Comparison of Tear Evaporation Rate With DAILIES TOTAL1 and Biotrue ONEday
Phase: NA
Conditions: Evaporative Dry Eye
Sponsor: University of Waterloo

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MALTESE Protocol 24jul2019 
 
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MALTESE Protocol 24jul2019 
 
4 
 
DOCUMENT CHANGE HISTORY 
 
Version 
date 
Author 
Description of change(s) 
25Jun2019 
 
Original protocol 
24Jul2019 
 
 
 
 
Section 4.2.3 “11. Has a wearable pair of spectacles.” 
has been added as an inclusion criterion. 
 
Section 4.4.3 updated to clarify that the participant will 
apply the petroleum jelly. 
 
Section 4.4.3 and 4.4.4 updated to clarify that the 
participant will remove the petroleum jelly. 
 
Section 4.5.11: 
• 
Removed “The syringe also be wiped with an 
alcohol wipe prior to use.”  
• 
Added “A new sterile, syringe will be used for 
each participant.” 
 
Section 6 added “Participants may experience 
temporary discomfort including: blurred vision and light 
sensitivity.” 
 
 
 
 
 

 
MALTESE Protocol 24jul2019 
 
5 
Table of contents 
Document change history ............................................................................................................ 4 
1 
Introduction .......................................................................................................................... 9 
2 
Objectives.......................................................................................................................... 10 
3 
Hypothesis......................................................................................................................... 10 
4 
Materials and methods ...................................................................................................... 10 
4.1 
Study design .............................................................................................................. 10 
4.1.1 
Overall design .................................................................................................... 10 
4.1.2 
Randomization ................................................................................................... 11 
4.1.3 
Masking ............................................................................................................. 12 
4.2 
Study population ........................................................................................................ 12 
4.2.1 
Sample size calculation ...................................................................................... 12 
4.2.2 
Number of participants ....................................................................................... 12 
4.2.3 
Inclusion and exclusion criteria ........................................................................... 12 
4.2.4 
Repeated screenings ......................................................................................... 13 
4.3 
Study materials .......................................................................................................... 14 
4.3.1 
Lenses ............................................................................................................... 14 
4.3.2 
Lens care system ............................................................................................... 14 
4.3.3 
Rewetting drops & saline .................................................................................... 14 
4.3.4 
Ordering consumables ....................................................................................... 15 
4.3.5 
Disposing of consumables ................................................................................. 15 
4.3.6 
Product accountability ........................................................................................ 15 
4.3.7 
Contact lens dispensing ..................................................................................... 15 
4.4 
Scheduled and unscheduled visits ............................................................................. 15 
4.4.1 
Study visits ......................................................................................................... 15 
4.4.2 
Visit 1: Screening ............................................................................................... 16 

 
MALTESE Protocol 24jul2019 
 
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4.4.3 
Visit 2: Baseline and dispensing visit .................................................................. 17 
4.4.4 
Visit 3: Follow up & study exit ............................................................................. 19 
4.4.5 
Unscheduled visits ............................................................................................. 20 
4.5 
Study procedures ....................................................................................................... 20 
4.5.1 
Demographics .................................................................................................... 21 
4.5.2 
Contact lens history ............................................................................................ 21 
4.5.3 
Medical history ................................................................................................... 21 
4.5.4 
Contact lens dry eye questionnaire (CLDEQ-8) .................................................. 22 
4.5.5 
logMAR visual acuity .......................................................................................... 22 
4.5.6 
Meibomian gland assessment ............................................................................ 22 
4.5.7 
Lid margin assessment ...................................................................................... 22 
4.5.8 
Slit lamp biomicroscopy ...................................................................................... 23 
4.5.9 
Contact lens fitting .............................................................................................. 24 
4.5.10 
Anterior eye photographs ................................................................................... 24 
4.5.11 
Measurement of volume inside the goggle ......................................................... 24 
4.5.12 
Slit lamp biomicroscopy (safety variable)............................................................ 25 
4.5.13 
Application of petroleum jelly .............................................................................. 26 
4.5.14 
Removal of petroleum jelly ................................................................................. 26 
4.5.15 
Subjective comfort ratings .................................................................................. 26 
4.5.16 
Evaporimetry ...................................................................................................... 26 
4.5.17 
Non-invasive tear film break up time (NITBUT) (Keeler Tearscope) ................... 27 
4.5.18 
Lipid layer thickness (Keeler Tearscope) ............................................................ 28 
4.5.19 
Lipid layer thickness (TearScience Lipiview II) ................................................... 28 
5 
Monitoring protocol adherence .......................................................................................... 28 
6 
Potential risks and benefits to human participants ............................................................. 28 
7 
Adverse events .................................................................................................................. 29 

 
MALTESE Protocol 24jul2019 
 
7 
8 
Discontinuation from the study ........................................................................................... 30 
9 
Study completion and remuneration .................................................................................. 31 
10 
Statistical analysis and data management ......................................................................... 31 
10.1 
Statistical analysis...................................................................................................... 31 
10.2 
Data management ..................................................................................................... 32 
10.3 
Comments on source documents ............................................................................... 32 
11 
Protocol training................................................................................................................. 32 
12 
Study monitoring................................................................................................................ 33 
13 
Study management ........................................................................................................... 33 
13.1 
Statement of compliance............................................................................................ 33 
13.2 
Ethics review.............................................................................................................. 33 
13.3 
Clinical trial registration .............................................................................................. 33 
13.4 
Protocol deviations..................................................................................................... 33 
13.4.1 
Major protocol deviations ................................................................................... 34 
13.4.2 
Minor protocol deviations ................................................................................... 34 
13.4.3 
Reporting and documenting protcol deviations ................................................... 34 
13.5 
Premature termination of the study ............................................................................ 35 
13.6 
Study participant records ........................................................................................... 35 
13.7 
Retention of study records and data .......................................................................... 35 
14 
Report ............................................................................................................................... 35 
15 
References ........................................................................................................................ 35 
 
 

 
MALTESE Protocol 24jul2019 
 
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 Confidentiality 
This is a private document and the property of the Centre for Ocular Research & Education. It 
is therefore confidential to the recipient and must not be quoted from or distributed beyond the 
company to which it is sent without the express written permission of the Director (or her/his 
designate) of the Centre for Ocular Research & Education. Release of information from this 
document is governed by the research agreement on file. 
 
Disclaimer 
This study will be conducted for research purposes only and is not intended to be used to support safety 
and efficacy in a regulatory submission. 
 
 
 

 
MALTESE Protocol 24jul2019 
 
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1 
INTRODUCTION 
There are estimated to be more than 140 million contact lens (CL) wearers throughout the world 
and approximately 50-75% of CL wearers report suffering from symptoms of irritation while 
wearing their lenses.1 CL-related dryness is a leading cause of CL discontinuation1  2 and two 
factors reportedly related to CL dryness include a rapid pre-lens tear film thinning time and lenses 
with a higher nominal water content.3  
Evaporimetry is a non-invasive method of assessing the rate of evaporation of the tear film from 
the front surface of the eye. At present, there is only one commercial evaporimeter, the Eye-
VapoMeter (Delfin Technologies Ltd., Finland), available for clinical use. The 2017 TFOS DEWS 
II Tear Film report noted that there is currently a lack of reliable, commercially available 
evaporimeters. The report stressed that the development of evaporimeters that can be used in a 
clinical setting under a variety of temperatures and humidities would be extremely useful.4  
The Eye-VapoMeter was initially designed as a dermatological device to measure the rate of skin 
evaporation. The device was modified by incorporating an eye cup from a swimming goggle onto 
the base of the instrument and was validated for ocular use in 2014.5  
All other evaporimeters previously described in the literature have only been used within a 
research setting. To our knowledge, there has only been one previous evaporimeter which was 
capable of binocularly measuring the tear evaporation rate (TER). Tsubota and Yamada reported 
on the development of an evaporimeter capable of simultaneously measuring both eyes in 1992.6 
The evaporimeter consisted of a modified swimming goggle which had a 44 ml closed cylinder 
attached to each side of the goggle. The cylinders were needed to accommodate the large size 
of the sensors, which were used to record the temperature and relativity humidity.  
To overcome various problems associated with the Eye-VapoMeter and the Yamada/Tsubota 
evaporimeter, a novel, prototype goggle-based evaporimeter has been designed to 
simultaneously measure TER from both eyes at the same time. The benefit of a simultaneous 
TER measurement is less chair time for both the patient and practitioner.  
The prototype evaporimeter incorporates a small 2.5 x 2.5 mm2 temperature and humidity sensor 
into each lens of a swimming goggle, which eliminates the need to alter the original design of the 
goggle. The sensors sample the humidity and temperature 4 times per second and are positioned 
closer to the eye than inside the Eye-VapoMeter or the Yamada/Tsubota evaporimeter. The 
location of the sensor can provide a more accurate measurement of the humidity at the ocular 
surface by reducing the amount of extraneous air volume within the goggle. 

 
MALTESE Protocol 24jul2019 
 
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Due to the relative lack of previously published research investigating evaporimetry and CLs, the 
purpose of this pilot study is to compare the effect of DAILIES TOTAL1, a low water content 
silicone hydrogel lens, and Biotrue ONEday, a high water content hydrogel lens, on TER. The 
study will also serve to validate the novel, in-house developed evaporimeter. 
2 
OBJECTIVES 
The objective of the study is to compare the rate of tear evaporation, measured with a novel 
evaporimeter, before and after DAILIES TOTAL1 and Biotrue ONEday CLs are worn in 
symptomatic and asymptomatic contact lens wearers. 
The primary outcome variable for this study are the slopes calculated from the change in relative 
humidity over time.   
Other variables of interest include:  
• 
Contact lens dry eye questionnaire-8 (CLDEQ-8) score  
• 
Comfort (subjective rating) 
• 
Dryness (subjective rating) 
• 
Non-invasive break up time 
• 
Lipid layer thickness (Tearscope, LipiView II) 
• 
Ocular surface area (mm2) 
• 
Volume inside the goggle (cm3) 
3 
HYPOTHESIS 
The study hypothesis is that there will be a higher rate of tear evaporation with CL wear compared 
to when CLs are not worn.  
There will also be a significant difference in the rate of tear evaporation of DAILIES TOTAL1 (DT1) 
and Biotrue ONEday (BOD) after a minimum of 6 hours of CL wear. 
There will also be a higher rate of tear evaporation in symptomatic contact lens wearers compared 
to asymptomatic lens wearers.   
4 
MATERIALS AND METHODS 
4.1 STUDY DESIGN 
4.1.1 OVERALL DESIGN 

 
MALTESE Protocol 24jul2019 
 
12 
calculation of the sample size required to complete the study, study investigators will remain 
masked to the remainder of the randomization schedule until the study is completed and the 
database is locked.  
4.1.3 MASKING 
Participants will be masked to the brand of contact lens worn in each eye at Visit 2 and Visit 3. In 
order to mask the participant, a research assistant will transfer the lenses and blister pack solution 
directly from the blister packs and will place them in a contact lens cup. The investigator will be 
masked as much as possible; however, it may not be possible to fully mask the investigator, 
because identifying lens markings may be visible during the biomicroscopy examination.  
4.2 STUDY POPULATION 
4.2.1 SAMPLE SIZE CALCULATION 
Because this is a pilot study, a sample size calculation has not been completed. An interim data 
analysis will be undertaken after 20 participants (10 symptomatic and 10 asymptomatic) have 
completed the study. The results of the interim data analysis will be used to calculate a sample 
size using G*Power.  
A p-value of < 0.05 will be considered statistically significant. 
4.2.2 NUMBER OF PARTICIPANTS 
Up to 50 participants will be screened using CORE records and advertising approved by the UW 
Office of Research Ethics. Up to 50 participants will be dispensed/randomized with study products, 
with a target of at least 10 symptomatic and 10 asymptomatic participants completing the study. 
Informed consent will be obtained for all participants prior to their enrolment in the study. 
4.2.3 INCLUSION AND EXCLUSION CRITERIA 
A person is eligible for inclusion in the study if he/she: 
1. Is at least 17 years of age and has full legal capacity to volunteer; 
2. Has read and signed an information consent letter; 
3. Is willing and able to follow instructions and maintain the appointment schedule; 
4. Has worn soft contact lenses for a minimum of 6 months; 
5. Currently wears soft contact lenses for at least 4 days per week and 8 hours per day; 
6. Has an acceptable fit and comfort with both study contact lenses in the powers available; 
7. Has £1.00DS difference between eyes in their habitual contact lenses; 

 
MALTESE Protocol 24jul2019 
 
13 
8. Is willing to be awake for at least 2 hours before visit 2;  
9. Is willing to not wear eye makeup on the day of visit 2 and 3; 
10. Is willing to not use eye drops or artificial tears on the day of visits 1, 2, and 3; 
11. Has a wearable pair of spectacles. 
A person will be excluded from the study if he/she: 
1. Is participating in any concurrent clinical or research study; 
2. Has any known active* ocular disease and/or infection; 
3. Has a systemic condition that in the opinion of the investigator may affect a study 
outcome variable; 
4. Is using any systemic or topical medications that in the opinion of the investigator may 
affect a study outcome variable; 
5. Has known sensitivity to sodium fluorescein dye; 
6. Is pregnant, lactating or planning a pregnancy at the time of enrolment (by verbal 
confirmation at the screening visit); 
7. Is aphakic; 
8. Has undergone refractive error surgery; 
9. Has a known sensitivity to petroleum jelly (Vaseline); 
10. Has epilepsy and/or a sensitivity to flashing lights; 
11. Wears toric contact lenses; 
12. Has any physical impairment that would interfere with holding the evaporimeter; 
13. Has taken part in another research study within the last 14 days. 
* For the purposes of this study, active ocular disease is defined as infection or inflammation which 
requires therapeutic treatment. Mild (i.e. not considered clinically relevant) lid abnormalities 
(blepharitis, meibomian gland dysfunction, papillae), corneal and conjunctival staining and dry eye 
are not considered active ocular disease. Neovascularization and corneal scars are the result of 
previous hypoxia, infection or inflammation and are therefore not active. 
4.2.4 REPEATED SCREENINGS 
In some circumstances a repeated screening may need to be scheduled. Examples include, but 
are not limited to: 
1. Incomplete information available at time of screening to determine eligibility (e.g. current 
lens brands worn, history from current eye care practitioner etc.) 
2. Study procedures unable to be completed in time scheduled for visit; 

 
MALTESE Protocol 24jul2019 
 
15 
Saline solution may be used to rinse residual sodium fluorescein from the eyes following corneal 
staining assessment.  
The use of saline for rinsing the CL prior to insertion is permitted, if necessary. If initial CL 
discomfort is reported after a lens has been inserted, a CL may be removed, rinsed with saline, 
and re-inserted. 
4.3.4 ORDERING CONSUMABLES 
Study products will be obtained through commercial sources. 
4.3.5 DISPOSING OF CONSUMABLES 
Lenses worn at the scheduled visits will be collected from the participants and disposed of 
according to UW guidelines.  
4.3.6 PRODUCT ACCOUNTABILITY 
Accountability logs will be kept to include the number of lenses dispensed. All products dispensed 
to participants will be recorded in the study binder. 
4.3.7 CONTACT LENS DISPENSING 
At Visit 1, participants will insert the CLs directly from the labelled blister pack in order to ensure 
an acceptable lens fit.  
At Visit 2, the CLs will be provided to the participant after being transferred, complete with the 
blister pack solution, to a CL cup; in order to maintain participant and investigator masking.  
The use of saline for rinsing the CL prior to insertion or just after insertion is permitted, if necessary. 
Saline will not be dispensed during the study.  
4.4 SCHEDULED AND UNSCHEDULED VISITS 
This study has a total of 3 study visits, including the screening visit, including:  
• 
Visit 1: Screening and fitting of study lenses, 
• 
Visit 2: Baseline measurements and dispensing of study lenses, 
• 
Visit 3: Follow-up visit with study lenses on the same day as Visit 2 and study exit. 
4.4.1 STUDY VISITS 
The study has a total of 3 study visits, including the screening visit. Visit 2 and Visit 3 will occur on 
the same day and will be scheduled up to 14 days after the screening visit (Visit 1). The total time 

 
MALTESE Protocol 24jul2019 
 
17 
• 
Trial fitting of both study lenses will be done:  
o The lenses will be inserted by the participant directly from the blister pack based 
on their current contact lens power. 
o The contact lenses will be allowed to settle for 10 minutes. 
o Monocular and binocular logMAR visual acuity will be recorded with high contrast 
letters under high illumination with the study lenses.  
o Spherical over-refraction 
o Monocular and binocular logMAR visual acuity will be recorded with high contrast 
letters under high illumination with the study lenses and over-refraction.  
o Contact lens fit will be assessed.  
• 
Anterior eye photographs of each eye will be taken with a slit lamp camera. 
• 
Participants will practice evaporimetry measurements.  
• 
Removal of study lenses. 
• 
Measurement of volume within the goggle. 
• 
Slit lamp biomicroscopy (safety check) 
• 
Monocular and binocular logMAR visual acuity will be recorded with high contrast letters 
under high illumination with spectacles or spectacle refraction.  
• 
The investigator will confirm that the participant meets the eligibility specifications set out 
in the inclusion criteria and exclusion criteria and is eligible to continue with the study.  
4.4.3 VISIT 2: BASELINE AND DISPENSING VISIT 
• 
Participants will attend the visit having been awake for at least 2 hours.  
• 
Participants will not have worn any contact lenses, used any eye drops or artificial tears, 
or worn any eye makeup on the day of the visit. Participants who have worn lenses, used 
eye drops, used artificial tears, or worn eye makeup on the day of the visit will be 
rescheduled.  
• 
Monocular and binocular logMAR visual acuity will be recorded with high contrast letters 
under high illumination with spectacles or spectacle refraction.  
• 
Slit lamp biomicroscopy using white light. 
The participant will be assigned a randomization ID in order to determine which type of CL will be 
inserted into each eye. 
Participants will be required to adapt to the room environment for at least 15 minutes prior to 
reporting subjective monocular ratings and performing baseline evaporimetry measurements. The 

 
MALTESE Protocol 24jul2019 
 
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participant will apply thin layer of petroleum jelly will be applied to the skin surrounding the eye 
using a cotton tipped applicator to minimize the amount of evaporation from the skin. 
• 
The participant will be asked to give subjective monocular ratings for: 
o Comfort 
o Dryness 
o Burning or stinging 
• 
Baseline evaporimetry measurements without contact lenses 
• 
Non-invasive pre-ocular tear film break up time (Tearscope) 
• 
Lipid layer thickness (Tearscope) 
• 
Lipid layer thickness (LipiView II) 
• 
Evaporimetry measurements will be repeated at least 15 minutes after the initial baseline 
measurement. 
• 
Non-invasive pre-ocular tear film break up time (Tearscope) 
• 
Lipid layer thickness (Tearscope) 
• 
Lipid layer thickness (LipiView II) 
• 
The participant will wipe away petroleum jelly from skin surrounding the ocular surface 
using a tissue. 
• 
Contact lenses will be given to the participants in a masked manner (Section 4.3.7).  
• 
The study contact lenses will be inserted by the participant.  
• 
The lenses will be allowed to settle for at least 15 minutes.  
• 
The participant will apply a thin layer of petroleum jelly will be applied to the skin 
surrounding the eye using a cotton tipped applicator to minimize the amount of 
evaporation from the skin. 
• 
The participant will be asked to give subjective monocular ratings for: 
o Comfort 
o Dryness 
o Burning or stinging 
• 
Baseline evaporimetry measurements with contact lenses. 
• 
Non-invasive pre-lens tear film break up time (Tearscope) 
• 
Lipid layer thickness (Tearscope) 
• 
Lipid layer thickness (LipiView II) 
• 
Contact lens fit will be assessed. 

 
MALTESE Protocol 24jul2019 
 
19 
• 
Monocular and binocular logMAR visual acuity will be recorded with high contrast letters 
under high illumination with contact lenses. 
• 
The participant will wipe away petroleum jelly from surrounding the ocular surface using 
a tissue. 
Participants will continue to wear the study lenses and will be advised not to use any eye drops 
or eye makeup. Participants will be instructed to return to CORE in 5.5 hours ± 30 minutes for 
their next visit.  
4.4.4 VISIT 3: FOLLOW UP & STUDY EXIT 
Participants will attend the visit having not used any eye drops or eye makeup on the day of the 
visit.  
• 
Monocular and binocular logMAR visual acuity will be recorded with high contrast letters 
under high illumination.  
• 
Contact lens fit will be assessed.  
Participants will be required to adapt to the room environment for at least 15 minutes prior to 
reporting subjective monocular ratings and performing evaporimetry measurements. The 
participant will apply thin layer of petroleum jelly will be applied to the skin surrounding the eye 
using a cotton tipped applicator to minimize the amount of evaporation from the skin. 
• 
The participant will be asked to give subjective monocular ratings for: 
o Comfort 
o Dryness 
o Burning or stinging 
• 
Evaporimetry measurements with contact lenses. Evaporimetry measurements will not 
be taken until the study lenses have been worn for a minimum of 6 hours.  
• 
Non-invasive pre-lens tear film break up time (Tearscope) 
• 
Lipid layer thickness (Tearscope) 
• 
Lipid layer thickness (LipiView II) 
• 
The participant will wipe away petroleum jelly from the skin surrounding the ocular 
surface using a tissue. 
• 
Contact lens removal. 
• 
Slit lamp biomicroscopy. 
• 
Exit monocular and binocular logMAR visual acuity will be recorded with high contrast 
letters under high illumination with spectacles or spectacle refraction.  

 
MALTESE Protocol 24jul2019 
 
22 
4.5.4 CONTACT LENS DRY EYE QUESTIONNAIRE (CLDEQ-8)  
The CLDEQ-8 is a dry eye questionnaire that asks the participant to reflect and rate their 
symptoms of eye discomfort and dryness over the past two weeks. A higher composite score 
indicates more severe dryness and the range is 0-37. A score of <12 will be considered 
asymptomatic and a score ³12 will be symptomatic.  
4.5.5 LOGMAR VISUAL ACUITY  
Distance logMAR visual acuity will be measured using high contrast computer-generated acuity 
charts in high illumination room lighting. Participants will be asked to read letters, which 
progressively decrease in size on a computer screen at a viewing distance of 6 meters, with their 
habitual glasses/spectacle refraction or study contact lenses. 
4.5.6 MEIBOMIAN GLAND ASSESSMENT  
Participants will be seated at a slit lamp biomicroscope with the magnification set to 10x or 16x. 
The participant will be asked to look up and away from their nose. The meibomian glands will be 
manually expressed using the MG Evaluator (TearScience/J&J). The MG Evaluator will be 
depressed halfway to apply a pressure of 1.2 g/mm2 to three separate areas (nasal, central, 
temporal) on the lower eyelid just below the lash line and angled down approximately 15 to 45 
degrees. Five consecutive glands in each area will be assessed for expressibility as follows: 0: no 
secretion (including capped orifices), 1: inspissated (semi-solid, toothpaste like), 2; colored/cloudy 
liquid, 3: clear liquid oil. The results for each eye will be summed (Meibomian Gland Score).   
4.5.7 LID MARGIN ASSESSMENT 
The participant will be seated at a slit lamp biomicroscope. 
Vascularity of the margin (erythema)  
The vascularity of the lid margin will be graded (0-4 scale; 0: none, 1: minimal, 2: mild, 3: moderate, 
4: severe). 
Amount of lash loss 
The amount of lash loss will be assessed (0-4 scale; 0: none, 1: minimal, 2: mild, 3: moderate, 4: 
severe). 
Lid margin edema 
The presence or absence of lid margin edema will be recorded. 

 
MALTESE Protocol 24jul2019 
 
23 
Lid margin telangiectasia 
Lid margin telangiectasia will be graded (0-4 scale, 0: none; 1: single telangiectasia; 2: 2 to 5 
telangiectasia; 3: >5 telangiectasia; 4: severe-entire lid involvement). 
Tear film debris 
The presence or absence of tear film debris will be recorded. 
4.5.8 SLIT LAMP BIOMICROSCOPY 
A slit lamp biomicroscopy examination will be conducted to assess anterior segment ocular health. 
Ocular findings will be graded using the Efron grading scale (0-4, 0.5 steps – unless otherwise 
stated): 
External adnexa anomalies 
The presence or absence of external adnexa anomalies will be recorded. If adnexa anomalies are 
detected, the anomaly will be described. 
Bulbar and limbal hyperemia 
The redness of the bulbar and limbal conjunctiva of both eyes will be assessed using the Efron 
Grading scale (0 to 4, 0.5 steps).  
Scars or other corneal observations 
The presence or absence of scars or other corneal observations will be recorded. If scars or other 
corneal observations are detected, the finding(s) will be described. 
Infiltrates 
The presence or absence of infiltrates will be recorded. If present, the number and location will be 
recorded. The size (diameter in mm) and depth of the largest infiltrate (0-4 scale, 1 step) in the 
central, mid-periphery and periphery will be noted.  
Endothelium abnormalities: 
The presence or absence of endothelium abnormalities will be recorded. If endothelium 
abnormalities are detected, the finding(s) will be described. 
Anterior chamber 

 
MALTESE Protocol 24jul2019 
 
24 
The presence or absence of anterior chamber reaction will be recorded. If an anterior chamber 
reaction is detected, the finding(s) will be described. 
Other abnormalities 
The presence or absence of other abnormalities will be recorded. If other abnormalities are 
detected, the finding(s) will be described. 
Corneal and conjunctival staining and indentation  
A sodium fluorescein strip, wetted with a few drops of saline, will be applied to the superior bulbar 
conjunctiva of both eyes. Corneal staining type will be graded using the Efron scale (0 to 4, 0.5 
steps), staining extent and depth will be graded on a (0 to 4 scale, 1 step) while viewing with cobalt 
blue light and Wratten filter (if available). Conjunctival staining and indentation will be graded using 
a 0 to 4 scale (0.5 steps), with larger values indicating increasing severity. 
Mucin ball impressions 
The number of mucin ball impressions will be recorded. 
Palpebral conjunctival hyperemia and papillae (roughness) 
The redness and roughness of the upper and lower eyelids will be assessed using the Efron scale 
(0 to 4, 0.5 steps). 
4.5.9 CONTACT LENS FITTING 
The acceptability of the fit of the study lenses will be assessed using a slit lamp biomicroscope 
after the lenses have settled for at least 10 minutes. Lens fit (centration, movement, limbal 
coverage, tightness/push up test, overall fit) will be determined to be either acceptable or 
unacceptable. Lens deposits will be recorded as present/absent. The participants will be asked to 
report if the lenses are subjectively comfortable (yes/no) at the screening visit. 
4.5.10 ANTERIOR EYE PHOTOGRAPHS 
The participant will be seated at a Zeiss slit lamp attached to a Canon EOS 60D digital camera. A 
photograph of each eye will be taken at 5x magnification with additional external illumination 
provided by a Canon Macro Twin Lite flash. The participant will hold a ruler underneath each eye 
while the photographs are taken. The ruler will serve as a calibration reference when the images 
are analysed with ImageJ in order to determine the size of the ocular surface in mm2. The ruler 
will be cleaned with an alcohol wipe prior to being given to each participant.  
4.5.11 MEASUREMENT OF VOLUME INSIDE THE GOGGLE 

 
MALTESE Protocol 24jul2019 
 
25 
The participant will be seated in a consulting chair and will be asked to rest their head on the 
headrest. A pair of swimming goggles (Arena Zoom X-Fit), which are the same make and model 
as the prototype evaporimeter, will be used. The swimming goggle has been modified by drilling 
a small hole into the top of each lens. The participant will be asked to place the goggle over both 
eyes and to tighten the strap. A plastic, needleless syringe, with a 200 µl pipette tip attached to 
the end of the syringe, will be filled with saline (Bausch & Lomb Sensitive Eyes Saline Plus). 
Participants will be asked to keep their eyes closed while saline is added to the goggle. Saline will 
be added to each swimming goggle until the goggle has been filled with saline. The amount of 
saline added to each goggle will be recorded in milliliters. When the goggle is ready to be removed, 
the participant will be advised to tilt their head forward and continue to keep their eyes closed. A 
plastic tub will be placed below the participant’s face and paper towels will be placed around the 
goggle to catch any saline that may spill out of the goggle. When the goggle has been removed, 
the participant will be advised to wipe their face with a paper towel while their eyes are kept closed. 
The swimming goggle will be cleaned with an alcohol wipe prior to use on each participant. A new 
sterile, syringe will be used for each participant. New saline and a new pipette tip be used to fill 
each goggle.  
4.5.12 SLIT LAMP BIOMICROSCOPY (SAFETY VARIABLE)  
The participant will be seated at a slit lamp at the following will be assessed in both eyes for:  
External adnexa anomalies 
The presence or absence of external adnexa anomalies will be recorded. If adnexa anomalies are 
detected, the anomaly will be described. 
Bulbar and limbal hyperemia 
The redness of the bulbar and limbal conjunctiva of both eyes will be assessed using the Efron 
Grading scale (0 to 4, 0.5 steps).  
Scars or other corneal observations 
The presence or absence of scars or other corneal observations will be recorded. If scars or other 
corneal observations are detected, the finding(s) will be described. 
Infiltrates 

 
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The presence or absence of infiltrates will be recorded. If present, the number and location will be 
recorded. The size (diameter in mm) and depth of the largest infiltrate (0-4 scale, 1 step) in the 
central, mid-periphery and periphery will be noted.  
Corneal and conjunctival staining and indentation  
A sodium fluorescein strip, wetted with a few drops of saline, will be applied to the superior bulbar 
conjunctiva of both eyes. Corneal staining type will be graded using the Efron scale (0 to 4, 0.5 
steps), staining extent and depth will be graded on a (0 to 4 scale, 1 step) while viewing with cobalt 
blue light and Wratten filter (if available). Conjunctival staining and indentation will be graded using 
a 0 to 4 scale (0.5 steps), with larger values indicating increasing severity. 
4.5.13 APPLICATION OF PETROLEUM JELLY   
Petroleum jelly will be removed from the original container using a cotton tipped applicator and 
placed in a new paper cup for each participant. Another cotton tipped applicator will be given to 
each participant to apply thin layer of petroleum jelly to the skin surrounding the eye using a mirror. 
A new cotton tipped applicator and paper cup will be used for each application. Any remaining 
petroleum jelly will be disposed of according to UW guidelines.  
4.5.14 REMOVAL OF PETROLEUM JELLY   
To remove petroleum jelly from the skin, the participant will close their eyes and wipe with a tissue 
in a nasal to temporal direction, with extra care being paid wiping near the lid margin to avoid 
contaminating the tear film or contact lenses.  
4.5.15 SUBJECTIVE COMFORT RATINGS 
Participants will be asked to fill a numerical analog scale for comfort, dryness, and burning or 
stinging for each eye on a 0-100 scale:  
• 
At Visit 2, before & 15 minutes after lens insertion 
• 
At Visit 3, after at least 6 hours of contact lens wear. 
4.5.16 EVAPORIMETRY 
The participant will be seated at an adjustable height table and will place their elbows on the table. 
The participant will hold a pair of modified swimming goggles (Figures 1A and 1B) over their eyes 
for 20 seconds while their eyes are open. The participant will be prompted to blink every 3 seconds 
during the measurement using a metronome (https://www.youtube.com/watch?v=9ypeNJJeKIs). 
The goggle will be removed and ventilated in front of a fan until the relative humidity returns to 

 
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28 
of the tear film while the participant is sitting behind the slit lamp. This device is not computerized 
and does not generate data. The timer on the instrument will be used to measure the non-invasive 
break-up time. The non-invasive break-up time will be recorded as the time taken after a blink until 
the appearance of the first dark spot.7 Three measurements will be taken from each eye and the 
average value will be calculated for each eye. 
4.5.18 LIPID LAYER THICKNESS (KEELER TEARSCOPE) 
The participant will be seated at a slit lamp and a diffuse white light will be shone onto the 
participant’s eye. Lipid layer thickness will be graded according to the interference pattern 
observed based on Guillon and Guillon’s classification system7 (open meshwork, closed 
meshwork, wave, amorphous, colour fringe, and other).  
4.5.19 LIPID LAYER THICKNESS (TEARSCIENCE LIPIVIEW II) 
The participant will be seated at the LipiView II instrument which will image and compute the lipid 
layer thickness (average, minimum, maximum) of the tear film. Prior to the commencement of this 
test, no history of seizures or discomfort with rapidly blinking lights will be confirmed. 
5 
MONITORING PROTOCOL ADHERENCE 
Guidelines to be included on adherence to visit windows and windows around other data collection 
points (i.e. subjective ratings) will be monitored by CORE. Deviations from the windows described 
in the protocol will be reported in the study report. Major protocol deviations will be reported to the 
University of Waterloo’s Office of Research Ethics (ORE) within 7 days of becoming aware of them 
(as per ORE’s guidelines).  
6 
POTENTIAL RISKS AND BENEFITS TO HUMAN PARTICIPANTS 
This is a minimal risk study because of the use of marketed products and standard optometric 
assessments with two investigational, non-invasive devices (the prototype evaporimeter and the 
modified swimming goggles used to measure volume). 
Contact lenses in this study will be worn on a daily wear basis, for approximately 6 to 7 hours. 
Adverse events and/or complications in daily wear of soft contact lenses can occur (eg: 
inflammation and infection). When contact lenses are worn on a daily wear basis there is a small 
risk of an adverse event compared to not wearing contact lenses. When contact lenses are worn 
on an extended wear basis, there is a significantly increased risk of an adverse reaction compared 
with wearing contact lenses on a daily wear basis. 

 
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29 
Additionally, it is possible that participants may experience temporary discomfort associated with 
the study procedures (saline)/products/devices including: burning and stinging, blurred vision, 
sandiness or grittiness, light sensitivity, dryness, itching, crusty eyes and foreign body sensation. 
A dye (fluorescein) normally used for eye exams is being used in this study. Although rare, it is 
possible that participants may have an allergic reaction to the dye. This could cause discomfort to 
their eye.   
Routine clinical procedures including visual acuity, anterior ocular health assessment, and contact 
lens fitting will be used.  
One clinical procedure (evaporimetry) will be conducted with an investigational device consisting 
of a pair of modified swimming goggles containing a temperature and humidity sensor embedded 
in each lens of the goggle. This procedure poses minimal risk to the participants as the device is 
does not touch the eye and the portion of the goggle which will come in contact with the skin 
surrounding the eye will be cleaned with alcohol wipes between each use. Participants may 
experience temporary discomfort associated with petroleum jelly including; burning, stinging, 
irritation, blurred vision, and foreign body sensation.  
One clinical procedure (measurement of volume inside the goggle) will be conducted with an 
investigational device consisting of a pair of modified swimming goggles containing small hole 
inserted into the top of each lens. This procedure poses minimal risk to the participants as the 
device is does not touch the eye and the portion of the goggle which will come in contact with the 
skin surrounding the eye will be cleaned with alcohol wipes between each use. Commercially 
available saline designed for use with the eyes will be inserted into the goggle. Participants may 
experience temporary discomfort associated with saline including; burning, stinging, irritation, 
blurred vision, and foreign body sensation.  
One of the instruments in this study uses rapidly blinking lights to image the tear film. Participants 
will be asked to inform the investigator if they have a history of discomfort and seizures due to 
rapidly blinking lights. Participants may experience temporary discomfort including: blurred vision 
and light sensitivity. 
Participants may not benefit directly from taking part in this study. Information from this study may 
help researchers come up with new devices to help others in the future. This study may help 
CORE to better understand the performance of the products being used in this study. 
7 
ADVERSE EVENTS 

 
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30 
See CORE SOP012_v02 for a description of all adverse events, including management and 
reporting. 
A number of conditions may result in temporary suspension until resolution. These include corneal 
infiltrates, corneal staining, limbal injection, bulbar injection or tarsal conjunctival abnormalities.   
8 
DISCONTINUATION FROM THE STUDY 
Participants may be discontinued at the discretion of the investigator or sponsor in consideration 
of participant safety or protocol compliance, or at discretion of the participant.  Participants 
discontinued from a study will be reimbursed $20 per hour for their active involvement in the study 
(including the initial screening visit).  Upon discontinuing, a participant will be offered the option of 
their data being withdrawn from future statistical analysis. The following is a list of possible reasons 
for discontinuation from the study: 
• 
Screening failure: Participants will be discontinued if they do not meet the inclusion and 
exclusion criteria outlined in section 4.2.3. 
• 
Unacceptable performance with products to be used in study: Participants may be 
discontinued if they are unable to achieve acceptable comfort and /or vision with the 
study products. 
• 
Positive slit lamp finding:  Participants may be permanently discontinued from the study 
depending on the severity of the condition and on the judgement of the investigator.   
• 
Adverse event: If a participant experiences an adverse event during the study they may 
be discontinued based on the clinical judgement of the investigator. 
• 
Symptoms: If the participant has persistent symptoms they may be discontinued based 
on the clinical judgement of the investigator. 
• 
Disinterest, relocation or illness: The participant may choose to discontinue due to 
reasons within or beyond their control. 
• 
Violation of protocol or non-compliance:  The participant will be discontinued if they are 
unable or unwilling to follow the protocol specified visit schedules and/or study 
procedures. 
• 
Instillation of topical ocular medication:  The participant will be discontinued if they elect 
to use a topical ocular medication during the study unless that topical ocular medication 
is prescribed for a limited duration (less than two weeks) to treat a transient condition; in 

 
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31 
this case the participant may remain an active participant (at the discretion of the 
investigator) after stopping topical ocular medication following resolution of the ocular 
condition). 
• 
Lost to follow-up:  The participant will be discontinued if they cannot be contacted and do 
not return for a final exit visit, and if the investigator has made a reasonable effort to 
contact the participant for a final study visit. 
• 
Premature termination of the study by the sponsor, CORE or the Office of Research 
Ethics at the University of Waterloo. 
A discontinuation form, stating the reason for discontinuation will be completed, which requires 
the signatures of both the participant and the investigator except where the participant is lost to 
follow-up in which case only the signature of the investigator is required.   
All discontinuations including their reasons will be included in the final report. 
9 
STUDY COMPLETION AND REMUNERATION 
At the last scheduled protocol visit a study completion form will be completed, which requires the 
signatures of both the participant and the investigator.    
Once their involvement in the study is complete, participants will be informed about receiving 
feedback following study completion in the Letter of Appreciation. 
Participant remuneration will be $80 for completing the study. In the event that participants 
withdraw or are discontinued from the study, they will receive $20 per hour for the time that they 
were involved in the study. 
10 STATISTICAL ANALYSIS AND DATA MANAGEMENT 
10.1 STATISTICAL ANALYSIS 
All data will be analyzed by CORE at the University of Waterloo on unmasked data using Microsoft 
Excel and statistical analysis software such as GraphPad and SPSS. Interim data analysis will be 
conducted after 10 symptomatic and 10 asymptomatic participants have completed the study to 
determine the optimal time period over which to calculate the slope. The results of the interim data 
analysis will also be used to calculate the sample size.  
Descriptive statistics will be provided on information regarding baseline variables (age, sex, 
contact lens refractive error distribution, etc.). Data may be evaluated for individual groups 

 
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All study personnel will be required to complete training prior to their involvement in the study. A 
series of training modules will be developed for the study and records of training will be kept at 
CORE. 
12 STUDY MONITORING 
Study monitoring will be conducted by CORE personnel. Consent documentation will be reviewed 
by a person not involved in the consent process. To improve data integrity, data entry will be 
double-entered and the entries will be compared for discrepancies. All adverse events and 
protocol deviations will be reviewed by the Lead Investigator. All serious adverse events and major 
protocol deviations will be reviewed by the Principal Investigator. 
13 STUDY MANAGEMENT 
13.1 STATEMENT OF COMPLIANCE 
This clinical study is designed to be in compliance with the ethical principles in the Declaration of 
Helsinki, with the ICH guidelines for Good Clinical Practice (GCP), with the University of 
Waterloo’s Guidelines for Research with Human Participants and with the Tri-Council Policy 
Statement: Ethical Conduct for Research Involving Humans, 2nd Edition. 
• 
Declaration of Helsinki 
• 
ICH E6 - International Conference on Harmonisation; Good Clinical Practice 
• 
http://iris.uwaterloo.ca/ethics/human/guidelines/index.htm 
• 
http://iris.uwaterloo.ca/ethics/human/ethicsReview/UWStatement.htm 
• 
http://www.pre.ethics.gc.ca/eng/policy-politique/initiatives/tcps2-eptc2/Default/ 
 
13.2 ETHICS REVIEW 
This protocol will be submitted to and reviewed through the Office of Research Ethics (ORE) at 
the University of Waterloo. Notification of ethics clearance of the application is required prior to 
the commencement of the study. 
13.3 CLINICAL TRIAL REGISTRATION 
The study will be registered with clinicaltrials.gov.   
13.4 PROTOCOL DEVIATIONS 
Protocol deviations are unanticipated or unintentional changes to a study after it has received prior 
sponsor approval and ethics clearance. Protocol deviations can be major or minor.  

 
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34 
13.4.1 MAJOR PROTOCOL DEVIATIONS 
Major protocol deviations may impact the research protocol, information consent document or 
other study materials, usually cannot be anticipated ahead of time and are often necessary to 
ensure the safety and welfare of the participants. 
The following are examples of protocol deviations that must be reported to the ORE: 
• 
Changes in procedures initiated to eliminate immediate risks/hazards to participants; 
• 
Enrollment of participants outside the protocol inclusion/exclusion criteria whether agreed 
to or not by the sponsor; 
• 
Medication / device / intervention errors (i.e. incorrect drug or dosage of drug / incorrect 
contact lens(es) dispensed / incorrect care system dispensed); 
• 
Inadvertent deviation in specific research intervention procedures or timing of the research 
intervention which could impact upon the safety or efficacy of the study-related intervention 
or upon the experimental design; 
• 
Information consent documentation violations: no documentation of informed consent; 
incorrect version of, or incomplete, informed consent documentation used. 
13.4.2 MINOR PROTOCOL DEVIATIONS 
Protocol deviations caused by or which originate with research participants are considered minor, 
and normally are not reported to the ORE unless these result in increased risk to the participant(s). 
The following are examples of protocol deviations that are considered minor and do not require 
reporting to the ORE: 
• 
Logistical or administrative aspects of the study (e.g., study participant missed 
appointment, change in appointment date); 
• 
Inadvertent deviation in specific research intervention procedures or timing of the 
research intervention which would not impact upon the safety or efficacy of the study-
related intervention or upon the experimental design (i.e., missing a measurement during 
a session that is not considered critical for the study).  
13.4.3 REPORTING AND DOCUMENTING PROTCOL DEVIATIONS 
Major protocol deviations must be reported to the ORE within 7 days of the deviation occurring (or 
its discovery) using the Protocol Deviation Report Form 107 (PDRF).  Information from the PDRF 
is provided to the Clinical Research Ethics Committee (CREC) at the next monthly meeting. 

 
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All protocol deviations (major and minor) occurring during the study will be documented and 
included in the final report. 
13.5 PREMATURE TERMINATION OF THE STUDY 
CORE or the Office of Research Ethics at the University of Waterloo may terminate the study at 
any time for any reason. 
13.6 STUDY PARTICIPANT RECORDS 
Study participant records will be completed to comply with GCP guidelines. Records will contain: 
• 
Unique study acronym and/or code; 
• 
Participant ID; 
• 
Date enrolled; 
• 
Confirmation by investigator that participant met eligibility criteria; 
• 
Confirmation that participant received a signed and dated copy of informed consent; 
• 
Exit date; 
• 
Investigator’s signature confirming study exit. 
13.7 RETENTION OF STUDY RECORDS AND DATA 
Records and data from this study will be retained for a minimum of 25 years. Details regarding 
storage procedures are given in CORE SOP014_v02 Clinical data management.  
14 REPORT 
A report will be generated after completion of the study. An internal reviewer will review the report.  
15 REFERENCES 
1. 
The epidemiology of dry eye disease: report of the epidemiology subcommittee of the 
international dry eye workshop (2007). Ocul Surf, 2007. 5(2): p. 93-107. 
2. 
The definition and classification of dry eye disease: report of the definition and 
classification subcommittee of the international dry eye workshop (2007). Ocul Surf, 
2007. 5(2): p. 75-92. 
3. 
Nichols, J.J. and L.T. Sinnott, Tear film, contact lens, and patient-related factors 
associated with contact lens-related dry eye. Invest Ophthalmol Vis Sci, 2006. 47(4): p. 
1319-28. 
4. 
Willcox, M.D.P., et al., TFOS DEWS II tear film report. Ocul Surf, 2017. 15(3): p. 366-
403. 

 
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5. 
Rohit, A., et al., Validating a new device for measuring tear evaporation rates. 
Ophthalmic Physiol Opt, 2014. 34(1): p. 53-62. 
6. 
Tsubota, K. and M. Yamada, Tear evaporation from the ocular surface. Invest 
Ophthalmol Vis Sci, 1992. 33(10): p. 2942-50. 
7. 
Guillon, J.-P. and M. Guillon, Contact lens practice, M. Ruben and M. Guillon, Editors. 
1994, Chapman & Hall: London, UK ; New York, NY, USA. p. 453-483.