Dacryocystorhinostomy with Intraoperative Mitomycin C

Shine C. S. Kao, MD, Chiu L. Liao, MD, Jason H. S. Tseng, MD, Muh S. Chen, MD, Ping K. Hou, MD

Purpose: To observe the effect of intraoperative mitomycin C on the size of the osteotomy site after dacryocystorhinostomy.

Methods: A total of 15 eyes of 14 patients diagnosed with primary acquired nasolac­rimal duct obstruction were assigned randomly to either a mitomycin C group or a control group. The surgical procedures in both groups were exactly the same, except that in the patients in the mitomycin C group, a piece of neurosurgical cottonoid soaked with 0.2 mg/ml mitomycin C was applied to the osteotomy site and then after 30 minutes was removed transnasally. Nasoendoscopic findings were recorded at the completion of the surgery and at 1 month, 3 months, and 6 months after surgery for the two groups. A computer-aided digitizer was used to calculate the surface area of the osteotomy site, and a Student's t test was used to compare the difference between the two groups.

Results: All patients in the mitomycin C group remained symptom free after removal of their silicone tube (100% success), and there was one patient in the control group who had recurrent epiphora (87.5% success). Septo-osteotomy adhesion was found in two patients in the control group (25%), but there was no such adhesion found in the patients in the mitomycin C group. In the mitomycin C group, the average final surface area of the osteotomy at the end of the sixth postoperative month was 27.10 ± 5.78 mm2

, whereas that of the control group was only 10.83 ± 3.37 mm2. Although the

immediate postoperative surface area of the osteotomy showed no significant difference between the two groups, a statistically significant difference was noted at 6 months.

Conclusion: Intraoperative mitomycin C is effective in maintaining a larger osteot­omy size. This modification may possibly improve success rates over the traditional dacryocystorhinostomy procedure. Ophthalmology 1997; 104:86-91

Most ophthalmic surgeons accept dacryocystorhinostomy (DCR) as a highly successful procedure in managing epiphora because of nasolacrimal duct obstruction. From previous studies, it appears that the success rate for this procedure is approximately 90%.1-3 The two most fre­quent causes of DCR failure are obstruction of the com­mon canaliculus and closure of the osteotomy site.4

-6

Thus, if we can inhibit fibrous tissue growth and scarring by applying antiproliferative agents over the anastomosed

flaps and osteotomy site, the failure rate may be de­creased.

Mitomycin C, an antiproliferative agent, has been widely used in pterygium excision and trabeculectomy with favorable results.7

-9 In this article, we present a con­

trol study by using mitomycin C to soak the area of the anastomosed flaps and osteotomy site and evaluate the long-term effect on osteotomy size after DCR surgery.

Originally received: June 3, 1996. Revision accepted: August 12, 1996.

From the Department of Ophthalmology, National Taiwan University Hospital, Taipei.

Reprint requests to Shine C. S. Kao, MD, Department of Ophthalmology National Taiwan University Hospital 7, Chung-Shan S. Rd, Taipei, Tai­wan.

86

Subjects and Methods

During 1994, 14 patients diagnosed with primary acquired nasolacrimal duct obstruction were assigned randomly into a mitomycin C DCR group (mitomycin C group) and regular DCR group (control group). A total of 15 DCRs were performed by one surgeon (SCSK). In one patient with bilateral nasolacrimal duct obstruction, a DCR was

Kao et al . Dacryocystorhinostomy with Intraoperative Mitomycin C

performed simultaneously in both eyes and one eye under­went a mitomycin C application, whereas the other eye did not. The mean age of the mitomycin C group was 55.0 :::':: 9.5 (mean:::,:: standard deviation) years and that of the control group was 52.0 :::':: 14.7 years.

The standard surgical techniques of an external DCR was used in all patients of both groups. Local infiltrative anesthesia consisting of 2% xylocaine (Fujisawa Pharmaceutical Co. Ltd., Osaka, Japan) and 1:100,000 epinephrine was adminis­tered in the region of the medial canthus and lower lid. The nasal mucosa was anesthetized and vasoconstricted with pled­gets saturated with a mixture of 5% cocaine and 1:100,000 epinephrine. A skin incision was performed, and blunt dissec­tion to the periosteum overlying the anterior lacrimal crest was undertaken. The periosteum then was incised and elevated off the lacrimal sac fossa. The osteotomy was created over the lacrimal fossa with an electric drill. The lacrimal sac was opened in a longitudinal fashion to form anteroposterior flaps. The nasal mucosa was cut in a similar fashion to the lacrimal sac. Then, the posterior nasal and lacrimal sac flaps were joined with 5-0 polyglactin suture. In the mitomycin C group, a piece of neurosurgical cottonoid saturated with 0.2 mglrnl mitomycin C was placed over the anastomosed posterior flaps and osteotomy site and then was removed transnasally after an application time of 30 minutes. Once the mitomycin C­saturated neurosurgical cottonoid was in place, a silicone tube was used to intubate the lacrimal system and followed by being tied together with a 4-0 silk suture. The anterior nasal and lacrimal sac flaps were closed with additional 5-0 poly­glactin sutures, as were the periosteum and orbicularis muscle in separate layers. The skin incision was sutured with a run­ning 6-0 nylon suture. The mitomycin C-saturated cottonoid was removed transnasally after a 30-minute soak. In the con­trol group, the same procedures were performed except for the absence of the mitomycin C application.

The osteotomy size was documented by a transnasal endoscopic photograph of the osteotomy site with the silicone tube in situ. Transnasal endoscopic photos were taken at the completion of the surgery and at 1 month, 3 months, and 6 months after surgery for both groups (Figs 1 and 2). A computer-aided digitizer was used to calculate the measured surface area of the osteotomy size and the diameter of the silicone tube on the photograph. Because the actual diameter of the silicone tube is 1 mm, we can calculate the actual surface area of the osteotomy size by multiplying the measured surface area with a converting factor ([actual diameter/measured diameterf of the sili­cone tube). All the calculations were done by one of our staff members who did not know whether he was looking at a photograph of a mitomycin C group or a control group patient.

A Student's t test was used to compare the actual oste­otomy area of each group immediately after surgery and at 1 month, 3 months, and 6 months after DCR surgery.

Results

In our study, there were 14 patients, 1 of whom had bilateral nasolacrimal duct obstruction. Thus, we had

seven eye samples in the mitomycin C group and eight eye samples in the control group. The mean age of the mitomycin C group was 55.0 :::':: 9.5 years old and for the control group, it was 52.0 :::':: 14.7 years old. There was no significant difference in age between the two groups (P> 0.05).

All patients in the mitomycin C group remained symp­tom free after removal of their silicone tube (100% suc­cess). One eye sample in the control group was noted to have recurrent epiphora (87.5% success). Septo-osteot­omy adhesion was found in two eye samples in the control group (25%), but no such adhesion was found in the mitomycin C group. During the follow-up period, no com­plications such as delayed wound healing, abnormal nasal bleeding, mucosal necrosis, or infection were noted in any patients.

In the mitomycin C group, the actual surface area of the osteotomy site immediately after operation was 66.28 :::':: 11.06 mm2 on average. In the control group, it was 65.55 :::':: 8.66 mm2

• The immediate postoperative surface area of the osteotomy site was not significantly different between the two groups (P > 0.05). The actual surface area of the osteotomy site 1 month after surgery in the mitomycin C group was 29.36 :::':: 9.29 mm2 on average, whereas in the control group it was 15.67 :::':: 4.26 mm2

•

Thus, there appeared to be a significant difference in the osteotomy size between the two groups 1 month after surgery (P < 0.005). Three months after surgery, the mean actual surface area of the osteotomy site in the mitomycin C group was 27.96 :::':: 10.45 mm2

, whereas in the control group it was 12.22 :::':: 3.02 mm2

• A significant difference in the osteotomy size between the two groups was noted (P < 0.005). Results at 6 months after surgery showed that the mean actual surface area of the osteotomy site in the mitomycin C group was 27.10 :::':: 5.78 mm2

,

whereas that of the control group was 10.83 :::':: 3.37 mm2•

There appeared to be a significant difference in the osteo­tomy size between the two groups (P < 0.005).

In addition, we also analyzed the percentage of the remaining osteotomy size in comparison with the osteot­omy size immediately after surgery in each follow-up period between the two groups. In the mitomycin C group, the percentage of the remaining osteotomy size after 1 month was 44.9:::':: 8.71 % on average, whereas the control group showed a 23.9:::':: 6.51 % on average. Thus, a statisti­cally significant difference was noted (P < 0.005). The percentage of the remaining osteotomy size at 3 months after surgery in the mitomycin C group was 42.18 :::':: 9.18% on average and 18.64 :::':: 4.7% in the control group. There was statistically significant difference between the two groups (P < 0.005). As for the percentage of the remaining osteotomy size 6 months after DCR surgery, in the mitomycin C group it was 40.89 :::':: 7.67%, and in the control group it was 16.52 :::':: 5.17%. A significant difference was noted between the two groups (P < 0.005).

In our study, we had one patient who received a bilat­eral DCR, of which one eye underwent mitomycin C soaking and the other eye did not. The actual surface area of the osteotomy site in the mitomycin C-soaked eye immediately after surgery was 50.85 mm2

• Records

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Ophthalmology Volume 104 , Number 1, January 1997

Figure 1. Transnasal endoscopic photograph of one patient in the mitomycin C group (A) immediately after surgery, (B) 1 month after surgery , and (C) 3 months after surgery. D, the osteotomy site remained wide open 6 months after surgery.

showed that at 1 month, 3 months, and 6 months after surgery, it was 21.2 mm2

, 18.0 mm2, and 17.2 mm2

,

respectively. In the control group, the actual surface area of the osteotomy site without the mitomycin C soaking immediately after surgery and at 1 month, 3 months, and 6 months after surgery was 50.89 mm2

, 12.2 mm2, 8.72

mm2, and 5.52 mm2

, respectively. It appears that mitomy­cin C inhibits fibroproliferative activity and scar forma­tion in the same way, to maintain a final larger osteotomy area in long-term follow-up.

Discussion

Dacryocystorhinostomy has been accepted as a highly successful procedure in dealing with epiphora from naso­lacrimal duct obstruction. A review of the literature shows an average failure rate of 9.4%.1 -3 Failure generally is defined as the existence of symptoms of excessive tearing with the inability to irrigate. McPherson and Egelston 10

noted that three of the seven patients in their study who underwent a second operation were found to have dense scar tissue present at the osteotomy site. Pico ll stated that, "in every instance, the cause of failure was found at the secondary surgery to be an obstruction of the new drain­age channel by an occluding membrane, which on his to-

88

logic examination was shown to be composed of orga­nized granulation tissue." Allen and Berlin,4 in 1989, reported 20 failed DCRs with the preoperative obstruction distal to common canaliculus. In their study, there were 13 patients with cicatricial closure of the rhinotomy with granulation tissue and 3 with scan-ing of the osteotomy to the turbinate or septum. McLachlan et al,6 conversely, proposed the higher incidence of common canalicular ob­structions as a cause of DCR failures.

From the literature described above, we see that fibrous tissue growth, scan-ing, and granulation tissue formation during the healing process will decrease or compromise the created surface area of the osteotomy site, leading to surgical failure. The same healing process also will pro­mote adhesion of the osteotomy to the turbinate and sep­tum or induce obstruction of the common canaliculus. Lindberg and Anderson (presented at the American Soci­ety of Ophthalmic Plastic and Reconstructive Surgery An­nual Meeting, November 1980) showed that an appropri­ately large osteotomy made during surgery can narrow down to a final size of approximately 2 mm because of ti ssue growth and scarring.4 Thus, if we can reduce fibrous proliferation at the osteotomy site and at the anastomosed flaps, the success rate of DCRs will become much higher.

We know that mitomycin C, an anticancer agent iso­lated from Streptomyces caespitosus, has the ability to

Kao et al . Dacryocystorhinostomy with Intraoperative Mitomycin C

Figure 2. Transnasal endoscopic photograph of one patient in the control group (A) immediately after surgery, (B) 1 month after surgery, and (C) 3 months after surgery. D, the osteotomy size constricted to a smaller area after 6 months of follow-up.

significantly suppress fibrosis and vascular ingrowth after exposure to the filtration site of the trabeculectomy for glaucoma. 12

,13 The effect of the mitomycin C in glaucoma­filtering surgery has been discussed widely and proved to be effective in reducing intraocular pressure.9

,14 In DCR surgery, we used mitomycin C soaking over the oste­otomy site and the anastomosed flaps to suppress fibrous proliferation and scar formation. Theoretically, this modi­fication should reduce the fibrous adhesion between the osteotomy site and the nasal septum as well as inhibit scarring around the opening of the common canaliculus. Thus, mitomycin C should prevent further shrinkage of

the final surface area of the osteotomy and prevent the obstruction of the common canaliculus opening.

In our study, patients were assigned randomly to each group, with age between the two groups not being a sig­nificant factor. There were no selection bias and other confounders due to the age factor. The mean actual osteot­omy size immediately after surgery was 66.28 :±: 11.06 mm2 in the mitomycin C group as compared with 65.55 :±: 8.66 mm2 in the control group. Thus, there was no statistically significant difference between the two groups immediately after surgery. The initial osteotomy size of the DCR between the two groups was nearly the same.

Table 1. Surface Area of the Osteotomy Site

Mitomycin C Control p

lmmediate*

66.28 ± 11.06 65.55 ± 8.66

>0.05

DCR = dacryocystorhinostomy

1 Mo

29.26 ± 9.29 15.67 ± 4.26

<0.005

3 Mos

27.96 ± 10,45 12.22 ± 3.02

<0.005

* Surface area measured immediately after DCR surgery; surface area measured in mm'.

6 Mos

27.10 ± 5.78 10.83 ± 3.37

<0.005

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Ophthalmology Volume 104, Number 1, January 1997

Table 2. Percentage of Remaining Osteotomy Site

Mitomycin C Control p

Immediate* (%)

100 100

DCR = dacryocystorhinostomy

1 Mo (%)

44.9 ±: 8.17 15.67 ±: 4.26

<0.005

3 Mos (%)

42.18 ±: 9.18 18.64 ±: 4.7

<0.005

6 Mos (%)

40.89 ±: 7.67 16.52 ±: 5.17

<0.005

* Percentage of remaining osteotomy site immediately after DCR surgery.

The mean actual osteotomy size 1 month, 3 months, and 6 months after surgery in the mitomycin C group was 29.76 ± 9.29 mm2

, 27.96 ± lO.45 mm2, and 27.1 ± 5.78

mm2, respectively, as compared with 15.67 ± 4.26 mm2

,

12.22 ± 3.02 mm2, and lO.83 ± 3.37 mm2 in the control

group, respectively. We found that the initially created osteotomy area shrank most rapidly within the first month after DCR surgery (from 66.28 mm to 29.76 mm in the mitomycin C group, and 65.55 mm to 15.67 mm in the control group) due to active fibrous proliferation and scar formation in both groups (Table 1). The difference in the surface area of the osteotomy site between the two groups was statistically significant at the first month follow-up. It appears that the mitomycin C played an important role in reducing proliferative activity and preventing shrinkage of the osteotomy size (44.9% remaining osteotomy size in the mitomycin C group as compared with 23.9% in the control group at 1 month after surgery). In the mito­mycin C group, a minimal change in the osteotomy size was noted after a longer follow-up period (from 29.26 mm at 1 month to 27.lO mm 6 months after surgery), and the osteotomy size seemed to remain stable at the end of the sixth postoperative month. Conversely, the osteotomy size changed more in the control group (from 15.67 mm to lO.83 mm 6 months after surgery). Thus, there was a statistically significant difference in the oste­otomy size between the two groups in each follow-up period (P all < 0.005). One patient with bilateral nasolac­rimal duct obstruction was operated on simultaneously, and one eye underwent mitomycin C soaking and the other eye did not. The initial actual surface area of the osteotomy site was about the same size in each eye. After 6 months of follow-up, the remaining area of the osteot­omy size in the mitomycin C-soaked eye was three times that of the osteotomy size in the control eye. From among all patients, septo-osteotomy adhesion was found in two patients in the control group, but no such adhesion was noted in the mitomycin C group. Therefore, it appears that adhesion between the osteotomy and septum or turbinate could be minimized by a mitomycin C application. From the data described above, the application of the mitomycin C over the osteotomy site should maintain the final sur­face area of osteotomy site to a larger extent and, hence, improve the success rate of DCR surgery.

Many complications due to a mitomycin C application have been reported in both pterygium and glaucoma fil­tration operations. Severe secondary glaucoma, corneal perforation, corectopia, secondary cataract, and scleral

90

calcification are several complications noted in using topi­cal mitomycin C as a medical adjunct to pterygium sur­gery.IS Hypotony-related maculopathy, infection, and en­dophthalmitis have been found in patients undergoing glaucoma filtration surgery after exposure to mitomycin c.9 Fortunately, in our study, there were no complications such as delayed wound healing, abnormal nasal bleeding, mucosal necrosis, or infection noted with mitomycin C soaking. However, a longer follow-up period must be undertaken before a definite conclusion can be made.

In summary, although a high success rate of external DCR surgery has been reported, there still are 10% of patients who do not respond. In our experience, DCR with intraoperative mitomycin C soaking over the osteot­omy and anastomosed flaps can maintain a larger final osteotomy area as well as minimize the adhesion around the opening of the common canaliculus. We propose that using mitomycin C soaking is a useful modified procedure that may possibly increase the success rate of external DCR Recently, new reports have shown that endonasal laser-assisted DCR can be an alternative to conventional external DCR 16

-18 It has been reported that the success

rate of this new technique is approximately 70% in the primary operation. 17

•18 Thus, it is a topic of interest

whether applying mitomycin C over a laser-created oste­otomy site can increase the success rate of laser-assisted DCR More studies must be done on this topic before we can make any further conclusions.

References

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2. Walland MJ, Rose GE. Factors affecting the success rate of open lacrimal surgery. Br J Ophthalmol 1994;78:888-91.

3. Becker BB. Dacryocystorhinostomy without flaps. Ophthal­mic Surg 1988; 19:419-27.

4. Allen K, Berlin AJ. Dacryocystorhinostomy failure: associ­ation with nasolacrimal silicone intubation. Ophthalmic Surg 1989;20:486-9.

5. Rosen N, Sharir M, Moverman DC, Rosner M. Dacryocyst­orhinostomy with silicone tubes: evaluation of 253 cases. Ophthalmic Surg 1989;20:115-9.

6. McLachlan DL, Shannon GM, Flanagan JC. Results of da­cryocystorhinostomy: analysis of the reoperations. Ophthal­mic Surg 1980; 11:427-30.

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7. Singh G, Wilson MR, Foster CS. Mitomycin eye drops as treatment for pterygium. Ophthalmology 1988;95:813-21.

8. Cano-Parra J, Diaz-Llopis M, Maldonado MJ, et al. Pro­spective trial of intraoperative mitomycin C in the treatment of primary pterygium. Br J Ophthalmol 1995;79:439-41.

9. Megevand GS, Salmon JF, Scholtz RP, Murray AD. The effect of reducing the exposure time of mitomycin C in glaucoma filtering surgery. Ophthalmology 1995; 102:84-90.

10. McPherson SD, Egelston D. Dacryocystorhinostomy: a re­view of 106 operations. Am J Ophthalmol 1959;47:328-31.

11. Pico G. A modified technique of external dacryocystorhi­nostomy. Am J Ophthalmol 1971;72:679-90.

12. Lee DA, Lee TC, Cortes AE, Kitada S. Effects of mithra­mycin, mitomycin, daunorubicin, and bleomycin on human subconjunctival fibroblast attachment and proliferation. In­vest Ophthalmol Vis Sci 1990; 31 :2136-44.

13. Bergstrom TJ, Wilkinson WS, Skuta GL, et al. The effects of subconjunctival mitomycin C on glaucoma filtration sur­gery in rabbits. Arch OphthalmoI1991;109:1725-30.

14. Kupin TH, Juzych MS, Shin DH, et al. Adjunctive mitomy­cin C in primary trabeculectomy in phakic eyes. Am J Ophthalmol 1995; 119:30-9.

15. Rubinfield RS, Pfister RR, Stein RM, et al. Serious compli­cations of topical mitomycin C after pterygium surgery. Ophthalmology 1992;99:1647-54.

16. Massaro BM, Gonnering RS, Harris GJ. Endonasal laser dacryocystorhinostomy: a new approach to nasolacrimal duct obstruction. Arch Ophthalmol 1990; 108: 1172-6.

17. Boush GA, Lemke BN, Dortzbach RK. Results of endona­sal laser-assisted dacryocystorhinostomy. Ophthalmology 1994; 101:955-9.

18. Kong YT, Kim TI, Kong BW. A report of 131 cases of endoscopic laser lacrimal surgery. Ophthalmology 1994; 101: 1793-800.

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