REVIEW

Monovision Versus Multifocality for Presbyopia:Systematic Review and Meta-Analysis of RandomizedControlled Trials

Lidija Kelava . Hrvoje Baric . Mladen Busic . Ivan Cima .

Vladimir Trkulja

Received: May 15, 2017 / Published online: July 3, 2017� Springer Healthcare Ltd. 2017

ABSTRACT

Introduction: Refractive surgery in presbyopiatends to achieve spectacle independence withminimal optical disturbances. We comparedmonovision to multifocality proceduresregarding these outcomes.Methods: We conducted a systematic review ofpublished (till November 21, 2016) randomizedcontrolled trials (RCTs) comparing any

monovision to any multifocality method orcomparing different monovision/multifocalitymethods to each other that enabled direct orindirect comparisons between particularmonovision and particular multifocality proce-dures in presbyopic patients undergoingcataract-related or unrelated surgery in respectto spectacle independence, unaided binocularvisual acuity (VA), contrast sensitivity (CS), andadverse events.Results: Three trials comparing monovision(monofocal lenses, LASIK) to multifocalintraocular lenses (MFIOLs; Isert refractive orTecnis diffractive) and 6 comparing otherMFIOLs to Tecnis were included (1–12 monthsduration). Spectacle independence. All reportingtrials were of sufficient quality. Directly, pseu-dophakic monovision was inferior to Isert (1trial, N = 75, RR = 0.49, 95% CI 0.28–0.80) andTecnis (1 trial, N = 211, RR = 0.36, 95% CI0.25–0.52) in cataract patients, and LASIK wascomparable to Tecnis (1 trial, N = 100,RR = 0.93, 0.78–1.10) in refractive surgery. Innetwork meta-regression (6 trials, 14 arms)pseudophakic monovision in cataract patientswas inferior to Tecnis. Indirect data suggest alsothat it is inferior (ReZoom refractive, TwinSetdiffractive) or tends to be inferior (Arrayrefractive) to other MFIOLs. LASIK was compa-rable to Tecnis in refractive surgery. Indirectdata suggest also that it tends to superiority vs.ReZoom or Array refractive MFIOLs. Adverseevents. No pooling was possible (heterogeneity

Enhanced content To view enhanced content for thisarticle go to http://www.medengine.com/Redeem/40A8F0604EF5CA24.

Electronic supplementary material The onlineversion of this article (doi:10.1007/s12325-017-0579-7)contains supplementary material, which is available toauthorized users.

L. Kelava � M. BusicDepartment of Ophthalmology, Clinical Hospital‘‘Sveti Duh’’, Zagreb, Croatia

H. BaricDepartment of Neurosurgery, University HospitalCentre Zagreb, Zagreb, Croatia

I. CimaSt. Erik Eye Hospital, Stockholm, Sweden

V. Trkulja (&)Department of Pharmacology, Zagreb UniversitySchool of Medicine, Zagreb, Croatiae-mail: vtrkulja@mef.hr

Adv Ther (2017) 34:1815–1839

DOI 10.1007/s12325-017-0579-7

of assessment and reporting). One quality directRCT indicated less glare/dazzle with pseu-dophakic monovision vs. Tecnis in cataractpatients. Unaided VA and CS data were bur-dened with heterogeneity (assessment, report-ing) and insufficient quality.Conclusions: Randomized comparisons ofmonovision to multifocality are scarce. Existingestimates regarding spectacle independence(imprecision, indirectness) and particularlyregarding unaided VA and CS (assessment/re-porting heterogeneity, bias, imprecision, indi-rectness) are burdened with uncertainty.Dysphotopsia is less common with monovision,but estimate uncertainty is high (bias,imprecision).

Keywords: Meta-analysis; Ophthalmology;Presbyopia; Refractive surgery; Systematicreview

INTRODUCTION

Presbyopia is expected to affect around 1.4 bil-lion people worldwide by the year 2020 [1].Techniques developed to improve optical out-comes of cataract surgery have been alsoimplemented for correction of presbyopia notrelated to cataracts. These include application ofintraocular lenses (IOLs) [monofocal, monofo-cal to achieve monovision, multifocal (diffrac-tive, refractive), or accommodating];application of corneal inlays; scleral modifica-tions; excimer and femtosecond lasers in phakicpatients [e.g., laser-assisted in situ keratomileu-sis (LASIK) to achieve monovision or presbyopiaLASIK (presbyLASIK) to achieve multifocality];and conductive keratoplasty [2]. Consideringthese developments, patients undergoing cat-aract surgery increasingly expect to achievepostoperative spectacle independence [3].Spectacle independence is clearly the mainobjective of purely refractive surgery. Idealspectacle independence implies a satisfactorybinocular uncorrected visual acuity (VA)—dis-tance (UDVA), intermediate (UIVA), and near(UNVA).

Several systematic reviews [4–13] (supple-mentary material Table S1) have addressed the

performance of various IOLs in respect tofunctional outcomes using different method-ologies: (a) evaluating a particular type of IOLper se by combining observational data (i.e.,patient series) and specific arms from random-ized controlled trials (RCTs) trying to quantify‘‘post- vs. pre- changes’’ or report absolute valuesof certain optical outcomes [5, 7–9, 13]. Typi-cally, data were taken from reports of variableduration, unknown quality, and differentmethods of outcome assessment with unclearmethods of data synthesis; (b) meta-analyses ofRCTs [4, 6, 10–12], burdened commonly withsimilar limitations of the primary trials. Overall,synthesized data indicate (a) no clear benefit ofaccommodative vs. standard monofocal IOLswith likely more posterior capsule opacifica-tions [6, 11]; (b) a tendency of better UDVA orUNVA and a tendency of less spectacle depen-dence with multifocal vs. monofocal IOLs, buthaving more common occurrence of glare andhalos [4, 7, 10, 12]. In general, data point outthe potential of multifocal IOLs (MFIOLs) toprovide the desired goal, at least when glare andhalos are avoided. However, not all MFIOLsseem to perform equally well, as diffractivelenses might yield better UNVA and less spec-tacle dependence than the refractive ones(supplementary material Table S1) [7].

An online survey conducted among USophthalmologists in 2015, although with a rel-atively low response rate (10%), indicated theirpreferences about methods for correction ofpre-cataract presbyopia: monovision or modi-fied monovision appeared to be the most pre-ferred approaches, whereas MFIOLs werepreferred over accommodative IOLs [14]. Arecent Cochrane Collaboration review addres-sed the issue of multifocality vs. monovisionand identified two RCTs [12]. A recent narrativereview [15] addressed the issue of pseudophakicmonovision vs. MFIOLs in respect to presbyopiacombining data from case series and the twoaforementioned RCTs. A cumulative conclusion[12, 15] could be summarized as follows:monovision bears a lower risk of glare andhalos, whereas MFIOLs are more likely toachieve spectacle independence.

Having in mind that different MFIOLs maydiffer in performance and that there are

1816 Adv Ther (2017) 34:1815–1839

different options for monovision, we undertookthe present systematic review in an attempt toidentify randomized comparisons of individualmonovision procedures vs. individual multifo-cal procedures, evaluate their quality and, iffeasible, try to provide synthesized quantitativeestimates. We focused on spectacle indepen-dence and complementary optical outcomes—unaided binocular VA, contrast sensitivity, anddysphotopsia.

METHODS

This article is based on previously conductedstudies and does not involve any new studies ofhuman or animal subjects performed by any ofthe authors.

Literature search, study selection, qualityassessment, and data extraction were performedby two independent investigators, agreementwas assessed after each step, and disagreementswere resolved through discussions with a thirdinvestigator.

Criteria for Inclusion of Studiesin the Present Review

Types of Studies, Interventions,and ParticipantsEligible for inclusion were RCTs directly com-paring efficacy and/or safety of monovision(e.g., monofocal IOLs, laser-induced monovi-sion) to multifocal procedures (e.g., MFIOLs,laser-induced corneal multifocality) or differentmodes of monovision or of multifocality toeach other in a way that could contribute toindirect comparisons of a specific monovisionto a specific multifocality procedure, in patientswith presbyopia related or unrelated to cataractsurgery. Studies published by November 21,2016 (last search update) in English or Germanwere considered if available in full text. In thecase of multiple publications of the same study,the one with the most complete data wasincluded. Only published data were used in thisreview. Several authors were contacted to clarifyuncertainties about measurement units, alloca-tion procedures, and data reporting.

Types of OutcomesPrimary outcome was proportion of patientswith complete post-procedural spectacle inde-pendence. Secondary outcomes were(i) post-procedural binocular uncorrected near,intermediate, and distance VA; (ii) contrastsensitivity; and (iii) incidence of adverse events(primarily optical phenomena, i.e., dysphotop-sia-like halos, glare, shadows, or any otherreported by the patient).

Information Sources and Literature SearchWe searched six literature databases [PubmedMEDLINE, Ovid MEDLINE, EBM Reviews (allCochrane Library), Scopus—Health Sciences, ISIWeb of Knowledge, EBSCO (Academic SearchComplete, CINAHL and ERIC)] and hand-searched reference lists of included articles andpreviously published systematic reviews. Thesearch terms ‘‘presbyopia’’ AND ‘‘randomized’’were used for all databases (only languagerestrictions).

Data Extraction

Data were extracted at the point of longest fol-low-up: spectacle independence as n/N using allpatients who received the assigned treatment asa denominator; complications as n/N withnumber of patients for which reported as adenominator; continuous data as mean ± SDfor the number of patients for which actuallymeasured. For contrast sensitivity, numericaldata were extracted if available; otherwise, themain conclusion was quoted. Where possible,acuity data were converted to logMAR [16].Studies with no reference to complications (e.g.,lack of events was not explicitly stated) were notconsidered as a source of data for this purpose.Collected were also data on actual interven-tions, follow-up time, methods of outcomeassessment, conflict of interest statements, andpatient inclusion/exclusion criteria.

Assessment of Risk of Bias (Study Quality)We used the Cochrane Collaboration Risk ofBias Assessment Tool to evaluate study quality[17]. In addition to the elements evaluatingselection, performance, detection, attrition, and

Adv Ther (2017) 34:1815–1839 1817

reporting bias, we added assessment of a risk ofbias arising from differential expertise andmethods to evaluate subjective patient difficul-ties (e.g., dysphotopsia) as we considered thatthe use of non-validated tools might haveintroduced a form of detection bias. We ratedstudies as being of ‘‘sufficient’’ (or ‘‘insufficient’’)quality in respect to each individual outcome:(a) spectacle independence—a study was con-sidered to be of ‘‘sufficient quality’’ if (i) the riskof selection bias and of differential expertisebias was low or unclear; (ii) considering theexplicit nature of the outcome, the risk of biasarising from (non)blinding of participants, per-sonnel, and assessors was allowed to be high, aswell as the risk of attrition bias since all reportedcounts or percentages were used to derive n/N with all subjects who received the assignedtreatment as a denominator; (b) VA and con-trast sensitivity—a study was considered to be of‘‘sufficient quality’’ if (i) the risk of selection anddifferential expertise bias was low or unclear; (ii)considering the objective nature of assessment,we allowed the risk of bias arising from(non)blinding of participants, personnel, andassessors to be high; (iii) the risk of attrition biaswas low; (c) subjective patient outcomes, i.e.,dysphotopsia—a study was considered to be of‘‘sufficient quality’’ if (i) the risk of selectionbias, differential expertise bias, and risk of biasarising from methods of dysphotopsia assess-ment was low or unclear; (ii) we allowed the riskof bias arising from non-blinded assessors to behigh; (iii) risk of bias arising from non-blindingof participants and risk of attrition bias werelow.

Data Synthesis (Meta-Analysis)

Considering the limited number of RCTsdirectly comparing monovision to multifocalprocedures and their clinical heterogeneity, wedid not perform any pooling of direct compar-isons. For network analysis we used theapproach based on reconstructed patient-leveldata described by Kessels et al. [18]. For binaryoutcomes, a study is reconstructed so that eachcontributing patient is represented by a recordwith a variable representing the study, a

variable representing the treatment, and avariable depicting the outcome. For continuousoutcomes (summarized as mean ± SD), a studyis reconstructed so that for each arm a samplefrom a normal distribution with these parame-ters is drawn (n = number of subjects per arm)and a difference in mean (SD) of the drawnsample vs. the reported parameters is adjustedfor using linear transformation [18]. Themethod essentially provides the option ofindividual (notional) patient-level analysis.Patient-level covariates are not available, butmay be substituted by average values by arm[18]. The method maintains randomization,ensures that each patient contributes equally tothe estimates, and allows for inclusion of two-and multi-arm studies to generate direct, indi-rect, and combined estimates [18]. The methodhas been successfully used in several publishedmeta-analyses [18]. Originally [18], analysisemploys ordinary logistic or linear regressionand is a generalization of the fixed-effectmeta-analysis. Considering the clinical hetero-geneity of the included studies, we considered itmore appropriate to apply random-effectsanalysis by fitting generalized linear mixedmodels to binary data, as described by Brownand Prescott [19], or general linear mixedmodels to continuous data, as described byWhitehead [20] using SAS 9.4 (SAS Inc. Cary,NC) (proc glimmix for binary and proc mixedfor continuous data).

RESULTS

Study Eligibility and Characteristics

Study selection is depicted in Fig. 1. A total of 33[21–53] potentially relevant RCTs comparingdifferent treatments (supplementary materialTable S2) were identified and evaluated in fulltext. Of those, three [25, 38, 52] were directcomparisons of monovision to multifocality(always by MFIOLs) (Fig. 1). Monovision wasachieved by monofocal IOLs in two studies(pseudophakic monovision) in patients under-going cataract surgery [38, 52], and by LASIK inphakic subjects (purely refractive surgery) in

1818 Adv Ther (2017) 34:1815–1839

one study [25] (Fig. 2). Two studies [25, 52] usedthe same type of MFIOL as a reference (Tecnisdiffractive, although models were different—ZA9003 [25] and ZM900 [52]), hence six RCTs[23, 24, 29, 40, 43, 47] comparing differentother MFIOLs to Tecnis diffractive MFIOL(models ZMA00 or ZM900, see Table 1) wereincluded for indirect comparisons to monovi-sion procedures (via Tecnis) (Figs. 1, 2). Table 1summarizes the main characteristics of these

nine RCTs: seven reported on spectacle inde-pendence [24, 25, 29, 38, 40, 43, 52], sixexplicitly reported on binocular VA[23, 38, 40, 43, 47, 52], seven reported on con-trast sensitivity [23, 29, 38, 40, 43, 47, 52], andall nine reported on complications (primarilydysphotopsia); follow-up periods varied from 1to 12 months; different evaluation methodswere used.

Fig. 1 PRISMA flowchart of the study selection process. MFIOL multifocal intraocular lens, RCT randomized controlledtrial

Adv Ther (2017) 34:1815–1839 1819

Risk of Bias (Study Quality) (Table 2)

All seven trials reporting on spectacle indepen-dence were considered to be of ‘‘sufficient’’quality; four out of six trials reporting onbinocular visual acuity and five out of sevenreporting on contrast sensitivity were consid-ered to be of ‘‘sufficient’’ quality, whereas otherswere burdened by uncertainty about attritionsince no explicit statements were made whetheror not all treated patients were actually evalu-ated; four out of nine studies were considered of‘‘sufficient’’ quality in respect to complications,while others were burdened by uncertaintyabout blinding of participants and/or attrition.

Spectacle Independence

In direct comparisons in cataract patients,incidence of spectacle independence was con-siderably lower for monovision by a monofocalIOL vs. Isert PY refractive MFIOL in one study[38] (Table 3) or vs. Tecnis diffractive MFIOL in

another study [52], while there was no differ-ence between monovision by LASIK (phakicpatients) vs. Tecnis MFIOL in a third study (re-fractive surgery) [25] (Table 3). A total of sixtrials [24, 25, 29, 40, 43, 52] evaluating sixtreatments—two monovision procedures (oneby LASIK, one by monofocal IOL) and four typesof MFIOLs—in 14 arms were included in net-work meta-analysis (Table 3). Only Tecnis,ReZoom, and Array MFIOLs were evaluated inmore than one trial/arm (Table 3). The overallnumber of patients was low. Pooled proportionsacross treatment arms by type of surgery(Table 4) indicated a somewhat higher successrate for Tecnis MFIOL in younger patientsundergoing purely refractive surgery (two trials,high heterogeneity and inconsistency) than inolder patients undergoing cataract surgery (fourtrials, mild heterogeneity and inconsistency)(81.2% vs. 70.5%). Similar was observed forReZoom MFIOL (Table 4), while Array wasevaluated only in cataract patients (Table 4).Results of network meta-analysis are

Fig. 2 Comparisons between monovision and multifocal procedures enabled by the nine selected randomized controlledtrials. IOL intraocular lens

1820 Adv Ther (2017) 34:1815–1839

Table1

Maincharacteristicsof

theincluded

trialsof

monovisionprocedures

andmultifocalintraocularlenses

(MFIOL)(asreported)

Stud

y(ref.)

Indication

andpatients

Treatments

(manufacturer);N

treated

(meanage,

years)

Evaluation

time

(mon

ths)

Spectacle

independ

ence

Visualacuity

Con

trastsensitivity

Com

plications

assessment

Labiris

2015

[38]

Bilateralage-related

cataract;overallmean

(SD)age60

(10)

years,

*1:1M/F

Monovision:

SN60

WFIO

L

(Alcon

Labs);N=

38

(59.5)

MFIOL:RefractiveIsert

PY60MV(H

oyaSurgical

Optics);N

=37

(61.3)

6Likertscale

Binocular

ETDRScharts

Distance:4m

Interm

.Not

exam

ined

Near:Not

specified

Pelli-Robson

Not

stated

whether

bi-or

monocular

Standardized

script

(not

referenced)

Barisic

2010

[25]

Bilateral,refractive

purpose;

overallm

ean(SD)age50

(2)years,*

1:2M/F

Monovision:

LASIK

(machine

notspecified);

N=

50(47)

MFIOL:DiffractiveTecnis

ZA9003

(AbbottMedical

Optics);N

=50

(53)

6Not

explained

how

exam

ined

Not

explained

how

exam

ined

Not

exam

ined

Not

explained

how

exam

ined

Wilkins

2013

[52]

Bilateralcataract;overall

mean(SD)age68

(12)

years,*

1:1M/F

Monovision:

AkreosIO

L

(Bausch&

Lom

b,

Rochester,N

Y);N

=105

(68.7)

MFIOL:DiffractiveTecnis

ZM900(AbbottMedical

Optics);N

=106(67.0)

4Questionn

aire

orinterview

Binocular

ETDRScharts

Distance:4m

Interm

.1m

Near:0.4m

Pelli-Robson

Not

stated

whether

bi-or

monocular

Validated

questionnaire

Barisic

2008

[24]

Bilateral,refractive

purpose;

overallm

ean(SD)age53

(3)years,*

1:1M/F

MFIOLrefractive

ReZoom

(nodetails);N=

50(54)

MFIOLdiffractiveTecnis

(nodetails);N=

50(52)

6Not

explained

how

exam

ined

Not

explained

how

exam

ined

Not

exam

ined

Not

explained

how

exam

ined

Adv Ther (2017) 34:1815–1839 1821

Table1

continued

Stud

y(ref.)

Indication

andpatients

Treatments

(manufacturer);N

treated

(meanage,

years)

Evaluation

time

(mon

ths)

Spectacle

independ

ence

Visualacuity

Con

trastsensitivity

Com

plications

assessment

Pepose

2014

[47]

Bilateralage-related

cataract;overallmean

(SD)age64

(8)years,

*1:2M/F

MFIOLdiffractiveAcrySof

IQReSTOR?

3D

(SN6A

D1,

Alcon

Labs);

N=

26(64.2)

MFIOLdiffractiveTecnis

ZMA00

(AbbottMedical

Optics);N

=26

(63)

4–6

Not

assessed

Mono&

binocular

Optec

6500/6500P

Distance:6m

Interm

.:0.8m

Near:0.4m

Optec

6500/6500P

Mesopiccond

itions

Bi-andmonocular

Glarometer

5-pointscale

Ang

2013

[23]

Bilateralage-related

cataract;meanage65

(range

40–8

0)years,

*1:3M/F

MFIOLdiffractive

ReSTOR?

3D

(SN6A

D1,

Alcon

Labs);

N=

27(65)

MFIOLdiffractiveTecnis

ZMA00

(AbbottMedical

Optics);N

=25

(65)

4–6

Not

assessed

Mono&

binocular

Optec

6500/6500P

Distance:6m

Interm

.:0.8m

Near:0.4m

Optec

6500/6500P

Mesopiccond

itions

Bi-andmonocular

Glarometer

5-pointscale

Und

ilated

pupils

Cillino

2008

[29]

Bilateralcataract;overall

mean(SD)age62

(12)

years,*

1:1M/F

MFIOLrefractive

ReZoom

(AbbottMedicalOptics);

N=

17(64.9)

MFIOLrefractive

Array

SA40

N(AbbottMedical

Optics);N

=17

(57.4)

MFIOLdiffractiveTecnis

ZM900(AbbottMedical

Optics);N

=17

(59.7)

12Modified

validated

questionnaire

Monocular

Sloan

optotypes&

letterscharts

Distance:5m

Interm

.:0.8m

Near:0.35

cm

VisionContrastTest

System

VCTS-6500

Photopiccond

itions

Binocular

and

monocular

Modified

validated

questionnaire

1822 Adv Ther (2017) 34:1815–1839

Table1

continued

Stud

y(ref.)

Indication

andpatients

Treatments

(manufacturer);N

treated

(meanage,years)

Evaluation

time

(mon

ths)

Spectacle

independ

ence

Visualacuity

Con

trastsensitivity

Com

plications

assessment

Martınez

Palmer

2008

[40]

Bilateralcataract;overall

mean(SD)age73

(5)

years*

1:1or

1:2M/F

MFIOLrefractive

ReZoom

(AbbottMedicalOptics);

N=

32(71.6)

MFIOLdiffractiveTwinSet

(Acri.T

ec.H

emmingsdorf,

Germany);N=

32(74.4)

MFIOLdiffractiveTecnis

ZM900(AbbottMedical

Optics);N=

26(72.8)

1and3

Questionn

aire,

probablynot

validated

Mono&

binocular

Snellencharts

Distance:Not

specified

Interm

.Not

exam

ined

Near:Not

exam

ined

FunctionalAcuity

ContrastTest

charts(FACT);

Optec

6500

Mesopicand

scotopic

Monocular

Questionn

aire,

likelynot

validated

Mester

2007

[43]

Bilateralcataract;overall

mean(SD)age70

(6)

years,gend

ernot

specified

MFIOLrefractive

Array

SA40

(AbbottMedical

Optics);N=

25(71.2)

MFIOLdiffractiveTecnis

ZM900(AbbottMedical

Optics);N=

25(68.3)

1–2and

3–4

Questionn

aire,

likelynot

validated

Binocular

ETDRS

charts,

Cardiffnear

acuity

charts

Distance:Not

specified

Interm

.:Not

exam

ined

Near:0.4m

FunctionalAcuity

ContrastTest

charts(FACT);

GinsburgBox

Photopicand

mesopic

Binocular

Questionn

aire,

likelynot

validated

*approxim

ately,M

men,F

wom

en

Adv Ther (2017) 34:1815–1839 1823

Table2

Assessm

entof

risk

ofbias

(quality)

intheincluded

rand

omized

controlledtrials

Stud

y(ref.)

Sequ

ence

generated

Allo

cation

concealed

Blin

ded

participants

Blin

ded

assessor

Incomplete

outcom

esSelective

repo

rting

Differential

expertise

Dysph

otop

sia

assessmenta

Sufficientqu

alityforassessmentof

Spectacles

Binoc.

VA

Con

trast

Com

plic.

Labiris

2015

[38]

Low

Unclear

Unclear

Unclear

Unclearb

Low

Low

Low

Yes

No

No

No

Barisic

2010

[25]

Unclear

Unclear

Unclear

Unclear

Unclearb

Low

Low

High

Yes

No

NR

No

Wilkins

2013

[52]

Low

Low

Low

High

Low

Low

Unclearc

Low

Yes

Yes

Yes

Yes

Barisic

2008

[24]

Unclear

Unclear

Unclear

Unclear

Unclearb

Low

Low

High

Yes

No

NR

No

Pepose

2014

[47]

Low

Low

Low

Low

Low

Low

Uncleard

Low

NR

Yes

Yes

Yes

Ang

2013

[23]

Low

Unclear

Low

High

Low

Low

Uncleard

Low

NR

Yes

Yes

Yes

Cillino

2008

[29]

Low

Low

Low

Low

Low

Low

Low

Low

Yes

NR

Yes

Yes

Martınez

Palmer

2008

[40]

Unclear

Low

Low

Low

Unclearb

Low

Uncleard

Unclear

Yes

No

No

No

Mester

2007

[43]

Low

Unclear

Unclear

Unclear

Low

Low

Low

Unclear

Yes

Yes

Yes

No

NRoutcom

enotreported,V

Avisualacuity

aReferstorecordingoccurrence

ofsubjective

difficultiessuch

asglare,halos,dazzle,shadows.The

risk

ofbiaswasconsidered

‘‘high’’w

henno

referencewasmadeto

themethodor

itwasclearlyinappropriate;

‘‘unclear’’whenastructured

questioningwas

employed

butitsvaliditywas

uncertain;

and‘‘lo

w’’whenvalidated

toolswereused

bThe

actualnu

mberof

evaluatedpatientsnotexplicitlystated

(unclear

attrition)

cProcedures

wereperformed

bynine

cataract

surgeons,allwelltrained,

yetpotentially

notequally

skilled

dNoreferencemadein

thetext

1824 Adv Ther (2017) 34:1815–1839

Table3

Incidence[n/N

(%)]

ofcompletepost-proceduralspectacleindepend

ence

bystudy(treatmentarm)

Stud

y(ind

ication:

R—refractive;C—cataract)

Mon

ovisionprocedures

Com

parative

multifocalIO

Ls

SN60WF

IOL

LASIK

Akreos

IOL

IsertPY

refractive

Tecnis

diffractive

ReZ

oom

refractive

Array

refractive

TwinSet

diffractive

Labiris2015

[38]

(C)

12/38(31.6)

,24/37(64.9)

RRa=

0.49

(0.28–

0.80)

Barisic2010

[25]

(R)

42/50(84.0)

,45/50(90.0)

RRa=

0.93

(0.78–

1.10)

Wilkins2013

[52]

(C)

24/105

(22.9)

,67/106

(63.2)

RRa=

0.36

(0.25–

0.52)

Barisic2008

[24]

(R)

36/50(72.0)

34/50(68.0)

Cillino2008

[29]

(C)

14/17(82.4)

8/17

(47.1)

7/17

(41.2)

Martinez-Palmer

2008

[40]

(C)

20/26(76.9)

14/32(43.8)

28/32(87.5)

Mester2007

[43]

(C)

19/25(76.0)

8/25

(32.0)

Forthreestudieswithdirect

monovisionvs.m

ultifocalitycomparisons

relative

risks(RR)with95%

confi

denceintervalsaredepicted.B

oldvalues

depictsstudies

(arm

s)included

inanetworkmeta-analysis

aRelativerisks(RR)arecalculated

from

reported

frequencies;approxim

ateconfi

denceintervals

Adv Ther (2017) 34:1815–1839 1825

Table4

Pooled

estimates

(%)of

completepost-proceduralspectacleindepend

ence

acrosstreatm

entarmsforprocedures

[exclusivelymultifocalIO

Ls(M

FIOL)]

evaluatedin

atleasttwotrials(arm

s)

MFIOL

Indication

Stud

ies(m

eanage)

Total

n/N

Estim

ate

(95%

CI)a

s2I2 (95%

CI)

Tecnisdiffractive(ZA9003

orZM900)

Purelyrefractive

surgery

Barisic2010

[25]

(53)

Barisic2008

[24]

(52)

81/100

81.2

(61.3–

95.0)

0.084

81%

Cataractsurgery

Wilkins2013

[52]

(67)

Cillino2008

[29]

(59.7)

Martinez-Palmer

2008

[40]

(72.8)

Mester2007

[43]

(68.3)

120/174

70.5

(61.6–

78.7)

0.010

26%

(0–7

5)

Bothcombined

(Allsixtrials)

201/274

75.8

(66.0–

84.4)

0.046

66%

(0–8

4)

ReZoom

refractive

Purelyrefractive

surgery

Barisic2008

[24]

(54)

34/50

68.0

(53.3–

80.5)b

––

Cataractsurgery

Cillino2008

[29]

(64.9)

Martinez-Palmer

2008

[40]

(71.6)

22/49

45.1

(31.6–

58.9)

0.000

0%

Bothcombined

(Allthreetrials)

56/99

54.3

(37.7–

70.4)

0.054

63%

(0–8

7)

Array

refractive

Cataractsurgery

Cillino2008

[29]

(57.4)

Mester2007

[43]

(71.2)

15/42

36.3

(22.7–

51.0)

0.000

0%

Meta-analysisbasedon

rawdata

depicted

inTable3

s2mom

ent-basedestimated

ofbetween-studyvariance,I

2inconsistencyindex

aPo

oled

estimates

byFreeman–T

ukey

double-arcsine

transformationrand

om-effectsmethod

bExact

Clopper–P

earson

confi

denceintervalforthissinglestudy

1826 Adv Ther (2017) 34:1815–1839

summarized in Figs. 3 and 4. As a result of thelimited number of studies and patients, allestimates are imprecise. Initial model wascharacterized by rather high heterogeneity(s2 = 0.194, SE = 0.153, P = 0.102). Considering

a potential moderator effect of the indication(refractive surgery in generally younger patientsvs. cataract surgery in generally older patients),we used meta-regression (type of surgery andtreatment 9 surgery interaction) to generate

Fig. 3 Results of network (six trials, 14 arms, six differenttreatments) meta-regression of complete post-proceduralspectacle independence (type of surgery as a moderator).Estimated probabilities are given by type of surgery, bytreatment-by-surgery, and by treatment overall (a). Mono-vision procedures (LASIK or Akreos intraocular lens, IOL)

were compared to multifocal lenses (MFIOLs) by surgeryand overall through combined direct and indirect com-parisons (where feasible) or only through indirect(arm-level) comparisons (b). s2 variance between treat-ment-by-study effects by residual profile likelihood

Adv Ther (2017) 34:1815–1839 1827

Fig. 4 Results of network (six trials, 14 arms, six differenttreatments) meta-regression of complete post-proceduralspectacle independence (mean age per treatment arm as amoderator). a Regression of estimated probability ofspectacle independence on mean age across all treatmentarms (left) and across treatments evaluated in more thanone arm (right). Symbol size is proportional to the number

of patients per arm. b Estimated probability of spectacleindependence per treatment. c Age-adjusted comparisonsof interest: each of the two monovision procedures vs. aspecific multifocal intraocular lens (MFIOL). s2 variancebetween treatment-by-study effects by residual profilelikelihood

1828 Adv Ther (2017) 34:1815–1839

Table5

Uncorrected

binocularvisualacuity

bystudy(treatmentarm)—

distance

(UDVA),interm

ediate

(UIVA),andnear

(UNVA)

Outcomestud

y(units)

Mon

ovisionprocedures

Com

parative

multifocalIO

Ls

SN60WF

IOL

LASIK

AkreosIO

LIsertPYrefractive

Tecnisdiffractive

ReSTOR1

3Ddiffractive

ReZ

oom

refractive

TwinSet

diffractive

Array

refractive

UDVA

Labiris2015

[38]

(decim

al)

0.95

±0.07

n=

?,

ReportedP=

0.150

0.92

±0.09

n=

?

Barisic2010

[25]

a0.92

±0.09

n=

47

,P=

0.951

0.952±

0.093

n=

46

Wilkins2013

[52]

(logMAR)

0.06

–0.16

n=92

,ReportedP=0.377

0.08

–0.12

n=94

Pepose

2014

[47]

(logMAR)

20.053–0.104

n=24

20.061–0.080

n=25

Ang

2013

[23]

(logMAR)

0.034–0.102

n=25

0.058–0.143

n=27

Martinez-Palmer

2008

[40]

(logMAR)

0.18

–0.10

n=26

(?)

0.14

–0.12

n=32

(?)

0.16

–0.12

n=32

(?)

Mester2007

[43]

(logMAR)

0.088–0.145

n=23

0.07

6–0.12

7

n=24

UIVA

Wilkins2013

[52]

(logMAR)

0.15

–0.12

n=91

,ReportedP<0.001

0.22

–0.12

n=90

Pepose

2014

[47]

(logMAR)

0.175–0.146

n=24

0.169–0.144

n=25

Ang

2013

[23]

(logMAR)

0.096–0.112

n=25

0.100–0.094

n=27

UNVA

Labiris2015

[38]

(decim

al)

1.95

±0.87

n=

?

,ReportedP=

0.470

1.21

±0.41

n=

?

Barisic2010

[25]

b

(Jaeger)

J1=

19;J2

=18;

J3=

10

n=

47

,Reported‘‘nodifference’’

J1=

35;J2

=10;

J3=

2

n=

46

Wilkins2013

[52]

(logMar)

0.01

–0.12

n=92

,ReportedP=0.037

20.03

–0.13

n=94

Pepose

2014

[47]

(logMAR)

0.043–0.130

n=24

20.061–0.087

n=25

Adv Ther (2017) 34:1815–1839 1829

estimates by surgery and by treat-ment-by-surgery (Fig. 3): model heterogeneitywas reduced (s2 = 0.124, P = 0.197); successappeared greater in younger patients withrefractive surgery than in cataract patients(Fig. 3a); and estimated probabilities by treat-ment-by-indication (Fig. 3a) were closely similarto those generated by simple moment-basedpooling (Table 4). Although for Tecnis andReZoom probabilities were somewhat lower incataract patients than in those undergoingrefractive surgery (Fig. 3a), the estimates acrossindications for each of the two MFIOLs largelyoverlapped. Also, lower success rates in cataractpatients (than in refraction surgery) appearedmore related to the used MFIOL than to indi-cation (high rates for Tecnis and TwinSet)(Fig. 3a). Consequently, it appeared feasible(a) to generate estimates for Tecnis and ReZoomacross indications (Fig. 3a); and (b) to use Tecnisas a link for indirect comparisons of monovi-sion procedures [used either in refraction sur-gery (LASIK) or cataract surgery (Akreos IOL)] toother MFIOLs not only when used in the samerespective indication, but also in differentindications. Under these circumstances, LASIK(refractive surgery) was comparable to Tecnis inrefractive surgery and overall (Fig. 3b). Indi-rectly, data in refractive surgery and overallsuggest that LASIK could be superior to ReZoomrefractive MFIOL (should it be used in refractivesurgery) (Fig. 3b). Indirect comparisons alsosuggest that LASIK could be superior to Arrayrefractive MFIOL and similar to TwinSetdiffractive MFIOL (Fig. 3b). Pseudophakicmonovision by Akreos IOL (cataract surgery) isinferior to Tecnis in cataract patients and over-all (Fig. 3b). Indirect data suggest that it alsotends to be inferior to ReZoom MFIOL in cat-aract patients and overall (Fig. 3b), and inferiorto TwinSet diffractive and comparable to Arrayrefrective MFIOL in cataract patients (Fig. 3b).Since treatments (e.g., Tecnis, ReZoom) couldapparently be considered regardless of theindication, and since type of surgery might havebeen ‘‘aliased’’ by the effect of age, we con-ducted another meta-regression with overalltreatment estimates (regardless of indication)and adjustment for mean age by treatment arm(Fig. 4). Heterogeneity was even more reducedT

able5

continued

Outcomestud

y(units)

Mon

ovisionprocedures

Com

parative

multifocalIO

Ls

SN60WF

IOL

LASIK

AkreosIO

LIsertPYrefractive

Tecnisdiffractive

ReSTOR1

3Ddiffractive

ReZ

oom

refractive

TwinSet

diffractive

Array

refractive

Ang

2013

[23]

(logMAR)

0.052–0.103

n=25

0.052–0.147

n=27

Mester2007

[43]

(logMAR)

20.073–0.137

n=23

0.16

6–0.18

1

n=24

Forthreestudieswithdirect

comparisons

betweenmonovisionandmultifocality,

Pvalues

forbetween-treatm

entcomparisons

aredepicted.Boldvalues

depictsstudies(arm

s)included

innetwork

meta-analysis

?Unclear

actualnu

mberof

evaluatedpatients

aNeither

themethodnorun

itsreported.D

atapresentedas

distribution

acrossvalues

from

which

thedepicted

data

wererecalculated

andcomparedby

anun

equalvariance

ttest

bReportedisdistribution

(ascoun

ts)acrossJvalues;overalldistribution

retested

byaChi

2testforn9

mtables—Chi

2=

12.36,

P=

0.002

1830 Adv Ther (2017) 34:1815–1839

(s2 = 0.107) and older age appeared associatedwith a lower probability of spectacle indepen-dence (Fig. 4a) (the same trend is seen overalland in three treatments evaluated in more thanone trial) (Fig. 4a). In agreement with the anal-ysis in Fig. 3, LASIK monovision appearedcomparable to Tecnis diffractive MFIOL(Fig. 4c), with a trend of superiority vs. ReZoomand Array refractive MFIOLs and a trend ofinferiority vs. TwinSet diffractive MFIOL(Fig. 4c). Monovision by Akreos monofocal IOLwas inferior to Tecnis, ReZoom, and TwinSetMFIOLs, with a trend of inferiority vs. ArrayMFIOL (Fig. 4c).

Uncorrected Binocular Visual Acuity

None of the direct comparisons (in cataract orrefractory surgery) indicated any relevant dif-ferences in UDVA between any monovisionprocedures vs. comparative MFIOLs (Table 5). Atotal of five trials [23, 40, 43, 47, 52] evaluatingsix treatments—pseudophakic monovision byAkreos IOL and five types of MFIOLs—in 11arms, all in patients undergoing cataract surgerywere included in network meta-analysis(Table 5). Only Tecnis and ReSTOR ? 3Ddiffractive MFIOLs were evaluated in more thanone arm/trial. The overall number of patientswas low (Table 5). Results of networkmeta-analysis are summarized in Fig. 5. Overall,higher mean age was associated with worseUDVA (higher logMAR) (Fig. 5a) and the sametrend was observed for MFIOL evaluated inmore than one trial (Fig. 5a): adjustment for agereduced heterogeneity (s2 = 0.010 tos2 = 0.001). Age-adjusted comparisons indi-cated no relevant difference between monovi-sion and any of the MFIOLs, but the estimateswere imprecise (Fig. 5b).

Only one direct comparison provided data onUIVA (cataract patients) indicating better resultswith monovision using Akreos monofocal IOL vs.Tecnis diffractive MFIOL [52] (Table 5). Overallthree RCTs [23, 47, 52] evaluating three treat-ments in cataract patients—monovision byAkreos IOL, Tecnis (three arms), andReSTOR ? 3D (two arms) diffractive MFIOLs withlow number of patients were included in network

meta-analysis (Table 5). No relevant differenceswere apparent between monovision and MFIOLs,but estimates were highly imprecise (Fig. 5).

In respect to UNVA, in cataract patientsmonovision by a monofocal IOL did not differfrom Isert PY MFIOL in one trial [38] and wasworse than with Tecnis MFIOL in another trial[52] (Table 5), while no difference between LASIKmonovision and Tecnis MFIOL was reported inthe third trial with a direct comparison inrefractive surgery [25] (Table 5). However, recal-culated data from the latter study [25] indicatedworse UNVA with LASIK monovision vs. TecnisMFIOL (Table 5). A total of four trials[23, 43, 47, 52], all in cataract patients, evaluatingfour treatments—monovision by Akreos IOL andthree different MFIOLs—in eight treatment armswith an overall low number of patients wereincluded in a network meta-analysis. Only Tecnisand ReSTOR ? 3D diffractive MFIOLs were eval-uated in more than one arm (Table 5). No rele-vant differences were apparent betweenmonovision and any of the MFIOLs, but esti-mates were highly imprecise (Fig. 5).

Contrast Sensitivity (CS)

In one direct comparison [38] in cataractpatients CS for monovision by a monofocalIOL was comparable to Isert PY MFIOL([log(CS) 1.39 ± 0.11, n = not explicitlyreported vs. 1.40 ± 0.17, n = not explicitlyreported; reported P = 0.470], while inanother one [52] it was better than with TecnisMFIOL [log(CS) 1.45 ± 0.13, n = 93 vs.1.39 ± 0.18, n = 94; reported P = 0.009].Overall, considering different or unclear CStesting conditions (mono- or binocular,mesopic or photopic conditions, with orwithout glare, undeclared or a range of spatialfrequencies), data were not suitable for indi-rect comparisons between monovision proce-dures and other MFIOLs.

Dysphotopsia and Other Unwanted Events

Despite the differences in modes of reportingdysphotopsia, all three direct comparisons (twoin cataract patients, one in refractive surgery)

Adv Ther (2017) 34:1815–1839 1831

[25, 38, 52] demonstrated that presence of glare/halos/dazzle was clearly more common or morepronounced with MFIOLs than with monovision(IOL or LASIK) (Table 6). One comparison alsoindicated presence of shadows as more pro-nounced with a MFIOL [38] while another indi-cated no difference [52] (Table 6). As a result ofheterogeneity in dysphotopsia reporting, datawere not suitable for indirect comparisonsbetween monovision procedures and otherMFIOLs. None of the three direct comparisonsreported any other unwanted phenomena.

DISCUSSION

Refractive surgery in non-cataract-related presby-opia aims at achievement of spectacle indepen-dence, preferably complete, with concurrentlyminimal optical disturbances [15]. It was recentlysuggested that monovision by monofocal IOLs orMFIOLs were both feasible options, accounting forindividual patient’s vision and expectations [15].Having in mind that monovision could beachieved by other means and that not all MFIOLsseem to perform equally well [7], we conducted asystematic review of randomized comparisons ofmonovision (any mode) vs. MFIOLs incataract-related or non-related presbyopia in orderto evaluate evidence of their (relative) potential inachieving spectacle independence (primary effi-cacy outcome) and relevant complementary opti-cal outcomes: uncorrected binocular visual acuity,contrast sensitivity, and dysphotopsia.

Strengths and Limitations of the PresentReview

A comprehensive literature search based on asensitive strategy is unlikely to have missed anyRCT of relevance, and their quality was con-sidered on the basis of criteria adjusted to spe-cifics of each of the evaluated outcomes.Because only three direct comparisons wereidentified [25, 38, 52], we extended theattempts of quantitative synthesis to a ‘‘simplestar’’ network with a primary objective ofincreasing the power for the reference treat-ment estimates. All purely indirect comparisons

made possible through this approach areinherently of a limited value. However, themain limitations are due to limitations of theprimary trials, many of which are out-come-specific. General limitations include(a) scarce data (three direct comparisons with386 patients, two in cataract surgery, one inrefractive surgery; and six additional RCTs with395 patients, five in cataract surgery, one inrefractive surgery, considered in the networkanalysis) resulting in imprecise estimates;(b) likely inadequate power at the individualstudy level. Only one out three direct compar-isons [52] and three out of six other trials[23, 29, 47] declared sample size calculations;(c) follow-up limited to 1–12 months, which islikely too short of a period for finite conclusionsregarding spectacle independence and uncor-rected visual acuity, e.g., at least in youngerpatients who are candidates for LASIK; (d) con-flict of interest statement was included in sevenout of nine studies and should have beenunambiguously reported.

Spectacle Independence

The present review suggests that no generaliza-tion on ‘‘monovision overall’’ vs. ‘‘MFIOLs

Fig. 5 Results of network meta-analysis of uncorrectedbinocular visual acuity—distance (UDVA) (five RCTs, sixtreatments in 11 arms), intermediate (UIVA) (threeRCTs, three treatments in six arms) and near (UNVA)(four RCTs, four treatments in eight arms). The model forUDVA was characterized by moderate heterogeneity(s2 = 0.010) which was reduced (s2 = 0.001) with adjust-ment for mean age per arm. Heterogeneity was lower inmodels for UIVA and UNVA and no apparent relation-ship between age and visual acuity was observed. Upperpanel (a) Regression of UDVA (logMAR) on mean ageacross all treatment arms (left) and across treatmentsevaluated in five arms (right). Symbol size is proportionalto the number of patients per arm. b Mean differences (D)between monovision by Akreos monofocal IOL andmultifocal IOLs (MFIOL) regarding UDVA. Middle panelmean differences (D) between monovision by Akreosmonofocal IOL and MFIOLs regarding UIVA. Lowerpanel mean differences (D) between monovision by Akreosmonofocal IOL and MFIOLs regarding UNVA. s2

variance between treatment-by-study effects by restrictedmaximum likelihood

c

1832 Adv Ther (2017) 34:1815–1839

overall’’ is possible since the results appearmethod/device-specific, and could also bedependent on the indication—purely refractive

or cataract-related surgery. On the basis of onesmall direct comparison [38], monovision by amonofocal IOL is considerably inferior to a

Adv Ther (2017) 34:1815–1839 1833

refractive Isert PY MFIOL in cataract patients.On the basis of one medium-sized direct com-parison in cataract patients [52] and a networkanalysis (five additional arms with the referenceMFIOL), pseudophakic monovision is consider-ably inferior to Tecnis diffractive MFIOL. Indi-rect comparisons suggest the same vs. tworefractive (ReZoom, Array) or vs. TwinSetdiffractive MFIOL. However, in refractive sur-gery in younger patients, monovision by LASIKappears at least as successful as Tecnis MFIOL onthe basis of one small direct comparison [25]and a network analysis. Purely indirect datasuggest the same vs. ReZoom and ArraysMFIOLs, and a considerable uncertainty vs.TwinSet MFIOL. Reasons for postoperativespectacle use were not reported; therefore, wewere unable to determine whether this was dueto impaired binocular vision, inadequate visual

acuity, or both. Only two studies in cataractpatients [38, 52] examined stereo acuity (Titmustest) and reported it to be superior with MFIOLs.Meta-regression indicated a trend of decliningprobability of spectacle independence withincreasing age. The reason(s) for this observa-tion are unclear. Considering individual trialinclusion/exclusion criteria, it is unlikely that itwas due to, e.g., age-related macular degenera-tion. It is known that the pupil size decreaseswith age [54], while data on accommodativeconvergence/accommodation ratio changeswith age are ambiguous [55]. The observedtrend of declining UDVA with older age (catar-act patients) should also encourage authors tore-evaluate exclusion criteria in similar studies,and to reopen the issue of neuroadaptation andstereopsis in complete adjustment to monovi-sion/multifocal vision.

Table 6 Dysphotopsia outcomes in randomized trials directly comparing monovision procedures to multifocal intraocularlenses (MFIOL)

Labiris 2015 [38]

Monovision by SN60WF IOL Comparative MFIOLISERT PY refractive

Monovision vs. multifocality

Glare 0.06 ± 0.24

n = ?

0.21 ± 0.41

n = ?

Reported P = 0.08

Shadows 0.21 ± 0.48

n = ?

0.57 ± 0.75

n = ?

Reported P = 0.02

Barisic 2010 [25]

Monovision by LASIK Comparative MFIOL Tecnis diffractive Monovision vs. multifocality

Halos or glare 0/50 21/50 (42%) RR = 0 (0–0.171); P\0.001

Wilkins 2013 [52]

Monovision by Akreos IOL Comparative MFIOLTecnis diffractive

Monovision vs. multifocality

Relevanta glare/dazzle 18/100 (18.0%) 42/99 (42.4%) RR = 0.424 (0.262–0.674)

Relevanta unwanted images 14/100 (14.0%) 13/99 (13.1%) RR = 1.066 (0.536–2.215)

Relevanta shadows 8/100 (8.0%) 9/99 (9.1%) RR = 0.880 (0.364–2.125)

Relative risks (RR) were calculated from reported frequencies; approximate confidence intervals? Actual number of evaluated patients uncleara Defined as ‘‘annoying’’ or ‘‘debilitating’’

1834 Adv Ther (2017) 34:1815–1839

Uncorrected Binocular Visual Acuity

The present review points out that evaluation ofthis outcome is particularly burdened withlimitations. One arises from methodological(clinical) heterogeneity, i.e., use of differentmethods (EDTRS charts, Snellen charts, CardiffAcuity Test, Jaeger charts) and assessments atdifferent distances. Another one arises frominadequate reporting, i.e., not reporting theused method/distances. Combined with inade-quate quality—two out of three direct compar-isons were judged to be of insufficient qualitybecause of a high risk of attrition bias—thisresults in a high level of uncertainty aboutindividual study findings as well as aboutpooled estimates. In particular, we find com-parative evaluation regarding UIVA and UNVA,important outcomes in terms of avoidance ofoptical aids for working/reading activities, to beburdened with uncertainty. Only one directcomparison, judged in this respect to be of‘‘sufficient quality’’ (attrition was around 12% ineach arm but with a fair ‘‘symmetry’’ in respectto reasons [52]) reported on UIVA (EDTRScharts) suggesting a better result for monofocalIOL monovision (0.15 logMAR) vs. TecnisMFIOL (0.22 logMAR) in cataract patients.However, in the network analysis including twoadditional ‘‘sufficient quality’’ arms with TecnisMFIOL in cataract patients (visual acuity byOptec 6500/6500P at a similar distance) [23, 47]this advantage was lost (Tecnis overall 0.169logMAR). Similarly, in respect to UNVA thesame direct comparison [52] reported worseresults for monofocal monovision (logMAR0.01) than for Tecnis MFIOL (logMAR -0.03).However, in the network analysis includingthree additional ‘‘sufficient quality’’ arms withTecnis MFIOL (visual acuity by Optec6500/6500P or EDTRS charts, at the same dis-tance) [23, 43, 47], this disadvantage was lost(Tecnis overall 0.000 logMAR). Finally, thereported ‘‘no difference’’ for LASIK monovisionvs. Tecnis MFIOL in a single comparative RCT inrefractive surgery [25] is dubious—the trial wasburdened with an unclear risk of attrition biasand actual distribution of patients across theJaeger chart scores after recalculation turned outto indicate a worse result for LASIK.

Contrast Sensitivity

Evaluation of this outcome is burdened withlimitations similar to VA evaluation. Hetero-geneity of methods (equipment, testing condi-tions) and reporting (methods/conditions notreported; numerical or graphical presentations)precluded any direct or indirect pooled esti-mates. Combined with inadequate quality, thisreduced monovision vs. MFIOL comparison to asingle trial: of the two RCTs comparing mono-focal monovision to MFIOLs in cataractpatients, one was burdened with an unclear riskof attrition bias [38], while the other one [52]indicated a better result for monovision vs.Tecnis MFIOL, but leaving a high level ofuncertainty. This clearly calls for standardizedcontrast sensitivity examinations and reporting,at least for research purposes.

Adverse Effects

As a result of methodological/reportingheterogeneity, no direct or indirect pooledestimates were possible. However, the mainlimitation in respect to adverse outcomes (onlyoptical were reported across the trials) is lim-ited trial quality (one out of three direct com-parisons and three out of six other trials wereconsidered of ‘‘sufficient’’ quality in thisrespect) due to participant non-blinding, attri-tion, and unreliable methods of assessment(i.e., non-validated questionnaires). Still, halosand glare are clearly a much greater problemwith MFIOLs than monovision (pseudophakicor LASIK in phakic patients), but uncertaintyabout the actual size of the differences is con-siderable. One study [52] used wavefront anal-ysis to assess higher-order aberrations thatcause subjective phenomena like glare andhalos. On the other hand, some have arguedthat the connection between objective exami-nations and subjective symptoms is not clear[56], but that validated questionnaires shouldbe used [52]. We suggest that the use of vali-dated questionnaires and wavefront analysisshould be considered a standard in reportingpost-surgical subjective visual function.

Adv Ther (2017) 34:1815–1839 1835

CONCLUSIONS

Overall experience with refractive surgeries(cataract-related or not related) clearly suggeststhat the optimum choice for each individualpatient is largely determined by his/her actualvisual status, ocular morbidity, age, and expec-tations. The same applies for the choice ofrefractive methods in presbyopia, where spec-tacle independence with a minimum of opticaldisturbances is the ultimate goal. The presentreview attempted to evaluate comparative pop-ulation estimates (i.e., ‘‘general potential’’) fortwo concepts suggested as comparably feasiblein this respect—monovision vs. multifocal pro-cedures. In respect to spectacle independencethe main conclusions are (a) the body of evi-dence is extremely modest; (b) no generaliza-tion about monovision or multifocality isreasonable, because the results seem to be pro-cedure/device-specific; (c) pseudophakic mono-vision appears inferior to Isert PY refractive orTecnis diffractive MFIOL in cataract patients. Asa result of data scarceness, however, the level ofuncertainty about true differences is consider-able; (d) purely indirect comparisons suggestthat this applies also to other refractive ordiffractive MFIOLs, but the level of uncertaintyabout true effects is even higher; (e) LASIKmonovision seems to be comparable to TecnisMFIOL in younger patients with refractive sur-gery, and indirect data suggest the same forother refractive or diffractive MFIOLs, butuncertainty is considerable. The body of evi-dence about optical disturbances is modest insize and burdened with modest or low trialquality (blinding, attrition, detection) andassessment/reporting heterogeneity. Expect-edly, glare and halos are a greater problem withMFIOLs than with pseudophakic or LASIKmonovision, but uncertainty about true differ-ences vs. individual MFIOLs is considerable. It isparticularly high considering other optical dis-turbances like shadows or unwanted images.Finally, in respect to complementary opticaloutcomes, VA and contrast sensitivity, the bodyof evidence is modest in size and compromisedby inadequate trial quality and heterogeneity ofimplemented methods and modes of reporting

resulting in a high level of uncertainty aboutthe direction and size of potential differencesbetween pseudophakic or LASIK monovision vs.specific individual MFIOL. The review demon-strates that a number of high quality RCTs withharmonized methodology of outcome assess-ment and reporting are needed before accurateand precise estimates about comparative effi-cacy/safety of a particular monovision proce-dure vs. a particular multifocal procedure in thissetting are possible.

ACKNOWLEDGEMENTS

We are thankful to Dr. Juan Carlos Martinezfor providing several full-text articles and toDrs. Mirjana Bjelos and Biljana KumanovicElabjer for valuable suggestions. No fundingor sponsorship was received for this study orpublication of this article. All named authorsmeet the International Committee of MedicalJournal Editors (ICMJE) criteria for authorshipfor this manuscript, take responsibility for theintegrity of the work as a whole, and havegiven final approval to the version to bepublished.

Disclosures. Lidija Kelava, Hrvoje Baric,Mladen Busic, Ivan Cima, and Vladimir Trkuljahave nothing to disclose.

Compliance with Ethics Guidelines. Thisarticle is based on previously conducted studiesand does not involve any new studies of humanor animal subjects performed by any of theauthors.

Data Availability. All datasets used in theanalysis are available upon request form thecorresponding author.

REFERENCES

1. Holden BA. Global vision impairment due touncorrected presbyopia. Arch Ophthalmol.2008;126:1731–9.

1836 Adv Ther (2017) 34:1815–1839

2. Davidson RS, Dhaliwal D, Hamilton DR, et al. Sur-gical correction of presbyopia. J Cataract RefractSurg. 2016;42:920–30.

3. Hawker MJ, Madge SN, Baddeley PA, Perry SR.Refractive expectations of patients having cataractsurgery. J Cataract Refract Surg. 2005;31:1970–5.

4. Leyland M, Zinicola E. Multifocal versus monofocalintraocular lenses in cataract surgery. Ophthalmol-ogy. 2003;110:1789–98.

5. Findl O, Leydolt C. Meta-analysis of accommodat-ing intraocular lenses. J Cataract Refract Surg.2007;33:522–7.

6. Takakura A, Iyer P, Adams JR, Pepin SM. Functionalassessment of accommodating intraocular lensesversus monofocal intraocular lenses in cataractsurgery: metaanalysis. J Cataract Refract Surg.2010;36:380–8.

7. Cochener B, Lafuma A, Khoshnood B, Courouve L,Berdeaux G. Comparison of outcomes with multi-focal intraocular lenses: a meta-analysis. ClinOphthalmol. 2011;5:45–56.

8. Agresta B, Knorz MC, Kohnen T, Donatti C, JacksonD. Distance and near visual acuity improvementafter implantation of multifocal intraocular lensesin cataract patients with presbyopia: a systematicreview. J Refract Surg. 2012;28:426–35.

9. Agresta B, Knorz MC, Donatti C, Jackson D. Visualacuity improvements after implantation of toricintraocular lenses in cataract patients with astig-matism: a systematic review. BMC Ophthalmol.2012;12:41. doi:10.1186/1471-2415-12-41.

10. Calladine D, Evans JR, Shah S, Leyland M. Multifocalversus monofocal intraocular lenses after cataractextraction. Cochrane Database Syst Rev.2012;9:CD003169. doi:10.1002/14651858.cd003169.pub3.

11. Ong HS, Evans JR, Allan BD. Accommodativeintraocular lens versus standard monofocalintraocular lens implantation in cataract surgery.Cochrane Database Syst Rev. 2014;5:CD009667.doi:10.1002/14651858.cd009667.pub2.

12. de Silva SR, Evans JR, Kirthi V, Ziaei M, Leyland M.Multifocal versus monofocal intraocular lenses aftercataract extraction. Cochrane Database Syst Rev.2016;12:CD003169. doi:10.1002/14651858.cd003169.pub4.

13. Rosen E, Alio JL, Dick HB, Dell S, Slade S. Efficacyand safety of multifocal intraocular lenses followingcataract and refractive lens exchange: metaanalysisof peer-reviewed publications. J Cataract RefractSurg. 2016;42:310–28.

14. Duffey R, Leaming D. U.S. trends in refractive sur-gery: 2015 ISRS survey. 1st ed. Las Vegas; 2015.https://isrs.aao.org/resources/2015-isrs-u-s-trends-survey. Accessed 12 Mar 2017.

15. Greenstein S, Pineda R. The quest for spectacleindependence: a comparison of multifocal intraoc-ular lens implants and pseudophakic monovisionfor patients with presbyopia. Semin Ophthalmol.2017;32:111–5.

16. Bailey IL, Lovie-Kitchin JE. Visual acuity testing.From the laboratory to the clinic. Vis Res.2013;90:2–9.

17. Higgins JPT, Green S, editors. Cochrane handbookfor systematic reviews of interventions version 5.1.0[updated March 2011]. The Cochrane Collabora-tion, 2011. http://handbook.cochrane.org.

18. Kessels AGH, ter Riet G, Puhan MA, Kleijnen J,Bachmann LM, Minder C. A simple regressionmodel for network meta-analysis. OA Epidemiol-ogy. 2013;1(1):7. doi:10.13172/2053-079x-1-1-690.

19. Brown H, Prescott R. Applied mixed models inmedicine. 3rd ed. Chichester: Wiley; 2013.

20. Whitehead A. Meta-analysis of controlled clinicaltrials. Chichester: Wiley; 2002.

21. Alio JL, Plaza-Puche AB, Javaloy J, Ayala MJ,Vega-Estrada A. Clinical and optical intraocularperformance of rotationally asymmetric multifocalIOL plate-haptic design versus C-loop hapticdesign. J Refract Surg. 2013;29:252–9.

22. Allen ED, Burton RL, Webber SK, et al. Comparisonof a diffractive bifocal and a monofocal intraocularlens. J Cataract Refract Surg. 1996;22:446–51.

23. Ang R, Martinez G, Cruz E, Tiongoson A, Dela CruzA. Prospective evaluation of visual outcomes withthree presbyopia-correcting intraocular lenses fol-lowing cataract surgery. Clin Ophthalmol.2013;7:1811–23.

24. Barisic A, Dekaris I, Gabric N, et al. Comparison ofdiffractive and refractive multifocal IOLs in pres-byopia treatment. Coll Antropol. 2008;32:27–31.

25. Barisic A, Gabric N, Dekaris I, Romac I, Bohac M,Juric B. Comparison of different presbyopia treat-ments: refractive lens exchange with multifocalintraocular lens implantation versus LASIK mono-vision. Coll Antropol. 2010;34:95–8.

26. Beiko GH. Comparison of visual results withaccommodating intraocular lenses versusmini-monovision with a monofocal intraocularlens. J Cataract Refract Surg. 2013;39:48–55.

Adv Ther (2017) 34:1815–1839 1837

27. Chiam PJ, Chan JH, Haider SI, Karia N, Kasaby H,Aggarwal RK. Functional vision with bilateralReZoom and ReSTOR intraocular lenses 6 monthsafter cataract surgery. J Cataract Refract Surg.2007;33:2057–61.

28. El-Maghraby A, Marzouky A, Gazayerli E, Van DerKarr M, DeLuca M. Multifocal versus monofocalintraocular lenses visual and refractive compar-isons. J Cataract Refract Surg. 1992;18:147–52.

29. Cillino S, Casuccio A, Di Pace F, et al. One-yearoutcomes with new-generation multifocal intraoc-ular lenses. Ophthalmology. 2008;115:1508–16.

30. Gunenc U, Celik L. Long-term experience withmixing and matching refractive array and diffrac-tive CeeOn multifocal intraocular lenses. J RefractSurg. 2008;24:233–42.

31. Haaskjold E, Allen ED, Burton RL, et al. Contrastsensitivity after implantation of diffractive bifocaland monofocal intraocular lenses. J Cataract RefractSurg. 1998;24:653–8.

32. Harman FE, Maling S, Kampougeris G, et al. Com-paring the 1CU accommodative, multifocal, andmonofocal intraocular lenses. Ophthalmology.2008;115:993–1001.

33. Javitt JC, Steinert RF. Cataract extraction withmultifocal intraocular lens implantation: a multi-national clinical trial evaluating clinical, func-tional, and quality-of-life outcomes.Ophthalmology. 2000;107:2040–8.

34. Joshi RS. Diffractive multifocal intraocular lenscompared to pseudo-accommodative intraocularlens implant for unilateral cataracts in pre-presby-opic patients. Middle East Afr J Ophthalmol.2013;20:207–11.

35. Jusufovic V, Sarajlic D, Zvornicanin J, Musanovic Z,Halilbasic M. Comparison of the binocular visionquality after implantation of monofocal and mul-tifocal intraocular lenses. Acta Med Salin.2011;40:63–8.

36. Kamlesh Dadeya S, Kaushik S. Contrast sensitivityand depth of focus with aspheric multifocal versusconventional monofocal intraocular lens. Can JOphthalmol. 2001;36:197–201.

37. Khoramnia R, Fitting A, Rabsilber TM, Thomas BC,Auffarth GU, Holzer MP. Intrastromal femtosecondlaser surgical compensation of presbyopia with sixintrastromal ring cuts: 3-year results. Br J Ophthal-mol. 2015;99:170–6.

38. Labiris G, Giarmoukakis A, Patsiamanidi M, Papa-dopoulos Z, Kozobolis VP. Mini-monovision versus

multifocal intraocular lens implantation. J CataractRefract Surg. 2015;41:53–7.

39. Leyland MD, Langan L, Goolfee F, Lee N, Bloom PA.Prospective randomised double-masked trial ofbilateral multifocal, bifocal or monofocal intraoc-ular lenses. Eye. 2002;16:481–90.

40. Martınez Palmer A, Gomez Faina P, Espana AlbeldaA, Comas Serrano M, Nahra Saad D, CastillaCespedes M. Visual function with bilateralimplantation of monofocal and multifocalintraocular lenses: a prospective, randomized, con-trolled clinical trial. J Refract Surg. 2008;24:257–64.

41. Mastropasqua R, Toto L, Vecchiarino L, Falconio G,Nicola MD, Mastropasqua A. Multifocal IOLimplant with or without capsular tension ring:study of wavefront error and visual performance.Eur J Ophthalmol. 2013;23:510–7.

42. Maxwell WA, Cionni RJ, Lehmann RP, Modi SS.Functional outcomes after bilateral implantation ofapodized diffractive aspheric acrylic intraocularlenses with a ?3.0 or ?4.0 diopter addition power.J Cataract Refract Surg. 2009;35:2054–61.

43. Mester U, Hunold W, Wesendahl T, Kaymak H.Functional outcomes after implantation of TecnisZM900 and Array SA40 multifocal intraocular len-ses. J Cataract Refract Surg. 2007;33:1033–40.

44. Nijkamp MD, Dolders MG, de Brabander J, van denBorne B, Hendrikse F, Nuijts RM. Effectiveness ofmultifocal intraocular lenses to correct presbyopiaafter cataract surgery. Ophthalmology.2004;111:1832–9.

45. Nuijts RM, Jonker SM, Kaufer RA, et al. Bilateralimplantation of ?2.5 D multifocal intraocular lensand contralateral implantation of ?2.5 D and ?3.0D multifocal intraocular lenses: clinical outcomes.J Cataract Refract Surg. 2016;42:194–202.

46. Patel S, Alio JL, Feinbaum C. Comparison of Acri.Smart multifocal IOL, crystalens AT-45 accom-modative IOL, and technovision presbyLASIK forcorrecting presbyopia. J Refract Surg.2008;24:294–9.

47. Pepose JS, Qazi MA, Chu R, Stahl J. A prospectiverandomized clinical evaluation of 3 presby-opia-correcting intraocular lenses after cataractextraction. Am J Ophthalmol. 2014;158:436–46.

48. Percival SP, Setty SS. Prospectively randomized trialcomparing the pseudoaccommodation of the AMOARRAY multifocal lens and a monofocal lens.J Cataract Refract Surg. 1993;19:26–31.

49. Rossetti L, Carraro F, Rovati M, Orzalesi N. Perfor-mance of diffractive multifocal intraocular lenses in

1838 Adv Ther (2017) 34:1815–1839

extracapsular cataract surgery. J Cataract RefractSurg. 1994;20:124–8.

50. Sen HN, Sarikkola AU, Uusitalo RJ, Laatikainen L.Quality of vision after AMO Array multifocalintraocular lens implantation. J Cataract RefractSurg. 2004;30:2483–93.

51. Steinert RF, Post CT, Brint SF, et al. A prospective,randomized, double-masked comparison of azonal-progressive multifocal intraocular lens and amonofocal intraocular lens. Ophthalmology.1992;99:853–61.

52. Wilkins MR, Allan BD, Rubin GS, et al. Randomizedtrial of multifocal intraocular lenses versus mono-vision after bilateral cataract surgery. Ophthalmol-ogy. 2013;120:2449–55.

53. Zhao G, Zhang J, Zhou Y, Hu L, Che C, Jiang N.Visual function after monocular implantation ofapodized diffractive multifocal or single-piecemonofocal intraocular lens. J Cataract Refract Surg.2010;36:282–5.

54. Kasthurirangan S, Glasser A. Age related changes inthe characteristics of the near pupil response. VisRes. 2006;46:1393–403.

55. Atchison DA. Accommodation and presbyopia.Ophthalmic Physiol Opt. 1995;15:255–72.

56. Dick HB, Krummenauer F, Schwenn O, Krist R,Pfeiffer N. Objective and subjective evaluation ofphotic phenomena after monofocal and multifocalintraocular lens implantation. Ophthalmology.1999;106:1878–86.

Adv Ther (2017) 34:1815–1839 1839

本文献由“学霸图书馆-文献云下载”收集自网络，仅供学习交流使用。

学霸图书馆（www.xuebalib.com）是一个“整合众多图书馆数据库资源，

提供一站式文献检索和下载服务”的24 小时在线不限IP

图书馆。

图书馆致力于便利、促进学习与科研，提供最强文献下载服务。

图书馆导航：

图书馆首页 文献云下载 图书馆入口 外文数据库大全 疑难文献辅助工具