Comparative Study 27G Vitrectomy vs Larger Gauge Surgery
Phase: NA
Conditions: Vitreoretinal Surgery
Sponsor: Universitaire Ziekenhuizen KU Leuven

 
 
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27G compared to larger gauge sizes_protocol_Version 2_20200420 
Clinical Investigation Title:  
Comparative study 27G vitrectomy vs larger gauge surgery 
Two-arm, mono-center, prospective, interventional comparative case study to compare 
postoperative recovery between the 27G and larger gauge surgical approach. 
 
Clinical Investigation Acronym: 27G vs larger gauge 
 
 
Sponsor 
 
UZ Leuven 
 
 
Coordinating Investigator  
 
 
Prof. Dr. Peter Stalmans 
 
Sponsor Reference Number 
 
S 63610 
 
 
Version Number and Date 
 
27G compared to larger gauge 
Version 2  
Date: 20/04/2020 
 
 
Confidentiality Statement 
This document contains confidential information that must not be disclosed to anyone 
other than the Sponsor, the Investigator Team, regulatory authorities, and members of 
the Research Ethics Committee.   
 
 
 
 
 
 
 
 

 
 
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27G compared to larger gauge sizes_protocol_Version 2_20200420 
CLINICAL INVESTIGATION PLAN AUTHORISATION 
Coordinating Investigator  
 
Name: Peter Stalmans 
Title: Prof. Dr.  
Signature: 
Date: 
Site: UZ Leuven (Belgium) 
 
Principle Investigator(s)  
 
Name: Christiane Falkner-Radler  
Title: Dr.  
Signature: 
Date: 
Site: Rudolf Foundation Hospital (Austria) 
 
Name: Chérif Mazit , Mounir Benzerroug 
Title: Dr.  
Site: Anjou Clinic – Centre Retine Anjou (France) 
 
Name: Mitrofanis Pavlidis 
Title: Prof. Dr.  
Signature: 
Date: 
Site: Augencentrum Köln (Germany) 
 
Name: Luigi Caretti  
Title: Dr. 
Signature: 
Date: 
Site: Caretti Rovigo (Italy) 
 
Name: Virgilio Morales Canton 
Title: Dr.  
Signature: 
Date: 
Site: TBD (Mexico) 
 
Name: Luis Arias 
Title: Dr. 
Signature: 
Date: 
Site: Bellvitge University Hospital (Spain) 
 
 
 
Name: Renardel de Lavalette 
Title: Prof. Dr. 
Signature: 

 
 
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27G compared to larger gauge sizes_protocol_Version 2_20200420 
Date: 
Site: UMC Groningen (The Netherlands) 
 
Name: Aysegul Mavi 
Title: Dr. 
Signature: 
Date: 
Site: Retina Göz Hastanesi (Turkey) 
 
Name: Zac Koshy 
Title: Dr. 
Signature: 
Date: 
Site: University Hospital Ayr (United Kingdom) 
 
Statistician  
 
Name: Ars Statistica, Jean-Francois Fils 
Title: Medical statistician 
Signature: 
Date: 
 
Sponsor 
 
Name: UZ Leuven 
Title: 
Signature: 
Date: 
 
 
 
 

 
 
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27G compared to larger gauge sizes_protocol_Version 2_20200420 
TABLE OF CONTENTS 
Contents 
1. 
AMENDMENT HISTORY ................................................................................................................... 8 
2. 
List of appendices ........................................................................................................................... 9 
3. 
ABBREVIATIONS .............................................................................................................................. 9 
4. 
CLINICAL INVESTIGATION SUMMARY ............................................................................................. 9 
5. 
INTRODUCTION ............................................................................................................................. 11 
6. 
OBJECTIVES ................................................................................................................................... 13 
6.1 Primary objective ........................................................................................................................ 13 
7. 
CLINICAL INVESTIGATION DESIGN ................................................................................................ 13 
7.1 Trial Design .................................................................................................................................. 13 
7.2 Study diagram ............................................................................................................................. 14 
7.3 Study Flowchart ...................................................................................................................... 14 
8. 
CLINICAL INVESTIGATION POPULATION ....................................................................................... 14 
8.1. 
Number of participants ......................................................................................................... 14 
8.2. 
Inclusion criteria .................................................................................................................... 14 
8.3. 
Exclusion criteria ................................................................................................................... 14 
9. 
PARTICIPANT SELECTION AND ENROLMENT ................................................................................ 15 
9.1. 
Identifying participants ......................................................................................................... 15 
9.2. 
Consenting participants ........................................................................................................ 15 
9.3. 
Randomisation ...................................................................................................................... 16 
9.4. 
Withdrawal of participants ................................................................................................... 16 
10. 
Investigational DEVICE .............................................................................................................. 16 
10.1. 
Investigational device details ............................................................................................ 16 
10.2. 
Device manufacturer......................................................................................................... 18 
10.3. 
Device accountability ........................................................................................................ 18 
10.4. 
Storage conditions ............................................................................................................ 18 
10.5. 
Concomitant Treatments .................................................................................................. 18 
11. 
CLINICAL INVESTIGATION ASSESSMENTS ................................................................................. 18 
11.1. 
Subject Characteristics ...................................................................................................... 18 
11.2. 
Clinical investigation assessments .................................................................................... 20 
11.3. 
Surgical procedure ............................................................................................................ 21 
11.4. 
Safety assessments ........................................................................................................... 21 

 
 
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27G compared to larger gauge sizes_protocol_Version 2_20200420 
11.4.1 Adverse events that do not require reporting ................................................................... 21 
12. 
Data Quality Assurance ............................................................................................................. 21 
12.1. 
Monitoring, Audit and Inspections ................................................................................... 21 
12.2. 
Training of staff ................................................................................................................. 21 
12.3. 
Data Management ............................................................................................................ 21 
13. 
STATISTICS ................................................................................................................................. 22 
 
Description of statistical methods ............................................................................................ 22 
13.1. .................................................................................................................................................. 22 
13.2. 
The number of participants .............................................................................................. 24 
13.3. 
The level of statistical significance .................................................................................... 24 
13.4. 
Criteria for the termination of the clinical investigation .................................................. 24 
13.5. 
Procedure for accounting for missing, unused and spurious data ................................... 24 
13.6. 
Procedures for reporting any deviations from the original statistical plan ...................... 24 
13.7. 
Inclusion in analysis ........................................................................................................... 25 
14. 
CLINICAL INVESTIGATION MANAGEMENT ................................................................................ 25 
14.1. 
Clinical investigation management group and parties involved ....................................... 25 
14.2. 
Clinical investigation steering committee ......................................................................... 27 
14.3. 
Data monitoring committee ............................................................................................. 27 
14.4. 
Monitoring plan ................................................................................................................ 27 
15. 
GOOD CLINICAL PRACTICE ........................................................................................................ 27 
15.1. 
Declaration of Helsinki ...................................................................................................... 27 
15.2. 
Guidelines for GCP ............................................................................................................ 27 
15.3. 
Ethics review ..................................................................................................................... 27 
15.4. 
Patient Information and Consent Form ............................................................................ 28 
15.5. 
Subject data protection .................................................................................................... 28 
15.6. 
Procedures in case of medical emergency ........................................................................ 28 
16. 
CLINICAL INVESTIGATION CONDUCT RESPONSIBILITITES ......................................................... 28 
16.1. 
Clinical investigation plan amendments ........................................................................... 28 
16.2. 
Clinical investigation plan violations, deviations and serious breaches ........................... 28 
16.3. 
End of clinical investigation............................................................................................... 29 
16.4. 
Insurance and indemnity .................................................................................................. 29 
16.5. 
Funding.............................................................................................................................. 29 
17. 
REPORTING, PUBLICATIONS AND NOTIFICATIONS OF RESULTS ............................................... 29 
17.1. 
Authorship policy .............................................................................................................. 29 

 
 
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27G compared to larger gauge sizes_protocol_Version 2_20200420 
17.2. 
Publication ........................................................................................................................ 29 
18. 
REFERENCES .............................................................................................................................. 29 
19. 
SAFETY REPORTING ................................................................................................................... 30 
19.1. 
Definitions ......................................................................................................................... 30 
19.2. 
Procedures for reporting SAE /SADE or DD that could have led to a SADE ...................... 32 
19.3. 
Procedures for Device Deficiency reporting ..................................................................... 32 
19.4. 
Causality Assessment ........................................................................................................ 32 
19.5. 
Recording of safety information ....................................................................................... 32 
19.6. 
Reporting procedure for all SAEs/SADEs .......................................................................... 33 
19.7. 
Annual reports .................................................................................................................. 33 
 
 
 
 
 
 
 

 
 
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27G compared to larger gauge sizes_protocol_Version 2_20200420 
 
 
This CIP describes the 27G vs larger gauge clinical investigation and provides information 
about procedures for entering participants.  Every care was taken in its drafting, but 
corrections or amendments may be necessary. These will be circulated to investigators in 
the clinical investigation.  Problems relating to this clinical investigation should be referred, 
in the first instance, to the Principal Investigator.  
 
This clinical investigation will adhere to the principles outlined in the ISO 14155:2011. It 
will be conducted in compliance with the CIP, the Data Protection Act and other regulatory 
requirements as appropriate. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
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27G compared to larger gauge sizes_protocol_Version 2_20200420 
 
1. AMENDMENT HISTORY 
 
Amendment 
No. 
CIP 
Version No. 
Date 
Issued 
Author(s) of 
Changes 
Details of Changes  
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
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27G compared to larger gauge sizes_protocol_Version 2_20200420 
2. LIST OF APPENDICES 
 
Appendix A 
Assessment of eye reddishness – Reference photographs 
Appendix B 
Investigator’s Brochure  
Appendix C 
Case Report Form 
Appendix D 
Case Report Form (S)AEs reporting 
Appendix E 
Inform Consent Form 
3. ABBREVIATIONS 
 
AE 
Adverse Event 
CIP 
Clinical Investigation Plan 
CRA 
Clinical Research Associate 
CRF 
Case Report Form 
EC 
Ethics Committee  
GCP 
Good Clinical Practise 
IB 
Investigator Brochure 
ICF 
Informed Consent Form 
PI 
Principle Investigator 
SAE 
Serious Adverse Event 
 
 
4. CLINICAL INVESTIGATION SUMMARY 
 
Title 
Comparative study 27G to larger gauge vitrectomy  
Reference Number 
(Acronym) 
27G compared to larger gauge sizes 
Clinical Phase 
Post-Market stage 
Objectives 
To perform a prospective randomized comparison of 
postoperative recovery between 27G and larger gauge surgical 
approaches 
 
Endpoints 
Primary endpoint: determine whether ultra-small gauge surgery 
(27G) improves postoperative outcome and patient morbidity 
Design 
Investigator-initiated, comparative double-arm, mono-center, 
prospective, interventional case study 

 
 
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27G compared to larger gauge sizes_protocol_Version 2_20200420 
Data Collection  
Total duration of study for each patient will be 1 week or less 
(from surgery to last follow-up). 
See Study Flow Chart 7.3 
Planned Clinical 
investigation Period 
2020-2021 
Clinical investigation 
population 
Patients that are scheduled for a vitrectomy surgery for either 
floater removal or macular surgery, with or without combined 
cataract (phaco) surgery.  
Number of 
Participants 
Target 500 patients  
Inclusion/Exclusion 
Criteria 
Inclusion criteria  
• Patients aged over 18 
• No prior vitrectomy surgery in the study eye (for the same 
eye) 
• No prior inclusion in this trial 
• Scheduled for vitrectomy for floater removal or macular 
surgery (including macular holes) without endotamponades 
such as PFCL, Gas or Silicone oil. Air tamponade is allowed. 
 
Exclusion criteria  
• Patients with serious heart, lung, liver, or kidney dysfunction 
• Patients with proliferative diabetic retinopathy, 
endophthalmitis, uveitis, eyes with refraction >+5D or <-8D 
, or other eye disease that impacts the outcome of 
vitrectomy surgery 
• Patient with HIV 
• Patients with history of drug abuse or alcoholism 
• Patients participating in other drug or medical device clinical 
trials before screening for this trial 
• Pregnancy, preparation for pregnancy during clinical trial, or 
breast-feeding 
• Belief by the investigator that a patient’s condition would 
hinder the clinical trial, such as a patient prone to mental 
stress, loss of control of mood, or depression 
Device Name 
EVA used in combination with a trocar system, light fiber, 
vitrectome and laser fiber either in 27G or larger gauge sizes. In 
case of a combined surgery also a phaco hand piece and phaco 
needle are used. 
Principle Intended 
Use 
All devices are used within their claimed intended use.  
In general, all devices are intended to be used during 
ophthalmic surgery. 
Manufacturer Name 
D.O.R.C. Dutch Ophthalmic Research Center (International) 
B.V. 
 

 
 
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27G compared to larger gauge sizes_protocol_Version 2_20200420 
5. INTRODUCTION 
 
Vitrectomy surgery was first described by Machemer in 1971 and became more common 
in the early 1980’s 1. At that time, vitrectomy was performed transscleral after peritomy 
of the conjunctiva and exposing the sclera to make the vitrectomy incisions. These 
incisions need suturing at the end of the surgery. The size of the commercially available 
instruments was 0.91 mm, commonly referred to as “20 gauge”. 
 
In 2002, the first 25 gauge vitrectomy instruments became available: the TSV-25 
system from Bausch & Lomb, introduced into the market by De Juan 2. With these 
instruments, a new surgical approach was introduced: transconjunctival surgery. In this 
technique, the conjunctival is left untouched, and the vitrectomy surgery is performed 
through funnel-shaped instrument cannulas, which are retracted from the eye at the end 
of the surgery. In ideal conditions, these incisions did not require suturing at the end of 
the surgery. Both the smaller size of the incisions, the transconjunctival approach and 
omitting the need for sutures at the end reduced markedly the postoperative morbidity 
for the patient and accelerated recovery after vitrectomy surgery.  
However, the TSV-25 system had many disadvantages. Firstly, the inserters of the 
instrument cannulas lacked sharpness, hence required a huge force on the eye to be 
inserted. Also, the smaller diameter of the instruments made them very flexible, making 
the surgery much more difficult. Furthermore, the smaller inner lumen of the vitrectome 
reduced the flow of vitreous aspiration which increased significantly the duration of the 
surgery. Finally, the smaller diameter of the endo-illumination instrument reduced 
extensively the amount of intra-ocular light coming from a (halogen) light source. 
Personally, I started using the TSV-25 system in 2002 and used it till 2005. Even at the 
      
 
The size of vitrectomy instruments is named to the sizing used for steel wire, namely gauge.  
Left: comparative table of different sizes, Right: measurement tool for steel wire. 

 
 
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27G compared to larger gauge sizes_protocol_Version 2_20200420 
end of this 3-year period, I was not able to perform more than 5% of my vitrectomy 
cases with the TSV-25 system, falling back to 20G surgery in all other cases. 
In 2005, the use of 23 gauge instruments was introduced by Eckardt 3. These 
instruments allowed the surgeon to perform transconjunctival vitrectomy surgery, but 
the instruments were a little larger in size and were also technically enhanced to have 
less flex and improved inner lumen allowing better flow and light throughput. I started 
using the 23 gauge system in 2005, and after 6 weeks I already performed 50% of my 
cases using this system. A few years later, we completely abandoned the 20G approach, 
and performed all cases 23 gauge. In 2009, we published a comparative report between 
the 20G and 23G approach, clearly indicating better postoperative morbidity in favor of 
the 23G system4. Nevertheless, in spite of improved shape and sharpness of incision 
blades, suturing of the incisions still remains required in a significant percentage of 
patients. 
More recently, 27 gauge instruments became available 5. Although these are even 
smaller than the TSV-25 instruments introduced 15 years ago, we found that the 
improved design of these instruments (e.g. twin duty cycle cutters), in combination with 
improved vitrectomy devices allowing good vacuum and flow rate, and markedly 
improved light sources (xenon and LED) do allow the surgeon to perform more than half 
of the cases using this technique. Because of the extremely small size of the incision, 
suturing is almost never required, the incisions are closed upon the moment when the 
instruments are retracted from the eye. We also found that the postoperative recovery is 
spectacular: the day after the surgery, it is often difficult to see which eye was operated.  
 
Size comparison between vitrectomes (left picture) and intra-ocular forceps (right picture). 
Left to right: 20 gauge – 23 gauge – 25 gauge – 27 gauge 
 
 
Intra-operative view of 20 gauge transscleral surgery (left) and 27 gauge transconjunctival surgery (right). 

 
 
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The aim of this study is to objectively measure a possible difference in postoperative 
outcome after vitrectomy surgery for either floater removal or macular surgery, with or 
without combined cataract (phaco) surgery either in 27G and a larger gauge size.  
At present, in most centers 27G instruments are used besides larger gauge instruments 
of 23G of 25G. In this clinical trial, in each individual center the use of 27G instruments 
will be compared to the other instrument size being used in the standard of care. Also, 
the pre- and postoperative eye care (including medication) that is currently used in each 
site will be used for all patients included in that center. For statistical analysis, a 
comparison will be made between both study arms included in each center. Using this 
approach, it will be possible to evaluate the possible benefit of the use of ultra-small 
instruments compared to the larger gauge being used in different surgical settings.  
6. OBJECTIVES  
6.1 Primary objective 
The primary objective and primary endpoint are shown in the table below: 
 
The secondary objective and secondary parameters are shown in the table below: 
 
7. CLINICAL INVESTIGATION DESIGN 
7.1 Trial Design 
Investigator-initiated, comparative double-arm, mono-center, prospective, interventional 
case study 
50 patients as a target will be enrolled for each site. The study will consist of 3 patient 
visits. Study follow-up is one week after the vitrectomy surgery.  
Primary objective 
Primary endpoint 
The aim of this study is to perform a 
prospective randomized comparison of 
postoperative recovery between the 27G 
and larger gauge surgical approach. 
Patients will be randomized to be 
operated using 27 gauge or a larger 
gauge size.  
The outcome of the trial is to 
prospectively determine whether ultra-
small gauge surgery (27G) improves 
postoperative outcome and patient 
morbidity.  
 
For this purpose, the following 
postoperative parameters will be used:  
- 
Post-operative redness (Eye Photo) 
- 
Ophthalmic examination including 
biomicroscopy to evaluate the 
amount of intra-ocular 
inflammation. 
 
Secondary objective 
Secondary endpoint 
To obtain additional outcome parameters 
for both the 27 gauge and larger gauge 
surgery 
Postoperative parameters: 
- 
Visual Acuity (LogMAR BCVA) 
- 
Intra-ocular pressure (mmHg) 
- 
Pain assessment (Questionnaire 
with visual analogue scale) 

 
 
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7.2 Study diagram 
  
7.3 Study Flowchart 
 
Day 0: Surgery  
Day 1 Postoperative  
(+/- 0 days) 
Week 1 Postoperative  
(+/- 2 days) 
Surgery 
X 
0 
0 
Visual Acuity 
0 
X 
0 
Pain assessment 
0 
X 
0 
Intra-Ocular Pressure 
0 
X 
0 
Slit lamp 
0 
X 
0 
Eye photo 
0 
X 
0 
Questionnaire 
0 
0 
X 
8. CLINICAL INVESTIGATION POPULATION 
8.1. 
Number of participants 
A total of 500 patients will be included (up to 50 per site).  
Enrolment time is 12 months. 
8.2. 
Inclusion criteria  
• 
Patients aged over 18 
• 
No prior vitrectomy surgery in the study eye (for the same eye) 
• 
No prior inclusion in this trial 
• 
Scheduled for vitrectomy for floater removal or macular surgery (including 
macular holes) without endotamponades such as PFCL, Gas, Silicone oil).  
(Air tamponade is allowed ) 
8.3. 
Exclusion criteria  
The participant may not enter the clinical investigation if ANY of the following apply: 
• 
Patients with serious heart, lung, liver, or kidney dysfunction 
• 
Patients with proliferative diabetic retinopathy, endophthalmitis, uveitis, eyes 
with refraction >+5D or exceeding -8D , or other eye disease that impacts 
the outcome of vitrectomy surgery 
• 
Patients with HIV 
• 
Patients with history of drug abuse or alcoholism 
• 
Patients participating in other drug or medical device clinical trials before 
screening for this trial 
Randomisation
Group 1: Larger gauge size
Group 2: 27G

 
 
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27G compared to larger gauge sizes_protocol_Version 2_20200420 
• 
Pregnancy, preparation for pregnancy during clinical trial, or breast-feeding 
• 
Belief by the investigator that a patient’s condition would hinder the clinical 
trial, such as a patient prone to mental stress, loss of control of mood, or 
depression 
 
It should be noted that smoking or vaping is not considered an exclusion criteria. 
9. PARTICIPANT SELECTION AND ENROLMENT 
9.1. 
Identifying participants 
Patients that are scheduled for vitrectomy surgery that is commonly performed either 
using 27G or larger gauge instruments will be included. 
Similar to the normal clinical path, patients that are referred to the surgical center for 
either vitreous floaters or macular surgery will be suggested to undergo surgery. After 
obtaining consent from the patient to be enrolled for surgery, an explanation will be 
given by the investigator about this clinical trial, and the patient will be invited to 
participate in the trial. The informed consent will be handed over to the patient at that 
time to allow to read this through at home. After 1-2 weeks the patient will be called by 
the study nurse to ask for final approval or disapproval to be enrolled in the trial, and to 
answer any questions on the trial. 
 
Alternatively, patients that are already waitlisted for vitrectomy for vitreous floaters or 
macular surgery will be called by the investigator or study nurse to inform them about 
the ongoing clinical trial. After this informative call, the informed consent form will be 
mailed to the patient. After 1-2 weeks, the patient will be called again to ask for final 
approval or disapproval to be enrolled in the trial and to answer any questions, if 
required.  
9.2. 
Consenting participants 
Patients that are scheduled for vitrectomy surgery for either floater removal or macular 
surgery will be given the informed consent and will be asked to participate in the clinical 
trial. Per patient, only one eye will be eligible for inclusion in the study.  
Following Ethics Committee (EC) approval and before any investigation related 
procedure, potential participant must personally sign and date the latest approved 
version of the informed consent form before any clinical investigation specific procedures 
are performed. 
 
Written and verbal versions of the participant information and Informed consent will be 
presented to the participants detailing no less than: the exact nature of the clinical 
investigation; the implications and constraints of the clinical investigation plan; the 
known side effects and any risks involved in taking part.  It will be clearly stated that the 
participant is free to withdraw from the clinical investigation at any time for any reason 
without prejudice to future care, and with no obligation to give the reason for 
withdrawal. 
 
The participant will be allowed as much time as wished to consider the information, and 
the opportunity to question the Investigator, their GP or other independent parties to 
decide whether they will participate in the clinical investigation. Written Informed 
Consent will then be obtained by means of participant dated signature and dated 

 
 
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27G compared to larger gauge sizes_protocol_Version 2_20200420 
signature of the person who presented and obtained the informed consent. The person 
who obtained the consent must be suitably qualified and experienced, and have been 
authorised to do so by the Coordinating/Principal Investigator. A copy of the signed 
Informed Consent will be given to the participants. The original signed form will be 
retained at the clinical investigation site. See also document “recruitment”. 
 
In case of updates of the participant information and Informed consent the participant 
must personally sign and date the latest approved version of the informed consent form 
before any further clinical investigation specific procedures are performed. 
 
For this clinical trial, signature for approval from the patient will be obtained at the 
moment of admittance in the hospital on the day of the surgery.  
9.3. 
Randomisation  
A 25:25 patient randomization list will be generated in the eCRF (RedCap) to determine 
whether the surgery will be performed using 27G or larger gauge instruments.  
This randomization list will be masked for the surgeon: only prior to the next patient 
scheduled for surgery, the study arm will be visible for the surgeon since the difference 
in size will be visible during surgery.  
9.4. 
Withdrawal of participants 
Subjects are free to discontinue participation in the investigation at any time, and 
without prejudice to further treatment. Subjects who discontinue the investigation 
should always be asked about the reason(s) for their discontinuation and about the 
presence of any Adverse Event/Adverse Device Effect or Device Deficiency and, if 
possible, be assessed by an investigator. Adverse Event/Adverse Device Effect should be 
followed up. 
 
Subjects may be withdrawn from investigation treatment and assessments at any time, 
at the discretion of the investigator. 
 
Incorrectly enrolled subjects will be withdrawn from further investigation treatment and 
assessments. A subject may, however, continue the investigation under special 
circumstances (i.e. if continuation of investigation treatment or follow-up actions are 
necessary for the subject’s safety and well-being, or if only a follow-up period remains, 
and the continuation of the investigation is not expected to be associated with any risk 
or discomfort for the subject) 
10. INVESTIGATIONAL DEVICE 
10.1. Investigational device details 
The following devices are used within the clinical investigation: 
 
 

 
 
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27G compared to larger gauge sizes_protocol_Version 2_20200420 
 
 
Product 
Product name 
Reference  
number 
Disposable/
reusable 
CE-
marked/ 
registered 
EVA cassette 
EVA Cartridge with 0.5 L Collection Bag 8100.CAR01 Disposable 
Yes 
Dual Air Fluid 
Tubing 
Disposable EVA Air Fluid  Dual Tubing   
8110.AFD01 Disposable 
Yes 
VGPC Input Set 
Disposable EVA VGPC Input Set 
8110.VGP01 Disposable 
Yes 
23G Vitrectome 
Disposable High Speed TDC Cutter 23 G 
/ 8000 CPM DORC Continuum range 
 8268.VIT23 Disposable 
Yes 
23G Light fiber 
shielded wide 
Shielded TotalView Endoillumination 
Probe, including illuminated scleral 
depressor.(23 gauge / 0.6 mm) 
3269.SBS06 
Disposable 
Yes 
23G Trocar set 
Disposable One step Cannula 
System.(23 gauge / 0.6 mm) 
1272.ED206 Disposable 
Yes 
23G Laser fiber 
Directional Laser Probe with DORC 
connector.(23 gauge / 0.6 mm) 
7223.DORC 
Disposable 
Yes 
25G Vitrectome 
Disposable High Speed TDC Cutter 25 G 
/ 8000 CPM DORC Continuum range 
8268.VIT25 
Disposable 
Yes 
25G Light fiber 
shielded wide 
Shielded TotalView Endoillumination 
Probe, including illuminated scleral 
depressor.(25 gauge / 0.5 mm) 
3269.SBS05 
Disposable 
Yes 
25G Trocar set 
Disposable One Step Cannula System 
(25 gauge/0.5 mm) 
1272.ED205 Disposable 
Yes 
25G Laser fiber 
Directional Laser Probe with DORC 
connector.(25 gauge / 0.5 mm) 
7225.DORC 
Disposable 
Yes 
27G Vitrectome 
Disposable High Speed TDC Cutter 27 G 
/ 8000 CPM DORC Continuum range 
8268.VIT27 
Disposable 
Yes 
27 Light fiber 
shielded wide 
Shielded TotalView Endoillumination 
Probe, including illuminated scleral 
depressor.(27 gauge / 0.4 mm) 
3269.SBS04 
Disposable 
Yes 
27G Trocar set 
Disposable One step Cannula 
System.(27 gauge / 0.4 mm) 
1272.ED204 Disposable 
Yes 
27G Laser fiber 
Laser Probe, Stepped, Curved with 
DORC® Connector 27 gauge / 0.4 mm  
7527.DORC 
Disposable 
Yes 
Phaco 
handpiece* 
Phaco Sure Touch Handpiece 
3002.P 
Reusable 
(steam 
sterilized) 
Yes 
Phaco needle* 
EVA Custom Phaco Pack VGPC 2.2 mm 
Triple step angled flared phaco needle 
with 45 degrees tip  
8510.22AF2  Disposable 
Yes 
Membrane Blue 
Dual liquid 
MembraneBlue Dual 
MBD-05-S 
Disposable 
Yes 
ILM Blue Liquid 
ILM-Blue 
ILMB-05-S 
Disposable 
Yes 
*Other phaco handpiece or needles (i.e. larger or different angle) are allowed 
 
All of the above device are presently in use in the UZLeuven for daily vitrectomy surgery. Hence, 
there is no need for any dedicated device or instrument in this clinical trial.  

 
 
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27G compared to larger gauge sizes_protocol_Version 2_20200420 
10.2. Device manufacturer 
Manufacturer of devices included in section 10.1 is D.O.R.C. Dutch Ophthalmic Research 
Center (International) B.V., Scheijdelveweg 2, 3214 VN Zuidland, The Netherlands. 
10.3. Device accountability 
Devices used for each surgery will be documented. In the hospital, there is a standard 
procedure for returning faulty products. This procedure will be followed, similar to the 
standard clinical path. 
10.4. Storage conditions 
All disposable devices come pre-sterilized and will be used before expiration date. The 
reusable instruments will be steam-sterilized according to the guidelines provided by the 
manufacturer.  
10.5. Concomitant Treatments 
Before, during and after the surgery, the same medication and antiseptic treatment will be 
applied as in patients following the standard clinical path. This includes: 
• 
Preoperative application of mydriasert to dilate the pupil 
• 
Preoperative antiseptic treatment with betadine 
• 
BSS plus infusion liquid during the surgery 
• 
Injection of parabulbar triamcinolone and clindamycin at the end of the surgery 
• 
Postoperative dexamethasone anti-inflammatory eyedrops 
At the discretion of the investigator, additional medication may be prescribed.   
 
11. CLINICAL INVESTIGATION ASSESSMENTS 
11.1. Subject Characteristics  
The following parameters will be collected: 
1. History: prior eye surgery (excluding previous vitrectomy) 
2. Surgical parameters: 
• 
Indication of the surgery 
• 
Anesthesia type: local / general / local with sedation / general with parabulbar 
• 
Technique: 23G, 25G or 27G 
• 
Combined phacovitrectomy: yes / no 
If yes: Phaco power used: Total phaco time, effective phaco time and average 
phaco power 
• 
Surgery time: 
o 
total time of surgery 
o 
phaco time 
o 
vitrectomy time 
o 
peeling time 
• 
Tamponade(s) used (only air allowed) 
• 
Diathermy applied (Yes/No) 
• 
Phaco femto applied (Yes/No) 
• 
Cryo applied (Yes/No)  
• 
Laser applied (Yes/No) 
• 
Vital dyes used: yes/no 
If yes: type:  
• 
ILM peeling performed: yes/no 

 
 
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27G compared to larger gauge sizes_protocol_Version 2_20200420 
PVD created: yes/no 
• 
Vitreous stain used: yes/no 
If yes: Type: 
 
• 
Anticoagulants used by subject: recorded in the eCRF in list of concomitant 
medication(s): 
o 
 Yes/No 
o 
Type 
o 
Stopped: Yes/No 
o 
Time stopped 
• 
Medications used: 
o 
Preoperative disinfection: 
o 
Preoperative preparation (dilation drugs): 
o 
Infusion liquid use: 
o 
Additives in infusion liquid: 
o 
Intra-operative: intra-cameral or intravitreal medication 
o 
Postoperative: 
 
Parabulbar: 
 
Topical: 
 
General: 
• 
Actions required to close the eye at the end of the surgery 
o 
None 
o 
Sclerotomy massage 
o 
Sclerotomy squeezing 
o 
Injection of air bubble 
o 
Suturing of the sclerotomy 
If yes: number of sutures placed 
• 
Adverse events during surgery6,7,8,9: 
• 
Phaco: 
o 
Zip in capsulorhexis 
o 
Posterior capsule tear 
o 
Vitreous prolapse 
o 
Iris prolapse 
o 
Dropped nucleus 
• 
Vitrectomy: 
o 
Iatrogenic retinal tear 
o 
Lens touch 
o 
Choroidal hematoma 
o 
Infuse subchoroidal 
o 
Iatrogenic retinal damage 
o 
Subretinal haemorrhage 
o 
Iris trauma 
o 
Retinal incarceration 
o 
PFCL subretinal 
o 
Oil subretinal 
o 
Hemorrhage from retinal vessel 
o 
Hemorrhage from choroid 
3. Postoperative parameters: 
• 
Amount of pain during the first 24 postoperative hours (using pain scale) 
• 
Visual acuity day 1 postoperative  

 
 
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27G compared to larger gauge sizes_protocol_Version 2_20200420 
• 
Intra-ocular pressure day 1 postoperative 
• 
Slit-lamp examination day 1 postoperative: flare and cells in the anterior chamber 
• 
Photograph of the external eye to assess reddishness and swelling of eyelids 
4. Questionnaire 
To be completed by the patient about postoperative morbidity during the first 
postoperative week 
11.2. Clinical investigation assessments 
Patients that are scheduled for vitrectomy surgery that is commonly performed either 
23G or 27G instruments will be included. The preoperative preparation of the patient and 
the surgery itself will not be different from the standard of care. In the postoperative 
period, some additional examinations will be performed on the first postoperative day: 
• 
The patient will be asked to grade the amount of postoperative pain experienced 
(using a pain scale as below) 
 
• 
A photograph will be taken from the outside eye, and the amount of reddishness 
will be graded by and independent observer. See annex A. Photos to be made 
without flash, with eyes looking in all directions (e.g. 4 directions with lid up and 
down) and distance chosen such to have the eyes on photo with subjects not 
recognizable. 
 
• 
A questionnaire will be given to the patient upon discharge from the hospital with 
questions to assess the postoperative recovery. The patient will be asked to mail 
us these questions back after one week.  
1. Are you self-employed / employed/ retired / disabled / other: 
2. Did you sleep less well during the first night after surgery due to eye pain? Yes / 
No 
3. Did you sleep less well during the first week after surgery due to eye pain? Yes / 
No 
4. Did you wake up during the first night due to eye pain? Yes / No 
5. Did you wake up during the first week due to eye pain? Yes / No 
6. Did you take pain medication during the first night after surgery due to eye pain? 
Yes / No 
7. Did you take pain medication during the first week after surgery due to eye pain? 
Yes / No 
8. Did you use an eye cream after the surgery during pain or abrasive feeling? Yes / 
No 

 
 
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27G compared to larger gauge sizes_protocol_Version 2_20200420 
11.3. Surgical procedure 
The patient will be operated under local anesthesia, local anesthesia with sedation or 
general anesthesia, depending on the surgeon’s and patient’s preferences and general 
status of health. In the patients is phakic, the surgery may be combined with a cataract 
surgery (phaco-emulsification). As in the standard of care in each surgical center, the 
patients may stay overnight in the hospital after the surgery or can be treated on an 
outpatient basis. 
11.4. Safety assessments 
Medical device incidents will be routinely collected and reported under the national rules 
at the discretion of the Investigator. 
11.4.1 Adverse events that do not require reporting 
After vitrectomy, the following transient adverse events are commonly present during 
the first week after surgery, hence will not require reporting: 
• 
Decreased visual acuity compared to preoperative measurement 
• 
Reddish eye 
• 
Increased ocular pressure 
• 
Mild to moderate intra-ocular inflammation 
• 
Mild corneal edema 
12. DATA QUALITY ASSURANCE 
12.1. Monitoring, Audit and Inspections 
Investigator and the institution(s) will permit trial-related monitoring, audits, EC review, 
and regulatory inspections (where appropriate) by providing direct access to source data 
and other documents. 
12.2. Training of staff 
The Principal Investigator will ensure that appropriate training relevant to the 
investigation is given to the medical, nursing and other staff at the site involved and that 
new information of relevance to the performance of this investigation is forwarded to the 
staff involved. 
 
The staff at the investigational site will sign a confirmation document that they are 
trained.   
12.3. Data Management 
In this study, an electronic case report form (eCRF) within the RedCap platform will be 
used for data capture. For each surgical center, a different RedCap database will we 
created, allowing only access to the corresponding investigator and CRO (in case 
assigned by the CTC). Hence, there will be no sharing of data between the different 
surgical centers. Also, the data of the different centers will not be pooled for comparison 
between the centers, only comparison within each center will be performed (see section 
statistical analysis). Hence, during the whole trial there will be a strict separation of 
study data between each center.  
 
All documents will be stored safely in confidential conditions. On all clinical investigation-
specific documents, other than the signed consent, the participant will be referred to by 
the clinical investigation participant number/code, not by name. 

 
 
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27G compared to larger gauge sizes_protocol_Version 2_20200420 
 
All clinical investigation documentation will be kept for 10 years from the clinical 
investigation plan defined end of clinical investigation point. When the minimum 
retention period has elapsed, clinical investigation documentation will not be destroyed 
without permission from the sponsor. 
13. STATISTICS 
General comment: for the statistical analysis, a comparison will be made between both 
study arms included in each center. Hence, there will only be a comparison between 
both study arms in each site. No pooling of the data from the different sites will be 
performed nor will there be a comparison between the different study sites.  
13.1. Description of statistical methods 
Missing data handling 
The missing processes was described by Rubin (1987) who made a distinction between 
(a) Missing Completely At Random (MCAR), (b) Missing At Random (MAR), and (c) 
Missing Not At Random (MNAR)1. We will test with the statistical test of Jamshidian and 
Jalal (2010), implemented in the MissMech R Package (Jamshidian  et al., 2014), 
whether missing data were MCAR. If they are not MCAR, we will investigate whether or 
not the missing mechanism could be explained by baseline characteristics (eg, 
sociodemographic, medical features) of patients using logistic regression, which would 
suggest an MAR mechanism. If missing data are not MCAR or MAR, they will considered 
as MNAR. As indicated by Molenberghs et al. (2008) one can never totally exclude a 
MNAR process, but every MNAR model has an MAR counterpart with equal fit. Therefore, 
in case of MCAR, MAR, or MNAR missing processes, maximum likelihood (ML) and 
multiple imputation (MI) were used, using the mice R package for the last one 
(Raghunathan et al. (2001) ; van Buuren & Oudshoorn (2016)) with a predefined seed. 
Indeed, ML and MI use all available data in the study and produce unbiased estimates of 
the treatment effect and correct P values. MI is also a method of choice because it allows 
not only to impute missing values on the outcome but also on the covariate (Dziura, 
2013) and is valid for MCAR, MAR, and MNAR. (Molenberghs et al. (2008)) Molenberghs 
and Kenward (2007) recommended ML estimation without imposing a structure on the 
covariances among the repeated measures. 
 
Analysis of primary outcomes 
The primary outcomes will be analysed by a set of Wilcoxon-Mann-Whitney tests, but  
complementary tests will be done using mixed models for ordinal data (Hedeker & 
Gibbons, 2006) to take the multicenter nature of this trial into account. It is likely that 
patients in the same centre will tend to have correlated outcomes, meaning that they are 
more similar to other patients recruited within the same centre that to patients: same 
clinical care paths within centres will be observed, medical centre having their own 
medical practice preferences, and, therefore, the independence assumption underlying 
classical statistical tests is likely to be violated. We will therefore take this correlation 
between the patients of a same centre into account by using mixed models with the 
centre included as random effect for continuous outcomes (Chu et al., 2001; Kahan & 
                                                          
1 (a) Missing Completely At Random (MCAR): the missingness pattern is independent from observed and unobserved data; (b) Missing At 
Random (MAR): conditional on the observed data, the dropout is independent of the unobserved measurement; and (c) Missing Not At Random 
(MNAR): when neither MCAR nor MAR hold, the missingness depends on the observed, as well as on the unobserved data. 

 
 
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27G compared to larger gauge sizes_protocol_Version 2_20200420 
Morris, 2013) and mixed models for discrete data will be used to model binary outcomes 
(Kahan & Harhay, 2015). 
For demographic and baseline data, continuous data will be compared by means of T-test 
when homogeneity of variances, tested with the Bartlett’s test, and normality of the 
residuals, tested with the Shapiro-Wilks test, will be reached and means and standard 
deviations (means ± StDev) will be reported. When homogeneity of the variance or 
normality of the residuals won’t be proved, Wilcoxon signed rank test will be performed 
on rank data and medians and inter-quartile ranges (median [Q25 – Q75]) will reported. 
For count data, the Pearson Chi-Squared test will be performed to compare proportions. 
We will use the software R, version 3.6.2 or above (R Core Team, 2017) to perform the 
statistical analyses. 
Chu, R., Thabane, L., Ma, J., & al. (2011). Comparing methods to estimate treatment 
effects on a continuous outcome in multicentre randomized controlled trials: A simulation 
study. BMC Medical Research Methodology, 11:21.  
Hedeker D, Gibbons RD (2006). Longitudinal Data Analysis. Wiley-Interscience, 
Hoboken, NJ. 
Kahan, B.C. & Haray, M.O. (2015). Many multicentre trials had few events per centre, 
requiring analysis via random-effects models or GEEs. Journal of Clinical Epidemiology, 
68(12), 1504-1511. 
Kahan, B.C. & Morris, T.P. (2013). Analysis of multicentre trials with continuous 
outcomes: when and how should we account for centre effects? Statistics in Medicine, 
32(7), 1136-1149. 
Verbeke G, Molenberghs G. Linear Mixed Models for Longitudinal Data. Springer Series in 
Statistics. New-York: Springer-Verlag; 2000. 
 
Rubin DB. Inference and missing data. Biometrika.1976;63:581–592. 
 
Jamshidian M, Jalal S. Tests of homoscedasticity, normality, and missing completely at 
random for incomplete multivariate data. Psychometrika. 2010;75:649–674. 
 
Jamshidian M, Jalal S, Jansen C. MissMech: an R package for testing homoscedasticity, 
multivariate normality, and missing completely at random (MCAR). J Stat Software. 
2014;56:1–31. 
 
Molenberghs G, Beunckens C, Sotto C, Kenward MG. Every missing not at random model 
has got a missing at random counterpart with equal fit. J R Stat Soc. 2008;70:371–388. 
 
Raghunathan TE, Lepkowski JM, Van Hoewyk J, Solenberger P. A multivariate technique 
for multiply imputing missing values using a sequence of regression models. Surv 
Methodol. 2001;27:85–95. 
 
van Buuren S, Oudshoorn CGM. Multivariate Imputation by Chained Equations: MICE 
V1.0 User’s Manual.” TNO Report PG/VGZ/00.038, TNO Preventie en Gezond-heid, 
Leiden. 2000. Available at: http://www.stefvanbuuren.nl/publications/mice%20v1.0%20 
manual%20tno00038%202000.pdf. Accessed June 15, 2016. 

 
 
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Dziura JD, Post LA, Zhao Q, Fu Z, Peduzzi P. Strategies for dealing with missing data in 
clinical trials: from design to analysis. Yale J Biol Med. 2013;86:343–358. 
 
Molenberghs G, Kenward MG. Missing Data in Clinical Studies. Chichester, UK: John 
Wiley and Sons Ltd; 2007. 
13.2. The number of participants 
We estimated the number of participants by calculating the number of participants 
needed for the three chosen outcomes (bio cellen, bio tyndall and redness of the eye), 
based on the pilot data. The target p-value was 0.5/3 (=0.0167) in order to correct for 
multiple testing, and the power was set to 80%. Because we want to see a difference on 
the three outcomes, we choose the highest sample size estimation, based on the work of 
Zaho, Rahardja & Yongming (2008), who proposed sample size estimators ordinal data 
using the Wilcoxon-Mann-Whitney test and available in the R package sample size. The 
percentages for each categories of the ordinal variables by group are used as input for 
the sample size estimations. The next table presents the results obtained. 
 
 
Total by group 
Total individuals 
Bio cellen 
428 
858 
Bio tyndall 
430 
860 
Redness eye 
27 
54 
 
Based on this table, a total of 860 patients would be required by group in order to show 
a difference between 23G and 27G on the three parameters of the outcome: bio tyndall, 
bio cellen and redness eye. 
 
Zhao YD, Rahardja D, Qu Yongming. Sample size calculation for the Wilcoxon-Mann-
Whitney test adjusting for ties. Statistics in Medicine 2008; 27:462-468 
 
For each surgical site 25 patients will be recruited by group (i.e. 50 patients will be 
included at each site). 
13.3. The level of statistical significance 
 For all analyses, the level of significance will be 5% two-sided significant level. P-values will be 
adjusted for any multiple comparisons in order to maintain an overall type I error rate of 5%. 
13.4. Criteria for the termination of the clinical investigation 
Clinical investigation will be terminated 1 week post-op.  
13.5. Procedure for accounting for missing, unused and spurious data 
 Missing data will be reported with reasons given where available, and the missing data pattern will 
be examined. We will explore the mechanism of missing data by means of logistic regression models 
which will explore if missingness (i.e. whether the primary outcome is missing or not) is related to 
measured baseline variables. Covariates found to be predictive of missingness will, where 
appropriate, be included as a covariate in the analysis model. 
13.6. Procedures for reporting any deviations from the original 
statistical plan 
The final statistical plan will be agreed prior to final data lock and prior to any analyses taking place. 
Any deviation thereafter will be reported in the final trial report. 

 
 
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27G compared to larger gauge sizes_protocol_Version 2_20200420 
13.7. Inclusion in analysis 
All randomised patients will be included in the trial. 
14. CLINICAL INVESTIGATION MANAGEMENT  
14.1. Clinical investigation management group and parties involved 
 
The clinical investigation management group consists of the following 
participants: 
Coordinating Investigator  
 
Name: Peter Stalmans 
Title: Vitreoretinal surgeon 
Address: UZ Leuven, Herestraat 49 3000 Leuven 
Email: peter.stalmans@uzleuven.be 
Statistician 
 
Name: Mr. Jean-François Fils, Ars Statisica 
Title: Bio-Statistician 
Address: Boulevard des Archers  40, 1400  Nivelles 
  
Clinical investigation Management 
 
Name: Ingeborg Vriens 
Title: Clinical Trial Assistant (CTA) 
Address: UZ Leuven, Herestraat 49, 3000 Leuven  
Telephone: + 32 16 34 22 29 
Email: ingeborg.vriens@uzleuven.be 
 
Clinical investigation Coordination Centre  
 
For general queries, supply of clinical investigation documentation, and collection of 
data, please contact the Clinical Investigation Coordinator: 
 
Name: Ingeborg Vriens 
Title: Clinical Trial Assistant (CTA) 
Address: UZ Leuven, Herestraat 49, 3000 Leuven  
Telephone: + 32 16 34 22 29 
Email: ingeborg.vriens@uzleuven.be 
 
Clinical Queries 
 
Clinical queries should be directed to oogziekten@uzleuven.be who will direct the query 
to the appropriate person. 
 
Investigation sites 
 
Name: UZ Leuven 
Address: Herestraat 49, 3000 Leuven 

 
 
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Email: oogziekten@uzleuven.be 
 
Additional investigational sites: 
 
Name: Christiane Falkner-Radler  
Title: Dr.  
Signature: 
Date: 
Site: Rudolf Foundation Hospital (Austria) 
 
Name: Chérif Mazit , Mounir Benzerroug 
Title: Dr.  
Site: Anjou Clinic – Centre Retine Anjou (France) 
 
Name: Mitrofanis Pavlidis 
Title: Prof. Dr.  
Signature: 
Date: 
Site: Augencentrum Köln (Germany) 
 
Name: Luigi Caretti  
Title: Dr. 
Signature: 
Date: 
Site: Caretti Rovigo (Italy) 
 
Name: Virgilio Morales Canton 
Title: Dr.  
Signature: 
Date: 
Site: Mexico 
 
Name: Luis Arias 
Title: Dr. 
Signature: 
Date: 
Site: Bellvitge University Hospital (Spain) 
 
Name: Renardel de Lavalette 
Title: Prof. Dr. 
Signature: 
Date: 
Site: UMC Groningen (The Netherlands) 
 
Name: Aysegul Mavi 
Title: Dr. 
Signature: 
Date: 
Site: Retina Göz Hastanesi (Turkey) 
 

 
 
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27G compared to larger gauge sizes_protocol_Version 2_20200420 
Name: Zac Koshy 
Title: Dr. 
Signature: 
Date: 
Site: University Hospital Ayr (United Kingdom) 
 
 
Sponsor 
 
Name: UZ Leuven 
Address: Herestraat 49, 3000 Leuven 
Email: oogziekten@uzleuven.be 
14.2. Clinical investigation steering committee  
Patients included in this clinical trial follow the standard clinical path, using the standard 
vitrectomy device and using the currently used instruments. Hence, there is no increased 
safety risk for patients enrolled in this investigation. For this this reason, no steering 
committee or DMC will be constituted.  
14.3. Data monitoring committee 
 
N/A, see section 14.2. 
14.4. Monitoring plan 
 
The study protocol will be reviewed by the CTC prior to study approval. If the CTC 
evaluates that the study should be monitored, a monitor will be appointed by the CTC.  
In this case, the monitor will visit the Investigator site prior to the start of the clinical 
investigation and during the course of the clinical investigation if required, in accordance 
with the monitoring plan. Monitoring will be performed according to ISO 14155:2011. 
Data will be evaluated for compliance with the clinical investigation plan and accuracy in 
relation to source documents. Following written standard operating procedures, the 
monitors will verify that the clinical investigation is conducted and data are generated, 
documented and reported in compliance with the clinical investigation plan, GCP and the 
applicable regulatory requirements.  
15. GOOD CLINICAL PRACTICE 
15.1. Declaration of Helsinki  
The Investigator will ensure that this clinical investigation is conducted in full conformity 
with the current revision of the Declaration of Helsinki (last amended October 2000, with 
additional footnotes added 2002 and 2004). 
15.2. Guidelines for GCP 
The Investigator will ensure that this clinical investigation is conducted in full conformity 
with relevant regulations and with the International standard for Good Clinical Practice 
for clinical investigations of medical devices for human subjects (ISO 14155:2011). 
15.3. Ethics review 
The clinical investigation plan, Investigator’s Brochure, Case Report Forms (CRFs), 
informed consent form, participant information sheet and any other documents needed 

 
 
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27G compared to larger gauge sizes_protocol_Version 2_20200420 
for review by an appropriate Ethics Committee (EC) or regulatory authority will be 
submitted to obtain written approval.  Any additional requirements imposed by the EC or 
regulatory authority will be followed, if appropriate. 
 
The Investigator will submit and, where necessary, obtain approval for all amendments 
to the original approved documents.  Furthermore, the clinical investigation will not 
begin until the required approval/favourable opinion of the EC or regulatory authority 
has been obtained. 
15.4. Patient Information and Consent Form 
The Principal Investigator will ensure that the subject is given full and adequate oral and 
written information about the nature, purpose, possible risks and benefits of the 
investigation. Subjects must also be notified that they are free to discontinue 
participation in the investigation at any time. The subject should be given the 
opportunity to ask questions and time for consideration. 
 
The subject’s signed informed consent has to be obtained before conducting any 
investigation related procedures. The original must be filed by the Principal Investigator. 
A copy of the Patient Information including the signed Consent Form should be given to 
the subject. If modifications are made according to local requirements, the new version 
must be approved by the EC. 
15.5. Subject data protection 
The clinical investigation staff will ensure that the participants’ anonymity is maintained.  
The participants will be identified only by initials and a participants ID number on the 
CRF and any electronic database.  All documents will be stored securely and only 
accessible by clinical investigation staff and authorised personnel. The clinical 
investigation will comply with the Data Protection Act which requires data to be  
pseudonymized as soon as it is practical to do so.  
15.6. Procedures in case of medical emergency 
The Principal Investigator is responsible for ensuring that procedures and expertise are 
available to cope with medical emergencies during the investigation. 
16. CLINICAL INVESTIGATION CONDUCT RESPONSIBILITITES 
16.1. Clinical investigation plan amendments 
Amendments to the clinical investigation plan must be submitted to the Sponsor for 
review before submitting to the appropriate EC and Regulatory Authority for approval. 
16.2. Clinical investigation plan violations, deviations and serious 
breaches 
The Clinical investigator will not implement any deviation from the clinical investigation 
plan without agreement from the Sponsor, except where necessary to eliminate an 
immediate hazard to clinical investigation participants. 
In the event that the Clinical investigator needs to deviate from the clinical investigation 
plan, the nature of and reasons for the deviation will be recorded in the CRF and notified 
to the Sponsor. If this necessitates a subsequent clinical investigation plan amendment, 
this will be submitted to the Sponsor for approval and then to the appropriate REC and 

 
 
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27G compared to larger gauge sizes_protocol_Version 2_20200420 
Regulatory Authority for review and approvals as appropriate. It is Sponsor policy that 
waivers to the clinical investigation plan will not be approved. 
In the event that a serious breach of GCP is suspected, this will be reported to the 
Sponsor immediately.  
16.3. End of clinical investigation  
The end of clinical investigation is defined as the last participant’s last visit.   
The investigator and/or the clinical investigation steering committee have the right at 
any time to terminate the clinical investigation for clinical or administrative reasons.  
 
The end of the clinical investigation will be reported to the EC and Regulatory Authority 
within 90 days, or 15 days if the clinical investigation is terminated prematurely.  The 
Investigators will inform participants of the premature clinical investigation closure and 
ensure that the appropriate follow up is arranged for all participants involved. 
A summary report of the clinical investigation will be provided to the EC and Regulatory 
Authority within 1 year of the end of the clinical investigation. 
16.4. Insurance and indemnity  
In accordance with the Belgian Law relating to experiments on human persons dated 
May 7, 2004, Sponsor shall assume, even without fault, the responsibility of any 
damages incurred by a Study Patient and linked directly or indirectly to the participation 
to the Study, and shall provide compensation therefore through its insurance.” 
 
16.5. Funding 
Study grant from D.O.R.C. Dutch Ophthalmic Research Center (International) B.V. 
(DORC), Zuidland, The Netherlands. 
17. REPORTING, PUBLICATIONS AND NOTIFICATIONS OF RESULTS 
17.1. Authorship policy  
Ownership of the data arising from this clinical investigation resides with the clinical 
investigation team.  On completion of the clinical investigation, the clinical investigation 
data will be analysed and tabulated, and a clinical investigation report will be prepared in 
accordance with ISO14155:2011.  
17.2. Publication 
The Principal Investigator may decide to publish the obtained study data. The statistician 
will provide a study report, which will be used as source data to write the results section 
of the manuscript. The publication will also cover authorship, acknowledgements 
(mentioning the grant provider of the trial), and an overview of relevant scientific 
publications.   
Before submitting for publication, the manuscript will be send to the grant provider, 
allowing the grant provider give feedback on the manuscript within 2 weeks. It is up to 
the Principal Investigator to decide to make any changes to the manuscript based on this 
feedback.  
18. REFERENCES 
 

 
 
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1. Vitrectomy: a pars plana approach. Machemer R, Buettner H, Norton EW, Parel JM. 
Trans Am Acad Ophthalmol Otolaryngol. 1971 Jul-Aug;75(4):813-20. 
2. A new 25-gauge instrument system for transconjunctival sutureless vitrectomy 
surgery. Fujii GY, De Juan E Jr, Humayun MS, Pieramici DJ, Chang TS, Awh C, Ng E, 
Barnes A, Wu SL, Sommerville DN. Ophthalmology. 2002 Oct;109(10):1807-12; 
discussion 1813. Erratum in: Ophthalmology. 2003 Jan;110(1):9. 
3. Transconjunctival sutureless 23-gauge vitrectomy. Eckardt C. Retina. 2005 Feb-
Mar;25(2):208-11 
4. Comparison of postoperative comfort in 20 gauge versus 23 gauge pars plana 
vitrectomy. Mentens R, Stalmans P. Bull Soc Belge Ophtalmol. 2009;(311):5-10. 
5. A 27-gauge instrument system for transconjunctival sutureless microincision 
vitrectomy surgery. Oshima Y, Wakabayashi T, Sato T, Ohji M, Tano Y. 
Ophthalmology. 2010 Jan;117(1):93-102. 
6. Pars plana vitrectomy for vitreomacular traction syndrome: a systematic review and 
metaanalysis of safety and efficacy. Jackson TL, Nicod E, Angelis A, Grimaccia F, 
Prevost AT, Simpson AR, Kanavos P. Retina. 2013 Nov-Dec;33(10):2012-7 
7. United Kingdom National Ophthalmology Database Study of Vitreoretinal Surgery 
Report 3, Retinal Detachment. Timothy L. Jackson, PhD, FRCOphth, Paul H.J. 
Donachie, MSc, Ahmed Sallam, PhD, FRCOphth, John M. Sparrow, DPhil, FRCOphth, 
Robert L. Johnston, FRCOphth. Ophthalmology 2014;121:643-648 
8. The Royal College of Ophthalmologists’ National Ophthalmology Database Study of 
Vitreoretinal Surgery Report 6, Diabetic Vitrectomy. Timothy L. Jackson, PhD, 
FRCOphth; Robert L. Johnston, FRCOphth; Paul H. J. Donachie, MSc; TomH. 
Williamson, MD, FRCOphth; John M. Sparrow, DPhil, FRCOphth; David H.W. Steel, 
FRCOphth. JAMA Ophthalmol. 2016;134(1):79-85. doi:10.100United Kingdom 
National Ophthalmology Database Study of Vitreoretinal Surgery: Report 2, Macular 
Hole. Timothy L. Jackson, PhD, FRCOphth, Paul H. J. Donachie, MSc, John M. 
Sparrow, DPhil, FRCOphth, Robert L. Johnston, FRCOphth. Ophthalmology 
2013;120:629–634 
9. THE ROYAL COLLEGE OF OPHTHALMOLOGISTS’ NATIONAL OPHTHALMOLOGY 
DATABASE STUDY OF VITREORETINAL SURGERY Report 4, Epiretinal Membrane. 
TIMOTHY L. JACKSON, PHD, FRCOPHTH, PAUL H.J. DONACHIE, MSC, TOM H. 
WILLIAMSON, MD, FRCOPHTH, JOHN M. SPARROW, DPHIL, FRCOPHTH, ROBERT L. 
JOHNSTON, FRCOPHTH. RETINA 35:1615–1621, 2015 
10. R Core Team (2017). R: A language and environment for statistical computing. R 
Foundation for Statistical Computing, Vienna, Austria. ISBN 3-900051-07-0, URL 
http://www.R-project.org/. 
This list is open to changes. 
19. SAFETY REPORTING 
19.1. Definitions 
 
Device Deficiency (DD) 
 
Inadequacy of a medical device with respect to its identity, quality, durability, reliability, 
safety or performance. 
 
Note: 
• 
Device Deficiencies include malfunctions, use errors, and inadequate labelling. 

 
 
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All Device Deficiencies that might have led to a Serious Adverse Device Effect shall be 
reported in accordance with Serious Adverse Event reporting procedures, as specified 
below. 
 
Adverse Event (AE) 
Any untoward medical occurrence, unintended disease or injury, or any untoward clinical 
signs (including abnormal laboratory findings) in subjects, users or other persons, 
whether or not related to the investigational device. 
 
Note: 
• 
This definition includes events related to the investigational device or the 
comparator. 
• 
This definition includes events related to the procedures involved. 
• 
For users or other persons, this definition is restricted to events related to 
investigational devices. 
 
Adverse Device Effect (ADE) 
Adverse Event related to the use of an investigational device. 
 
Note: 
• 
This definition includes adverse events resulting from insufficient or inadequate 
instructions for use, deployment, implantation, or operation, or any malfunction 
of the investigational device. 
• 
This definition includes any event resulting from use error or from intentional 
misuse of the investigational device. 
 
Serious Adverse Event (SAE) 
Adverse Event that led to any of the following: 
a) death, 
b) serious deterioration in the health of the subject, that resulted in any of the following: 
1) a life-threatening illness or injury,  
2) permanent impairment of a body structure or a body function, 
3) hospitalization or prolongation of patient hospitalization, 
4) medical or surgical intervention to prevent life-threatening illness or injury or 
permanent impairment to a body structure or a body function. 
5) chronic disease 
c) foetal distress, foetal death or a congenital physical or mental impairment or birth 
defect. 
 
Note: 
Planned hospitalization for a pre-existing condition, or a procedure required by the CIP, 
without serious deterioration in health, is not considered a serious adverse event. 
 
Serious Adverse Device Effect (SADE) 
Adverse Device Effect that has resulted in any of the consequences characteristic of a 
Serious Adverse Event. 

 
 
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19.2. Procedures for reporting SAE /SADE or DD that could have led to a 
SADE 
 
All SAEs/SADEs that occurs during the Clinical Investigation shall be reported, whether 
or not they are considered causally related to the investigational device. 
 
Device Deficiencies that might have led to SADE must be reported as a SADE if either  
a) suitable action had not been taken, 
b) if intervention had not been made, or  
c) if circumstances had been less fortunate  
 
The investigator is responsible for informing the EC/IRB and/or the Competent Authority 
of the SAE/SADE as per local requirements. For this reason, medical device incidents will 
be routinely collected and reported under the national materiovigilance rules at the 
discretion of the Investigator.  
19.3. Procedures for Device Deficiency reporting  
 
Device Deficiencies will be routinely collected and reported to the corresponding 
manufacturer(s) as soon as possible, without unjustified delay (i.e. on the same working 
day). If the Device Deficiency might have led to a SADE the reporting requirements for 
SADE described above must be followed. 
19.4. Causality Assessment 
The relationship between the use of the investigational device and the occurrence of 
each AE/SAE shall be assessed by the investigator and the manufacturer and classified 
as investigational device related or not related to investigational device. 
19.5. Recording of safety information 
All safety issues occurring during the clinical investigation observed by the investigator 
or reported by the participant, whether or not attributed to the device under 
investigation will be recorded on the CRF as specified in the clinical investigation plan.   
 
The following information will be recorded: description, date of onset and end date, 
severity, assessment of relatedness to device, other suspect drug or device and action 
taken.  Follow-up information should be provided as necessary.  
 
The relationship to the device will be assessed by a medically qualified investigator or 
the sponsor and will be followed up until resolution or the event is considered stable.  
 
All ADE that result in a participant’s withdrawal from the clinical investigation or are 
present at the end of the clinical investigation, should be followed up until a satisfactory 
resolution occurs. 
 
Where relevant, any pregnancy occurring during the clinical investigation and the 
outcome of the pregnancy should be recorded and followed up for congenital abnormality 
or birth defect. 

 
 
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19.6. Reporting procedure for all SAEs/SADEs 
Reporting to the local national competent authority and the manufacturer will be done by 
the Principal Investigator.  
 
• 
The principal investigator has a legal obligation to report all events that need to be 
reported to the Nominated Competent Authority immediately (without any 
unjustifiable delay) after a link is established between the event and the device, but 
no more than:2 days following the awareness of the event for Serious Public Health 
Threat. 
• 
10 days following awareness of the event for Death or unanticipated serious 
deterioration in health. 
• 
30 days following the awareness of the event for all other event meeting the SAE 
criteria. 
 
Device Deficiencies, including SAEs/SADEs  will be reported to the corresponding 
manufacturer(s) as soon as possible, without unjustified delay (i.e. on the same working 
day). 
19.7. Annual reports 
In addition to the expedited reporting above, the Principal Investigator shall submit once 
a year throughout the clinical investigation or on request a Safety Report to the 
Competent Authority and Ethics Committee. 
 
 

 
 
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Appendix A: Assessment of eye reddishness – Reference photographs 
 
Grade 0: no reddishness 
 
 
Grade 1: barely visible 
 
 
Grade 2: partially bloodshed 
 
 
 
 

 
 
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Grade 3: diffuse bloodshed, globe only 
 
 
 
Grade 4: diffuse bloodshed, including eyelids / orbit