MiSight Lens Wear Cessation Study
Phase: NA
Conditions: Myopia
Sponsor: CooperVision, Inc.



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ABBREVIATIONS AND DEFINITIONS 
AE 
Adverse Event 
AL 
Axial Length 
CFR 
Code of Federal Regulations 
CRF 
Case Report Form 
CL 
Contact lens 
CRO 
Contract Research Organisation 
D 
Dioptre 
EDC 
Electronic data Capture 
eCRF 
Electronic CRF 
FDA 
United States Food and Drug Administration 
GCP 
Good Clinical Practice 
ICH 
International Conference on Harmonisation 
IOL 
Intra Ocular Lens 
IRB/IEC 
Institutional Review Board/Independent Ethics Committee 
ISO 
International Standards Organisation 
MK 
Microbial Keratitis 
mm 
Millimetre 
NIH 
US National Institutes of Health 
PD 
Pupillary Distance 
SD 
Standard Deviation 
SEALs 
Superior Epithelial Arcuate Lesion 
SERE 
Spherical Equivalent Refractive Error 
SOP 
Standard Operating Procedure 
US 
United States 
VA 
Visual acuity 
 
 

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MiSight® Lens Wear Cessation Study 
MIST-402 
TABLE OF CONTENTS 
 
 
Page 
1 
INTRODUCTION 
10 
2 
STUDY OBJECTIVES 
10 
3 
STUDY DESIGN & RATIONALE 
10 
3.1 
Study Design 
10 
3.2 
Study Rationale 
11 
3.3 
Primary Outcome Hypothesis 
12 
3.4 
Secondary Outcome Hypotheses 
12 
3.5 
Tertiary Outcome Hypotheses 
12 
3.6 
Safety Hypothesis 
12 
3.7 
Masking 
12 
3.8 
Randomisation 
12 
4 
STUDY POPULATION 
13 
4.1 
Number of Sites 
13 
4.2 
Investigator Recruitment 
13 
4.3 
Number of Subjects 
13 
4.4 
Inclusion Criteria 
13 
4.5 
Exclusion Criteria 
14 
4.6 
Subject Identification 
14 
4.7 
Study Withdrawal Criteria 
15 
4.8 
Subject Replacement 
15 
4.9 
Medications/Treatments Permitted and Not Permitted During the Study 
15 
4.10 
Procedures for Monitoring Subject Adherence 
15 
5 
MATERIALS 
16 
5.1 
Study Lenses 
16 
5.2 
Lens Care Products and Other Study Products 
16 
5.3 
Product Accountability 
16 
5.4 
Lens Wearing Schedule 
17 
5.5 
Potential Risks and Benefits for Human Subjects 
17 
5.6 
Study Documents and eCRFs 
17 
6 
TREATMENT 
18 
6.1 
Study Product Formulations 
18 
6.2 
Lens Administration 
18 
7 
METHODS AND ASSESSMENTS 
18 
7.1 
Subject Recruitment 
18 
7.2 
Study Visits 
18 
7.3 
Clinical Variables 
30 
7.4 
Subject Discontinuation 
31 
7.5 
Unscheduled Visits 
32 
7.6 
Site Training and Visits 
32 
8 
ADVERSE EVENTS 
32 
8.1 
Adverse Event Categorization 
34 
8.2 
Adverse Event Reporting 
34 
8.3 
Adverse Event Documentation 
34 
8.4 
Adverse Event Follow-up 
35 
8.5 
Study Completion 
35 

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9 
DATA MANAGEMENT 
36 
9.1 
Electronic Case Report Forms/Data Collection 
36 
9.2 
Data Quality Assurance 
36 
9.3 
Data Entry and Storage 
36 
10 
SAMPLE SIZE AND STATISTICAL METHODS 
36 
10.1 
Sample Size Rationale 
36 
10.2 
Primary End-points 
37 
10.3 
Statistical Considerations 
37 
10.4 
Analysis Population 
38 
10.5 
Descriptive Statistics 
38 
10.6 
Data Pooling 
38 
10.7 
Primary Statistical Analysis 
38 
10.8 
Secondary Statistical Analysis 
39 
10.9 
Tertiary Statistical Analysis 
39 
10.10 
Additional Statistical Analysis 
39 
10.11 
Interim Analysis 
39 
11 
GENERAL STUDY MANAGEMENT 
40 
11.1 
Relevant Standards 
40 
11.2 
Ethics Review 
40 
11.3 
Protocol Deviations 
40 
11.4 
Premature Termination of the Study 
40 
11.5 
Source Documentation 
40 
11.6 
Monitoring 
41 
11.7 
Audits 
41 
11.8 
Records Retention 
42 
11.9 
Confidentiality and Publication 
42 
12 
REFERENCES 
43 
APPENDIX A    PROCEDURES, EQUIPMENT AND GRADING SCALES 
44 
APPENDIX B   ADVERSE EVENT FORMS 
62 

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MiSight® Lens Wear Cessation Study 
MIST-402 
PERSONNEL AND FACILITIES 
 
SPONSOR: 
CooperVision Inc. 
6150 Stoneridge Mall Road 
Suite 370 
Pleasanton, CA 94588 
USA 
CLINICAL PROJECT LEADER: 
 
 
Tel:  
  
Email
  
INVESTIGATORS:  
 
(listed separately) 
STUDY LOCATION: 
UK, Portugal, Singapore and Canada 
CLINICAL RESEARCH ORGANISATION: 
Visioncare Research Ltd 
 
 
 
 
 
 
Tel:  
 
Fax:  
 
MEDICAL MONITOR: 
 
  
Tel:  
 
Email: 
 
STATISTICIAN: 
 
  
Tel:  
 
Email: 
 
DATA MANAGER: 
 
  
Tel:  
  
Email: 
 
 
 

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MiSight® Lens Wear Cessation Study 
MIST-402 
SYNOPSIS 
STUDY OBJECTIVES:  
To quantify the effect of ceasing MiSight treatment after 3 or 6 years’ use. 
STUDY DESIGN:  
This will be a bilateral, open label, dispensing study with approximately 
90 MiSight subjects refit to Proclear 1-day lens for 1 year. 
RANDOMISATION:  
All subjects will be refit to Proclear 1 Day. As such, no randomization will 
take place. 
MASKING: 
There will be no masking for this study. 
TEST PRODUCTS: 
Lenses to be worn are shown below: 
Brand 
Proclear 1 Day 
Manufacturer 
CooperVision 
Material/ water content 
omafilcon A / 62% 
Design 
Single vision 
Base curve (mm) 
8.70 
Diameter (mm) 
14.2 
Sphere powers (D) 
-0.25 to -8.00 
(0.50D steps after -6.00D) 
LENS CARE PRODUCTS:  
These are daily disposable lenses and, therefore, contact lens 
cleaning, soaking and disinfecting products should not be required 
Rewetting/comfort drops given to the subject by the investigator may 
be used in this study as needed to lubricate and rewet lenses. 
STUDY POPULATION: 
Approximately 90 existing MiSight (CL) wearers will be enrolled in the 
study: 
Inclusion Criteria: 
• 
Successfully completed the CVI08008 (MIST-401)- Part 2 study 
• 
Visual acuity (VA) with CLs better than +0.25 log MAR (>6/12 or 
>20/40) in both eyes 
• 
No ocular pathology or other contraindication to contact lens wear. 
• 
Where applicable (dependent on local requirements), have: 
o 
read the Informed Assent 
o 
been given an explanation of the Informed Assent,  
o 
indicated an understanding of the Informed Assent and  
o 
signed the Informed Assent Form. 
 
 
 
 
Or  
o 
read the Informed Consent,  
o 
been given an explanation of the Informed Consent,  
o 
indicated an understanding of the Informed Consent and  
o 
signed the Informed Consent Form. 
• 
Where applicable (dependent on local requirements), have their 
parent or legal guardian: 

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o 
read the Informed Consent,  
o 
been given an explanation of the Informed Consent,  
o 
indicated an understanding of the Informed Consent and  
o 
signed the Informed Consent Form. 
• 
Along with their parent or guardian (if applicable), be capable of 
comprehending the nature of the study, and be willing and able to 
adhere to the instructions set forth in this protocol. 
• 
Along with their parent or guardian (if applicable), agree to 
maintain the visit schedule and be able to keep all appointments 
as specified in the study protocol for the duration of the study (see 
Visit Schedule, Section 7.2.1). 
• 
Agree to wear the assigned contact lenses for a minimum of 10 
hours per day, at least 6 days per week, for the duration of the 
study and to inform the study investigator if this schedule is 
interrupted.  (Wearing time may be modified by the study staff for 
health reasons.) 
• 
Be 
in 
good 
general 
health, 
based 
on 
his/her 
and 
parent’s/guardian’s (if applicable) knowledge.  
• 
Have best-corrected visual acuity by manifest refraction of +0.10 
logMAR (20/25 Snellen equivalent) or better in each eye. 
Exclusion Criteria: 
• 
Regular use of ocular medications (prescription or over-the-
counter). 
• 
Current use of systemic medications which may significantly affect 
contact lens wear, tear film production, pupil size, accommodation 
or refractive state.   
• 
Pregnant or lactating or planning a pregnancy at the time of 
enrolment. 
• 
Known ocular or systemic disease such as, but not limited to: 
anterior uveitis or iritis, episcleritis or scleritis, glaucoma, Sjogren's 
syndrome, lupus erythematosus, scleroderma, or diabetes. 
• 
Any ocular, systemic or neuro-developmental conditions that could 
influence refractive development. 
• 
Keratoconus or an irregular cornea. 
• 
Biomicroscope findings that would contraindicate contact lens 
wear including, but not limited to: 
o 
Any active anterior segment ocular disease that would 
contraindicate contact lens wear. 
o 
clinically significant (Grade 3 or 4) abnormalities of the 
anterior segment, lids, conjunctiva, sclera or associated 
structures. 
• 
The investigator for any reason considers that it is not in the best 
interest of the subject to participate in the study. 
NO. SITES: 
Four sites (UK, Portugal, Singapore and Canada). 
END-POINTS:  
Efficacy End-points 
Primary: 
• 
Change in spherical equivalent refractive error (SERE) 
• 
Change in axial length (AL) 
Safety End-points 
As the study lens is approved in Europe (CE marked) as well as Canada 
and Singapore, no safety end points are required.  Safety will be 

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monitored through routine biomicroscopy and reporting of adverse 
events. 
STUDY VISITS:  
There will be a maximum of four scheduled visits 
Visit 1:  Baseline / Trial Fit / Lens Dispensing 
Visit 2:  2-week Follow Up (Optional)* (14 days ± 5 days from dispensing) 
Visit 3:  6-month Follow Up (180 days ± 14 days from dispensing) 
Visit 4:  12-month Follow Up and Exit (360 days ± 44 days from 
dispensing) 
* This is an optional visit if, in the investigator’s opinion, it is needed to 
confirm adaptation to the new lenses. 
STUDY VARIABLES:   
Key Variables: 
Cycloplegic refraction (Seiko WR5100K) – Baseline, 6 & 12-months 
Axial length (Zeiss IOL Master) 
Other Variables: 
 
 
 
 
 
 
 
 
 
 

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1 
INTRODUCTION  
The three-year pivotal study (MIST-401; CVI08008) noted a significant reduction in myopic 
progression and axial growth with MiSight in comparison with a single vision control.1  
Myopia progression studies with atropine eyedrop treatment have noted what appeared to be 
an acceleration of progression when the treatment with atropine was ceased.  During the 
12-months after cessation, with 1% concentration the average rate of myopia progression was 
greater than that shown by a control group.2  Subsequent studies by the same group studied 
both the efficacy and post study acceleration following treatment and then cessation of lower 
concentrations of atropine (0.01%, 0.1%, 0.5%). These concentrations showed a dose 
dependent post-treatment acceleration compared to the 1% concentration.3  
There is only one published study involving soft contact lenses with positive spherical aberration 
that has investigated myopia progression following cessation of treatment. This study found no 
evidence of a rebound effect after ceasing treatment.4 
The purpose of this study will be to investigate the effect of ceasing treatment with MiSight 
contact lenses.  
In MIST-401, subjects were randomly assigned to one of two groups: the test group wore 
MiSight contact lenses while the control group wore Proclear 1 Day lenses. After completion of 
this 3-year pivotal study (“Part 1”), all subjects were offered the opportunity to enrol for an 
additional three-year study, all wearing MiSight lenses (MIST-401 Part 2). 
Subjects who have completed the MIST-401 MiSight study (Part 1 and Part 2) will be invited to 
enrol on this 1-year follow-on study (MIST-402). Thus, subjects entering the study will have 
worn MiSight lenses for either 3 or 6 years. 
2 
STUDY OBJECTIVES 
The aim of this study will be to determine the rate of myopic progression following cessation of 
wear of MiSight contact lenses. 
Specifically, 
i. 
To quantify spherical equivalent refractive error (SERE) progression following 
cessation of 3 or 6 years’ use of MiSight contact lenses. 
ii. 
To quantify axial length (AL) progression following cessation of 3 or 6 years’ use of 
MiSight contact lenses. 
3 
STUDY DESIGN & RATIONALE 
3.1 
Study Design 
This will be a bilateral, open label, dispensing study with approximately 90 subjects currently 
wearing MiSight lenses refit to Proclear 1-day lenses for one year. 
Subjects who have completed MIST-401 – Parts 1 and 2 will be invited to participate in the 
study.   
Thus, there will be two groups of subjects, as described earlier and shown in the following 
diagram: 

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3.3 
Primary Outcome Hypothesis 
i. 
The mean myopic progression (Δ SERE) after cessation of MiSight wear will be non-
inferior to (i.e. not greater than) the mean annual myopic progression of the Control 
group in MIST-401-Part 1. 
ii. 
The mean myopic progression (Δ AL) after cessation of MiSight wear will be non-
inferior to (i.e. not greater than) the mean annual myopic progression of the Control 
group in MIST-401-(Part 1). 
A non-inferiority margin of 0.25D or 0.1mm will be used for SERE and AL respectively. 
3.4 
Secondary Outcome Hypotheses 
i. 
The mean myopic progression (Δ SERE) after cessation of MiSight wear will be greater 
than the mean annual myopic progression for the immediately previous 3 year’s 
MiSight treatment (MIST-401-Part 2). 
ii. 
The mean myopic progression (Δ AL) after cessation of MiSight wear will be greater 
than the mean annual myopic progression for the immediately previous 3 year’s 
MiSight treatment (MIST-401-Part 2). 
3.5 
Tertiary Outcome Hypotheses 
i. 
 
. 
ii. 
 
 
 
 
3.6 
Safety Hypothesis 
The study lenses are approved in all the countries where the study is taking place, therefore, 
no safety end points are required. 
However, in order to ensure the continued safety of the subjects in the trial, slit lamp findings 
will be assessed at all visits and the entrance spectacle refraction and VA will be collected at 
the start and end of the study.  Adverse events will also be recorded and monitored following 
the procedures listed in Section 8. 
3.7 
Masking 
There will be no masking for this study. 
3.8 
Randomisation 
All subjects will be refit to Proclear 1 Day, as such no randomization will take place. 

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4 
STUDY POPULATION 
4.1 
Number of Sites 
There are four investigational sites (UK, Portugal, Singapore and Canada) 
4.2 
Investigator Recruitment 
The investigators will be those that have already taken part in the MIST-401 study Parts 1 and 
2). 
For the MIST-401 study the study sites were colleges of optometry.   Study sites were selected 
based on the experience of the site investigator and staff in conducting clinical trials, the 
availability of potential study subjects, and the interest of the site in performing the trial.   
4.3 
Number of Subjects 
Approximately 90 existing soft contact lens wearers who have successfully completed the 
MIST-401 Parts 1 and 2 study will be enrolled. 
Each subject will be required to attend up to four scheduled study visits over a period of 
approximately 12 months.  
The study population has been chosen as they have already completed either 3 or 6 years of 
wear in MiSight contact lenses 
4.4 
Inclusion Criteria 
All subjects must satisfy the following conditions prior to inclusion in the study: 
i. 
Successfully completed the CVI08008 (MIST-401) Parts 1 and 2 
ii. 
Visual acuity (VA) with CLs better than +0.25 log MAR (>6/12 or >20/40) in both eyes 
iii. 
No ocular pathology or other contraindication to contact lens wear 
iv. 
Where applicable (dependent on local requirements), have: 
a. 
read the Informed Assent 
b. 
been given an explanation of the Informed Assent,  
c. 
indicated an understanding of the Informed Assent and  
d. 
signed the Informed Assent Form. 
Or  
e. 
read the Informed Consent,  
f. 
been given an explanation of the Informed Consent,  
g. 
indicated an understanding of the Informed Consent and  
h. 
signed the Informed Consent Form. 
v. 
Where applicable (dependent on local requirements), have their parent or legal guardian: 
a. 
read the Informed Consent,  
b. 
been given an explanation of the Informed Consent,  
c. 
indicated an understanding of the Informed Consent and  

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d. 
signed the Informed Consent Form. 
vi. 
Along with their parent or guardian (if applicable), be capable of comprehending the 
nature of the study, and be willing and able to adhere to the instructions set forth in this 
protocol. 
vii. 
Along with their parent or guardian (if applicable), agree to maintain the visit schedule 
and be able to keep all appointments as specified in the study protocol for the duration 
of the study (see Visit Schedule, Section 7.2.1). 
viii. 
Agree to wear the assigned contact lenses for a minimum of 10 hours per day, at least 6 
days per week, for the duration of the study and to inform the study investigator if this 
schedule is interrupted.  (Wearing time may be modified by the study staff for health 
reasons.) 
ix. 
Be in good general health, based on his/her and parent’s/guardian’s (if applicable) 
knowledge.  
x. 
Have best-corrected visual acuity by manifest refraction of +0.10 logMAR (20/25 Snellen 
equivalent) or better in each eye. 
4.5 
Exclusion Criteria 
Any of the following will render a subject ineligible for inclusion: 
i. 
Regular use of ocular medications (prescription or over-the-counter). 
ii. 
Current use of systemic medications which, in the investigators opinion, may significantly 
affect contact lens wear, tear film production, pupil size, accommodation or refractive 
state. 
iii. 
Pregnant or lactating or planning a pregnancy at the time of enrolment. 
iv. 
Known ocular or systemic disease such as, but not limited to: anterior uveitis or iritis, 
episcleritis or scleritis, glaucoma, Sjogren's syndrome, lupus erythematosus, 
scleroderma, or diabetes. 
v. 
Any ocular, systemic or neuro-developmental conditions that in the investigators opinion, 
could influence refractive development.   
vi. 
Keratoconus or an irregular cornea. 
vii. 
Biomicroscope findings that would contraindicate contact lens wear including, but not 
limited to: 
a. 
Any active anterior segment ocular disease that would contraindicate contact lens 
wear. 
b. 
clinically significant (Grade 3 or 4) abnormalities of the anterior segment, lids, 
conjunctiva, sclera or associated structures. 
viii. 
The investigator for any reason considers that it is not in the best interest of the subject 
to participate in the study. 
4.6 
Subject Identification 
Subjects will be identified by a four-digit code made up of the site number and their enrolment 
number. 
As data will be compared back to the MIST-401 Parts 1 and 2 data, the sites and subjects will 
keep the same number as they had in that study. Therefore, the subject numbers will not be 
sequential as subject numbers that were discontinued in the previous study, will not be used in 
this study.  

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4.7 
Study Withdrawal Criteria 
Due to the nature of the study, no circumstances are foreseen whereby this study would be 
prematurely terminated.  However, if during the study it becomes evident to either the sponsor 
or VCR that the study contact lenses pose a threat to subject well-being, the study will be 
terminated and the Research Ethics Committee (REC) will be advised of the reason for 
termination.   
4.8 
Subject Replacement 
Subjects that are discontinued or drop out of the study will not be replaced. 
4.9 
Medications/Treatments Permitted and Not Permitted During the Study 
Preservative free rewetting/comfort drops may be used in this study as needed to lubricate and 
rewet lenses, if agreed by the investigator.  
The use of topical ocular medications is contraindicated at all times during this study unless 
prescribed as part of a treatment for an adverse event.  The use of any ocular medications to 
treat conditions that arise will require temporary suspension of lens wear, an adverse event 
report, and evaluation of the subject for discontinuation from the study.   
For any adverse event where lens wear is suspended, an unscheduled follow-up evaluation of 
the subject must be performed before allowing the subject to return to lens wear.  Subjects may 
not return to lens wear until all topical ocular medications have been discontinued and a 
documented exam has verified the resolution of the adverse event. 
4.9.1 
Concomitant Medications 
Changes in concomitant medications from those recorded at the initial visit should be indicated 
on the follow-up visit forms by checking ‘Yes’ on the concomitant medication question and 
recording the change in the appropriate EDC forms. 
4.10 
Procedures for Monitoring Subject Adherence 
To track compliance, subjects will be asked their average contact lens wearing times, average 
number of days lenses are worn per week and about their contact lens experience at each 
follow-up visit.  This will be in the form of a questionnaire given to the subjects or questions on 
the CRF. 

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5 
MATERIALS 
5.1 
Study Lenses 
Table 1: 
Lens Details 
Brand 
Proclear 1 Day 
Manufacturer 
CooperVision 
Material/ water content 
omafilcon A / 62% 
Design 
Single vision 
Base curve (mm) 
8.70 
Diameter (mm) 
14.2 
Sphere powers (D) 
-0.25D to -8.00D 
(0.50D steps after -
6.00D) 
Only lenses distributed by VCR may be used for the study.  
If additional lenses are required, investigators should contact VCR.  
5.2 
Lens Care Products and Other Study Products 
Subjects will be instructed to dispose of their contact lenses every night and insert a new pair 
of lenses in the morning; therefore, contact lens cleaning, soaking and disinfecting products 
should not be required.  If the contact lenses must be removed briefly during the day for 
swimming or other activities then the subject should throw the lenses away and replace with a 
new pair afterwards.  Subjects should always carry a spare pair of contact lenses and 
spectacles in case the contact lenses need to be removed for any reason when not at home.   
Rewetting/comfort drops given to the subject by the investigator may be used in this study as 
needed to lubricate and rewet lenses. 
5.3 
Product Accountability 
The applicable study initiation documents (including but not limited to: investigator agreement, 
Statement of Investigator, IRB/IEC approval, protocol signature document, financial disclosure 
form, etc.) must be received by the CRO before investigational materials can be shipped to the 
investigational site.  If applicable, approval from the appropriate regulatory authorities must be 
obtained before shipping lenses to the investigational site.   
All study lenses will be sent to the investigational site by the CRO (see page 6).  An initial bank 
of lenses will be sent to the investigational site for initial dispensing.   
All study lenses must be inventoried upon receipt, recorded on the Lens Accountability Form 
by the investigational site and stored in a secure area, segregated from any other materials, 
and issued only as directed in the protocol.  The investigational site must document the 
dispensing and return (unused lenses only) of each investigational lens for each subject using 
the Lens Dispensing Forms provided in each subject’s study record.  
Study sites will not be required to retain any packaging from used lenses.   

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Study subjects must discontinue wearing the study lenses at the exit visit and all used lenses 
must be discarded.  All unused lenses must be returned to the study site and recorded on the 
subject’s Lens Dispensing Form.  All unused lenses must be returned at the 12-month visit. 
Study product accountability will be checked by the study monitor (assigned by the sponsor or 
CRO) during site monitoring.  All unused lenses, returned from subjects or never dispensed to 
the study subjects, must be available to the study monitor for verification of lens accountability 
at the completion of the study.  Any discrepancies in study lens accountability must be 
explained by the investigator.  After the study monitor has verified product accountability, any 
unused materials will be returned to the CRO or the sponsor at the end of the study unless the 
investigator is otherwise directed by the CRO or the study sponsor.  All product returned to the 
CRO or sponsor will be documented on the Lens Accountability Form.   
5.4 
Lens Wearing Schedule 
Subjects should be instructed to wear the study lenses for at least 6 days per week and 
preferably for 7 days per week. Subjects should wear the lenses for a minimum of 10 hours per 
day. 
Subject who do not wear for the minimum time will not be discontinued from the study but the 
data may be analysed separately. 
5.5 
Potential Risks and Benefits for Human Subjects 
Potential Risks and benefits for human subjects wearing contact lenses are summarised in the 
Informed consent document (separate document). 
5.6 
Study Documents and eCRFs 
The following forms will be completed where appropriate: 
eCRFs: 
A) Baseline forms (including eligibility checklist) 
B) 
Trial Fit / Dispensing form 
C) Follow-up forms (including Unscheduled Visit) 
D) Adverse Event forms 
E) 
Study Exit forms 
  
 
 
Additional Forms 
A) Patient Information Sheet/Statement of Informed Consent 
B) Participant Information Guide 
C) Enrolment Log 
D) Product Accountability Log 
E) Dispensing Log 
F) Source Document Record Labels 

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6 
TREATMENT 
6.1 
Study Product Formulations 
The test lenses will be shipped in blister packs containing a buffered saline packaging solution.  
The labelling of lenses and packaging will be the standard packaging which will indicate lens 
power, base curve, diameter, lot number and expiration date.   
6.2 
Lens Administration 
Lenses will be used on a daily disposable wear basis. Subjects should be instructed to wear 
the study lenses for at least 6 days per week and preferably for 7 days per week. Subjects 
should wear the lenses for a minimum of 10 hours per day. 
7 
METHODS AND ASSESSMENTS 
7.1 
Subject Recruitment 
Subjects on the MIST-401 Part 2 study will be sent a letter inviting them to take part in this 
study. 
The procedures listed below will be conducted on all subjects.  Variables must be collected in 
the order they are listed on the eCRF. 
7.2 
Study Visits 
7.2.1 
Visit Schedule 
There will be a maximum of four scheduled visits as follows: 
Visit 1:  
Baseline / Trial Fit / Lens Dispensing 
Visit 2:  
2-week Follow Up (Optional)* (14 days ± 5 days from dispensing) 
Visit 3:  
6-month Follow Up (180 days ± 14 days from dispensing) 
Visit 4:  
12-month Follow Up and Exit (360 days ± 44 days from Dispensing) 
* This is an optional visit if, in the investigator’s opinion, it is needed to confirm adaptation to 
the new lenses 
A Visit Schedule will be supplied to all sites and will list the visit windows; this can assist in the 
scheduling of visits within the appropriate window. 
The Investigator should confirm with the subject that they are able to attend the follow-up visit 
within the visit window before enrolling them in the study.  If, in extreme situations (sickness, 
unforeseen circumstances), the subject can only attend outside the visit window, the 
Investigator should discuss with VCR whether this visit can be considered a scheduled visit. 
A scheduled follow-up visit may only take place when the subject attends wearing the study 
lenses.  If this is not the case and the subject is not experiencing any problems with the lenses, 
the appointment will be re-scheduled, ideally within the visit window. 
See Section 7.5 for instructions regarding unscheduled visits. 

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7.3 
Clinical Variables 
Table 2 summarises the clinical measurements to be taken at each visit. 
The Baseline visit for MIST-402 is expected to be on the same day as MIST-401 Part 2 Exit 
Visit and will take place straight after the visit. 
The MIST-402 Exit Visit will ordinarily take place immediately following Visit 4, but may take 
place earlier if a subject discontinues from the study.  Slit lamp assessment to be performed if 
Exit Visit does not take place immediately after a follow-up visit. 

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Table 2: 
Summary of Clinical Measurements 
PROCEDURES 
BASELINE 
DISPENSE 
FOLLOW UP VISITS 
 
Day 0 
2 wk 
6 Mo 
12 Mo 
UN-
SCHED 
Exit 
Informed Consent and 
Assent 
X 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
Med History 
X 
 
 
 
 
 
 
 
 
X* 
 
X 
X 
X 
 
 
Concomitant medications 
review 
X 
 
X 
X 
X 
X 
 
Lensometry 
X* 
 
 
 
X 
 
 
Entrance VA 
X 
 
X 
X 
X 
X 
 
 
 
X 
X 
X 
X 
 
 
 
  
X* 
 
 
 
 
 
 
 
X* 
 
 
 
X 
 
X+ 
 
 
X* 
 
 
 
X 
 
X+ 
 
) 
X 
 
 
 
X 
 
 
 
X 
 
X 
X 
X 
X 
 
 
) 
 
X 
X 
X 
X 
 
 
Contact lens over-refraction 
 
X 
X 
X 
X 
 
 
 
 
X 
X 
X 
X 
 
 
 
X* 
 
 
X 
X 
 
 
Cycloplegic auto-refraction 
X* 
 
 
X 
X 
 
 
Cycloplegic biometry (axial 
length) 
X* 
 
 
X 
X 
 
 
 
 
X* 
 
 
 
X 
 
 
 
 
 
 
X 
X 
 
 
Exit VA 
 
 
X 
X 
X 
 
X+ 
Dispense study lenses 
 
X 
X 
X 
 
 
 
Complications, Adverse 
Events &device 
malfunctions 
Complete where applicable 
Parent/Guardian Informed 
Consent (if applicable) 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
* If already collected for the MIST-401 Part 2 study final visit, this measurement does not need to be repeated and the 
information can be taken from that final visit CRF as long as within a week of enrolment in MIST-402. 
+ if not completed at the associated visit.  
7.4 
Subject Discontinuation 
Subjects may be discontinued from the study in the event of any of the following occurring: 
i. 
Unacceptable subjective discomfort (i.e. lens cannot be tolerated or worn) 

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ii. 
Unacceptable slit lamp findings 
iii. 
Unacceptable fit (i.e. lens too tight or too loose) 
iv. 
At the discretion of the Investigator or the subject 
v. 
Subject out of Rx range for the lenses.  
In the event of discontinuation, the Study Exit eCRF must be completed and the study exit date 
recorded on the Source Document Record.  The Investigator will indicate the primary reason 
for discontinuation by selecting one of the boxes provided on the Exit eCRF.  Comments can 
be added to the eCRF if necessary. 
If a subject is discontinued outside of a visit window, an Unscheduled Visit eCRF must also be 
completed 
7.5 
Unscheduled Visits 
An unscheduled visit is defined as any follow-up that occurs outside the visit window of the 
scheduled visit.  A visit is also classified as unscheduled if the subject is seen a second time 
within the scheduled visit window. 
Investigators should try as far as possible to schedule follow-up visits within the window.  If this 
is not possible, and the visit falls outside the window, the visit will be an unscheduled visit, 
unless it has been agreed with VCR that it can be considered a scheduled visit. 
Alternatively, the Investigator might judge that a follow-up visit is in the best interest of the 
subject and schedule two visits within the same window, e.g. follow-up of an adverse event.  
Unscheduled visits are also made available anytime at the subject’s request. 
Unscheduled visits will be recorded on the Unscheduled Visit eCRF.  All variables listed on the 
forms must be completed unless the subject exhibits a condition that prohibits the completion 
of a full visit.  If this is the case, a written explanation is required in the comments section (e.g. 
not wearing lenses due to discomfort). 
Presenting VA and slit lamp variables must always be completed and the reason for the visit 
and any actions taken must be indicated on the forms. 
7.6 
Site Training and Visits 
The study initiation will take place via on-line training modules and a phone call. 
The sponsor or VCR may choose to initiate a site visit as deemed appropriate.  If this occurs, 
VCR will email prior to the visit to arrange a convenient time.  Interim and close-out monitoring 
visits will be documented in the Monitoring Plan which is a separate document. 
8 
ADVERSE EVENTS 
An Adverse Event (AE) is defined as any unfavourable or unintended sign (including an 
abnormal finding), symptom or disease temporarily associated with the use of a study device 
whether or not related to the study device.  All ocular AEs and related (to the study device 
and/or to the study procedures) non-ocular AEs, will be monitored and reported on throughout 
the study. 
 
 

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8.1 
Adverse Event Categorization 
The Investigator will be required to rate the likelihood of an event being device-related 
(Possible, Probable, Highly Probable) or non-device-related (unlikely, definitely not) in their AE 
evaluation.   
All device-related AEs will be tabulated and reported in the final report. 
8.2 
Adverse Event Reporting 
On finding an AE the Investigator will complete an Adverse Event form (AE form) in EDC to 
capture the event. 
The Investigator must notify Visioncare Research of the AE, so that they are able to provide 
advice and support to the Investigator on how to proceed. 
The Investigator must do this by providing the information on the AE eCRF as soon as possible 
and no later than: 
• 
24 hours from discovery if event is Serious or Significant 
• 
5 working days from discovery if event is Non-Significant 
Once the form is saved, an automatic email will be sent to VCR and the Sponsor to notify them 
of the event.  If the AE form in EDC cannot be completed on the day of discovery of the AE, 
then the VCR monitor and the Sponsor (via email address
) 
must be contacted to notify them of the AE.  
If applicable, VCR will advise the Investigator to notify the REC as per the REC requirements.  
VCR may notify the REC on behalf of the Investigator. 
The Investigator must notify VCR in writing that the AE has been reported to the REC. 
8.3 
Adverse Event Documentation 
Investigators are required to document and follow-up all AEs. 
All AEs are documented on an AE form in EDC upon event discovery.  For all ocular AEs, one 
AE form is used per eye. For AEs which are non-ocular but related to the study device or to the 
study procedures only one AE form needs to be completed in EDC per AE.   
 
 
 
  
 
 
   
 
 
 
 
  
 
 
 
 
 

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8.4 
Adverse Event Follow-up 
The Investigator will conduct follow-up examinations until the condition: 
• 
Has returned to pre-event status,  
• 
Is considered stabilized 
• 
Or has been satisfactorily explained. 
If the subject is referred for medical attention, they will be tracked by the Investigator until the 
aforementioned conditions are met. 
Follow-up data will be collected on an unscheduled visit eCRF and on the AE form in EDC. 
The Investigator should use his/her clinical judgement as to whether or not the subject reporting 
with an AE should continue in the study. 
8.4.1 
Device Malfunction 
A malfunction means the failure of the device to meet its performance specification or otherwise 
perform as intended. A malfunction is considered reportable to the Sponsor if it would be likely 
to cause or contribute to a Serious Adverse Event. 
The Investigator will be required to report all reportable device malfunctions to the study 
CRO/Sponsor via the applicable form in the EDC system. 
8.4.2 
Sponsor Safety Responsibilities 
The sponsor will ensure that all participating Investigators are promptly informed of significant 
new safety information with respect to the study devices as per regulatory requirements. 
To comply with this, the sponsor is responsible for promptly advising (in writing, via VCR) all 
Investigators conducting clinical studies of any incidents of serious or unexpected adverse 
events/unanticipated adverse device effects reported for the devices/products involved in those 
studies. 
8.5 
Study Completion 
The study is completed when all subjects have completed visit 4 or been discontinued, and 
have been exited from the study. 

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9 
DATA MANAGEMENT 
9.1 
Electronic Case Report Forms/Data Collection 
The clinical data for this study will be entered by designated study site personnel onto electronic 
report forms (eCRFs) using the electronic data collection (EDC) system Medrio. Paper 
questionnaires will be given to subjects to complete. 
Medrio is compliant with all relevant aspects of ICH/Good Clinical Practices and 21 CFR Part 
11 (Electronic Records & Electronic Signatures) regulations. 
9.2 
Data Quality Assurance 
When eCRFs are reviewed at VCR, they will be subjected to error checking and data queries 
will be raised electronically via the EDC system for resolution of omissions and discrepancies 
by the investigator.   
Before the final closing of the database, the data will be checked and approved for analysis as 
per VCR SOPs.  This includes checking for missing or erroneous data entries  
9.3 
Data Entry and Storage 
All study data shall be entered into the study eCRFs. Completed subject questionnaires (paper) 
will be sent to VCR on a regular basis and data from the questionnaires will be hand entered 
into a database using DaCS software and then exported to an Excel database (Microsoft).   
All statistical analyses will be completed by VCR using SAS software (SAS Institute Inc., 
Version 9.4 or later). 
10 
SAMPLE SIZE AND STATISTICAL METHODS 
10.1 
Sample Size Rationale 
All eligible subjects that complete the MIST-401 Part 2 study will be invited to continue in this 
study.  No new subjects will be enrolled.  Based on the current study, there will be approximately 
90 subjects completing the study: 44 with six years of MiSight experience (Group T6; original 
test group in Part 1) and 46 with three years of MiSight experience (Group T3; original control 
group in Part 1).   
Primary Hypothesis 
From the MIST-401 Part 1 study, the standard deviations for the paired mean difference and 
the 2-sample means were estimated.  From these the sample sizes of 44 in group T6 and 46 
in group T3 will provide at least 99% power to detect non-inferiority. 

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The mean annual myopic progression will be calculated by dividing the myopic progression for 
the years in question by the number of years for each subject.   
The overall type I error rate will be preserved at 5%.  The co-primary hypotheses will be 
simultaneously evaluated using α=0.05. 
Data from unscheduled visits will not be included in the analysis. 
10.4 
Analysis Population 
The statistical analysis for efficacy hypothesis testing will be performed as follows: 
1. All available data – this will include all data from subjects that have completed follow-
up visits. Counts of missing data will be included in the summary statistics. 
2. Intent-to-treat – this will include any subject that has completed at least the 6-month 
visit. Missing data for 12-month myopia progression and axial length will be 
extrapolated, where possible, from the 6-month data for the intent-to-treat analysis. 
10.5 
Descriptive Statistics 
Descriptive statistics will be reported at dispensing and each follow-up visit. Continuous 
variables will be summarized using mean, standard deviation, and range; and categorical data 
variables will be summarized using percent frequency distribution, mean, and SD. Nominal 
variables will be summarized using percentages. 
Summaries will be presented by group (T3: 3 years of MiSight wear and T6: 6 years of MiSight 
wear. 
10.6 
Data Pooling 
Data will be pooled from multiple study sites for this analysis, the basis for pooling comes from 
three factors: 
• 
The study sites must implement one common protocol.  
• 
The CRO must closely monitor study site protocol compliance. 
• 
The study sites must use common data collection procedures. 
10.7 
Primary Statistical Analysis 
T3 Group:  The mean myopic progression after cessation of MiSight wear will be compared to 
the mean annual progression for the first three years (MIST-401 Part 1) for this same group of 
subjects (“T3 Baseline”) on a pairwise basis using linear mixed models.  The model will include 
part, site, and the interaction of site-by-part as fixed effects and subject (nested in site) and eye 
as random effects.  The fixed covariates: subject age group, sex, ethnicity, and baseline myopia 
(refractive error or axial length) may also be included.  If there are convergence issues with the 
model some or all the covariates may be removed as required. 
Statistical non-inferiority will be concluded if the 95% confidence limit of the mean difference of 
the progression rate after cessation compared to the T3 Baseline rate is greater than 
­0.25D/year for spherical equivalent refractive error or less than +0.1mm/year for axial length. 

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T6 Group:  The mean myopic progression after cessation of MiSight wear will also be 
compared to the T3 Baseline mean annual progression using a linear mixed model.  The model 
will include group (T6 or T3), site, and the interaction of site-by-group as fixed effects and 
subject (nested in site) and eye as random effects. The fixed covariates: subject age group, 
sex, ethnicity, and baseline myopia (refractive error or axial length) may also be included.  If 
there are convergence issues with the model, some or all the covariates may be removed as 
required. 
Statistical non-inferiority will be concluded if the 95% confidence limit of the mean difference of 
the progression rate after cessation compared to the T3 Baseline rate is greater than 
­0.25D/year for spherical equivalent refractive error or less than +0.1mm/year for axial length. 
10.8 
Secondary Statistical Analysis 
The myopic progression after cessation of MiSight wear will be compared to the mean annual 
myopic progression for previous 3 year’s MiSight treatment (MIST-401 – Part 2) on a pairwise 
basis using linear mixed models.  The model will include treatment, site, years of MiSight wear 
(T6 or T3), and the interaction of site-by-treatment as fixed effects and subject (nested in site) 
and eye as random effects.  The fixed covariates: subject age group, sex, ethnicity, and 
baseline myopia (refractive error or axial length) may also be included.  If there are convergence 
issues with the model some or all the covariates may be removed as required. 
A statistical difference will be concluded if the 95% confidence limit of the mean (test-control) 
difference is greater than 0 for spherical equivalent refractive error or less than 0 for axial length. 
10.9 
Tertiary Statistical Analysis 
  
 
  
 
 
 
 
 
 
10.10 
Additional Statistical Analysis 
 
 
Any deviations from this analysis plan will be detailed in the study report. 
10.11 
Interim Analysis 
There are no planned interim analyses for this study.  

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11 
GENERAL STUDY MANAGEMENT 
11.1 
Relevant Standards 
This protocol has been developed in accordance with the following:   
• 
ISO 14155-1:2011 Clinical Investigation of Medical Devices for Human Subjects 
• 
ISO 11980:2012 Contact Lenses and Contact Lens Care Products – Guidance for Clinical 
Investigations. 
• 
ICH Harmonized Tripartite Guideline for Good Clinical Practice 
• 
Declaration of Helsinki 
The study will also be carried out in accordance with the VCR Quality Management System 
(ISO 9001:2015) and all the applicable local guidelines. 
11.2 
Ethics Review 
The study protocol, Participant Information Sheet and Informed Consent Form, Informed Assent 
Form (where applicable) and all other required documents will be submitted to local REC/IRB 
for each site.  A favourable opinion will be received prior to undertaking the study. 
If significant protocol changes which require the preparation of an amendment are necessary, 
written REC/IRB approval will be obtained prior to implementation. 
11.3 
Protocol Deviations 
The Investigators will not deviate from the protocol without written approval from the REC and 
VCR.   
In medical emergencies, Investigators will use their judgement and remove the subject from 
immediate hazard.  Any significant changes or deviations in the protocol will be the subject of 
a protocol amendment and must be pre-approved by the REC 
If an unexpected deviation from the protocol occurs the Investigator must notify the CRO (VCR) 
immediately and the deviation from the protocol will be reported on a Protocol Deviation form 
in EDC and appropriate action taken. 
11.4 
Premature Termination of the Study 
The sponsor reserves the right to terminate the study at any time for any reason including 
adverse effects.  If it is determined that an unanticipated adverse device effect presents an 
unreasonable risk, then the entire investigation or part of the investigation presenting the risk 
shall be terminated as soon as possible.  A written statement fully documenting the reasons for 
such termination will be provided to the REC. 
11.5 
Source Documentation 
Unless otherwise documented, the eCRFs will be considered the source document.  The 
sponsor or sponsor’s representatives will be authorized to gain access to the source 
documentation for the purposes of monitoring and auditing the study (See Sections 11.6, 11.7). 

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The Source Document Record must be completed to comply with GCP guidelines.  It is a 
permanent record within the patient’s chart/notes that documents the subject’s involvement in 
a clinical research study. 
Contents of the source document record: 
• 
Study number 
• 
Subject ID 
• 
Confirmation that subject met eligibility criteria 
• 
Confirmation that subject signed the informed consent 
• 
Confirmation that subject received a signed and dated copy of informed consent 
• 
Date enrolled 
• 
Details of lenses worn on study 
• 
General notes 
• 
Adverse events 
• 
Reportable Protocol deviations 
• 
Exit date 
• 
Whether subject completed the study or discontinued 
• 
Investigator’s signature 
The Source Document Record will be completed for each subject upon enrolment and then 
updated when required, e.g. when subject exits the study. 
Note:  If study information is collected using an automated piece of equipment, the information 
should be recorded directly from the instrument display to the eCRF or from an instrument 
printout if there is no display.  The eCRF will become the source document if there is no printout.  
If a printout is obtained from the instrument, the original printout must be placed into the 
subject’s study record as a source document with the subject number and date of recording 
noted on the printout.   
11.6 
Monitoring 
Investigational site monitoring will be performed by a qualified study monitor identified by the 
sponsor or VCR.  On-site visits will be completed at each site.  The frequency and procedure 
of the monitoring visits will be documented in the Monitoring Plan which is in a separate 
document.  The Investigator will allow the study monitor and sponsor representatives or REC 
to observe procedures and inspect study records and subjects’ medical records throughout the 
study to verify protocol compliance, case report completeness, and investigational material 
accountability.  Should the Investigator be found to be non-compliant and unwilling or unable 
to convert noncompliant practices, VCR in consultation with the sponsor will terminate the 
Investigator’s role in the investigation and the REC will be notified. 
11.7 
Audits 
The Investigator shall permit VCR, the sponsor and the REC to inspect its facilities, equipment, 
and study-related records, data and other documents upon reasonable notice.  In addition, the 
REC may conduct such inspections as they deem necessary at any time whether or not 
advanced notice is given by them.  The Investigator agrees to notify the sponsor or VCR within 
24 hours (or as soon as reasonably practicable) of the start of any unannounced inspection by 
the REC or of the receipt from the REC of a notice of inspection whether given in writing or 
orally.  If such notice is in writing, a copy with any attachments thereto shall be provided to VCR 
or the sponsor. 

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11.8 
Records Retention 
According to the ICH GCP guidelines the essential documents should be retained until at least 
two years after the last approval of a marketing application in an ICH region and until there are 
no pending or contemplated marketing applications in an ICH region or at least two years have 
elapsed since the formal discontinuation of clinical development of the investigational product.  
It is the responsibility of the sponsor to inform the Investigator/institution as to when these 
documents no longer need to be retained.  The study lens material is already on the market 
and therefore the study documents should be kept for a minimum of two years after the end of 
the study.  As the clinical research organisation supervising the study, VCR will also retain the 
written records for the same period of time.  Following such retention period, the Investigator 
or the Clinical Site shall deliver to the sponsor all such Research Results, unless otherwise 
instructed in writing by the sponsor.  Notwithstanding the foregoing, all information provided by 
or with respect to subjects in the Study will be furnished by Investigator and Clinical Site without 
patient names. 
11.9 
Confidentiality and Publication 
This study is confidential in nature.  The Investigator shall make no public statement, whether 
in written, oral or electronic form, relating to the CRO, the Sponsor, the substances, materials, 
products and devices being investigated or the Study itself without obtaining the prior written 
consent of the CRO or the Sponsor. 
All information gathered during this study is proprietary and should be made available only to 
those directly involved in the study who have a need to know.  
Authorised recipients of this data include: 
 
Investigator and co-investigator(s) 
 
Other allied health care personnel necessary for the conduct of the study 
 
IRB/IEC personnel 
 
Sponsor representatives 
 
Contract Research Organisation 
 
Designated study monitor 
 
Designated medical monitor  
 
FDA or other government regulatory agencies 
All above personnel who are provided with data concerning this study will be informed of its 
confidential and proprietary nature.  Release of this data (through presentation, publication or 
other written or oral communication) to other than the above listed personnel requires the prior 
written permission from the study Sponsor.  Study investigators and all office personnel are 
prohibited from acknowledging participation in the study to individuals and organisations except 
those listed above.  This includes sales representatives and other departments or subsidiaries 
of the sponsor without the direct written permission of the sponsor. 
The study will conform to the requirements of the General Data Protection Regulation (GDPR).  
By signing the Informed Consent form the subject authorizes the sponsor and the sponsor’s 
representatives (VCR) to access their optometric clinical records.  The authorization will be 
indefinite; however, subjects will have the right to reverse this authorization at any time. 
All patient information will have the patient name (or any information that can identify the patient 
apart from the mobile phone number) removed before leaving the Principal Investigator’s site. 
In accordance with the VCR Confidentiality Policy, the data, information, and reports arising 
from this project are the property of the sponsor company located in the USA.  By signing the 
Informed Consent Form the subject also understands that their data will be sent to VCR 
 

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and the sponsor 
.  VCR will not release to a third party any information arising 
from this study unless required to do so by a legal or regulatory body.  The electronic records 
will also be handled in accordance with the General Data Protection Regulation (GDPR) (2018).  
The Medrio EDC system is compliant with the U.S.-EU Safe Harbor Framework and the U.S.-
Swiss Safe Harbor Framework as set forth by the U.S. Department of Commerce regarding the 
collection, use, and retention of personal information from European Union member countries 
and Switzerland. Medrio has certified that it adheres to the Safe Harbor Privacy Principles of 
notice, choice, onward transfer, security, data integrity, access, and enforcement to ensure the 
privacy of all information collected. 
The trial results will be reported on the NIH website, www.ClinicalTrials.gov. 
12 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 

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APPENDIX A 
 
 
 
PROCEDURES, EQUIPMENT 
 
 
 

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AUTO-REFRACTION 
The following procedures apply to all auto-refraction measurements in the study (non-cycloplegic and 
cycloplegic): 
Equipment 
Binocular Auto Refractor/Keratometer WR-5100K or WAM-5500 (Grand Seiko) 
Consult the Operating Manual for Proper Care of the Instrument, Preliminary Set-Up and more information 
on operating procedures. 
Preparation 
Important Considerations 
The WR-5100K and WAM-5500 are precision optical instruments. Always handle with care especially 
when moving. 
1. Ensure that the instrument is OFF before connecting to a power source. Connect instrument to 
safety power strip used for computers. 
2. Do not touch the optical parts (i.e. mirrors or lenses) with fingers and be sure to avoid dust. When 
not in use, protect the instrument with a supplied dustproof cover and lock instrument down with 
anti-sliding screw lock. 
3. If the instrument is not used for any length of time, disconnect the safety power strip, with the 
power cord, from the wall or floor outlet.  
Calibration 
At the beginning of EACH MEASUREMENT WEEK, check the calibration of the instrument and document 
on the instrument calibration / service record.  
1. Set PD CENTRE to OFF and VD to 0 when measuring the supplied model eye. 
2. When the measurement result of the model eye falls within the tolerance limits, proceed with the 
measurements. If the result exceeds the tolerance, contact CVI immediately and arrange for a 
Service Call for the instrument. Make a note on eCRF. 
 
TOLERANCE= +/-0.25 sph, +/-0.25 cyl, +/-0.03 Radius of curvature.  
3. Set the model eye in the contact lens holder and be sure that it is level and centred relative to the 
optical axis of the instrument.  
4. Proceed as you would for autorefraction of a real eye (see below). 
Mode Selection Screen 
1. Press the MODE switch on the right side of the LCD monitor 

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2. The following settings should be selected:  
STEP  
 
0.12 
VD 
0 
CYL 
- 
START 
QUICK(5)† 
REF 
NORMAL 
KERATO 
DIOPT 
SE 
OFF 
PRINT FORM 
ALL 
DATA SCREEN 
OFF 
W-D (cm) 
OFF 
SCREEN ADJ 
AS NEEDED 
SAVE (min) 
5 
PD CENTRE 
OFF 
BUZZER 
LOW 
OPTION* 
No. 
DATE FORM 
YMD 
DATE 
 
TIME 
 
 
† Press ‘+’ to change default setting from 3 to 5. 
*This function allows you to input a message, set patients ID number, and download data to external 
computer 
MESSAGE: Shifts to the screen for registering message. Enter your clinic's name the first time you use 
the WR-5100K or WAM 5500. After that it should print on all printouts. 
No: Shifts to the screen for setting Subjects ID number. SET THIS FOR EACH NEW PATIENT. 
Accom R/K Selection Switch:  This switch is used to change the measurement mode. 
The mode changes every time the switch is pressed as follows: 
FAR → -2.0 D/50 cm → -2.5 D/40 cm → -3.0 D/33 cm → -4.0 D/2.5 cm→ -5.0 D/20 cm  
R/K → R → K → FAR 
Select R/K (refraction & keratometry) 
Procedure 
Patient Set Up 
1. Check that there is sufficient printer paper in the printer and tissue paper on the chin rest. Follow 
manual instructions to replace. 
2. Enter the Subject's ID using the OPTION mode above. For parent’s auto-refraction, use Subject’s 
ID and record ‘father’ or ‘mother’ on the printout.  
3. Clean the chin rest, head rest and occluder with hydrogen peroxide or alcohol swab. 
4. Establish the most comfortable and convenient position for the subject by vertically adjusting the 
instrument table to meet his/her eye level. Adjust chin rest until subject's outer canthus is aligned 
with the eye mark on the head rest. 
Alignment 
1. Use the joystick to image the subject's eye on the monitor.  
2. A kerato ring will appear. (If the eyelid is over the illumination ring, ask the subject to open his/her 
eyes wider.) 
3. Have subject view the appropriate target. 

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4. Align the reticule mark to the centre of the eye and focus on the subject's eye by moving the 
joystick forward or back.  
5. An alignment mark (+) will appear. 
6. Operate the joystick to bring the alignment mark (+) into the centre of the reticule mark. 
7. It may be necessary to move the target to achieve alignment. When alignment is not achieved, 
values tend to fluctuate during measurement. If the subject moves his/her head during 
measurement, the AXIS value on the cyl reading will be in error.  
Alignment Tips: 
Move the fixation target in the opposite direction to how the reticule mark and reflected corneal image 
(ring image) are imaged relative to the pupil centre. Example, for the RE, if the reticule mark and kerato 
ring are on the left side of the subject's pupil, his/her gaze is too nasal. Thus, move the fixation point 
temporally. If difficulty with alignment occurs, examiner should place him or herself behind autorefractor 
and observe the brief flash of the measurement light, a faint red measurement pattern. Have a helper 
move the target until your eye is aligned with the centre of the pattern. Note location of the target. Minor 
adjustments will be needed for other subjects.   
Measurement 
Keeping the alignment mark (+) in the centre of the reticule mark, focus the subject's eye. This occurs 
when the kerato ring is thinnest. 
1. Have the subject blink and regain fixation. Note: A blink ensures that tear residue or eye mucus 
trapped on the corneal surface does not cause measurement error. 
2. Press the measurement start switch and record 5 measurements.  
3. Move to the other eye and repeat the measurement procedure. 
Note: 
In the data analysis, potentially erroneous cylinder values or sphere values (identified as being greater 
than 1.0D from the mode), due to unsteady fixation, may be excluded.   

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 AXIAL LENGTH 
 
Equipment 
IOL Master (Carl Zeiss) 
Preparation 
1. Ensure that the child is not wearing contact lenses or spectacles. 
2. Seat the child behind the IOL Master; adjust headrest, instrument and seat height to ensure comfort 
and to discourage unnecessary eye movements. 
3. Enter the child’s name, date of birth and study ID number. 
4. Enter ‘Overview Mode’. Adjust the instrument to measure the RE first. With the child viewing the yellow 
fixation light with the RE, adjust the instrument-to-eye distance until the six light reflections on the 
cornea are in focus. The small circle of lights and the cross-hairs should be centred in the child's pupil. 
Procedure 
1. Select ALM (Axial Length Measurement) mode. (In ALM mode, the fixation light turns to red.) 
2. Ask the child whether they see the red fixation light clearly. If necessary, adjust the instrument until 
they do, and ask the child to keep looking at the fixation light. 
3. Ask the child to blink before each measurement. 
4. Take measurements of axial length by pressing the button on the joystick. The display next to the 
video image will show the measured axial length in millimetres (mm). The video image will be overlaid 
with a line graph similar to those from A-scan instruments. The signal-to-noise ratio (SNR) of the 
measuring signal will also be displayed. See ‘Data Evaluation’ section below for the significance of 
SNR. 
5. After the second measurement, the mean of the axial length measurements will also be displayed. 
This value will be updated with each measurement. If the result of one measurement differs by more 
than 0.1 mm from the others, an ‘Evaluation’ message will be displayed in place of the mean value. 
This indicates that the results should be evaluated later (see ‘Data Evaluation’ section below). 
6. ‘Error’ in the display field denotes readings with an SNR smaller than 1.6. These individual readings 
are excluded from the computation of the mean value, but they should not be deleted. 
7. The number of measurements that have been taken on the eye on this particular day is displayed in 
the ‘Mode’ field of the status bar next to ‘ALM’. If the count reaches 20, no further measurements of 
this eye can be taken on this day (date). This is for safety reasons. The counter cannot be reset and 
deleting readings does not affect the measurement counter. 
8. Continue taking measures until 5 measurements of axial length have been made on the RE. 
9. Do not delete any readings under any circumstances. 
10. Re-align the instrument to measure the LE as described above for the RE. 
11. Record 5 measurements of axial length of the LE. 
12. Print out the Results. Check that the name of the child, their ID number and the date of measurement 
are correct on the printout. 
13. Make at least one copy and store the paper version of the results in a master file.  
Note: The IOLMaster is not intended as a data archive. The maximum length of time that data can be held 
on the IOLMaster is 100 days. The machine will then delete the data automatically. 
Axial Length Data Evaluation 
1. The signal to noise ratio (SNR) indicates the quality of measurement. Measurements with an SNR 
between 1.6 and 1.9 appear with an exclamation mark (!) after the measured value and the message 
‘Borderline value’ will appear. ‘Borderline value’ does not necessarily mean that the reading must be 
rejected, but suggests that all axial length measurements for the eye should be checked for plausibility 
and consistency. If the ‘uncertain’ values are consistent with the other readings, the readings marked 

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‘Borderline value’ should be accepted as valid axial length measures. (In the DIMENZ trial we have 
only accepted data in which the SNR ≥ 2.0) 
2. The hard-copy printout of the data will be used for verification in data audit. Although there is a backup 
facility on the IOLMaster, the saved files will only record the mean axial length, not each individual 
reading. Thus, print-out of the results is mandatory. 
 
 

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APPENDIX B