Clinical Investigation of AcrySof IQ PanOptix Toric Intraocular Lens Model TFNT20
Phase: NA
Conditions: Aphakia, Corneal Astigmatism
Sponsor: Alcon Research



 
Document ID: 
V-CLN-0001330
Status: Approved, Version: 4.0 
Approved Date: 19 Apr 2021 
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Investigator Agreement: 
I have read the clinical study described herein, recognize its confidentiality, and agree to 
conduct the described trial in compliance with Good Clinical Practice (GCP), the 
ethical principles contained within the Declaration of Helsinki, this protocol, all 
applicable regulatory authority regulations, and conditions of approval imposed by 
the reviewing IRB or regulatory authority. 
I will supervise all testing of the device involving human subjects and ensure that the 
requirements relating to obtaining informed consent and IRB review and approval 
are met in accordance with applicable local and governmental regulations. 
I have read and understand the appropriate use of the investigational product(s) as 
described in the protocol, current Investigator’s Brochure, or other sources provided 
by the Sponsor. 
I understand the potential risks and side effects of the investigational product(s). 
I agree to maintain adequate and accurate records in accordance with government 
regulations and to make those records available for inspection. 
I agree to comply with all other requirements regarding the obligations of clinical 
Investigators and all other pertinent requirements of the Sponsor and government 
agencies. 
I agree to ensure that all associates, colleagues, and employees assisting in the conduct 
of the study are informed of their obligations in meeting the above commitments. 
Have you ever been disqualified as an Investigator by any Regulatory Authority? 
No
Yes
Have you ever been involved in a study or other research that was terminated? 
No
Yes
If yes, please explain here: 
Principal Investigator: 
Signature 
Date 
Name and professional 
position: 
Address: 

 
Document ID: 
V-CLN-0001330
Status: Approved, Version: 4.0 
Approved Date: 19 Apr 2021 
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Table of Contents 
Table of Contents ..................................................................................................................... 3 
List of Tables ............................................................................................................................ 6 
List of Figures ........................................................................................................................... 6 
1 
GLOSSARY OF TERMS .................................................................................... 7 
2 
LIST OF ACRONYMS AND ABBREVIATIONS .......................................... 10 
3 
PROTOCOL SUMMARY ................................................................................. 11 
4 
PROTOCOL AMENDMENTS ......................................................................... 16 
4.1 
Amendments .................................................................................................... 16 
5 
INTRODUCTION .............................................................................................. 17 
5.1 
Rationale and Background ............................................................................. 17 
5.2 
Purpose of the Study ....................................................................................... 18 
5.3 
Risks and Benefits............................................................................................ 18 
6 
STUDY OBJECTIVES ...................................................................................... 19 
6.1 
Primary Objective(s) ....................................................................................... 19 
6.2 
Secondary Endpoint(s) .................................................................................... 19 
 
 
 
 
6.5 
Safety Objective(s) ........................................................................................... 20 
7 
INVESTIGATIONAL PLAN ............................................................................ 21 
7.1 
Study Design..................................................................................................... 21 
7.2 
Rationale for Study Design ............................................................................. 23 
7.2.1 
Purpose and Timing of Interim Analyses and Resulting Design 
Adaptations ...................................................................................... 23 
7.3 
Rationale for Duration of Treatment/Follow-Up ......................................... 23 
7.4 
Data Monitoring Committee .......................................................................... 23 
8 
STUDY POPULATION ..................................................................................... 24 
8.1 
Inclusion Criteria............................................................................................. 24 
8.2 
Exclusion Criteria Prior to Cataract Surgery .............................................. 25 
8.3 
Exclusion Criteria During Cataract Surgery................................................ 26 
8.4 
Rescreening of Subjects .................................................................................. 27 

 
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Approved Date: 19 Apr 2021 
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9 
TREATMENTS ADMINISTERED .................................................................. 28 
9.1 
Investigational Product(s) ............................................................................... 28 
9.2 
Other Medical Device or Medication Specified for Use During the Study 30 
9.3 
Treatment Assignment / Randomization ....................................................... 30 
9.4 
Accountability Procedures .............................................................................. 30 
9.5 
Changes to concomitant medications, treatments/ procedures ................... 31 
10 
STUDY PROCEDURES AND ASSESSMENTS ............................................. 32 
10.1 Description of Study Procedures and Assessments ...................................... 32 
10.1.1 
Preoperative Examination (Visit 0/0A) ......................................... 32 
10.1.2 
Surgery Day (Visit 00/00A) ............................................................. 34 
10.1.3 
Postoperative Examinations (Visit 1/1A, Visit 2/2A and Visit 
3/3A) .................................................................................................. 36 
10.2 Unscheduled Visits........................................................................................... 38 
10.3 Discontinued Subjects ..................................................................................... 39 
10.3.1 
Screen Failures ................................................................................. 39 
10.3.2 
Discontinuations .............................................................................. 39 
10.4 Clinical Study Termination ............................................................................ 40 
10.4.1 
Follow-up of subjects after study participation has ended .......... 40 
11 
ADVERSE EVENTS AND DEVICE DEFICIENCIES .................................. 41 
11.1 General Information ....................................................................................... 41 
11.2 Procedures for Recording and Reporting ..................................................... 42 
11.3 Unmasking of the Study Information ............................................................ 43 
11.4 Follow-Up of Safety Information ................................................................... 43 
11.5 Pregnancy in the Clinical Study ..................................................................... 44 
12 
ANALYSIS PLAN .............................................................................................. 45 
12.1 Subject Evaluability ........................................................................................ 45 
12.2 Analysis Sets ..................................................................................................... 45 
12.3 Demographic and Baseline Characteristics .................................................. 45 
12.4 Effectiveness Analyses ..................................................................................... 46 
12.4.1 
Analysis of Primary Effectiveness Endpoint(s) ............................ 46 
12.4.1.1 
Statistical Hypotheses ............................................................................. 46 
12.4.1.2 
Analysis Methods .................................................................................... 46 
12.4.2 
Analysis of Secondary Effectiveness Endpoint(s) ......................... 47 
12.4.2.1 
Statistical Hypotheses ............................................................................. 47 

 
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12.4.3.1 
Statistical Hypotheses ............................................................................. 47 
12.4.3.2 
Analysis Methods .................................................................................... 48 
12.5 Handling of Missing Data ............................................................................... 48 
12.6 Safety Analyses ................................................................................................ 48 
12.7 Interim Analyses and Reporting .................................................................... 49 
12.8 Sample Size Justification ................................................................................ 49 
13 
DATA HANDLING AND ADMINISTRATIVE REQUIREMENTS ........... 50 
13.1 Subject Confidentiality ................................................................................... 50 
13.2 Completion of Source Documents and Case Report Forms ........................ 50 
13.3 Data Review and Clarifications ...................................................................... 51 
13.4 Sponsor and Monitoring Responsibilities ..................................................... 51 
13.5 Regulatory Documentation and Records Retention ..................................... 52 
13.6 Quality Assurance and Quality Control ........................................................ 52 
14 
ETHICS ............................................................................................................... 53 
15 
REFERENCES ................................................................................................... 56 
 
 
 

 
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Status: Approved, Version: 4.0 
Approved Date: 19 Apr 2021 
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List of Tables 
Table 2–1 
List of Acronyms and Abbreviations Used in This Protocol ........................... 10 
Table 3–1 
Schedule of Study Procedures and Assessments ............................................. 15 
Table 6–1 
Primary Endpoint(s) ......................................................................................... 19 
Table 6–2 
Secondary Endpoint(s) ..................................................................................... 19 
 
 
Table 6–4 
Safety Endpoint(s) ........................................................................................... 20 
Table 9–1 
Test Product ..................................................................................................... 28 
 
List of Figures 
Figure .7 1 
Study Design .................................................................................................... 22 
Figure .11 1 
Categorization of All Adverse Events .............................................................. 41 
Figure .11 2 
Categorization of All Serious Adverse Events ................................................. 41 
 
 
 

 
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1 GLOSSARY OF TERMS 
Names of test product(s) 
Throughout this document, test product(s) will be referred to 
as TFNT20 
Name of Control Product(s) N/A 
Adverse Device Effect 
(ADE) 
 
Adverse event related to the use of an investigational 
medical device (test product) or control product. Note: This 
definition includes adverse events resulting from insufficient 
or inadequate instructions for use, deployment, 
implantation, installation, or operation; any malfunction; 
and use error or intentional misuse of the test product or 
control product. 
Adverse Event (AE) 
 
Any untoward medical occurrence, unintended disease or 
injury, or untoward clinical signs (including abnormal 
laboratory findings) in subjects, users or other persons, 
whether or not related to the investigational medical device 
(test product). Note: For subjects, this definition includes 
events related to the test product, the control product, or the 
procedures involved. For users or other persons, this 
definition is restricted to events related to the test product. 
Requirements for reporting Adverse Events in the study can 
be found in Section 11. 
Anticipated Serious 
Adverse Device Effect 
(ASADE) 
Serious adverse device effect which by its nature, incidence, 
severity, or outcome has been identified in the risk 
management file. 
Device Deficiency 
Inadequacy of a medical device with respect to its identity, 
quality, durability, reliability, safety, or performance. Note: 
This definition includes malfunctions, use errors, and 
inadequate labeling. 
Requirements for reporting Device Deficiencies in the study 
can be found in Section 11. 
Enrolled Subject 
Any subject who signs an informed consent form for 
participation in the study. 

 
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Investigational Product 
Is defined as a preventative (vaccine), a therapeutic (drug or 
biologic), device, diagnostic, or palliative used as a test or 
control product in a clinical trial, including a product with a 
marketing authorization when used or assembled 
(formulated or packaged) in a way different from the 
authorized form, or when used for an unauthorized 
indication, or when used to gain further information about 
the authorized form. 
Malfunction 
Failure of a medical device to perform in accordance with its 
intended purpose when used in accordance with the 
instructions for use or clinical investigation plan. 
Non-serious Adverse Event 
Adverse event that does not meet the criteria for a serious 
adverse event. 
Serious Adverse Device 
Effect (SADE) 
Adverse device effect that has resulted in any of the 
consequences characteristic of a serious adverse event. 
Serious Adverse Event 
(SAE) 
Adverse event that led to any of the following: 
• 
Death. 
• 
A serious deterioration in the health of the subject 
that either resulted in: 
a. a life-threatening illness or injury. 
Note: Life-threatening means that the 
individual was at immediate risk of death from 
the event as it occurred, ie, it does not include 
an event which hypothetically might have 
caused death had it occurred in a more severe 
form. 
b. any potentially sight-threatening event or 
permanent impairment to a body structure or a 
body function. 

 
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c. in-patient hospitalization or prolonged 
hospitalization. 
Note: Planned hospitalization for a pre-
existing condition, without serious 
deterioration in health, is not considered a 
serious adverse event. In general, 
hospitalization signifies that the individual 
remained at the hospital or emergency ward 
for observation and/or treatment (usually 
involving an overnight stay) that would not 
have been appropriate in the physician's office 
or an out-patient setting. Complications that 
occur during hospitalization are adverse 
events. If a complication prolongs 
hospitalization or fulfills any other serious 
criteria, the event is serious. When in doubt as 
to whether “hospitalization” occurred, the 
event should be considered serious. 
d. a medical or surgical intervention to prevent 
a), b) or any ocular secondary surgical 
intervention excluding posterior 
capsulotomy”.] 
e. any indirect harm as a consequence of 
incorrect diagnostic test results when used 
within manufacturer’s instructions for use. 
• 
Fetal distress, fetal death, or a congenital 
abnormality or birth defect. 
Refer to Section 11 for additional SAEs. 
Unanticipated Serious 
Adverse Device Effect 
(USADE) 
Serious adverse device effect which by its nature, incidence, 
severity or outcome has not been identified in Investigator’s 
Brochure.  
Use Error 
Act or omission of an act that results in a different medical 
device response than intended by manufacturer or expected 
by user. Note: This definition includes slips, lapses, and 
mistakes. An unexpected physiological response of the 
subject does not in itself constitute a use error. 

 
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2 LIST OF ACRONYMS AND ABBREVIATIONS 
Table 2–1 
List of Acronyms and Abbreviations Used in This Protocol 
Abbreviation 
Definition 
ADE 
Adverse device effect 
AE 
Adverse event 
ARMD 
Age-related macular degeneration 
cd 
Candela 
CI 
Confidence interval 
CRF 
Case report form 
D 
Diopter(s) 
GCP 
Good Clinical Practice 
IB 
Investigator’s brochure 
ICF 
Informed consent form 
IOL 
Intraocular lens 
IOP 
Intraocular pressure 
IP 
Investigational product 
IRB 
Investigational review board 
LASIK 
Laser-assisted in situ keratomileusis 
LRI 
Limbal relaxing incision 
mm 
millimeter 
MOP 
Manual of procedures 
PCO 
Posterior capsule opacification 
PRK 
Photorefractive keratectomy 
SAE 
Serious adverse event 
SADE 
Serious adverse device effect 
SD 
Standard deviation 
SOP 
Standard operating procedure 
SSI 
Secondary Surgical Intervention(s) 
VA 
Visual acuity 
YAG 
Yttrium aluminum garnet laser 
 
 

 
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3 PROTOCOL SUMMARY 
This study is a prospective, single-center and non-comparative study. The study will include 
subjects must be ≥ 20 years of age with cataract who would be eligible to receive a TFNT20 
lens in at least one eye based on a new Alcon Toric calculator that incorporates ocular trends 
in Toric IOL planning. Subject with no ocular pathology that could confound study outcome, 
must require clear cornea cataract extraction, and must desire an IOL that provides the 
potential for near, intermediate and distance vision and corrects astigmatism. Potential 
subjects will be screened for enrollment into this clinical trial. Those qualifying will attend a 
total 5 visits. If the investigational products will be implanted to both eye, the maximum 
number of visits is total 9 visits. Primary endpoint data will be collected at the final visit, 
Visit3/3A (30-60 days post implantation). No interim analysis is planned. 
Investigational 
product type 
Device 
Study type 
Interventional 
Investigational 
products 
Test Product: AcrySof IQ PanOptix Toric Intraocular Lens Model 
TFNT20 (hereinafter called "TFNT20") 
Control Product: Not applicable 
Purpose and 
rationale 
The purpose of this study is to evaluate effectiveness and safety of 
the TFNT20 when implanted to replace the natural lens following 
cataract removal. 
 this is intended to confirm the safety of the 
test product and examine its effectiveness as a Toric lens by 
examining the subject’s astigmatism power.  
Objective(s) 
To evaluate effectiveness and safety of the TFNT20 when 
implanted to replace the natural lens following cataract removal. 
Endpoint(s)  
Primary Effectiveness  
• 
Percentage of eyes with ≤ 0.25 D refractive cylinder at 
Visit 3/3A (Day 30-60) 
Secondary Effectiveness  
• 
Percentage of eyes with ≤ 0.5 D refractive cylinder at Visit 
3/3A (Day 30-60) 

 
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• 
Average manifest refractive cylinder at Visit 3/3A (Day 30-
60) 
 
 
 
 
 
 
 
 
 
 
 
Safety 
• 
Adverse events including SSI 
• 
Device deficiencies 
• 
Posterior capsular opacification 
• 
Posterior capsulotomy 
• 
IOL position change (tilt and decentration) 
• 
Intraocular pressure 
• 
Surgical problems 
• 
Slit Lamp Examination 
• 
Dilated Fundus Examination 
• 
IOL Observations 
Assessment(s)  
 
 
 
 
 
 
 
 
 
 
 
Safety 
• 
Adverse events including SSI 

 
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• 
Device deficiencies 
• 
Posterior capsular opacification 
• 
Posterior capsulotomy 
• 
IOL position change (tilt and decentration) 
• 
Intraocular pressure 
• 
Surgical problems 
• 
Slit Lamp Examination 
• 
Dilated Fundus Examination 
• 
IOL Observations 
Study Design 
This study is a prospective, single-center and non-comparative 
study. 
Subject population 
Subjects must be ≥ 20 years of age with cataract who would be 
eligible to receive a TFNT20 lens in at least one eye based on a 
new Alcon Toric calculator that incorporates ocular trends  in 
Toric IOL planning.  
Planned number of subjects implanted: 32 eyes for first surgery 
(32 subjects) 
 
 
 
Key inclusion 
criteria 
(See Section 8.1 for a 
complete list of 
inclusion criteria) 
• 
Eligible to be implanted with TFNT20 as determined by a new 
Alcon Toric calculator in at least one eye that incorporates 
ocular trends in surgical planning. 
• 
Subjects for whom postoperative emmetropia is planned 
(spherical equivalent ± 0.50 D). 
Key exclusion 
criteria 
(See Section 8.2 for a 
complete list of 
exclusion criteria) 
• 
Irregular corneal astigmatism as assessed by topographer per 
investigator decision. 

 
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• 
History of anterior segment (corneal, anterior chamber, 
sulcus) or posterior segment (uveal, vitreo-retinal) pathology 
including retinal vascular occlusive disease, retinal 
detachment or peripheral retinal laser photocoagulation, 
ARMD, glaucoma (uncontrolled or controlled with 
medication) or ocular hypertension, diabetic retinopathy, 
retinitis pigmentosa and any optic nerve pathology. 
• 
History of previous intraocular or corneal (refractive or 
trauma related) surgery. 
• 
Any other planned ocular surgical procedures including but 
not limited to limbal relaxing incision (LRI)/Astigmatic 
Keratotomy and LASIK 
Data analysis and 
sample size 
justification 
To enroll more than or equal to 30 eligible T2 eyes used for 
analysis, at least 30 subjects will be evaluated by a new Alcon 
Toric calculator that incorporates ocular trends in Toric IOL 
planning and unilaterally or bilaterally implanted with the AcrySof 
IQ PanOptix IOL (TFNT20).   
Using a new Alcon calculator that incorporates ocular trends in 
Toric IOL planning, percentage of eyes with ≤ 0.25 D refractive 
cylinder at Visit 3/3A (Day 30-60) in T2 group was estimated as 
60.9% based on a previous 
(T2) study conducted in US.  
Using the same calculator, the percentage in T0 group was 
recalculated as 29.2% from the combined result of studies (non-
Toric (T0) lenses) conducted in Japan 
 
  Statistical test will be conducted to compare 
percentage of T2 with a constant of 29.2% as percentage of T0.  
With 30 eyes from 30 subjects in T2 group, assuming the 
percentage of T2 is equal to 60.9% 
 the 
statistical power to demonstrate superiority of T2 to T0 is 91.6% 
with one-sided alpha of 2.5%, using an exact test of binomial 
proportion. 
Anticipated study 
period 
Sep, 2020 ~ Sep, 2021 
Key words 
Cataract, intraocular lens, Toric, astigmatism 
Associated materials Not applicable. 
 
 

 
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Table 3–1 
Schedule of Study Procedures and Assessments 
Activity 
Visit 0/0A 
(Day-60 to 0) 
Visit 
00/00A 
(Day 0) 
Visit 1/1A 
(Day 1-2) 
Visit 2/2A 
(Day 7-14) 
Visit 3/3A 
(Day 30-60) 
Informed Consent* 
X 
 
 
 
 
Demographics 
X 
 
 
 
 
Medical History 
X 
X 
 
 
 
Concomitant 
Medications 
X 
X 
X 
X 
X 
Urine Pregnancy Test** 
X 
(Visit 0 only) 
 
 
 
 
Inclusion/Exclusion 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Subjective Manifest 
Refraction 
X 
 
X 
X 
X 
Slit-Lamp Examination 
X 
 
X 
X 
X 
Fundus exam with 
dilated pupil 
X 
 
 
 
X 
Keratometry 
X 
 
(X) 
(X) 
X 
Target Residual 
Refractive Error 
X 
 
 
 
 
Calculation by new 
Alcon Toric calculator 
that incorporates ocular 
trends in Toric IOL 
planning 
X 
 
 
 
 
Topography 
X 
 
(X) 
(X) 
X 
Axial Length 
X 
 
(X) 
(X) 
X 
Anterior chamber depth 
X 
 
(X) 
(X) 
X 
Intraocular Pressure 
X 
 
X 
X 
X 
 
 
 
 
 
 
 
Operation Record**** 
 
X 
 
 
 
Posterior capsular 
opacification 
 
 
X 
X 
X 
Posterior capsulotomy 
 
 
X 
X 
X 
IOL observations 
 
X 
X 
X 
X 
IOL position change (tilt 
an decentration) 
 
 
X 
X 
X 
Adverse Events 
X 
X 
X 
X 
X 
Secondary Surgical 
Intervention 
 
X 
X 
X 
X 
Device Deficiencies 
X 
X 
X 
X 
X 
(X): The data will be captured if the investigator judged to be able to conduct the examination based on the subject’s condition. 
* When a subject receives the bilateral study lens implantation, written informed consent form prior to the examinations at Visit 0A is 
needed. 
** Women of child-bearing potential only 
*** A slit lamp photograph shall be recorded and kept as a source document. 
**** Operative eye, lens information, final incision size, surgical problems and other surgical procedures during surgery will be collected. 

 
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4 PROTOCOL AMENDMENTS 
Modification of the protocol is prohibited without prior written agreement in the form of a 
protocol amendment. All amendments must be created by the Study Sponsor and must be 
approved by the IRB and global and regional Health Authorities, as applicable, prior to 
implementation except when required to mitigate immediate safety risks or when the changes 
involve only logistical or administrative revisions.  
Amendments may necessitate that the informed consent and other study-related material be 
revised. If the consent form is revised, all subjects currently enrolled in the study must sign 
the approved, revised informed consent (re-consent), as required by the IRB. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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5 INTRODUCTION 
5.1 Rationale and Background 
The first clinical results of the multifocal intraocular lenses were reported in the United States 
in 1987. The first Japanese clinical study was performed and reported in the early 1990’s 1). 
In general, multifocal intraocular lenses are roughly divided into diffractive and refractive 
types. Diffractive lenses are structured to separate incident light energy to far and near 
visions, while refractive lenses have an optical zone structure consisting of far and near 
vision zones arranged in an alternate, concentric manner 2). Since the diffractive multifocal 
intraocular lens product, “Alcon® AcrySof® ReSTOR® Single Piece” (medical device 
approval number: 21900BZX00605000, Alcon Japan Ltd.) was first approved in 2007, 
various multifocal intraocular lenses have been developed in Japan. As opposed to monofocal 
intraocular lenses, intraocular lenses with 2 or more focuses are collectively called multifocal 
intraocular lenses. Actually bifocal intraocular lenses focusing on far and intermediate or near 
objects account for most of multifocal intraocular lenses in Japan, however three trifocal 
intraocular lenses, “Alcon Acrysof IQ PanOptix Single Piece (medical device approval 
number: 23100BZX00042000, Alcon Japan Ltd.)” and “Alcon Acrysof IQ PanOptix Toric 
Single Piece (medical device approval number: 23100BZX00043000, Alcon Japan Ltd.)”, 
focusing on far, intermediate, and near objects were approved in 2019. 
The AcrySof IQ PanOptix Toric IOL is a diffractive multifocal lens with a toric optic to 
correct pre-existing corneal astigmatism. The ACRYSOF IQ PanOptix Toric IOL is 
commercially available in 4 cylinder powers to reduce pre-existing corneal astigmatism 
(ACRYSOF IQ PanOptix Toric IOL TFNT30 - TFNT60), but the TFNT20, having lower 
cylinder power than approved products, has not been approved.  
Levels of astigmatism 0.5 D to 1.0 D are estimated to represent 35.6% of all cataract cases in 
Japan 3). For those patients, a lack of astigmatism correction can limit their desired outcome 
of visual acuity. Correcting astigmatism concurrently during phacoemulsification cataract 
surgery eliminates the need for additional surgical procedures, such as excimer laser 
keratectomy and limbal and corneal relaxing incision techniques. For example, the excimer 
laser can be cost prohibitive 4) and limbal and corneal relaxation incision can have less 
predictable results compared to Toric IOL options 4) 5) 6) 7) 8). 
The effect of astigmatism on the visual acuity of a multifocal intraocular lens implamted eyes 
are greater than that of a monofocal intraocular lens, and in particular, reduction of 
postoperative residual astigmatism is desired for multifocal intraocular lenses 9). Therefore, 
even if the cylinder power is low, it is important to reduce cylinder power astigmatism. 

 
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The TFNT20, a multifocal IOL with an adequate cylinder power for low cylinder power 
astigmatism patients, will provide patients, as an additional treatment option, with post-
cataract surgery quality of vision as they wish for, and is expected to contribute to the 
improved quality of vision after cataract surgery. 
 
5.2 Purpose of the Study 
The purpose of this study is to evaluate effectiveness and safety of the TFNT20 when 
implanted to replace the natural lens following cataract removal. So this is intended to 
confirm the safety of the test product and examine its effectiveness as a Toric lens by 
examining the subject’s astigmatism power. 
At the end of the study, a clinical study report will be prepared in accordance with applicable 
regulatory requirements and standards. 
  
5.3 Risks and Benefits 
 
 
 
 
 
The TFNT20, a multifocal IOL with an adequate cylinder power for low cylinder power 
astigmatism patients, is expected to contribute to the improved quality of vision after cataract 
surgery. 
There may also be unknown risks to use of test product. Any risk to subjects in this clinical 
study will be minimized by compliance with the eligibility criteria and study procedures, 
clinical oversight and monitoring. 
 
 

 
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6 STUDY OBJECTIVES 
6.1 Primary Objective(s) 
Table 6–1 
Primary Endpoint(s) 
Objective(s) 
Endpoint(s) 
To evaluate primary effectiveness of the 
TFNT20 when implanted to replace the 
natural lens following cataract removal. 
・ Percentage of eyes with ≤ 0.25 D 
refractive cylinder at Visit 3/3A (Day 
30-60) 
 
6.2 Secondary Endpoint(s) 
Table 6–2 
Secondary Endpoint(s) 
Objective(s) 
Endpoint(s) 
To evaluate secondary effectiveness of the 
TFNT20 when implanted to replace the 
natural lens following cataract removal. 
・ Percentage of eyes with ≤ 0.5 D 
refractive cylinder at Visit 3/3A (Day 
30-60) 
・ Average manifest refractive cylinder at 
Visit 3/3A (Day 30-60) 
 

 
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6.5 Safety Objective(s)  
Table 6–4 
Safety Endpoint(s) 
Objective(s) 
Endpoint(s) 
To evaluate safety of the TFNT20 when 
implanted to replace the natural lens 
following cataract removal. 
・ Adverse events including SSI 
・ Device deficiencies 
・ Posterior capsular opacification 
・ Posterior capsulotomy 
・ IOL position change (tilt and 
decentration) 
・ Intraocular pressure 
・ Surgical problems 
・ Slit Lamp Examination 
・ Dilated Fundus Examination 
・ IOL Observations 
 
 
 

 
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7 INVESTIGATIONAL PLAN 
7.1 Study Design 
This study is a prospective, single-center and non-comparative study. The study will include 
subjects must be ≥ 20 years of age with cataract who would be eligible to receive a TFNT20 
lens in at least one eye based on a new Alcon Toric calculator that incorporates ocular trends 
in Toric IOL planning. Subject with no ocular pathology that could confound study outcome, 
must require clear cornea cataract extraction, and must desire an IOL that provides the 
potential for near, intermediate and distance vision and corrects astigmatism. Potential 
subjects will be screened for enrollment into this clinical trial. Those qualifying will attend a 
total 5 visits, 1 is preoperative, 1 is operative and 3 are postoperative visits. If the test 
products will be implanted to both eye, the maximum number of visits is 9 visits, 1 is 
preoperative, 2 are operative and 6 are postoperative visits. Unscheduled visits may be 
attended if needed for medical attention. 
An overview of the study design is depicted in Figure 7-1. 
 
 

 
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Figure .7-1 
Study Design 
 
 
 
 
When both eyes receive the IP implant, 
every visits are needed for each eyes. If 
visit window allows, examination can be 
done within one day visit. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1st Eye Surgery/Visit 00: Day 0 
Visit 0: Day -60 to Day 0 
Visit 1: Day 1 - 2 Post Visit 00 
Visit 2: Day 7 - 14 Post Visit 00 
Visit 3: Day 30 - 60 Post Visit 00 
2nd Eye Surgery/Visit 00A: Day 0 
Second eye surgery shall be 
done between Visit 1 
examination for the first eye and 
one month after the first surgery. 
Visit 0A: Day -60 to Day 0 
Visit 1A: Day 1 - 2 Post Visit 00 
Visit 2A: Day 7 - 14 Post Visit 00 
Visit 3A: Day 30 - 60 Post Visit 
00 
              First Eye                          |           Second Eye (if applicable) 

 
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7.2 Rationale for Study Design  
The purpose of this clinical study is to evaluate effectiveness and safety of the TFNT20 when 
implanted to replace the natural lens following cataract removal in at least one eye based on a 
new Alcon Toric calculator that incorporates ocular trends in Toric IOL planning. 
 
7.2.1 
Purpose and Timing of Interim Analyses and Resulting Design 
Adaptations 
Not applicable. 
 
7.3 Rationale for Duration of Treatment/Follow-Up 
Follow-up period required to properly evaluate effectiveness of astigmatism reduction of IP 
are set up. 
 
7.4 Data Monitoring Committee 
Not applicable 
 
 
 

 
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8 STUDY POPULATION 
The study population includes approximately 30 subjects to be enrolled at 1 site.  
To participate in the clinical trial, subjects must be ≥ 20 years of age with cataract who would 
be eligible to receive a TFNT20 lens in at least one eye based on a new Alcon Toric 
calculator that incorporates ocular trends in Toric IOL planning. Subject with no ocular 
pathology that could confound study outcome, must require clear cornea cataract extraction, 
and must desire an IOL that provides the potential for near, intermediate and distance vision 
and corrects astigmatism. Additional entry criteria are listed below in Sections 8.1 through 
8.3. 
Check all entry criteria at baseline (Visit 0/0A) and at both surgical visits (Visit 00/00A). 
If the implantation was aborted and the IOL did not touch the eye, then the subject is required 
to discontinue from the study and standard of care for IOL implantation is followed. Refer to 
Section 10.3 Discontinued Subjects for further details. If the implantation was aborted and 
the IOL did touch the eye, then the subject is followed for safety evaluation on this eye only. 
 
8.1 Inclusion Criteria 
Written informed consent must be obtained before any study specific assessment is performed. 
Upon signing informed consent, the subject is considered enrolled in the study. 
Subjects eligible for inclusion in this study must fulfill all of the following criteria: 
Among the criteria listed below, ocular criteria relates to the study eye only. 
1. 
Adults, 20 years of age or older at the time of informed consent for participating in 
this study, of either gender, Japanese patient diagnosed with age-related cataract.  
2. 
Planned routine cataract surgery (need determined by the expert opinion of the 
investigator). 
3. 
Eligible to be implanted with the TFNT20 as determined by a new Alcon Toric 
calculator in at least one eye that incorporates ocular trends in surgical planning. 
4. 
To qualify for fellow eye implant with TFNT20, subject must have no clinically 
significant findings at the Visit 1 examination of the first implanted eye. 

 
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Note: This criterion only applies to subjects who are eligible for both eyes and 
wishes to be implanted into fellow eye with TFNT20. 
5. 
Willing and able to complete all required postoperative visits. 
6. 
Subjects for able to comprehend and sign the informed consent form for 
participating in this study. 
For the subjects who are eligible for both eyes and wishes to be implanted into 
fellow eye with TFNT20, subject has to comprehend and sign the informed consent 
form for the second eye surgery and the study examinations prior to the 
examinations at Visit 0A. 
7. 
Clear intraocular media other than cataract. 
8. 
Subjects for whom postoperative emmetropia is planned (spherical equivalent ± 
0.50 D). 
9. 
Potential postoperative BCDVA of 0.5 decimal or better. 
 
8.2 Exclusion Criteria Prior to Cataract Surgery 
Subjects fulfilling any of the following criteria are not eligible for participation in this study. 
Among the criteria listed below, ocular criteria relates to the study eye only. 
1. 
Any disease or pathology, other than cataract, that (in the expert opinion of the 
investigator) is expected to reduce the postoperative BCDVA to a level worse than 
0.5 decimal 
2. 
Prior retinal detachment. 
3. 
Irregular corneal astigmatism as assessed by topographer per investigator decision. 
4. 
Pregnancy or lactation, current or planned, during the course of the study. 
5. 
Participation in another concurrent clinical trial. 
6. 
Pupil less than 6mm after dilation. 
7. 
History of anterior segment (corneal, anterior chamber, sulcus) or posterior segment 
(uveal, vitreo-retinal) pathology including retinal vascular occlusive disease, retinal 
detachment or peripheral retinal laser photocoagulation, ARMD, glaucoma 

 
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(uncontrolled or controlled with medication) or ocular hypertension, diabetic 
retinopathy, retinitis pigmentosa and any optic nerve pathology. 
8. 
History of previous intraocular or corneal (refractive or trauma related) surgery. 
9. 
Any other planned ocular surgical procedures including but not limited to 
LRI/Astigmatic Keratotomy and LASIK 
10. 
Subjects with conditions that increase the risk of zonular rupture during cataract 
extraction procedure that may affect the postoperative centration or tilt of the IOL. 
11. 
Presence or history of any condition or finding that makes the subject unsuitable as a 
candidate for cataract surgery or study participation or may confound the outcome of 
the study, in the opinion of the Investigator. 
 
8.3 Exclusion Criteria During Cataract Surgery 
The patient who meets any criteria specified in the following 1) through 9). 
1. 
Any other additional procedures during the cataract removal and IOL implant due to 
intraoperative complications that require further intervention (including but not 
limited to posterior capsule rupture, with vitreous loss, zonular dehiscence that may 
make the IOL implant less stable, etc.). 
2. 
Mechanical or surgical intervention required to manipulate the pupil. 
3. 
Excessive iris mobility. 
4. 
Significant vitreous loss. 
5. 
Significant anterior chamber hyphema. 
6. 
Zonular or capsular rupture. 
7. 
Unrecognized (pre-existing but discovered during surgery) ocular conditions or 
complications in which the IOL stability could be compromised, including zonular 
weakness. 
8. 
Haptic placement other than bag-bag. 
9. 
Incision other than temporal location 

 
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8.4 Rescreening of Subjects 
Rescreening of subjects is not allowed in this study. 
 
 
 

 
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9 TREATMENTS ADMINISTERED 
9.1 Investigational Product(s) 
Test Product(s): 
TFNT20 
Control Product(s) (If applicable): Not applicable 
 
Table 9–1 
Test Product 
Test Product 
TFNT20 
Indication for use and 
intended purpose in the 
current study  
The TFNT20 is intended for primary implantation in the 
capsular bag in the posterior chamber of the human eye for 
the visual correction of aphakia and pre-existing corneal 
astigmatism, secondary to removal of a cataractous lens in 
adult patients who desire near, intermediate, and distance 
vision with increased spectacle independence. 
Product description and 
parameters available for this 
study 
Single-piece construction lens consisting of the optic and 
the haptic made of the same material. The optic diffractive 
structure is in the central 4.5 mm portion of the optic zone 
(6.0mm), overall length: 13.0 mm, on the anterior surface 
and divides the incoming light to create a +2.17 D 
intermediate and a +3.25 D near add power. The posterior 
surface of Model TFNT20 is toric, and is designed with 1.00 
D of cylinder power (0.68 D at the corneal plane in an 
average pseudophakic human eye 10)). The flat meridian of 
the AcrySof IQ PanOptix Toric IOL is identified with the 
indentations on the posterior surface of the optic in the form 
of dots. 
The details of the test product can be found in the 
Investigator’s Brochure (#IB-0175). 
Formulation 
Not applicable. 

 
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Usage 
The investigational product will be placed within the 
capsular bag after removal of the natural crystalline lens 
following phacoemulsification. 
Packaging description 
Pack each test product into the carton. 
Labeling description 
The carton with labeling of: 
 
Name and address of the Sponsor 
 
Purpose (for use in clinical study) 
 
Lens model, serial number and refractive 
power, A-constant 
 
Method of storage and precautions 
The package contains the following adhesive labels besides 
the test products: 
 
Investigational lens control labels (to be 
attached to Investigational lens Control Log, 
medical record) 
 
Copy of the investigational lens information 
given to study subjects (to be attached to the 
Study Participants Card). 
Storage conditions 
Keep the lens not at a high temperature/humidity and away 
from direct light. Do not keep the lens at 45C or higher. 
Supply 
Refer to the management manual of test product for a 
detailed description.  
 
The TFNT20 must be maintained within specified environmental condition, per the labeling.  
A temperature log must be maintained documenting appropriate IP storage conditions as 
described in the management manual of test product, and must be made available for 
inspection. 
More information on the test product can be found in the Investigator’s Brochure (#IB-0175) 
and management manual of test product. 
 

 
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9.2 Other Medical Device or Medication Specified for Use During the 
Study 
No other medical devices or medications are required to be used in conjunction with the 
treatments during the clinical study. 
 
9.3 Treatment Assignment / Randomization 
Only after signing the ICF, a subject will be assigned a subject number by the electronic data 
capture system.  
The investigational product will be placed within the capsular bag after removal of the 
natural crystalline lens. When both eyes are eligible, the eye which has smaller anticipated 
residual refractive astigmatism based on a new Alcon Toric calculator that incorporates 
ocular trends in Toric IOL planning shall be the first eye, and the eye which has lager 
anticipated residual refractive astigmatism shall be the second eye. If both eyes have same 
anticipated residual refractive astigmatism, the eye with advanced cataract shall be the first 
eye and the fellow eye should be the second eye. 
 
9.4 Accountability Procedures 
Upon receipt of IPs, the Investigator or delegate must conduct an inventory of the test 
product by serial number, complete study-specific confirmation of receipt procedures as 
described in the management manual of test product , and retain any required documentation 
in the Investigator’s clinical study records. Throughout the study, the Investigator or delegate 
must maintain records of IP dispensation for each subject. This record must be made 
available to the study monitor for the purposes of verifying the accounting of IP supplies. 
Any discrepancies and/or deficiencies between the observed disposition and the written 
account must be recorded along with an explanation. All IPs sent to the Investigator must be 
accounted for by Study Sponsor personnel, and in no case be used in an unauthorized manner. 
• 
Return to the Study Sponsor investigational products associated with a device 
deficiency. Refer to Section 11 of this protocol for additional information on the 
reporting of device deficiencies and to the management manual of test product for 
information on return of study products associated with these events. 

 
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The Investigator is responsible for proper disposition of all unused IPs at the conclusion of 
the study, according to the instructions provided in the management manual of test product. 
 
9.5 Changes to concomitant medications, treatments/ procedures 
Changes in concomitant treatments after Visit 0 are not allowed unless needed for the proper 
medical care and treatment of the subject for a specific medical condition. 
After the subject is enrolled into the study, the Investigator must instruct the subject to notify 
the study site about: 
• 
Any new medications  
• 
Alterations in dose or dose schedules for current medications,  
• 
Any medical procedure or hospitalization that occurred or is planned 
• 
Any non-drug therapies (including blood transfusions).  
The Investigator must document this information in the subject’s case history source 
documents. 
The use of spectacles and contact lenses (excluding refraction corrective contact lens for 
orthokeratology) is permitted. However, concomitant application of other ways of correcting 
refraction, possibly affecting evaluation of the investigational lens, is prohibited during the 
study.  For example, laser in situ keratomileusis, PRK and refraction corrective contact lens 
(orthokeratology). 
 
 
 

 
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10 STUDY PROCEDURES AND ASSESSMENTS 
Below examinations and observations are carried out at Visit 0/0A, Visit 00/00A, Visit 1/1A, 
Visit 2/2A and Visit 3/3A. The same instruments and methods should be used for all 
measurements at all visits. Examinations and observations are outlined in tabular format in 
Section 6 of this protocol. Both the examination and the observation may be per Visited on 
the same day if the day is within the window for the examination and observation of the eye 
concerned (first or second operated eye). Also examination and observation can be performed 
separately over days if these are performed within the set window. 
 
10.1 Description of Study Procedures and Assessments 
10.1.1 Preoperative Examination (Visit 0/0A) 
・ Informed consent 
Routine test conducted for cataract subjects is performed. Subjects still qualifies after 
these tests are explained this study. Ensure that the subject has read, understood, and 
signed and dated a statement of informed consent prior to undergoing any study 
specific testing. Even though routine test was operated before informed consent, these 
data can be use as study data. 
・ Demographics 
Confirm sex , age and race/ethnicity. 
・ Medical history 
Confirm systemic and ophthalmologic complication, ophthalmologic surgical history. 
・ Concomitant medications 
Indicate the concomitant medications used by the subject at the time of the 
examination. 
・ Urine pregnancy test (female subjects only) 
Perform a urine pregnancy test if the subject is female and of childbearing potential. 
・ Inclusion/exclusion criteria 
Ensure that the subject meets inclusion/exclusion criteria and meet all qualifications 
for participation. 
・ Visual acuity 

 
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・ Manifest refraction 
Measure using an automated refractometer, and then perform a manifest refraction 
using the 100% contrast chart at 5m, under photopic lighting condition (100-180 
cd/m2). 
・ Slit lamp examination 
Record the presence or absence of clinically significant ophthalmologic findings. 
・ Dilated fundus examination 
Record the presence or absence of clinically significant ophthalmologic findings. 
・ Keratometry 
Keratometry will be performed using an automated keratometer. 
・ Target residual refractive error 
Indicate the amount of postoperative refractive error (±) anticipated based on the 
power calculation softwareused for the lens power that is chosen. The target for all 
eyes shall be emmetropia (based on the distance focus power). 
・ Calculation by a new Alcon Toric calculator that incorporates ocular trends in Toric 
IOL planning 
Calculate the IOL model by a new Alcon Toric calculator that incorporates ocular 
trends in Toric IOL planning. The formula should be the Holladay Total SIA formula. 
Record the Anticipated Residual Refractive Astigmatism and Indicated IOL 
Alignment.  
・ Topography 

 
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Corneal topography should be measured and indicate whether the astigmatism is 
regular or irregular. Irregular astigmatism is an exclusion criterion and these subjects 
should not be enrolled in the study. 
 
・ Axial length 
Obtain the axial length by A-mode or IOL master. 
・ Anterior chamber depth (ACD) 
The ACD should be measured from the apex of the cornea to the anterior surface of 
the natural crystalline lens with A-mode or IOL master. 
・ Intraocular pressure 
Perform tonometry using a contact or a non-contact ocular tonometer. 
・ Adverse events, Device deficiencies 
Presence/absence of adverse events and device deficiencies are recorded since 
informed consent. 
 
10.1.2 Surgery Day (Visit 00/00A) 
Record surgical information at Visit 00/00A. If subjects wish to be implanted into both eyes 
with TFNT20, obtain consent in continuation of the study from each subject prior to the 
surgery on the 2nd eye. 
・ Operative eye 
Indicate which eye is being implanted. 
・ Exclusion criteria during surgery 
Assess qualification according to the inclusion/exclusion criteria during the surgery. 
The incision site for this study is defined as temporal (± 15°, or approximately 1 mm, 
for the horizontal meridian (OS: 0°, OD: 180°)). 
・ Final incision size 
Indicate final incision size (mm) to the nearest 0.1 mm. 
・ Problems during surgery 

 
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Indicate what problems, if any, occurred during surgery.  If any exclusion criteria 
occur, discontinue the subject from the clinical study. 
・ Other procedures at this surgery 
Any other procedures performed at this surgery should be indicated.  Since other 
procedures at this surgery are included in the exclusion criteria, discontinue the 
subject from the clinical study. 
・ Lens information 
Provide the IOL information (IOL model, refractive power, serial No.) also in the 
event of discontinuation of implant. Attach the adhesive label contained in the 
package of the investigational lens to the Study Participants Card. 
・ IOL axis orientation (dilated) 
Record the orientation (in degrees; 0 ~180 degrees) of the investigational lens axis 
(designated by indentations on the IOL optic). 
 
 
・ Medical history 
Confirm systemic and ophthalmologic complication, ophthalmologic surgical history. 
・ Concomitant medications 
Indicate the concomitant ocular medications used during the surgery. 
・ IOL observation 
Observe the IOL surface and the inside of the haptic and optic of the investigational 
lens with a slit-lamp microscope, and record the presence/absence of visible abnormal 
findings (debris on IOL surface, forceps marks on IOL surface, IOL discoloration, 
IOL opacities, IOL scratch, membrane generated on IOL, pigmentation on IOL, 
surface haze, other.). And regarding the observed findings, evaluate the clinical 
significance. If the problem may negatively affect postoperative visual acuity, etc., 
handle it as the clinical significant, and if possible, take photos. 
・ Adverse events, Device deficiencies 
Presence/absence of adverse events and device deficiencies are recorded since 
informed consent. 
・ Secondary surgical intervention 

 
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Record the presence/absence of any postoperative surgical procedure that may be 
caused by the investigational lens. The SSI include iridotomy/ iridectomy for 
pupillary block, vitrectomy for pupillary block, adjustment of the position of the 
investigational lens, removal of the investigational lens due to inflammation, 
exchange of the investigational lens, etc., but not limited to them. Meanwhile, retinal 
reattachment surgery and posterior capsule resection are not included as SSI. 
 
10.1.3 Postoperative Examinations (Visit 1/1A, Visit 2/2A and Visit 3/3A) 
Below examination and observation are carried out at Visit 1/1A, Visit 2/2A and Visit 3/3A. 
・ Visual acuity (Visit 1/1A, Visit 2/2A and Visit 3/3A) 
・ Manifest refraction (Visit 1/1A, Visit 2/2A and Visit 3/3A) 
Measure using an automated refractometer, and then perform a manifest refraction 
using the 100% contrast chart at 5m, under photopic lighting condition (100-180 
cd/m2). 
・ Slit lamp examination (Visit 1/1A, Visit 2/2A and Visit 3/3A) 
Record the presence or absence of clinically significant ophthalmologic findings. 
・ Dilated fundus examination (Visit 3/3A) 
Record the presence or absence of clinically significant ophthalmologic findings. 
・ Keratometry (Visit 1/1A and Visit 2/2A (if needed). Visit 3/3A.) 
Keratometry will be performed using an automated keratometer. 
・ Topography (Visit 1/1A and Visit 2/2A (if needed). Visit 3/3A.) 

 
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Corneal topography should be measured and indicate whether the astigmatism is 
regular or irregular. 
・ Axial length (Visit 1/1A and Visit 2/2A (if needed). Visit 3/3A.) 
Obtain the axial length by A-mode or IOL master. 
・ Anterior chamber depth (ACD) (Visit 1/1A and Visit 2/2A (if needed). Visit 3/3A.) 
The ACD should be measured from the apex of the cornea to the anterior surface of 
the natural crystalline lens with A-mode or IOL master. 
・ Intraocular pressure (Visit 1/1A, Visit 2/2A and Visit 3/3A) 
Perform tonometry using a contact or a non-contact ocular tonometer. 
 
 
 
 
 
・ Posterior Capsule Opacification (Visit 1/1A, Visit 2/2A and Visit 3/3A) 
Indicate the presence/absence of PCO. If PCO is present, it will be graded as 
clinically non-significant, clinically significant or clinically significant requiring YAG 
as follows: 
1． Clinically Non-significant: Early development of PCO, including fibrosis and 
proliferation of lens epithelial cells, observable by slit-lamp biomicroscopy. 
Causes no apparent decrease in VA subjectively (e.g., glare) or objectively (e.g., 
decrease in visual acuity). 
2． Clinically Significant: Increased PCO with early subjective and objective VA 
changes but does not require posterior capsulotomy. 
3． Clinically Significant Requiring YAG: Clinically significant PCO adversely 
affecting subject's VA and requiring posterior capsulotomy. 
・ Posterior capsulotomy (Visit 1/1A, Visit 2/2A and Visit 3/3A) 
Indicate whether a posterior capsulotomy was performed or not. If it was performed, 
report the date of the procedure and size. 
・ IOL observation (Visit 1/1A, Visit 2/2A and Visit 3/3A) 
Observe the IOL surface and the inside of the haptic and optic of the investigational 
lens with a slit-lamp microscope, and record the presence/absence of visible abnormal 

 
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findings (debris on IOL surface, forceps marks on IOL surface, IOL discoloration, 
IOL opacities, IOL scratch, membrane generated on IOL, pigmentation on IOL, 
surface haze, other.). And regarding the observed findings, evaluate the clinical 
significance. If the problem may negatively affect postoperative visual acuity, etc., 
handle it as the clinical significant, and if possible, take photos. 
・ IOL position change (Visit 1/1A, Visit 2/2A and Visit 3/3A) 
Tilt and/or decentration should be reported if greater than 10 degrees or 0.5mm. 
・ Adverse events, Device deficiencies (Visit 1/1A, Visit 2/2A and Visit 3/3A) 
Presence/absence of adverse events and device deficiencies are recorded since 
informed consent. 
・ Secondary surgical intervention (Visit 1/1A, Visit 2/2A and Visit 3/3A) 
Record the presence/absence of any postoperative surgical procedure that may be 
caused by the investigational lens. The SSI include iridotomy/ iridectomy for 
pupillary block, vitrectomy for pupillary block, adjustment of the position of the 
investigational lens, removal of the investigational lens due to inflammation, 
exchange of the investigational lens, etc., but not limited to them. Meanwhile, retinal 
reattachment surgery and posterior capsule resection are not included as SSI. 
 
10.2 Unscheduled Visits 
When a subject makes an unscheduled visit for adverse events etc., inquire about the reason 
for the visit and retain the record.  The investigator will perform examinations/observations 
those are necessary and retain the record. If the visit is associated with any ophthalmologic 
symptom, identify the eye and retain the record. 
If during an Unscheduled Visit the subject is discontinuing the IP or discontinuing from the 
study, the Investigator must conduct Exit procedures according to Table 3-1 Schedule of 
Study Procedures and Assessments and Section 10.1, as possible. 
 

 
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10.3 Discontinued Subjects 
10.3.1 Screen Failures 
Subjects who were excluded from the study after signing the informed consent, not meeting 
the inclusion/excursion criteria. 
The Investigator must document the reason for screen failure in the subject’s case history 
source documents. 
Subject numbers must not be re-used. 
 
10.3.2 Discontinuations 
The subject is discontinued in the following cases: 
1) The investigational lens was removed for reasons of adverse events. 
2) The investigator (or sub-investigator) judged it necessary to replace the 
investigational lens with another IOL. 
3) The investigator (or sub-investigator) judged it necessary to discontinue the subject 
from the study. 
4) The subject canceled the consent once issued. 
5) The subject requested discontinuation of the study. 
6) Continuation of the study was judged as impossible because of subject’s referral or 
move during the study. 
7) Other (discontinuation is necessary) 
Upon discontinuation of the study, if the investigator or sub-investigator decided the 
examination or observation is necessary, the examination or observation should be carried out 
as far as possible under the subject’s consent, and the date and reason of discontinuation are 
entered in the electric case report form.  In case where continuation of the study is difficult 
because of discontinued visit of the subject to the clinic, the subject is followed over 
telephone, by mail or other appropriate means and the reason for discontinued visit, 
survival/death of the subject, presence/absence of adverse events, etc., are entered in the 
electric case report form.   

 
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If the investigational lens remained implanted in the subject after discontinuation of the 
study, the subject is informed as to the necessity of receiving periodical ophthalmological 
follow-up to assure safety at 30 – 60 days after surgery, and the subject is asked to extent 
cooperation as much as possible. 
 
10.4 Clinical Study Termination 
If discontinuation of the entire study has become inevitable for reasons of reports on serious 
safety information from any participating study site or overseas, problems pertaining to the 
quality of the investigational lens, and so on, the Sponsor is required to immediately inform 
the investigator and the head of each study site of discontinuation of the study and its reason 
in writing. 
 
10.4.1 Follow-up of subjects after study participation has ended  
Following this study, the subject will return to their eye care professional for their routine eye 
care. 
 
 

 
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11 ADVERSE EVENTS AND DEVICE DEFICIENCIES 
11.1 General Information 
An AE is any untoward medical occurrence, unintended disease or injury, or untoward 
clinical signs (including abnormal laboratory findings) in subjects, users, or other persons, 
whether or not related to the investigational medical device (test article). Refer to the 
Glossary of Terms and figures below for categories of AEs and SAEs. 
Figure .11-1 
Categorization of All Adverse Events 
 
 
Figure .11-2 
Categorization of All Serious Adverse Events  
 
ALL AEs
Device/
procedure-
related?
NO
AE
NO
SAE
ADE
YES
Meet 
seriousness 
criteria?
YES
Device/
procedure-
related?
SADE
YES
Anticipated?
Unanticipated 
SADE
NO
Anticipated 
SADE
YES
ALL SAEs
NO
SAE

 
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11.2 Procedures for Recording and Reporting 
If any serious adverse event occurs, the investigator will report the type of the serious adverse 
event to Alcon Japan within 24 hours after confirming the event. After obtainment of detailed 
information on the serious adverse event, the investigator will prepare a report and 
immediately submit it to Alcon Japan and the head of the study sites. 
All adverse events (related and unrelated to the medical device or test procedures) will be 
entered in the Adverse Event form. Surgically-related post-operative conditions that are 
normal consequences of the ocular surgery (see MOP) and not clinically relevant will be only 
reported as adverse events at the discretion of the investigator. 
In addition, the investigator must document all serious adverse events (related and unrelated) 
on the Serious Adverse Event Form. Any device deficiencies will be entered in the device 
deficiency form within 24 hours after confirming the event. 
Adverse events will also be reported for any clinically relevant change from informed 
consent in any protocol specific safety parameter evaluated during the study, based upon an 
assessment by the investigator following exposure to an investigational product.  
Regarding the relationship with the investigational lens, a judgment will be made whether 
“not related” or “related.” Adverse events will be reported for any change in an ongoing 
medication and/or addition of a new medication, based upon an assessment by the 
investigator. 
In addition, for all device deficiencies that have occurred, the details of it and the condition in 
which it have occurred will be entered in the device deficiency form within 24 hours after 
confirming the event. 
Study Sponsor contact information is provided in the Manual of Procedures (MOP). 
 
Causality and Intensity Assessments 
For every AE, the Investigator must assess the causality as Related or Not Related to the 
medical device or test procedure in the study.  

 
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Causality 
Related 
An AE classified as related may be either definitely related or possibly related 
where a direct cause and effect relationship with the test product has not been 
demonstrated, but there is a reasonable possibility that the AE or device 
deficiency was caused by the test product. 
Not Related 
An AE classified as not related may either be definitely unrelated or simply 
unlikely to be related (ie, there are other more likely causes for the AE). 
Where appropriate, the Investigator must assess the intensity (severity) of the AE as mild, 
moderate, or severe, based on medical judgment with consideration of any subjective 
symptom(s), as defined below:  
Intensity (Severity) 
Mild 
An AE is mild if the subject is aware of but can easily tolerate the sign or 
symptom. 
Moderate 
An AE is moderate if the sign or symptom results in discomfort significant 
enough to cause interference with the subject’s usual activities. 
Severe 
An AE is severe if the sign or symptom is incapacitating and results in the 
subject’s inability to work or engage in their usual activities. 
The Investigator must document any action taken (ie, medication, intervention, or treatment 
plan) and outcome of the AE or device deficiency when applicable. 
 
11.3 Unmasking of the Study Information 
Not applicable; this study is a single treatment study. 
 
11.4 Follow-Up of Safety Information 
The Investigator is responsible for adequate and safe medical care of patients during the trial 
and for ensuring that appropriate medical care and relevant follow-up procedures are 
maintained after the trial. For subjects who are experiencing ongoing unresolved adverse 
events at the time of their study completion or early discontinuation from the study, it is 

 
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recommended that the investigator schedule an appropriate follow-up visit in order to 
determine the outcome of the event. 
 
11.5 Pregnancy in the Clinical Study 
If the subject becomes pregnant during the study, the investigator or sub-investigator will 
report it to Alcon Japan immediately. However, pregnancy is not included in adverse event. 
Subjects who become pregnant during the study will not be discontinued; however, all data 
will be excluded from the Best-Case Analysis Set (BAS). 
 
 
 

 
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12 ANALYSIS PLAN 
12.1 Subject Evaluability 
Final subject evaluability must be determined prior to locking the database, based upon the 
Deviations and Evaluability Plan. 
 
12.2 Analysis Sets 
Analysis datasets used for safety and effectiveness analyses of this study are defined as 
follows. 
Safety Analysis Set 
The treatment-emergent safety analysis set will include all eyes with attempted implantation 
with the test article (successful or aborted after contact with the eye). 
All-Implanted Analysis Set (AAS) 
All-Implanted Analysis Set (AAS) will include all eyes with successful test article 
implantation. 
Best-Case Analysis Set (BAS) 
Best-Case Analysis Set (BAS) will include all eyes with successful test article implantation 
that had 
・ at least 1 postoperative visit; 
・ no macular degeneration at any time; and 
・ no major protocol violation 
 
12.3 Demographic and Baseline Characteristics 
For all analysis datasets (Safety Analysis Set, AAS and BAS), demographics (sex, age [<60, 
60-69, 70-79, ≥80], systemic complication [None/Yes, details] and past ocular surgery 
[None/Yes, details]) will be summarized with the number and percent of subjects in each 
category for the variable.  Age will also be summarized with descriptive statistics (mean, 
standard deviation, number of subjects or eyes, median, min and max). 
 

 
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12.4 Effectiveness Analyses 
The objective of this study is to evaluate safety and effectiveness of the investigational lens 
(TFNT20, T2 hereafter) when implanted to replace the natural lens following cataract 
removal. 
 
12.4.1 Analysis of Primary Effectiveness Endpoint(s) 
Primary effectiveness variables are as follows. 
・ Percentage of eyes with ≤ 0.25 D refractive cylinder at Visit 3/3A (Day 30-60) 
 
12.4.1.1 Statistical Hypotheses 
The primary analysis will be performed using an exact test of binomial proportion (one-sided 
alpha = 2.5%).  The null (H0) and alternative (H1) hypotheses are; 
H0: π(T2) = 29.2% 
H1: π(T2) > 29.2% 
, where π(T2) is the population proportion of eyes with ≤ 0.25 D refractive cylinder at Visit 
3/3A (Day 30-60) for T2 group.  The 29.2% is the percentage of non-Toric (T0, hereafter) 
group estimated from historically combined studies 
 that 
would have qualified for T2 according to the new Alcon Toric calculator that incorporates 
ocular trends in Toric IOL planning.  
 
12.4.1.2 Analysis Methods 
All eligible eyes will be used for the analysis.  For unilaterally implanted subjects, only the 
eligible eye, for bilaterally implanted subjects, both eyes will be used for the analysis.  The 
superiority of T2 to T0 regarding refractive cylinder is to be demonstrated when there is a 
statistically significant difference between the outcome in this study and the historical 
threshold of 29.2%. 
 

 
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12.4.2 Analysis of Secondary Effectiveness Endpoint(s) 
Secondary effectiveness variables are as follows. 
・ Percentage of eyes with ≤ 0.5 D refractive cylinder at Visit 3/3A (Day 30-60) 
・ Average manifest refractive cylinder at Visit 3/3A (Day 30-60) 
 
12.4.2.1 Statistical Hypotheses 
No confirmative statistical hypothesis testing is planned for secondary effectiveness variables 
 
12.4.2.2 Analysis Methods 
For continuous variables, descriptive statistics (mean, standard deviation, N, median, min and 
max) will be provided for actual value and change from baseline at each visit.  For 
categorical variables, N and percent will be provided for each category at each visit.  Any 
additional p-values from t-statistics or chi-square type statistics will be provided accordingly 
only for descriptive purpose. 
 

 
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12.5 Handling of Missing Data 
No missing data will be imputed. 
 
12.6 Safety Analyses 
The safety endpoints are:  
• 
Adverse events including secondary surgical intervention (SSI) 
• 
Device deficiencies 
• 
Posterior capsular opacification 
• 
Posterior capsulotomy 
• 
IOL position change (tilt and decentration) 
• 
Intraocular pressure 
• 
Surgical problems 
• 
Slit Lamp Examination 
• 
Dilated Fundus Examination 
• 
IOL Observations 
Patient listings will be provided for adverse experiences occurred from informed consent to 
exposure to the test article. Safety variables above will be analyzed using Treatment-
Emergent Safety Analysis Set. For continuous variables, descriptive statistics (mean, standard 
deviation, N, median, min and max) will be provided for actual value and change from 
baseline at each visit. For categorical variables, N and percent will be provided for each 
category at each visit. 

 
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12.7 Interim Analyses and Reporting 
No interim analysis is planned. 
 
12.8 Sample Size Justification 
To enroll more than or equal to  30 eligible T2 eyes used for analysis, at least 30 subjects will 
be evaluated by a new Alcon Toric calculator that incorporates ocular trends in Toric IOL 
planning and unilaterally or bilaterally implanted with the AcrySof IQ PanOptix IOL 
(TFNT20).   
Using a new Alcon calculator that incorporates ocular trends in Toric IOL planning, 
percentage of eyes with ≤ 0.25 D refractive cylinder at Visit 3/3A (Day 30-60) in T2 group 
was estimated as 60.9% based on a previous 
 (T2)  study conducted in US.  Using 
the same calculator, the percentage in T0 group was recalculated as 29.2% from the 
combined result of studies (non-Toric T0 lenses) conducted in Japan 
 
.  Statistical test will be conducted to compare percentage of T2 with a 
constant of 29.2% as percentage of T0.  With 30 eyes from 30 subjects in T2 group, assuming 
the percentage of T2 is equal to 60.9% 
, the statistical power to demonstrate 
superiority of T2 to T0 is 91.6% with one-sided alpha of 2.5%, using an exact test of 
binomial proportion. 
 
 

 
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13 DATA HANDLING AND ADMINISTRATIVE REQUIREMENTS 
13.1 Subject Confidentiality 
The Investigator must ensure that the subject’s anonymity is maintained throughout the 
course of the study. In particular, the Investigator must keep an enrollment log with 
confidential identifying information that corresponds to the subject numbers and initials of 
each study participant. At the end of the clinical study, the Study Sponsor will collect a copy 
of the enrollment log without any identifying subject information. All documents submitted 
to the Study Sponsor will identify the subjects exclusively by number and demographic 
information. No other personally identifying information will be transmitted to the Study 
Sponsor. 
The Study Sponsor may release anonymized study data to external researchers for purposes 
of future research directly related to the study objectives, or future research that is beyond the 
scope of the current study objectives. The Informed Consent Form explains this to study 
subjects. Anonymization means that all identifiable information will be removed from the 
dataset and all links to the subjects in the study will be removed. Anonymization of the data 
will maintain confidentiality of the subjects who participate in the study so that they cannot 
be identified by external researchers. The anonymized data set will contain records from all 
of the subjects in the current study, but the anonymization process might change the data set 
in some ways, so external researchers will be informed that they might not be able to 
duplicate some of the results from this study. 
 
13.2 Completion of Source Documents and Case Report Forms 
The nature and location of all source documents will be identified to ensure that original data 
required to complete the CRFs exist and are accessible for verification by the site monitor, 
and all discrepancies shall be appropriately documented via the query resolution process. Site 
monitors are appointed by the Study Sponsor and are independent of study site staff. 
If electronic records are maintained, the method of verification must be determined in 
advance of starting the study.  
At a minimum, source documents include the following information for each subject: 
• 
Subject identification (name, sex, race/ethnicity) 
• 
Documentation of subject eligibility 

 
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• 
Date of informed consent 
• 
Dates of visits 
• 
Documentation that protocol specific procedures were performed 
• 
Results of study parameters, as required by the protocol 
• 
IP accountability records 
• 
Documentation of AEs and other safety parameters (if applicable) 
• 
Records regarding medical histories and the use of concomitant therapies prior to and 
during the study 
• 
Date of study completion and reason for early discontinuation, if applicable 
It is required that the author of an entry in the source documents be identifiable. Direct access 
to source documentation (medical records) must be allowed for the purpose of verifying that 
the data recorded on the CRF are consistent with the original source data. 
Only designated individuals at the site will complete the CRFs. The CRFs must be completed 
at regular intervals following the clinical study visit schedule. It is expected that all data 
reported have corresponding entries in the source documents. The Principal Investigator is 
responsible for reviewing and certifying that the CRFs are accurate and complete. The only 
subject identifiers recorded on the CRFs will be subject number, and subject demographic 
information.  
 
13.3 Data Review and Clarifications 
A review of CRF data to the subject’s source data will be completed by the site monitor to 
ensure completeness and accuracy. After the CRFs have been completed, additional data 
clarifications and/or additions may be needed as a result of the data cleaning process. Data 
clarifications are documented and are part of each subject’s CRF. 
 
13.4 Sponsor and Monitoring Responsibilities 
The Study Sponsor will designate a monitor to conduct the appropriate site visits at the 
appropriate intervals according to the study monitoring plan. The clinical investigation will 
be monitored to ensure that the rights and well-being of the subjects are protected, the 
reported data are accurate, complete, and verifiable from the source documents, and the study 

 
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is conducted in compliance with the current approved protocol (and amendments[s], if 
applicable), with current GCP, and with applicable regulatory requirements. 
The site may not screen subjects or perform the informed consent process on any subject until 
it receives a notification from an appropriate Study Sponsor representative that the site may 
commence conducting study activities. (Note: Even though routine test was operated before 
informed consent, these data can be use as study data.) Monitoring will be conducted 
periodically while the clinical study is ongoing. Monitoring methods may include site visits, 
telephone, e-mail, written and fax correspondence. Close-out visits will take place after the 
last visit of the last subject at the site. 
 
13.5 Regulatory Documentation and Records Retention 
The Investigator is required to maintain up-to-date, complete regulatory documentation as 
indicated by the Study Sponsor and the Investigator’s files will be reviewed as part of the 
ongoing study monitoring.   
Additionally, the Investigator must keep study records and source documents consistent with 
the terms of the clinical study agreement with the Study Sponsor. If the Investigator retires, 
relocates, or for any other reason withdraws from responsibility of keeping the study records, 
then the Study Sponsor must be notified and suitable arrangements made for retention of 
study records and source documents needed to comply with national and international 
regulations. 
At expiration of the retention period of the records, the sponsor will notify the study sites 
thereof. 
 
13.6 Quality Assurance and Quality Control 
The Study Sponsor will secure agreement from all involved parties to ensure direct access to 
all study related sites, source data and documents, and reports for the purpose of monitoring 
and auditing by the Study Sponsor, and inspection by domestic and foreign regulatory 
authorities. Quality control will be applied to each stage of data handling to ensure that all 
data are reliable and have been processed correctly. Agreements made by the Study Sponsor 
with the Investigator/Institution and any other parties involved in the clinical study will be 
provided in writing as part of the protocol or as a separate agreement. 
 

 
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14 ETHICS 
This clinical study must be conducted in accordance with the ethical principles contained 
within:  
• 
The Declaration of Helsinki, and pursuant to the provisions of the protocol, Article 14 
Paragraph 3 and Article 80-2 of the Pharmaceutical and Medical Device Act, the 
Ministerial Ordinance on Clinical Studies of Medical Devices (No. 36, Ministry of 
Health, Labor and Welfare, March 23, 2005) and the Notification about Enforcement 
of the Ministerial Ordinance on Clinical Studies of Medical Devices (No. Yakushoku-
0720003, Director of Pharmaceutical and Food Safety Bureau, Ministry of Health, 
Labor and Welfare, July 20, 2005).  
• 
SOPs of the Study Sponsor and contract research organizations participating in the 
conduct of the clinical study and all other applicable regulations.  
• 
Notifications and timelines for reporting protocol deviations should be based upon 
applicable Ethics Committee requirements 
The Investigator must ensure that all personnel involved in the conduct of the study are 
qualified to perform their assigned responsibilities through relevant education, training, and 
experience. The Investigator and all clinical study staff must conduct the clinical study in 
compliance with the protocol. Deviations from this protocol, regulatory requirements and/or 
GCP must be recorded and reported to the Sponsor prior to database lock. If needed, 
corrective and preventive action should be identified, implemented, and documented within 
the study records. Use of waivers to deviate from the clinical protocol is prohibited. 
Before clinical study initiation, this protocol, the informed consent form, any other written 
information given to subjects, and any advertisements planned for subject recruitment must 
be approved by an IRB. Prior to the start of the study, the IRB of each study site is required to 
inspect and evaluate the planned study as to the acceptability of implementing the study, 
appropriateness of the contents of the protocol, case report form and informed consent 
document, and other matters related to the study from the ethical, scientific and medical 
points of view, with an ultimate goal of protecting the human rights and well-being of the 
subjects. The inspection and examination by the IRB may be performed again also during a 
certain period of time after the start of the study or when the head of the study site sees the 
necessity of additional inspection/examination so that the study may be monitored 
continuously.  At the end of the study, the Investigator must notify the head of the 
investigational site about the study’s completion. The IRB also must be notified if the study 
is terminated prematurely. Finally, the Investigator must submit the summary of progress 

 
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about clinical study to the head of the investigational site at intervals stipulated by the IRB 
and report it to the IRB. 
Voluntary informed consent must be obtained in writing from every subject and the process 
shall be documented before any procedure specific to the clinical investigation is applied to 
the subject. The Investigator must have a defined process for obtaining consent. Specifically, 
the Investigator, or their delegate, must explain the clinical study to each potential subject and 
the subject must indicate voluntary consent by signing and dating the approved informed 
consent form. The subject must be provided an opportunity to ask questions of the 
Investigator, and if required by local regulation, other qualified personnel. The Investigator 
must provide the subject with a copy of the consent form written in a language the subject 
understands. The consent document must meet all applicable local laws and provide subjects 
with information regarding the purpose, procedures, requirements, and restrictions of the 
study, along with any known risks and potential benefits associated with the IP and the study, 
the available compensation, and the established provisions for maintaining confidentiality of 
personal, protected health information. Subjects will be told about the voluntary nature of 
participation in the study and must be provided with contact information for the appropriate 
individuals should questions or concerns arise during the study. The subject also must be told 
that their records may be accessed by appropriate authorities and Sponsor-designated 
personnel. The Investigator must keep the original, signed copy of the consent (file in 
subject’s medical records) and must provide a duplicate copy to each subject according to 
local regulations.  
The Study Sponsor assures that the key design elements of this protocol will be registered on 
www.clinicaltrials.gov as required by current regulations and, if applicable, other public 
databases as required by local country regulations. In addition, results of this study will be 
made publicly available on www.clinicaltrials.gov regardless of outcome as required by 
current regulations and, if applicable, in other public databases as required by local country 
regulations. 
Specifications to secure safety of study subjects 
In the event of acknowledging any adverse events, the investigator or the sub-investigator 
should immediately take appropriate actions irrespective of the presence or absence of causal 
relationship with the investigational lens. 
In the case of obtaining safety-related new and significant information related to the clinical 
study, the sponsor should supply the information in writing to the investigator and the head of 
the study site and take necessary actions. 

 
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In the event of deviating from the study protocol to avoid the emergent risk and secure safety 
of the study subject or because of other unavoidable clinical reasons, the investigator will 
retain the record and submit the documentation and justification of the protocol deviation to 
the sponsor and the head of the study site. 
Compensation for health hazards 
If any subject has sustained health hazards arising from this study, best healthcare is provided 
to that subject.  The Sponsor needs to be covered by insurance for liability arising from 
medical devices. 
Payment to subjects 
As a reward to the cooperation of each subject with the study, the Sponsor pays an amount of 
money, predetermined through negotiation with each participating study site, to each subject.  
This payment is not intended to force any subject to remain in the study. 
 
 
 

 
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15 REFERENCES 
1) Bissen-Miyajima H.: Multifocal IOL; 3-9, 2008 
2) Bissen-Miyajima H.: Multifocal IOL; 13-23, 2008 
3) Miyake T, Kamiya K and Shimizu K.: Corneal Astigmatism before Cataract Surgery. 
Journal of Japanese Ophthalmological Society. 115:447-453, 2011. 
4) Till J, Yoder Jr P, Wilcox T and Spielman L.: Toric intraocular lens implantation: 100 
consecutive cases. Journal of Cataract & Refractive Surgery. 28:295-301, 2002. 
5) Ferrer-Blasco T, Montes-Mico R, Peixoto-de-Matos S, Gonzalez-Meijom J and Cervino 
A.: Prevalence of corneal astigmatism before cataract surgery. Journal of Cataract & 
Refractive Surgery. 35:70-75, 2009. 
6) Alio J, Agdeppa M, Pongo V and Kady B.: Microincision cataract surgery with toric 
intraocular lens implantation for correcting moderate and high astigmatism: Pilot study. 
Journal of Cataract & Refractive Surgery. 36:44-52, 2010. 
7) Hirnschall N, Gangwani V, Crnej A, Koshy J, Maurino V and Findl O.: Correction of 
moderate corneal astigmatism during cataract surgery: Toric intraocular lens versus 
peripheral corneal relaxing incisions. Journal of Cataract & Refractive Surgery. 40:354-
361, 2014. 
8) Ouchi M.: Astigmatism Correction During Cataract Surgery. Journal of the Eye. 
32(9):1251-1256, 2015. 
9) Hayashi K, Manabe S, Yoshida M and Hayashi H.: Effect of astigmatism on visual acuity 
in eyes with a diffractive multifocal intraocular lens. Journal of Cataract & Refractive 
Surgery. 36:1323-1329, 2010. 
10) Lane SS. The AcrySof Toric IOL’s FDA trial results: a look at the clinical data. Cataract 
Refract Surg Today. 6:66-68, 2006.