SIST EN ISO 11979-7:2018

Ophthalmic implants - Intraocular lenses - Part 7: Clinical investigations of intraocular lenses for the correction of aphakia (ISO 11979-7:2018)

ISO 11979-7:2018 specifies the particular requirements for the clinical investigations of intraocular lenses that are implanted in the eye in order to correct aphakia.

Ophthalmische Implantate - Intraokularlinsen - Teil 7: Klinische Prüfungen von Intraokularlinsen für die Korrektion von Aphakie (ISO 11979-7:2018)

Dieses Dokument legt die besonderen Anforderungen an die klinische Prüfung von Intraokularlinsen (IOL) fest, die zur Korrektur von Aphakie in das Auge implantiert werden.

Implants ophtalmiques - Lentilles intraoculaires - Partie 7: Investigations cliniques de lentilles intraoculaires pour la correction de l'aphakie (ISO 11979-7:2018)

L'ISO 11979-7:2018 spécifie les exigences particulières applicables aux investigations cliniques de lentilles intraoculaires destinées à être implantées dans l'?il pour corriger l'aphakie.

Očesni vsadki (implantati) - Intraokularne leče - 7. del: Klinične raziskave intraokularnih leč za korekcijo afakije (ISO 11979-7:2018)

Ta dokument določa posebne zahteve za klinične preiskave intraokularnih leč,
ki se vstavijo v oko za korekcijo afakije.

General Information

• Status: Withdrawn
• Public Enquiry End Date: 04-May-2017
• Publication Date: 11-Jun-2018
• Withdrawal Date: 08-Feb-2024
• ICS: 11.040.70 - Ophthalmic equipment
• Technical Committee: VAZ - Healthcare
• Current Stage: 9900 - Withdrawal (Adopted Project)
• Start Date: 05-Feb-2024
• Due Date: 28-Feb-2024
• Completion Date: 09-Feb-2024
• Ref Project: EN ISO 11979-7:2018 - Ophthalmic implants - Intraocular lenses - Part 7: Clinical investigations of intraocular lenses for the correction of aphakia (ISO 11979-7:2018)

Relations

• Replaces: SIST EN ISO 11979-7:2014 - Ophthalmic implants - Intraocular lenses - Part 7: Clinical investigations (ISO 11979-7:2014)
• Effective Date: 01-Jul-2018
• Replaces: SIST EN ISO 11979-9:2006 - Ophthalmic implants - Intraocular lenses - Part 9: Multifocal intraocular lenses (ISO 11979-9:2006)
• Effective Date: 01-Jul-2018
• Replaces: SIST EN ISO 11979-9:2006/A1:2014 - Ophthalmic implants - Intraocular lenses - Part 9: Multifocal intraocular lenses (ISO 11979-9:2006/Amd 1:2014)
• Effective Date: 01-Jul-2018
• Replaced By: SIST EN ISO 11979-7:2024 - Ophthalmic implants - Intraocular lenses - Part 7: Clinical investigations of intraocular lenses for the correction of aphakia (ISO 11979-7:2024)
• Effective Date: 01-Mar-2024

Standards Content (Sample)

SLOVENSKI STANDARD
01-julij-2018
1DGRPHãþD
SIST EN ISO 11979-7:2014
SIST EN ISO 11979-9:2006
SIST EN ISO 11979-9:2006/A1:2014
2þHVQLYVDGNLLPSODQWDWL,QWUDRNXODUQHOHþHGHO.OLQLþQHUD]LVNDYH
LQWUDRNXODUQLKOHþ]DNRUHNFLMRDIDNLMH,62
Ophthalmic implants - Intraocular lenses - Part 7: Clinical investigations of intraocular
lenses for the correction of aphakia (ISO 11979-7:2018)
Ophthalmische Implantate - Intraokularlinsen - Teil 7: Klinische Prüfungen von
Intraokularlinsen für die Korrektion von Aphakie (ISO 11979-7:2018)
Implants ophtalmiques - Lentilles intraoculaires - Partie 7: Investigations cliniques de
lentilles intraoculaires pour la correction de l'aphakie (ISO 11979-7:2018)
Ta slovenski standard je istoveten z: EN ISO 11979-7:2018
ICS:
11.040.70 Oftalmološka oprema Ophthalmic equipment
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.

EN ISO 11979-7
EUROPEAN STANDARD
NORME EUROPÉENNE
May 2018
EUROPÄISCHE NORM
ICS 11.040.70 Supersedes EN ISO 11979-7:2014, EN ISO 11979-
9:2006
English Version
Ophthalmic implants - Intraocular lenses - Part 7: Clinical
investigations of intraocular lenses for the correction of
aphakia (ISO 11979-7:2018)
Implants ophtalmiques - Lentilles intraoculaires - Ophthalmische Implantate - Intraokularlinsen - Teil 7:
Partie 7: Investigations cliniques de lentilles Klinische Prüfungen von Intraokularlinsen für die
intraoculaires pour la correction de l'aphakie (ISO Korrektion von Aphakie (ISO 11979-7:2018)
11979-7:2018)
This European Standard was approved by CEN on 28 February 2018.

CEN members are bound to comply with the CEN/CENELEC Internal Regulations which stipulate the conditions for giving this
European Standard the status of a national standard without any alteration. Up-to-date lists and bibliographical references
concerning such national standards may be obtained on application to the CEN-CENELEC Management Centre or to any CEN
member.
This European Standard exists in three official versions (English, French, German). A version in any other language made by
translation under the responsibility of a CEN member into its own language and notified to the CEN-CENELEC Management
Centre has the same status as the official versions.

CEN members are the national standards bodies of Austria, Belgium, Bulgaria, Croatia, Cyprus, Czech Republic, Denmark, Estonia,
Finland, Former Yugoslav Republic of Macedonia, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania,
Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Romania, Serbia, Slovakia, Slovenia, Spain, Sweden, Switzerland,
Turkey and United Kingdom.
EUROPEAN COMMITTEE FOR STANDARDIZATION
COMITÉ EUROPÉEN DE NORMALISATION

EUROPÄISCHES KOMITEE FÜR NORMUNG

CEN-CENELEC Management Centre: Rue de la Science 23, B-1040 Brussels
© 2018 CEN All rights of exploitation in any form and by any means reserved Ref. No. EN ISO 11979-7:2018 E
worldwide for CEN national Members.

Contents Page
European foreword . 3

European foreword
This document (EN ISO 11979-7:2018) has been prepared by Technical Committee ISO/TC 172 "Optics
and photonics" in collaboration with Technical Committee CEN/TC 170 “Ophthalmic optics” the
secretariat of which is held by DIN.
This European Standard shall be given the status of a national standard, either by publication of an
identical text or by endorsement, at the latest by November 2018, and conflicting national standards
shall be withdrawn at the latest by November 2018.
Attention is drawn to the possibility that some of the elements of this document may be the subject of
patent rights. CEN shall not be held responsible for identifying any or all such patent rights.
This document supersedes EN ISO 11979-7:2014 and EN ISO 11979-9:2006.
According to the CEN-CENELEC Internal Regulations, the national standards organizations of the
following countries are bound to implement this European Standard: Austria, Belgium, Bulgaria,
Croatia, Cyprus, Czech Republic, Denmark, Estonia, Finland, Former Yugoslav Republic of Macedonia,
France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta,
Netherlands, Norway, Poland, Portugal, Romania, Serbia, Slovakia, Slovenia, Spain, Sweden, Switzerland,
Turkey and the United Kingdom.
Endorsement notice
The text of ISO 11979-7:2018 has been approved by CEN as EN ISO 11979-7:2018 without any
modification.
INTERNATIONAL ISO
STANDARD 11979-7
Fourth edition
2018-03
Ophthalmic implants — Intraocular
lenses —
Part 7:
Clinical investigations of intraocular
lenses for the correction of aphakia
Implants ophtalmiques — Lentilles intraoculaires —
Partie 7: Investigations cliniques de lentilles intraoculaires pour la
correction de l'aphakie
Reference number
ISO 11979-7:2018(E)
©
ISO 2018
ISO 11979-7:2018(E)
© ISO 2018
All rights reserved. Unless otherwise specified, or required in the context of its implementation, no part of this publication may
be reproduced or utilized otherwise in any form or by any means, electronic or mechanical, including photocopying, or posting
on the internet or an intranet, without prior written permission. Permission can be requested from either ISO at the address
below or ISO’s member body in the country of the requester.
ISO copyright office
CP 401 • Ch. de Blandonnet 8
CH-1214 Vernier, Geneva
Phone: [phone]
Fax: [phone]
Email: [e-mail]
Website: www.iso.org
Published in Switzerland
ii © ISO 2018 – All rights reserved

ISO 11979-7:2018(E)
Contents Page
Foreword .iv
Introduction .v
1 Scope . 1
2 Normative references . 1
3 Terms, definitions and abbreviated terms . 1
3.1 Terms and definitions . 1
3.2 Abbreviated terms . 1
4 Justification for a clinical investigation . 2
5 Ethical considerations . 2
6 General requirements . 2
6.1 General . 2
6.2 Design of a clinical investigation . 2
6.2.1 Requirements for all types of IOLs . 2
6.2.2 Additional requirements for toric IOLs (TIOLs) . 3
6.2.3 Additional requirements for multifocal IOLs (MIOLs) . 3
6.2.4 Additional requirements for accommodating IOLs (AIOLs) . 3
6.2.5 Additional requirements for anterior chamber IOLs . 3
6.3 Characteristics of clinical investigations . 4
6.3.1 General. 4
6.3.2 Characteristics to be studied for all types of IOLs . 4
6.3.3 Additional characteristics to be studied for TIOLs . 4
6.3.4 Additional characteristics to be studied for MIOLs . 5
6.3.5 Additional characteristics to be studied for AIOLs . . 5
6.3.6 Additional characteristics applying to anterior chamber IOLs . 5
6.3.7 Additional characteristics . 5
6.4 Duration of the investigations . 5
6.5 Enrolment . 6
6.6 Bilateral implantation . 6
6.7 Surgical technique . 6
6.8 Examination and treatment of subjects. 6
6.9 Adverse events reports . 7
6.10 Inclusion and exclusion criteria . 7
6.10.1 General. 7
6.10.2 Additional inclusion criteria for TIOLs . 7
6.10.3 Additional exclusion criteria for MIOLs . 7
6.10.4 Additional exclusion criteria for anterior chamber IOLs . 8
Annex A (informative) General elements in the clinical investigation of IOLs .9
Annex B (informative) Additional elements for the clinical investigation of TIOLs.14
Annex C (informative) Additional elements for the clinical investigation of multifocal IOLs .19
Annex D (informative) Additional elements in the clinical investigation of accommodating IOLs .22
Annex E (informative) Evaluation of post-operative adverse events and visual acuity rates.27
Annex F (informative) Clinical tests .31
Annex G (informative) Statistical methods and sample size calculations .37
Bibliography .42
ISO 11979-7:2018(E)
Foreword
ISO (the International Organization for Standardization) is a worldwide federation of national standards
bodies (ISO member bodies). The work of preparing International Standards is normally carried out
through ISO technical committees. Each member body interested in a subject for which a technical
committee has been established has the right to be represented on that committee. International
organizations, governmental and non-governmental, in liaison with ISO, also take part in the work.
ISO collaborates closely with the International Electrotechnical Commission (IEC) on all matters of
electrotechnical standardization.
The procedures used to develop this document and those intended for its further maintenance are
described in the ISO/IEC Directives, Part 1. In particular the different approval criteria needed for the
different types of ISO documents should be noted. This document was drafted in accordance with the
editorial rules of the ISO/IEC Directives, Part 2 (see www .iso .org/ directives).
Attention is drawn to the possibility that some of the elements of this document may be the subject of
patent rights. ISO shall not be held responsible for identifying any or all such patent rights. Details of
any patent rights identified during the development of the document will be in the Introduction and/or
on the ISO list of patent declarations received (see www .iso .org/ patents).
Any trade name used in this document is information given for the convenience of users and does not
constitute an endorsement.
For an explanation on the voluntary nature of standards, the meaning of ISO specific terms and
expressions related to conformity assessment, as well as information about ISO's adherence to the
World Trade Organization (WTO) principles in the Technical Barriers to Trade (TBT) see the following
URL: www .iso .org/ iso/ foreword .html.
This document was prepared by Technical Committee ISO/TC 172, Optics and photonics, Subcommittee
SC 7, Ophthalmic optics and instruments.
This fourth edition cancels and replaces the third edition (ISO 11979-7:2014). It also cancels and
replaces the first edition of ISO 11979-9:2006 and its amendment ISO 11979-9:2006/Amd 1:2014.
The main changes compared to the previous edition are as follows:
— Integration of the multifocal intraocular lens document (ISO 11979-9:2006);
— Technical updates concerning the safety and efficacy of the intraocular lens subtypes monofocal,
multifocal, toric and accommodating;
— Recommendations for the clinical investigations of novel lens models; and
— The separation of guidance for intraocular lenses used in cases of aphakia, and intraocular lens used
for the correction of ametropia in phakic patients.
A list of all parts in the ISO 11979 series can be found on the ISO website.
iv © ISO 2018 – All rights reserved

ISO 11979-7:2018(E)
Introduction
Intraocular lenses (IOLs) are used to correct residual refractive errors in subjects who have aphakia.
Such residual refractive errors typically include sphere and astigmatism, but can also include
accommodation. Different designs of IOLs can be used to correct for specific refractive errors. In the
case where an IOL is designed to provide more than one type of refractive correction, that IOL will have
to satisfy each of the separate requirements of those correction designs.
This document provides requirements and recommendations for intraocular lens investigations of new
IOL models. In the case where an IOL model is a modification of a parent IOL model, a risk analysis can
be used in order to determine the appropriate level of testing.
INTERNATIONAL STANDARD ISO 11979-7:2018(E)
Ophthalmic implants — Intraocular lenses —
Part 7:
Clinical investigations of intraocular lenses for the
correction of aphakia
1 Scope
This document specifies the particular requirements for the clinical investigations of intraocular lenses
that are implanted in the eye in order to correct aphakia.
2 Normative references
The following documents are referred to in the text in such a way that some or all of their content
constitutes requirements of this document. For dated references, only the edition cited applies. For
undated references, the latest edition of the referenced document (including any amendments) applies.
ISO 11979-1, Ophthalmic implants — Intraocular lenses — Part 1: Vocabulary
ISO 11979-10:2018, Ophthalmic implants — Intraocular lenses — Part 10: Clinical investigations of
intraocular lenses for correction of ametropia in phakic eyes
ISO 14155, Clinical investigation of medical devices for human subjects — Good clinical practice
ISO 14971, Medical devices — Application of risk management to medical devices
3 Terms, definitions and abbreviated terms
3.1 Terms and definitions
For the purposes of this document the terms and definitions given in ISO 11979-1 and ISO 14155 apply.
ISO and IEC maintain terminological databases for use in standardization at the following addresses:
— IEC Electropedia: available at http:// www .electropedia .org/
— ISO Online browsing platform: available at https:// www .iso .org/ obp
3.2 Abbreviated terms
UDVA uncorrected distance visual acuity
UIVA uncorrected intermediate visual acuity
UNVA uncorrected near visual acuity
CDVA corrected distance visual acuity
CIVA corrected intermediate visual acuity
ISO 11979-7:2018(E)
CNVA corrected near visual acuity
DCIVA distance corrected intermediate visual acuity
DCNVA distance corrected near visual acuity
4 Justification for a clinical investigation
A risk analysis shall be implemented in accordance with ISO 14971. If the risk analysis identifies the
need for a clinical investigation, the requirements of ISO 14155 shall apply, with additional requirements
given in this document.
If a new IOL model is a modification of a parent IOL for which the safety and performance have already
been established through clinical investigation in accordance with this document, then a limited or
[1]
no additional clinical investigation can suffice. ISO/TR 22979 provides guidance in determining the
need for a clinical investigation.
5 Ethical considerations
For clinical investigations of medical devices for human subjects, the ethical requirements in
ISO 14155 apply.
6 General requirements
6.1 General
There are four main categories of intraocular lenses that are determined by optical design:
a) monofocal (IOL);
b) multifocal (MIOL);
c) toric (TIOL); and
d) accommodating (AIOL).
The same basic requirements apply to all of the IOL types. Additional requirements apply to MIOL,
TIOL, and AIOL.
There is a further subdivision depending on anatomic placement of the IOL:
— posterior chamber; and
— anterior chamber.
Posterior chamber lenses are placed behind (posterior to) the iris. Anterior chamber lenses are placed
in front of (anterior to) the iris. Additional requirements apply in the case of anterior chamber lenses.
6.2 Design of a clinical investigation
6.2.1 Requirements for all types of IOLs
A clinical investigation shall be designed to compare the rates of adverse events and visual acuities
above defined thresholds of the model IOL to the results of historical data. Annex A provides general
guidance for the design of a clinical investigation of IOLs. Historical data can be found in Annex E.
2 © ISO 2018 – All rights reserved

ISO 11979-7:2018(E)
6.2.2 Additional requirements for toric IOLs (TIOLs)
Prior to any clinical investigation of a toric intraocular lens, the rotational stability of a mechanically
and geometrically equivalent non-toric version of that IOL model shall be demonstrated.
The following performance criteria for rotational stability shall be fulfilled.
The IOL rotation is defined as the difference in postoperative orientation of the meridian defined by the
IOL axis indicator between that intended on the day of surgery (Form 0) and that measured at Form 4
and subsequent Forms. (See A.3 for recommendations on reporting periods). The absolute value of the
rotation shall be less than 10° in 90 % of the cases and less than 20° in 95 % of the cases.
Subsequently, if found necessary by risk analysis (e.g. to assess the clinical performance of low cylinder
power TIOLs), a clinical investigation can be performed using the toric version of the model.
Subjects that undergo a secondary surgery to correct postoperative IOL rotational misalignment shall
have their clinical results prior to the secondary surgery carried forward as the final results for that
subject, and examinations scheduled later in the clinical investigation shall be performed prior to the
secondary surgery, wherever possible. (See Annex D.)
Additional elements for investigations of TIOLs are outlined in Annex B.
6.2.3 Additional requirements for multifocal IOLs (MIOLs)
For multifocal designs with two or more intended foci, a clinical investigation shall evaluate the safety
and performance of vision at far as well as any additional intended focal distances.
The clinical investigation plan shall include a defocus evaluation.
A phased enrolment as outlined in Annex C shall be considered.
Additional elements for MIOLs are outlined in Annex C.
6.2.4 Additional requirements for accommodating IOLs (AIOLs)
A controlled clinical investigation of an AIOL shall evaluate the accommodative amplitude and the
additional safety and performance aspects related to the risk assessment. Annex D identifies safety
and performance aspects for consideration. The clinical investigation plan shall include at least one
objective method to measure accommodative amplitude.
The investigation enrolment shall consist of two phases (see Annex D). The second phase shall begin
only if the first phase has demonstrated that the IOL design provides an average of at least 1,0 D of
objective accommodation. In order for the design to be designated as an AIOL, the overall investigation
shall demonstrate objective accommodation of 1,0 D or more at the point of accommodative stability
(see Annex D).
Additional elements for AIOLs are outlined in Annex D.
6.2.5 Additional requirements for anterior chamber IOLs
A clinical investigation of an anterior chamber IOL shall evaluate the change in endothelial cell density,
hexagonality and coefficient of variation of endothelial cell area, the clearance between the surfaces
of the anterior chamber IOL and the posterior surface of the cornea and the iris, the anterior chamber
angle (including observations of pigment and synechiae), and any additional safety and performance
aspects related to the risk assessment.
ISO 11979-7:2018(E)
6.3 Characteristics of clinical investigations
6.3.1 General
The clinical investigation plan shall provide information regarding characteristics to be studied, and
instructions regarding the methods and documentation of these characteristics. Whenever possible,
objective methods, such as photographic imaging, shall be used.
If additional claims are to be made, additional corresponding characteristics shall be studied.
If several types of IOLs are combined, the characteristics of each IOL subtype in the combination shall
be fully considered.
6.3.2 Characteristics to be studied for all types of IOLs
The following characteristics shall be considered:
a) CDVA;
b) visual acuity at all intended distances with far correction;
c) intraocular pressure;
d) corneal status;
e) signs of inflammation:
— anterior chamber cells,
— anterior chamber flare,
— cystoid macular oedema,
— hypopyon, and
— endophthalmitis.
f) pupillary block;
g) retinal detachment;
h) status of anterior and posterior capsule;
[2]
i) IOL decentration ;
[2]
j) IOL tilt ;
k) IOL discoloration; and
l) IOL opacity.
6.3.3 Additional characteristics to be studied for TIOLs
a) IOL rotational stability; and
b) corneal astigmatism:
— prior to surgery;
— intended surgical position (Form 0); and
— post-surgical.
4 © ISO 2018 – All rights reserved

ISO 11979-7:2018(E)
6.3.4 Additional characteristics to be studied for MIOLs
a) uncorrected visual acuity at all intended focal distances;
b) contrast sensitivity;
c) defocus evaluation;
d) pupil size under photopic and mesopic conditions; and
e) fundus visualization.
6.3.5 Additional characteristics to be studied for AIOLs
a) objective accommodative amplitude;
b) uncorrected visual acuity at distance, intermediate and near;
c) visual acuity at near and intermediate using far correction;
d) additional refraction (over distance correction) required to achieve any improvement in near
visual acuity;
e) contrast sensitivity;
f) defocus evaluation; and
g) pupil size.
6.3.6 Additional characteristics applying to anterior chamber IOLs
a) specular microscopy;
b) anterior chamber depth measurement; and
c) gonioscopy.
6.3.7 Additional characteristics
If justified by the risk analysis, the following additional characteristics shall be considered:
a) cycloplegic refraction;
b) specular microscopy;
c) gonioscopic examination;
d) pupil size; and
e) anterior chamber depth measurement.
6.4 Duration of the investigations
[1]
Consult ISO/TR 22979 for guidance on investigation duration for modifications of lens models for
which safety and performance have previously been established through clinical investigation.
For posterior chamber IOLs that are not modifications of a model for which safety and performance
data have been previously established through clinical investigation, the minimum duration of the
clinical investigations shall be Form 5 (see Annex A for recommended visit window tolerances).
ISO 11979-7:2018(E)
For anterior chamber IOLs that are not modifications of a model for which safety and performance data
have been previously established through clinical investigation, the minimum duration of the clinical
investigations shall be 3 years (see Annex A for recommended visit window tolerances).
For all TIOLs, a study of the non-toric version of the IOL shall be performed to ensure rotational stability
through Form 4. TIOLs that are not a modification of a respective parent IOL shall require a full clinical
investigation through Form 5 for posterior chamber IOLs, and 3 years duration for anterior chamber IOLs.
For TIOLs that are a modification of an IOL parent, the rotational stability assessment shall have a
duration through Form 4. If a subsequent clinical investigation of the TIOL is performed, it shall also
have a duration through Form 4.
For all AIOLs, the minimum clinical study duration shall be Form 5, but can require up to 3 years, based
on accommodative stability.
All subjects in a clinical investigation that have not been discontinued shall complete all visits of the
investigation. The clinical investigation shall be considered completed when all subjects who have been
enrolled in the investigation, including subjects whose IOL was removed repositioned or replaced, have
either completed follow up according to protocol or have passed the final visit window.
6.5 Enrolment
To minimize the risks associated with the clinical investigation of a new IOL, subject enrolment shall
occur in stages. The subject data from each stage shall be evaluated and found acceptable by the
sponsor and the coordinating investigator (and by the regulatory body, where applicable) prior to the
continuation of the next phase of the clinical investigation. Guidance on phased enrolment is included in
Annex A (monofocal IOLs), Annex B (TIOLs), Annex C (MIOLs), and Annex D (AIOLs).
A risk analysis shall be performed to determine if an earlier additional phase (before Phase 1 listed in
the Annexes above) is needed to address specific safety issues associated with the IOL design.
6.6 Bilateral implantation
Any plans for fellow eye implantation shall be clearly described in the clinical investigation plan. Only
the first eye of each subject shall be included in the primary statistical analysis. When implantation
of fellow eyes is permitted, the clinical investigation plan shall specify the time period between
implantation of the first eye and the fellow eye. A risk analysis shall be used to guide necessary safety
and efficacy data requirements.
Bilateral implantation shall not be implemented until initial safety and performance data have been
collected, evaluated and found acceptable by the sponsor and coordinating investigator (and regulatory
body, where applicable).
The review of data from at least 50 eyes with six months of follow-up is recommended prior to fellow
eye implantation. Risk analysis can allow an earlier implantation in fellow eyes if sufficiently justified
by previous clinical experience.
6.7 Surgical technique
The clinical investigation plan shall contain descriptions of the surgical technique, the intraoperative
use of ophthalmic viscosurgical devices, and the use of preoperative, intraoperative and postoperative
medications. Any deviations shall be recorded on the case report forms.
6.8 Examination and treatment of subjects
The reporting periods are described in Annex A.
The clinical investigation plan shall describe how subject visits and ophthalmic adverse events that
occur between standard reporting periods will be handled in the data analyses.
6 © ISO 2018 – All rights reserved

ISO 11979-7:2018(E)
6.9 Adverse events reports
Refer to ISO 14155.
6.10 Inclusion and exclusion criteria
6.10.1 General
The general inclusion criteria in 6.10.1.1 and the general exclusion criteria in 6.10.1.2 shall be
considered. Additional criteria as given in 6.10.2, 6.10.3 and 6.10.4 shall be considered depending on
the risk analysis for the particular IOL model.
6.10.1.1 General inclusion criteria
a) adult;
b) cataract;
c) calculated IOL power is within the range of the investigational IOL;
d) signed informed consent form; and
e) clear intraocular media other than cataract.
6.10.1.2 General exclusion criteria
a) previous intraocular or corneal surgery;
b) traumatic cataract;
c) pregnancy or lactation;
d) concurrent participation in another drug or device investigation;
e) instability of keratometry or biometry measurements; and
f) irregular astigmatism.
Subjects shall be discontinued when certain conditions are present at the time of surgery, including:
— zonular instability;
— need for iris manipulation;
— capsular fibrosis or other opacity; and
— inability to fixate IOL in desired position.
In such cases, the subject shall be followed until the condition has stabilized.
6.10.2 Additional inclusion criteria for TIOLs
a) corneal astigmatism within the range defined in the clinical investigation plan;
b) stability of the corneal astigmatism (for a minimum of 4 weeks); and
c) dilated pupil size large enough to visualize TIOL axis markings postoperatively.
6.10.3 Additional exclusion criteria for MIOLs
a) more than 1 D of pre-operative corneal astigmatism.
ISO 11979-7:2018(E)
6.10.4 Additional exclusion criteria for anterior chamber IOLs
The criteria for the specific anterior chamber IOL platform shall comply with the specific intended IOL
design as described in this subclause, including TIOL, AIOL and MIOL.
a) angle abnormalities;
b) glaucoma or ocular hypertension;
c) angle or anterior chamber anatomy unsuitable to accept IOL design safely;
d) minimum anterior chamber depth related to design;
e) endothelial issues:
— endothelial cell density less than listed in ISO 11979-10:2018, Table 1;
— percent hexagonality of endothelial cell shape ≥45 %;
— coefficient of variation of endothelial cell area <0,45;
— any endothelial conditions putting the cornea at risk of failure.
f) corneal oedema.
8 © ISO 2018 – All rights reserved

ISO 11979-7:2018(E)
Annex A
(informative)
General elements in the clinical investigation of IOLs
A.1 General
This Annex provides elements of a clinical investigation plan (CIP) which can assist in collecting data
for the purpose of determining the safety and performance of all types of IOLs.
A.2 Investigation design and duration
A.2.1 General
The suggested clinical investigation design is an uncontrolled study to compare outcomes with the
historical safety and performance endpoints in Annex E at the final follow-up.
NOTE 1 In case of an investigation with a concurrent control group, the number of subjects will have to be
calculated to be sufficient to detect differences in the safety and performance endpoints in Annex E with similar
statistical power to the study mentioned above.
NOTE 2 Any additional claims beyond those for safety and performance require separate calculations of an
appropriate sample size for each of such claims.
To take into account that some subjects are lost to follow-up during the course of the clinical
investigation (including deceased subjects and subjects who have the IOL explanted), enrol as a target
(see also 6.4):
a) 340 subjects in the one-year investigation;
b) 420 subjects in the three-year investigation.
[1]
If risk analysis determines that a limited clinical investigation is sufficient (see ISO/TR 22979 ), then
enrol a target of 115 subjects to achieve a goal of 100 completed subjects.
In order to minimize exposure to the risks of a new IOL, significantly larger numbers of subjects than
above should not be enrolled.
To assist in achieving a balance in the number of subjects from each investigator, each surgeon should
contribute a minimum of 20 subjects, but no more than 25 % of the total subjects in the investigation.
A.2.2 Enrolment
To minimize potential risks, the clinical investigation consists of two phases:
a) Phase 1: A maximum of 100 subjects are included for the initial investigation. After at least 50 of
those have reached case report Form 4, their data are evaluated. If the results are acceptable, the
next phase can begin.
b) Phase 2: The remainder of the subjects are included.
In the case of the limited clinical investigation, the investigation is not phased.
ISO 11979-7:2018(E)
A.2.3 Standardization of procedures
Define criteria for evaluation of all studied variables. Define testing conditions for all measurements.
Before commencing the investigation, instruct and train all investigators to use these in order to obtain
data that can be combined for the purpose of statistical analysis.
The minimum number of completed case report forms for each reporting period is the minimum
number required for the investigation.
A.3 Reporting periods
The time frames for the reporting periods are defined below:
a) Case Report Form 0: Pre-operative/Operative reporting;
b) Case Report Form 1: Post-operative reporting 1 d to 2 d post-operatively;
c) Case Report Form 2: Post-operative reporting 7 d to 14 d post-operatively;
d) Case Report Form 3: Post-operative reporting 30 d to 60 d post-operatively;
e) Case Report Form 4: Post-operative reporting 120 d to 180 d post-operatively;
f) Case Report Form 5: Post-operative reporting 330 d to 420 d post-operatively;
g) Case Report Form 6: Post-operative reporting 630 d to 780 d post-operatively;
h) Case Report Form 7: Post-operative reporting 990 d to 1 140 d post-operatively.
A.4 Clinical tests
Slit lamp examination is performed at all Forms except Form 0 during surgery.
Uncorrected and corrected visual acuities are measured in logMAR under photopic conditions, and
performed at all Forms except for Form 0 during surgery. Methods are outlined in Annex F.
A.5 Outcomes
The outcomes to be considered are those listed in Annex E for comparison with historical data.
A.6 Data analyses
Besides comparisons with the historical data in Annex E, consider the following analyses:
a) Visual Acuity (VA) stratified by age (<65 and ≥65 years);
b) best-case VA;
c) VA stratified by adverse event;
d) VA stratified by investigator;
e) subject-by-subject analysis of reasons why subject failed to achieve 0,3 logMAR CDVA;
f) rates of, and the causes of loss of visual acuity of 0,2 logMAR;
g) rates of cumulative adverse events stratified by age (<65 and ≥65 years);
h) rates of persistent adverse events stratified by age (<65 and ≥65 years);
10 © ISO 2018 – All rights reserved

ISO 11979-7:2018(E)
i) adverse events stratified by investigator;
j) percentage of eyes that achieve intended vs. achieved SE within:
— ±0,50 D, and
— ±1,00 D.
k) percentage of eyes that achieve uncorrected visual acuity within:
— 0,0 logMAR or better, and
— 0,3 logMAR or better.
l) percentage of eyes that achieve corrected visual acuity within:
— 0,0 logMAR or better, and
— 0,3 logMAR or better.
m) serious ocular adverse events and adverse device events.
For the primary analyses of adverse events, the primary statistical analyses is performed using only the
first implanted eye for each subject; secondary analyses include all implanted eyes. For performance
endpoints, the primary analyses is performed using only the first implanted eye for each subject.
A.7 Subject accountability
The general requirements for the accountability of subjects are given in ISO 14155. Specific guidance
for subject accountability at each of the post-operative visits in IOL clinical investigation designs are
provided in Table A.1.
ISO 11979-7:2018(E)
Table A.1 — Accountability by post-operative visit
Total
number
a
Enrolled (N)
b
Implanted (N)
Form 1 Form 2, etc. Final Form
Subject status
(n, %) (n, %) (n, %)
c
Available for analysis
d
Discontinued
e
Missing at scheduled visit but seen later
f
Not seen but accounted for
g
Lost to follow-up
h
Active
a
Enrolled — represents the total number of subjects enrolled in the investigation.
b
Implanted — represents the total number of subjects implanted with the IOL.
c
Available for analysis — represents the total number of subjects for whom data is available at the Form.
d
Discontinued — represents the total number of subjects that have discontinued treatment prior to the Form for any
reason (e.g. death or device replacement, screen failure, or discontinued following not being implanted), but does not
include subjects that are lost to follow-up.
e
Missing at scheduled visit but seen later — represents the total number of subjects that were seen outside the time
window associated with the Form.
f
Not seen but accounted for — represents the total number of subjects that were missing at the scheduled visit but were
accounted for by being contacted (e.g. by phone).
g
Lost to follow-up — represents the total number of subjects that have missed the Form and there is no information
available about them.
h
Active — represents the total number of subjects that have not reached the time associated with the Form. The
investigation at the Form is considered completed when the number of active subjects is zero.
The following equation is used to determine the percent accountability for the investigation.
% Accountability = (Available for analysis)/(Enrolled – Discontinued − Active)
Depending upon the clinical investigation, the total number of subjects might not necessarily represent
the total number of eyes. However, for the purposes of this guidance, it is assumed that treatment is
unilateral and that the total number of subjects is equivalent to the total number of eyes.
Methods are outlined in Annex F.
A.8 Monofocal IOL recommended examination schedule
Use the tests and schedules outlined in Table A.2 for anterior and posterior monofocal IOLs.
12 © ISO 2018 – All rights reserved

ISO 11979-7:2018(E)
Table A.2 — Monofocal IOL examination schedule
Form 0
a a
Examination Preop Op Form 1 Form 2 Form 3 Form 4 Form 5 Form 6 Form 7
a a
Distance UCVA X X X X X X X X
a a
Distance BSCVA X X X X X X X
a a
Subjective refraction X X X X X X X
a a
IOL tilt and  X X X X X X X
decentration
a a
Slit lamp examination X X X X X X X X
a a
Fundus examination X   X X X
with dilated pupil
Keratometry X
a a a a
Pachymetry of corneal X  X X X X
thickness
Axial length X
a a
Anterior chamber X X X
depth
a a a a a
Gonioscopic exam. X  X X X X X
a a
Intraocular pressure X X X X X X X X
a a a a a a
Specular microscopy X  X X X X X
Sub-studies
a,b a a
Clearance analysis X  X
a
For anterior chamber IOLs only.
b
See ISO 11979–10 for guidance.
ISO 11979-7:2018(E)
Annex B
(informative)
Additional elements for the clinical investigation of TIOLs
B.1 General
The following additional elements for a TIOL clinical investigation plan (CIP) can assist in collecting
data for the purpose of determining the safety and performance of this device.
If the toric feature is being applied to a previously approved non-toric parent IOL, then a study of
rotational stability of the non-toric IOL model is performed.
If the TIOL is not associated with any previously approved model, then an initial study of rotational
stability of a non-toric version of the new model is performed, followed by a full clinical investigation as
described in Annex A. This full clinical investigation may include only non-toric IOLs or a combination
of TIOLs and non-toric IOLs.
Requirements for rotational stability are given in 6.2.2.
If risk assessment indicates th
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