Safety and Efficacy of the Slit Stent II Lacrimal Stent for the Treatment of Nasolacrimal Duct Obstruction
Phase: NA
Conditions: Epiphora, Dacryocystorhinostomy
Sponsor: Thomas Gardner

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Safety and Tolerance of the Slit Stent II Lacrimal Stent for the Treatment of 
Nasolacrimal Duct Obstruction  
 
PROTOCOL NUMBER:  
 
HUM00114919 
 
 
DATE: 
 
 
 
 
September 2, 2020 
 
VERSION:  
 
 
 
1.9 
 
 
SPONSOR INVESTIGATOR:  
Shannon Joseph, MD, MSc 
Assistant Professor 
University of Michigan 
 
 
 
 
MEDICAL MONITOR:  
 
Grant Comer, MD, MS  
 
 
 
 
 
 
Clinical Assistant Professor 
Ophthalmology and Visual Sciences 
 
 
CLINICAL MONITOR: 
University of Michigan Institute of Clinical 
and Health Research (MICHR)  
Clinical Research Monitoring Program 

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Investigator Signature Page 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
My signature below certifies that I have read and understand this protocol and agree to conduct 
the study in accordance with the specified protocol procedures and FDA’s Good Clinical 
Practice requirements. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PRINCIPAL INVESTIGATOR NAME (Printed):  
 
 
 
Date:  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PRINCIPAL INVESTIGATOR SIGNATURE: 
 
 
 
 
Date: 
 
 

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Table of Contents 
1.0 
Background .........................................................................................................................6 
1.1 
Preliminary Clinical Data / Prior Clinical Experience .............................................. 6 
1.2 
Rationale for Study and Use of the Slit Stent II Device............................................. 7 
2.0 
Product Description ............................................................................................................7 
2.1 
Intended Use .................................................................................................................. 7 
2.2 
Indications for Use ........................................................................................................ 7 
2.3 
Device Description ........................................................................................................ 7 
3.0 
Risk/Benefit Analysis ..........................................................................................................9 
3.1 
Comparison with Other Alternative Devices ............................................................. 9 
3.2 
Minimization of Potential Risks ................................................................................ 10 
3.3 
Potential Benefits ........................................................................................................ 10 
3.4 
Justification for the Investigation .............................................................................. 10 
4.0 
Objectives ...........................................................................................................................10 
5.0 
Outcomes Assessment Timetable ......................................................................................11 
6.0 
Study Design ......................................................................................................................11 
7.0 
Subject Population ............................................................................................................11 
7.1 
Inclusion Criteria ........................................................................................................ 11 
7.2 
Exclusion Criteria ....................................................................................................... 11 
8.0 
Study Duration and Examination Schedule ....................................................................12 
8.1 
Study Duration ............................................................................................................ 12 
8.2 
Examination Schedule ................................................................................................ 12 
9.0 
Study Procedures...............................................................................................................12 
9.1 
Slit Stent II Intubation Evaluation ............................................................................ 13 
9.1.1 
Referring Physicians ............................................................................................. 13 
9.1.2 
Bilateral and Fellow Eye Treatment ..................................................................... 13 
9.1.3 
Screening Eye Examination (Day -60 to Operative Day 0) .................................. 13 
9.2 
Concomitant Medication ............................................................................................ 14 
9.3 
Stent Intubation Procedure (Operative Day 0) ........................................................ 15 
9.3.1 
Subject Preparation ............................................................................................... 15 
9.3.2 
Stent Intubation General Surgical Procedure ........................................................ 15 
9.3.3 
Postoperative Care ................................................................................................ 16 

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9.4 
Follow-Up Visits (Day 1 phone call, Day 5-14 Postoperatively, Day 30-60 phone 
call, Day 30-120 Postoperatively, Month 5-7 Postoperatively) ........................................... 16 
9.5 
Secondary Surgical Interventions ............................................................................. 19 
9.6 
Safety Monitoring ....................................................................................................... 19 
9.7 
Post-Study Procedures................................................................................................ 20 
9.8 
Device Accountability ................................................................................................. 20 
9.9 
Early Withdrawal from Study ................................................................................... 20 
10.0 
Data Analysis and Statistical Considerations ..................................................................20 
10.1 
Sample Size ............................................................................................................... 21 
10.2 
Accountability ............................................................................................................. 22 
10.3 
Screening ...................................................................................................................... 22 
10.4 
Subject Characteristics ............................................................................................... 22 
10.5 
Outcome Criteria ........................................................................................................ 23 
10.5.1 
Adverse Events and Complications ...................................................................... 23 
10.5.2 
Glasgow Benefit Inventory (GBI) Questionnaire ................................................. 23 
10.5.4 
Other Outcome Measures ..................................................................................... 23 
10.6 
Dropouts/Lost-to-Follow-up....................................................................................... 24 
10.7 
Missing data ................................................................................................................. 24 
11.0 
Ethical and Regulatory Considerations ...........................................................................24 
11.1 
Informed Consent ....................................................................................................... 24 
11.2 
Institutional Review Board ........................................................................................ 24 
11.3 
Complications and Adverse Events ........................................................................... 24 
11.3.1 
Serious and Unanticipated Adverse Device Effects (UADE) ............................... 26 
11.3.2 
Non-serious or Anticipated Adverse Events ......................................................... 26 
11.4 
Monitoring ................................................................................................................... 27 
11.4.1  Medical Monitor ....................................................................................................... 27 
11.4.2  Clinical Trial Monitor ............................................................................................... 27 
11.5 
Source Documents / Case Report Forms .................................................................. 27 
11.6 
Deviation from the Protocol ....................................................................................... 27 
12.0 
Protocol Reference List .....................................................................................................29 
Appendix A: Glasgow Benefit Inventory (Adapted)............................................................ 32 
Appendix B: Lac-Q Questionnaire ........................................................................................ 41 
Appendix C: Patient Stent Tolerance and Irritation Assessment ...................................... 43 

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Appendix D: Study flow chart- .............................................................................................. 44 
Appendix E: Manifest Refraction and Visual Acuity .......................................................... 45 
 
 
 
 

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1.0 
BACKGROUND 
A stable tear film is essential for good visual function. On the other hand, excessive tearing (i.e., 
epiphora – a very common condition [1]) can be a major cause for loss of quality of life [2], 
interfering with activities such as driving, reading, watching TV, being outdoors, and social 
interactions, in addition to being a major risk for tear duct infection (dacryocystitis), especially in 
children [3]. The constant dabbing of the cheeks can also lead to skin irritation and puts the eyes 
at risk of infection. While the prevalence of epiphora is not known, the incidence of symptomatic 
nasolacrimal duct obstruction in 1996-2000 in the US was 30.47 per 100,000, or approximately 
120,000 new cases per year [1]. Globally, the incidence is even higher, with case series 
publications from India, Singapore and South Korea suggesting a significant global disease 
burden. In the treatment of epiphora, and in order to facilitate proper healing, surgeons frequently 
place a temporary silicone tube within the healing lacrimal drainage system to stent the passages 
during the healing process [4-7]. Many thousands of these procedures are performed each year, 
and the longer the stents stay in place, the higher the likelihood of long-term surgical success [8-
11]. However, the stents occupy space within the very narrow lacrimal drainage apparatus, 
delaying maximal improvement in tear drainage until the stent is removed weeks to months after 
the procedure. This issue is further exacerbated in cancer patients on chemotherapy such as 
docetaxel (Taxotere) chemotherapy for breast cancer [12], which requires prolonged stenting. 
Despite the fact that stents have a hollow lumen, there are no stents on the market in which the 
lumen is open to tear drainage – possibly because of the engineering challenge of creating an 
opening into the lumen that is large enough to allow tears to flow in but not so large that the stent 
becomes too weak and fragile that it breaks prematurely. Through an active collaboration between 
an ophthalmologist and a mechanical engineer, we have developed a lacrimal stent that has a slit 
opening strategically constructed to drain tears into the lumen, while optimizing the basic 
characteristics of the silicone tubing for the purpose of intraluminal drainage. Such a stent could 
revolutionize the use of stents in the treatment of symptomatic, debilitating epiphora.  
1.1 
Preliminary Clinical Data / Prior Clinical Experience 
 
This study is of the Slit Stent II medical device, a novel variation on a well-established surgical 
tool, namely a silicone tube used to temporarily stent the lacrimal drainage system following a 
recanalization procedure to treat epiphora. Hence, its use in human patients is based on a solid 
clinical foundation [see literature summary below.] Silicone stents have been used successfully 
for decades to maintain the patency of the lacrimal drainage apparatus as the tissues heal 
following dacryocystorhinostomy (DCR) surgery. The Slit Stent II is a modification of the 
“BIKA for DCR” silicone stent manufactured by FCI (FCI SAS; Besancon, France) and 
approved for use throughout the world, including in the United States [13-16]. 
 
Literature has reported the use of lacrimal stents since 1998 [6, 9, 14, 17-19]. In the following 20 
years, multiple articles involving over 1,000 patient subjects have examined DCR with and 
without stents, with techniques involving polyurethane or silicone stents, using bicanalicular or 
monocanalicular stents [3-7, 9-11, 16, 20-40]. In 2016, Fayers et al reported a prospective, 
randomized, controlled, interventional trial involving 300 adult subjects, half of whom received 

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bicanalicular stents, concluded that there is a statistically significantly higher success rate in EN-
DCR surgery with stents compared with no stent [31]. 
 
The specific stent used in this study (without our modifications, however) is the subject of four 
prior publications involving 485 adult subjects [13-16]. As previously mentioned, this is the 
BIKA for DCR bicanalicular stent manufactured by FCI SAS, Besancon, France. These 
publications looked at the relative success and complications of monocanalicular stents versus 
bicanalicular stents; external DCR versus endonasal DCR; and the unciformian endonasal 
technique versus the maxillary endonasal technique. Of note is that in all cases the silicone stent, 
BIKA for DCR, was used as the standard and its use was routine.  
 
 
 
1.2 
Rationale for Study and Use of the Slit Stent II Device 
 
The Slit Stent II has an internal lumen that is open to the ocular surface at the interpalpebral 
fissure, such that tears can drain through the lumen of the stent. After it is placed into the 
lacrimal system and into the nose, the slit openings into the lumen will allow tears to drain into 
the nose, which is where tears normally drain, rather than flow over the lid margin and onto the 
cheek (epiphora). 
 
2.0 
PRODUCT DESCRIPTION 
2.1 
Intended Use 
Temporary post DCR lacrimal stenting 
2.2 
Indications for Use 
Nasal bicanalicular intubation is indicated in treatment of epiphora in adults in cases of 
Dacryocystorhinostomy (conventional or laser). 
2.3 
Device Description 
 
A lacrimal stent is hollow silicone tubing with a non-traumatic tip. The tubing is securely 
attached into malleable stainless steel probes that are used to guide the silicone tubing through 
the lacrimal drainage apparatus. The device is used to maintain an open lacrimal path between 
the surface of the eye and the nasal passages, particularly during a healing process following 
injury or surgery. 
 
The BIKA for DCR lacrimal stent is a bicanalicular intubation device used for intubation of the 
lacrimal drainage apparatus, especially in cases of dacryocystorhinostomy (conventional or laser). 
The silicone tube acts as a conformer during the healing process while facilitating drainage of tears 

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through capillary action around the stent. In cases of canalicular lacerations, the silicone tube 
guides wound healing and prevents the onset of synechia. 
 
The BIKA lacrimal stent consists of a single unit including a silicone tube (length: 280 mm, 
external diameter: 0.94 mm), and one steel probe at each end of the silicone tube (length: 53 mm, 
external diameter: 0.8 mm) with round tips (see Figure 1, below). 
 
 
 
 
 
 
 
 
 
 
 
 
The BIKA for DCR is a sterile, single-use device, and is an FDA cleared device. 
 
 
 
 
The Slit Stent II (investigational) device is created by modifying an existing FDA cleared 
lacrimal stent (Bika, manufactured by FCI Opthalmics- see figure 1 above) by adding additional 
3 mm (+/- 0.5 mm) and 35 mm (+/- 3.5 mm) long slits of equal depth. See figure 2 below. 
 
 
 
 
 
 
 
Figure 2. A 3 mm long slit into the silicone tubing. 
 
The axial cutouts located on the stent allow drainage of tears from the ocular surface to the 
nasal/oropharynx cavities through the internal lumen of the stent. See figure 3.  
 
Fig. 1: BIKA for DCR  

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 Figure 3. Stent with multiple cut-outs placed as part of a standard DCR procedure allow for 
improved draining of tears and resolution of symptomatic tearing.  
 
 
All modifications to the stent are inspected under an optical microscope at a magnification of at 
least 5x to ensure they are free from cutting defects, which could impact the structural integrity 
of the Slit Stent II. To ensure that the Slit Stent II can withstand the forces experienced during 
implantation and removal, additional mechanical integrity tests were performed. Comparing the 
implantation forces to the maximum insertion and removal force, we determined that the 
modified Slit Stent II will have excellent tensile strength – essentially identical to unmodified 
stent –  to prevent mechanical failure in patient use. Each section was tested to determine the 
maximum elongation and force it can withstand before failure. 
 
After modification at the University of Michigan, the Slit Stent II is then packaged and sent to 
FCI Opthalmics for sterilization, packaging and return to Michigan for use in the clinical trial. 
 
 
3.0  RISK/BENEFIT ANALYSIS 
3.1 
Comparison with Other Alternative Devices 
Devices for post-DCR temporary stenting are ubiquitous and widely used. There are no 
foreseeable risks for the modified slit stents beyond the standard risks associated with DCR with 
stenting. 
 
As in any type of surgery, there are risks linked to the material or to developments of the initial 
pathology. Potential complications associated with the placement of the BIKA for DCR stents 
include, but are not limited to the following:  

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Post-operative complications:  
• 
bleeding from nose 
• 
infection 
• 
conjunctival or nasal pruritus  
• 
nasal mucosa or caruncular irritation  
• 
reversible shrinkage of the palpebral fissure  
• 
exteriorization or loss of the stent tubing  
• 
punctal/canalicular injury 
• 
canaliculitis  
 
Device related complications could include, but are not limited to: 
• 
Device dislocation into the oropharynx 
• 
Corneal abrasion 
• 
Conjunctival abrasion 
• 
Secondary surgical interventions related to the Slit Stent II device (surgical repositioning, 
removal, or replacement) 
 
This is the only device that will allow tears to drain through the lumen. 
3.2 
Minimization of Potential Risks 
Standard surgical technique will be used. Post-operative ocular surface antibiotic drops will be 
used in the usual manner. Subjects will be observed closely to detect any adverse events or 
complications that may have occurred.  
3.3 
Potential Benefits 
Benefits include more rapid resolution of epiphora symptoms and longer retention of the stent for 
a better long-term surgical outcome. 
3.4 
Justification for the Investigation 
- Investigate whether a stent with slits at the interpalpebral fissure is well tolerated 
- Determine whether epiphora improves following DCR and Slit Stent II placement 
 
4.0 
OBJECTIVES  
1) Assess tolerance of patients to placement of Slit Stent II (Glasgow Benefits Index and Patient 
Stent Tolerance and Irritation Assessment) 
2) Assess ocular surface irritation (objective and subjective) following stent placement (Glasgow 
Benefits Index and Patient Stent Tolerance and Irritation Assessment; Conjunctival and corneal 
epithelial surface exam and staining under the slit lamp) 
3) Assess change in quality of life following surgery (Glasgow Benefits Index and Lac-Q 
Questionnaire) 
4) Assess change in tearing/epiphora symptoms before and after surgery (Glasgow Benefits 
Index and Lac-Q Questionnaire)  

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5) Assess change in conjunctival tear lake measurement before and after surgery 
6) Assess bacterial growth on stents after removal 
 
All criteria will be summarized within the Slit Stent II treatment group. Formal comparisons will 
be made to no treatment effect and to the standard treatment (control group). 
 
5.0 
OUTCOMES ASSESSMENT TIMETABLE 
Patients will be assessed at 1-day post op by phone, and exams at 5-14 days post-DCR surgery 
(1st post-op visit), 2-4 months post-DCR surgery (usually 2nd post-op visit), and 4-7 months post-
DCR surgery. 
 
6.0 
STUDY DESIGN 
Double arm, single blind, prospective randomized study 
 
7.0 
SUBJECT POPULATION 
This is a single center study that will be conducted at the University of Michigan (Ann Arbor, 
Michigan). Fifty (50) subjects will be enrolled and treated with either the experimental Slit Stent 
II (25 patients) or the control stent BIKA for DCR (25 patients). Patients who are currently 
scheduled to undergo a DCR (dacryocystorhinostomy) as per standard of care will be offered 
participation in the study. Patients who elect to participate in the study will be consented and 
then randomized to the treatment or control arm. 
7.1 
Inclusion Criteria 
Subjects in whom the subject and study eye meet all of the following criteria are candidates for 
this study: 
1. 22 years of age or older. 
2. Eligible for unilateral DCR surgery with stenting for treatment of epiphora secondary to 
nasolacrimal duct obstruction. Ability to instill post-operative eye drop 
3. Signed written, informed consent. 
4. Willingness and ability to comply with schedule for follow-up visits and postoperative 
evaluations. 
 
7.2 
Exclusion Criteria 
All subjects in whom the subject or study eye meets any of the following criteria will be 
excluded from the study: 
 
• Subjects less than 22 years of age 
• Subjects scheduled for bilateral DCR surgery 
• Subjects with known sensitivity to silicone 
• Subjects with a current condition that, in the investigator’s opinion, would interfere with 
the treatment. 

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• Inability to use eye drops 
• Subjects with a known sensitivity to required study medications (e.g. antibiotic drops) if 
an alternative medication is not available. 
• Subjects under legal guardianship or who, in the investigator’s opinion, lack the mental 
capacity to provide written informed consent for study participation. 
 
8.0 
STUDY DURATION AND EXAMINATION SCHEDULE 
8.1 
Study Duration 
The study duration will be 6 months (+/- 1 month) for all study patients.  
 
8.2 
Examination Schedule 
The following examination schedule will be followed from screening through the postoperative 
visits: 
 
• Screening (Day -60 to Day 0 Preoperatively) 
• Device implantation operation 
• Phone call Assessment at 1 day post op 
• Phone call Assessment at 45 days post op (+/- 15 days) 
• Day 5-14 postoperatively  
• Day 30-120 postoperatively (with stent removal) 
• 5-7 month final post-operative exam 
 
The screening visit should be completed anytime within the 60 days prior to the scheduled 
surgery. Unscheduled visits may be completed at the investigator’s discretion or as medically 
necessary before or after the implant surgery. 
 
All final exam procedures will be completed at the second post-operative study visit. 
 
9.0 
STUDY PROCEDURES 
Subjects who elect to participate in this study will complete the study as outlined below. Subjects 
will be randomly assigned to the experimental vs. control stents using a randomized block design 
with 1:1 allocation to treatment and control. Stents will be provided to the surgical team on the 
day of surgery by the Study Coordinator. Surgical team, recruitment staff, and scheduling staff 
will be masked to treatment assignment until day of surgery. All tests and measurements should 
be obtained in accordance with the procedures specified in this protocol. If it is not possible to 
perform a measurement or examination due to the individual eye’s specific ocular pathology, the 
reason for not performing the test or measurement should be documented on the source 
documents. 
 

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The investigator may designate one or more surgeon sub-investigators at his/her investigative 
site. A surgeon sub-investigator may evaluate subjects for the study and perform the Slit Stent II 
lacrimal stent intubation. Surgeon sub-investigators will be listed on all applicable investigator 
regulatory documents (including the delegation of responsibilities log) and will complete all 
sponsor-required training for the study.  
 
For the pre-op and all post op study visits, the Lac-Q Questionnaire will be administered by an 
interviewer, and the interviewer will record the subject’s responses directly onto the 
corresponding questionnaire CRFs or source documents and calculate the Lac-Q score. For post 
op visits, the Lac-Q Questionnaire will be given prior to other questionnaires.  
 
For the two post-op study visits, the Quality of Life (QOL) questionnaire (Glasgow Benefit 
Inventory (GBI)- see Appendix A) and the Patient Stent Tolerance and Irritation Assessment (see 
Appendix C) will be administered by an interviewer, in this order, and the interviewer will 
record the subject’s responses directly onto the corresponding questionnaire CRFs or source 
documents and calculate the GBI score.  
 
When multiple questionnaires are given at the same visit, the order shall always be: 1) Lac-Q, 2) 
GBI QOL, and 3) Patient Stent Tolerance and Irritation Assessment. 
 
9.1 
Slit Stent II Intubation Evaluation 
Candidates for the Slit Stent II may be identified from the investigator’s clinical practice or may 
be referred by outside ophthalmologists. All screening examination procedures will be performed 
by the investigator or trained personnel working under the investigator’s supervision.  
 
9.1.1 Referring Physicians 
Subjects may be referred to the investigator for enrollment in the study. Evaluation of the 
lacrimal complaint and eligibility for DCR surgery and for the study will be assessed 
independently by the investigator. 
 
9.1.2 Bilateral and Fellow Eye Treatment 
Same day bilateral implantation of the Slit Stent II will not be allowed in the study. 
 
9.1.3 Screening Eye Examination (Day -60 to Operative Day 0) 
Informed consent must be signed and dated before any study procedures are performed that are 
specific for the study and not part of the routine evaluation or examination. A copy of the 
informed consent must be given to the subject and documented in the source documents. After 
informed consent is obtained, each potential Slit Stent II candidates will be evaluated in order to 
determine his/her eligibility for study participation. The complete ophthalmic clinical evaluation 
will take place before informed consent. Any assessment that is required on the screening CRF 
which was not completed as part of standard clinical exam will be completed after the consent is 

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obtained. Demographics and an ocular history, medical history, allergies and current medication 
list will be obtained. Please refer to the flow chart in Appendix D for the schedule of events for 
each listed study activity. The complete screening eye examination of the operative eye and 
subject histories will include, where medically possible: 
 
 Demographics (Date of birth, gender, ethnicity. Age is calculated from the subject’s 
date of birth and the informed consent date; subjects must be at least 22 years of age 
at the informed consent date.) 
 Medical history 
 Medication list (Baseline medication history should include all current prescribed 
medications and all routinely taken non-prescription medications) 
 Ocular history- Baseline ocular history at the screening examination should include 
known ophthalmic conditions and prior eye surgeries.  
 Lac-Q questionnaire (Appendix B) 
 Lacrimal system probing/irrigation 
 Corrected visual acuity and manifest refraction- Corrected visual acuity is 
measured in each eye after manifest refraction using the Early Treatment Diabetic 
Retinopathy Study (ETDRS) charts. The distance from the subject’s eyes to the 
ETDRS chart should be 3 meters. The standard ETDRS chart light box will be used. 
ETDRS Chart 1 will be used for the Right eye and Chart 2 for the Left Eye. Chart R 
will be used for manifest refraction. Room illumination will be at highest illumination 
(Appendix E). 
 Intraocular pressure- Intraocular pressure measurement is measured by the iCare 
tonometry method. IOP measurement should be performed after visual acuity 
measurements. 
 Slit lamp biomicroscopy of lid margins, puncta, conjunctiva and cornea- Slit lamp 
biomicroscopy with use of fluorescein should include a complete survey of the lid 
margins, puncta, conjunctiva and cornea. The Oxford scheme will be used to grade 
corneal and conjunctival staining. Any abnormalities such as corneal infiltrates and 
punctate erosions should be documented. The tear lake is measured using a slit lamp 
by narrowing the slit and shortening it to 1 mm or 0.2 mm, placing the slit light beam 
on the inferior lid margin tear lake, and using the beam to measure the vertical height 
of the fluid between the lid margin and the location of the top of the tear lake on the 
conjunctiva or cornea. 
 
Other optional diagnostic tests may be performed at the investigator’s discretion (e.g., 
dacryoscintigraphy, Jones test, etc.) to further evaluate the subject for nasolacrimal duct 
obstruction surgery or as dictated by the clinical situation. The results of optional diagnostic tests 
will be maintained in the source documents but will not be recorded on the CRFs. 
 
9.2 
Concomitant Medication 
Subjects are permitted to take prescribed or non-prescription medications and supplements 
before and after the DCR procedure, at the discretion of the investigator. Medications used 

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during the operative procedure will be documented in the source documents for the operative 
procedure but will not be captured on the case report forms, unless the medication was used to 
treat an intraoperative adverse event or complication. 
 
9.3 
Stent Intubation Procedure (Operative Day 0) 
The staff should confirm that the informed consent form (ICF) for the study has been signed, 
dated and a copy was given to the subject. The surgical staff is responsible for assuring that any 
additional surgical consent forms or HIPAA forms required by the clinic or institution are signed 
before surgery. Subject history and other tests or measurements from the screening examination 
or that are otherwise dictated by the subject’s condition may be performed at the discretion of the 
investigator, to provide accurate baseline measurements or to determine continuing eligibility for 
the nasolacrimal duct intubation surgery. 
 
The study statistician will create (via randomized block design) a treatment assignment list and 
provide it to the study coordinator only. The study coordinator will provide the correct stent at 
the time of the operation. Type of stent will not be recorded in patient record. Patient will not be 
told which stent was installed.  
 
9.3.1 Subject Preparation 
The subject will be prepared for surgery, and the operated side will be prepped and draped in the 
surgeon’s usual sterile fashion for ophthalmic surgery. The DCR surgical procedure will be 
performed under standard Anesthesia conditions as per standard clinical care at the University of 
Michigan. Medications administered perioperatively may include sedation or anesthesia, 
antibiotics, and other surgical antimicrobials (e.g., povidone iodine) or medications used during 
any concomitant surgical procedure (e.g., steroids, antimetabolites). Local anesthesia will be 
performed at the surgeon’s discretion based on the subject’s clinical condition and surgical plan 
using the surgeon’s standard drug regimen fashion.  
 
9.3.2 Stent Intubation General Surgical Procedure 
DCR surgery with stenting will be performed in a standard fashion opening the lacrimal sac, 
creation of an osteotomy connecting the nose to the lacrimal sac, and placing the stent under 
direct visualization. There are two techniques: External DCR and Endonasal DCR. 
 
The external DCR involves (1) skin incision over the lacrimal sac, (2) exposure of lacrimal bone, 
(3) creation of an osteotomy into the nasal cavity using a bone-removal instrument, (4) opening 
of the lacrimal sac, (5) opening of the nasal mucosa, (6) placement of the lacrimal stent, (7) 
closure of the mucosa and surgical wound.  
 
The endonasal DCR involves (1) visualizing the middle meatus in the nose, (2) identifying the 
position of the lacrimal sac (using a canalicular probe or light source), (3) creation of an 
osteotomy with a bone removal device to expose the lacrimal sac to the nasal cavity, (4) opening 
of the lacrimal sac, (5) placement of the lacrimal stent. 

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The selection of the DCR surgical technique will be determined by the surgeon and dictated by 
the clinical condition and lacrimal duct anatomy and pathology. This study does not aim to 
assess the efficacy of DCR surgery, and considers DCR surgery to be a well-established and 
efficacious surgical procedure for the treatment of epiphora secondary to nasolacrimal duct 
obstruction. 
 
Operative records should be kept during the procedure or dictated postoperatively that describe 
medications used, the surgical technique for stent placement, concomitant surgical procedures, 
any operative complications or adverse events, and any planned or anticipated secondary surgical 
procedures. The position of the stent with respect to the location of central slit position relative to 
medial canthal interpalpebral function will be recorded on the CRFs. Medications used in 
conjunction with the surgical procedure will be described in the operative records and will not be 
recorded on the CRFs. The operative records will be retained in the source documents. 
 
9.3.3 Postoperative Care 
Written postoperative instructions will be given to each subject and reviewed prior to discharge. 
The following postoperative eye drops will be prescribed for the following minimum times:1 
 
• An antibiotic-steroid combination eye drop (e.g. Tobramycin-Dexamethasone or 
Neomycin-Polymyxin-Dexamethasone) placed 4 times daily for 2 weeks, then twice 
daily for 2 weeks, then once daily for at least 2 weeks or until stent removal, as 
determined by the surgeon. 
 
Additional medications including, but not limited to, erythromycin ointment and bacitracin 
ointment will be used at the discretion of the operating surgeon. All postoperative eye drop usage 
will be recorded on the source documents and on the CRFs. Other prescription or 
nonprescription medications, including pain medications, may be taken as needed throughout the 
study. 
9.4 
Follow-Up Visits (Day 1 phone call, Day 5-14 Postoperatively, Day 30-60 
phone call, Day 30-120 Postoperatively, Month 5-7 Postoperatively) 
A study flow chart summarizing the follow-up examination schedule and required procedures to 
be performed at each study visit is provided in Appendix D. All subjects will be seen for a 1st 
post-operative visit 5-14 days after the DCR with intubation, for a 2nd post-operative visit at 30-
120 days after intubation, and for a final visit at month 5-7 postoperatively, with the exact timing 
dependent on patient findings and surgeon discretion. Unscheduled visits may be completed at 
the investigator’s discretion or as medically necessary. 
 
During the Day 1 and Day 30-60 phone assessments, the patient will be asked about any 
 
1 An alternative antibiotic or anti-inflammatory drug and dosage regimen may be used to conform with clinic or 
hospital formulary or prescribing requirements, with sponsor approval. An example would be neomycin-polymyxin-
dexametasone eye drop (i.e. “Maxitrol”). 

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postoperative swelling or pain or other adverse effects. If the patient reports any symptoms that 
would require a follow-up visit, we will ask the patient to return to the University of Michigan if 
possible. If this is not possible due to transportation issues, we will have them return to their 
referring ophthalmologist.  
 
The following procedures will be performed at the day 5-14 and day 30-120 post-operative 
visits unless noted otherwise. 
 Documentation of interim medical, ocular, and medication histories since 
previous visit. The ocular history should capture any changes in the study eye since 
the previous visit; and, any relevant changes to the fellow eye that are necessary to 
evaluate an adverse event or anomaly in the study eye. The medication history should 
capture any changes in prescribed medications or routinely taken non-prescription 
medication since the previous visit.  
 Subjective reports of tearing- we will capture the subject’s report of their tearing 
symptoms since the surgery procedure 
 Corrected distance visual acuity - Corrected visual acuity is measured in each eye 
by the ETDRS chart at 3 meters using the manifest refraction obtained at the previous 
visit. If there is a 2-line or more reduction in visual acuity from the last corrected 
visual acuity, a repeat manifest refraction in each eye will be performed.  
 Intraocular pressure- Intraocular pressure measurement is measured by the ICare 
tonometry method, performed after visual acuity measurement had been completed. 
 Slit lamp biomicroscopy (including conjunctiva and cornea), with use of 
fluorescein- Slit lamp biomicroscopy should include a complete survey of the 
conjunctiva and cornea, and of the tear lake. The Oxford scheme will be used to grade 
corneal and conjunctival staining. The tear lake is measured using a slit lamp by 
narrowing the slit and shortening it to 1 mm or 0.2 mm, placing the slit light beam on 
the inferior lid margin tear lake, and using the beam to measure the vertical height of 
the fluid between the lid margin and the location of the top of the tear lake on the 
conjunctiva or cornea. 
 Visual inspection of stent integrity and slit positioning- External and slit lamp 
exam of the medial canthal area and the medial commissure. The presence of the 
lacrimal stent within the medial commissure, between the puncta, will be documented 
as (1) present, slit in fissure, (2) present, slit not in fissure, or (3) not present. 
 Lac-Q questionnaire (Appendix B) 
• Glasgow Benefit Inventory Questionnaire (Appendix A). 
• Patient Stent Tolerance and Irritation Assessment (Appendix C) 
• The 3 questionnaires will always be given in the same order: 1) Lac-Q, 2) 
GBI, and 3) Stent Tolerance Assessment. 
• Other diagnostic tests– Jones I, Jones II or lacrimal irrigation at investigator’s 
discretion 
• Adverse events, complications, visual disturbances- Visual disturbances are any 
unexpected, expected, or pre-existing sight related occurrences that are not captured 
in any of the examinations or measurements, such as nystagmus or diplopia. 

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Unexpected or new reports of visual disturbances related to the device or surgical 
procedure should be recorded on the complications/adverse event case report form. 
 
 
In addition to the above procedures, at the day 30-120 visit, we will collect, examine (photo) 
and culture all stents after retrieval from the nose. Culturing will consist of placing the retrieved 
stent in a standard container and submitting it to microbiology for culture and sensitivities. 
 
Removal of the stent entails cutting the holding suture in the nose with scissors under direct 
visualization, with the help of a nasal speculum if needed, cutting the stent itself with scissors 
once to linearize it, and then pulling the stent out either from the nose or from the puncta using 
forceps. 
 
Upon stent removal, the surgeon will comment on whether stent removal was technically simple, 
moderate or difficult (binary). This will be recorded on the CRF. 
 
At the Final Visit, month 5-7, the following procedures will be performed: 
 
 Documentation of interim medical, ocular, and medication histories since 
previous visit. The ocular history should capture any changes in the study eye since 
the previous visit; and, any relevant changes to the fellow eye that are necessary to 
evaluate an adverse event or anomaly in the study eye. The medication history should 
capture any changes in prescribed medications or routinely taken non-prescription 
medication since the previous visit.  
 Lac-Q questionnaire (Appendix B) 
• Glasgow Benefit Inventory Questionnaire (Appendix A). 
• The 2 questionnaires will always be given in the same order: 1) Lac-Q, 2) 
GBI. 
 Corrected distance visual acuity - Corrected visual acuity is measured in each eye 
by the ETDRS chart at 3 meters. If there is a 2-line or more reduction in visual acuity 
from the last corrected visual acuity, a repeat manifest refraction in - each eye will be 
performed. 
 External exam of the medial canthal area and the medial commissure 
 Slit lamp biomicroscopy of the puncta, lid margins and ocular surface. The 
Oxford scheme will be used to grade corneal and conjunctival staining. The tear lake 
is measured using a slit lamp by narrowing the slit and shortening it to 1 mm or 0.2 
mm, placing the slit light beam on the inferior lid margin tear lake, and using the 
beam to measure the vertical height of the fluid between the lid margin and the 
location of the top of the tear lake on the conjunctiva or cornea. 
 Adverse events, complications, visual disturbances- Visual disturbances are any 
unexpected, expected, or pre-existing sight related occurrences that are not captured 
in any of the examinations or measurements, such as nystagmus or diplopia. 

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Unexpected or new reports of visual disturbances related to the device or surgical 
procedure should be recorded on the complications/adverse event case report form. 
 
 
Because of the distances involved, we can anticipate that some patients will not be able to make 
the trip to Ann Arbor due to distance or transportation issues, especially in the case of successful 
surgery with symptomatic resolution. In those cases, we will document this matter in the report 
form and make a phone-call assessment of patient status, which will be reported. 
 
Other optional diagnostic tests such as lacrimal irrigation/ or Jones 1 or Jones 2 tests may be 
performed at the investigator’s discretion to further evaluate the subject’s postoperative outcome 
or as dictated by the clinical situation. These tests and their results will be recorded accordingly 
on the CRFs. 
 
Extensive effort will be made by telephone and mail to contact subjects who miss a scheduled 
follow-up visit to arrange a new appointment. 
 
Postoperative observations and adverse events will be documented in the subject’s medical 
records. Complications or adverse events that are observed by the investigator or reported by the 
subject should be recorded on the CRFs. For all adverse events and complications, a description 
of the event, date first observed, any action taken, and ultimate outcome will be recorded.  
 
For all adverse effects, sufficient information will be pursued and/or obtained so as to permit 1) 
an adequate determination of the outcome of the effect (i.e., whether the effect should be 
classified as a serious adverse effect) and; 2) an assessment of the causal relationship between 
the adverse effect and the investigational device or, if applicable, the other study treatment or 
diagnostic product(s). Adverse events present at the end of study will be followed until resolved 
or the Sponsor Investigator determines no further follow-up for the study is required. Any 
findings related to the adverse event that are obtained after the final study visit is completed will 
be documented in the subject’s medical records and the relevant findings will be recorded on the 
adverse event and adverse event summary CRFs. 
 
9.5 
Secondary Surgical Interventions 
All secondary surgical interventions will be recorded in the subject’s medical records and CRFs 
and recorded as an adverse event and reported to the IRB according to local policies and to the 
FDA according the regulations found in 21 CFR 812.  
9.6 
Safety Monitoring 
Subjects will be observed closely to detect any adverse events or complications that may have 
occurred. On the day of treatment and at each follow-up visit, subjects should be asked a non-
leading question, such as “How are your eyes?” to determine whether any complications or 
adverse events might have occurred since the last visit. The presence or absence of adverse 

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events or complications will be documented. All exam findings, work-up, management, and 
sequelae relevant to an AE will be recorded on the AE CRF. 
 
Ophthalmic safety will be evaluated by slit lamp biomicroscopy of the operated eye. In the case 
of an adverse event or complication, these tests, and any others deemed necessary, may be 
repeated before the next scheduled visit at the investigator’s discretion. Appropriate supportive 
and/or definitive therapy may be administered as required. Any complications or adverse events 
will be recorded in the medical record/CRF.  
9.7 
Post-Study Procedures 
Subjects will be discharged from the study after the second scheduled examination is complete.  
9.8 
Device Accountability 
All use of the Slit Stent II will be under the direct supervision of the principal investigator or 
his/her designee. The investigational stents will be clearly labeled as investigational use only, 
and will have a clearly marked serial number. The receipt date and serial number will be 
recorded. The stents will be stored at the Kellogg Eye Center in a secure fashion, with access 
limited to the study team and their designee. 
 
All records of receipt, use, and disposition of the devices will be maintained by the study team. 
At the completion of the study, there will be a final reconciliation by study personnel of devices 
shipped, implanted, and devices remaining. Any discrepancies noted will be investigated, 
resolved, and documented prior to return or destruction of unused devices. Stents destroyed on 
site will be documented in the study files. 
9.9 
Early Withdrawal from Study 
Subjects will be advised that they are free to withdraw from the study at any time. The 
investigator may discontinue a subject if a serious adverse event occurs and it is in the subject's 
best interest not to continue in the study, or if the subject moves and the subject cannot complete 
the remainder of the follow-up visits. When a subject withdraws early from the study, a final 
examination will be performed at the time of withdrawal, if possible.  
 
10.0 DATA ANALYSIS AND STATISTICAL CONSIDERATIONS 
A detailed statistical analysis plan (SAP) will be developed for analysis of all data for this study. 
Required analyses and target endpoints that will be included in this SAP are summarized below. 
The methods by which each of these analyses is performed will be included in the SAP. The 
required analyses and target endpoints for the Slit Stent II include, but are not limited to, those 
listed below. If there are any discrepancies between the statistical analyses described in the SAP 
versus this protocol, the SAP will prevail. Tabulation of summary statistics, graphical 
presentations, and statistical analyses will be performed using SAS and/or R software. All 
subjects who are enrolled in this study will be included in the safety analysis. All testing and 
confidence intervals will use a two-sided significance level of 5%. 
 

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Specific analyses for the six listed objectives are very similar to one another. Data will be 
summarized by treatment group (Slit Stent II or BIKA for DCR): counts and percentages for 
categorical variables, means and standard deviations for continuous variables. Additionally, 95% 
confidence intervals will be provided for each treatment group and for the difference between 
treatment groups. The confidence intervals for differences are keys to exhibiting the similarity 
between the Slit Stent II and the existing BIKA stent. 
 
As this is a randomized experiment, control for pre-treatment variables is not necessary.  
However, a sensitivity analysis controlling for the baseline measurement of the outcome variable 
will be conducted.  For example, post-surgery Lac-Q will be regressed on treatment and pre-
surgery Lac-Q. If pre- and post-surgery measures are highly correlated, the confidence interval 
for the treatment effect will be narrower (more precise). If measurements are made at multiple 
post-surgery time-points, (generalized) linear mixed models will be used to estimate an overall 
(fixed) treatment effect while accounting for any correlation between measurements on the same 
person (random intercept). 
 
10.1 Sample Size 
 
 
The recommended study size is 50 subjects: 25 in the treatment arm (Slit Stent II) and 25 in the 
control arm (BIKA for DCR).  The sample size recommendation is based on two factors. 
• It provides reasonable accuracy for estimates of proportions, means, and differences of 
proportions and of means. For categorical variables, the maximum half width of a 95% 
Wilson confidence interval for a single proportion is 0.18 (for n=25) and for a difference 
of two proportions is 0.27 (n1=n2=25). For continuous variables, the margin of error for 
a Welch t-interval for a mean is 0.41 standard deviations, and for a difference of two 
means it is 0.57 standard deviations.  For example, if the standard deviation of the GBI 
score is 25 points, the margin of error for the confidence interval for the difference of 
treatment group GBI means is 14 points. 
• It provides excellent power to show the new variation is non-inferior to the common 
lacrimal stent as measured by the GBI:  Based on previous studies of lacrimal stents [11, 
41-47] that assessed GBI, we estimate the standard deviation is about 25 points on the 
GBI scale and we set a non-inferiority boundary of 𝛿𝛿= 20 points (20/25 = 0.80, a 
‘large’ effect in Cohen’s taxonomy).  If in fact the devices are equivalent (i.e., they have 
equal mean GBI scores, 𝜇𝜇𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆= 𝜇𝜇𝐵𝐵𝐵𝐵𝐵𝐵𝐵𝐵), then we have 87% power to demonstrate non-
inferiority based on a single GBI measurement.  Using all repeated observations would 
increase power even against a tighter non-inferiority boundary. 
 
 

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10.2 Accountability 
Accountability by postoperative visit will be calculated as illustrated in Table 10.2-1 below. 
 
Table 10.2-1: Accountability by Postoperative Visit 
 
Day 0 
Day 5-14 
Day 30-120 
Available for Analysis2 
n/N1(%)  
 
 
 
Missed Visit3 
n/N1 (%) 
 
 
 
Discontinued4 
n/N1 (%) 
 
 
 
Active5 
n/N1 (%) 
 
 
 
Lost to follow-up6 
n/N1 (%) 
 
 
 
% Accountability = Available for Analysis 
(Enrolled - Discontinued - Active) 
 
 
 
 
Where,  
1 
Enrolled (N) = total number of subject eyes enrolled in the study.  
2  
Available for analysis = total number of eyes for whom data are available at each postoperative 
interval.  
3  
Missed visit = total number of eyes that missed the visit, but were otherwise accounted for. 
Includes those eyes that missed the visit but were seen at a later visit. 
4  
Discontinued = total number of eyes that discontinued follow-up prior to completion of the study 
for any reason (e.g., device explant, moved away).  
5  
Active (not yet eligible for the interval) = total number of eyes that have not yet reached the visit 
interval.  
6  
Lost to follow-up = total number of eyes for whom a visit at the prescribed visit or later was not 
completed and who are not considered to be active or discontinued. 
 
10.3 Screening 
The screening data for all subjects who are screened, but do not meet eligibility criteria, will not 
be analyzed or tabulated nor collected on the CRFs. The reason for screen failure will be 
captured on the CRFs. 
10.4 Subject Characteristics 
The number of subjects included in the safety and/or effectiveness evaluations, subjects 
completing the study, and the reasons for any withdrawals will be tabulated by counts and 
percentages. Continuous data will be summarized by mean, standard deviation, and Tukey’s 
five-number summary. Categorical demographic data will be summarized using counts and 
percentages. Abnormal medical histories, ocular histories, and prior/concurrent medications 
obtained on the screening visit will be presented in data line listings. 

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10.5 Outcome Criteria  
Complications and adverse events are the primary safety outcomes to be evaluated. All 
complications and adverse events and their rates of occurrence will be reported. Changes in the 
subject’s symptoms (tearing, irritation) and quality of life as measured by the GBI are the primary 
effectiveness outcomes. 
 
10.5.1 Adverse Events and Complications  
All subject questionnaire data, complications, and adverse events will be tabulated and 
summarized. 
 
10.5.2 Glasgow Benefit Inventory (GBI) Questionnaire 
The effectiveness parameter evaluated will be the mean composite score for the GBI 
administered post-treatment at the 1-4 month post-operative follow-up visit. The GBI will be 
administered at each post-operative visit. It is believed that the positive effect of the surgery will 
have manifested itself in GBI score by the 2nd follow-up visit. A 95% t confidence interval will 
be used to estimate the mean score. 
 
Scoring the GBI will follow the standard protocol (Appendix A). Positive scores indicate 
improvement from pre-treatment; negative scores indicate deterioration. 
 
As part of the GBI protocol, it is expected that researchers may need to change the format or 
appearance of items to suit their purposes. 
 
10.5.3. Lac-Q Questionnaire (Appendix B) 
This study does not aim to assess the effectiveness of the DCR procedure, which is a well-
established surgical procedure for the treatment of epiphora secondary to nasolacrimal duct 
obstruction. Furthermore, the study does not aim to assess the effectiveness of using a silicone 
lacrimal stent as part of a lacrimal procedure. Rather, the primary goal of this study is to assess 
patient tolerance of the Slit Stent II, which introduces novel cuts into the traditional stent that 
allow for intraluminal tear drainage. The secondary goal of the study is to confirm that the Slit 
Stent II functions like any other silicone lacrimal stent as an adjunct to a lacrimal procedure. The 
effectiveness of the procedure in relieving the tearing symptoms and associated social isolation 
will be assessed at the pre-op visit and at each post-op visit. Scoring will follow the standard 
protocol (Appendix B). The Lac-Q questionnaire will always be given first among the 
questionnaires. 
 
10.5.4 Other Outcome Measures 
Other outcome measures, such as slit lamp biomicroscopy, will be reported in data line listings. 

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10.6 Dropouts/Lost-to-Follow-up 
Subjects may drop out at any time during the study. All treated subjects/eyes will be included in 
the safety analysis. 
 
10.7 Missing data 
The amount of missing data will be minimized by careful recordkeeping and diligent follow-up. 
Modern imputation methods will be used to complete specified analyses. To assess the impact of 
missing data, sensitivity analyses will be conducted. The primary endpoints will be assessed in 
worst case and best case scenarios. The number of missing data points in this type of study is 
anticipated to be small. The sensitivity analyses will likely yield results similar to the main 
analysis. 
 
The study results will be submitted for publication or presentation regardless of the study 
outcome following the conclusion or termination of the trial. 
 
 
11.0 ETHICAL AND REGULATORY CONSIDERATIONS 
This study will be conducted in accordance with FDA’s Good Clinical Practice regulations.  
11.1 Informed Consent 
In accordance with the provision of 21 CFR Part 50, each subject will provide written informed 
consent for participation in this study prior to enrollment into the study.  
 
The study will be explained to the prospective subject by the investigator or his designee. The 
nature of the experimental product will be explained together with potential hazards of the 
surgical procedure, including any possible adverse reactions. The subject will be informed that 
he/she is free to terminate participation in the study for any reason. One copy of the signed 
consent form will be retained in the medical record, and one copy will be given to the subject. 
 
11.2 Institutional Review Board 
This protocol and the ICF will be approved initially and reviewed annually by the University of 
Michigan Institutional Review Board (IRB). Progress reports will be submitted at the completion 
of the study or at least once yearly, whichever comes first, to the IRB. Serious adverse events 
will be reported to the IRB and the FDA in accordance with IRB Reporting Criteria Guidelines 
and applicable FDA regulations for serious adverse events. 
 
11.3 Complications and Adverse Events 
Adverse events will be recorded from the time of surgical implantation of the device until the 
final visit. Ophthalmic complications or adverse events that are observed by the investigator or 

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reported by the subject should be recorded on the CRFs. For all adverse events and 
complications, a description of the event, date first observed, any action taken, and ultimate 
outcome will be recorded.  
 
For all adverse effects, sufficient information will be pursued and/or obtained so as to permit 1) 
an adequate determination of the outcome of the effect (i.e., whether the effect should be 
classified as a serious adverse effect) and; 2) an assessment of the causal relationship between 
the adverse effect and the investigational device or, if applicable, the other study treatment or 
diagnostic product(s).    
 
Adverse effects felt to be associated with the investigational device or, if applicable, other study 
treatment or diagnostic product(s) will be followed until the effect (or its sequelae) or the 
abnormal test finding resolves or stabilizes at a level acceptable to the Sponsor Investigator. 
 
All adverse events will be reported to the IRB according to local policies and to the FDA 
according the regulations found in 21 CFR 812.150. 
 
Complications and adverse events that occur in the study can be caused by the Slit Stent II, by 
the standard stent, or by the surgical DCR procedure, and are identical to the risks already 
associated with DCR surgery and BIKA for DCR stent placement (see Section 3.1).  
Potential complications include, but are not limited to the following:  
 
  
• 
bleeding from nose 
• 
infection 
• 
irritation or discomfort 
• 
conjunctival or nasal pruritus  
• 
nasal mucosa or caruncular irritation  
• 
reversible shrinkage of the palpebral fissure  
• 
exteriorization or loss of the stent tubing  
• 
punctal/canalicular injury 
• 
canaliculitis  
• 
Synechia of the nasal mucosa 
• 
Induced mucocele 
• 
Device dislocation into the oropharynx 
• 
Corneal abrasion 
• 
loss of the device (falling out or inadvertently swallowing) 
• 
Conjunctival abrasion 
• 
Secondary surgical interventions related to the Slit Stent II device (surgical repositioning, 
removal, or replacement) 
• 
False passages 
• 
Separation of the silicone from the steel guide 

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• 
Breakage of the stent during insertion or postoperatively 
• 
Stricturotomy 
 
All ophthalmic adverse events should be recorded on the adverse event forms in the CRFs. 
Adverse device effects /events that are determined by the sponsor investigator to be vision-
threatening should be considered to be reportable as described below. 
 
Adverse events that occur in association with a device that is used in conjunction with the Slit 
Stent II will be reported separately. 
 
Postoperative observations that, after sponsor investigator review, are determined to be part of 
the normal healing process that occurs after the nasolacrimal intubation procedure are not 
considered to be reportable events. 
 
11.3.1 Serious and Unanticipated Adverse Device Effects (UADE) 
An unanticipated adverse device effect is defined as “any serious adverse effect on health or 
safety or any life-threatening problem or death caused by, or associated with, a device if that 
effect, problem, or death was not previously identified in nature, severity, or degree of incidence 
in the investigational plan, or any other unanticipated serious problem associated with a device 
that relates to the rights, safety or welfare of subjects.” 
 
11.3.1.1   Sponsor Investigator Responsibilities  
The Sponsor-Investigator will promptly review documented adverse effects and abnormal test 
findings to determine 1) if the abnormal test finding should be classified as an adverse effect; 2) 
if there is a reasonable possibility that the adverse effect was caused by the investigational device 
or, if applicable, other study treatment or diagnostic product(s); and 3) if the adverse effect meets 
the criteria for a serious adverse effect. 
 
In accordance with 21 CFR Part 812.150(a)(1) and (b)(1), the sponsor shall promptly report the 
results of an evaluation of any serious and unanticipated adverse device effect to FDA as soon as 
possible, but not later than 10 working days after the sponsor investigator first receives notice of 
the effect. The UADE should also be reported to the University of Michigan IRB according to 
the IRB reporting guidelines. Complications and non-serious or anticipated adverse events 
should be documented and tabulated but need not be submitted by the sponsor investigator to the 
FDA as individual reports. All vision threatening adverse events should also be reported to FDA, 
and the reviewing IRB, and all participating investigators in the same manner as reporting a 
serious and unanticipated adverse device effect. 
11.3.2 Non-serious or Anticipated Adverse Events 
Non-serious or anticipated adverse events and complications should be documented on the CRFs 
and tabulated for reporting as required according to the FDA and IRB reporting guidelines.  

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11.4 Monitoring 
 
11.4.1  Medical Monitor 
An independent Medical Monitor will be appointed to review each Serious Advent Event. Any 
Serious Adverse Events will be reported to Dr. Joseph, the sponsor of the study, who will in turn 
notify the Medical Monitor. The Medical Monitor will review the event, request any additional 
data if necessary, and make a determination regarding expectedness and relatedness. Also, the 
Medical Monitor will determine if this safety data increases the risks to subjects on the trial. All 
non-serious adverse events will also be reviewed by the Medical Monitor on a quarterly basis.  
 
Dr. Joseph will be responsible for reporting the events to the IRB and the FDA as appropriate.. 
The Medical Monitor review will be maintained in the study records. 
 
The Medical Monitor may meet in person or through a teleconference with other 
individuals with clinical expertise as needed. 
 
11.4.2  Clinical Trial Monitor 
To assure adequate protection of the rights of human subjects, per 21 CFR §812.40, 812.43 and 
812.46, this study will be monitored by the University of Michigan Institute of Clinical and 
health research (MICHR). Routine monitoring will be scheduled at appropriate intervals, with 
more frequent visits occurring at the beginning of the study. A site activation visit will take 
place, followed by routine monitoring visits. Additional visits can be scheduled at the request of 
the Sponsor-Investigator. 
 
The established monitoring plan will ensure the quality and integrity of the data throughout the 
study conduct to verify adherence to the protocol, completeness and accuracy of study data and 
samples collected, dispensing and inventory of the device, and compliance with regulations. 
11.5 Source Documents / Case Report Forms 
Adequate records will be maintained for the study including subject medical and surgical 
records, signed ICFs, and device use records. All original source documentation will remain at 
the investigative site. Study data that are stored at the investigator site in any electronic medical 
records system, including measurements that are obtained electronically, will be printed and 
retained in the study files. 
 
All study data will be recorded onto CRFs designed for the study. Copies of the CRFs will be 
retained with the Sponsor-investigator’s study files. 
11.6 Deviation from the Protocol 
The sponsor investigator will not intentionally deviate from the protocol without prior IRB 
approval, unless such deviation is necessary to manage a medical or ocular urgency or 
emergency. The sponsor investigator will notify the IRB of any protocol deviation to protect the 

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life, vision, or physical well-being of a subject in an emergency. Such notice shall be given as 
soon as possible, but in no event any later than 5 working days after the emergency occurred. All 
other revisions and/or amendments to the protocol that affect subject treatment, study outcome, 
or subject safety should be submitted in writing to the IRB for approval prior to implementation. 
The sponsor investigator should maintain a record of all protocol deviations showing the dates 
of, and the reason for, each protocol deviation. 
 
Changes that affect the scientific soundness of the study or the rights, safety, or welfare of 
human subjects may also require FDA approval, in addition to sponsor and IRB approval, prior 
to implementation. The sponsor investigator will obtain such approvals, if required, according to 
the regulations found in 21 CFR 812.35. 
 

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12.0 PROTOCOL REFERENCE LIST 
 
1. 
Woog, J.J., The incidence of symptomatic acquired lacrimal outflow obstruction among 
residents of Olmsted County, Minnesota, 1976-2000 (an American Ophthalmological 
Society thesis). Trans Am Ophthalmol Soc, 2007. 105: p. 649-66. 
2. 
Shin, J.H., Y.D. Kim, and K.I. Woo, Impact of epiphora on vision-related quality of life. 
BMC Ophthalmol, 2015. 15: p. 6. 
3. 
Mandeville, J.T. and J.J. Woog, Obstruction of the lacrimal drainage system. Curr Opin 
Ophthalmol, 2002. 13(5): p. 303-9. 
4. 
Perena, M.F., et al., Nasolacrimal polyurethane stent placement: preliminary results. Eur 
J Ophthalmol, 2001. 11(1): p. 25-30. 
5. 
Song, H.Y., et al., Nonsurgical placement of a nasolacrimal polyurethane stent. 
Radiology, 1995. 194(1): p. 233-7. 
6. 
Song, H.-Y., et al., Nasolacrimal duct stenting. Tech Vasc Interv Radiol, 1999. 2(1): p. 
32-38. 
7. 
Yazici, B., Z. Yazici, and M. Parlak, Treatment of nasolacrimal duct obstruction in 
adults with polyurethane stent. Am J Ophthalmol, 2001. 131(1): p. 37-43. 
8. 
Fayers, T., et al., Lacrimal surgery success after external dacryocystorhinostomy: 
functional and anatomical results using strict outcome criteria. Ophthalmic Plast 
Reconstr Surg, 2009. 25(6): p. 472-5. 
9. 
Lee, J.S., et al., Clinical efficacy of the polyurethane stent without fluoroscopic guidance 
in the treatment of nasolacrimal duct obstruction. Ophthalmology, 2000. 107(9): p. 1666-
70. 
10. 
Pabon, I.P., et al., Nasolacrimal polyurethane stent placement for epiphora: technical 
long-term results. J Vasc Interv Radiol, 2001. 12(1): p. 67-71. 
11. 
Kintzel, P.E., L.B. Michaud, and M.K. Lange, Docetaxel-associated epiphora. 
Pharmacotherapy, 2006. 26(6): p. 853-67. 
12. 
Fayet, B., E. Racy, and M. Assouline, Complications of standardized endonasal 
dacryocystorhinostomy with unciformectomy. Ophthalmology, 2004. 111(4): p. 837-45. 
13. 
Hartikainen, J., et al., Prospective randomized comparison of external 
dacryocystorhinostomy and endonasal laser dacryocystorhinostomy. Ophthalmology, 
1998. 105(6): p. 1106-13. 
14. 
Lee, H., et al., Clinical effectiveness of monocanalicular and bicanalicular silicone 
intubation for congenital nasolacrimal duct obstruction. J Craniofac Surg, 2012. 23(4): p. 
1010-4. 
15. 
Zuercher, B., et al., Analysis of functional and anatomic success following endonasal 
dacryocystorhinostomy. Ann Otol Rhinol Laryngol, 2011. 120(4): p. 231-8. 
16. 
Hartikainen, J., et al., Prospective randomized comparison of endonasal endoscopic 
dacryocystorhinostomy and external dacryocystorhinostomy. Laryngoscope, 1998. 
108(12): p. 1861-6. 
17. 
Pe, M.R., et al., Ritleng intubation system for treatment of congenital nasolacrimal duct 
obstruction. Arch Ophthalmol, 1998. 116(3): p. 387-91. 

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18. 
Mullner, K., Ritleng intubation set: a new system for lacrimal pathway intubation. 
Ophthalmologica, 2000. 214(4): p. 237-9. 
19. 
Anastas, C.N., M.J. Potts, and J. Raiter, Mini Monoka silicone monocanalicular lacrimal 
stents: Subjective and objective outcomes. Orbit, 2001. 20(3): p. 189-200. 
20. 
Chiang, S.Y., Self-securing monocanalicular stent for treatment of nasolacrimal duct 
obstruction. J Med Sci, 2004. 24(4): p. 199-204. 
21. 
Yalaz, M., et al., Lacrimal intubation with the Ritleng system in recurrent congenital 
nasolacrimal duct obstruction in children. ORL J Otorhinolaryngol Relat Spec, 2004. 
66(1): p. 35-7. 
22. 
Naik, M.N., et al., Management of canalicular lacerations: epidemiological aspects and 
experience with Mini-Monoka monocanalicular stent. Am J Ophthalmol, 2008. 145(2): p. 
375-380. 
23. 
Pelit, A., et al., Silicone intubation with the Ritleng method using intranasal endoscopy to 
treat congenital nasolacrimal duct obstruction. Int J Pediatr Otorhinolaryngol, 2009. 
73(11): p. 1536-8. 
24. 
Fayet, B., et al., Pushed monocanalicular intubation. Pitfalls, deleterious side effects, and 
complications. J Fr Ophtalmol, 2011. 34(9): p. 597-607. 
25. 
Fayet, B., et al., Pushed monocanalicular intubation: an alternative stenting system for 
the management of congenital nasolacrimal duct obstructions. J AAPOS, 2012. 16(5): p. 
468-72. 
26. 
Hussain, R.N., H. Kanani, and T. McMullan, Use of mini-monoka stents for 
punctal/canalicular stenosis. Br J Ophthalmol, 2012. 96(5): p. 671-3. 
27. 
Nam, S.M., Microscope-assisted reconstruction of canalicular laceration using Mini-
Monoka. J Craniofac Surg, 2013. 24(6): p. 2056-8. 
28. 
Zadeng, Z., M. Singh, and U. Singh, Role of lacrimal canalicular trephination and mini-
monoka stent in the management of idiopathic distal canalicular obstructions: our 
experience of 23 cases Asia Pac J Ophthalmol (Phila), 2014. 3(1): p. 27-31. 
29. 
Oh, J.R., et al., Change in quality of life of patients undergoing silicone stent intubation 
for nasolacrimal duct stenosis combined with dry eye syndrome. Br J Ophthalmol, 2015. 
99(11): p. 1519-22. 
30. 
Orge, F.H. and S.A. Dar, Canalicular laceration repair using a viscoelastic injection to 
locate and dilate the proximal torn edge. J AAPOS, 2015. 19(3): p. 217-9. 
31. 
Fayers, T. and P.J. Dolman, Bicanalicular silicone stents in endonasal 
dacryocystorhinostomy: results of a randomized clinical trial. Ophthalmology, 2016. 
123(10): p. 2255-9. 
32. 
Rajabi, M.T., et al., Bicanalicular versus monocanalicular intubation after failed probing 
in congenital nasolacrimal duct obstruction. Int J Ophthalmol, 2016. 9(10): p. 1466-
1470. 
33. 
Alam, M.S., N.S. Mehta, and B. Mukherjee, Anatomical and functional outcomes of 
canalicular laceration repair with self retaining mini-MONOKA stent. Saudi J 
Ophthalmol, 2017. 31(3): p. 135-139. 
34. 
Eshraghi, B., M. Jamshidian-Tehrani, and A. Mirmohammadsadeghi, Comparison of the 
success rate between monocanalicular and bicanalicular intubations in incomplete 
complex congenital nasolacrimal duct obstruction. Orbit, 2017. 36(4): p. 215-217. 

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35. 
Eshraghi, B., et al., Pushed monocanalicular intubation versus probing for the treatment 
of simple and incomplete complex types of congenital nasolacrimal duct obstruction in 
children older than 18 months old. Orbit, 2017. 36(4): p. 218-222. 
36. 
Khatib, L., et al., Use of the Masterka for complex nasolacrimal duct obstruction in 
children. J AAPOS, 2017. 21(5): p. 380-383. 
37. 
Singh, S., et al., Canalicular lacerations: Factors predicting outcome at a tertiary eye 
care centre. Orbit, 2017. 36(1): p. 13-18. 
38. 
Tavakoli, M., et al., Traumatic canalicular laceration repair with a new monocanalicular 
silicone tube. Ophthalmic Plast Reconstr Surg, 2017. 33(1): p. 27-30. 
39. 
Fayet, B., et al., Intralacrimal migration of Masterka((R)) stents. J Fr Ophtalmol, 2018. 
41(3): p. 206-211. 
40. 
Or, L., D. Zadok, and M.E. Hartstein, Mini-monoka stenting for patients with perennial 
allergic conjunctivitis. Orbit, 2018: p. 1-5. 
41. 
Hii, B.W., A.A. McNab, and J.D. Friebel, A comparison of external and endonasal 
dacryocystorhinostomy in regard to patient satisfaction and cost. Orbit, 2012. 31(2): p. 
67-76. 
42. 
Ho, A., et al., Quality of life assessment after non-laser endonasal 
dacryocystorhinostomy. Clin Otolaryngol, 2006. 31(5): p. 399-403. 
43. 
Jutley, G., et al., Patient satisfaction following endoscopic endonasal 
dacryocystorhinostomy: a quality of life study. Eye (Lond), 2013. 27(9): p. 1084-9. 
44. 
Nour, R., A. Robson, and G. Ainsworth, The impact of dacryocystorhinostomy (DCR) on 
the quality of life in patients with epiphora, as assessed by the Glasgow Benefit 
Inventory, in Poster presented at: BACO International. Manchester, UK. 
45. 
Sipkova, Z., et al., Assessment of patient-reported outcome and quality of life 
improvement following surgery for epiphora. Eye (Lond), 2017. 31(12): p. 1664-1671. 
46. 
Smirnov, G., et al., Symptom score questionnaire for nasolacrimal duct obstruction in 
adults--a novel tool to assess the outcome after endoscopic dacryocystorhinostomy. 
Rhinology, 2010. 48(4): p. 446-51. 
47. 
Spielmann, P.M., et al., The impact of endonasal dacryocystorhinostomy (DCR), on 
patient health status as assessed by the Glasgow benefit inventory. Rhinology, 2009. 
47(1): p. 48-50. 
 
 
 
 

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Appendix A: Glasgow Benefit Inventory (Adapted) 
 
THE GLASGOW HEALTH STATUS QUESTIONNAIRES 
MANUAL, 1998 
 
Introduction 
 
The overall success of any medical or surgical intervention cannot be obtained from measures of 
technical success alone and changes in patient quality of life resulting from the intervention must 
also be considered. Another area of interest is the state quality of life patients have due to their 
health problem. 
 
While there are existing measures of health status and patient satisfaction which can be used to 
assess state quality of life and changes brought about by ORL interventions; none of these 
measures were generated specifically for the ORL department. Therefore, limitations such as 
length, administration style and insensitivity to nonacute disorders, like those generally seen in an 
ORL clinic, mean that the evaluations generated from these measures for ORL interventions are 
not as sensitive as when these measures are used to assess other interventions. It was, therefore, 
decided to generate two health status questionnaires, a state questionnaire and a change 
questionnaire, which would be specifically sensitive to ORL health problems and interventions but 
also generalizable across different ORL health problems and interventions. The questions are 
independent of any specific intervention/health condition and the subject of the questions remains 
constant. Each of the questions addresses an aspect of health-related quality of life which is not 
dependent on the disease of interest or the context of the intervention. However, the text is altered 
for each question to allow focusing on to the intervention or health condition of interest to improve 
sensitivity. The questions are then generic in nature but referenced to a temporal event 
(intervention) in the GBI or condition in the GHSI. 
 
The change questionnaire, called the Glasgow Benefit Inventory (GBI), measures the change in 
health status produced by surgical interventions. For this measure, the definition of health status 
is the general perception of well-being, including total psychological, social and physical well-
being. Given that maximal sensitivity to change was critical, it was decided to ask directly about 
the change in health status resulting from surgery, rather than take pre- and post- operative 
measures and subtracting one from the other. The paper, (pages 18 to 31), shows the findings of a 
study investigating the sensitivity of the GBI to the change in health status resulting from 5 
different ORL interventions. 
 
The state measure we developed is called the Glasgow Health Status Inventory, (GHSI) which 
measures the effect of a health problem on the quality of life of a person and allows cross-

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comparison among many health conditions, among different health interventions, and among 
demographic and cultural subgroups.  
 
The GBI is a post-intervention questionnaire which assesses the interventions effects on the health 
status of the patients. The GHSI can be used at any point in time and measures the general quality 
of life the person experiences and how health problems affect this. While the GBI is maximally 
sensitive to a change in health status brought about by a specific event (e.g. an operation), the 
GHSI gives a general measure of the health status of the person at any specific time. 
 
GBI - Glasgow Benefit Inventory 
 
The GBI contains 18 change in health status questions which assess how the intervention has 
altered the quality of life of the person. The GBI is easily adapted to be used for different 
interventions. Before use, the GBI must be adapted so that the intervention of interest is 
specified. This is done by replacing the words in italics (operation/intervention) in each question 
into the intervention of interest. See the examples below. GBI was developed and validated as a 
measure of patient health for otorhinolaryngological procedures. It has been validated for use 
following oculoplastic procedures, including DCR 19,20,21,22,23, ptosis 24,25, ectropion and 
entropion surgery 26, and botulinum toxin for blepharospasm 27. 
 
Example of all-purpose GBI question: 
 Since your operation/intervention*, have you found it easier or harder to deal with 
company? 
 
Examples of focused GBI questions: 
Since your operation, have you found it easier or harder to deal with company? 
Since your received your hearing aid, have you found it easier or harder to deal with company? 
Since your speech therapy, have you found it easier or harder to deal with company? 
Does the condition of your nose affect how you deal with company? 
 
 
Scoring 
 
The response to each question is based on a five-point Likert scale ranging from a large deterioration in 
health status through to a large improvement in health status, (see example below). 
 
 
 
 
 

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1. Has the result of the operation/intervention* affected the things you do? 
 
 
Much  
A little or 
No 
A little or 
Much 
 
worse 
somewhat 
change 
somewhat  
better  
 
 
 
worse 
 
better 
  
    1 
     2 
   3 
       4 
        5  
 
 
 
To help control for response bias, half of the questions have the answers ranging from a large 
improvement to a large deterioration while the other half range the other way. The GBI 
questionnaire is scored into a total score and also 3 subscales:- a general subscale, (12 questions), 
a social support subscale, (3 questions), and a physical health subscale, (3 questions). All these 
scores range from –100 to +100. 
 
Score all questions so that a score of 1 is given to the answer with the worst change in health status 
and 5 to the answer with the best change in health status. 
 
Total Score 
- 
Sum all the responses (Qu. 1-18) 
- 
Divide by 18 (to obtain an average response score) 
- 
Subtract 3 from the average response score 
- 
Multiply by 50. 
 
General Subscale Score 
- 
Sum 12 of the responses (Qu. 1,2,3,4,5,6,9,10,14,16,17 and 18) 
- 
Divide by 12 (to obtain an average response score) 
- 
Subtract 3 from the average response score 
- 
Multiply by 50. 
 
Social Support Score 
- 
Sum 3 of the responses (Qu. 7,11,15) 
- 
Divide by 3(to obtain an average response score) 
- 
Subtract 3 from the average response score 
- 
Multiply by 50. 
 
Physical Health Score 
- 
Sum 3 of the responses (Qu. 8,12,13) 
- 
Divide by 3(to obtain an average response score) 
- 
Subtract 3 from the average response score 
- 
Multiply by 50. 
 

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The GBI questionnaire (Modified for this study): 
 
1. Has the result of the tear duct surgery affected the things you do? 
 
 
Much  
A little or 
No 
A little or 
Much 
 
worse 
somewhat 
change 
somewhat  
better  
 
 
 
worse 
 
better 
  
    1 
     2 
   3 
       4 
        5  
 
 
 
2. Have the results of the tear duct surgery made your overall life better or worse? 
 
 
Much  
A little or 
No 
A little or 
Much 
 
better 
somewhat 
change 
somewhat  
worse  
 
 
 
better 
 
worse 
  
    5 
     4 
   3 
       2 
        1  
 
 
 
3. Since your tear duct surgery, have you felt more or less optimistic about the 
future? 
 
 
Much more 
More 
No 
Less 
Much less 
 
optimistic 
optimistic 
change 
optimistic 
optimistic 
 
    5 
     4 
   3 
       2 
        1  
 
 
 
4. Since your tear duct surgery, do you feel more or less embarrassed when with 
a group of people? 
 
 
Much more 
 More 
No 
Less 
Much less 
 
embarrassed  embarrassed change            embarrassed     embarrassed 
 
    1 
   2 
   3 
   4 
    5 
 
 
 
 
5. Since your tear duct surgery, do you have more or less self-confidence? 
 
 
Much more 
More self- 
No 
Less self- 
Much less 
       self-confidence 
confidence 
change 
confidence 
self-confidence 
 
    5 
     4 
   3 
       2 
        1  
 
 
 
 
 
 
 

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6. Since your tear duct surgery,  have you found it easier or harder to deal with 
company? 
 
 
Much 
Easier 
No 
Harder 
Much 
 
easier 
 
change 
 
harder 
 
    5 
     4 
   3 
       2 
        1  
 
 
 
7. Since your tear duct surgery, do you feel that you have more or less support 
from your friends? 
 
 
Much 
More 
No 
Less 
Much 
 
more support support 
change 
support 
less support 
 
    5 
     4 
   3 
       2 
        1    
 
 
 
8. Have you been to your family doctor, for any reason, more or less often, since 
your tear duct surgery? 
 
 
Much more 
More 
No 
Less 
Much less 
 
often 
often 
change 
often 
often 
 
    1 
   2 
   3 
   4 
    5 
 
 
 
 
9. Since your tear duct surgery, do you feel more or less confident about job 
opportunities? 
 
 
Much  
More 
No 
Less 
Much 
    more confident 
confident 
change 
confident 
less confident 
 
    5 
     4 
   3 
       2 
        1  
 
 
 
10. Since your tear duct surgery, do you feel more or less self-conscious? 
 
 
Much more 
More self- 
No 
Less self- 
Much less 
 
self-conscious conscious 
change 
conscious 
self-conscious 
 
    1 
   2 
   3 
   4 
    5 
 
 
 
 
11. Since your tear duct surgery, are there more or fewer people who really care 
about you? 
 
 
 
Many 
More 
No 
Fewer 
Many 
 
more people 
people 
change 
people              fewer people 
 
    5 
     4 
   3 
       2 
        1  
 
 
 

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12. Since you had the tear duct surgery, do you catch colds or infections more or 
less often? 
 
 
 
Much more 
More 
No 
Less 
Much less 
 
often 
often 
change 
often 
often 
 
    1 
   2 
   3 
   4 
    5 
 
 
 
 
13. Have you had to take more or less medicine for any reason, since your tear 
duct surgery? 
 
 
Much more 
More 
No 
Less 
Much less 
 
medicine 
medicine 
change 
medicine 
medicine 
 
    1 
   2 
   3 
   4 
    5 
 
 
 
 
14. Since your tear duct surgery, do you feel better or worse about yourself? 
 
 
Much 
Better 
No 
Worse 
Much 
 
better 
 
change 
 
worse 
 
    5 
     4 
   3 
       2 
    1 
 
 
 
 
15. Since your tear duct surgery, do you feel that you have had more or less 
support from your family? 
 
 
Much more 
More 
No 
Less 
Much less 
 
support 
 support 
change 
support 
support 
 
    5 
     4 
   3 
       2 
      1  
 
 
 
16. Since your tear duct surgery, are you more or less inconvenienced by your 
tearing problem? 
 
Much more 
     More 
   No 
Less 
Much less 
inconvenienced    inconvenienced    change         inconvenienced      inconvenienced 
  
    1 
      2 
     3 
   4 
    5 
 
 
 
 
 
 
 
 
 
 
 

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17. Since your tear duct surgery, have you been able to participate in more or 
fewer social activities? 
 
 
Many more 
More 
No 
Fewer 
Many fewer 
 
activities 
activities 
change 
activities 
activities 
 
    5 
     4 
   3 
       2 
        1  
 
 
 
18. Since your tear duct surgery, have you been more or less inclined to withdraw 
from social situations? 
 
 
Much more 
More 
No 
Less 
Much less 
 
inclined 
inclined 
change 
inclined 
inclined 
 
    1 
   2 
   3 
   4 
    5 
 
 
 
 
 
 
 

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GLASGOW BENEFITS INVENTORY REFERENCES 
 
 
1 
McDowell I,Newell C. Measuring health: A guide to rating scales and questionnaires. 
Oxford:Oxford University Press. 
 
2 
Bowling A. Measuring health. A review of quality of life measurement scales. Milton 
Keynes:Open University Press. 
 
3 
Wilkin D,Hallam L,Doggett M-A. Measures of need and outcome for primary health care. 
Oxford:Oxford University Press. 
 
4 
Anderson RT, Aaronson NK, Wilkin D. Critical review of the international assessments of 
health-related quality of life.Qual Life Res 1993;2:369-95 
 
5 
Bergner M,Bobbitt RA,Carter WB,Gilson BS.   The Sickness Impact Profile: Development 
and final revision of a health status measure. Med Care 1981;19:787-805. 
 
6 
Patrick DL, Peach H, Gregg I.   Disablement and care: a comparison of patient views and 
general practitioner knowledge.   J R Coll Gen Pract 1982; 32:429-34. 
 
7 
Hunt SM,McEwan J,McKenna SP. Measuring health status. London:Croom Helm,1986. 
 
8  
Hunt SM, McEwan J, McKenna SP. Subjective health assessments and the perceived 
outcome of minor surgery. J Psychosom Res 1984; 28:105-14 
 
9 
Ware JE,Sherbourne CD. The MOS 36-item short-form health survey (SF 36).   I. 
Conceptual framework and item selection.   Med Care 1992;30:473-83. 
 
10 
Ware JE  Measuring patients' views: the optimum outcome measure.   BMJ 1993;306:1429-
30. 
 
11 
Garrett AM,Ruta DA,Abdalla MI,Buckingham JK,Russell IT.   The SF-36 health survey 
questionnaire: an outcome measure suitable for routine use within the NHS? BMJ 
1993;306:1440-4. 
 
12 
Carr-Hill RA. The measurement of patient satisfaction. J Pub Health Med 1992; 14:236-
249. 
 
13 
Scriven MW,Burgess NA,Edwards EA,Morgan AR,Bundred NJ,Lewis MH. 
Cholecystectomy: a study of patient satisfaction. J R Coll Surg Edinb 1993;38:79-81. 
 
14 
World Health Organization. The first ten years of the World Health Organization. Geneva: 
World Health Organization, 1958. 
 
15 
British Society of Audiology Recommended procedures for pure-tone audiometry.   Br J 
Audiol 1981;15:213-6. 
 
16 
Summerfield Q,Marshall D (personal communication). 
 

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17 
Stewart E,Robinson K,Wilson J.A. Assessment of patient benefit from rhinoplasty Rhinol, 
in press. 
 
18 
Fairley JW. Correlation of nasal symptoms with objective findings and surgical outcome 
measurement. Master of Surgery thesis, University of London, 1993. 
 
19 
Bakri SJ, Carney AS, Robinson K, Jones NS, Downes RN. Quality of life outcomes 
following dacryocystorhinostomy: external and endonasal laser techniques compared. Orbit 
1999; 18(2): 83–88 
 
20 
Spielmann PM, Hathorn I, Ahsan F, Cain AJ, White PS. The impact of endonasal 
dacryocystorhinostomy (DCR), on patient health status as assessed by the Glasgow  benefit 
inventory. Rhinology 2009; 47(1): 48–50. 
 
21 
Feretis M, Newton JR, Ram B, Green F. Comparison of external and endonasal 
dacryocystorhinostomy. J Laryngol Otol 2009; 123(3): 315–319. 
 
22 
Ho A, Sachidananda R, Carrie S, Neoh C. Quality of life assessment after non-laser 
endonasal dacryocystorhinostomy. Clin Otolaryngol 2006; 31(5): 399–403. 
 
23 
Smirnov G, Tuomilehto H, Kokki H, Kemppainen T, Kiviniemi V, Nuutinen J et al. 
Symptom score questionnaire for nasolacrimal duct obstruction in adults—a novel tool to 
assess the outcome after endoscopic dacryocystorhinostomy. Rhinology 2010; 48:  446–
451 
 
24 
Mahroo OA, Hysi PG, Dey S, Gavin EA, Hammond CJ, Jones CA. Outcomes of ptosis 
surgery assessed using a patient-reported outcome measure: an exploration of time  effects. 
Br J Ophthalmol 2014; 98(3): 387–390 
 
25 
Maycock N, MacGregor C, Saunders DA, Parkin B. Long term patient-reported benefit 
from ptosis surgery. Eye 2015; 29: 872–874. 
 
26 
Smith HB, Jyothi SB, Mahroo OA, Shams PN, Sira M, Dey S et al. Patient-reported benefit 
from oculoplastic surgery. Eye 2012; 26(11): 1418–1423 
 
27 
MacAndie K, Kemp E. Impact on quality of life of botulinum toxin treatments for essential 
blepharospasm. Orbit 2004; 23: 207–210 

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Appendix B: Lac-Q Questionnaire 
 
 
The Lac-Q Questionnaire: 
The Lac-Q questionnaire, published in 2011, is a patient symptom questionnaire developed for  
lacrimal drainage surgery.1-2 The questionnaire contains two scores, one is specific for eye- 
symptoms, and the other assesses the social impact of symptoms. (see below)  
 
   
 
 
 
 
 
 
 
 
 

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Scores for the filled in questionnaire:  
 
Social and lifestyle impact score (sum of social impact questions) 
 
Left eye symptom score (sum of “left” column of symptom questions) 
 
Right eye symptom score (sum of “right” column of symptom questions) 
 
Lac-Q score (sum of all three total scores above) 
 
 
 
 
 
 
LAC-Q QUESTIONNAIRE REFERENCES 
 
1 
Mistry, N., Rockley, T.J., Reynolds, T., Hopkins, C., Development and validation of 
a symptom questionnaire for recording outcomes in adult lacrimal surgery. Rhinology 
2011: 48:538-545.  
2 
Sipkova, Z., Vonica, O., Olurin, O., Obi, E.E., Pearson, A.R., Assessment of patient-
reported outcome and quality of life improvement following surgery for epiphora. 
Eye 2017 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Appendix C: Patient Stent Tolerance and Irritation Assessment 
The following questions were designed specifically for this study to assess the following concepts 
of interest 1) patient tolerance of the slit-stent II, and 2) ocular surface irritation secondary to 
the stent. These questions will be administered by an interviewer to patients at both the 5-14 and 
30-120 day post-op visits.   
 
Patient Stent Tolerance and Irritation Assessment 
 
1. Which of the following five statements best describe your tolerance of the 
Stent? 
 
 
Not tolerated Tolerated  
Tolerated 
Tolerated 
Well Tolerated 
 
 
with major 
with moderate with minor 
 
 
 
 
 
discomfort  
discomfort 
discomfort 
 
4 
3 
2 
1 
0 
 
2. Since your tear duct surgery, which of the following four statements best 
describe your eye irritation symptoms caused by the Stent? 
 
 
No eye 
  Minor eye 
  Moderate eye     Severe eye 
 
irritation 
  irritation 
  irritation 
     irritation 
 
 
 
 
 
 
                                                                       
 
1 
  2 
  3 
     4 
 
 
 
 
 
 
 
Scores for the filled in questionnaire:  
 
Tolerance Score (question 1) 
Irritation Score (question 2) 
 
Total score (sum of question 1 & 2) 
 

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Appendix D: Study flow chart- 
 
Procedure 
Screen 
(within 
60 days 
of 
Surgery) 
 
Surgery    
Postoperative Visits 
Day 1 
Phone 
call 
5-14 days  
Day 45 
(30-60) 
Phone call 
30-120 days  
Month 5-7 
Informed Consent 
X 
 
 
 
 
 
 
Medical History 
X 
 
 
X 
 
X 
X 
Ocular History 
X 
 
 
X 
 
X 
X 
Medication List 
X 
X 
 
X 
 
X 
X 
Demographics 
X 
 
 
 
 
 
 
Corrected Visual 
Acuity 1 
X 
 
 
X 
 
X 
X 
Manifest Refraction 
X 
 
 
X2 
 
X2 
X2 
Lac-Q 
Questionnaire 
X 
 
 
X 
 
X 
X 
GBI Questionnaire 
 
 
 
X 
 
X 
X 
Patient Stent 
Tolerance and 
Irritation 
Assessment 
 
 
 
X 
 
X 
 
Lacrimal system 
probing/ irrigation 
X 
 
 
 
 
 
 
Intraocular Pressure 
(IOP)3 
X 
 
 
X 
 
X 
X 
Slit Lamp 
biomicroscopy 
(cornea, 
conjunctiva) 
X 
 
 
X 
 
X 
X 
Stent Culture 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
Visual inspection 
of stent integrity 
 
 
 
X 
 
X 
 
External exam 
 
 
 
X 
 
X 
X 
Complications and 
Adverse Events 
 
X 
X 
X 
X 
X 
X 
DCR Surgery 
 
X 
 
 
 
 
 
 
1 ETDRS chart at 3 meters should be used 
2 Manifest Refraction will be performed if there is 2-line or more reduction in visual acuity from Screening 
3 IOP will be measured by ICare  
 
 

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Appendix E: Manifest Refraction and Visual Acuity 
Manifest Refraction 
Beginning approximate refraction: The patient's current spectacles (if worn for distance viewing) 
are measured with a lensometer; if no spectacles, retinoscopy or auto refraction is performed. One of 
these measurements is used as the beginning approximate refraction.  
Refraction must be performed at 3 meters from ETDRS chart R. Room illumination must be kept 
consistent throughout the study (highest illumination). The beginning approximate refraction at the 
first visit can be from lensometry of the patient’s distance spectacles, retinoscopy, or autorefractor 
findings. At subsequent follow-up visits, the manifest refraction recorded at the previous visit will be 
used as the beginning approximate refraction. The phoropter or trial frame may be used for 
refraction.  
 
Begin by testing the RIGHT eye. With the beginning approximate refraction in place,  
 
Determine Sphere Power: In general, instructions are to ‘push plus’ and to add minus correction 
only if the visual acuity is thereby improved demonstrably; i.e. the patient is able to read 1 or more 
additional letters on a line or to read letters on a smaller line. With the patient looking at the smallest 
line legible on the visual acuity chart, add + 0.25 spherical lens in front of the eye. Ask the patient, 
“Is it better, worse, or no change?”  
If the patient responds that vision is made better or is the same, replace the spherical lens with one 
that is +0.25 more plus. Continue checking to see if the patient will accept more plus by repeating the 
method above. Stop when presenting the additional +0.25 lens makes the patient’s vision worse.  
If the patient’s response to adding + 0.25 is that vision is made worse, remove the +0.25, then add a 
lens which is -0.25 more minus or less plus over the eye. If this lens improves the patient’s vision, 
even by one letter, continue checking to see if the vision improves by adding minus. Stop when there 
is no improvement in vision.  
Re-challenge with +0.25 sphere as before until the patient responds that the +0.25 sphere makes the 
vision worse. The sphere endpoint is the best vision with the most plus or least minus lens power.  

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Determine and Refine Cylinder Axis: Ask the patient to look at a line on the visual acuity chart, 
which is one or two line larger than the smallest line they can read. Ask the patient to focus on a 
round letter such as “C”, “G”, or “O”.  
 
If no cylinder is present in the beginning approximate refraction, place the Jackson cross-cylinder 
with the positive axis (white) first at 90º, then at 180º, then 45º and 135º. If the patient states that the 
vision is improved at any one of these four axis positions, place cylindrical lens power in the 
refractor at the preferred axis and proceed to refine the axis. If the patient prefers no power at any of 
the four positions, skip the refining cylinder power step.  
If cylinder is present in the beginning approximate refraction, position the cross-cylinder first with 
the positive axis 45º to the right of the cylinder axis (position one), the positive axis at 45º to the left 
of the cylinder axis (position two). Flip the cross cylinder and ask which position improves the 
vision. If the patient responds that neither position is better and if this was the first test of axis 
position, move the axis of the cylinder 15º to the right or left and repeat.  
If the patient prefers one position to the other, rotate the cylinder axis toward the preferred axis of the 
crossed-cylinder. For positive cylinder, in the direction of the white dot. (When the patient states 
there is no difference upon flipping the cross cylinder, i.e. that one position of the cross cylinder is no 
better than the other position, proceed to refining cylinder power).  
 
Refine cylinder power: Ask the patient to look at a line on the visual acuity chart, which is one or 
two line larger than the smallest line they can read and ask them to focus on a round letter. 
Align the cross cylinder first with the positive axis and then with the negative axis coincident with 
the cylinder axis. Ask the patient which is better.  
If the patient prefers the positive (white) axis coincident with the cylinder axis, increase the power of 
the cylinder by 0.25 diopter.  
If the patient prefers the negative (red) axis coincident with the cylinder axis, reduce the cylinder 
power by 0.25 diopters and retest.  
For each 0.50 diopter change in cylinder power, adjust the sphere by 0.25 diopters of the opposite 
power.  
 
End the refraction: End the refraction by challenging with +0.25 spherical power and adjust the 
sphere until the patient responds that the additional positive sphere makes the vision worse.  
Record the lens correction obtained in this refraction for the eye on the CRF.  
Visual Acuity  
Begin by testing the RIGHT eye. Best-corrected visual acuity will be measured at 3 meter using 
ETDRS charts. Chart 1 will be used for the right eye and Chart 2 for the left eye. Room lighting 
should be at maximum brightness. 

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Record each letter identified correctly by circling the corresponding letters on the Visual Acuity 
Form. Letters read incorrectly and letters for which no guesses are made are not marked on the 
form. Each letter read correctly is scored as one point. Record the total number of letters read 
correctly. The score for each line (which is zero if no letters are read correctly) and the total score 
for each eye is recorded on the Visual Acuity Form (CRF) after testing is completed. 
 
Record the visual acuity in Snellen Equivalents as the lowest line read with one or no misses.  
Repeat the entire process for the left eye. 
 
 
 
 

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