Evaluation of lacrimal duct probing in adults with 0.02% and 0.04% mitomycin-C in primary acquired nasolacrimal duct obstruction: A randomized comparative pilot study.

PURPOSE: The purpose of the study is to evaluate the safety and efficacy of adjunctive use of mitomycin-C (MMC) using two different concentrations 0.2 mg/ml and 0.4 mg/ml for lacrimal duct probing to treat the nasolacrimal duct obstruction (NLDO) in adults. SUBJECTS AND METHODS: Prospective, an interventional comparative randomized pilot study of lacrimal duct probing conducted in the two study groups 0.02% MMC group (n = 30) and 0.04% MMC group (n = 30) in confirmed primary acquired NLDO of <1-year duration. Patency of lacrimal duct probing confirmed by syringing was compared at 1, 3, and 6-month follow-up in the two study groups, and corresponding subjective improvement of watering was appraised according to Kraft and Crawford grading.
RESULTS: Patency of lacrimal duct probing in 0.02% MMC versus 0.04% MMC group was 66.66%/73.33% (P = 0.71) at 1 month, 46.66%/66.66% (P = 0.09) at 3 months and 46.66%/66.66% (P = 0.03) at 6-month follow-up, respectively. Subjective improvement of watering (no watering and mild watering) observed in 0.02% MMC versus 0.04% MMC group was 46.66%/73.33% (P = 0.03), at 1 month, 66.66%/83.33% (P = 0.13) at 3 months and 56.66%/73.33% (P = 0.17) at 6-month follow-up.
CONCLUSION: Adult lacrimal duct probing with 0.04% MMC was associated with significant higher objective success rate than adult lacrimal duct probing with 0.02% MMC, without added concurrently side effects. Copyright:

Introduction

Primary acquired nasolacrimal duct obstruction (NLDO) is a syndrome of unknown origin and is the major contributing factor for epiphora in adults. Inflammation of unknown etiology resulting in fibrosis of the nasolacrimal duct.[1] Success rate for adult dacryocystorhinostomy (DCR) surgery for NLDO documented is high, reported being approximately 90%.[2] However, probing nasolacrimal duct with mitomycin-C (MMC) offers an easy and safe alternative treatment substitute for elderly patients who are poor surgical candidates or who do not wish to undergo DCR surgery.[3] In the literature, only a few studies had evaluated the outcome of adult lacrimal duct probing enumerated subjective success between 40% and 52%,[45] and approximately 30% documented objective success, as complete patency.[6] The key to the success of probing lies in maintaining the patency of the lacrimal pathway, hence the application of anti-metabolite MMC, which inhibits fibrous tissue growth and scarring is prudent. However, there is a paucity of literature[347] that had investigated the utility of MMC for lacrimal duct probing to treat NLDO in adult patients.

The minimum effective MMC concentration reported in pterygium, filtering, and lacrimal duct surgeries varies from 0.2 mg/ml to 0.5 mg/ml.[8] You and Fang[9] studied the two different MMC concentrations 0.2 mg/ml and 0.5 mg/ml to discern the intraoperative effectiveness in external DCR surgery, however, no significant difference was observed in maintaining the lacrimal duct patent and osteotomy size. On the contrary, Ali et al.[10] recognized 0.2 mg/ml MMC as the minimum effective concentration to prevent fibroblast cell proliferation of the harvested nasal mucosa during DCR surgery. Nemet et al.[11] reported 80% efficacy with 0.03% mitomycin C in distal and common canalicular obstruction at 15.4-month follow-up.

Therefore, the authors do not have a collective opinion regarding the analogous concentration of MMC used in lacrimal surgery. Hence, the dearth of decisive MMC concentration, serving as a landmark, this study was intended to find out effective MMC concentration that adheres to sustained patency of the ostium, without concurrent side effects.

Subjects and Methods

A prospective comparative interventional randomized study comprising sixty eyes from sixty patients attending the oculoplastic clinic and general ophthalmology outdoor facility (during the period of September 2017 to March 2019) were enrolled. The patients were randomly divided using computer-generated sequence into two groups-30 eyes in each group. The study was conducted according to the tenets of the Declaration of Helsinki. Patients with proven diagnosis of primary acquired NLDO of <1-year duration, age more than 18 years, and willing to follow-up were included. Patients with lid malposition, acute dacryocystitis, associated with external fistula, canalicular obstruction, past history of probing/trauma/surgery, punctum agenesis, trichiasis/distichiasis, or ocular surface disease were excluded. Written informed consent was obtained from all the patients before enrolment and the institutional ethics committee (All India Institute of Medical Sciences, New Delhi) approval was sought and obtained.

Demographic characteristics including age, gender, duration of epiphora, associated discharge, redness/itching/pain in eyes, medial canthal swelling, previous trauma, surgeries, prior syringing and probing, and sinus disease/allergies, radiation exposure to the periocular or paranasal sinus area and study parameters data were recorded on a predesigned pro forma. The ocular examination included best-corrected visual acuity, anterior and posterior segment examination.

Lacrimal system examination comprised tear film height measurement, pressure regurgitation over the lacrimal sac, diagnostic syringing and probing, performed twice on two separate occasions to ensure NLDO in the study groups. Tear film height was measured using the illuminated slit width, by changing its horizontal orientation into vertical and altering its dimension until it appeared to match the tear film height on slit-lamp bio-microscopy. A value in millimeters was obtained by the calibration of the rotating knob controlling the slit width, provided with graduation scale.

Preoperative investigations of complete hemogram, bleeding time, clotting time, fasting blood glucose, and otolaryngologic evaluation were obtained to exclude the nasal abnormalities.

One surgeon (MS) performed all the procedures on an outpatient basis, under topical anesthesia using proparacaine hydrochloride 0.5% eye drops. The lower and upper puncta were gently dilated. A snuggly fitted Bowman's probe (size-0–000) was introduced through the upper punctum till reached the nasal bone of the lacrimal sac, subsequently, the probe was directed downward at 90 degree and posterior-laterally. Gentle pressure was applied to open the NLDO. Normal saline was used for irrigation to confirm the patency, followed by irrigation of 1 ml MMC (0.2 mg/ml in one study group and 0.4 mg/ml in another study group) through 27G cannula attached to tuberculin syringe into the lacrimal duct with 2% lignocaine hydrochloride gel soaked nasal pack. Then, the ocular surface was flushed with 10 ml physiological saline and the patient was instructed not to swallow the MMC solution. The nasal pack was left for 15 min to minimize its systemic absorption and soak up excess of the irrigating solution. At the completion of the procedure, water was offered to the patient for gargling, to clear up any residual MMC solution.

Postoperative, topical steroid drops in the tapering dose and antibiotic ointment were prescribed for 6 weeks with nasal decongestant and isotonic saline nasal drops for a period of 2 weeks.

Repeated probing was attempted in the recurrent cases, who experienced a return of watering symptoms and nonpatency of the lacrimal duct on syringing after apparent improvement with the same initial MMC concentration during a follow-up visit. Lacrimal surgery was considered when a second probing with adjunctive MMC failed or in whom the first attempt of probing did not achieve patency or when probing was contraindicated. All data were recorded by a blinded evaluator and patients were followed up at 1 week, 4 weeks, 3 months, and 6 months. At each follow-up, the patients were questioned about subjective improvement in symptoms and slit-lamp examination of the punctum, caruncle, tear film height, and any side effects development. Patency of lacrimal duct was confirmed by syringing. Nasal examination was also conducted to look for the development of any mucosal edema or other possible side effects.

Amount of watering was classified according to the Kraft and Crawford subjective grading[12] :0-no watering, 1+ watering only at outdoors (mild), 2+ for watering at indoors (moderate) and 3+ ensure constant epiphora. Patient's satisfaction was graded as fully satisfied, partially satisfied, or not satisfied.

Success was defined as being asymptomatic or improvement in tearing and patency of lacrimal drainage.[13] In this study, the success rate was measured objectively by syringing, confirm the patency of lacrimal duct, and subjective success was assessed using Kraft and Crawford grading.

Statistical analysis

Qualitative variables (expressed in percentage) were compared between 0.04% MMC group and 0.02% MMC group using Chi-square tests, independent samples test with P < 0.05 considered statistically significant. SPSS version 21 program (SPSS Inc., Chicago, IL, US) was used for statistical analysis.

Results

A total of 30 eyes of mean age 47.61 ± 16.16 in 0.04% MMC group and 30 eyes of mean age 41.2 ± 13.58 in 0.02% MMC group were enrolled in the study. It is interesting to acknowledge that the NLDO affects frequently female than male but in this study, the participants were more male shown in Table 1.

Table 1

Demographic characteristics of the study groups

Demographic details	0.04% MMC group	0.02% MMC group	P
Number of eyes	30	30	_
Gender: Male/female	22/8	18/12	0.273
Age (years), mean±SD (range)	47.61±16.16 (19-72)	41.2±13.58 (19-65)	0.099

MMC: Mitomycin C, SD: Standard deviation

Tear film height in the two groups at their respective follow-up visits is shown in Table 2. A statistically significant difference was observed between the two different concentrations at their respective follow-up (P < 0.05). Lacrimal patency rate over the duration of follow-up in the two study groups is summarized in Table 3, with 20 eyes (66.66%) in 0.04% MMC group and 14 eyes (46.66%) in 0.02% MMC group remained patent on syringing at 6-month follow-up. Six eyes in the 0.02% MMC group and two eyes in the 0.04% MMC group had undergone a repeat probing procedure using the same MMC concentration. However, the repeat procedure did not yield objective and subjective improvement at 6-month follow-up. On comparing the objective success in the two study groups, a statistically significant improvement (P = 0.03) of lacrimal duct patency treated with 0.04% MMC than 0.02% MMC at 6-month follow-up period was noted.

Table 2

Comparison of tear film height (mean±standard deviation) in the study groups at their respective follow-up visits

Study parameters	Mean±SD		P
	0.04% MMC group	0.02% MMC group
1 month
Tear film height	1.16±0.52	1.60±0.72	0.003
3 months
Tear film height	1.06±0.25	1.53±0.62	0.001
6 months
Tear film height	1.06±0.71	1.39±0.50	0.030

MMC: Mitomycin C, SD: Standard deviation

Table 3

Success of adult lacrimal duct probing treated with two different concentration of mitomycin-C in the study groups at their respective follow-up visits

Study group	1 month (%)	3 months (%)	6 months (%)
Objective success
0.04% MMC group	22 (73.33)	20 (66.66)	20 (66.66)
0.02% MMC group	20 (66.66)	14 (46.66)	14 (46.66)
P	0.71	0.09	0.03
Subjective success
0.04% MMC group	22 (73.33)	25 (83.33)	22 (73.33)
0.02% MMC group	14 (46.66)	20 (66.66)	17 (56.66)
P	0.03	0.13	0.17

MMC: Mitomycin C

Table 4 summarizes the subjective improvement of watering among the 0.02% MMC group and 0.04% MMC group at their respective follow-up visits. No significant difference in subjective improvement was observed in the study groups at 6-month follow-up.

Table 4

Subjective improvement of watering in 0.04% mitomycin-C group and 0.02% mitomycin-C group at follow-up visits

Grading of watering	1 month (%)	3 months (%)	6 months (%)
0.04% MMC group
No watering	7 (23.33)	7 (23.33)	13 (43.33)
Mild watering	15 (50)	18 (60)	9 (30)
Moderate watering	5 (16.66)	3 (10)	6 (20)
Constant watering	3 (10)	2 (6.66)	2 (6.66)
0.02% MMC group
No watering	4 (13.335)	6 (20)	6 (20)
Mild watering	10 (33.33)	14 (46.66)	11 (36.66)
Moderate watering	14 (46.66)	4 (13.33)	4 (13.33)
Constant watering	2 (6.66)	6 (20)	9 (30)

MMC: Mitomycin C

No watering and mild watering grades were considered as fully satisfied, moderate watering as partially satisfied, and constant epiphora as not satisfied. Subjective success included fully satisfied patients in this study.

None of the patients developed significant side effects with concurrent use of MMC even with higher concentration, except for mild conjunctival redness that got resolved with topical antibiotics and steroid eye drops.

Discussion

MMC is the most common drug used in the lacrimal surgery to prevent the cicatrix formation. There are studies in the literature, which advocate the favorable outcome of DCR surgery with a higher concentration of MMC.[14] On the other end of the spectrum, there is published evidence suggesting equivocal response.[910] As lacrimal duct probing is a blind procedure, involves the creation of a small ostium than discernible large ostium pursued in the DCR surgery, therefore, it has more the propensity of closure, inspire us to study the efficacy and safety of using higher MMC concentration to achieve long-term success.

Our study documented the objective success rate of 46.66% in 0.02% MMC group and 66.66% in 0.04% MMC-treated group at 6 months, suggesting statistically significant patency (P = 0.03) in 0.04% MMC-treated group than 0.02% MMC group. Earlier studies on adult lacrimal duct probing had used 0.02% MMC concentration. Tsai et al.[3] reported a patency rate of 89% in a noncomparative study at a 9-month follow-up with 0.02% MMC concentration. Similarly, the patency rate of 30% at 3-month follow-up in adult lacrimal probing with 0.02% MMC was documented by Sinha et al.[4] The difference could be attributed to the inherent practical difficulty in creating a large ostium by the bowman probe and variable force strength applied during the procedure. At the same time, head to head the comparison was not possible because of the difference in follow-up duration and variability in time of MMC exposure. The repeated attempt of lacrimal duct probing in recurrent NLDO failed to achieve patency, reflecting added trauma[4] and accentuating inflammation to pre-existing lacrimal duct obstruction was the most likely explanation for incomplete ostium patency.

There is no study in the literature to ascertain superiority of one MMC concentration over the other or commensurate in the adult lacrimal duct probing. An in vitro study by Jampel[15] observed that the fibroblast inhibition was mainly dependent on the concentration rather than the duration of MMC exposure, concordant with greater success the rate in the 0.04% MMC group than 0.02% MMC in the long term.

Subjective success corresponding to complete satisfaction was observed in 73.33% of patients in the 0.04% MMC group as compared to 56.66% patients in 0.02% MMC group at 6 months, however not significant (P = 0.17). At 1 month, statistically significant improvement was observed on comparing the two groups, followed by upsurge improvement in both the groups at 3 months, later decline was noted at the 6-month visit, a distinct trajectory observed. Slight inflammation persistence for around 1 month, following a small spillage of irrigating MMC over the ocular surface during the procedure and their subsequent resolution was the most likely possibility of this improvement in both the groups at 3 months.

As subjective improvement was pertinent to the individual perception of symptoms, amenity, existence of confounding environmental factors, temperature, humidity, might explain for no statistically significant difference in the two groups and notably the existence of the incongruity between objective success and subjective success.

This study perceived that 0.04% MMC concentration in adult lacrimal duct probing is associated with a higher objective success rate without added side effects.

Conclusion

Our study replicates the results of adult lacrimal duct probing and reinforces the implementation of the cost-effective, timesaving procedure using 0.04% MMC in adult NLDO, particularly in debilitated elderly patients.

The limitation of the study was short duration follow-up. To conclusively establish the higher MMC concentration associated greater success rate, a relatively long-duration study would be desired.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.