Quantification of the Visual Benefits of Soft Toric Contact Lenses Compared to Soft Spherical Contact Lenses Over a Range of Refractive Astigmatism
Phase: NA
Conditions: Astigmatism
Sponsor: CooperVision, Inc.



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Contents 
Document control 
3 
Study summary 
 
Section 1. 
Overview 
6 
1.1 
Background 
6 
1.2 
Personnel 
6 
1.3 
Study objectives 
6 
1.4 
Study design 
6 
1.5 
Statistical considerations 
7 
1.6 
Risk analysis 
7 
1.7 
Clinical trial registration 
7 
Section 2. 
Resources 
8 
2.1 
Subject selection 
8 
2.2 
Subject discontinuation 
9 
2.3 
Safety parameters, adverse events and concurrent illnesses 
9 
2.4 
Study termination 
10 
2.5 
Protocol deviations 
10 
2.6 
Study resources 
10 
2.7 
Study control 
11 
2.8 
Documentation 
11 
2.9 
Data collection and analysis 
11 
2.10 Study completion 
11 
2.11 Confidentiality 
12 
2.12 Study monitoring 
12 
Section 3. 
Subject management 
13 
3.1 
Visit scheduling 
13 
3.2 
Visit conduct 
13 
3.3 
Monitoring subject compliance 
17 
3.4 
Missing, unused and spurious data 
17 
Section 4. 
Study co-ordination 
18 
4.1 
Document processing 
18 
4.2 
Disclosure 
18 
4.3 
Personnel 
18 
 
 
Appendices 
A  Adverse events 
B  Randomisation table 
C  Grading scales, questionnaires 
 

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Section 1. Overview 
1.1 
Background 
In some contact lens markets, the use of soft toric lenses is significantly lower than might 
be expected for the range of astigmatism in the population. The reasons for this are varied, 
but appear to include practitioner reluctance to fit and prescribe such lenses due to a 
perception of a limited clinical benefit in doing so. This study seeks to provide clinical data 
to highlight the benefits of prescribing soft toric lenses to astigmats. 
1.2 
Personnel 
 
 
 
1.3 
Study objectives 
The aim of this work is to undertake a range of vision-related measures with soft toric 
contact lenses (custom-made Biofinity XR Toric), soft spherical contact lenses (Biofinity) 
and spectacle lens correction across a range of levels of astigmatism, seven intervals from 
0.00DC to -1.50DC, and for three different pupil sizes. Pupil size will be controlled using a 
novel, automated room lighting/feedback system. This will lead to a quantification of the 
visual benefit of torics vs. spheres, and allow for the identification of the astigmatic threshold 
where the difference between these two lens designs becomes clinically meaningful. 
1.4 
Study design 
This will be a randomised, crossover, partially subject-masked (for contact lenses only), 
non-dispensing study, controlled by cross-comparison. Many subjects will have both eyes 
within the astigmatism range, and data from two eyes for these subjects will be in the 
analysis. Some subjects may only have one eye in range. Subjects with two suitable eyes 
will attend for three visits and those with only one suitable eye will attend for two visits. At 
the initial study visit, up to 55 subjects will be fiited with the toric (Biofinity XR toric) and 
spherical (Biofinity) contact lenses in order to provide 12 eyes in each of the seven cylinder 
powers studied (0.00 to -1.50DC). At visit 2, each subject will wear the spherical contact 
lens, custom-made toric contact lens and spectacle correction, in a randomised sequence. 
Visual acuity will be assessed for three different pupil sizes 
 
 using the novel automated room lighting/feedback system. 
 
 
 During clinical evaluation the eye which is not being studied will be 
patched. For subjects with both eyes within the required astigmatism range, they will return 
for visit 3, where the procedures undertaken at visit 2 will be repeated on the fellow eye. 

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1.5 
Statistical considerations 
The principal hypothesis to be tested in this work is that visual acuity 
 
for the different lens corrections and pupil sizes will be the same. 
 
Visual acuity assessment, biomicroscopy gradings 
 will generate 
data that are likely to be continuous and normally distributed. As such, these will be 
compared using linear regression models or other parametric methods. 
 
 
 
  Deviations may be necessary due to differences 
between the actual data distribution compared with the anticipated data distribution. 
1.5.1 
Power analysis 
An a priori power analysis has determined that 12 eyes are required for each 0.25DC level 
of astigmatism to provide 80% power to detect a meaningful difference of 0.1 logMAR units 
between correction types. To evaluate the seven intervals from 0.00DC to -1.50DC, 84 eyes 
are required. 
 
This analysis assumes a two-tailed paired analysis and an alpha of 0.05. To allow for 
discontinuations, up to 55 subjects will be fiited with the study lenses.   
1.6 
Risk analysis 
This study is considered to be a non-significant risk study based on United States Food and 
Drug administration (FDA) and International Standards Organization (ISO) guidelines due 
to the daily wear nature of the study and non-invasive study procedures. Subjects may not 
benefit directly from taking part in this study; however, information from this study may help 
researchers gain new insights about contact lens wear and to help others in the future. With 
the potential benefit of this study, the work is considered to be ethically justifiable. Ethical 
approval will be sought from the University of Manchester Senate Committee on the Ethics 
of Research on Human Beings (hereafter referred to as Manchester UREC). The work 
where practical will be conducted in accordance with the ICH Good Clinical Practice 
Guidelines and the international standard BS EN ISO 14155:2011 ‘Clinical investigation of 
medical devices for human subjects’.  
1.7 
Clinical trial registration 
This study will be registered with clinicaltrials.gov in accordance with section 801 of the 
Food and Drug Administration (FDA) Act which mandates the registration of certain 
clinical trials of drugs and medical devices. 

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Section 2. Resources 
2.1 
Subject selection 
In this work, up to 55 subjects will be fitted with the study lenses, with the aim of 84 eye 
evaluations completing the study (12 per cylinder power in 0.25DC steps, from 0.00 to               
-1.50DC).  
2.1.1 
Subject withdrawal and replacement 
This study includes three clinical visits (two clinical visits if only one eye is suitable). Once 
the study consent form is signed, the subject is considered to be enrolled on the study.  
Subjects who have signed the consent form, but who have not completed the initial visit will 
usually be replaced.  All subject data will be included in the final analyses unless there are 
strong grounds for exclusion; such grounds will be detailed in the final report.  
2.1.2 
Subject recruitment 
Subjects will be recruited by one or more of following means: 
1. Posting study details on The University of Manchester’s ‘Research Volunteers’ 
website. 
2. Correspondence to existing wearers on the Eurolens Research database of 
subjects. 
3. Advertising through a variety of media via a format separately approved by 
Manchester UREC. 
2.1.3 
Inclusion criteria 
Subjects will only be eligible for the study if: 
1. They are of legal age between 18 and 40 years.   
2. They understand their rights as a research subject and are willing and able to sign a 
Statement of Informed Consent. 
3. They are willing and able to follow the protocol. 
4. They are current wearers of any soft contact lens (i.e. have worn lenses in the last six 
months). 
5. They have refractive ocular astigmatism between 0.00DC and -1.50DC in one or both 
eyes. 
6. They have a spherical component to their ocular refractive error between 0.00 and -
6.00 DS. 
7. They could attain at least 0.10 logMAR distance high contrast visual acuity in one eye 
with the study lenses within the available power range. 
8. They can be fitted satisfactorily with both lens types. 
9. They own an acceptable pair of spectacles. 
10. They agree not to participate in other clinical research for the duration of this study. 

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2.1.4 
Exclusion criteria 
Subjects will not be eligible to take part in the study if: 
1. They have an ocular disorder which would normally contra-indicate contact lens  
wear. 
2. They have a systemic disorder which would normally contra-indicate contact lens 
wear. 
3. They are using any topical medication such as eye drops or ointment. 
4. They have had corneal refractive surgery. 
5. They have any corneal distortion resulting from previous hard or rigid lens wear or 
have keratoconus. 
6. They are pregnant or breastfeeding. 
7. They have any ocular abnormality which would, in the opinion of the investigator, 
normally contraindicate contact lens wear. 
8. They have an amblyopic eye, in which case only dominant eye will be assessed for 
that subject. 
9. They have an infectious disease (e.g. hepatitis), any immunosuppressive disease 
(e.g. HIV) or diabetes. 
10. They have a history of severe allergic reaction or anaphylaxis. 
11. They have taken part in any other contact lens clinical trial or research, within two 
weeks prior to starting this study. 
2.2 
Subject discontinuation 
In general, subjects should be discontinued at any time, if it is in their best interests, as 
judged by the investigator.  Reasons for this may include clinical signs of grade 3 or more, 
lack of motivation, discomfort, or repeated refusal to follow instructions. Subjects will be 
discontinued if a serious adverse event occurs or if they miss two or more planned 
consecutive visits. Subjects who fail to satisfy all the inclusion and exclusion criteria will be 
discontinued and replaced. Subjects may choose to leave the study at their own request.  
All discontinuations will be carefully recorded. 
2.3 
Safety parameters, adverse events and concurrent illnesses 
The key safety parameters are the serious and significant ocular adverse events 
 
  
Clinical assessment is made at the study visit(s) for these parameters. The presence of an 
adverse event will be reported on the case report forms and those described as ‘serious’ or 
‘significant’ will be detailed in the final report.  Similarly, any concurrent illness that is likely 
to impact on the relevance and quality of the captured data will be noted on the case report 
form. 

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2.6.1.1 Use of lenses 
This is a non-dispensing study. Subjects will wear the contact lenses in the clinic only. (i.e. 
lenses will be removed at the end of the study visit and discarded).  
2.6.2 
Care regimen 
No care system will be used on this study. 
2.6.3 
Inventory control 
A bank of Biofinity Toric lenses (used for fitting at visit 1 only), custom-made Biofinity XR 
lenses (used for clinical evalution at visits 2 and 3) and spherical Biofinity lenses (used for 
all visits) will be supplied by CooperVision Inc.  Wide aperture trial frame lenses will be used 
to provide optimal spectacle correction at study visits 2 and 3. All worn contact lenses will 
be discarded. On completion of this study, unworn contact lenses will be discarded and a 
copy of the lens destruction form will be sent to the sponsor. There will be an accurate 
accounting of the study test product at the completion of the study. All used study test 
products will be recorded (Lot number; Expiry date etc.). 
2.6.4 
Clinical equipment 
Clinical equipment is regularly maintained and calibrated as required.  Standard operating 
procedures and international standards are used where appropriate. 
2.7 
Study control 
This study is controlled by cross-comparison. Bias will be minimised by randomising the 
order of assessment. Subjects will be masked to the two contact lens types (toric versus 
spherical) – contact lenses will be over-labelled. 
2.8 
Documentation 
Documents related to this work that require archiving will be kept by Eurolens Research for 
a period of 20 years after completion of the final report.  The Sponsor’s permission will be 
sought before the documents are destroyed.   
2.9 
Data collection and analysis 
Data collected in this work will be recorded on a custom-developed database and an 
established data trail.  Data handling will include export of the study information from the 
clinical database into spreadsheet format for manipulation, followed by export into a 
statistical package for analysis. Most clinical data will be entered directly onto the electronic 
case report form and are considered to be source data.   
2.10 
Study completion 
The clinical phase of the study will be considered as complete when all subjects have 
attended their last visit.  

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2.11 
Confidentiality 
All matters related to this work will remain confidential within Eurolens Research, the 
funding company and any regulatory authority (e.g. Manchester UREC).  Eurolens 
Research will take all reasonable steps to ensure that specific lens-related information is 
not passed on to study participants unless this is required for clinical management of an 
adverse event.  Personal subject information will not be made available.  To cater for this, 
subjects will only be referred by their unique identity number in the study report.  The data 
activities of Eurolens Research are registered with the data protection officer at The 
University of Manchester. 
2.12 
Study monitoring 
In order to provide quality control and quality assurance as part of this work, the study 
monitor will: 
1. Liaise closely with the Principal Investigator. 
2. Monitor and ensure the safety of the subjects. 
3. Ensure that the investigation is being conducted according to the protocol. 
4. Monitor and review (or oversee review of) the study records to ensure accuracy. 
5. Ensure accountability of the study test product. 
6. Document their observations and make them available to relevant authorised parties 
(e.g. Manchester UREC). 
7. Implement the Eurolens Research clinical monitoring standard operating procedure. 
 
 

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contrast) will be carried out 
 
 
 
 
 
 
 
 
9. Steps 6-8 will then be repeated for the Biofinity sphere lens type.  
10. The custom-made Biofinity XR Toric lenses and spherical Biofinity lenses will then 
be ordered (Note: the Biofinity XR Toric lens type will be ordered on the desired 
cylinder axis and ± 10 degrees of the desired axis to allow lens rotation to be 
optimised, if required, at visit(s) 2 and 3). 
11. The subject will then be discharged and asked to return for Visit 2.  
Subjects may wear their habitual lenses between study visits. 
3.2.3 
Visit 2 
Subjects should attend wearing their habitual spectacles. The following procedures will be 
performed on the randomised eye only, with the fellow eye being patched: 
1. Any medical or ocular issues since the last visit will be recorded. 
2. The investigator will perform distance monocular logMAR visual acuity (both high 
and low contrast), in accordance with the current Eurolens Research Standard 
Operating Procedure ‘The set-up, measurement of visual acuity and procedures 
for carrying out an over refraction using the Eurolens computerised logMAR VA 
chart’. 
3. Slit lamp biomicroscopy will be carried out for the signs outlined in Table 4 and in 
accordance with the current Eurolens Research Standard Operating Procedure 
‘Examination of the anterior segment using slit lamp biomicroscopy’. Grades will 
be scored to the nearest 0.1 unit in the best judgement of the investigator using 
Efron Grading Scales. Corneal staining will be graded for five regions (central, 
superior, temporal, inferior and nasal) 
 The 
predominant type of corneal staining present will also be recorded. 
4. First randomised lens correction (custom-made toric contact lens, spherical 
contact lens or trial frame correction) will be applied.  
5. If a contact lens is applied, allow to settle for five minutes. 
6. Monocular logMAR visual acuity (high contrast) will be recorded before 
performing an over-refraction, and then monocular logMAR visual acuity (high and 
low contrast) will be carried out with the over-refraction in place, and in 

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accordance with the current Eurolens Research Standard Operating Procedure 
‘Assessment of visual performance using the Bailey-Lovie logMAR visual acuity 
 
 
 
 
 
  
8. For the Toric contact lens only: If the toric lens is misaligned from its desired 
orientation by >10 degrees, a new toric lens which compensates for this mis-
rotation should be applied and the procedures in steps 4-7 repeated. 
9. For the Toric contact lens only: If the investigator is unable to achieve an 
acceptable toric contact lens fit, but feels that this could be achieved by ordering 
a new lens specification, the visit should be brought to a premature end (by 
completion of step 17) and a repeat visit scheduled once the updated custom-
made toric lens is available.  
10. Fellow eye (non-tested eye) will be covered with an eye patch.  
11. Monocular logMAR visual acuity (high and low contrast) will be performed for the 
first correction type at three different pupil sizes 
. Pupil size will 
be controlled using a novel, automated room lighting/feedback system.  
12. 
 
 
 
 
13. Removal of first lens correction and fitting of second randomised correction. 
14. The same procedures described above (points 5-13) will be conducted for the 
second lens correction.  
15. The same procedures described above (points 5-13) will be conducted for the 
third lens correction.  
16. 
 
 
17. The investigator will then measure exit VAs and conduct an exit biomicroscopic 
examination as detailed in section 3.2.2 in accordance with the current Eurolens 
Research Standard Operating Procedure ‘Examination of the anterior segment 
using slit lamp biomicroscopy’. 
18. If only one eye of the subject is to be assessed, payment will be issued and the 
subject exited from the study. 

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3.2.4 
Visit 3 
For those subjects whose second eye is to be assessed.  Subjects should attend wearing 
their habitual spectacles. The following procedures will be performed on the randomised 
eye only, with the fellow eye being patched: 
1. The same procedures as at Visit 2 (3.2.3) will be carried out, for the evaluation of 
the fellow eye in subjects where both eyes were suitable.  
2. At the final visit (or when the subject is discontinued at an earlier visit) the subject 
will be issued with their payment and discharged, although they may have been 
asked by the investigator to attend a post-study follow-up visit. They should 
continue to use their lenses and solutions as advised, and seek aftercare for their 
contact lenses.   
3.2.5 
Post-study follow-up visit 
In the case of a subject who exits the study with significant clinical signs or symptoms, the 
investigator must undertake to examine the subject at intervals he/she determines to be 
clinically appropriate until the sign or symptom has resolved or returned to a level that is 
considered to be clinically acceptable.  Details from these visits will be recorded on a post-
study follow-up visit form. 
3.3 
Monitoring subject compliance 
Subjects are required to adhere to the instructions provided during this clinical investigation.  
This will be confirmed at the study visits by verbal questioning of the subject by the 
investigator. 
3.4 
Missing, unused and spurious data 
The absence of any data will be carefully and critically considered.  If appropriate, partial 
datasets will be included in the final analysis.  Any data missing from a subject visit will be 
outlined in the report by indicating the number of subjects included for each analysis.  Data 
that are unused or considered to be spurious will be detailed and discussed in the report. 

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Section 4. Study co-ordination 
4.1 
Document processing 
All case report forms will be processed and evaluated by Eurolens Research, who will 
produce the final report with full statistical analysis.  A draft report will be sent to the Sponsor 
Contact Person in order to make comments and ask for re-drafts.  If no comments are 
received from the Sponsor Contact Person within eight weeks, a final report will be released 
with a separate document control page (in duplicate), requesting the Sponsor Contact 
Person to sign both copies, one to keep and the other to be returned to Eurolens Research. 
4.2 
Disclosure 
All matters relating to this clinical study are confidential and should only be disclosed to 
relevant authorised parties.  More precise details relating to disclosure are outlined in the 
Research Agreement.  None of the investigators involved in this work owns equity in the 
funding company. 
4.3