A Prospective Randomized Trial Comparing Cataract Surgery as Stand Alone and Cataract Surgery Combined With Kahook Dual Blade Glide Goniotomy or Istent Inject W Trabecular Micro-Bypass Stent in Open-Angle Glaucoma.
Phase: NA
Conditions: Open Angle Glaucoma, Cataract, Kahook Dual Blade Glide, Istent Inject W, MIGS, Goniotomy
Sponsor: Umeå University

1 
 
The SMIGS-study  
(Swedish MicroInvasive Glaucoma Surgery Study) 
 
A Prospective Randomized (Multiarm) Study Comparing Cataract Surgery 
as Stand Alone and Cataract Surgery Combined with Kahook Dual Blade 
Glide Goniotomy or iStent Inject W Trabecular Micro-Bypass Stent in 
Open-Angle Glaucoma. 
 
NCT05035394 
 
Date of the document: Oct 18, 2022 

2 
 
Statistical Analysis Plan and Study Protocol 
 
Principal Investigator  
 
Anna Barkander, MD 
Protocol identification number 
2021-02970 
ClinicalTrials.gov identifier  
NCT05035394 
Date 
 
 
 
 
October 18, 2022 
Version 
 
 
 
1.0 
Corresponding Author 
 
Anna Barkander, MD  
- 
Department of Clinical Sciences, Ophthalmology, 
Umeå University, Umeå, Sweden 
- 
Eye clinic, Östersund Hospital, Region Jämtland 
Härjedalen, Sweden 
 
 
Contributing authors   
 
Gauti Jóhannesson, MD, PhD 
- 
Department of Clinical Sciences, Ophthalmology, 
Umeå University, Sweden.  
- 
Wallenberg Centre for Molecular Medicine, Umeå 
University, Sweden 
 
M A Economou, MD, PhD 
- 
Division of Ophthalmology and Vision, Department of 
Clinical Neuroscience, Karolinska Institutet, 
Stockholm, Sweden 
Senior statistician responsible 
Anna Lindam, PhD 
- 
Unit of Research, Education and Development, 
Östersund Hospital. Region Jämtland Härjedalen, 
Sweden 
- 
Affiliation: Department of Public Health and Clinical 
Medicine, Umeå University, Sweden 
 
 
 

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Table of Contents 
1.0 Introduction…………………………………………………….………….….………………6 
1.1 Background and rationale………………………………….…….….………………...6 
1.2 Objectives………………………………………………………...…………………...6 
2.0 Clinical Procedures………………………………………………….……….….…………….7 
2.1 Visual acuity with Snellen………………………………………...……….………….7 
2.2 Testing for finger counting…………………………………………...……………….7 
2.3 Testing for hand motions……………………………………….…….….……………7 
2.4 Testing for light perception…………………………………….……….….………….7 
2.5 Subjective refraction…………………………………………….………………....….7 
2.6 Slit lamp biomicroscopy……………………………………….….….……………….8 
2.7 Goldmann applanation tonometry…………………………….…….….….………….8 
2.8 Gonioscopy………………………………………………………. …….…….………8 
2.9 Perimetry………………………………………………………….….……….……….8 
2.10 
Pachymetry………………………………………………………………………..8 
2.11 
Quality of life assessment……………………………………….….…….……….9 
3.0 Surgical Procedures……………………………………………………………….….….……9 
3.1 Cataract extraction…………………………………………………….….…..….……9 
3.2 Kahook Dual Blade Glide…………………...………………………………. …….…9 
3.3 iStent Inject W………………………………………………………………….……10 
4.0 Postoperative Care……………….….……………………………………………….………10 
5.0 Policy Matters………………………………………………………………………….….…11 
5.1 Participant consent……………………………………………………….….…….…11 
6.0 Clinical Center Procedures………………………………………….….……………………11 

4 
 
6.1 Qualifying assessment………………………………………………………….……11 
6.2 Assignment of participant identification number………………………….….….….11 
6.3 Schedule of visits…………………………………………………………….………11 
7.0 Study Methods………………………………………………………………………….……12 
7.1 Trial design…………………………………………………………….…………….12 
7.2 Randomization……………………………………………………………………….13 
7.3 Sample size calculation………………………………………………………………13 
7.4 Framework……………………………………………………………………….…..13 
7.5 Statistical interim analyses and stopping guidelines…………………………………13 
7.6 Timing of final analyses………………………………...……………………………14 
7.7 Timing of outcome assessments……...…………………………….….……….……14 
8.0 Statistical Principles………………………………………………………………………….14 
8.1 Confidence intervals and P values……………...……………………………………14 
8.2 Adherence and protocol deviations………………………….……………………….14 
8.3 Analysis populations…………………...…………………………………………….15 
9.0 Trial Population…………………………………………………………….….…………….15 
9.1 Screening data………………………………………………………….…………….15 
9.2 Eligibility……………………………………….……………………………………15 
9.3 Recruitment……………………………………………….……………………….…15 
9.4 Withdrawal/follow-up……………………………………………………….……….16 
9.5 Baseline participant characteristics……………………….……………………….…16 
10.0 
Analysis………………………………………………………………………….……….16 
10.1 
Data management and security………….….……………………………………16 
10.2 
Outcome definitions……………………...………………………………………16 

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10.3 
Analysis methods…………...……………………………………………………17 
10.4 
Missing data……………………………………………………………………...18 
10.5 
Harms……………………...……………………………………….…………….18 
10.6 
Statistical software……………………………………………………………….19 
11.0 
References………………………………………………………..………………………19 
12.0 
CONSORT flow chart……………………………………………………………………20 
 
Abbreviations 
AC = anterior chamber; BCVA = best corrected visual acuity;  BSS = balanced salt solution; dB 
=decibels; GAT = Goldman applanation tonometry; IOP = intraocular pressure; I/A = 
irrigation/aspiration; IQR = inter-quartile range; KDB = Kahook Dual Blade; LogMAR = 
logarithm of the minimum angle of resolution; MD = mean deviation; MIGS = microinvasive 
glaucoma surgery; PEXG = pseudoexfoliation glaucoma; POAG = primary open-angle 
glaucoma; SC = Schlemm’s canal; SD = standard deviation; TCP = transscleral 
photocoagulation; TM = trabecular meshwork. 
 
 
 
 
 
 
 
 
 
 
 
 

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1. Introduction  
1.1 Background and rationale 
Kahook Dual Blade Glide (New World Medical Inc, CA, USA) and iStent Inject W 
(Glaukos Corp, CA, USA) are two microinvasive Schlemm’s canal (SC) surgeries that 
can be performed in combination with cataract extraction. Although KDB and iStent are 
in clinical use around the world, there is a need for prospective randomized trials, 
showing it´s efficacy over time. A three-arm trial with Kahook Dual Blade Glide (KDB), 
iStent Inject W (iStent) and cataract extraction as stand-alone has not been conducted 
before.  
If KDB and/or iStent in combination with cataract extraction result in better intraocular 
pressure (IOP)-control over time compared to cataract extraction alone, this can have 
important implications for the increasing glaucoma population. If glaucoma patients that 
receive KDB or iStent in addition to cataract surgery get a lower IOP compared to 
patients that receive cataract surgery as stand-alone, they may get less visual field 
progression over time and/or need less medications compared to patients that do not 
receive this treatment.  
1.2 Objectives 
The objective of this project is to test - in a single-center multi-arm randomized clinical 
trial (RCT), if KDB and/or iStent in combination with cataract extraction, result in better 
IOP-control over time, compared to cataract extraction as stand-alone. iStent is a more 
widespread and studied procedure compared to KDB, although retrospective studies have 
found a trend toward better efficacy of KDB compared to iStent.1 2 The rational for using 
a multi-arm design is to investigate whether KDB and iStent are equally effective, and to 
see if they differ in terms of adverse events. Since cataract surgery as stand-alone can 
have an IOP-lowering effect,3 there is a rational for using this group as one of the 
treatment arms as well.  
We hypothesize that participants receiving KDB or iStent in combination with cataract 
surgery will have a larger IOP-reduction and/or less need for IOP-lowering medications 
postoperatively, compared to participants receiving cataract surgery as stand-alone. Over 
time there may even be less need for further surgery for participants receiving KDB 
and/or iStent. We further hypothesize that IOP will not be significantly different between 
eyes receiving KDB and iStent, but there may be differences in number of reduced 
medications postoperatively.  
The study will be conducted according to the Declaration of Helsinki and the principles 
of good clinical practice.  

7 
 
2. Clinical Procedures 
2.1 Visual acuity with Snellen 
Visual acuity is measured before pupil dilation, tonometry, gonioscopy or any other 
technique that may affect vision.  
Snellen visual acuity is measured using any standard visual acuity chart. Standardized 
refraction is performed prior to Snellen visual acuity testing. The fellow eye is properly 
occluded, and the participant is not allowed to lean forward or backward, so that a 
constant testing distance is maintained. After proper instruction and refraction, 
progressively smaller lines are presented to the participant until two or more errors in a 
line are made. When the participant is unable to read a letter, the examinator encourages 
the participant to guess. If two letters on a line are missed, a second chance is provided 
by asking the participant to read the line backwards. The Snellen visual acuity is recorded 
as the smallest line in which the participant misses one or fewer optotypes. If the 
participant´s visual acuity is so poor that the 20/400 line cannot be read, finger counting 
is tested. Visual acuity will be tested within two (preferable one) months before surgery, 
and thereafter at each visit up until five years after surgery. 
2.2 Testing for finger counting 
After proper instruction and refraction, the examiner´s hand is viewed at a distance of 
two feet (approximately 60 cm) from the participant´s eye. The fellow eye is occluded. If 
the number of fingers presented cannot be identified, hand motion is tested. 
2.3 Testing for hand motions 
In testing for hand motion, the examiner´s hand is viewed with all fingers extended and 
separated at a distance of two feet (approximately 60 centimeters) from the participant´s 
eye. The fellow eye is occluded. If hand motions cannot be identified, light perception is 
tested. 
2.4 Testing for light perception 
Light perception is tested using the same complete occlusion of the fellow eye with no 
other bright lights visible from the participant´s position. The participant is asked to 
report “on” when he or she sees the light, and “off” when it disappears. 
2.5 Subjective refraction 
An approximate beginning refraction may be determined by automated or subjective 
refraction from a prior visit. 

8 
 
2.6 Slit lamp biomicroscopy 
Slit lamp biomicroscopy may be performed with any commercially available instrument, 
and it is used in a standard fashion starting anteriorly and working posteriorly. 
2.7 Goldmann applanation tonometry 
The calibration of the Goldmann applanation tonometry (GAT) is checked as described 
by the manufacturer. One drop with premixed fluorescein and anesthetic is instilled in the 
eye and the participant´s head is properly positioned in the chin rest and against the 
forehead rest without leaning forward or straining. The participant is asked to look 
straight ahead and is instructed not to hold his or her breath. The investigator looks 
through the slit lamp and gently brings the tip of the prism in contact with the center of 
the cornea. The investigator adjusts the measuring drum until the inner borders of the two 
mires just touch each other. When the “two-person method” is used, the investigator is 
performing the measurement as described above, and an assistant are recording the IOP 
measurement. Pre-operatively at least two IOP-recordings will be performed within two 
months, and at least one of those with the two-person method. The two-person method is 
used at postoperative controls up to two years after surgery. Participants will be followed 
annually for up to five years after surgery with applanation tonometry and visual field 
testing. These controls will be performed by an examinator not involved in the trial. 
2.8 Gonioscopy 
Gonioscopy is performed with the participant sitting at the slit lamp using a gonioscopy 
lens to examine the anterior chamber for grading of depth. Gonioscopy will be performed 
preoperatively in all participants, and at six, 12 and 24 months for participants receiving 
KDB or iStent. Postoperative gonioscopy is performed to evaluate placement of stents in 
the iStent-group, and presence of scarring or synechia in the KDB-group.   
2.9 Perimetry 
Perimetry is performed before surgery (within three months) and after six,12 and 24 
months. Thereafter yearly examinations up until five years after surgery. Perimetry is 
performed before tonometry and gonioscopy. Standardized refraction is performed to 
determine the participant´s distance refraction and visual acuity prior to visual field 
testing. Standard automatic perimetry with Humphrey ® Field Analyzer (SITA faster) is 
used, and the technician is monitoring the participant during testing. 
2.10 
Pachymetry 
Pachymetry is performed within six months prior to surgery. 

9 
 
2.11 
Quality-of-life assessment 
Participants will be asked to perform a quality-of-life assessment preoperatively and after 
six months, using the National Eye Institute Visual Function Questionnaire (25 items) 
(NEI-VFQ25). 
3. Surgical Procedures 
3.1 Cataract extraction 
Cataract extraction is performed in a standardized fashion. Prior to surgery, topical 
cyclopentolate (Cyclopentolat ®) 1% and tetracaine (Tetrakain ®) 1% is instilled in the 
eye. In the beginning of surgery an intracameral mixture of phenylephrine (0.2 mg/ml), 
lidocaine (3.1 mg/ml) and tropicamide (10 mg/ml) (Mydrane ®) is given. Intracameral 
cefuroxime (Aprokam ®) 1 mg and ampicilline (Doktacillin ®) 0.1 mg is given at the end 
of surgery, which is standardized routine at the clinic. 
3.2 Kahook Dual Blade Glide 
In this study, goniotomy with KDB is done after cataract surgery has been successfully 
performed. The anterior chamber is filled with additional cohesive viscoelastic, and the 
operating microscope is tilted about 35°, while the head of the participant is turned 35° 
from the surgeon to ensure an optimal view into the chamber angle.  
The previously made temporal cataract incision is used. After the goniotomy with KDB, 
all viscoelastic is removed with the I/A instrument and the eyed is filled with balanced 
salt solution (BSS). Intracameral cefuroxime 1 mg and ampicilline 0.1 mg is given at the 
end of surgery. 
KDB is designed to excise a strip of the trabecular meshwork and inner wall of SC, while 
minimizing damage to adjacent structures. The KDB has a distal tip that pierces the 
trabecular meshwork (TM), enters SC, and as it is advanced along the trajectory of the 
canal, elevates the TM up toward two parallel blades that excise a strip of TM, leaving a 
clear path for aqueous humor to drain into SC and the distal collector channels. This 
excisional technique removes between three to five clock hours of TM.  
In 2020, the FDA approved a second-generation KDB instrument (KDB Glide, New 
World Medical), that has incorporated features intended to enhance both its performance 
and its ease of use. The KDB Glide has incorporated beveled edges and rounded corners 
to the footplate, reducing its width for enhanced fit within SC to facilitate smooth passage 
while excising the TM. This second-generation instrument maintains the same ramp 
technology and distance between the parallel blades (230 microns) as the original 
instrument. 

10 
 
3.3 iStent Inject W 
The iStent is inserted after cataract surgery has been successfully performed. The anterior 
chamber is filled with additional cohesive viscoelastic, and the operating microscope is 
tilted about 35°, while the head of the participant is turned 35° from the surgeon to ensure 
an optimal view into the chamber angle.  
The previously made temporal cataract incision is used. After the two stents have been 
placed in the TM, all viscoelastic is removed with the I/A instrument and the eyed is 
filled with BSS. Cefuroxime 1 mg and ampicilline 0.1 mg is given intracameral at the end 
of surgery. 
The iStent Inject W is a second generation iStent that comes packed in a two-stent, 
preloaded, autoinject mechanism. It is made of surgical-grade, heparin-coated, non-
ferromagnetic titanium. With a length of only 360 μm and a diameter of 230 μm, a single 
iStent inject stent is currently the smallest medical implant approved for use in the human 
body. The iStent inject stents are delivered in an injector system which injects the stents 
automatically into SC through a stainless-steel insertion tube. The injector is released by 
the surgeon by pressing a button. Two stents are implanted nasally into the TM and SC 
with a distance of 30 to 60°. 
4. Postoperative Care 
After planned surgery, topical nepafenac (Nevanac ®) 3 mg/ml is given one time daily 
and topical dexamethasone (Isopto-Maxidex ®) 1 mg/ml three times daily for three 
weeks.  
After surgery, glaucoma medications will generally be continued during the first three 
postoperative weeks. After that, medications will be discontinued if the glaucoma 
disease is stable and target IOP for the individual is lower than needed. Often, IOP-levels 
≤ 21 mmHg is accepted in medically treated intraocular hypertension, ≤ 18 mmHg in 
mild glaucoma, ≤ 15 mmHg in moderate glaucoma and ≤ 12 mmHg in advanced 
glaucoma. The Hodapp-Parrish-Anderson criteria will be used to determine glaucoma 
grade. If visual field progression is seen or IOP becomes unacceptable elevated, 
medications will be added. To guarantee the safety of participants, further glaucoma 
surgery or laser is allowed if needed during the follow-up of the study. 
Target IOP-levels are affected by factors such as age and rate of progression on visual 
field examinations, and the treatment strategy will therefore be individualized to ensure 
the safety of participants. Since participants with all stages of glaucoma will be included 
in this study, for safety reasons, washout of medications is not planned. 

11 
 
5. Policy Matters 
5.1  Participant consent 
This RCT requires that written consent is obtained from each participant enrolled in the 
study. The participant is requested to sign the consent form after participant education is 
completed, and written information about the study is provided to all participants. The 
signed consent form is kept with the study records at the clinical center and a copy is 
given to the participant. 
6. Clinical Center Procedures 
6.1  Qualifying Assessment 
Every eligible participant will be offered enrollment in the study 
6.2 Assignment of Participant Identification Number 
Any participant who is confirmed to meet the eligibility criteria and is enrolled in the 
study is assigned a participant identification number. 
6.3 Schedule of visits 
All study personnel must be familiar with the schedule of visits to ensure that required 
data is collected and that future visits are scheduled within the appropriate time 
windows. The need for continued follow-up visits will be stressed to the participant 
during the informed consent process and throughout the study.  
Table 1. Number of Days After Surgery 
Follow-Up Visit 
Ideal time 
Acceptable time 
1 Day 
1 day 
1-3 days 
6 Week 
42 days 
25-60 days 
3 Month 
90 days 
61-120 days 
6 Month 
182 days 
121-270 days 
1 Year 
365 days 
271-455 days 
2 Year 
730 days 
638-912 days 
3 Year 
1095 days 
913-1277 days 
4 Year 
1460 days 
1278-1642 days 
5 Year 
1825 days 
1643-2007 days 
 
 
 
 

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Table 2. Schedule of visits 
 
Pre-
operative 
1 
Day 
6 
Weeks 
3 
Months 
6 
Months 
1 
Year 
2 
Years 
3 
Years 
4 
Years 
5 
Years 
Snellen VA 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Slit lamp 
Biomicroscopy 
X 
X 
X 
X 
X 
X 
X 
 
 
 
Tonometry 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Gonioscopy 
X 
 
 
 
X 
X 
X 
 
 
 
Automated 
perimetry 
X 
 
 
 
X 
X 
X 
X 
X 
X 
Pachymetry 
X 
 
 
X 
 
 
 
 
 
 
Questionaire 
X 
 
 
 
X 
 
 
 
 
 
Informed 
consent 
X 
 
 
 
 
 
 
 
 
 
 
7. Study Methods 
7.1 Trial design  
This single-center multi-arm RCT is conducted at the eye-clinic at the Östersund hospital, 
Östersund, Sweden. Subjects likely to be eligible for the trial will be identified at their 
regular consultation for glaucoma and provided with a participant information leaflet. 
The principal investigator is responsible for deciding whether a patient is eligible for 
inclusion in the study. Eligible patients, who agree to take part, will sign a consent form 
before being randomized. 
The study is a multi-group RCT with three arms. Subjects will be randomized in a 1:1:1 
ratio to either: 
- 
Phacoemulsification (phaco) 
- 
Phacoemulsification in combination with KDB (Phaco-KDB)  
- 
Phacoemulsification in combination with iStent (Phaco-iStent) 
Clinical visits are performed preoperatively (preferrable within one month before 
surgery, acceptable within two months). Thereafter postoperative controls will be at day 

13 
 
1, week 6, month 3, month 6, month 12 and month 24. After participants have been 
controlled for two years, data will be collected annually from their regular glaucoma 
controls for three years. Recorded measures will include IOP, visual field examinations 
and need for further interventions (with medications, laser, or surgery).  
7.2 Randomization  
Randomization takes place at the time of surgery, before the participant is taken into the 
operating room. The randomization schedule is constructed using a computer pseudo-
random number generator and is randomized in blocks to ensure that there is equal 
number of participants in each treatment group early in the trial. Block sizes are varied in 
a random manner between three, six and nine. The randomization is performed by an 
independent clinical research unit not involved in the project. Sequential envelope system 
is used to reveal the assignment from the prespecified randomization sequence. 
Participants are given a study identification number based on their assigned treatment 
group. All preoperative data will be collected before the randomization. Masking is not 
applied in this study since the procedures of goniotomy and stent implantation cannot 
easily be performed with sham-procedures. 
7.3 Sample size calculation  
The primary outcome measure for the power calculation is the difference between 
cataract surgery as standalone and cataract surgery combined with either KDB or iStent. 
It`s currently not known if KDB and iStent are equally effective in terms of IOP-lowering 
effect since prospective studies comparing KDB and the second generation iStent are 
sparse. However, we hypothesize that KDB and iStent may be equally effective in terms 
of IOP-lowering effect. Cataract extraction in combination with KDB or iStent is 
estimated to have an IOP-lowering effect of 5.5 (7.8) (mean (standard deviation)) mmHg 
after one year.2 For cataract extraction, the IOP-reduction is estimated to 1.5 (3) mmHg.4 
For a power above 80%, 37 eyes per group will be needed. A drop-out rate of around 
10% is expected. Therefore, enrollment in the study will be offered to a total of 120 
participants (40 in each treatment group). 
7.4 Framework 
Superiority hypothesis testing will be performed between phaco-KDB and phaco, 
between phaco-iStent and phaco, and between phaco-KDB and phaco-iStent. 
7.5 Statistical interim analyses and stopping guidelines 
No interim analyses will be performed. Stopping/discontinuation rules for early 
termination of the trial are not defined since no main difference in safety outcome is 

14 
 
expected. Both iStent and KDB are FDA-approved devices, and no major safety issues 
has been observed in previous studies.1 5 6  
7.6 Timing of final analyses 
Outcomes will be analyzed according to the timetable displayed under “Schedule of 
visits”. The analyses of the main trial data for publication purposes will begin once the 
final randomized subject has reached the 12-month follow-up. 
7.7 Timing of outcome assessments 
Timing of outcome measures are displayed under “Schedule of visits”.  
8. Statistical principles 
8.1 Confidence intervals and P values 
Confidence intervals of 95% will be reported and P values < 0.05 considered statistically 
significant.  
8.2 Adherence and protocol deviations 
Adherence to the protocol is defined as the number of participants receiving the planned 
surgery and completes the final follow-up time points at 12 and 24 months. If a 
participant misses an intermediate control, he or she will still be included in the study. 
The proportion of participants missing each outcome will be summarized in each arm at 
each time point. Protocol deviations that will be summarized include failure to implant 
both stents, and failure to perform goniotomy with KDB. A capsular rupture will be 
recorded as a protocol deviation if vitreous is prolapsed into the anterior chamber and/or 
an intraocular lens cannot be placed in the capsular bag or sulcus. Other adverse events 
related to surgery such as choroidal effusion, choroidal hemorrhage or aqueous 
misdirection will also be recorded, as well as use of mechanical pupil dilation, use of 
capsular tension rings, iris hooks, capsule retractors or capsular staining with trypan blue.  
Time delay between controls will be recorded if they are outside acceptable time limits 
(se timetable in study protocol). Further glaucoma surgery or cyclodestructive laser will 
also be recorded as protocol deviations. Selective laser trabeculoplasty (SLT) and 
neodymium-doped yttrium aluminium garnet (nd:YAG) laser will be allowed, but SLT 
will be considered as additional glaucoma therapy if done postoperatively. 
 
 

15 
 
8.3 Analysis populations 
Intention to treat populations (ITT) will be analyzed. Complete cases will be participants 
that receive the planned surgery according to randomization and does not need further 
glaucoma surgery or cyclodestructive laser during follow-up. 
9. Trial Population 
9.1 Screening data 
Subjects that fulfill the eligibility criteria but are not included in the study will be 
reported and the reason for not participating given. Only one eye per participant will be 
included, and if both eyes are eligible, the first operated eye will be included. The 
participant can choose which eye he or she wishes to have surgery on first if both eyes 
are eligible (in most cases, this will be the eye with the most pronounced cataract). 
9.2 Eligibility 
Inclusion Criteria 
One eye per participant 
Over 18 years of age 
Clinically significant cataract 
Glaucoma or intraocular hypertension treated with one to four medications and no need 
for additional glaucoma surgery at the time of study enrollment 
Open chamber angle with Schaffer grading three to four in at least two quadrants 
Exclusion Criteria 
Previous glaucoma surgery, including cyclodestructive procedures 
SLT within 90 days prior to planned surgery 
Exudative age-related macular degeneration, proliferative diabetic retinopathy, clinically 
significant corneal dystrophy, other eye disease that affect intraocular pressure or visual 
field 
Unable to participate and make written consent due to another medical condition 
9.3 Recruitment 
See the Consort flow diagram in the end of this document. 

16 
 
9.4 Withdrawal/follow-up 
Withdrawal from the study will be done if the participant for some reason wishes to be 
excluded. Withdrawal from intervention is not likely since the randomization will be 
performed at the day of surgery. Loss of follow-up data will be recorded, and the reasons 
and details presented. 
9.5 Baseline participant characteristics 
List of baseline characteristics: 
Age 
Ethnicity 
Gender 
Visual acuity (measured with Snellen and converted to logMAR) 
Pachymetry (central corneal thickness) 
Goldmann applanation tonometry (a mean of two preoperative measurements) 
Presence of pseudoexfoliations 
Glaucoma grade (ocular hypertension, mild, moderate, or severe glaucoma according to 
ICD-10)  
Diagnosis (intraocular hypertension, primary open angle glaucoma, pseudoexfoliation 
glaucoma, pigmentary glaucoma or normal-tension glaucoma) 
Number of glaucoma medications (number of substances used) 
10. Analysis 
10.1 
Data Management and security 
A master log is kept for enrolled participants. An appointment schedule is made for each 
participant. All data will be kept confidential and only involved researchers will have 
access to it. All data will be de-identified before publication.  
10.2 
Outcome definitions 
Primary outcome  

17 
 
Number of participants in each group with ≥ 20% IOP-reduction and/or reduction of  ≥ 1 
medication after 12 and 24 months. This goal must be achieved without added medical 
therapy, SLT, cyclodestructive laser or further glaucoma surgery. 
Change in number of IOP-lowering medications compared to baseline. 
Secondary outcomes  
Number of participants with IOP-levels ≤ 12 mmHg, ≤ 15 mmHg, ≤ 18 mmHg and ≤ 
21mmHg after 12 and 24 months. 
Number of participants that need further surgery or cyclodestructive laser during follow-
up. 
Number of participants that need additional medical therapy or SLT during follow-up. 
Subgroup analyses are planned for presence of pseudoexfoliations, age, glaucoma 
grading (according to MD ≤ − 6 and MD > − 6 dB), preoperative IOP-levels and number 
of preoperative medications. 
Surveys     
Participants will be asked to perform a quality-of-life assessment before surgery and after 
six months. NEI-VFQ25 will be used for this purpose.  
10.3 
Analysis methods 
Subject demographics and baseline characteristics will be descriptively summarized with 
means and standard deviation (SD) for continuous, symmetric variables, and medians and 
inter-quartile range (IQR) for continuous, skewed variables, and frequencies and 
percentages for categorical variables. 
Independent-samples t-test (for parametric data) or Mann-Whitney U test (for non-
parametric data) will be used to detect and compare differences between groups. One-
way ANOVA (for parametric data) or Kruskal-Wallis test (for non-parametric data) will 
be used when comparing the three treatment arms. Chi-square test or Fisher´s exact test 
will be used to analyze categoric data. For paired variables, dependent samples t-test (for 
parametric data) or Wilcoxon matched pairs signed ranks test (for non-parametric data) 
will be used.  
Linear or logistic regression models will be fit to the data to adjust for any baseline 
characteristics which are found to differ between treatment arms. In addition, generalized 
linear mixed models will be fit to the repeated measures obtained at postoperative visits. 

18 
 
All outcomes will be presented using descriptive statistics; normally distributed data by 
the mean and SD and skewed distributions by the median and IQR. Binary and 
categorical variables will be presented using counts and percentages.  
Kaplan-Meier analysis will be performed for comparing failure rates between groups 
during follow up. 
IOP-measurements, changes in visual field mean deviation and number of IOP-lowering 
medications will be compared between the three groups at postoperative visits. P-values 
< 0.05 will be considered statistically significant. Snellen visual acuity will be converted 
to logarithm of the mean angle of resolution (LogMAR) and compared between groups. 
For subjects requiring additional surgery, no further data regarding visual acuity or IOP 
will be included in the analysis after the procedure. For pre-operative IOP-measurements, 
the mean of at least two measurements within one to two months will be used. At least 
one of these measurements will be performed with the two-person method. All 
postoperative IOP-measurements up to 24 months will be with the two-person method. 
NEI-VFQ25 scores will be analyzed using generalized linear models adjusting for 
baseline NEI-VFQ25 score and other prognostic variables, like the amount of vision loss, 
number of glaucoma medications and visual status of the fellow eye. 
10.4 
 Missing data 
In the event of non-response after each follow-up, the subjects will receive two telephone 
calls and then two written reminders. Even with the reminders, some loss to follow-up is 
expected over 24 months. The proportion of participants missing each outcome will be 
summarized in each arm and at each time point. 
10.5 
Harms  
To assess the safety of study participants, intermediate controls at any time-point will be 
allowed if needed. Planned extra controls will not be considered as adverse events and 
intermediate controls between the yearly study-appointments after the first postoperative 
year will generally be necessary to ensure participant safety. 
Postoperative complications that will be registered are hyphema over one mm, IOP-spike 
≥ 10 units from baseline, cyclodialysis cleft, postoperative inflammation with prolonged 
need for treatment after the first three postoperative weeks, and corneal oedema. Capsular 
opacifications or retinal complications such as macular oedema will also be reported, as 
well as loss of  ≥ two lines on Snellen chart at 12 and 24 months. If a rare event such as 
an endophthalmitis or prolonged hypotony (IOP ≤ 6 mm Hg with shallow anterior 

19 
 
chamber, choroidal effusion or hypotonus maculopathy) occur, this will be registered. If 
other adverse events occur, they will be reported as well. 
After goniotomy with KDB or trabecular implantation with iStent stents, postoperative 
bleeding from SC can occur. If a hyphema develops, it usually resolves within a week. If 
an anterior chamber bleeding does not resolve spontaneously or IOP is elevated due to a 
blood clot, anterior chamber washout will be allowed. If necessary, aqueous release 
through the existing paracentesis will also be allowed if IOP is elevated in the early 
postoperative period. This will not be considered as further glaucoma surgery. 
All complications that may occur, such as prolonged inflammation, hyphema, IOP-spike 
or macular oedema will be treated according to standard routine at the clinic.  
If a participant needs further glaucoma surgery (microinvasive surgery, filtering surgery 
or cyclodestructive laser), this will be allowed but future examinations such as IOP and 
visual field results will not be included for analyses. If a participant develops a medical 
condition that will interfere with the IOP or visual field such as a retinal vascular event or 
stroke with hemianopsia, affected examinations after the event will not be included.  
Safety will be assessed by monitoring complication rates after surgery. Other measures, 
such as visual field changes, will also be performed. All adverse events related to the 
procedures will be reported at each clinic visit. 
Safety analyses will be primarily assessed by adverse events, best corrected visual acuity 
(BCVA) and evaluation with slit-lamp biomicroscopy. Loss of  ≥ two lines on Snellen 
chart will be reported.  
10.6 
Statistical software 
SPSS Statistics version 28 (SPSS Inc, Chicago,IL, USA) will be used for statistical 
analyses. 
11. References 
1.  
Falkenberry S, Singh IP, Crane CJ, et al. Excisional goniotomy vs trabecular microbypass 
stent implantation: a prospective randomized clinical trial in eyes with mild to moderate 
open-angle glaucoma. J Cataract Refract Surg. 2020;46(8). 
doi:10.1097/j.jcrs.0000000000000229 
2.  
Arnljots TS, Economou MA. Kahook dual blade goniotomy vs istent inject: Long-term 
results in patients with open-angle glaucoma. Clin Ophthalmol. 2021;15. 
doi:10.2147/OPTH.S284687 
3.  
Melancia D, Pinto LA, Marques-Neves C. Cataract surgery and intraocular pressure. 

20 
 
Ophthalmic Res. 2015;53(3). doi:10.1159/000377635 
4.  
Damji KF, Konstas AGP, Liebmann JM, et al. Intraocular pressure following 
phacoemulsification in patients with and without exfoliation syndrome: A 2 year 
prospective study. Br J Ophthalmol. 2006;90(8). doi:10.1136/bjo.2006.091447 
5.  
Sieck EG, Epstein RS, Kennedy JB, et al. Outcomes of Kahook Dual Blade Goniotomy 
with and without Phacoemulsification Cataract Extraction. Ophthalmol Glaucoma. 
2018;1(1). doi:10.1016/j.ogla.2018.06.006 
6.  
Samuelson TW, Sarkisian SR, Lubeck DM, et al. Prospective, Randomized, Controlled 
Pivotal Trial of an Ab Interno Implanted Trabecular Micro-Bypass in Primary Open-
Angle Glaucoma and Cataract: Two-Year Results. Ophthalmology. 2019;126(6). 
doi:10.1016/j.ophtha.2019.03.006 
 
 
 
 
 
 
12. CONSORT Flow chart 
Se below. 

21 
 
CONSORT Flow Diagram 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Assessed for eligibility (n=  ) 
Excluded  (n=   ) 
   Not meeting inclusion criteria (n=  ) 
   Declined to participate (n=  ) 
   Other reasons (n=  ) 
Analysed  (n=  ) 
 Excluded from analysis  
(give reasons) (n=  ) 
Lost to follow-up (give reasons) 
(n=  ) 
Discontinued intervention (give 
reasons) (n=  ) 
Allocated to intervention (n=  ) 
 Received allocated intervention  
(n=  ) 
 Did not receive allocated 
intervention (give reasons) (n=  ) 
Lost to follow-up  
(give reasons) (n=  ) 
Discontinued intervention (give 
reasons) (n=  ) 
Allocated to intervention (n=  ) 
 Received allocated intervention  
(n=  ) 
 Did not receive allocated 
intervention (give reasons) (n=  ) 
Analysed  (n=  ) 
 Excluded from analysis  
(give reasons) (n=  ) 
Allocation 
Analysis 
Follow-Up 
Randomized (n=  ) 
Enrollment 
Allocated to intervention (n=  ) 
 Received allocated intervention (n=  
) 
 Did not receive allocated 
intervention (give reasons) (n=  ) 
Lost to follow-up (give reasons) (n=  ) 
Discontinued intervention (give 
reasons) (n=  ) 
Analysed  (n=  ) 
 Excluded from analysis  
(give reasons) (n=  )