DOI: https://doi.org/10.21203/rs.3.rs-1182481/v1
We compared the difference in postoperative patency rates due to the differences in the diameter of silicone tubes used for bicanalicular intubation for the treatment of nasolacrimal duct obstruction (NLDO).
Patients diagnosed with NLDO at Ehime University Hospital between August 2013 and November 2020 who underwent endoscopic-assisted nasolacrimal duct intubation (ENDI) were included in the study. The patients involved were 130 cases and 157 sides (age 72.6 ± 11.3 years) who were eligible for follow-up for more than six months after the removal of the lacrimal silicone tube. The postoperative recurrence rate was compared retrospectively based on the difference in tube caliber. The patients were divided into two groups: those intubated with a 1.5-mm large diameter tube (Group LD) and those with a 1.0-mm normal diameter tube (Group ND). The survival rates of the two groups at one year after tube removal were compared by Kaplan-Meier's curve and Restricted mean survival time (RMST) method with τ = 365 days.
There were no significant differences in age, gender, or observation period after tube removal between the two groups. Meanwhile, the preoperative occlusion period was significantly longer in the ND group. The recurrence rate after tube removal was significantly lower in the LD group (12 / 85 sides, 14.1%) compared to the ND group (27 / 72 sides, 37.5%) (p = 0.001). The patency rate at one year after removal of the lacrimal tube was 0.857 (0.754-0.919) in the LD group and 0.739 (0.617-0.828) in the ND group. In comparing patency rates by the RMST method at τ = 365 days, the RMST difference, RMST ratio, and RMTL ratio were significantly higher in the LD group at p = 0.045, 0.052, and 0.046, respectively.
Regarding the bicanalicular silicone tube intubation, the patency rate at one year after removal was significantly higher in the thicker tubes with a diameter of 1.5 mm compared with that of a diameter of 1.0 mm for the treatment of NLDO.
Primary acquired nasolacrimal duct obstruction (PANDO) is an organic obstruction of the lacrimal tract that can occur anywhere from the punctum to the nasolacrimal duct opening.1 Cases with obstruction from the punctum to the internal common punctum are classified as pre-saccal obstruction, while cases with obstruction from the lacrimal sac to the nasolacrimal duct opening are classified as post-saccal obstruction. Although the pathophysiology of PANDO is still unclear, it is suggested that descending inflammation from the eye or ascending inflammation from the nose triggers mucosal membrane swelling, connective tissue remodeling, and dysfunction of the subepithelial cavernous body with reactive hyperemia, resulting in temporary lacrimal duct obstruction.2 Furthermore, chronic recurrent inflammation in the lacrimal duct leads to structural alterations in the epithelium and subepithelial tissue, resulting in fibrous organic obstruction of the lumen.
The first line treatment for post-saccal obstruction in adults is a bypass surgery, dacryocystorhinostomy (DCR). With the development of the dacryoendoscope and the advancement of the fiber-optic system, the recanalization procedure is steadily spreading. Lacrimal recanalization surgery includes endoscopic-guided trephination dacryocystorhinostomy, dacryorhinotomy, microdrill dacryoplasty, laser dacryoplasty, anterograde balloon dacryoplasty.3− 10 For the partial obstruction or stenosis of the lacrimal duct, silicone intubation or anterograde balloon dacryoplasty with silicone tube intubation is commonly indicated.11− 13 In Northeast Asia, silicone intubation has been proposed as an alternative to DCR in the treatment of post-saccal obstruction. This is primarily due to improving postoperative outcomes with refined silicone tubes 14, and expansive application of endoscopic-assisted nasolacrimal duct intubation (ENDI) as a minimally invasive treatment for PANDO in Northeast Asia. 15− 18 The ENDI procedure is conducted while directly observing the obstructed area in the lacrimal duct with a dacryoendoscope and observing the nasal cavity with a nasal endoscope. This procedure reduces complications from false passage formation compared to conventional blind direct silicone intubation (DSI). ENDI can ordinarily be performed under local anesthesia, and it has evolved into a less invasive and securer procedure, which makes increasingly widespread use in Northeast Asia. Furthermore, Northeast Asians have relatively flat facial features, with a less elevated superior orbital rim than other ethnical populations. This allows for relatively easy manipulation of a dacryoendoscope.19 Since the first report of nasolacrimal duct intubation using silicon tubes by Gibbs et al. and Keith et al. in the 1960s 20,21, various improvements have been made in surgical techniques, instruments for stent placement, tube materials, and designs. 4,22 The silicone tubes inserted into the lacrimal duct prevents adhesion of the mucosal surface of the duct while the mucosal membrane heals, promotes regeneration of the lacrimal duct epithelium, and helps maintain long-term patency after the tube removal. Typical silicon tubes include the Ritleng® lacrimal intubation set (FCI Ophthalmics, Pembroke, MA) and the Crawford tube, which have been used in many institutions worldwide for many years. Nevertheless, these techniques use a thin metal probe for insertion and carry the risk of iatrogenic trauma to the canaliculi and nasolacrimal ducts.22 The Nunchaku-style tube (NST) is a 'push-style' stent designed with a metal guide probe concealed inside the tube without being exposed to the surface.23 In addition, the nunchaku-style tube has the advantage of improved surgical efficacy since it does not require retrieval of the stent or tying the distal end of the tubes within the nose during the placement.23,24 The diameter of a typical NST is 1.0mm, which is thicker than that of a typical Crawford tube, namely 0.64mm. It has been reported that the larger the diameter of the tube, the wider the isolation between the walls of the lumen. 25,26 Recently, a thicker 1.5-mm diameter NST has been introduced and is currently available for clinical use. Accordingly, this study aimed to compare the patency rates of ENDI treatment for post-saccal obstruction in adults with 1.0 mm and 1.5 mm NSTs at 1 year after the removal of the tubes.
An overview of both groups is shown in Table 1. The composition of the LD group was as follows. Of the total 70 cases and 85 sides with post-saccal obstruction, males were 23 cases and 29 sides (32.8% and 34.1%, respectively), and females were 47 cases and 56 sides (67.1% and 65.9%, respectively). The mean age of the cases was 72.5 ± 11.1 years. The mean period of preoperative obstruction was 29.6 ± 40.0 months. The mean observation period after tube removal was 9.8 ± 5.9 months. 12 cases (14.0%) in the LD group had recurrence after ENDI treatment, and the average time from tube removal to recurrence was 3.4 ± 4.6 months. On the other hand, the detail of the ND group was as follows. Of the total 60 cases and 72 sides with post-saccal obstruction, males were 17 cases and 21 sides (28.3% and 29.2%, respectively), and females were 43 cases and 51 sides (71.7% and 70.8%, respectively). The mean age of the cases was 72.9 ± 11.5 years. The mean period of preoperative obstruction was 63.0 ± 91.8 months. The mean observation period after tube removal was 14.0 ± 14.7 months. 27 cases (37.5%) in the ND group carried recurrence after ENDI, and the average time from tube removal to recurrence was 11.0 ± 16.0 months.
No statistically significant differences were found in the age, gender ratio, and observation period after tube removal between LD and ND groups (p > 0.05). Meanwhile, the period of preoperative obstruction was significantly longer in the ND group (p < 0.05, Figure 1). In addition, the number of recurrences after ENDI was significantly lower in the LD group than in the ND group (p = 0.001). The time to recurrence after tube removal was 3.4 ± 4.6 months in the LD group and 11.0 ± 16.0 months in the ND group, with no significant difference between the two groups (p = 0.82). Since the preoperative obstruction period was significantly longer in the ND group than in the LD group, we conducted a logistic regression analysis with ‘period of preoperative obstruction’ and ‘Group’ as explanatory variables and ‘recurrence’ as the objective variable to examine whether the longer duration of preoperative obstruction contributed to recurrence after ENDI surgery. The results showed that OR for ‘period of preoperative obstruction’ was 0.999 (0.994 - 1.000, p = 0.699) and OR for ‘Group’ was 3.770 (1.71 - 8.34, p = 0.001). Hence, the ‘period of preoperative obstruction’ was not significantly correlated with ‘recurrence.’
The Kaplan-Meier's curve of lacrimal duct patency at one year after tube removal is shown in Figure 2. One year after tube removal, the patency rate of the lacrimal duct was 0.857 (0.754 - 0.919) in the LD group and 0.739 (0.617 - 0.828) in the ND group. There were 11 recurrences and 23 censored cases in the LD group; meanwhile, in the ND group, there were 18 recurrences and 14 censorings within one year after tube removal. The RMST with τ = 365 days was 326.65 and 284.59 in LD and ND groups, respectively. RMST (LD) - (ND) = 42.058 (0.996 - 83.121, p = 0.045), RMST (LD) / (ND) = 1.148 (0.999 - 1.319, p = 0.052), and RMTL (LD) / (ND) = 0.477 (0.230 - 0.988, p = 0.046). The survival rate of the LD group was significantly higher than that of the ND group at one year after tube removal (Figure 3).
There are not many studies that examined the effect of tube diameter differences on the prognosis of PANDO treatment. Several reports introduced attempts to prevent restenosis after tube removal by enlarging the lacrimal duct after surgery. One method is to insert two 0.64mm Crawford tubes into the canaliculus. 10,27,28 These studies reported a higher patency rate after canaliculoplasty for pre-saccal obstruction. Another study showed that double silicone intubation of a 0.64mm Crawford tube and a 0.94mm single wide-diameter Crawford tube were equally effective.25 Our study demonstrated that one year after NST intubation for post-saccal obstruction, the patency rate was 0.857 (0.754 - 0.919) when a 1.5 mm thick tube was utilized and 0.739 (0.617 - 0.828) when a standard 1.0 mm diameter tube was applied. Furthermore, comparison of survival rates between the two groups by the RMST method showed that the patency rate of the LD group was significantly higher, suggesting that the larger diameter tubes had better outcomes in post-saccal obstruction.
1.5 mm diameter NST was developed and applied clinically in recent years. As a result, the period for determining the effectiveness became shorter than that of the conventionally used 1.0 mm NST. Therefore, the RMST method was applied to compare the treatment efficacy between the two groups because the proportional hazard property was not established in the late stage of the Kaplan-Meier curve. The τ of RMST was determined as 365days, considering the following conditions. 1) Clinically, recurrence was mostly observed within one year after tube removal. 2) In our institution, follow-up was usually completed without recurrence for one year after tube removal. 3) The ratio of censoring in Kaplan-Meier's curve increases after one year of removal due to reasons such as completion of follow-up or transfer to other facilities.
Additionally, compared to the preconditions between the two groups, the preoperative obstruction period was significantly longer in the ND group. Previous studies identified that the preoperative occlusion period conferred as a risk for recurrence after silicone intubation.29 Therefore, we performed a logistic regression analysis of the involvement of the preoperative obstruction period in recurrence between the two groups; however, we found no significant correlation in our cohort (p = 0.69).
In general, the long-term therapeutic outcomes of ENDI are not equivalent to DCR. Nevertheless, evidence has accumulated that the outcomes of ENDI are almost as effectual as DCR for canaliculus obstruction and PANDO (in cases of non-inflammatory or partial obstruction). 15,17,18,29−31 However, it has been reported that patients with prolonged preoperative occlusions, extended length obstruction, or a history of dacryocystitis tend to relapse after ENDI treatment. 17,22,29,31,32 Since ENDI is a minimally invasive procedure for the treatment of PANDO, which can be performed under local anesthesia, and there are various advantages in terms of surgical time, facial surgical scars, bleeding, and downtime compared to DCR. 3,4,11,17,18,22,23,31,33 ENDI can also be performed in patients receiving systemic anticoagulation and antiplatelet therapy because the risk of bleeding is minimal. Hence, further studies are needed to compare the long-term treatment outcomes of DCR and ENDI in PANDO, in terms of pathological conditions (e.g., site of obstruction, cause of obstruction, and duration of obstruction).
This study involves several limitations. First, this study was a single facility retrospective cohort study; thus, long-term follow-up was limited. It is necessary to evaluate the prolonged outcomes with a larger number of postoperative patients in a multi-center study. Second, since 1.5 mm NST was recently applied clinically, the period to evaluate its efficacy was relatively shorter than that of the conventional 1.0 mm NST. The long-term outcome of the 1.5 mm NST requires extended follow-up time to be determined.
In conclusion, this is the first report to compare the postoperative patency rate of silicone tube intubation for post-saccal obstruction according to the difference in tube caliber. We propose that the use of larger diameter tubes could provide improved therapeutic outcomes.
We reviewed 130 patients on 157 sides diagnosed with post-saccal obstruction and treated by three ophthalmologists (TK, AM, AS) at Ehime University Hospital between August 2013 and November 2020. The mean age of the patients was 72.6 ± 11.3 years. The male population was 40 cases (50 sides), and the female population was 90 cases (107 sides). The diagnosis of post-saccal obstruction was made based on dye disappearance tests, lacrimal irrigation test, cone beam computed tomography digital subtraction dacryocystography, and dacryoendoscopic examinations. Patients with functional nasolacrimal duct obstruction were excluded. Patients with a previous history of systemic chemotherapy, radiation therapy, or post-traumatic bone deformity were also excluded. In addition, patients with unsuccessful surgery, such as cases in which the stent could not be placed because the occlusion was too solid, or cases in which a false passage was created, were excluded from the present evaluation. Patients with a previous history of lacrimal duct reconstruction, such as postoperative recurrence, were also excluded, and all patients were treated for the first time.
All patients were treated with ENDI as previously described. 16,17 In this procedure, the surgeons performed lacrimal duct reconstruction while observing the lacrimal canal under the dacryoendoscope instead of performing the procedure blindly. Briefly, the procedure was as follows: after performing infratrochlear anesthesia and topical nasolacrimal anesthesia, the upper and lower lacrimal punctum were dilated. Dacryoendoscope (FT-201, Fibertech, Tokyo, Japan) was inserted through the punctum, and the endoscope was then advanced to the occlusion site while monitoring the lumen. An 18-gage catheter (SR-FF1864, Terumo, Tokyo, Japan) attached to the tip of the endoscope was used to release the obstruction (sheath-guided endoscopic probing technique 34 ). Self-retaining bicanalicular lacrimal stents were inserted using the sheath as a guide after the obstructed area of the lacrimal canal was released. The sheath with the tube connected was removed from the open end of the nasolacrimal duct on the inferior meatus using a nasal endoscope. The same procedure was performed from the other punctum, and the tube was retained in the lacrimal duct. The NST stent was either a large diameter 1.5 mm (Lacrifast EX®; Kaneka Co., Ltd., Osaka, Japan) or a conventional diameter 1.0 mm (Lacrifast® or Lacrifast CL®; Kaneka Co., Ltd., Osaka, Japan), Japan) were used. The only difference between the 1.0mm diameter Lacrifast® and Lacrifast CL® is whether the tube stent has an open end or a blind end, and the rest of the structure, including the tube diameter, total length, and material, is identical. After the ENDI surgery, all patients were treated with topical 0.1% fluorometholone and 0.3% gatifloxiacin four times a day. Irrigation with saline to flush the tear ducts was performed periodically until the stent was removed. The silicone tube was routinely removed 10 to 12 weeks after ENDI surgery.
Patients who were followed up for at least six months after NST removal were evaluated. The present study was conducted to evaluate the patency rate of pos-saccal obstruction after ENDI treatment; hence the cases of pre-saccal obstruction were excluded. Recurrence was defined as no passage or pus or viscous fluid reflux in the postoperative irrigation test, and structural re-occlusion in the dacryoendoscope findings.
The group intubated with a large diameter tube (1.5 mm) was designated as the LD group, and the group intubated with a normal diameter tube (1.0 mm) was designated as the ND group. To avoid selection bias, the LD group consisted of patients treated after the deployment of the 1.5-mm NST at our institution (treated between August 2017 and November 2020), and the ND group consisted of patients treated with the 1.0-mm NST before the deployment of the 1.5-mm NST (treated between August 2013 and July 2017). Gender, age, period of obstruction, observation period after removal, number of recurrences, and time from tube removal to recurrence for each group are evaluated. The period of obstruction was denoted based on the duration of chronic epiphora symptoms as described in the patient questionnaire. Furthermore, by defining 'recurrence' as an event, Kaplan-Meier's curve was created. Based on the rationale listed below, restricted mean survival time (RMST) was compared between the two groups with τ = 365 days. 1) Clinically, recurrence is usually observed within one year after removal. 2) In our institution, follow-up is usually completed when no recurrence is observed for one year after removal; therefore, the censoring rate increases beyond one year after removal.
All statistical analyses were performed with EZR (Saitama Medical Center, Jichi Medical University, Saitama, Japan), a graphical user interface for R (The R Foundation for Statistical Computing, Vienna, Austria).35 In comparing the two groups, the ratio of male to female and the number of recurrent cases were tested by Pearson's χ2 test. Meanwhile, age, period of obstruction, and observation period after tube removal were tested by Mann-Whitney's U test. The creation of Kaplan-Meier's curve and comparing survival rates between the two groups using the RMST method were analyzed with the survRM2 package.36,37 A p-value < 0.05 was considered statistically significant.
This investigation and data collection protocol were authorized by the institutional review board of Ehime University (Ethical approval number: 1601003). The research was recorded with the University Hospital Medical Information Network Clinical Trials Registry (UMIN 000025180). Documented informed consent was received from each patient before registration. All procedures employed in this study were conducted following the principles of the Declaration of Helsinki.
Endoscopic-assisted nasolacrimal duct intubation
Primary acquired nasolacrimal duct obstruction
Nunchaku-style tube
Acknowledgements
This study was supported by the Japan Society for the Promotion of Science (JSPS) Postdoctoral Fellowship for Research Abroad (Kaitoku-NIH, #24112 to JN). The funding source had no role in the study design, data collection, analysis, publication decision, or manuscript preparation.
Conflict of interest
The authors declare that they have no competing interests. The authors alone are responsible for the content and writing of the paper.
Author Contributions
JN contributed to the conception, data extraction, analysis, and drafting. TK, AM, and AS worked for the surgical operations, data extraction, interpretation of the results, and drafting. TK, AM, and AS provided statistical advice. NM and AS provided general management of the study and critically revised the protocol and main manuscript.
Data availability
The datasets analyzed during the current study are available from the corresponding author (JN) on reasonable requests.
Table 1. Overview of the comparison of the elements that constitute the LD and ND groups
|
|
Group |
p - value |
|
|
LD |
ND |
|
|
|
Tube diameter (mm) |
1.5 |
1 |
|
|
Number of cases |
70 |
60 |
|
|
Number of sides |
85 |
72 |
|
|
Age (years) |
72.5 ± 11.1 |
72.9 ± 11.5 |
0.73 |
|
Gender (male / female) |
23 / 47 |
17 / 43 |
0.58 |
|
Period of preoperative obstruction (months) |
29.6 ± 40.0 |
63.0 ± 91.8 |
0.009 |
|
Observation period after tube removal (months) |
9.8 ± 5.9 |
14.0 ± 14.7 |
0.38 |
|
Number of recurrences |
12 (14.0%) |
27(37.5%) |
0.001 |
|
Time from tube removal to recurrence (months) |
3.4 ± 4.6 |
11.0 ± 16.0 |
0.82 |
|
Number of recurrences within 1 year |
11 (92%) |
18 (67%) |
0.13 |
In comparing the LD and ND groups, the ratio of male to female, the number of recurrent cases, and the number of recurrences within 1 year were tested by Pearson's χ2 test. Meanwhile, age, period of preoperative obstruction, and observation period after tube removal were tested by Mann-Whitney's U test. Results showed the period of preoperative obstruction was significantly longer in the ND group (p = 0.009).