Randomised Clinical Investigation of the Bi Flex M Multifocal Intraocular Lens
Phase: PHASE4
Conditions: Cataract
Sponsor: Dr Phillip J Buckhurst

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Randomised clinical investigation of the Bi flex M multifocal 
Intraocular lens  
 
 
 
Research Protocol 
Version 1.0 
23rd January 2015 
 
Principal investigator 
Phillip Buckhurst 
 
Co-investigators 
Elizabeth Law 
Rajesh Aggarwal 
Hosam Kasaby 
Hetal Buckhurst 
 
Proposed Site: 
 

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BMI Southend Private Hospital, Westcliff-on-Sea, SS0 9AG 
 
Table of Contents 
Introduction 
3 
Aims: 
4 
Methodology: 
4 
Inclusion Criteria: 
4 
Exclusion Criteria: 
5 
Surgical Technique: 
5 
Methods 
5 
Statistical Analysis: 
6 
Sample Size 
6 
Ethics & Regulatory Approvals 
7 
Data Handling 
7 
Dissemination 
7 
References: 
7 
 
 
 
 

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Introduction 
With an ageing population, cataract surgery has become the most common surgical 
procedure carried out in the developed world. Approximately 2.5 million surgeries are 
preformed in the USA each year and approximately 250,000 are preformed in the 
UK.[1] Cataract surgery is also known as phacoemulsification and involves the 
extraction of the natural lens from its capsular bag and implantation of an artificial 
intraocular lens (IOL). The evolution of IOL designs has been rapid and extensive 
development of new advanced IOLs has occurred in recent years; spherical 
monofocal IOL designs are no longer the only pseudophakic option. Multifocal IOLs 
(MIOLs) are popular for the surgical correction of presbyopia because their 
mechanism of action is independent of ciliary body function. MIOLs provide high 
levels of spectacle independence[2] and currently are the most reliable lens for 
attaining both distance and near vision. This has lead to refractive lens exchange 
gaining popularity as increasing numbers of presbyopic patients look for refractive 
solutions. Monofocal intraocular lenses are the staple of cataract surgery providing 
excellent distance vision, however as patients expectations and demands rise, the 
need for correction of intermediate and near vision has become increasingly 
important. MIOLs restore some visual function at different distances by creating at 
least two focal points within the eye, corresponding to different working distances. 
Several mechanisms can be employed to create the simultaneous focal points and it 
is important to consider an MIOL’s method of action as each lens has its own unique 
optical properties. The design of the MIOL affects the light distribution, the number of 
focal points, the distance of their separation, and ultimately the quality of the images. 
MIOLs can be divided into diffractive and refractive designs. Refractive designs can 
be subdivided into concentric and sectorial, while diffractive designs can be 
categorised as fully diffractive or partially diffractive. 
Intermediate visual function has posed a problem with MIOL implantation. A 
drop in acuity in the intermediate range has been reported with bifocal multifocal 
lenses. [3-5] Good intermediate vision is a requirement for certain individuals for 
occupational or recreational purposes and a sub-optimal acuity in the intermediate 
range can have a negative influence on the individual’s quality of life[6] To this end 
recent MIOLs have been designed to improve intermediate vision by the use of a 

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lower add. These lenses provided good distance and near acuity as well as 
acceptable intermediate vision.[7-10]  
With intermediate and near vision being essential in most individual’s daily 
routine, it is clear that a solution is required and an IOL that can provide good vision 
at intermediate and near, without detriment to distance vision is needed. 
Visual acuity alone is not an adequate measure of success with MIOLs. All MIOLs 
create two or more simultaneous focal points within the eye. Therefore, at any one 
time at least one focal point will not be convergent on the retina. This defocused 
image causes a reduction in contrast and a distinctive photopic phenomenon known 
as Dysphotopsia.[2,12] This phenomenon, is one of the most common complaints 
with multifocal implantation and needs to be investigated to fully understand how the 
optical properties of an MIOL affect this photopic phenomenon. 
Aims:  
 
This study aims to evaluate the visual function and patient satisfaction of patients 
who have been implanted with the BiFlex M Multifocal IOL (Medicontur) and to 
compare the results with patients implanted with the BiFlex 1.8 monofocal IOL. 
Methodology: 
 
This prospective randomised control study will evaluate 100 patients (200 
eyes) having undergone bilateral implantation with either the multifocal or 
monofocal IOLs for either cataract or clear lens extraction surgery. 
 
Preoperatively all patients have comprehensive ophthalmological 
examination, including detailed history, refraction, dilated fundus examination, 
tonometry and slit lamp examination to exclude pre-existing conditions which may 
limit the refractive outcome. IOL power calculations will be performed using a Haag 
Streit LS900 Lenstar biometer. All patients will be adequately informed and sign a 
consent form. 
Inclusion Criteria: 
 Age 50-75 years, bilateral IOL implantation. 

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Exclusion Criteria:  
 
 
Amblyopia, post-op corneal astigmatism of ≥1.50D, visual axis eccentricity of 
greater than 0.7mm, macular pathology, glaucoma, retinal disease, corneal 
disease, abnormal iris, pupil deformation and any previous corneal or intraocular 
surgery. 
 
 
Surgical Technique: 
 
All surgeries will be performed by one of two experienced ophthalmic 
surgeons using a standard, sutureless, microincision, phacoemulsification 
technique under topical anaesthesia. Routine post-op drug regime will be followed.  
Methods 
Each subject will be evaluated at three visits following IOL implantation; visit 1 (1 
month), Visit 2 (3-6 months) and visit 3 (12-18 months). 
At each visit the following non-invasive visual function tests will be conducted: 
Monocular and binocular Unaided (UCVA) and Best Corrected Visual Acuity (BCVA) 
will be measured at 6 meters in LogMAR units using a calibrated computerised 
test chart. 
Subjective and objective refraction will be used to determine if there is any residual 
refractive error. 
Defocus curve profiles (visual acuity over imposed defocus) will be measured for 
each patient over a defocus range of +1.50D to -5.00D in 0.50D steps. The 
presentation of the letters and lenses will be randomised.  
Contrast sensitivity will be evaluated monocularly under photopic and mesopic 
conditions using the Pelli-Robson Contrast Sensitivity Chart and CSV-1000. 
Best distance corrected near and intermediate reading performance will be 
evaluated using the Radner Reading Charts and LogMAR charts and reading  
speed will be assessed in photopic conditions 
Uncorrected and best distance corrected near acuity will be measured at 40cm  
Uncorrected and best distance corrected intermediate acuity will be measured at 
70cm.  
The subject will be shown the Glare Simulator (Carl Zeiss Meditec) in order to 
assess the type of dysphotopsia present at each visit 

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A Halometer will be used to determine the size of the dysphotopsia 
In order to assess the ocular biometry and record features of the IOL, at each visit 
the following imaging tests will be conducted following instillation of Tropicamide 
1% to dilate the pupil: 
 The Lenstar (Haagstreit) will be used to determine the post-operative axial 
position of the IOL following implantation. 
 The A digital slit lamp camera will be used to image the IOL. This image will 
be used to determine if any decentration is present and if posterior 
supcapsular opacification is present using the EPCO 2000 software 
programme. 
At each visit the following subjective assessment tests will be given to the patient to 
complete: 
 The Visual satisfaction questionnaire will be used to determine the patient’s 
overall satisfaction with their vision 
 Near Assessment Visual Questionnaire (NAVQ) will be used to assess the 
patients satisfaction with their near and intermediate vision[14] 
Statistical Analysis: 
Normal distribution will be determined through examining histogram plots and with 
the Kolmogorov-Smirnov test. For analysis of the defocus curves the data will first be 
transformed into the defocus area metric[15] and the Radner reading chart data will 
also be converted according to the reading performance index.[16] Following this the 
means from each group will be assessed using two-way repeated measures ANOVA 
and a Pearson’s coefficient will be used to look for correlations within the data. The 
results from the visual satisfaction questionnaire and NAVQ will be converted into 
Log RASCH units to provide a linear scale.  
Sample Size 
Using GPower 3 a sample size of 50 subjects (100 eyes) per group was calculated 
for this study, therefore a total of 100 subjects will be recruited for the study.   

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Ethics & Regulatory Approvals 
The study will be conducted in compliance with the principles of the Declaration of 
Helsinki (1996), the principles of GCP and in accordance with all applicable 
regulatory requirements including but not limited to the Research Governance 
Framework. Ethical approval will be sought from Plymouth University 
Data Handling 
All of the investigators are UK registered optometrists or UK registered 
Ophthalmologists who are bound by a code of conduct for confidentiality and data 
protection. 
The information collected during this study will be stored electronically on a 
password protected hard drive on the chief investigator’s computer, in a document 
file which is also password protected.  Data will be backed-up on CD-ROMs as 
encrypted files, stored in a locked cabinet in a locked office.   
Data will only be used for this research study and will be archived at BMI Southend 
for the recommended 10-year period.  This may be looked at during this time by an 
auditing team for monitoring purposes. 
To ensure anonymity is maintained throughout this study, subjects will be allocated a 
participant number to which their individual data will be assigned too.  A key for 
participant numbers will be kept securely electronically on a memory stick, which will 
be kept in a locked cupboard in a locked room.  Access to this key will be limited to 
the principle investigators and co-investigators.   
Any research data generated from electronic equipment will be coded and 
anonymised. 
Dissemination  
It is intended that the results of the study will be reported and disseminated at 
national and international conferences and in peer-reviewed scientific journals.  
References: 
1 
Dua HS, Said DG, Otri AM. Are we doing too many cataract operations? 
Cataract surgery: a global perspective. Br J Ophthalmol 2009;93:1–2. 
doi:10.1136/bjo.2008.143685 

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2 
Packer M, Chu YR, Waltz KL, et al. Evaluation of the aspheric tecnis multifocal 
intraocular lens: one-year results from the first cohort of the food and drug 
administration clinical trial. Am J Ophthalmol 2010;149:577–584.e1. 
doi:10.1016/j.ajo.2009.10.022 
3 
Blaylock JF, Si Z, Vickers C. Visual and refractive status at different focal 
distances after implantation of the ReSTOR multifocal intraocular lens. J 
Cataract Refract Surg 2006;32:1464–73. doi:10.1016/j.jcrs.2006.04.011 
4 
Auffarth GU, Hunold W, Wesendahl TA, et al. Depth of focus and functional 
results in patients with multifocal intraocular lenses: a long-term follow-up. J 
Cataract Refract Surg 1993;19:685–9. 
5 
Weghaupt H, Pieh S, Skorpik C. Comparison of pseudoaccommodation and 
visual quality between a diffractive and refractive multifocal intraocular lens. J 
Cataract Refract Surg 1998;24:663–5. 
6 
Cochener B, Vryghem J, Rozot P, et al. Visual and refractive outcomes after 
implantation of a fully diffractive trifocal lens. Clin Ophthalmol 2012;6:1421–7. 
doi:10.2147/OPTH.S32343 
7 
Alfonso JF, Fernández-Vega L, Señaris A, et al. Prospective study of the 
Acri.LISA bifocal intraocular lens. J Cataract Refract Surg 2007;33:1930–5. 
doi:10.1016/j.jcrs.2007.06.067 
8 
Alfonso JF, Fernández-Vega L, Amhaz H, et al. Visual function after 
implantation of an aspheric bifocal intraocular lens. J Cataract Refract Surg 
2009;35:885–92. doi:10.1016/j.jcrs.2009.01.014 
9 
Alfonso JF, Fernández-Vega L, Puchades C, et al. Intermediate visual function 
with different multifocal intraocular lens models. J Cataract Refract Surg 
2010;36:733–9. doi:10.1016/j.jcrs.2009.11.018 
10 Petermeier K, Messias A, Gekeler F, et al. Effect of +3.00 diopter and +4.00 
diopter additions in multifocal intraocular lenses on defocus profiles, patient 
satisfaction, and contrast sensitivity. J Cataract Refract Surg 2011;37:720–6. 
doi:10.1016/j.jcrs.2010.11.027 
11 Sen HN, Sarikkola A-U, Uusitalo RJ, et al. Quality of vision after AMO Array 
multifocal intraocular lens implantation. J Cataract Refract Surg 2004;30:2483–
93. doi:10.1016/j.jcrs.2004.04.049 
12 Pieh S, Lackner B, Hanselmayer G, et al. Halo size under distance and near 
conditions in refractive multifocal intraocular lenses. Br J Ophthalmol 
2001;85:816–21. 
13 Rosales P, De Castro A, Jiménez-Alfaro I, et al. Intraocular lens alignment from 
purkinje and Scheimpflug imaging. Clin Exp Optom 2010;93:400–8. 
doi:10.1111/j.1444-0938.2010.00514.x 
14 Buckhurst PJ, Wolffsohn JS, Gupta N, et al. Development of a questionnaire to 
assess the relative subjective benefits of presbyopia correction. J Cataract 

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Refract Surg 2012;38:74–9. doi:10.1016/j.jcrs.2011.07.032 
15 Buckhurst PJ, Wolffsohn JS, Naroo SA, et al. Multifocal Intraocular Lens 
Differentiation Using Defocus Curves. Invest Ophthalmol Vis Sci Published 
Online First: 15 May 2012. doi:10.1167/iovs.11-9234 
16 Buckhurst PJ, Wolffsohn JS, Shah S, et al. Evaluation of multifocal and 
accommodating intraocular lenses using the reading performance index, a new 
MNRead metric. Proceedings of the XXIX congress of the European Society of 
Cataract and Refractive Surgeons 2012