgery . while the core surgical principle of dcr remains constant ; newer techniques are constantly evolving toward making it a lesser invasive , safer procedure with long lasting success . the role that mmc has played in improving the success rate of dcr appears to be useful in the wake of recent evidence ; regardless of the route chosen : external or endoscopic endonasal . having more or less established the safety and efficacy of mmc , the focus perhaps could shift on newer delivery techniques of the drug : intra mucosal depot injection of mmc intra - operatively or even an mmc - coated intubation tube which could provide sustained drug delivery and that may affect the outcomes of the surgery . the search for the ideal dosage , the most efficacious mode of drug delivery and minimum effective duration of application of the drug is still on . the journey of mmc in dcr from experimentation to implementation has yielded promising results ; the next step , naturally is standardization . the answer lies in larger , multi - centric , uniform protocol guided , double - masked randomized control trials . mja receives royalties from springer for his textbook  principles and practice of lacrimal surgery . mja receives royalties from springer for his textbook  principles and practice of lacrimal surgery .
dacryocystorhinostomy ( dcr ) is the procedure of choice in patients with epiphora due to primary acquired nasolacrimal duct obstruction . 
 the evolution of surgical tools , fiber - optic endoscopes , effective anesthesia techniques , and the adjunct use of antimetabolites intraoperatively ; namely mitomycin - c ( mmc ) have significantly contributed to the advancement of dcr surgery . 
 mmc is a systemic chemotherapeutic agent derived from streptomyces caespitosus that inhibits the synthesis of dna , cellular rna , and protein by inhibiting the synthesis of collagen by fibroblasts . 
 even the cellular changes in the human nasal mucosal fibroblasts induced by mmc at an ultrastructural level have been documented . there 
 , however , seems to be a lack of consensus regarding mmc : the dosage , the route of delivery / application , the time of exposure and subsequently what role each of these variables plays in the final outcome of the surgery . in this review 
 , an attempt is made to objectively examine all the evidence regarding the role of mmc in dcr . 
 mmc appears to improve the success rate of dcr .