Nasolacrimal probing has proved effective for children with congenital NLD obstruction. However it shows a decline in success with increase in age due to longstanding blockage, chronic inflammation, and fibrosis of NLD. Tsai et al. in 2002 first used adjunctive MMC to improve the success rate of lacrimal probing for patients with NLD obstruction [8]. They introduced a Bowman 0- or 00-gauge probe into NLD and left in place for 30 s to minimize bleeding. After irrigating with normal saline to confirm duct patency, lacrimal irrigation was performed by introducing 1 ml of 0.02 % MMC into the duct with a syringe three times. To reduce systemic absorption of MMC, a cotton-tipped applicator was placed into the nasal cavity and patients were instructed not to swallow the solution. A following comparative randomized study by Sinha et al. showed an overall subjective improvement in 65 % of cases with MMC-adjunctive probing (1 ml of 0.2 mg/ml, once), as compared to 40 % of cases with probing alone [9].

In comparison to dacryocystorhinostomy, balloon dacryocystoplasty is associated with less morbidity and simple technique, but has a relative lower long-term success rate especially in cases with complete NLD obstruction. An analysis by Kim and associates showed that MMC irrigation at a concentration of 0.2 mg/ml in three different sessions (immediately, 1 week, and 1 month) after balloon dacryocystoplasty was effective in increasing the cumulative patency rate [10]. The balloon was soaked in MMC solution (0.2 mg/ml) before use. In addition, MMC irrigation was only performed in the NLD that revealed patency by dacryocystography, which was performed just after balloon dacryocystoplasty. Irrigation was performed twice with 1.5 ml of MMC solution (0.2 mg/ml) by using a syringe through the lower punctum for 1 min. MMC irrigation after balloon dacryocystoplasty could be an alternative to stent placement, especially in cases of complete NLD obstruction.

In 1997, Kao and Liao first used MMC to maintain a larger osteotomy size [11]. A meta-analysis study of nine randomized controlled trials indicates that adjunctive intraoperative MMC application with primary external dacryocystorhinostomy had a significantly higher success rate than external dacryocystorhinostomy without MMC (p = 0.01) [12]. Among which, two randomized controlled trials showed the mean osteotomy size 6 months postoperatively was significantly larger in the MMC group than in the control group [11, 13]. In most studies, a cotton pledget soaked in 0.2–1.0 mg/ml MMC was placed over the anastomosed posterior flaps and osteotomy site for approximately 2–30 min followed by copious irrigation with normal saline (Fig. 20.2). No complications except two cases with delayed healing of the external skin wound were noted in the MMC group of their systematic review [12].

Adjunctive MMC has also been applied for primary or revision endoscopic dacryocystorhinostomy, transcanalicular laser-assisted dacryocystorhinostomy, or endonasal endoscopic laser-assisted dacryocystorhinostomy to enhance the success rate. However, these results are not completely consistent. A meta-analysis study by Cheng and associates revealed that the success rate of the patency of the nasolacrimal canal and symptomatic improvement was significantly higher in the group with adjunctive intraoperative MMC application in primary and revision endoscopic dacryocystorhinostomy, as compared to those without MMC (p = 0.041) [14]. Among which, the mean ostium size in three studies was significantly bigger in MMC group than that in control group at 3 and 6 months postoperatively, though the difference was not significant at 12 months [15–17]. No MMC-associated complications were reported in their systematic review [14].

There are limited studies to investigate the efficacy of 5-FU in lacrimal surgery. By observing the postoperative structural change of the intranasal ostium through endoscopy, Costa et al. suggested that adjunctive 5-FU in external dacryocystorhinostomy does not significantly influence the final size of the surgical fistula [18]. Bakri et al. also showed that intraoperative use of 5-FU failed to increase the patency rate in endonasal laser dacryocystorhinostomy [19].

Although MMC has proven efficacy, it also increases the risk of complications. Some complications caused by MMC application have been reported in ophthalmic practice such as pterygium surgery, glaucoma filtration surgery, and topical use for of conjunctival-corneal intraepithelial neoplasia. It includes secondary glaucoma or cataract, corneal ulcer, limbal stem cell deficiency, scleral melting, hypotony, and endophthalmitis and maculopathy [20–22]. Nevertheless, the application of MMC in lacrimal surgery appears to be safe, and there are very few MMC-related complications have been reported in the lacrimal surgery. One case with adjunctive MMC irrigation in balloon dacryocystoplasty developed superficial punctate keratitis which was transient and resolved promptly with the use of artificial tears [10]. Two cases with delayed wound healing were reported in the use of MMC in external dacryocystorhinostomy [23, 24]. Strategies to minimize the incidence of complications associated with antimetabolite use in lacrimal surgery include using minimum effective concentration of MMC (0.2 mg/ml) and irrigating with copious normal saline after use of MMC. Doctors should be always aware of the potential complications associated with its use.